2,3,6-Trisubstituted-4-pyrimidone derivatives

Information

  • Patent Grant
  • 7504411
  • Patent Number
    7,504,411
  • Date Filed
    Friday, March 26, 2004
    20 years ago
  • Date Issued
    Tuesday, March 17, 2009
    15 years ago
Abstract
A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C1-C12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C1-C8 alkyl group, an optionally partially hydrogenated C6-C10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each independently represents a halogen atom, a hydroxy group, a cyano group, a C1-C6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group.
Description
TECHNICAL FIELD

The present invention relates to compounds that are useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of diseases mainly caused by abnormal activity of tau protein kinase 1, such as neurodegenerative diseases (e.g. Alzheimer disease).


BACKGROUND ART

Alzheimer disease is progressive senile dementia, in which marked cerebral cortical atrophy is observed due to degeneration of nerve cells and decrease of nerve cell number. Pathologically, numerous senile plaques and neurofibrillary tangles are observed in brain. The number of patients has been increased with the increment of aged population, and the disease arises a serious social problem. Although various theories have been proposed, a cause of the disease has not yet been elucidated. Early resolution of the cause has been desired.


It has been known that the degree of appearance of two characteristic pathological changes of Alzheimer disease well correlates to the degree of intellectual dysfunction. Therefore, researches have been conducted from early 1980's to reveal the cause of the disease through molecular level investigations of components of the two pathological changes. Senile plaques accumulate extracellularly, and β amyloid protein has been elucidated as their main component (abbreviated as “A β” hereinafter in the specification: Biochem. Biophys. Res. Commun., 120, 855 (1984); EMBO J., 4, 2757 (1985); Proc. Natl. Acad. Sci. USA, 82, 4245 (1985)). In the other pathological change, i.e., the neurofibrillary tangles, a double-helical filamentous substance called paired helical filament (abbreviated as “PHF” hereinafter in the specification) accumulate intracellularly, and tau protein, which is a kind of microtubule-associated protein specific for brain, has been revealed as its main component (Proc. Natl. Acad. Sci. USA, 85, 4506 (1988); Neuron, 1, 827 (1988)).


Furthermore, on the basis of genetic investigations, presenilins 1 and 2 were found as causative genes of familial Alzheimer disease (Nature, 375, 754 (1995); Science, 269, 973 (1995); Nature. 376, 775 (1995)), and it has been revealed that presence of mutants of presenilins 1 and 2 promotes the secretion of A β (Neuron, 17, 1005 (1996); Proc. Natl. Acad. Sci. USA, 94, 2025 (1997)). From these results, it is considered that, in Alzheimer disease, A β abnormally accumulates and agglomerates due to a certain reason, which engages with the formation of PHF to cause death of nerve cells. It is also expected that extracellular outflow of glutamic acid and activation of glutamate receptor responding to the outflow may possibly be important factors in an early process of the nerve cell death caused by ischemic cerebrovascular accidents (Sai-shin Igaku [Latest Medicine], 49, 1506 (1994)).


It has been reported that kainic acid treatment that stimulates the AMPA receptor, one of glutamate receptor, increases mRNA of the amyloid precursor protein (abbreviated as “APP” hereinafter in the specification) as a precursor of A β (Society for Neuroscience Abstracts, 17, 1445 (1991)), and also promotes metabolism of APP (The Journal of Neuroscience, 10, 2400 (1990)). Therefore, it has been strongly suggested that the accumulation of A β is involved in cellular death due to ischemic cerebrovascular disorders. Other diseases in which abnormal accumulation and agglomeration of A β are observed include, for example, Down syndrome, cerebral bleeding due to solitary cerebral amyloid angiopathy, Lewy body disease (Shin-kei Shinpo [Nerve Advance], 34, 343 (1990); Tanpaku-shitu Kaku-san Koso [Protein, Nucleic Acid, Enzyme], 41, 1476 (1996)) and the like. Furthermore, as diseases showing neurofibrillary tangles due to the PHF accumulation, examples include progressive supranuclear palsy, subacute sclerosing panencephalitic parkinsonism, postencephalitic parkinsonism, pugilistic encephalitis, Guam parkinsonism-dementia complex, Lewy body disease and the like (Tanpakushitu Kakusan Koso [Protein, Nucleic Acid, Enzyme], 36, 2 (1991); Igaku no Ayumi [Progress of Medicine], 158, 511 (1991); Tanpakushitu Kakusan Koso [Protein, Nucleic Acid, Enzyme], 41, 1476 (1996)).


The tau protein is generally composed of a group of related proteins that forms several bands at molecular weights of 48-65 kDa in SDS-polyacrylamide gel electrophoresis, and it promotes the formation of microtubules. It has been verified that tau protein incorporated in the PHF in the brain suffering from Alzheimer disease is abnormally phosphorylated compared with usual tau protein (J. Biochem., 99, 1807 (1986); Proc. Natl. Acad. Sci. USA, 83, 4913 (1986)). An enzyme catalyzing the abnormal phosphorylation has been isolated. The protein was named as tau protein kinase 1 (abbreviated as “TPK1” hereinafter in the specification), and its physicochemical properties have been elucidated (Seikagaku [Biochemistry], 64, 308 (1992); J. Biol. Chem., 267, 10897 (1992)). Moreover, cDNA of rat TPK1 was cloned from a rat cerebral cortex cDNA library based on a partial amino acid sequence of TPK1, and its nucleotide sequence was determined and an amino acid sequence was deduced (Japanese Patent Un-examined Publication [Kokai] No. 6-239893/1994). As a result, it has been revealed that the primary structure of the rat TPK1 corresponds to that of the enzyme known as rat GSK-3 β (glycogen synthase kinase 3 β, FEBS Lett., 325, 167 (1993)).


It has been reported that A β, the main component of senile plaques, is neurotoxic (Science, 250, 279 (1990)). However, various theories have been proposed as for the reason why A β causes the cell death, and any authentic theory has not yet been established. Takashima et al. observed that the cell death was caused by A β treatment of fetal rat hippocampus primary culture system, and then found that the TPK1 activity was increased by A β treatment and the cell death by A β was inhibited by antisense of TPK1 (Proc. Natl. Acad. Sci. USA, 90, 7789 (1993); Japanese Patent Un-examined Publication [Kokai] No. 6-329551/1994).


In view of the foregoing, compounds which inhibit the TPK1 activity may possibly suppress the neurotoxicity of A β and the formation of PHF and inhibit the nerve cell death in the Alzheimer disease, thereby cease or defer the progress of the disease. The compounds may also be possibly used as a medicament for therapeutic treatment of ischemic cerebrovascular disorder, Down syndrome, cerebral amyloid angiopathy, cerebral bleeding due to Lewy body disease and the like by suppressing the cytotoxicity of A β. Furthermore, the compounds may possibly be used as a medicament for therapeutic treatment of neurodegenerative diseases such as progressive supranuclear palsy, subacute sclerosing panencephalitic parkinsonism, postencephalitic parkinsonism, pugilistic encephalitis, Guam parkinsonism-dementia complex, Lewy body disease, Pick's disease, corticobasal degeneration, frontotemporal dementia, vascular dementia, acute stroke and traumatic injuries, brain and spinal cord trauma, peripheral neuropathies, retinopathies and glaucoma; non-insulin dependent diabetes (such as diabetes type II), and obesity, manic depressive illness, schizophrenia, alopecia, cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus-induced tumors.


As structurally similar compounds to the compounds of the present invention represented by formula (I) described later, compounds represented by the following formula (A) are known:




embedded image



wherein R represents 2,6-dichlorobenzyl group, 2-(2-chlorophenyl)ethylamino group, 3-phenylpropylamino group, or 1-methyl-3-phenylpropylamino group (WO98/24782). The compounds represented by formula (A) are characterized to have 4-fluorophenyl group at the 5-position of the pyrimidine ring and a hydroxy group at the 4-position, and not falling within the scope of the present invention. Moreover, main pharmacological activity of the compounds represented by formula (A) is anti-inflammatory effect, whereas the compounds of the present invention represented by formula (I) are useful as a TPK1 inhibitor or a medicament for therapeutic treatment of neurodegenerative diseases, and therefore, their pharmacological activities are totally different to each other.


Patent Document 1: WO 00/18758


Patent Document 2: WO 01/70728


Patent Document 3: WO 01/70729


DISCLOSURE OF THE INVENTION

An object of the present invention is to provide compounds useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of diseases such as Alzheimer disease. More specifically, the object is to provide novel compounds useful as an active ingredient of a medicament that enables radical prevention and/or treatment of the neurodegenerative diseases such as Alzheimer disease by inhibiting the TPK1 activity to suppress the neurotoxicity of A β and the formation of the PHF and by inhibiting the death of nerve cells.


In order to achieve the foregoing object, the inventors of the present invention conducted screenings of various compounds having inhibitory activity against the phosphorylation of TPK1. As a result, they found that compounds represented by the following formula (I) had the desired activity and were useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of the aforementioned diseases. The present invention was achieved on the basis of these findings.


The present invention thus provides 3-substituted-4-pyrimidone derivatives represented by formula (I) or salts thereof, or solvates thereof or hydrates thereof:




embedded image



wherein Q represents CH or nitrogen atom;

  • R represents a C1-C12 alkyl group which may be substituted;
  • the ring of:




embedded image


  • represents piperazine ring or piperidine ring;

  • each X independently represents

    X1—X2

  • wherein X1 represents an oxo group; a C1-C8 alkyl group which may be substituted;

  • a C3-C8 cycloalkyl-group which may be substituted; an optionally partially hydrogenated C6-C10 aryl ring which may be substituted; an indan ring which may be substituted; an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total; an aralkyloxy group; a group represented by —N(Ra)(Rb) wherein Ra and Rb are the same or different and each is hydrogen, a C1-C4 alkyl group which may be substituted, an aralkyl group which may be substituted, a C3-C8 cycloalkyl group which may be substituted, an aryl group which may be substituted, C1-C8 alkylcarbonyl group which may be substituted,

  • C3-C8 cycloalkylcarbonyl group which may be substituted,

  • aralkycarbonyl group which may be substituted,

  • C6-C10 arylcarbonyl group which may be substituted,

  • C1-C8 alkysulfonyl group which may be substituted,

  • C3-C8 cycloalkylsulfonyl group which may be substituted,

  • aralkysulfonyl group which may be substituted,

  • C6-C10 arylsulfonyl group which may be substituted,

  • C1-C8 alkyloxycarbonyl group which may be substituted,

  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,

  • aralkyoxycarbonyl group which may be substituted,

  • C6-C10 aryloxycarbonyl group which may be substituted,

  • aminocarbonyl,

  • N—C1-C8 alkylaminocarbonyl group which may be substituted,

  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • aralkylaminocarbonyl group which may be substituted,

  • N,N′-diaralkylaminocarbonyl group which may be substituted,

  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C6-C10 arylaminocarbonyl group which may be substituted,

  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,

  • or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total; or Ra and Rb together with the adjacent nitrogen atom form a 4 to 7 membered heterocyclic ring which may further contain 1 to 4 groups selected from an oxygen atom, a sulfur atom, N-Rc (wherein Rc represents a hydrogen atom, a C1-C4 alkyl group which may be substituted, an aralkyl group which may be substituted, C3-C8 cycloalkyl group which may be substituted or an aryl group which may be substituted,

  • C1-C8 alkylcarbonyl group which may be substituted,

  • C3-C8 cycloalkylcarbonyl group which may be substituted,

  • aralkycarbonyl group which may be substituted,

  • C6-C10 arylcarbonyl group which may be substituted,

  • C1-C8 alkysulfonyl group which may be substituted,

  • C3-C8 cycloalkylsulfonyl group which may be substituted,

  • aralkysulfonyl group which may be substituted,

  • C6-C10 arylsulfonyl group which may be substituted,

  • C1-C8 alkyloxycarbonyl group which may be substituted,

  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,

  • aralkyoxycarbonyl group which may be substituted,

  • C6-C10 aryloxycarbonyl group which may be substituted,

  • aminocarbonyl,

  • N—C1-C8 alkylaminocarbonyl group which may be substituted,

  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • aralkylaminocarbonyl group which may be substituted,

  • N,N′-diaralkylaminocarbonyl group which may be substituted,

  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C6-C10 arylaminocarbonyl group which may be substituted,

  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,

  • or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total),

  • a carbonyl group, a sulfinyl group or a sulfonyl group in the ring, and said 4 to 7 membered heterocyclic ring may optionally be fused with an aryl group which may be substituted;

  • X2 represents a bond, a carbonyl group, a sulfinyl group, a sulfonyl group, an oxygen atom, a sulfur atom, a C1-C4 alkylene group which may be substituted or

  • N-Rd (Rd represents a hydrogen atom, a C1-C4 alkyl group which may be substituted, an aralkyl group which may be substituted, C3-C8 cycloalkyl group which may be substituted or an aryl group which may be substituted,

  • C1-C8 alkylcarbonyl group which may be substituted,

  • C3-C8 cycloalkylcarbonyl group which may be substituted,

  • aralkycarbonyl group which may be substituted,

  • C6-C10 arylcarbonyl group which may be substituted,

  • C1-C8 alkysulfonyl group which may be substituted,

  • C3-C8 cycloalkylsulfonyl group which may be substituted,

  • aralkysulfonyl group which may be substituted,

  • C6-C10 arylsulfonyl group which may be substituted,

  • C1-C8 alkyloxycarbonyl group which may be substituted,

  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,

  • aralkyoxycarbonyl group which may be substituted,

  • C6-C10 aryloxycarbonyl group which may be substituted,

  • aminocarbonyl,

  • N—C1-C8 alkylaminocarbonyl group which may be substituted,

  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • aralkylaminocarbonyl group which may be substituted,

  • N,N′-diaralkylaminocarbonyl group which may be substituted,

  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C6-C10 arylaminocarbonyl group which may be substituted,

  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,

  • or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total);

  • m represents an integer of 1 to 3;

  • each Y independently represents a halogen atom, a hydroxy group, a cyano group,

  • Y1-Y3—wherein Y1 represents a C1-C8 alkyl group which may be substituted; a C3-C8 cycloalkyl group which may be substituted or a C6-C10 aryl ring which may be substituted; Y3 represents a carbonyl group, a sulfinyl group, a sulfonyl group, an oxygen atom, a sulfur atom, a C1-C4 alkylene group which may be substituted or N-Re (Re represents a hydrogen atom, a C1-C4 alkyl group which may be substituted,

  • an aralkyl group which may be substituted, C3-C8 cycloalkyl group which may be substituted or an aryl group which may be substituted,

  • C1-C8 alkylcarbonyl group which may be substituted,

  • C3-C8 cycloalkylcarbonyl group which may be substituted,

  • aralkycarbonyl group which may be substituted,

  • C6-C10 arylcarbonyl group which may be substituted,

  • C1-C8 alkysulfonyl group which may be substituted,

  • C3-C8 cycloalkylsulfonyl group which may be substituted,

  • aralkysulfonyl group which may be substituted,

  • C6-C10 arylsulfonyl group which may be substituted,

  • C1-C8 alkyloxycarbonyl group which may be substituted,

  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,

  • aralkyoxycarbonyl group which may be substituted,

  • C6-C10 aryloxycarbonyl group which may be substituted,

  • aminocarbonyl,

  • N—C1-C8 alkylaminocarbonyl group which may be substituted,

  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,

  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,

  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • aralkylaminocarbonyl group which may be substituted,

  • N,N′-diaralkylaminocarbonyl group which may be substituted,

  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,

  • C6-C10 arylaminocarbonyl group which may be substituted,

  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,

  • or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total),

  • n represents an integer of 0 to 8;

  • when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group;

  • and when m is 1, n is 0, and X is X1—CO—,
    • (1) X does not bind to 3-position of unsubstituted 1-piperazinyl group or does not bind to 3-position of a 4-alkyl-1-piperazinyl group; or
    • (2) X does not bind to 3-position or 4-position of non-substituted 1-piperidinyl group.



According to another aspect of the present invention, there is provided a medicament comprising as an active ingredient a substance selected from the group consisting of the 3-substituted-4-pyrimidone derivatives represented by formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof. As preferred embodiments of the medicament, there are provided the aforementioned medicament which is used for preventive and/or therapeutic treatment of diseases caused by tau protein kinase 1 hyperactivity, and the aforementioned medicament which is used for preventive and/or therapeutic treatment of neurodegenerative diseases.


As further preferred embodiments of the present invention, there are provided the aforementioned medicament wherein the diseases are selected from the group consisting of Alzheimer disease, ischemic cerebrovascular accidents, Down syndrome, cerebral bleeding due to cerebral amyloid angiopathy, progressive supranuclear palsy, subacute sclerosing panencephalitic parkinsonism, postencephalitic parkinsonism, pugilistic encephalitis, Guam parkinsonism-dementia complex, Lewy body disease, Pick's disease, corticobasal degeneration and frontotemporal dementia, vascular dementia, acute stroke and traumatic injuries, brain and spinal cord trauma, peripheral neuropathies, retinopathies and glaucoma, non-insulin dependent diabetes (such as diabetes type II), and obesity, manic depressive illness, schizophrenia, alopecia, cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus-induced tumors; and the aforementioned medicament in the form of pharmaceutical composition containing the above substance as an active ingredient together with one or more pharmaceutical additives.


The present invention further provides an inhibitor of tau protein kinase 1 comprising as an active ingredient a substance selected from the group consisting of the 3-substituted-4-pyrimidone derivatives of formula (I) and the salts thereof, and the solvates thereof and the hydrates thereof.


According to further aspects of the present invention, there are provided a method for preventive and/or therapeutic treatment of diseases caused by tau protein kinase 1 hyperactivity, which comprises the step of administering to a patient a preventively and/or therapeutically effective amount of a substance selected from the group consisting of the 3-substituted-4-pyrimidone derivatives of formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof, and a use of a substance selected from the group consisting of the 3-substituted-4-pyrimidone derivatives of formula (I) and the physiologically acceptable salts thereof, and the solvates thereof and the hydrates thereof for the manufacture of the aforementioned medicament.







BEST MODE FOR CARRYING OUT THE INVENTION

In the present specification, each group has the following meanings.


The alkyl group used herein may be either linear or branched.


The C1-C12 alkyl group represented by R may be, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, 1,1-dimethylpropyl group, n-hexyl group, isohexyl group, or a linear or branched heptyl group, octyl group, nonyl group, decyl group, undecyl group or dodecyl group. Particularly preferred R is methyl group.


In the specification, when a functional group is defined as “which may be substituted” or “optionally substituted”, the number of substituents as well as their types and substituting positions are not particularly limited, and when two or more substituents are present, they may be the same or different.


When the C1-C12 alkyl group represented by R has one or more substituents, the alkyl group may have one or more substituents selected from, for example, the groups consisting of a C3-C8 cycloalkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cyclooctyl group; a C1-C5 alkoxy group such as methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group; C1-C8 alkylamino group or C2-C6 dialkylamino group; a C6-C10 aryl group such as phenyl group, 1-naphthyl group, and 2-naphthyl group.


The C1-C8 alkyl group may be, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, neopentyl group, 1,1-dimethylpropyl group, n-hexyl group, isohexyl group, or a linear or branched heptyl group or octyl group.


The C1-C4 alkyl group may be, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group or tert-butyl group.


The C3-C8 cycloalkyl group may be, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group or cyclooctyl group.


The optionally partially hydrogenated C6-C10 aryl ring may be, for example a benzene ring, a naphthalene ring, an indan ring or a 1,2,3,4-tetrahydronaphthalene ring.


The heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total may be, for example, furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, benzofuran ring, dihydrobenzofuran, isobenzofuran ring, benzodioxol ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, 2-oxopyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridine oxide ring, piperidine ring, 4-oxopiperidine ring, pyrazine ring, piperazine ring, homopiperazine ring, pyrimidine ring, pyridazine ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzimidazole ring, benzotriazole ring, tetrahydroisoquinoline ring, benzothiazolinone ring, benzoxazolinone ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthyridine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, oxadiazole ring, thiazole ring, benzothiazole ring, thiazylidine ring, isothiazole ring, isothiazolidine ring, benzodioxole ring, dioxane ring, benzodioxane ring, dithian ring, morpholine ring, thiomorpholine ring, or phthalimide ring.


The aralkyl group may be, for example, benzyl group, 2-phenylethyl group, 3-phenylpropyl group or 4-phenylbutyl group.


The C1-C4 alkylene group may be, for example, methylene, ethylene, trimethylene or tetramethylene.


The 4 to 7 membered heterocyclic ring which may further contain 1 to 4 groups may be, for example, pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine, homopiperazine, 2-oxopyrrolidine, pyrrole, imidazoline, imidazole, pyrazole, pyrroline, pyrrolidine, imidazolidine, imidazolone, succinimide or glutarimide.


The C6-C10 aryl ring may be, for example, a benzene ring or a naphthalene ring, and the aryl group or the C6-C10 aryl group may be, for example, a phenyl group or naphthyl group.


When the ring represented by X or X1 has one or more substituents, the ring may have one or more substituents selected from the group consisting of a C1-C5 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, 1,1-dimethylpropyl group; C3-C6 cycloalkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; a C3-C6 cycloalkyl-C1-C4 alkyl group such as cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl; a C1-C4 hydroxyalkyl group such as hydroxymethyl, hydroxyethyl, hydroxypropyl; a halogen atom such as fluorine atom, chlorine atom, bromine atom, and iodine atom; a C1-C5 halogenated alkyl group such as trifluoromethyl group; hydroxyl group; cyano group; nitro group; formyl group; a benzene ring which may be substituted; a naphthalene ring which may be substituted; an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total (same as the above); an amino group; an N—C3-C6 cycloalkyl-N—C1-C4 alkylaminoalkyl group wherein said C1-C4 alkyl may be substituted by hydroxy group or C1-C4 alkoxy group such as N-cyclopropyl-N-methylaminomethyl group, N-cyclohexyl-N-methylaminomethyl group; a C1-C6 monoalkylaminomethyl group such as methylaminomethyl group, ethylaminomethyl group, propylaminomethyl group, isoproylaminomethyl group, butylaminomethyl group, isobutylaminomethyl group, tert-butylaminomethyl group, pentylaminomethyl group, isopentylaminomethyl group; a C2-C10 dialkylaminomethyl group such as dimethylaminomethyl group, diethylaminomethyl group, ethylmethylaminomethyl group, methylpropylaminomethyl group; pyrrolidinylmethyl group; piperidinylmethyl group; morpholinomethyl group; piperazinylmethyl group; pyrrolylmethyl group; imidazolylmethyl group; pyrazolylmethyl group; triazolylmethyl group; and a group of the formula -E-Rf wherein E represents O, S, SO, SO2, CO or N(R4) and Rf represents a C1-C5 alkyl group (same as the above), a C4-C7 cycloalkyl group (same as the above), a C4-C7 cycloalkylalkl group (same as the above), a C1-C5 hydroxyalkyl group (same as the above), a benzene ring which may be substituted, a naphthalene ring which may be substituted, an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total (same as the above), an N—C3-C6 cycloalkyl-N—C1-C4 alkylaminoalkyl group (same as the above), a C1-C5 monoalkylaminoalkyl group (same as the above), C2-C10 dialkylaminoalkyl group (same as the above), pyrrolidinylmethyl group, piperidinylmethyl group, morpholinomethyl group, piperazinylmethyl group, pyrrolylmethyl group, imidazolylmethyl group, pyrazolylmethyl group or triazolylmethyl group,

  • C1-C8 alkylcarbonyl group which may be substituted,
  • C3-C8 cycloalkylcarbonyl group which may be substituted,
  • aralkycarbonyl group which may be substituted,
  • C6-C10 arylcarbonyl group which may be substituted,
  • C1-C8 alkysulfonyl group which may be substituted,
  • C3-C8 cycloalkylsulfonyl group which may be substituted,
  • aralkysulfonyl group which may be substituted,
  • C6-C10 arylsulfonyl group which may be substituted,
  • C1-C8 alkyloxycarbonyl group which may be substituted,
  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,
  • aralkyoxycarbonyl group which may be substituted,
  • C6-C10 aryloxycarbonyl group which may be substituted,
  • aminocarbonyl,
  • N—C1-C8 alkylaminocarbonyl group which may be substituted,
  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,
  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,
  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,
  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • aralkylaminocarbonyl group which may be substituted,
  • N,N′-diaralkylaminocarbonyl group which may be substituted,
  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • C6-C10 arylaminocarbonyl group which may be substituted,
  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,
  • and R4 represents a hydrogen atom, a C1-C4 alkyl group which may be substituted,
  • an aralkyl group which may be substituted, C3-C8 cycloalkyl group which may be substituted or an aryl group which may be substituted,
  • C1-C8 alkylcarbonyl group which may be substituted,
  • C3-C8 cycloalkylcarbonyl group which may be substituted,
  • aralkycarbonyl group which may be substituted,
  • C6-C10 arylcarbonyl group which may be substituted,
  • C1-C8 alkysulfonyl group which may be substituted,
  • C3-C8 cycloalkylsulfonyl group which may be substituted,
  • aralkysulfonyl group which may be substituted,
  • C6-C10 arylsulfonyl group which may be substituted,
  • C1-C8 alkyloxycarbonyl group which may be substituted,
  • C3-C8 cycloalkyloxycarbonyl group which may be substituted,
  • aralkyoxycarbonyl group which may be substituted,
  • C6-C10 aryloxycarbonyl group which may be substituted,
  • aminocarbonyl,
  • N—C1-C8 alkylaminocarbonyl group which may be substituted,
  • N,N′—C1-C8 dialkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′—C3-C8 cycloalkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′-aralkylaminocarbonyl group which may be substituted,
  • N—C1-C8 alkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • C3-C8 cycloalkylaminocarbonyl group which may be substituted,
  • N,N′—C3-C8 dicycloalkylaminoycarbonyl group which may be substituted,
  • N—C3-C8 cycloalkyl-N′-aralkylaminocarbonyl group which may be substituted,
  • N—C3-C8 cycloalkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • aralkylaminocarbonyl group which may be substituted,
  • N,N′-diaralkylaminocarbonyl group which may be substituted,
  • N-aralkyl-N′—C6-C10 arylaminocarbonyl group which may be substituted,
  • C6-C10 arylaminocarbonyl group which may be substituted,
  • N,N′—C6-C10 diarylaminocarbonyl group which may be substituted,
  • or an optionally substituted heterocyclic ring having 1 to 4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.


When the C6-C10 aryl ring represented by Y1 has one or more substituents, the ring may be substituted by one or more substituents selected from the groups consisting of halogen atoms, a C1-C5 alkyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkyloxy group, a C1-C5 alkoxy group, a C4-C7 cycloalkylalkoxy, a C1-C5 alkylthio group, a C1-C5 alkylsulfonyl group, a C1-C5 halogenated alkyl, and a benzene ring.


When the ring represented by X, X1 or Y1 has one or more substituents, the substituent may further have one or more substituents selected from the group consisting of a C1-C5 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, 1,1-dimethylpropyl group; C3-C6 cycloalkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group; a C3-C6 cycloalkyloxy group such as cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group; C1-C4 hydroxyalkyl group such as hydroxymethyl group, hydroxyethyl group, hydroxypropyl group, hydroxybutyl group; a C1-C5 alkoxy group such as methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, and isopentyloxy group; a C4-C7 cycloalkylalkoxy group such as cyclopropylmethoxy group, cyclopentylmethoxy group; a C1-C5 alkylthio group such as methylthio group, ethylthio group, propylthio group, butylthio group, and pentylthio group; a C1-C5 alkylsulfonyl group such as methanesulfonyl group, ethanesulfonyl group, propanesulfonyl group, butanesulfonyl group, and pentanesulfonyl group; a halogen atom such as fluorine atom, chlorine atom, bromine atom, and iodine atom; a C1-C5 halogenated alkyl group such as trifluoromethyl group; a C1-C5 halogenated alkoxy group such as trifluoromethoxy group, 2,2,2-trifluoroethoxy group; hydroxyl group; cyano group; nitro group; formyl group; a C2-C6 alkylcarbonyl group such as acetyl group, propionyl group, butyryl group, and valeryl group; amino group; a C1-C5 monoalkylamino group such as methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, tert-butylamino group, pentylamino group, and isopentylamino group; a C2-C10 dialkylamino group such as dimethylamino group, ethylmethylamino group, diethylamino group, methylpropylamino group, and diisopropylamino group; a cyclic amino group such as pyrrolidinyl group, piperidino group, morpholino group; a C2-C10 monoalkylaminomethyl group such as methylaminomethyl group, ethylaminomethyl group, propylaminomethyl group, isoproylaminomethyl group, butylaminomethyl group, isobutylaminomethyl group, tert-butylaminomethyl group, pentylaminomethyl group, isopentylaminomethyl; a C3-C11 dialkylaminomethyl group such as dimethylaminomethyl group, diethylaminomethyl group, ethylmethylaminomethyl group, methylpropylaminomethyl group; a phenyl group; an aralkyloxy group such as benzyloxy, 2-phenylethyloxy, 3-phenylpropyloxy; an aralkyloxycarbonyl group such as benzyloxycarbonyl, 2-phenylehoxycarbonyl; an C2-C4 alkanoyloxy-C1-C4 alkyl group such as acetyloxymethyl, 2-acetyloxyethyl, 2-propionyloxyethyl; an alkanoylamino group such as acetylamino, propionylamino, butyrylamino; N—C1-C4 alkyl-N-alkanoylamino group such as N-methyl-N-acetylamino, N-ethyl-N-acetylamino, N-methyl-N-propionylamino, N-methyl-N-butyrylamino; a heterocyclic ring amino group such as pyridylamino, pyrimidinylamino, thienylamino, furylamino; N—C1-C4 alkyl-N-heterocyclic ring amino group such as N-methyl-N-pyridylamino, N-methyl-N-pyrimidinylamino, N-methyl-N-thienylamino, N-methyl-N-furylamino; a diheterocyclic ring amino group such as dipyridylamino, dipyrimidinylamino, dithienylamino, difurylamino, and the like.


R may preferably be a C1-C3 alkyl group, more preferably a methyl group or an ethyl group. The substituent of the alkyl group may preferably be a C3-C8 alkyl group.


X may preferably be a benzene ring which may be substituted, a benzyl group which may be substituted, a naphthyl group which may be substituted, a benzofuran ring which may be substituted, a dihydrobenzofuran ring which may be substituted, a benzoxazole ring which may be substituted, a benzisoxazole ring which may be substituted, a benzothiophene ring which may be substituted, a benzothiazole ring which may be substituted, a benzisothiazole ring which may be substituted, and a benzopyrazole ring which may be substituted; more preferably a benzene ring which may be substituted, a benzyl group which may be substituted. Substituent of X may preferably be selected from the group consisting of a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a hydroxy group, a nitro group, a cyano group, a perhalogenated C1-C4 alkyl group, a carboxyl group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkylthio group, a C1-C4 alkoxysulfonyl group, amino group which may be substituted by a C1-C4 alkyl group, a benzene ring which may be substituted, and a cyclic amino group which may be substituted.


The compounds represented by the aforementioned formula (I) may form a salt. Examples of the salt include, when an acidic group exists, salts of alkali metals and alkaline earth metals such as lithium, sodium, potassium, magnesium, and calcium; salts of ammonia and amines such as methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, and L-glucamine; or salts with basic amino acids such as lysine, δ-hydroxylysine, and arginine. When a basic group exists, examples include salts with mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; salts with organic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, and salicylic acid; or salts with acidic amino acids such as aspartic acid, and glutamic acid.


In addition to the 3-substituted-4-pyrimidone derivatives represented by the aforementioned formula (I) and salts thereof, their solvates and hydrates also fall within the scope of the present invention. The 3-substituted-4-pyrimidone derivatives represented by the aforementioned formula (I) may have one or more asymmetric carbon atoms. As for the stereochemistry of such asymmetric carbon atoms, they may independently be in either (R) and (S) configuration, and the pyrimidone derivative may exist as stereoisomers such as optical isomers, or diastereoisomers. Any stereoisomers in a pure form, any mixtures of stereoisomers, racemates and the like fall within the scope of the present invention.


Preferred compounds of the present invention are represented by formula (II):




embedded image


  • wherein Q, R, X, Y are the same as those defined above; p is 0 or 1; q is 0 or 1; r is an integer of 0 to 6; p+q is 1 or 2;

  • and Z represents N or CZ1 wherein Z1 represents hydrogen atom or Y.



Examples of more preferred classes of compounds represented by formula (II) include:

  • (1) those wherein R represents a C1-C3 alkyl group which may be substituted by a C3-C8 cycloalkyl group;
  • (2) the compounds of the above (1) wherein R is methyl group or ethyl group; Y is in 3-, 4- or 5-position of the piperazine ring or the piperidine ring; p+q is 1; and r is an integer of 0 to 3;
  • (3) the compounds of the above (2) wherein X is a C1-C8 alkyl group which may be substituted or a C6-C10 aryl ring which may be substituted; Y is a C1-C6 alkyl group which may be substituted; p is 1; q is 0; r is an integer of 0 to 3; and Z is N or CH;
  • (4) the compounds of the above (3) wherein X is a benzene ring which may be substituted, a benzyl group which may be substituted; Y is a methyl group which may be substituted; Z is N and r is 0 or 1;
  • (5) the compounds of the above (2) wherein X is a benzene ring which may be substituted, a benzyl group which may be substituted, a benzoyl group which may be substituted, or a benzisothiazol ring which may be substituted; Y is a methyl group which may be substituted; Z is N and p is 0;
  • (6) the compounds of the above (2) wherein X is a C1-C8 alkyl group substituted by a benzene ring which may be substituted or a benzene ring which may be substituted;
  • Y is a hydroxy group, a cyano group, or Y1—CO— wherein Y1 is a C1-C8 alkyl group; Z is CH or C—Y and r is 0 or 1; and
  • (7) the compounds of the above (6) wherein X is a benzyl group which may be substituted or a benzene ring which may be substituted; Y is a hydroxy group, a cyano group, or an acetyl group; Z is CH or C—Y and r is 0 or 1.


Examples of particularly preferred classes of compounds represented by formula (II) include:

  • (1) those wherein R is methyl group, Y is CH3O—CO— group or CH3CH2O—CO— group, Z is N, p is, 0, q is 1, r is 0 or 1 and Y is in 3-position of the piperazine ring;
  • (2) those wherein R is methyl group, Y is methyl group, benzyl group or acetyl group, Z is N, p is 1, q is 0, r is 0 or 1 and Y is in 4-position of the piperazine ring;
  • (3) those wherein R is methyl group, Y is methyl group, Z is N, p is 1, q is 0, r is 1 to 3 and Y is in 3-, 4-, or 5-position of the piperazine ring;
  • (4) those wherein R is methyl group, Y is hydroxyl group or cyano group, Z is CH, p is 1, q is 0, r is 0 or 1 and X and Y are attached on the same carbon atom;
  • (5) those wherein R is methyl group, Y is hydroxyl group, cyano group or acetyl group, Z is C—Y, p is 0, q is 1 and r is 1.


Examples of preferred compounds of the present invention are shown in the tables below. However, the scope of the present invention is not limited to the following compounds.














TABLE 1




embedded image


















No.
R1
R2
R3
R4
R5
R6





XA1
CH3—
H
H
CH3—
H
H


XA2
CH3—
H
H
CH3CH2—
H
H





XA3
CH3—
H
H


embedded image


H
H





XA4
CH3—
H
H


embedded image


H
H





XA5
CH3—
H
H


embedded image


H
H





XA6
CH3—
H
H


embedded image


H
H





XA7
CH3—
H
H


embedded image


H
H





XA8
CH3—
H
H


embedded image


H
H





XA9
CH3—
H
H


embedded image


H
H





XA10
CH3—
H
H


embedded image


H
H





XA11
CH3—
H
H


embedded image


H
H





XA12
CH3—
H
H


embedded image


H
H





XA13
CH3—
H
H


embedded image


H
H





XA14
CH3—
H
H


embedded image


H
H





XA15
CH3—
H
H


embedded image


H
H





XA16
CH3—
H
H


embedded image


H
H





XA17
CH3—
H
H
n-C8H17—
H
H





XA18
CH3—
H
H


embedded image


H
H





XA19
CH3—
H
H


embedded image


H
H





XA20
CH3—
H
H


embedded image


H
H





XA21
CH3—
H
H


embedded image


H
H





XA22
CH3—
H
H


embedded image


H
H





XA23
CH3—
H
H


embedded image


H
H





XA24
CH3—
H
H


embedded image


H
H





XA25
CH3—
H
H


embedded image


H
H





XA26
CH3—
H
H


embedded image


H
H





XA27
CH3—
H
H


embedded image


H
H





XA28
CH3—
H
H


embedded image


H
H





XA29
CH3—
H
H


embedded image


H
H





XA30
CH3—
H
H


embedded image


H
H





XA31
CH3—
H
H


embedded image


H
H





XA32
CH3—
H
H


embedded image


H
H





XA33
CH3—
H
H


embedded image


H
H





XA34
CH3—
H
H


embedded image


H
H





XA35
CH3—
H
H


embedded image


H
H





XA36
CH3—
H
H


embedded image


H
H





XA37
CH3—
H
H


embedded image


H
H





XA38
CH3—
H
H


embedded image


H
H





XA39
CH3—
H
H


embedded image


H
H





XA40
CH3—
H
H


embedded image


H
H





XA41
CH3—
H
H


embedded image


H
H





XA42
CH3—
H
H


embedded image


H
H





XA43
CH3—
H
H


embedded image


H
H





XA44
CH3—
H
H


embedded image


H
H





XA45
CH3—
H
H


embedded image


H
H





XA46
CH3—
H
H


embedded image


H
H





XA47
CH3—
H
H


embedded image


H
H





XA48
CH3—
H
H


embedded image


H
H





XA49
CH3—
H
H


embedded image


H
H





XA50
CH3—
H
H


embedded image


H
H





XA51
CH3—
H
H


embedded image


H
H





XA52
CH3—
H
H


embedded image


H
H





XA53
CH3—
H
H


embedded image


H
H





XA54
CH3—
H
H


embedded image


H
H





XA55
CH3—
H
H


embedded image


H
H





XA56
CH3—
H
H


embedded image


H
H





XA57
CH3—
H
H


embedded image


H
H





XA58
CH3—
H
H


embedded image


H
H





XA59
CH3—
H
H


embedded image


H
H





XA60
CH3—
H
H


embedded image


H
H





XA61
CH3—
H
H


embedded image


H
H





XA62
CH3—
H
H


embedded image


H
H





XA63
CH3—
H
H


embedded image


H
H





XA64
CH3—
H
H


embedded image


H
H





XA65
CH3—
H
H


embedded image


H
H





XA66
CH3—
H
H


embedded image


H
H





XA67
CH3—
H
H


embedded image


H
H





XA68
CH3—
H
H


embedded image


H
H





XA69
CH3—
H
H


embedded image


H
H





XA70
CH3—
H
H


embedded image


H
H





XA71
CH3—
H
H


embedded image


H
H





XA72
CH3—
H
H


embedded image


H
H





XA73
CH3—
H
H


embedded image


H
H





XA74
CH3—
H
H


embedded image


H
H





XA75
CH3—
H
H


embedded image


H
H





XA76
CH3—
H
H


embedded image


H
H





XA77
CH3—
H
H


embedded image


H
H





XA78
CH3—
H
H


embedded image


H
H





XA79
CH3—
H
H


embedded image


H
H





XA80
CH3—
H
H


embedded image


H
H





XA81
CH3—
H
H


embedded image


H
H





XA82
CH3—
H
H


embedded image


H
H





XA83
CH3—
H
H


embedded image


H
H





XA84
CH3—
H
H


embedded image


H
H





XA85
CH3—
H
H


embedded image


H
H





XA86
CH3—
H
H


embedded image


H
H





XA87
CH3—
H
H


embedded image


H
H





XA88
CH3—
H
H


embedded image


H
H





XA89
CH3—
H
H


embedded image


H
H





XA90
CH3—
H
H


embedded image


H
H





XA91
CH3—
H
H


embedded image


H
H





XA92
CH3—
H
H


embedded image


H
H





XA93
CH3—
H
H


embedded image


H
H





XA94
CH3—
H
H


embedded image


H
H





XA95
CH3—
H
H


embedded image


H
H





XA96
CH3—
H
H


embedded image


H
H





XA97
CH3—
H
H


embedded image


H
H





XA98
CH3—
H
H


embedded image


H
H





XA99
CH3—
H
H


embedded image


H
H





XA100
CH3—
H
H


embedded image


H
H





XA101
CH3—
H
H


embedded image


H
H





XA102
CH3—
H
H


embedded image


H
H





XA103
CH3—
H
H


embedded image


H
H





XA104
CH3—
H
H


embedded image


H
H





XA105
CH3—
H
H


embedded image


H
H





XA106
CH3—
H
H


embedded image


H
H





XA107
CH3—
H
H


embedded image


H
H





XA108
CH3—
H
H


embedded image


H
H





XA109
CH3—
H
H


embedded image


H
H





XA110
CH3—
H
H


embedded image


H
H





XA111
CH3—
H
H


embedded image


H
H





XA112
CH3—
H
H


embedded image


H
H





XA113
CH3—
H
H


embedded image


H
H





XA114
CH3—
H
H


embedded image


H
H





XA115
CH3—
H
H


embedded image


H
H





XA116
CH3—
H
H


embedded image


H
H





XA117
CH3—
H
H


embedded image


H
H





XA118
CH3—
H
H


embedded image


H
H





XA119
CH3—
H
H


embedded image


H
H





XA120
CH3—
H
H


embedded image


H
H





XA121
CH3—
H
H


embedded image


H
H





XA122
CH3—
H
H


embedded image


H
H





XA123
CH3—
H
H


embedded image


H
H





XA124
CH3—
H
H


embedded image


H
H





XA125
CH3—
H
H


embedded image


H
H





XA126
CH3—
H
H


embedded image


H
H





XA127
CH3—
H
H


embedded image


H
H





XA128
CH3—
H
H


embedded image


H
H





XA129
CH3—
H
H


embedded image


H
H





XA130
CH3—
H
H


embedded image


H
H





XA131
CH3—
H
H


embedded image


H
H





XA132
CH3—
H
H


embedded image


H
H





XA133
CH3—
H
H


embedded image


H
H





XA134
CH3—
H
H


embedded image


H
H





XA135
CH3—
H
H


embedded image


H
H





XA136
CH3—
H
H


embedded image


H
H





XA137
CH3—
H
H


embedded image


H
H





XA138
CH3—
H
H


embedded image


H
H





XA139
CH3—
H
H


embedded image


H
H





XA140
CH3—
H
H


embedded image


H
H





XA141
CH3—
H
H


embedded image


H
H





XA142
CH3—
H
H


embedded image


H
H





XA143
CH3—
H
H


embedded image


H
H





XA144
CH3—
H
H


embedded image


H
H





XA145
CH3—
H
H


embedded image


H
H





XA146
CH3—
H
H


embedded image


H
H





XA147
CH3—
H
H


embedded image


H
H





XA148
CH3—
H
H


embedded image


H
H





XA149
CH3—
H
H


embedded image


H
H





XA150
CH3—
H
H


embedded image


H
H





XA151
CH3—
H
H


embedded image


H
H





XA152
CH3—
H
H


embedded image


H
H





XA153
CH3—
H
H


embedded image


H
H





XA154
CH3—
H
H


embedded image


H
H





XA155
CH3—
H
H


embedded image


H
H





XA156
CH3—
H
H


embedded image


H
H





XA157
CH3—
H
H


embedded image


H
H





XA158
CH3—
H
H


embedded image


H
H





XA159
CH3—
H
H


embedded image


H
H





XA160
CH3—
H
H


embedded image


H
H





XA161
CH3—
H
H


embedded image


H
H





XA162
CH3—
H
H


embedded image


H
H





XA163
CH3—
H
H


embedded image


H
H





XA164
CH3—
H
H


embedded image


H
H





XA165
CH3—
H
H


embedded image


H
H





XA166
CH3—
H
H


embedded image


H
H





XA167
CH3—
H
H


embedded image


H
H





XA168
CH3—
H
H


embedded image


H
H





XA169
CH3—
H
H


embedded image


H
H





XA170
CH3—
H
H


embedded image


H
H





XA171
CH3—
H
H


embedded image


H
H





XA172
CH3—
H
H


embedded image


H
H





XA173
CH3—
H
H


embedded image


H
H





XA174
CH3—
H
H


embedded image


H
H





XA175
CH3—
H
H


embedded image


H
H





XA176
CH3—
H
H


embedded image


H
H





XA177
CH3—
H
H


embedded image


H
H





XA178
CH3—
H
H


embedded image


H
H





XA179
CH3—
H
H


embedded image


H
H





XA180
CH3—
H
H


embedded image


H
H





XA181
CH3—
H
H


embedded image


H
H





XA182
CH3—
H
H


embedded image


H
H





XA183
CH3—
H
H


embedded image


H
H





XA184
CH3—
H
H


embedded image


H
H





XA185
CH3—
H
H


embedded image


H
H





XA186
CH3—
H
H


embedded image


H
H





XA187
CH3—
H
H


embedded image


H
H





XA188
CH3—
H
H


embedded image


H
H





XA189
CH3—
H
H


embedded image


H
H





XA190
CH3—
H
H


embedded image


H
H





XA191
CH3—
H
H


embedded image


H
H





XA192
CH3—
H
H


embedded image


H
H





XA193
CH3—
H
H


embedded image


H
H





XA194
CH3—
H
H


embedded image


H
H





XA195
CH3—
H
H


embedded image


H
H





XA196
CH3—
H
H


embedded image


H
H





XA197
CH3—
H
H


embedded image


H
H





XA198
CH3—
H
H


embedded image


H
H





XA199
CH3—
H
H


embedded image


H
H





XA200
CH3—
H
H


embedded image


H
H





XA201
CH3—
H
H


embedded image


H
H





XA202
CH3—
H
H


embedded image


H
H





XA203
CH3—
H
H


embedded image


H
H





XA204
CH3—
H
H


embedded image


H
H





XA205
CH3—


embedded image


H
H
H
H





XA206
CH3—


embedded image


H
CH3—
H
H





XA207
CH3—


embedded image


H
CH3CH2—
H
H





XA208
CH3—


embedded image


H


embedded image


H
H





XA209
CH3—


embedded image


H


embedded image


H
H





XA210
CH3—


embedded image


H


embedded image


H
H





XA211
CH3—


embedded image


H


embedded image


H
H





XA212
CH3—


embedded image


H


embedded image


H
H





XA213
CH3—


embedded image


H


embedded image


H
H





XA214
CH3—


embedded image


H


embedded image


H
H





XA215
CH3—


embedded image


H


embedded image


H
H





XA216
CH3—


embedded image


H


embedded image


H
H





XA217
CH3—


embedded image


H


embedded image


H
H





XA218
CH3—


embedded image


H


embedded image


H
H





XA219
CH3—


embedded image


H


embedded image


H
H





XA220
CH3—


embedded image


H


embedded image


H
H





XA221
CH3—


embedded image


H


embedded image


H
H





XA222
CH3—


embedded image


H
n-C8H17—
H
H





XA223
CH3—


embedded image


H


embedded image


H
H





XA224
CH3—


embedded image


H


embedded image


H
H





XA225
CH3—


embedded image


H


embedded image


H
H





XA226
CH3—


embedded image


H


embedded image


H
H





XA227
CH3—


embedded image


H


embedded image


H
H





XA228
CH3—


embedded image


H


embedded image


H
H





XA229
CH3—


embedded image


H


embedded image


H
H





XA230
CH3—


embedded image


H


embedded image


H
H





XA231
CH3—


embedded image


H


embedded image


H
H





XA232
CH3—


embedded image


H


embedded image


H
H





XA233
CH3—


embedded image


H


embedded image


H
H





XA234
CH3—


embedded image


H


embedded image


H
H





XA235
CH3—


embedded image


H


embedded image


H
H





XA236
CH3—


embedded image


H


embedded image


H
H





XA237
CH3—


embedded image


H


embedded image


H
H





XA238
CH3—


embedded image


H


embedded image


H
H





XA239
CH3—


embedded image


H


embedded image


H
H





XA240
CH3—


embedded image


H


embedded image


H
H





XA241
CH3—


embedded image


H


embedded image


H
H





XA242
CH3—


embedded image


H


embedded image


H
H





XA243
CH3—


embedded image


H


embedded image


H
H





XA244
CH3—


embedded image


H


embedded image


H
H





XA245
CH3—


embedded image


H


embedded image


H
H





XA246
CH3—


embedded image


H


embedded image


H
H





XA247
CH3—


embedded image


H


embedded image


H
H





XA248
CH3—


embedded image


H


embedded image


H
H





XA249
CH3—


embedded image


H


embedded image


H
H





XA250
CH3—


embedded image


H


embedded image


H
H





XA251
CH3—


embedded image


H


embedded image


H
H





XA252
CH3—


embedded image


H


embedded image


H
H





XA253
CH3—


embedded image


H


embedded image


H
H





XA254
CH3—


embedded image


H


embedded image


H
H





XA255
CH3—


embedded image


H


embedded image


H
H





XA256
CH3—


embedded image


H


embedded image


H
H





XA257
CH3—


embedded image


H


embedded image


H
H





XA258
CH3—


embedded image


H


embedded image


H
H





XA259
CH3—


embedded image


H


embedded image


H
H





XA260
CH3—


embedded image


H


embedded image


H
H





XA261
CH3—


embedded image


H


embedded image


H
H





XA262
CH3—


embedded image


H


embedded image


H
H





XA263
CH3—


embedded image


H


embedded image


H
H





XA264
CH3—


embedded image


H


embedded image


H
H





XA265
CH3—


embedded image


H


embedded image


H
H





XA266
CH3—


embedded image


H


embedded image


H
H





XA267
CH3—


embedded image


H


embedded image


H
H





XA268
CH3—


embedded image


H


embedded image


H
H





XA269
CH3—


embedded image


H


embedded image


H
H





XA270
CH3—


embedded image


H
H
H
H





XA271
CH3—


embedded image


H
CH3—
H
H





XA272
CH3—


embedded image


H
CH3CH2—
H
H





XA273
CH3—


embedded image


H


embedded image


H
H





XA274
CH3—


embedded image


H


embedded image


H
H





XA275
CH3—


embedded image


H


embedded image


H
H





XA276
CH3—


embedded image


H


embedded image


H
H





XA277
CH3—


embedded image


H


embedded image


H
H





XA278
CH3—


embedded image


H


embedded image


H
H





XA279
CH3—


embedded image


H


embedded image


H
H





XA280
CH3—


embedded image


H


embedded image


H
H





XA281
CH3—


embedded image


H


embedded image


H
H





XA282
CH3—


embedded image


H


embedded image


H
H





XA283
CH3—


embedded image


H


embedded image


H
H





XA284
CH3—


embedded image


H


embedded image


H
H





XA285
CH3—


embedded image


H


embedded image


H
H





XA286
CH3—


embedded image


H


embedded image


H
H





XA287
CH3—


embedded image


H
n-C8H17—
H
H





XA288
CH3—


embedded image


H


embedded image


H
H





XA289
CH3—


embedded image


H


embedded image


H
H





XA290
CH3—


embedded image


H


embedded image


H
H





XA291
CH3—


embedded image


H


embedded image


H
H





XA292
CH3—


embedded image


H


embedded image


H
H





XA293
CH3—


embedded image


H


embedded image


H
H





XA294
CH3—


embedded image


H


embedded image


H
H





XA295
CH3—


embedded image


H


embedded image


H
H





XA296
CH3—


embedded image


H


embedded image


H
H





XA297
CH3—


embedded image


H


embedded image


H
H





XA298
CH3—


embedded image


H


embedded image


H
H





XA299
CH3—


embedded image


H


embedded image


H
H





XA300
CH3—


embedded image


H


embedded image


H
H





XA301
CH3—


embedded image


H


embedded image


H
H





XA302
CH3—


embedded image


H


embedded image


H
H





XA303
CH3—


embedded image


H


embedded image


H
H





XA304
CH3—


embedded image


H


embedded image


H
H





XA305
CH3—


embedded image


H


embedded image


H
H





XA306
CH3—


embedded image


H


embedded image


H
H





XA307
CH3—


embedded image


H


embedded image


H
H





XA308
CH3—


embedded image


H


embedded image


H
H





XA309
CH3—


embedded image


H


embedded image


H
H





XA310
CH3—


embedded image


H


embedded image


H
H





XA311
CH3—


embedded image


H


embedded image


H
H





XA312
CH3—


embedded image


H


embedded image


H
H





XA313
CH3—


embedded image


H


embedded image


H
H





XA314
CH3—


embedded image


H


embedded image


H
H





XA315
CH3—


embedded image


H


embedded image


H
H





XA316
CH3—


embedded image


H


embedded image


H
H





XA317
CH3—


embedded image


H


embedded image


H
H





XA318
CH3—


embedded image


H


embedded image


H
H





XA319
CH3—


embedded image


H


embedded image


H
H





XA320
CH3—


embedded image


H


embedded image


H
H





XA321
CH3—


embedded image


H


embedded image


H
H





XA322
CH3—


embedded image


H


embedded image


H
H





XA323
CH3—


embedded image


H


embedded image


H
H





XA324
CH3—


embedded image


H


embedded image


H
H





XA325
CH3—


embedded image


H


embedded image


H
H





XA326
CH3—


embedded image


H


embedded image


H
H





XA327
CH3—


embedded image


H


embedded image


H
H





XA328
CH3—


embedded image


H


embedded image


H
H





XA329
CH3—


embedded image


H


embedded image


H
H





XA330
CH3—


embedded image


H


embedded image


H
H





XA331
CH3—


embedded image


H


embedded image


H
H





XA332
CH3—


embedded image


H


embedded image


H
H





XA333
CH3—


embedded image


H


embedded image


H
H





XA334
CH3—


embedded image


H


embedded image


H
H





XA335
CH3—
CH3—
H
H
H
H


XA336
CH3—
CH3CH2—
H
H
H
H





XA337
CH3—


embedded image


H
H
H
H





XA338
CH3—


embedded image


H
H
H
H





XA339
CH3—


embedded image


H
H
H
H





XA340
CH3—


embedded image


H
H
H
H





XA341
CH3—


embedded image


H
H
H
H





XA342
CH3—


embedded image


H
H
H
H





XA343
CH3—


embedded image


H
H
H
H





XA344
CH3—


embedded image


H
H
H
H





XA345
CH3—


embedded image


H
H
H
H





XA346
CH3—


embedded image


H
H
H
H





XA347
CH3—


embedded image


H
H
H
H





XA348
CH3—


embedded image


H
H
H
H





XA349
CH3—


embedded image


H
H
H
H





XA350
CH3—


embedded image


H
H
H
H





XA351
CH3—
n-C8H17—
H
H
H
H





XA352
CH3—


embedded image


H
H
H
H





XA353
CH3—


embedded image


H
H
H
H





XA354
CH3—


embedded image


H
H
H
H





XA355
CH3—


embedded image


H
H
H
H





XA356
CH3—


embedded image


H
H
H
H





XA357
CH3—


embedded image


H
H
H
H





XA358
CH3—


embedded image


H
H
H
H





XA359
CH3—


embedded image


H
H
H
H





XA360
CH3—


embedded image


H
H
H
H





XA361
CH3—


embedded image


H
H
H
H





XA362
CH3—


embedded image


H
H
H
H





XA363
CH3—


embedded image


H
H
H
H





XA364
CH3—


embedded image


H
H
H
H





XA365
CH3—


embedded image


H
H
H
H





XA366
CH3—


embedded image


H
H
H
H





XA367
CH3—


embedded image


H
H
H
H





XA368
CH3—


embedded image


H
H
H
H





XA369
CH3—


embedded image


H
H
H
H





XA370
CH3—


embedded image


H
H
H
H





XA371
CH3—


embedded image


H
H
H
H





XA372
CH3—


embedded image


H
H
H
H





XA373
CH3—


embedded image


H
H
H
H





XA374
CH3—


embedded image


H
H
H
H





XA375
CH3—


embedded image


H
H
H
H





XA376
CH3—


embedded image


H
H
H
H





XA377
CH3—


embedded image


H
H
H
H





XA378
CH3—


embedded image


H
H
H
H





XA379
CH3—


embedded image


H
H
H
H





XA380
CH3—


embedded image


H
H
H
H





XA381
CH3—


embedded image


H
H
H
H





XA382
CH3—


embedded image


H
H
H
H





XA383
CH3—


embedded image


H
H
H
H





XA384
CH3—


embedded image


H
H
H
H





XA385
CH3—


embedded image


H
H
H
H





XA386
CH3—


embedded image


H
H
H
H





XA387
CH3—


embedded image


H
H
H
H





XA388
CH3—


embedded image


H
H
H
H





XA389
CH3—


embedded image


H
H
H
H





XA390
CH3—


embedded image


H
H
H
H





XA391
CH3—


embedded image


H
H
H
H





XA392
CH3—


embedded image


H
H
H
H





XA393
CH3—


embedded image


H
H
H
H





XA394
CH3—


embedded image


H
H
H
H





XA395
CH3—


embedded image


H
H
H
H





XA396
CH3—


embedded image


H
H
H
H





XA397
CH3—


embedded image


H
H
H
H





XA398
CH3—


embedded image


H
H
H
H





XA399
CH3—


embedded image


H
H
H
H





XA400
CH3—


embedded image


H
H
H
H





XA401
CH3—


embedded image


H
H
H
H





XA402
CH3—


embedded image


H
H
H
H





XA403
CH3—


embedded image


H
H
H
H





XA404
CH3—


embedded image


H
H
H
H





XA405
CH3—


embedded image


H
H
H
H





XA406
CH3—


embedded image


H
H
H
H





XA407
CH3—


embedded image


H
H
H
H





XA408
CH3—


embedded image


H
H
H
H





XA409
CH3—


embedded image


H
H
H
H





XA410
CH3—


embedded image


H
H
H
H





XA411
CH3—


embedded image


H
H
H
H





XA412
CH3—


embedded image


H
H
H
H





XA413
CH3—


embedded image


H
H
H
H





XA414
CH3—


embedded image


H
H
H
H





XA415
CH3—


embedded image


H
H
H
H





XA416
CH3—


embedded image


H
H
H
H





XA417
CH3—


embedded image


H
H
H
H





XA418
CH3—


embedded image


H
H
H
H





XA419
CH3—


embedded image


H
H
H
H





XA420
CH3—


embedded image


H
H
H
H





XA421
CH3—


embedded image


H
H
H
H





XA422
CH3—


embedded image


H
H
H
H





XA423
CH3—


embedded image


H
H
H
H





XA424
CH3—


embedded image


H
H
H
H





XA425
CH3—


embedded image


H
H
H
H





XA426
CH3—


embedded image


H
H
H
H





XA427
CH3—


embedded image


H
H
H
H





XA428
CH3—


embedded image


H
H
H
H





XA429
CH3—


embedded image


H
H
H
H





XA430
CH3—


embedded image


H
H
H
H





XA431
CH3—


embedded image


H
H
H
H





XA432
CH3—


embedded image


H
H
H
H





XA433
CH3—


embedded image


H
H
H
H





XA434
CH3—


embedded image


H
H
H
H





XA435
CH3—


embedded image


H
H
H
H





XA436
CH3—


embedded image


H
H
H
H





XA437
CH3—


embedded image


H
H
H
H





XA438
CH3—


embedded image


H
H
H
H





XA439
CH3—


embedded image


H
H
H
H





XA440
CH3—


embedded image


H
H
H
H





XA441
CH3—


embedded image


H
H
H
H





XA442
CH3—


embedded image


H
H
H
H





XA443
CH3—


embedded image


H
H
H
H





XA444
CH3—


embedded image


H
H
H
H





XA445
CH3—


embedded image


H
H
H
H





XA446
CH3—


embedded image


H
H
H
H





XA447
CH3—


embedded image


H
H
H
H





XA448
CH3—


embedded image


H
H
H
H





XA449
CH3—


embedded image


H
H
H
H





XA450
CH3—


embedded image


H
H
H
H





XA451
CH3—


embedded image


H
H
H
H





XA452
CH3—


embedded image


H
H
H
H





XA453
CH3—


embedded image


H
H
H
H





XA454
CH3—


embedded image


H
H
H
H





XA455
CH3—


embedded image


H
H
H
H





XA456
CH3—


embedded image


H
H
H
H





XA457
CH3—


embedded image


H
H
H
H





XA458
CH3—


embedded image


H
H
H
H





XA459
CH3—


embedded image


H
H
H
H





XA460
CH3—


embedded image


H
H
H
H





XA461
CH3—


embedded image


H
H
H
H





XA462
CH3—


embedded image


H
H
H
H





XA463
CH3—


embedded image


H
H
H
H





XA464
CH3—


embedded image


H
H
H
H





XA465
CH3—


embedded image


H
H
H
H





XA466
CH3—


embedded image


H
H
H
H





XA467
CH3—


embedded image


H
H
H
H





XA468
CH3—


embedded image


H
H
H
H





XA469
CH3—


embedded image


H
H
H
H





XA470
CH3—


embedded image


H
H
H
H





XA471
CH3—


embedded image


H
H
H
H





XA472
CH3—


embedded image


H
H
H
H





XA473
CH3—


embedded image


H
H
H
H





XA474
CH3—


embedded image


H
H
H
H





XA475
CH3—


embedded image


H
H
H
H





XA476
CH3—


embedded image


H
H
H
H





XA477
CH3—


embedded image


H
H
H
H





XA478
CH3—


embedded image


H
H
H
H





XA479
CH3—


embedded image


H
H
H
H





XA480
CH3—


embedded image


H
H
H
H





XA481
CH3—


embedded image


H
H
H
H





XA482
CH3—


embedded image


H
H
H
H





XA483
CH3—


embedded image


H
H
H
H





XA484
CH3—


embedded image


H
H
H
H





XA485
CH3—


embedded image


H
H
H
H





XA486
CH3—


embedded image


H
H
H
H





XA487
CH3—


embedded image


H
H
H
H





XA488
CH3—


embedded image


H
H
H
H





XA489
CH3—


embedded image


H
H
H
H





XA490
CH3—


embedded image


H
H
H
H





XA491
CH3—


embedded image


H
H
H
H





XA492
CH3—


embedded image


H
H
H
H





XA493
CH3—


embedded image


H
H
H
H





XA494
CH3—


embedded image


H
H
H
H





XA495
CH3—


embedded image


H
H
H
H





XA496
CH3—


embedded image


H
H
H
H





XA497
CH3—


embedded image


H
H
H
H





XA498
CH3—


embedded image


H
H
H
H





XA499
CH3—


embedded image


H
H
H
H





XA500
CH3—


embedded image


H
H
H
H





XA501
CH3—


embedded image


H
H
H
H





XA502
CH3—


embedded image


H
H
H
H





XA503
CH3—


embedded image


H
H
H
H





XA504
CH3—


embedded image


H
H
H
H





XA505
CH3—


embedded image


H
H
H
H





XA506
CH3—


embedded image


H
H
H
H





XA507
CH3—


embedded image


H
H
H
H





XA508
CH3—


embedded image


H
H
H
H





XA509
CH3—


embedded image


H
H
H
H





XA510
CH3—


embedded image


H
H
H
H





XA511
CH3—


embedded image


H
H
H
H





XA512
CH3—


embedded image


H
H
H
H





XA513
CH3—


embedded image


H
H
H
H





XA514
CH3—


embedded image


H
H
H
H





XA515
CH3—


embedded image


H
H
H
H





XA516
CH3—


embedded image


H
H
H
H





XA517
CH3—


embedded image


H
H
H
H





XA518
CH3—


embedded image


H
H
H
H





XA519
CH3—


embedded image


H
H
H
H





XA520
CH3—


embedded image


H
H
H
H





XA521
CH3—


embedded image


H
H
H
H





XA522
CH3—


embedded image


H
H
H
H





XA523
CH3—


embedded image


H
H
H
H





XA524
CH3—


embedded image


H
H
H
H





XA525
CH3—


embedded image


H
H
H
H





XA526
CH3—


embedded image


H
H
H
H





XA527
CH3—


embedded image


H
H
H
H





XA528
CH3—


embedded image


H
H
H
H





XA529
CH3—


embedded image


H
H
H
H





XA530
CH3—


embedded image


H
H
H
H





XA531
CH3—


embedded image


H
H
H
H





XA532
CH3—


embedded image


H
H
H
H





XA533
CH3—


embedded image


H
H
H
H





XA534
CH3—


embedded image


H
H
H
H





XA535
CH3—


embedded image


H
H
H
H





XA536
CH3—


embedded image


H
H
H
H





XA537
CH3—


embedded image


H
H
H
H





XA538
CH3—


embedded image


H
H
H
H





XA539
CH3—


embedded image


H
H
H
H





XA540
CH3—


embedded image


H
H
H
H





XA541
CH3—


embedded image


H
H
H
H





XA542
CH3—


embedded image


H
H
H
H





XA543
CH3—


embedded image


H
H
H
H





XA544
CH3—


embedded image


H
H
H
H





XA545
CH3—


embedded image


H
H
H
H





XA546
CH3—


embedded image


H
H
H
H





XA547
CH3—


embedded image


H
H
H
H





XA548
CH3—


embedded image


H
H
H
H





XA549
CH3—


embedded image


H
H
H
H





XA550
CH3—


embedded image


H
H
H
H





XA551
CH3—


embedded image


H
H
H
H





XA552
CH3—


embedded image


H
H
H
H





XA553
CH3—


embedded image


H
H
H
H





XA554
CH3—


embedded image


H
H
H
H





XA555
CH3—


embedded image


H
H
H
H





XA556
CH3—


embedded image


H
H
H
H





XA557
CH3—


embedded image


H
H
H
H





XA558
CH3—


embedded image


H
H
H
H





XA559
CH3—


embedded image


H
H
H
H





XA560
CH3—


embedded image


H
H
H
H





XA561
CH3—


embedded image


H
H
H
H





XA562
CH3—


embedded image


H
H
H
H





XA563
CH3—


embedded image


H
H
H
H





XA564
CH3—


embedded image


H
H
H
H





XA565
CH3—


embedded image


H
H
H
H





XA566
CH3—


embedded image


H
H
H
H





XA567
CH3—


embedded image


H
H
H
H





XA568
CH3—


embedded image


H
H
H
H





XA569
CH3—


embedded image


H
H
H
H





XA570
CH3—


embedded image


H
H
H
H





XA571
CH3—


embedded image


H
H
H
H





XA572
CH3—


embedded image


H
H
H
H





XA573
CH3—


embedded image


H
H
H
H





XA574
CH3—


embedded image


H
H
H
H





XA575
CH3—


embedded image


H
H
H
H





XA576
CH3—


embedded image


H
H
H
H





XA577
CH3—


embedded image


H
H
H
H





XA578
CH3—


embedded image


H
H
H
H





XA579
CH3—


embedded image


H
H
H
H





XA580
CH3—


embedded image


H
H
H
H





XA581
CH3—


embedded image


H
H
H
H





XA582
CH3—


embedded image


H
H
H
H





XA583
CH3—


embedded image


H
H
H
H





XA584
CH3—


embedded image


H
H
H
H





XA585
CH3—


embedded image


H
H
H
H





XA586
CH3—


embedded image


H
H
H
H





XA587
CH3—


embedded image


H
H
H
H





XA588
CH3—


embedded image


H
H
H
H





XA589
CH3—


embedded image


H
H
H
H





XA590
CH3—


embedded image


H
H
H
H





XA591
CH3—


embedded image


H
H
H
H





XA592
CH3—


embedded image


H
H
H
H





XA593
CH3—


embedded image


H
H
H
H





XA594
CH3—


embedded image


H
H
H
H





XA595
CH3—


embedded image


H
H
H
H





XA596
CH3—


embedded image


H
H
H
H





XA597
CH3—


embedded image


H
H
H
H





XA598
CH3—


embedded image


H
H
H
H





XA599
CH3—


embedded image


H
H
H
H





XA600
CH3—


embedded image


H
H
H
H





XA601
CH3—


embedded image


H
H
H
H





XA602
CH3—


embedded image


H
H
H
H





XA603
CH3—


embedded image


H
H
H
H





XA604
CH3—


embedded image


H
H
H
H





XA605
CH3—


embedded image


H
H
H
H





XA606
CH3—


embedded image


H
H
H
H





XA607
CH3—


embedded image


H
H
H
H





XA608
CH3—


embedded image


H
H
H
H





XA609
CH3—


embedded image


H
H
H
H





XA610
CH3—


embedded image


H
H
H
H





XA611
CH3—


embedded image


H
H
H
H





XA612
CH3—


embedded image


H
H
H
H





XA613
CH3—


embedded image


H
H
H
H





XA614
CH3—


embedded image


H
H
H
H





XA615
CH3—


embedded image


H
H
H
H





XA616
CH3—


embedded image


H
H
H
H





XA617
CH3—


embedded image


H
H
H
H





XA618
CH3—


embedded image


H
H
H
H





XA619
CH3—


embedded image


H
H
H
H





XA620
CH3—


embedded image


H
H
H
H





XA621
CH3—


embedded image


H
H
H
H





XA622
CH3—


embedded image


H
H
H
H





XA623
CH3—
CH3—
H
CH3
H
H


XA624
CH3—
CH3CH2—
H
CH3
H
H





XA625
CH3—


embedded image


H
CH3
H
H





XA626
CH3—


embedded image


H
CH3
H
H





XA627
CH3—


embedded image


H
CH3
H
H





XA628
CH3—


embedded image


H
CH3
H
H





XA629
CH3—


embedded image


H
CH3
H
H





XA630
CH3—


embedded image


H
CH3
H
H





XA631
CH3—


embedded image


H
CH3
H
H





XA632
CH3—


embedded image


H
CH3
H
H





XA633
CH3—


embedded image


H
CH3
H
H





XA634
CH3—


embedded image


H
CH3
H
H





XA635
CH3—


embedded image


H
CH3
H
H





XA636
CH3—


embedded image


H
CH3
H
H





XA637
CH3—


embedded image


H
CH3
H
H





XA638
CH3—


embedded image


H
CH3
H
H





XA639
CH3—
n-C8H17—
H
CH3
H
H





XA640
CH3—


embedded image


H
CH3
H
H





XA641
CH3—


embedded image


H
CH3
H
H





XA642
CH3—


embedded image


H
CH3
H
H





XA643
CH3—


embedded image


H
CH3
H
H





XA644
CH3—


embedded image


H
CH3
H
H





XA645
CH3—


embedded image


H
CH3
H
H





XA646
CH3—


embedded image


H
CH3
H
H





XA647
CH3—


embedded image


H
CH3
H
H





XA648
CH3—


embedded image


H
CH3
H
H





XA649
CH3—


embedded image


H
CH3
H
H





XA650
CH3—


embedded image


H
CH3
H
H





XA651
CH3—


embedded image


H
CH3
H
H





XA652
CH3—


embedded image


H
CH3
H
H





XA653
CH3—


embedded image


H
CH3
H
H





XA654
CH3—


embedded image


H
CH3
H
H





XA655
CH3—


embedded image


H
CH3
H
H





XA656
CH3—


embedded image


H
CH3
H
H





XA657
CH3—


embedded image


H
CH3
H
H





XA658
CH3—


embedded image


H
CH3
H
H





XA659
CH3—


embedded image


H
CH3
H
H





XA660
CH3—


embedded image


H
CH3
H
H





XA661
CH3—


embedded image


H
CH3
H
H





XA662
CH3—


embedded image


H
CH3
H
H





XA663
CH3—


embedded image


H
CH3
H
H





XA664
CH3—


embedded image


H
CH3
H
H





XA665
CH3—


embedded image


H
CH3
H
H





XA666
CH3—


embedded image


H
CH3
H
H





XA667
CH3—


embedded image


H
CH3
H
H





XA668
CH3—


embedded image


H
CH3
H
H





XA669
CH3—


embedded image


H
CH3
H
H





XA670
CH3—


embedded image


H
CH3
H
H





XA671
CH3—


embedded image


H
CH3
H
H





XA672
CH3—


embedded image


H
CH3
H
H





XA673
CH3—


embedded image


H
CH3
H
H





XA674
CH3—


embedded image


H
CH3
H
H





XA675
CH3—


embedded image


H
CH3
H
H





XA676
CH3—


embedded image


H
CH3
H
H





XA677
CH3—


embedded image


H
CH3
H
H





XA678
CH3—


embedded image


H
CH3
H
H





XA679
CH3—


embedded image


H
CH3
H
H





XA680
CH3—


embedded image


H
CH3
H
H





XA681
CH3—


embedded image


H
CH3
H
H





XA682
CH3—


embedded image


H
CH3
H
H





XA683
CH3—


embedded image


H
CH3
H
H





XA684
CH3—


embedded image


H
CH3
H
H





XA685
CH3—


embedded image


H
CH3
H
H





XA686
CH3—


embedded image


H
CH3
H
H





XA687
CH3—


embedded image


H
CH3
H
H





XA688
CH3—


embedded image


H
CH3
H
H





XA689
CH3—


embedded image


H
CH3
H
H





XA690
CH3—


embedded image


H
CH3
H
H





XA691
CH3—


embedded image


H
CH3
H
H





XA692
CH3—


embedded image


H
CH3
H
H





XA693
CH3—


embedded image


H
CH3
H
H





XA694
CH3—


embedded image


H
CH3
H
H





XA695
CH3—


embedded image


H
CH3
H
H





XA696
CH3—


embedded image


H
CH3
H
H





XA697
CH3—


embedded image


H
CH3
H
H





XA698
CH3—


embedded image


H
CH3
H
H





XA699
CH3—


embedded image


H
CH3
H
H





XA700
CH3—


embedded image


H
CH3
H
H





XA701
CH3—


embedded image


H
CH3
H
H





XA702
CH3—


embedded image


H
CH3
H
H





XA703
CH3—


embedded image


H
CH3
H
H





XA704
CH3—


embedded image


H
CH3
H
H





XA705
CH3—


embedded image


H
CH3
H
H





XA706
CH3—


embedded image


H
CH3
H
H





XA707
CH3—


embedded image


H
CH3
H
H





XA708
CH3—


embedded image


H
CH3
H
H





XA709
CH3—


embedded image


H
CH3
H
H





XA710
CH3—


embedded image


H
CH3
H
H





XA711
CH3—


embedded image


H
CH3
H
H





XA712
CH3—


embedded image


H
CH3
H
H





XA713
CH3—


embedded image


H
CH3
H
H





XA714
CH3—


embedded image


H
CH3
H
H





XA715
CH3—


embedded image


H
CH3
H
H





XA716
CH3—


embedded image


H
CH3
H
H





XA717
CH3—


embedded image


H
CH3
H
H





XA718
CH3—


embedded image


H
CH3
H
H





XA719
CH3—


embedded image


H
CH3
H
H





XA720
CH3—


embedded image


H
CH3
H
H





XA721
CH3—


embedded image


H
CH3
H
H





XA722
CH3—


embedded image


H
CH3
H
H





XA723
CH3—


embedded image


H
CH3
H
H





XA724
CH3—


embedded image


H
CH3
H
H





XA725
CH3—


embedded image


H
CH3
H
H





XA726
CH3—


embedded image


H
CH3
H
H





XA727
CH3—


embedded image


H
CH3
H
H





XA728
CH3—


embedded image


H
CH3
H
H





XA729
CH3—


embedded image


H
CH3
H
H





XA730
CH3—


embedded image


H
CH3
H
H





XA731
CH3—


embedded image


H
CH3
H
H





XA732
CH3—


embedded image


H
CH3
H
H





XA733
CH3—


embedded image


H
CH3
H
H





XA734
CH3—


embedded image


H
CH3
H
H





XA735
CH3—


embedded image


H
CH3
H
H





XA736
CH3—


embedded image


H
CH3
H
H





XA737
CH3—


embedded image


H
CH3
H
H





XA738
CH3—


embedded image


H
CH3
H
H





XA739
CH3—


embedded image


H
CH3
H
H





XA740
CH3—


embedded image


H
CH3
H
H





XA741
CH3—


embedded image


H
CH3
H
H





XA742
CH3—


embedded image


H
CH3
H
H





XA743
CH3—


embedded image


H
CH3
H
H





XA744
CH3—


embedded image


H
CH3
H
H





XA745
CH3—


embedded image


H
CH3
H
H





XA746
CH3—


embedded image


H
CH3
H
H





XA747
CH3—


embedded image


H
CH3
H
H





XA748
CH3—


embedded image


H
CH3
H
H





XA749
CH3—


embedded image


H
CH3
H
H





XA750
CH3—


embedded image


H
CH3
H
H





XA751
CH3—


embedded image


H
CH3
H
H





XA752
CH3—


embedded image


H
CH3
H
H





XA753
CH3—


embedded image


H
CH3
H
H





XA754
CH3—


embedded image


H
CH3
H
H





XA755
CH3—


embedded image


H
CH3
H
H





XA756
CH3—


embedded image


H
CH3
H
H





XA757
CH3—


embedded image


H
CH3
H
H





XA758
CH3—


embedded image


H
CH3
H
H





XA759
CH3—


embedded image


H
CH3
H
H





XA760
CH3—


embedded image


H
CH3
H
H





XA761
CH3—


embedded image


H
CH3
H
H





XA762
CH3—


embedded image


H
CH3
H
H





XA763
CH3—


embedded image


H
CH3
H
H





XA764
CH3—


embedded image


H
CH3
H
H





XA765
CH3—


embedded image


H
CH3
H
H





XA766
CH3—


embedded image


H
CH3
H
H





XA767
CH3—


embedded image


H
CH3
H
H





XA768
CH3—


embedded image


H
CH3
H
H





XA769
CH3—


embedded image


H
CH3
H
H





XA770
CH3—


embedded image


H
CH3
H
H





XA771
CH3—


embedded image


H
CH3
H
H





XA772
CH3—


embedded image


H
CH3
H
H





XA773
CH3—


embedded image


H
CH3
H
H





XA774
CH3—


embedded image


H
CH3
H
H





XA775
CH3—


embedded image


H
CH3
H
H





XA776
CH3—


embedded image


H
CH3
H
H





XA777
CH3—


embedded image


H
CH3
H
H





XA778
CH3—


embedded image


H
CH3
H
H





XA779
CH3—


embedded image


H
CH3
H
H





XA780
CH3—


embedded image


H
CH3
H
H





XA781
CH3—


embedded image


H
CH3
H
H





XA782
CH3—


embedded image


H
CH3
H
H





XA783
CH3—


embedded image


H
CH3
H
H





XA784
CH3—


embedded image


H
CH3
H
H





XA785
CH3—


embedded image


H
CH3
H
H





XA786
CH3—


embedded image


H
CH3
H
H





XA787
CH3—


embedded image


H
CH3
H
H





XA788
CH3—


embedded image


H
CH3
H
H





XA789
CH3—


embedded image


H
CH3
H
H





XA790
CH3—


embedded image


H
CH3
H
H





XA791
CH3—


embedded image


H
CH3
H
H





XA792
CH3—


embedded image


H
CH3
H
H





XA793
CH3—


embedded image


H
CH3
H
H





XA794
CH3—


embedded image


H
CH3
H
H





XA795
CH3—


embedded image


H
CH3
H
H



























XA796
CH3—


embedded image


H
CH3
H
H





XA797
CH3—


embedded image


H
CH3
H
H





XA798
CH3—


embedded image


H
CH3
H
H





XA799
CH3—


embedded image


H
CH3
H
H





XA800
CH3—


embedded image


H
CH3
H
H





XA801
CH3—


embedded image


H
CH3
H
H





XA802
CH3—


embedded image


H
CH3
H
H





XA803
CH3—


embedded image


H
CH3
H
H





XA804
CH3—


embedded image


H
CH3
H
H





XA805
CH3—


embedded image


H
CH3
H
H





XA806
CH3—


embedded image


H
CH3
H
H





XA807
CH3—


embedded image


H
CH3
H
H





XA808
CH3—


embedded image


H
CH3
H
H





XA809
CH3—


embedded image


H
CH3
H
H





XA810
CH3—


embedded image


H
CH3
H
H





XA811
CH3—


embedded image


H
CH3
H
H





XA812
CH3—


embedded image


H
CH3
H
H





XA813
CH3—


embedded image


H
CH3
H
H





XA814
CH3—


embedded image


H
CH3
H
H





XA815
CH3—


embedded image


H
CH3
H
H





XA816
CH3—


embedded image


H
CH3
H
H





XA817
CH3—


embedded image


H
CH3
H
H





XA818
CH3—


embedded image


H
CH3
H
H





XA819
CH3—


embedded image


H
CH3
H
H





XA820
CH3—


embedded image


H
CH3
H
H





XA821
CH3—


embedded image


H
CH3
H
H





XA822
CH3—


embedded image


H
CH3
H
H





XA823
CH3—


embedded image


H
CH3
H
H





XA824
CH3—


embedded image


H
CH3
H
H





XA825
CH3—


embedded image


H
CH3
H
H





XA826
CH3—


embedded image


H
CH3
H
H





XA827
CH3—


embedded image


H
CH3
H
H





XA828
CH3—


embedded image


H
CH3
H
H





XA829
CH3—


embedded image


H
CH3
H
H





XA830
CH3—


embedded image


H
CH3
H
H





XA831
CH3—


embedded image


H
CH3
H
H





XA832
CH3—


embedded image


H
CH3
H
H





XA833
CH3—


embedded image


H
CH3
H
H





XA834
CH3—


embedded image


H
CH3
H
H





XA835
CH3—


embedded image


H
CH3
H
H





XA836
CH3—


embedded image


H
CH3
H
H





XA837
CH3—


embedded image


H
CH3
H
H





XA838
CH3—


embedded image


H
CH3
H
H





XA839
CH3—


embedded image


H
CH3
H
H





XA840
CH3—


embedded image


H
CH3
H
H





XA841
CH3—


embedded image


H
CH3
H
H





XA842
CH3—


embedded image


H
CH3
H
H





XA843
CH3—


embedded image


H
CH3
H
H





XA844
CH3—


embedded image


H
CH3
H
H





XA845
CH3—


embedded image


H
CH3
H
H





XA846
CH3—


embedded image


H
CH3
H
H





XA847
CH3—


embedded image


H
CH3
H
H





XA848
CH3—


embedded image


H
CH3
H
H





XA849
CH3—


embedded image


H
CH3
H
H





XA850
CH3—


embedded image


H
CH3
H
H





XA851
CH3—


embedded image


H
CH3
H
H





XA852
CH3—


embedded image


H
CH3
H
H





XA853
CH3—


embedded image


H
CH3
H
H





XA854
CH3—


embedded image


H
CH3
H
H





XA855
CH3—


embedded image


H
CH3
H
H





XA856
CH3—


embedded image


H
CH3
H
H





XA857
CH3—


embedded image


H
CH3
H
H





XA858
CH3—


embedded image


H
CH3
H
H





XA859
CH3—


embedded image


H
CH3
H
H





XA860
CH3—


embedded image


H
CH3
H
H





XA861
CH3—


embedded image


H
CH3
H
H





XA862
CH3—


embedded image


H
CH3
H
H





XA863
CH3—


embedded image


H
CH3
H
H





XA864
CH3—


embedded image


H
CH3
H
H





XA865
CH3—


embedded image


H
CH3
H
H





XA866
CH3—


embedded image


H
CH3
H
H





XA867
CH3—


embedded image


H
CH3
H
H





XA868
CH3—


embedded image


H
CH3
H
H





XA869
CH3—


embedded image


H
CH3
H
H





XA870
CH3—


embedded image


H
CH3
H
H





XA871
CH3—


embedded image


H
CH3
H
H





XA872
CH3—


embedded image


H
CH3
H
H





XA873
CH3—


embedded image


H
CH3
H
H





XA874
CH3—


embedded image


H
CH3
H
H





XA875
CH3—


embedded image


H
CH3
H
H





XA876
CH3—


embedded image


H
CH3
H
H





XA877
CH3—


embedded image


H
CH3
H
H





XA878
CH3—


embedded image


H
CH3
H
H





XA879
CH3—


embedded image


H
CH3
H
H





XA880
CH3—


embedded image


H
CH3
H
H





XA881
CH3—


embedded image


H
CH3
H
H





XA882
CH3—


embedded image


H
CH3
H
H





XA883
CH3—
CH3—
H


embedded image


H
H





XA884
CH3—
CH3CH2—
H


embedded image


H
H





XA885
CH3—


embedded image


H


embedded image


H
H





XA886
CH3—


embedded image


H


embedded image


H
H





XA887
CH3—


embedded image


H


embedded image


H
H





XA888
CH3—


embedded image


H


embedded image


H
H





XA889
CH3—


embedded image


H


embedded image


H
H





XA890
CH3—


embedded image


H


embedded image


H
H





XA891
CH3—


embedded image


H


embedded image


H
H





XA892
CH3—


embedded image


H


embedded image


H
H





XA893
CH3—


embedded image


H


embedded image


H
H





XA894
CH3—


embedded image


H


embedded image


H
H





XA895
CH3—


embedded image


H


embedded image


H
H





XA896
CH3—


embedded image


H


embedded image


H
H





XA897
CH3—


embedded image


H


embedded image


H
H





XA898
CH3—


embedded image


H


embedded image


H
H





XA899
CH3—
n-C8H17—
H


embedded image


H
H





XA900
CH3—


embedded image


H


embedded image


H
H





XA901
CH3—


embedded image


H


embedded image


H
H





XA902
CH3—


embedded image


H


embedded image


H
H





XA903
CH3—


embedded image


H


embedded image


H
H





XA904
CH3—


embedded image


H


embedded image


H
H





XA905
CH3—


embedded image


H


embedded image


H
H





XA906
CH3—


embedded image


H


embedded image


H
H





XA907
CH3—


embedded image


H


embedded image


H
H





XA908
CH3—


embedded image


H


embedded image


H
H





XA909
CH3—


embedded image


H


embedded image


H
H





XA910
CH3—


embedded image


H


embedded image


H
H





XA911
CH3—


embedded image


H


embedded image


H
H





XA912
CH3—


embedded image


H


embedded image


H
H





XA913
CH3—


embedded image


H


embedded image


H
H





XA914
CH3—


embedded image


H


embedded image


H
H





XA915
CH3—


embedded image


H


embedded image


H
H





XA916
CH3—


embedded image


H


embedded image


H
H





XA917
CH3—


embedded image


H


embedded image


H
H





XA918
CH3—


embedded image


H


embedded image


H
H





XA919
CH3—


embedded image


H


embedded image


H
H





XA920
CH3—


embedded image


H


embedded image


H
H





XA921
CH3—


embedded image


H


embedded image


H
H





XA922
CH3—


embedded image


H


embedded image


H
H





XA923
CH3—


embedded image


H


embedded image


H
H





XA924
CH3—


embedded image


H


embedded image


H
H





XA925
CH3—


embedded image


H


embedded image


H
H





XA926
CH3—


embedded image


H


embedded image


H
H





XA927
CH3—


embedded image


H


embedded image


H
H





XA928
CH3—


embedded image


H


embedded image


H
H





XA929
CH3—


embedded image


H


embedded image


H
H





XA930
CH3—


embedded image


H


embedded image


H
H





XA931
CH3—


embedded image


H


embedded image


H
H





XA932
CH3—


embedded image


H


embedded image


H
H





XA933
CH3—


embedded image


H


embedded image


H
H





XA934
CH3—


embedded image


H


embedded image


H
H





XA935
CH3—


embedded image


H


embedded image


H
H





XA936
CH3—


embedded image


H


embedded image


H
H





XA937
CH3—


embedded image


H


embedded image


H
H





XA938
CH3—


embedded image


H


embedded image


H
H





XA939
CH3—


embedded image


H


embedded image


H
H





XA940
CH3—


embedded image


H


embedded image


H
H





XA941
CH3—


embedded image


H


embedded image


H
H





XA942
CH3—


embedded image


H


embedded image


H
H





XA943
CH3—


embedded image


H


embedded image


H
H





XA944
CH3—


embedded image


H


embedded image


H
H





XA945
CH3—


embedded image


H


embedded image


H
H





XA946
CH3—


embedded image


H


embedded image


H
H





XA947
CH3—


embedded image


H


embedded image


H
H





XA948
CH3—


embedded image


H


embedded image


H
H





XA949
CH3—


embedded image


H


embedded image


H
H





XA950
CH3—


embedded image


H


embedded image


H
H





XA951
CH3—


embedded image


H


embedded image


H
H





XA952
CH3—


embedded image


H


embedded image


H
H





XA953
CH3—


embedded image


H


embedded image


H
H





XA954
CH3—


embedded image


H


embedded image


H
H





XA955
CH3—


embedded image


H


embedded image


H
H





XA956
CH3—


embedded image


H


embedded image


H
H





XA957
CH3—


embedded image


H


embedded image


H
H





XA958
CH3—


embedded image


H


embedded image


H
H





XA959
CH3—


embedded image


H


embedded image


H
H





XA960
CH3—


embedded image


H


embedded image


H
H





XA961
CH3—


embedded image


H


embedded image


H
H





XA962
CH3—


embedded image


H


embedded image


H
H





XA963
CH3—


embedded image


H


embedded image


H
H





XA964
CH3—


embedded image


H


embedded image


H
H





XA965
CH3—


embedded image


H


embedded image


H
H





XA966
CH3—


embedded image


H


embedded image


H
H





XA967
CH3—


embedded image


H


embedded image


H
H





XA968
CH3—


embedded image


H


embedded image


H
H





XA969
CH3—


embedded image


H


embedded image


H
H





XA970
CH3—


embedded image


H


embedded image


H
H





XA971
CH3—


embedded image


H


embedded image


H
H





XA972
CH3—


embedded image


H


embedded image


H
H





XA973
CH3—


embedded image


H


embedded image


H
H





XA974
CH3—


embedded image


H


embedded image


H
H





XA975
CH3—


embedded image


H


embedded image


H
H





XA976
CH3—


embedded image


H


embedded image


H
H





XA977
CH3—


embedded image


H


embedded image


H
H





XA978
CH3—


embedded image


H


embedded image


H
H





XA979
CH3—


embedded image


H


embedded image


H
H





XA980
CH3—


embedded image


H


embedded image


H
H





XA981
CH3—


embedded image


H


embedded image


H
H





XA982
CH3—


embedded image


H


embedded image


H
H





XA983
CH3—


embedded image


H


embedded image


H
H





XA984
CH3—


embedded image


H


embedded image


H
H





XA985
CH3—


embedded image


H


embedded image


H
H





XA986
CH3—


embedded image


H


embedded image


H
H





XA987
CH3—


embedded image


H


embedded image


H
H





XA988
CH3—


embedded image


H


embedded image


H
H





XA989
CH3—


embedded image


H


embedded image


H
H





XA990
CH3—


embedded image


H


embedded image


H
H





XA991
CH3—


embedded image


H


embedded image


H
H





XA992
CH3—


embedded image


H


embedded image


H
H





XA993
CH3—


embedded image


H


embedded image


H
H





XA994
CH3—


embedded image


H


embedded image


H
H





XA995
CH3—


embedded image


H


embedded image


H
H





XA996
CH3—


embedded image


H


embedded image


H
H





XA997
CH3—


embedded image


H


embedded image


H
H





XA998
CH3—


embedded image


H


embedded image


H
H





XA999
CH3—


embedded image


H


embedded image


H
H





XA1000
CH3—


embedded image


H


embedded image


H
H





XA1001
CH3—


embedded image


H


embedded image


H
H





XA1002
CH3—


embedded image


H


embedded image


H
H





XA1003
CH3—


embedded image


H


embedded image


H
H





XA1004
CH3—


embedded image


H


embedded image


H
H





XA1005
CH3—


embedded image


H


embedded image


H
H





XA1006
CH3—


embedded image


H


embedded image


H
H





XA1007
CH3—


embedded image


H


embedded image


H
H





XA1008
CH3—


embedded image


H


embedded image


H
H





XA1009
CH3—


embedded image


H


embedded image


H
H





XA1010
CH3—


embedded image


H


embedded image


H
H





XA1011
CH3—


embedded image


H


embedded image


H
H





XA1012
CH3—


embedded image


H


embedded image


H
H





XA1013
CH3—


embedded image


H


embedded image


H
H





XA1014
CH3—


embedded image


H


embedded image


H
H





XA1015
CH3—


embedded image


H


embedded image


H
H





XA1016
CH3—


embedded image


H


embedded image


H
H





XA1017
CH3—


embedded image


H


embedded image


H
H





XA1018
CH3—


embedded image


H


embedded image


H
H





XA1019
CH3—


embedded image


H


embedded image


H
H





XA1020
CH3—


embedded image


H


embedded image


H
H





XA1021
CH3—


embedded image


H


embedded image


H
H





XA1022
CH3—


embedded image


H


embedded image


H
H





XA1023
CH3—


embedded image


H


embedded image


H
H





XA1024
CH3—


embedded image


H


embedded image


H
H





XA1025
CH3—


embedded image


H


embedded image


H
H





XA1026
CH3—


embedded image


H


embedded image


H
H





XA1027
CH3—


embedded image


H


embedded image


H
H





XA1028
CH3—


embedded image


H


embedded image


H
H





XA1029
CH3—


embedded image


H


embedded image


H
H





XA1030
CH3—


embedded image


H


embedded image


H
H





XA1031
CH3—


embedded image


H


embedded image


H
H





XA1032
CH3—


embedded image


H


embedded image


H
H





XA1033
CH3—


embedded image


H


embedded image


H
H





XA1034
CH3—


embedded image


H


embedded image


H
H





XA1035
CH3—


embedded image


H


embedded image


H
H





XA1036
CH3—


embedded image


H


embedded image


H
H





XA1037
CH3—


embedded image


H


embedded image


H
H





XA1038
CH3—


embedded image


H


embedded image


H
H





XA1039
CH3—


embedded image


H


embedded image


H
H





XA1040
CH3—


embedded image


H


embedded image


H
H





XA1041
CH3—


embedded image


H


embedded image


H
H





XA1042
CH3—


embedded image


H


embedded image


H
H





XA1043
CH3—


embedded image


H


embedded image


H
H





XA1044
CH3—


embedded image


H


embedded image


H
H





XA1045
CH3—


embedded image


H


embedded image


H
H





XA1046
CH3—


embedded image


H


embedded image


H
H





XA1047
CH3—


embedded image


H


embedded image


H
H





XA1048
CH3—


embedded image


H


embedded image


H
H





XA1049
CH3—


embedded image


H


embedded image


H
H





XA1050
CH3—


embedded image


H


embedded image


H
H





XA1051
CH3—


embedded image


H


embedded image


H
H





XA1052
CH3—


embedded image


H


embedded image


H
H





XA1053
CH3—


embedded image


H


embedded image


H
H





XA1054
CH3—


embedded image


H


embedded image


H
H





XA1055
CH3—


embedded image


H


embedded image


H
H





XA1056
CH3—


embedded image


H


embedded image


H
H





XA1057
CH3—


embedded image


H


embedded image


H
H





XA1058
CH3—


embedded image


H


embedded image


H
H





XA1059
CH3—


embedded image


H


embedded image


H
H





XA1060
CH3—


embedded image


H


embedded image


H
H





XA1061
CH3—


embedded image


H


embedded image


H
H





XA1062
CH3—


embedded image


H


embedded image


H
H





XA1063
CH3—


embedded image


H


embedded image


H
H





XA1064
CH3—


embedded image


H


embedded image


H
H





XA1065
CH3—


embedded image


H


embedded image


H
H





XA1066
CH3—


embedded image


H


embedded image


H
H





XA1067
CH3—


embedded image


H


embedded image


H
H





XA1068
CH3—


embedded image


H


embedded image


H
H





XA1069
CH3—


embedded image


H


embedded image


H
H





XA1070
CH3—


embedded image


H


embedded image


H
H





XA1071
CH3—


embedded image


H


embedded image


H
H





XA1072
CH3—


embedded image


H


embedded image


H
H





XA1073
CH3—


embedded image


H


embedded image


H
H





XA1074
CH3—


embedded image


H


embedded image


H
H





XA1075
CH3—


embedded image


H


embedded image


H
H





XA1076
CH3—


embedded image


H


embedded image


H
H





XA1077
CH3—


embedded image


H


embedded image


H
H





XA1078
CH3—


embedded image


H


embedded image


H
H





XA1079
CH3—


embedded image


H


embedded image


H
H





XA1080
CH3—


embedded image


H


embedded image


H
H





XA1081
CH3—


embedded image


H


embedded image


H
H





XA1082
CH3—


embedded image


H


embedded image


H
H





XA1083
CH3—


embedded image


H


embedded image


H
H





XA1084
CH3—


embedded image


H


embedded image


H
H





XA1085
CH3—


embedded image


H


embedded image


H
H





XA1086
CH3—


embedded image


H


embedded image


H
H





XA1087
CH3—


embedded image


H


embedded image


H
H





XA1088
CH3—


embedded image


H


embedded image


H
H





XA1089
CH3—


embedded image


H


embedded image


H
H





XA1090
CH3—


embedded image


H


embedded image


H
H





XA1091
CH3—


embedded image


H


embedded image


H
H





XA1092
CH3—


embedded image


H


embedded image


H
H





XA1093
CH3—


embedded image


H


embedded image


H
H





XA1094
CH3—


embedded image


H


embedded image


H
H





XA1095
CH3—


embedded image


H


embedded image


H
H





XA1096
CH3—


embedded image


H


embedded image


H
H





XA1097
CH3—


embedded image


H


embedded image


H
H





XA1098
CH3—


embedded image


H


embedded image


H
H





XA1099
CH3—


embedded image


H


embedded image


H
H





XA1100
CH3—


embedded image


H


embedded image


H
H





XA1101
CH3—


embedded image


H


embedded image


H
H





XA1102
CH3—


embedded image


H


embedded image


H
H





XA1103
CH3—


embedded image


H


embedded image


H
H





XA1104
CH3—


embedded image


H


embedded image


H
H





XA1105
CH3—


embedded image


H


embedded image


H
H





XA1106
CH3—


embedded image


H


embedded image


H
H





XA1107
CH3—


embedded image


H


embedded image


H
H





XA1108
CH3—


embedded image


H


embedded image


H
H





XA1109
CH3—


embedded image


H


embedded image


H
H





XA1110
CH3—


embedded image


H


embedded image


H
H





XA1111
CH3—


embedded image


H


embedded image


H
H





XA1112
CH3—


embedded image


H


embedded image


H
H





XA1113
CH3—


embedded image


H


embedded image


H
H





XA1114
CH3—


embedded image


H


embedded image


H
H





XA1115
CH3—


embedded image


H


embedded image


H
H





XA1116
CH3—


embedded image


H


embedded image


H
H





XA1117
CH3—


embedded image


H


embedded image


H
H





XA1118
CH3—


embedded image


H


embedded image


H
H





XA1119
CH3—


embedded image


H


embedded image


H
H





XA1120
CH3—


embedded image


H


embedded image


H
H





XA1121
CH3—


embedded image


H


embedded image


H
H





XA1122
CH3—


embedded image


H


embedded image


H
H





XA1123
CH3—


embedded image


H


embedded image


H
H





XA1124
CH3—


embedded image


H


embedded image


H
H





XA1125
CH3—


embedded image


H


embedded image


H
H





XA1126
CH3—


embedded image


H


embedded image


H
H





XA1127
CH3—


embedded image


H


embedded image


H
H





XA1128
CH3—


embedded image


H


embedded image


H
H





XA1129
CH3—


embedded image


H


embedded image


H
H





XA1130
CH3—


embedded image


H


embedded image


H
H





XA1131
CH3—


embedded image


H


embedded image


H
H





XA1132
CH3—


embedded image


H


embedded image


H
H





XA1133
CH3—


embedded image


H


embedded image


H
H





XA1134
CH3—


embedded image


H


embedded image


H
H





XA1135
CH3—


embedded image


H


embedded image


H
H





XA1136
CH3—


embedded image


H


embedded image


H
H





XA1137
CH3—


embedded image


H


embedded image


H
H





XA1138
CH3—


embedded image


H


embedded image


H
H





XA1139
CH3—


embedded image


H


embedded image


H
H





XA1140
CH3—


embedded image


H


embedded image


H
H





XA1141
CH3—


embedded image


H


embedded image


H
H





XA1142
CH3—


embedded image


H


embedded image


H
H





XA1143
CH3—
CH3—
H


embedded image


H
H





XA1144
CH3—
CH3CH2—
H


embedded image


H
H





XA1145
CH3—


embedded image


H


embedded image


H
H





XA1146
CH3—


embedded image


H


embedded image


H
H





XA1147
CH3—


embedded image


H


embedded image


H
H





XA1148
CH3—


embedded image


H


embedded image


H
H





XA1149
CH3—


embedded image


H


embedded image


H
H





XA1150
CH3—


embedded image


H


embedded image


H
H





XA1151
CH3—


embedded image


H


embedded image


H
H





XA1152
CH3—


embedded image


H


embedded image


H
H





XA1153
CH3—


embedded image


H


embedded image


H
H





XA1154
CH3—


embedded image


H


embedded image


H
H





XA1155
CH3—


embedded image


H


embedded image


H
H





XA1156
CH3—


embedded image


H


embedded image


H
H





XA1157
CH3—


embedded image


H


embedded image


H
H





XA1158
CH3—


embedded image


H


embedded image


H
H





XA1159
CH3—
n-C8H17—
H


embedded image


H
H





XA1160
CH3—


embedded image


H


embedded image


H
H





XA1161
CH3—


embedded image


H


embedded image


H
H





XA1162
CH3—


embedded image


H


embedded image


H
H





XA1163
CH3—


embedded image


H


embedded image


H
H





XA1164
CH3—


embedded image


H


embedded image


H
H





XA1165
CH3—


embedded image


H


embedded image


H
H





XA1166
CH3—


embedded image


H


embedded image


H
H





XA1167
CH3—


embedded image


H


embedded image


H
H





XA1168
CH3—


embedded image


H


embedded image


H
H





XA1169
CH3—


embedded image


H


embedded image


H
H





XA1170
CH3—


embedded image


H


embedded image


H
H





XA1171
CH3—


embedded image


H


embedded image


H
H





XA1172
CH3—


embedded image


H


embedded image


H
H





XA1173
CH3—


embedded image


H


embedded image


H
H





XA1174
CH3—


embedded image


H


embedded image


H
H





XA1175
CH3—


embedded image


H


embedded image


H
H





XA1176
CH3—


embedded image


H


embedded image


H
H





XA1177
CH3—


embedded image


H


embedded image


H
H





XA1178
CH3—


embedded image


H


embedded image


H
H





XA1179
CH3—


embedded image


H


embedded image


H
H





XA1180
CH3—


embedded image


H


embedded image


H
H





XA1181
CH3—


embedded image


H


embedded image


H
H





XA1182
CH3—


embedded image


H


embedded image


H
H





XA1183
CH3—


embedded image


H


embedded image


H
H





XA1184
CH3—


embedded image


H


embedded image


H
H





XA1185
CH3—


embedded image


H


embedded image


H
H





XA1186
CH3—


embedded image


H


embedded image


H
H





XA1187
CH3—


embedded image


H


embedded image


H
H





XA1188
CH3—


embedded image


H


embedded image


H
H





XA1189
CH3—


embedded image


H


embedded image


H
H





XA1190
CH3—


embedded image


H


embedded image


H
H





XA1191
CH3—


embedded image


H


embedded image


H
H





XA1192
CH3—


embedded image


H


embedded image


H
H





XA1193
CH3—


embedded image


H


embedded image


H
H





XA1194
CH3—


embedded image


H


embedded image


H
H





XA1195
CH3—


embedded image


H


embedded image


H
H





XA1196
CH3—


embedded image


H


embedded image


H
H





XA1197
CH3—


embedded image


H


embedded image


H
H





XA1198
CH3—


embedded image


H


embedded image


H
H





XA1199
CH3—


embedded image


H


embedded image


H
H





XA1200
CH3—


embedded image


H


embedded image


H
H





XA1201
CH3—


embedded image


H


embedded image


H
H





XA1202
CH3—


embedded image


H


embedded image


H
H





XA1203
CH3—


embedded image


H


embedded image


H
H





XA1204
CH3—


embedded image


H


embedded image


H
H





XA1205
CH3—


embedded image


H


embedded image


H
H





XA1206
CH3—


embedded image


H


embedded image


H
H





XA1207
CH3—


embedded image


H


embedded image


H
H





XA1208
CH3—


embedded image


H


embedded image


H
H





XA1209
CH3—


embedded image


H


embedded image


H
H





XA1210
CH3—


embedded image


H


embedded image


H
H





XA1211
CH3—


embedded image


H


embedded image


H
H





XA1212
CH3—


embedded image


H


embedded image


H
H





XA1213
CH3—


embedded image


H


embedded image


H
H





XA1214
CH3—


embedded image


H


embedded image


H
H





XA1215
CH3—


embedded image


H


embedded image


H
H





XA1216
CH3—


embedded image


H


embedded image


H
H





XA1217
CH3—


embedded image


H


embedded image


H
H





XA1218
CH3—


embedded image


H


embedded image


H
H





XA1219
CH3—


embedded image


H


embedded image


H
H





XA1220
CH3—


embedded image


H


embedded image


H
H





XA1221
CH3—


embedded image


H


embedded image


H
H





XA1222
CH3—


embedded image


H


embedded image


H
H





XA1223
CH3—


embedded image


H


embedded image


H
H





XA1224
CH3—


embedded image


H


embedded image


H
H





XA1225
CH3—


embedded image


H


embedded image


H
H





XA1226
CH3—


embedded image


H


embedded image


H
H





XA1227
CH3—


embedded image


H


embedded image


H
H





XA1228
CH3—


embedded image


H


embedded image


H
H





XA1229
CH3—


embedded image


H


embedded image


H
H





XA1230
CH3—


embedded image


H


embedded image


H
H





XA1231
CH3—


embedded image


H


embedded image


H
H





XA1232
CH3—


embedded image


H


embedded image


H
H





XA1233
CH3—


embedded image


H


embedded image


H
H





XA1234
CH3—


embedded image


H


embedded image


H
H





XA1235
CH3—


embedded image


H


embedded image


H
H





XA1236
CH3—


embedded image


H


embedded image


H
H





XA1237
CH3—


embedded image


H


embedded image


H
H





XA1238
CH3—


embedded image


H


embedded image


H
H





XA1239
CH3—


embedded image


H


embedded image


H
H





XA1240
CH3—


embedded image


H


embedded image


H
H





XA1241
CH3—


embedded image


H


embedded image


H
H





XA1242
CH3—


embedded image


H


embedded image


H
H





XA1243
CH3—


embedded image


H


embedded image


H
H





XA1244
CH3—


embedded image


H


embedded image


H
H





XA1245
CH3—


embedded image


H


embedded image


H
H





XA1246
CH3—


embedded image


H


embedded image


H
H





XA1247
CH3—


embedded image


H


embedded image


H
H





XA1248
CH3—


embedded image


H


embedded image


H
H





XA1249
CH3—


embedded image


H


embedded image


H
H





XA1250
CH3—


embedded image


H


embedded image


H
H





XA1251
CH3—


embedded image


H


embedded image


H
H





XA1252
CH3—


embedded image


H


embedded image


H
H





XA1253
CH3—


embedded image


H


embedded image


H
H





XA1254
CH3—


embedded image


H


embedded image


H
H





XA1255
CH3—


embedded image


H


embedded image


H
H





XA1256
CH3—


embedded image


H


embedded image


H
H





XA1257
CH3—


embedded image


H


embedded image


H
H





XA1258
CH3—


embedded image


H


embedded image


H
H





XA1259
CH3—


embedded image


H


embedded image


H
H





XA1260
CH3—


embedded image


H


embedded image


H
H





XA1261
CH3—


embedded image


H


embedded image


H
H





XA1262
CH3—


embedded image


H


embedded image


H
H





XA1263
CH3—


embedded image


H


embedded image


H
H





XA1264
CH3—


embedded image


H


embedded image


H
H





XA1265
CH3—


embedded image


H


embedded image


H
H





XA1266
CH3—


embedded image


H


embedded image


H
H





XA1267
CH3—


embedded image


H


embedded image


H
H





XA1268
CH3—


embedded image


H


embedded image


H
H





XA1269
CH3—


embedded image


H


embedded image


H
H





XA1270
CH3—


embedded image


H


embedded image


H
H





XA1271
CH3—


embedded image


H


embedded image


H
H





XA1272
CH3—


embedded image


H


embedded image


H
H





XA1273
CH3—


embedded image


H


embedded image


H
H





XA1274
CH3—


embedded image


H


embedded image


H
H





XA1275
CH3—


embedded image


H


embedded image


H
H





XA1276
CH3—


embedded image


H


embedded image


H
H





XA1277
CH3—


embedded image


H


embedded image


H
H





XA1278
CH3—


embedded image


H


embedded image


H
H





XA1279
CH3—


embedded image


H


embedded image


H
H





XA1280
CH3—


embedded image


H


embedded image


H
H





XA1281
CH3—


embedded image


H


embedded image


H
H





XA1282
CH3—


embedded image


H


embedded image


H
H





XA1283
CH3—


embedded image


H


embedded image


H
H





XA1284
CH3—


embedded image


H


embedded image


H
H





XA1285
CH3—


embedded image


H


embedded image


H
H





XA1286
CH3—


embedded image


H


embedded image


H
H





XA1287
CH3—


embedded image


H


embedded image


H
H





XA1288
CH3—


embedded image


H


embedded image


H
H





XA1289
CH3—


embedded image


H


embedded image


H
H





XA1290
CH3—


embedded image


H


embedded image


H
H





XA1291
CH3—


embedded image


H


embedded image


H
H





XA1292
CH3—


embedded image


H


embedded image


H
H





XA1293
CH3—


embedded image


H


embedded image


H
H





XA1294
CH3—


embedded image


H


embedded image


H
H





XA1295
CH3—


embedded image


H


embedded image


H
H





XA1296
CH3—


embedded image


H


embedded image


H
H





XA1297
CH3—


embedded image


H


embedded image


H
H





XA1298
CH3—


embedded image


H


embedded image


H
H





XA1299
CH3—


embedded image


H


embedded image


H
H





XA1300
CH3—


embedded image


H


embedded image


H
H





XA1301
CH3—


embedded image


H


embedded image


H
H





XA1302
CH3—


embedded image


H


embedded image


H
H





XA1303
CH3—


embedded image


H


embedded image


H
H





XA1304
CH3—


embedded image


H


embedded image


H
H





XA1305
CH3—


embedded image


H


embedded image


H
H





XA1306
CH3—


embedded image


H


embedded image


H
H





XA1307
CH3—


embedded image


H


embedded image


H
H





XA1308
CH3—


embedded image


H


embedded image


H
H





XA1309
CH3—


embedded image


H


embedded image


H
H





XA1310
CH3—


embedded image


H


embedded image


H
H





XA1311
CH3—


embedded image


H


embedded image


H
H





XA1312
CH3—


embedded image


H


embedded image


H
H





XA1313
CH3—


embedded image


H


embedded image


H
H





XA1314
CH3—


embedded image


H


embedded image


H
H





XA1315
CH3—


embedded image


H


embedded image


H
H





XA1316
CH3—


embedded image


H


embedded image


H
H





XA1317
CH3—


embedded image


H


embedded image


H
H





XA1318
CH3—


embedded image


H


embedded image


H
H





XA1319
CH3—


embedded image


H


embedded image


H
H





XA1320
CH3—


embedded image


H


embedded image


H
H





XA1321
CH3—


embedded image


H


embedded image


H
H





XA1322
CH3—


embedded image


H


embedded image


H
H





XA1323
CH3—


embedded image


H


embedded image


H
H





XA1324
CH3—


embedded image


H


embedded image


H
H





XA1325
CH3—


embedded image


H


embedded image


H
H





XA1326
CH3—


embedded image


H


embedded image


H
H





XA1327
CH3—


embedded image


H


embedded image


H
H





XA1328
CH3—


embedded image


H


embedded image


H
H





XA1329
CH3—


embedded image


H


embedded image


H
H





XA1330
CH3—


embedded image


H


embedded image


H
H





XA1331
CH3—


embedded image


H


embedded image


H
H





XA1332
CH3—


embedded image


H


embedded image


H
H





XA1333
CH3—


embedded image


H


embedded image


H
H





XA1334
CH3—


embedded image


H


embedded image


H
H





XA1335
CH3—


embedded image


H


embedded image


H
H





XA1336
CH3—


embedded image


H


embedded image


H
H





XA1337
CH3—


embedded image


H


embedded image


H
H





XA1338
CH3—


embedded image


H


embedded image


H
H





XA1339
CH3—


embedded image


H


embedded image


H
H





XA1340
CH3—


embedded image


H


embedded image


H
H





XA1341
CH3—


embedded image


H


embedded image


H
H





XA1342
CH3—


embedded image


H


embedded image


H
H





XA1343
CH3—


embedded image


H


embedded image


H
H





XA1344
CH3—


embedded image


H


embedded image


H
H





XA1345
CH3—


embedded image


H


embedded image


H
H





XA1346
CH3—


embedded image


H


embedded image


H
H





XA1347
CH3—


embedded image


H


embedded image


H
H





XA1348
CH3—


embedded image


H


embedded image


H
H





XA1349
CH3—


embedded image


H


embedded image


H
H





XA1350
CH3—


embedded image


H


embedded image


H
H





XA1351
CH3—


embedded image


H


embedded image


H
H





XA1352
CH3—


embedded image


H


embedded image


H
H





XA1353
CH3—


embedded image


H


embedded image


H
H





XA1354
CH3—


embedded image


H


embedded image


H
H





XA1355
CH3—


embedded image


H


embedded image


H
H





XA1356
CH3—


embedded image


H


embedded image


H
H





XA1357
CH3—


embedded image


H


embedded image


H
H





XA1358
CH3—


embedded image


H


embedded image


H
H





XA1359
CH3—


embedded image


H


embedded image


H
H





XA1360
CH3—


embedded image


H


embedded image


H
H





XA1361
CH3—


embedded image


H


embedded image


H
H





XA1362
CH3—


embedded image


H


embedded image


H
H





XA1363
CH3—


embedded image


H


embedded image


H
H





XA1364
CH3—


embedded image


H


embedded image


H
H





XA1365
CH3—


embedded image


H


embedded image


H
H





XA1366
CH3—


embedded image


H


embedded image


H
H





XA1367
CH3—


embedded image


H


embedded image


H
H





XA1368
CH3—


embedded image


H


embedded image


H
H





XA1369
CH3—


embedded image


H


embedded image


H
H





XA1370
CH3—


embedded image


H


embedded image


H
H





XA1371
CH3—


embedded image


H


embedded image


H
H





XA1372
CH3—


embedded image


H


embedded image


H
H





XA1373
CH3—


embedded image


H


embedded image


H
H





XA1374
CH3—


embedded image


H


embedded image


H
H





XA1375
CH3—


embedded image


H


embedded image


H
H





XA1376
CH3—


embedded image


H


embedded image


H
H





XA1377
CH3—


embedded image


H


embedded image


H
H





XA1378
CH3—


embedded image


H


embedded image


H
H





XA1379
CH3—


embedded image


H


embedded image


H
H





XA1380
CH3—


embedded image


H


embedded image


H
H





XA1381
CH3—


embedded image


H


embedded image


H
H





XA1382
CH3—


embedded image


H


embedded image


H
H





XA1383
CH3—


embedded image


H


embedded image


H
H





XA1384
CH3—


embedded image


H


embedded image


H
H





XA1385
CH3—


embedded image


H


embedded image


H
H





XA1386
CH3—


embedded image


H


embedded image


H
H





XA1387
CH3—


embedded image


H


embedded image


H
H





XA1388
CH3—


embedded image


H


embedded image


H
H





XA1389
CH3—


embedded image


H


embedded image


H
H





XA1390
CH3—


embedded image


H


embedded image


H
H





XA1391
CH3—


embedded image


H


embedded image


H
H





XA1392
CH3—


embedded image


H


embedded image


H
H





XA1393
CH3—


embedded image


H


embedded image


H
H





XA1394
CH3—


embedded image


H


embedded image


H
H





XA1395
CH3—


embedded image


H


embedded image


H
H





XA1396
CH3—


embedded image


H


embedded image


H
H





XA1397
CH3—


embedded image


H


embedded image


H
H





XA1398
CH3—


embedded image


H


embedded image


H
H





XA1399
CH3—


embedded image


H


embedded image


H
H





XA1400
CH3—


embedded image


H


embedded image


H
H





XA1401
CH3—


embedded image


H


embedded image


H
H





XA1402
CH3—


embedded image


H


embedded image


H
H





XA1403
CH3—
CH3—
CH3—
H
H
H


XA1404
CH3—
CH3CH2—
CH3—
H
H
H





XA1405
CH3—


embedded image


CH3—
H
H
H





XA1406
CH3—


embedded image


CH3—
H
H
H





XA1407
CH3—


embedded image


CH3—
H
H
H





XA1408
CH3—


embedded image


CH3—
H
H
H





XA1409
CH3—


embedded image


CH3—
H
H
H





XA1410
CH3—


embedded image


CH3—
H
H
H





XA1411
CH3—


embedded image


CH3—
H
H
H





XA1412
CH3—


embedded image


CH3—
H
H
H





XA1413
CH3—


embedded image


CH3—
H
H
H





XA1414
CH3—


embedded image


CH3—
H
H
H





XA1415
CH3—


embedded image


CH3—
H
H
H





XA1416
CH3—


embedded image


CH3—
H
H
H





XA1417
CH3—


embedded image


CH3—
H
H
H





XA1418
CH3—


embedded image


CH3—
H
H
H





XA1419
CH3—
n-C8H17—
CH3—
H
H
H





XA1420
CH3—


embedded image


CH3—
H
H
H





XA1421
CH3—


embedded image


CH3—
H
H
H





XA1422
CH3—


embedded image


CH3—
H
H
H





XA1423
CH3—


embedded image


CH3—
H
H
H





XA1424
CH3—


embedded image


CH3—
H
H
H





XA1425
CH3—


embedded image


CH3—
H
H
H





XA1426
CH3—


embedded image


CH3—
H
H
H





XA1427
CH3—


embedded image


CH3—
H
H
H





XA1428
CH3—


embedded image


CH3—
H
H
H





XA1429
CH3—


embedded image


CH3—
H
H
H





XA1430
CH3—


embedded image


CH3—
H
H
H





XA1431
CH3—


embedded image


CH3—
H
H
H





XA1432
CH3—


embedded image


CH3—
H
H
H





XA1433
CH3—


embedded image


CH3—
H
H
H





XA1434
CH3—


embedded image


CH3—
H
H
H





XA1435
CH3—


embedded image


CH3—
H
H
H





XA1436
CH3—


embedded image


CH3—
H
H
H





XA1437
CH3—


embedded image


CH3—
H
H
H





XA1438
CH3—


embedded image


CH3—
H
H
H





XA1439
CH3—


embedded image


CH3—
H
H
H





XA1440
CH3—


embedded image


CH3—
H
H
H





XA1441
CH3—


embedded image


CH3—
H
H
H





XA1442
CH3—


embedded image


CH3—
H
H
H





XA1443
CH3—


embedded image


CH3—
H
H
H





XA1444
CH3—


embedded image


CH3—
H
H
H





XA1445
CH3—


embedded image


CH3—
H
H
H





XA1446
CH3—


embedded image


CH3—
H
H
H





XA1447
CH3—


embedded image


CH3—
H
H
H





XA1448
CH3—


embedded image


CH3—
H
H
H





XA1449
CH3—


embedded image


CH3—
H
H
H





XA1450
CH3—


embedded image


CH3—
H
H
H





XA1451
CH3—


embedded image


CH3—
H
H
H





XA1452
CH3—


embedded image


CH3—
H
H
H





XA1453
CH3—


embedded image


CH3—
H
H
H





XA1454
CH3—


embedded image


CH3—
H
H
H





XA1455
CH3—


embedded image


CH3—
H
H
H





XA1456
CH3—


embedded image


CH3—
H
H
H





XA1457
CH3—


embedded image


CH3—
H
H
H





XA1458
CH3—


embedded image


CH3—
H
H
H





XA1459
CH3—


embedded image


CH3—
H
H
H





XA1460
CH3—


embedded image


CH3—
H
H
H





XA1461
CH3—


embedded image


CH3—
H
H
H





XA1462
CH3—


embedded image


CH3—
H
H
H





XA1463
CH3—


embedded image


CH3—
H
H
H





XA1464
CH3—


embedded image


CH3—
H
H
H





XA1465
CH3—


embedded image


CH3—
H
H
H





XA1466
CH3—


embedded image


CH3—
H
H
H





XA1467
CH3—


embedded image


CH3—
H
H
H





XA1468
CH3—


embedded image


CH3—
H
H
H





XA1469
CH3—


embedded image


CH3—
H
H
H





XA1470
CH3—


embedded image


CH3—
H
H
H





XA1471
CH3—


embedded image


CH3—
H
H
H





XA1472
CH3—


embedded image


CH3—
H
H
H





XA1473
CH3—


embedded image


CH3—
H
H
H





XA1474
CH3—


embedded image


CH3—
H
H
H





XA1475
CH3—


embedded image


CH3—
H
H
H





XA1476
CH3—


embedded image


CH3—
H
H
H





XA1477
CH3—


embedded image


CH3—
H
H
H





XA1478
CH3—


embedded image


CH3—
H
H
H





XA1479
CH3—


embedded image


CH3—
H
H
H





XA1480
CH3—


embedded image


CH3—
H
H
H





XA1481
CH3—


embedded image


CH3—
H
H
H





XA1482
CH3—


embedded image


CH3—
H
H
H





XA1483
CH3—


embedded image


CH3—
H
H
H





XA1484
CH3—


embedded image


CH3—
H
H
H





XA1485
CH3—


embedded image


CH3—
H
H
H





XA1486
CH3—


embedded image


CH3—
H
H
H





XA1487
CH3—


embedded image


CH3—
H
H
H





XA1488
CH3—


embedded image


CH3—
H
H
H





XA1489
CH3—


embedded image


CH3—
H
H
H





XA1490
CH3—


embedded image


CH3—
H
H
H





XA1491
CH3—


embedded image


CH3—
H
H
H





XA1492
CH3—


embedded image


CH3—
H
H
H





XA1493
CH3—


embedded image


CH3—
H
H
H





XA1494
CH3—


embedded image


CH3—
H
H
H





XA1495
CH3—


embedded image


CH3—
H
H
H





XA1496
CH3—


embedded image


CH3—
H
H
H





XA1497
CH3—


embedded image


CH3—
H
H
H





XA1498
CH3—
CH3—
H
H
CH3—
H


XA1499
CH3—
CH3CH2—
H
H
CH3—
H





XA1500
CH3—


embedded image


H
H
CH3—
H





XA1501
CH3—


embedded image


H
H
CH3—
H





XA1502
CH3—


embedded image


H
H
CH3—
H





XA1503
CH3—


embedded image


H
H
CH3—
H





XA1504
CH3—


embedded image


H
H
CH3—
H





XA1505
CH3—


embedded image


H
H
CH3—
H





XA1506
CH3—


embedded image


H
H
CH3—
H





XA1507
CH3—


embedded image


H
H
CH3—
H





XA1508
CH3—


embedded image


H
H
CH3—
H





XA1509
CH3—


embedded image


H
H
CH3—
H





XA1510
CH3—


embedded image


H
H
CH3—
H





XA1511
CH3—


embedded image


H
H
CH3—
H





XA1512
CH3—


embedded image


H
H
CH3—
H





XA1513
CH3—


embedded image


H
H
CH3—
H





XA1514
CH3—
n-C8H17—
H
H
CH3—
H





XA1515
CH3—


embedded image


H
H
CH3—
H





XA1516
CH3—


embedded image


H
H
CH3—
H





XA1517
CH3—


embedded image


H
H
CH3—
H





XA1518
CH3—


embedded image


H
H
CH3—
H





XA1519
CH3—


embedded image


H
H
CH3—
H





XA1520
CH3—


embedded image


H
H
CH3—
H



























XA1521
CH3—


embedded image


H
H
CH3—
H





XA1522
CH3—


embedded image


H
H
CH3—
H





XA1523
CH3—


embedded image


H
H
CH3—
H





XA1524
CH3—


embedded image


H
H
CH3—
H





XA1525
CH3—


embedded image


H
H
CH3—
H





XA1526
CH3—


embedded image


H
H
CH3—
H





XA1527
CH3—


embedded image


H
H
CH3—
H





XA1528
CH3—


embedded image


H
H
CH3—
H





XA1529
CH3—


embedded image


H
H
CH3—
H





XA1530
CH3—


embedded image


H
H
CH3—
H





XA1531
CH3—


embedded image


H
H
CH3—
H





XA1532
CH3—


embedded image


H
H
CH3—
H





XA1533
CH3—


embedded image


H
H
CH3—
H





XA1534
CH3—


embedded image


H
H
CH3—
H





XA1535
CH3—


embedded image


H
H
CH3—
H





XA1536
CH3—


embedded image


H
H
CH3—
H





XA1537
CH3—


embedded image


H
H
CH3—
H





XA1538
CH3—


embedded image


H
H
CH3—
H





XA1539
CH3—


embedded image


H
H
CH3—
H





XA1540
CH3—


embedded image


H
H
CH3—
H





XA1541
CH3—


embedded image


H
H
CH3—
H





XA1542
CH3—


embedded image


H
H
CH3—
H





XA1543
CH3—


embedded image


H
H
CH3—
H





XA1544
CH3—


embedded image


H
H
CH3—
H





XA1545
CH3—


embedded image


H
H
CH3—
H





XA1546
CH3—


embedded image


H
H
CH3—
H





XA1547
CH3—


embedded image


H
H
CH3—
H





XA1548
CH3—


embedded image


H
H
CH3—
H





XA1549
CH3—


embedded image


H
H
CH3—
H





XA1550
CH3—


embedded image


H
H
CH3—
H





XA1551
CH3—


embedded image


H
H
CH3—
H





XA1552
CH3—


embedded image


H
H
CH3—
H





XA1553
CH3—


embedded image


H
H
CH3—
H





XA1554
CH3—


embedded image


H
H
CH3—
H





XA1555
CH3—


embedded image


H
H
CH3—
H





XA1556
CH3—


embedded image


H
H
CH3—
H





XA1557
CH3—


embedded image


H
H
CH3—
H





XA1558
CH3—


embedded image


H
H
CH3—
H





XA1559
CH3—


embedded image


H
H
CH3—
H





XA1560
CH3—


embedded image


H
H
CH3—
H





XA1561
CH3—


embedded image


H
H
CH3—
H





XA1562
CH3—


embedded image


H
H
CH3—
H





XA1563
CH3—


embedded image


H
H
CH3—
H





XA1564
CH3—


embedded image


H
H
CH3—
H





XA1565
CH3—


embedded image


H
H
CH3—
H





XA1566
CH3—


embedded image


H
H
CH3—
H





XA1567
CH3—


embedded image


H
H
CH3—
H





XA1568
CH3—


embedded image


H
H
CH3—
H





XA1569
CH3—


embedded image


H
H
CH3—
H





XA1570
CH3—


embedded image


H
H
CH3—
H





XA1571
CH3—


embedded image


H
H
CH3—
H





XA1572
CH3—


embedded image


H
H
CH3—
H





XA1573
CH3—


embedded image


H
H
CH3—
H





XA1574
CH3—


embedded image


H
H
CH3—
H





XA1575
CH3—


embedded image


H
H
CH3—
H





XA1576
CH3—


embedded image


H
H
CH3—
H





XA1577
CH3—


embedded image


H
H
CH3—
H





XA1578
CH3—


embedded image


H
H
CH3—
H





XA1579
CH3—


embedded image


H
H
CH3—
H





XA1580
CH3—


embedded image


H
H
CH3—
H





XA1581
CH3—


embedded image


H
H
CH3—
H





XA1582
CH3—


embedded image


H
H
CH3—
H





XA1583
CH3—


embedded image


H
H
CH3—
H





XA1584
CH3—


embedded image


H
H
CH3—
H





XA1585
CH3—


embedded image


H
H
CH3—
H





XA1586
CH3—


embedded image


H
H
CH3—
H





XA1587
CH3—


embedded image


H
H
CH3—
H





XA1588
CH3—


embedded image


H
H
CH3—
H





XA1589
CH3—


embedded image


H
H
CH3—
H





XA1590
CH3—


embedded image


H
H
CH3—
H





XA1591
CH3—


embedded image


H
H
CH3—
H





XA1592
CH3—


embedded image


H
H
CH3—
H





XA1593
CH3—
CH3—
H
H
CH3—
CH3—


XA1594
CH3—
CH3CH2—
H
H
CH3—
CH3—





XA1595
CH3—


embedded image


H
H
CH3—
CH3—





XA1596
CH3—


embedded image


H
H
CH3—
CH3—





XA1597
CH3—


embedded image


H
H
CH3—
CH3—





XA1598
CH3—


embedded image


H
H
CH3—
CH3—





XA1599
CH3—


embedded image


H
H
CH3—
CH3—





XA1600
CH3—


embedded image


H
H
CH3—
CH3—





XA1601
CH3—


embedded image


H
H
CH3—
CH3—





XA1602
CH3—


embedded image


H
H
CH3—
CH3—





XA1603
CH3—


embedded image


H
H
CH3—
CH3—





XA1604
CH3—


embedded image


H
H
CH3—
CH3—





XA1605
CH3—


embedded image


H
H
CH3—
CH3—





XA1606
CH3—


embedded image


H
H
CH3—
CH3—





XA1607
CH3—


embedded image


H
H
CH3—
CH3—





XA1608
CH3—


embedded image


H
H
CH3—
CH3—





XA1609
CH3—
n-C8H17—
H
H
CH3—
CH3—





XA1610
CH3—


embedded image


H
H
CH3—
CH3—





XA1611
CH3—


embedded image


H
H
CH3—
CH3—





XA1612
CH3—


embedded image


H
H
CH3—
CH3—





XA1613
CH3—


embedded image


H
H
CH3—
CH3—





XA1614
CH3—


embedded image


H
H
CH3—
CH3—





XA1615
CH3—


embedded image


H
H
CH3—
CH3—





XA1616
CH3—


embedded image


H
H
CH3—
CH3—





XA1617
CH3—


embedded image


H
H
CH3—
CH3—





XA1618
CH3—


embedded image


H
H
CH3—
CH3—





XA1619
CH3—


embedded image


H
H
CH3—
CH3—





XA1620
CH3—


embedded image


H
H
CH3—
CH3—





XA1621
CH3—


embedded image


H
H
CH3—
CH3—





XA1622
CH3—


embedded image


H
H
CH3—
CH3—





XA1623
CH3—


embedded image


H
H
CH3—
CH3—





XA1624
CH3—


embedded image


H
H
CH3—
CH3—





XA1625
CH3—


embedded image


H
H
CH3—
CH3—





XA1626
CH3—


embedded image


H
H
CH3—
CH3—





XA1627
CH3—


embedded image


H
H
CH3—
CH3—





XA1628
CH3—


embedded image


H
H
CH3—
CH3—





XA1629
CH3—


embedded image


H
H
CH3—
CH3—





XA1630
CH3—


embedded image


H
H
CH3—
CH3—





XA1631
CH3—


embedded image


H
H
CH3—
CH3—





XA1632
CH3—


embedded image


H
H
CH3—
CH3—





XA1633
CH3—


embedded image


H
H
CH3—
CH3—





XA1634
CH3—


embedded image


H
H
CH3—
CH3—





XA1635
CH3—


embedded image


H
H
CH3—
CH3—





XA1636
CH3—


embedded image


H
H
CH3—
CH3—





XA1637
CH3—


embedded image


H
H
CH3—
CH3—





XA1638
CH3—


embedded image


H
H
CH3—
CH3—





XA1639
CH3—


embedded image


H
H
CH3—
CH3—





XA1640
CH3—


embedded image


H
H
CH3—
CH3—





XA1641
CH3—


embedded image


H
H
CH3—
CH3—





XA1642
CH3—


embedded image


H
H
CH3—
CH3—





XA1643
CH3—


embedded image


H
H
CH3—
CH3—





XA1644
CH3—


embedded image


H
H
CH3—
CH3—





XA1645
CH3—


embedded image


H
H
CH3—
CH3—





XA1646
CH3—


embedded image


H
H
CH3—
CH3—





XA1647
CH3—


embedded image


H
H
CH3—
CH3—





XA1648
CH3—


embedded image


H
H
CH3—
CH3—





XA1649
CH3—


embedded image


H
H
CH3—
CH3—





XA1650
CH3—


embedded image


H
H
CH3—
CH3—





XA1651
CH3—


embedded image


H
H
CH3—
CH3—





XA1652
CH3—


embedded image


H
H
CH3—
CH3—





XA1653
CH3—


embedded image


H
H
CH3—
CH3—





XA1654
CH3—


embedded image


H
H
CH3—
CH3—





XA1655
CH3—


embedded image


H
H
CH3—
CH3—





XA1656
CH3—


embedded image


H
H
CH3—
CH3—





XA1657
CH3—


embedded image


H
H
CH3—
CH3—





XA1658
CH3—


embedded image


H
H
CH3—
CH3—





XA1659
CH3—


embedded image


H
H
CH3—
CH3—





XA1660
CH3—


embedded image


H
H
CH3—
CH3—





XA1661
CH3—


embedded image


H
H
CH3—
CH3—





XA1662
CH3—


embedded image


H
H
CH3—
CH3—





XA1663
CH3—


embedded image


H
H
CH3—
CH3—





XA1664
CH3—


embedded image


H
H
CH3—
CH3—





XA1665
CH3—


embedded image


H
H
CH3—
CH3—





XA1666
CH3—


embedded image


H
H
CH3—
CH3—





XA1667
CH3—


embedded image


H
H
CH3—
CH3—





XA1668
CH3—


embedded image


H
H
CH3—
CH3—





XA1669
CH3—


embedded image


H
H
CH3—
CH3—





XA1670
CH3—


embedded image


H
H
CH3—
CH3—





XA1671
CH3—


embedded image


H
H
CH3—
CH3—





XA1672
CH3—


embedded image


H
H
CH3—
CH3—





XA1673
CH3—


embedded image


H
H
CH3—
CH3—





XA1674
CH3—


embedded image


H
H
CH3—
CH3—





XA1675
CH3—


embedded image


H
H
CH3—
CH3—





XA1676
CH3—


embedded image


H
H
CH3—
CH3—





XA1677
CH3—


embedded image


H
H
CH3—
CH3—





XA1678
CH3—


embedded image


H
H
CH3—
CH3—





XA1679
CH3—


embedded image


H
H
CH3—
CH3—





XA1680
CH3—


embedded image


H
H
CH3—
CH3—





XA1681
CH3—


embedded image


H
H
CH3—
CH3—





XA1682
CH3—


embedded image


H
H
CH3—
CH3—





XA1683
CH3—


embedded image


H
H
CH3—
CH3—





XA1684
CH3—


embedded image


H
H
CH3—
CH3—





XA1685
CH3—


embedded image


H
H
CH3—
CH3—





XA1686
CH3—


embedded image


H
H
CH3—
CH3—





XA1687
CH3—


embedded image


H
H
CH3—
CH3—





XA1688
CH3—
CH3—
H
CH3—
CH3—
CH3—


XA1689
CH3—
CH3CH2—
H
CH3—
CH3—
CH3—





XA1690
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1691
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1692
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1693
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1694
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1695
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1696
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1697
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1698
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1699
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1700
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1701
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1702
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1703
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1704
CH3—
n-C8H17—
H
CH3—
CH3—
CH3—





XA1705
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1706
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1707
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1708
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1709
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1710
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1711
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1712
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1713
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1714
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1715
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1716
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1717
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1718
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1719
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1720
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1721
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1722
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1723
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1724
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1725
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1726
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1727
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1728
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1729
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1730
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1731
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1732
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1733
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1734
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1735
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1736
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1737
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1738
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1739
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1740
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1741
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1742
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1743
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1744
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1745
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1746
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1747
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1748
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1749
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1750
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1751
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1752
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1753
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1754
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1755
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1756
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1757
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1758
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1759
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1760
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1761
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1762
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1763
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1764
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1765
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1766
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1767
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1768
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1769
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1770
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1771
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1772
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1773
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1774
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1775
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1776
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1777
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1778
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1779
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1780
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1781
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1782
CH3—


embedded image


H
CH3—
CH3—
CH3—





XA1783
CH3CH2—
CH3—
H
H
H
H


XA1784
CH3CH2—
CH3CH2—
H
H
H
H





XA1785
CH3CH2—


embedded image


H
H
H
H





XA1786
CH3CH2—


embedded image


H
H
H
H





XA1787
CH3CH2—


embedded image


H
H
H
H





XA1788
CH3CH2—


embedded image


H
H
H
H





XA1789
CH3CH2—


embedded image


H
H
H
H





XA1790
CH3CH2—


embedded image


H
H
H
H





XA1791
CH3CH2—


embedded image


H
H
H
H





XA1792
CH3CH2—


embedded image


H
H
H
H





XA1793
CH3CH2—


embedded image


H
H
H
H





XA1794
CH3CH2—


embedded image


H
H
H
H





XA1795
CH3CH2—


embedded image


H
H
H
H





XA1796
CH3CH2—


embedded image


H
H
H
H





XA1797
CH3CH2—


embedded image


H
H
H
H





XA1798
CH3CH2—


embedded image


H
H
H
H





XA1799
CH3CH2—
n-C8H17—
H
H
H
H





XA1800
CH3CH2—


embedded image


H
H
H
H





XA1801
CH3CH2—


embedded image


H
H
H
H





XA1802
CH3CH2—


embedded image


H
H
H
H





XA1803
CH3CH2—


embedded image


H
H
H
H





XA1804
CH3CH2—


embedded image


H
H
H
H





XA1805
CH3CH2—


embedded image


H
H
H
H





XA1806
CH3CH2—


embedded image


H
H
H
H





XA1807
CH3CH2—


embedded image


H
H
H
H





XA1808
CH3CH2—


embedded image


H
H
H
H





XA1809
CH3CH2—


embedded image


H
H
H
H





XA1810
CH3CH2—


embedded image


H
H
H
H





XA1811
CH3CH2—


embedded image


H
H
H
H





XA1812
CH3CH2—


embedded image


H
H
H
H





XA1813
CH3CH2—


embedded image


H
H
H
H





XA1814
CH3CH2—


embedded image


H
H
H
H





XA1815
CH3CH2—


embedded image


H
H
H
H





XA1816
CH3CH2—


embedded image


H
H
H
H





XA1817
CH3CH2—


embedded image


H
H
H
H





XA1818
CH3CH2—


embedded image


H
H
H
H





XA1819
CH3CH2—


embedded image


H
H
H
H





XA1820
CH3CH2—


embedded image


H
H
H
H





XA1821
CH3CH2—


embedded image


H
H
H
H





XA1822
CH3CH2—


embedded image


H
H
H
H





XA1823
CH3CH2—


embedded image


H
H
H
H





XA1824
CH3CH2—


embedded image


H
H
H
H





XA1825
CH3CH2—


embedded image


H
H
H
H





XA1826
CH3CH2—


embedded image


H
H
H
H





XA1827
CH3CH2—


embedded image


H
H
H
H





XA1828
CH3CH2—


embedded image


H
H
H
H





XA1829
CH3CH2—


embedded image


H
H
H
H





XA1830
CH3CH2—


embedded image


H
H
H
H





XA1831
CH3CH2—


embedded image


H
H
H
H





XA1832
CH3CH2—


embedded image


H
H
H
H





XA1833
CH3CH2—


embedded image


H
H
H
H





XA1834
CH3CH2—


embedded image


H
H
H
H





XA1835
CH3CH2—


embedded image


H
H
H
H





XA1836
CH3CH2—


embedded image


H
H
H
H





XA1837
CH3CH2—


embedded image


H
H
H
H





XA1838
CH3CH2—


embedded image


H
H
H
H





XA1839
CH3CH2—


embedded image


H
H
H
H





XA1840
CH3CH2—


embedded image


H
H
H
H





XA1841
CH3CH2—


embedded image


H
H
H
H





XA1842
CH3CH2—


embedded image


H
H
H
H





XA1843
CH3CH2—


embedded image


H
H
H
H





XA1844
CH3CH2—


embedded image


H
H
H
H





XA1845
CH3CH2—


embedded image


H
H
H
H





XA1846
CH3CH2—


embedded image


H
H
H
H





XA1847
CH3CH2—


embedded image


H
H
H
H





XA1848
CH3CH2—


embedded image


H
H
H
H





XA1849
CH3CH2—


embedded image


H
H
H
H





XA1850
CH3CH2—


embedded image


H
H
H
H





XA1851
CH3CH2—


embedded image


H
H
H
H





XA1852
CH3CH2—


embedded image


H
H
H
H





XA1853
CH3CH2—


embedded image


H
H
H
H





XA1854
CH3CH2—


embedded image


H
H
H
H





XA1855
CH3CH2—


embedded image


H
H
H
H





XA1856
CH3CH2—


embedded image


H
H
H
H





XA1857
CH3CH2—


embedded image


H
H
H
H





XA1858
CH3CH2—


embedded image


H
H
H
H





XA1859
CH3CH2—


embedded image


H
H
H
H





XA1860
CH3CH2—


embedded image


H
H
H
H





XA1861
CH3CH2—


embedded image


H
H
H
H





XA1862
CH3CH2—


embedded image


H
H
H
H





XA1863
CH3CH2—


embedded image


H
H
H
H





XA1864
CH3CH2—


embedded image


H
H
H
H





XA1865
CH3CH2—


embedded image


H
H
H
H





XA1866
CH3CH2—


embedded image


H
H
H
H





XA1867
CH3CH2—


embedded image


H
H
H
H





XA1868
CH3CH2—


embedded image


H
H
H
H





XA1869
CH3CH2—


embedded image


H
H
H
H





XA1870
CH3CH2—


embedded image


H
H
H
H





XA1871
CH3CH2—


embedded image


H
H
H
H





XA1872
CH3CH2—


embedded image


H
H
H
H





XA1873
CH3CH2—


embedded image


H
H
H
H





XA1874
CH3CH2—


embedded image


H
H
H
H





XA1875
CH3CH2—


embedded image


H
H
H
H





XA1876
CH3CH2—


embedded image


H
H
H
H





XA1877
CH3CH2—


embedded image


H
H
H
H





XA1878
CH3CH2—
CH3—
H
CH3—
H
H


XA1879
CH3CH2—
CH3CH2—
H
CH3—
H
H





XA1880
CH3CH2—


embedded image


H
CH3—
H
H





XA1881
CH3CH2—


embedded image


H
CH3—
H
H





XA1882
CH3CH2—


embedded image


H
CH3—
H
H





XA1883
CH3CH2—


embedded image


H
CH3—
H
H





XA1884
CH3CH2—


embedded image


H
CH3—
H
H





XA1885
CH3CH2—


embedded image


H
CH3—
H
H





XA1886
CH3CH2—


embedded image


H
CH3—
H
H





XA1887
CH3CH2—


embedded image


H
CH3—
H
H





XA1888
CH3CH2—


embedded image


H
CH3—
H
H





XA1889
CH3CH2—


embedded image


H
CH3—
H
H





XA1890
CH3CH2—


embedded image


H
CH3—
H
H





XA1891
CH3CH2—


embedded image


H
CH3—
H
H





XA1892
CH3CH2—


embedded image


H
CH3—
H
H





XA1893
CH3CH2—


embedded image


H
CH3—
H
H





XA1894
CH3CH2—
n-C8H17—
H
CH3—
H
H





XA1895
CH3CH2—


embedded image


H
CH3—
H
H





XA1896
CH3CH2—


embedded image


H
CH3—
H
H





XA1897
CH3CH2—


embedded image


H
CH3—
H
H





XA1898
CH3CH2—


embedded image


H
CH3—
H
H





XA1899
CH3CH2—


embedded image


H
CH3—
H
H





XA1900
CH3CH2—


embedded image


H
CH3—
H
H





XA1901
CH3CH2—


embedded image


H
CH3—
H
H





XA1902
CH3CH2—


embedded image


H
CH3—
H
H





XA1903
CH3CH2—


embedded image


H
CH3—
H
H





XA1904
CH3CH2—


embedded image


H
CH3—
H
H





XA1905
CH3CH2—


embedded image


H
CH3—
H
H





XA1906
CH3CH2—


embedded image


H
CH3—
H
H





XA1907
CH3CH2—


embedded image


H
CH3—
H
H





XA1908
CH3CH2—


embedded image


H
CH3—
H
H





XA1909
CH3CH2—


embedded image


H
CH3—
H
H





XA1910
CH3CH2—


embedded image


H
CH3—
H
H





XA1911
CH3CH2—


embedded image


H
CH3—
H
H





XA1912
CH3CH2—


embedded image


H
CH3—
H
H





XA1913
CH3CH2—


embedded image


H
CH3—
H
H





XA1914
CH3CH2—


embedded image


H
CH3—
H
H





XA1915
CH3CH2—


embedded image


H
CH3—
H
H





XA1916
CH3CH2—


embedded image


H
CH3—
H
H





XA1917
CH3CH2—


embedded image


H
CH3—
H
H





XA1918
CH3CH2—


embedded image


H
CH3—
H
H





XA1919
CH3CH2—


embedded image


H
CH3—
H
H





XA1920
CH3CH2—


embedded image


H
CH3—
H
H





XA1921
CH3CH2—


embedded image


H
CH3—
H
H





XA1922
CH3CH2—


embedded image


H
CH3—
H
H





XA1923
CH3CH2—


embedded image


H
CH3—
H
H





XA1924
CH3CH2—


embedded image


H
CH3—
H
H





XA1925
CH3CH2—


embedded image


H
CH3—
H
H





XA1926
CH3CH2—


embedded image


H
CH3—
H
H





XA1927
CH3CH2—


embedded image


H
CH3—
H
H





XA1928
CH3CH2—


embedded image


H
CH3—
H
H





XA1929
CH3CH2—


embedded image


H
CH3—
H
H





XA1930
CH3CH2—


embedded image


H
CH3—
H
H





XA1931
CH3CH2—


embedded image


H
CH3—
H
H





XA1932
CH3CH2—


embedded image


H
CH3—
H
H





XA1933
CH3CH2—


embedded image


H
CH3—
H
H





XA1934
CH3CH2—


embedded image


H
CH3—
H
H





XA1935
CH3CH2—


embedded image


H
CH3—
H
H





XA1936
CH3CH2—


embedded image


H
CH3—
H
H





XA1937
CH3CH2—


embedded image


H
CH3—
H
H





XA1938
CH3CH2—


embedded image


H
CH3—
H
H





XA1939
CH3CH2—


embedded image


H
CH3—
H
H





XA1940
CH3CH2—


embedded image


H
CH3—
H
H





XA1941
CH3CH2—


embedded image


H
CH3—
H
H





XA1942
CH3CH2—


embedded image


H
CH3—
H
H





XA1943
CH3CH2—


embedded image


H
CH3—
H
H





XA1944
CH3CH2—


embedded image


H
CH3—
H
H





XA1945
CH3CH2—


embedded image


H
CH3—
H
H





XA1946
CH3CH2—


embedded image


H
CH3—
H
H





XA1947
CH3CH2—


embedded image


H
CH3—
H
H





XA1948
CH3CH2—


embedded image


H
CH3—
H
H





XA1949
CH3CH2—


embedded image


H
CH3—
H
H





XA1950
CH3CH2—


embedded image


H
CH3—
H
H





XA1951
CH3CH2—


embedded image


H
CH3—
H
H





XA1952
CH3CH2—


embedded image


H
CH3—
H
H





XA1953
CH3CH2—


embedded image


H
CH3—
H
H





XA1954
CH3CH2—


embedded image


H
CH3—
H
H





XA1955
CH3CH2—


embedded image


H
CH3—
H
H





XA1956
CH3CH2—


embedded image


H
CH3—
H
H





XA1957
CH3CH2—


embedded image


H
CH3—
H
H





XA1958
CH3CH2—


embedded image


H
CH3—
H
H





XA1959
CH3CH2—


embedded image


H
CH3—
H
H





XA1960
CH3CH2—


embedded image


H
CH3—
H
H





XA1961
CH3CH2—


embedded image


H
CH3—
H
H





XA1962
CH3CH2—


embedded image


H
CH3—
H
H





XA1963
CH3CH2—


embedded image


H
CH3—
H
H





XA1964
CH3CH2—


embedded image


H
CH3—
H
H





XA1965
CH3CH2—


embedded image


H
CH3—
H
H





XA1966
CH3CH2—


embedded image


H
CH3—
H
H





XA1967
CH3CH2—


embedded image


H
CH3—
H
H





XA1968
CH3CH2—


embedded image


H
CH3—
H
H





XA1969
CH3CH2—


embedded image


H
CH3—
H
H





XA1970
CH3CH2—


embedded image


H
CH3—
H
H





XA1971
CH3CH2—


embedded image


H
CH3—
H
H





XA1972
CH3CH2—


embedded image


H
CH3—
H
H











No.
STRUCTURE





XA1973


embedded image







XA1974


embedded image







XA1975


embedded image







XA1976


embedded image







XA1977


embedded image







XA1978


embedded image







XA1979


embedded image







XA1980


embedded image







XA1981


embedded image







XA1982


embedded image







XA1983


embedded image







XA1984


embedded image







XA1985


embedded image







XA1986


embedded image







XA1987


embedded image







XA1988


embedded image







XA1989


embedded image







XA1990


embedded image







XA1991


embedded image







XA1992


embedded image







XA1993


embedded image







XA1994


embedded image







XA1995


embedded image







XA1996


embedded image







XA1997


embedded image







XA1998


embedded image







XA1999


embedded image







XA2000


embedded image







XA2001


embedded image







XA2002


embedded image







XA2003


embedded image







XA2004


embedded image







XA2005


embedded image







XA2006


embedded image







XA2007


embedded image







XA2008


embedded image







XA2009


embedded image







XA2010


embedded image







XA2011


embedded image







XA2012


embedded image







XA2013


embedded image







XA2014


embedded image







XA2015


embedded image







XA2016


embedded image







XA2017


embedded image







XA2018


embedded image







XA2019


embedded image







XA2020


embedded image







XA2021


embedded image







XA2022


embedded image







XA2023


embedded image







XA2024


embedded image







XA2025


embedded image







XA2026


embedded image







XA2027


embedded image







XA2028


embedded image







XA2029


embedded image







XA2030


embedded image







XA2031


embedded image







XA2032


embedded image







XA2033


embedded image







XA2034


embedded image







XA2035


embedded image







XA2036


embedded image







XA2037


embedded image







XA2038


embedded image







XA2039


embedded image







XA2040


embedded image







XA2041


embedded image







XA2042


embedded image







XA2043


embedded image







XA2044


embedded image







XA2045


embedded image







XA2046


embedded image







XA2047


embedded image







XA2048


embedded image







XA2049


embedded image







XA2050


embedded image







XA2051


embedded image







XA2052


embedded image







XA2053


embedded image







XA2054


embedded image







XA2055


embedded image


















TABLE 2









embedded image

















No
R1
R2
R3
R4
R5





XB1
CH3—
CH3—
H
H
H


XB2
CH3—
CH3CH2—
H
H
H





XB3
CH3—


embedded image


H
H
H





XB4
CH3—


embedded image


H
H
H





XB5
CH3—


embedded image


H
H
H





XB6
CH3—


embedded image


H
H
H





XB7
CH3—


embedded image


H
H
H





XB8
CH3—


embedded image


H
H
H





XB9
CH3—


embedded image


H
H
H





XB10
CH3—


embedded image


H
H
H





XB11
CH3—


embedded image


H
H
H





XB12
CH3—


embedded image


H
H
H





XB13
CH3—


embedded image


H
H
H





XB14
CH3—


embedded image


H
H
H





XB15
CH3—


embedded image


H
H
H





XB16
CH3—


embedded image


H
H
H





XB17
CH3—


embedded image


H
H
H





XB18
CH3—


embedded image


H
H
H





XB19
CH3—


embedded image


H
H
H





XB20
CH3—


embedded image


H
H
H





XB21
CH3—


embedded image


H
H
H





XB22
CH3—


embedded image


H
H
H





XB23
CH3—


embedded image


H
H
H





XB24
CH3—


embedded image


H
H
H





XB25
CH3—


embedded image


H
H
H





XB26
CH3—


embedded image


H
H
H





XB27
CH3—


embedded image


H
H
H





XB28
CH3—


embedded image


H
H
H





XB29
CH3—


embedded image


H
H
H





XB30
CH3—


embedded image


H
H
H





XB31
CH3—


embedded image


H
H
H





XB32
CH3—


embedded image


H
H
H





XB33
CH3—


embedded image


H
H
H





XB34
CH3—


embedded image


H
H
H





XB35
CH3—


embedded image


H
H
H





XB36
CH3—


embedded image


H
H
H





XB37
CH3—


embedded image


H
H
H





XB38
CH3—


embedded image


H
H
H





XB39
CH3—


embedded image


H
H
H





XB40
CH3—


embedded image


H
H
H





XB41
CH3—


embedded image


H
H
H





XB42
CH3—


embedded image


H
H
H





XB43
CH3—


embedded image


H
H
H





XB44
CH3—


embedded image


H
H
H





XB45
CH3—


embedded image


H
H
H





XB46
CH3—


embedded image


H
H
H





XB47
CH3—


embedded image


H
H
H





XB48
CH3—


embedded image


H
H
H





XB49
CH3—


embedded image


H
H
H





XB50
CH3—


embedded image


OH
H
H





XB51
CH3—


embedded image


OH
H
H





XB52
CH3—


embedded image


OH
H
H





XB53
CH3—


embedded image


OH
H
H





XB54
CH3—


embedded image


OH
H
H





XB55
CH3—


embedded image


OH
H
H





XB56
CH3—


embedded image


OH
H
H





XB57
CH3—


embedded image


OH
H
H





XB58
CH3—


embedded image


OH
H
H





XB59
CH3—


embedded image


OH
H
H





XB60
CH3—


embedded image


OH
H
H





XB61
CH3—


embedded image


OH
H
H





XB62
CH3—


embedded image


OH
H
H





XB63
CH3—


embedded image


OH
H
H





XB64
CH3—


embedded image


OH
H
H





XB65
CH3—


embedded image


OH
H
H





XB66
CH3—


embedded image


OH
H
H





XB67
CH3—


embedded image


OH
H
H





XB68
CH3—


embedded image


OH
H
H





XB69
CH3—


embedded image


OH
H
H





XB70
CH3—


embedded image


OH
H
H





XB71
CH3—


embedded image


OH
H
H





XB72
CH3—


embedded image


OH
H
H





XB73
CH3—


embedded image


OH
H
H





XB74
CH3—


embedded image


OH
H
H





XB75
CH3—


embedded image


OH
H
H





XB76
CH3—


embedded image


OH
H
H





XB77
CH3—


embedded image


OH
H
H





XB78
CH3—


embedded image


OH
H
H





XB79
CH3—


embedded image


OH
H
H





XB80
CH3—


embedded image


CN
H
H





XB81
CH3—


embedded image


CN
H
H





XB82
CH3—


embedded image


CN
H
H





XB83
CH3—


embedded image


CN
H
H





XB84
CH3—


embedded image


CN
H
H





XB85
CH3—


embedded image


CN
H
H





XB86
CH3—


embedded image


CN
H
H





XB87
CH3—


embedded image


CN
H
H





XB88
CH3—


embedded image


CN
H
H





XB89
CH3—


embedded image


CN
H
H





XB90
CH3—


embedded image


CN
H
H





XB91
CH3—


embedded image


CN
H
H





XB92
CH3—


embedded image


CN
H
H





XB93
CH3—


embedded image


CN
H
H





XB94
CH3—


embedded image


CN
H
H





XB95
CH3—


embedded image


CN
H
H





XB96
CH3—


embedded image


CN
H
H





XB97
CH3—


embedded image


CN
H
H





XB98
CH3—


embedded image


CN
H
H





XB99
CH3—


embedded image


CN
H
H





XB100
CH3—


embedded image


CN
H
H





XB101
CH3—


embedded image


CN
H
H





XB102
CH3—


embedded image


CN
H
H





XB103
CH3—


embedded image


CN
H
H





XB104
CH3—


embedded image


CN
H
H





XB105
CH3—


embedded image


CN
H
H





XB106
CH3—


embedded image


CN
H
H





XB107
CH3—


embedded image


CN
H
H





XB108
CH3—


embedded image


CN
H
H





XB109
CH3—


embedded image


CN
H
H





XB110
CH3—
H
H
CH3—
H


XB111
CH3—
H
H
CH3CH2—
H





XB112
CH3—
H
H


embedded image


H





XB113
CH3—
H
H


embedded image


H





XB114
CH3—
H
H


embedded image


H





XB115
CH3—
H
H


embedded image


H





XB116
CH3—
H
H


embedded image


H





XB117
CH3—
H
H


embedded image


H





XB118
CH3—
H
H


embedded image


H





XB119
CH3—
H
H


embedded image


H





XB120
CH3—
H
H


embedded image


H





XB121
CH3—
H
H


embedded image


H





XB122
CH3—
H
H


embedded image


H





XB123
CH3—
H
H


embedded image


H





XB124
CH3—
H
H


embedded image


H





XB125
CH3—
H
H


embedded image


H





XB126
CH3—
H
H


embedded image


H





XB127
CH3—
H
H


embedded image


H





XB128
CH3—
H
H


embedded image


H





XB129
CH3—
H
H


embedded image


H





XB130
CH3—
H
H


embedded image


H





XB131
CH3—
H
H


embedded image


H





XB132
CH3—
H
H


embedded image


H





XB133
CH3—
H
H


embedded image


H





XB134
CH3—
H
H


embedded image


H





XB135
CH3—
H
H


embedded image


H





XB136
CH3—
H
H


embedded image


H





XB137
CH3—
H
H


embedded image


H





XB138
CH3—
H
H


embedded image


H





XB139
CH3—
H
H


embedded image


H





XB140
CH3—
H
H


embedded image


H





XB141
CH3—
H
H


embedded image


H





XB142
CH3—
H
H


embedded image


H





XB143
CH3—
H
H


embedded image


H





XB144
CH3—
H
H


embedded image


H





XB145
CH3—
H
H


embedded image


H





XB146
CH3—
H
H


embedded image


H





XB147
CH3—
H
H


embedded image


H





XB148
CH3—
H
H


embedded image


H





XB149
CH3—
H
H


embedded image


H





XB150
CH3—
H
H


embedded image


H





XB151
CH3—
H
H


embedded image


H





XB152
CH3—
H
H


embedded image


H





XB153
CH3—
H
H


embedded image


H





XB154
CH3—
H
H


embedded image


H





XB155
CH3—
H
H


embedded image


H





XB156
CH3—
H
H


embedded image


H





XB157
CH3—
H
H


embedded image


H





XB158
CH3—
H
H


embedded image


H





XB159
CH3—
H
H


embedded image


H





XB160
CH3—
H
H


embedded image


H





XB161
CH3—
H
H


embedded image


H





XB162
CH3—
H
H


embedded image


H





XB163
CH3—
H
H


embedded image


H





XB164
CH3—
H
H


embedded image


H





XB165
CH3—
H
H


embedded image


H





XB166
CH3—
H
H


embedded image


H





XB167
CH3—
H
H


embedded image


H





XB168
CH3—
H
H


embedded image


H





XB169
CH3—
H
H


embedded image


OH





XB170
CH3—
H
H


embedded image


OH





XB171
CH3—
H
H


embedded image


OH





XB172
CH3—
H
H


embedded image


OH





XB173
CH3—
H
H


embedded image


OH





XB174
CH3—
H
H


embedded image


OH





XB175
CH3—
H
H


embedded image


OH





XB176
CH3—
H
H


embedded image


OH





XB177
CH3—
H
H


embedded image


OH





XB178
CH3—
H
H


embedded image


OH





XB179
CH3—
H
H


embedded image


OH





XB180
CH3—
H
H


embedded image


OH





XB181
CH3—
H
H


embedded image


OH





XB182
CH3—
H
H


embedded image


OH





XB183
CH3—
H
H


embedded image


OH





XB184
CH3—
H
H


embedded image


OH





XB185
CH3—
H
H


embedded image


OH





XB186
CH3—
H
H


embedded image


OH





XB187
CH3—
H
H


embedded image


OH





XB188
CH3—
H
H


embedded image


OH





XB189
CH3—
H
H


embedded image


OH





XB190
CH3—
H
H


embedded image


OH





XB191
CH3—
H
H


embedded image


OH





XB192
CH3—
H
H


embedded image


OH





XB193
CH3—
H
H


embedded image


OH





XB194
CH3—
H
H


embedded image


OH





XB195
CH3—
H
H


embedded image


OH





XB196
CH3—
H
H


embedded image


OH





XB197
CH3—
H
H


embedded image


OH





XB198
CH3—
H
H


embedded image


CN





XB199
CH3—
H
H


embedded image


CN





XB200
CH3—
H
H


embedded image


CN





XB201
CH3—
H
H


embedded image


CN





XB202
CH3—
H
H


embedded image


CN





XB203
CH3—
H
H


embedded image


CN





XB204
CH3—
H
H


embedded image


CN





XB205
CH3—
H
H


embedded image


CN





XB206
CH3—
H
H


embedded image


CN





XB207
CH3—
H
H


embedded image


CN





XB208
CH3—
H
H


embedded image


CN





XB209
CH3—
H
H


embedded image


CN





XB210
CH3—
H
H


embedded image


CN





XB211
CH3—
H
H


embedded image


CN





XB212
CH3—
H
H


embedded image


CN





XB213
CH3—
H
H


embedded image


CN





XB214
CH3—
H
H


embedded image


CN





XB215
CH3—
H
H


embedded image


CN





XB216
CH3—
H
H


embedded image


CN





XB217
CH3—
H
H


embedded image


CN





XB218
CH3—
H
H


embedded image


CN





XB219
CH3—
H
H


embedded image


CN





XB220
CH3—
H
H


embedded image


CN





XB221
CH3—
H
H


embedded image


CN





XB222
CH3—
H
H


embedded image


CN





XB223
CH3—
H
H


embedded image


CN





XB224
CH3—
H
H


embedded image


CN





XB225
CH3—
H
H


embedded image


CN





XB226
CH3—
H
H


embedded image


CN





XB227
CH3—
H
H


embedded image




embedded image







XB228
CH3—
H
H


embedded image




embedded image







XB229
CH3—
H
H


embedded image




embedded image







XB230
CH3—
H
H


embedded image




embedded image







XB231
CH3—
H
H


embedded image




embedded image







XB232
CH3—
H
H


embedded image




embedded image







XB233
CH3—
H
H


embedded image




embedded image







XB234
CH3—
H
H


embedded image




embedded image







XB235
CH3—
H
H


embedded image




embedded image







XB236
CH3—
H
H


embedded image




embedded image







XB237
CH3—
H
H


embedded image




embedded image







XB238
CH3—
H
H


embedded image




embedded image







XB239
CH3—
H
H


embedded image




embedded image







XB240
CH3—
H
H


embedded image




embedded image







XB241
CH3—
H
H


embedded image




embedded image







XB242
CH3—
H
H


embedded image




embedded image







XB243
CH3—
H
H


embedded image




embedded image







XB244
CH3—
H
H


embedded image




embedded image







XB245
CH3—
H
H


embedded image




embedded image







XB246
CH3—
H
H


embedded image




embedded image







XB247
CH3—
H
H


embedded image




embedded image







XB248
CH3—
H
H


embedded image




embedded image







XB249
CH3—
H
H


embedded image




embedded image







XB250
CH3—
H
H


embedded image




embedded image







XB251
CH3—
H
H


embedded image




embedded image







XB252
CH3—
H
H


embedded image




embedded image







XB253
CH3—
H
H


embedded image




embedded image







XB254
CH3—
H
H


embedded image




embedded image







XB255
CH3—
H
H


embedded image




embedded image













No.
STRUCTURE





XB256


embedded image







XB257


embedded image







XB258


embedded image







XB259


embedded image







XB260


embedded image







XB261


embedded image







XB262


embedded image







XB263


embedded image







XB264


embedded image







XB265


embedded image







XB266


embedded image







XB267


embedded image







XB268


embedded image







XB269


embedded image







XB270


embedded image







XB271


embedded image







XB272


embedded image







XB273


embedded image







XB274


embedded image







XB275


embedded image







XB276


embedded image







XB277


embedded image







XB278


embedded image







XB279


embedded image







XB280


embedded image







XB281


embedded image







XB282


embedded image







XB283


embedded image







XB284


embedded image







XB285


embedded image







XB286


embedded image







XB287


embedded image







XB288


embedded image







XB289


embedded image







XB290


embedded image







XB291


embedded image







XB292


embedded image







XB293


embedded image







XB294


embedded image







XB295


embedded image







XB296


embedded image







XB297


embedded image







XB298


embedded image







XB299


embedded image







XB300


embedded image







XB301


embedded image







XB302


embedded image























TABLE 3




embedded image
















No.
R1
R2
R3
R4





YA0001
CH3—
H
H
CH3—


YA0002
CH3—
H
H
CH3CH2—





YA0003
CH3—
H
H


embedded image







YA0004
CH3—
H
H


embedded image







YA0005
CH3—
H
H


embedded image







YA0006
CH3—
H
H


embedded image







YA0007
CH3—
H
H


embedded image







YA0008
CH3—
H
H


embedded image







YA0009
CH3—
H
H


embedded image







YA0010
CH3—
H
H


embedded image







YA0011
CH3—
H
H


embedded image







YA0012
CH3—
H
H


embedded image







YA0013
CH3—
H
H


embedded image







YA0014
CH3—
H
H


embedded image







YA0015
CH3—
H
H


embedded image







YA0016
CH3—
H
H


embedded image







YA0017
CH3—
H
H


embedded image







YA0018
CH3—
H
H


embedded image







YA0019
CH3—
H
H


embedded image







YA0020
CH3—
H
H


embedded image







YA0021
CH3—
H
H


embedded image







YA0022
CH3—
H
H


embedded image







YA0023
CH3—
H
H


embedded image







YA0024
CH3—
H
H


embedded image







YA0025
CH3—
H
H


embedded image







YA0026
CH3—
H
H


embedded image







YA0027
CH3—
H
H


embedded image







YA0028
CH3—
H
H


embedded image







YA0029
CH3—
H
H


embedded image







YA0030
CH3—
H
H


embedded image







YA0031
CH3—
H
H


embedded image







YA0032
CH3—
H
H


embedded image







YA0033
CH3—
H
H


embedded image







YA0034
CH3—
H
H


embedded image







YA0035
CH3—
H
H


embedded image







YA0036
CH3—
H
H


embedded image







YA0037
CH3—
H
H


embedded image







YA0038
CH3—
H
H


embedded image







YA0039
CH3—
H
H


embedded image







YA0040
CH3—
H
H


embedded image







YA0041
CH3—
H
H


embedded image







YA0042
CH3—
H
H


embedded image







YA0043
CH3—
H
H


embedded image







YA0044
CH3—
H
H


embedded image







YA0045
CH3—
H
H


embedded image







YA0046
CH3—
H
H


embedded image







YA0047
CH3—
H
H


embedded image







YA0048
CH3—
H
H


embedded image







YA0049
CH3—
H
H


embedded image







YA0050
CH3—
H
H


embedded image







YA0051
CH3—
H
H


embedded image







YA0052
CH3—
H
H


embedded image







YA0053
CH3—
H
H


embedded image







YA0054
CH3—
H
H


embedded image







YA0055
CH3—
H
H


embedded image







YA0056
CH3—
H
H


embedded image







YA0057
CH3—
H
H


embedded image







YA0058
CH3—
H
H


embedded image







YA0059
CH3—
H
H


embedded image







YA0060
CH3—
H
H


embedded image







YA0061
CH3—
H
H


embedded image







YA0062
CH3—
H
H


embedded image







YA0063
CH3—
H
H


embedded image







YA0064
CH3—
H
H


embedded image







YA0065
CH3—
H
H


embedded image







YA0066
CH3—
H
H


embedded image







YA0067
CH3—
H
H


embedded image







YA0068
CH3—
H
H


embedded image







YA0069
CH3—
H
H


embedded image







YA0070
CH3—
H
H


embedded image







YA0071
CH3—
H
H


embedded image







YA0072
CH3—
H
H


embedded image







YA0073
CH3—
H
H


embedded image







YA0074
CH3—
H
H


embedded image







YA0075
CH3—
H
H


embedded image







YA0076
CH3—
H
H


embedded image







YA0077
CH3—
H
H


embedded image







YA0078
CH3—
H
H


embedded image







YA0079
CH3—
H
H


embedded image







YA0080
CH3—
H
H


embedded image







YA0081
CH3—
H
H


embedded image







YA0082
CH3—
H
H


embedded image







YA0083
CH3—
H
H


embedded image







YA0084
CH3—
H
H


embedded image







YA0085
CH3—
H
H


embedded image







YA0086
CH3—
H
H


embedded image







YA0087
CH3—
H
H


embedded image







YA0088
CH3—
H
H


embedded image







YA0089
CH3—
H
H


embedded image







YA0090
CH3—
H
H


embedded image







YA0091
CH3—
H
H


embedded image







YA0092
CH3—
H
H


embedded image







YA0093
CH3—
H
H


embedded image







YA0094
CH3—
H
H


embedded image







YA0095
CH3—
H
H


embedded image







YA0096
CH3—
H
H


embedded image







YA0097
CH3—
H
H


embedded image







YA0098
CH3—
H
H


embedded image







YA0099
CH3—
H
H


embedded image







YA0100
CH3—
H
H


embedded image







YA0101
CH3—
H
H


embedded image







YA0102
CH3—
H
H


embedded image







YA0103
CH3—
H
H


embedded image







YA0104
CH3—
H
H


embedded image







YA0105
CH3—
H
H


embedded image







YA0106
CH3—
H
H


embedded image







YA0107
CH3—
H
H


embedded image







YA0108
CH3—
H
H


embedded image







YA0109
CH3—
H
H


embedded image







YA0110
CH3—
H
H


embedded image







YA0111
CH3—
H
H


embedded image







YA0112
CH3—
H
H


embedded image







YA0113
CH3—
H
H


embedded image







YA0114
CH3—
H
H


embedded image







YA0115
CH3—
H
H


embedded image







YA0116
CH3—
H
H


embedded image







YA0117
CH3—
H
H


embedded image







YA0118
CH3—
H
H


embedded image







YA0119
CH3—
H
H


embedded image







YA0120
CH3—
H
H


embedded image







YA0121
CH3—
H
H


embedded image







YA0122
CH3—
H
H


embedded image







YA0123
CH3—


embedded image


H
H





YA0124
CH3—


embedded image


H
CH3—





YA0125
CH3—


embedded image


H
CH3CH2—





YA0126
CH3—


embedded image


H


embedded image







YA0127
CH3—


embedded image


H


embedded image







YA0128
CH3—


embedded image


H


embedded image







YA0129
CH3—


embedded image


H


embedded image







YA0130
CH3—


embedded image


H


embedded image







YA0131
CH3—


embedded image


H


embedded image







YA0132
CH3—


embedded image


H


embedded image







YA0133
CH3—


embedded image


H


embedded image







YA0134
CH3—


embedded image


H


embedded image







YA0135
CH3—


embedded image


H


embedded image







YA0136
CH3—


embedded image


H


embedded image







YA0137
CH3—


embedded image


H


embedded image







YA0138
CH3—


embedded image


H


embedded image







YA0139
CH3—


embedded image


H


embedded image







YA0140
CH3—


embedded image


H


embedded image







YA0141
CH3—


embedded image


H


embedded image







YA0142
CH3—


embedded image


H


embedded image







YA0143
CH3—


embedded image


H


embedded image







YA0144
CH3—


embedded image


H


embedded image







YA0145
CH3—


embedded image


H


embedded image







YA0146
CH3—


embedded image


H


embedded image







YA0147
CH3—


embedded image


H


embedded image







YA0148
CH3—


embedded image


H


embedded image







YA0149
CH3—


embedded image


H


embedded image







YA0150
CH3—


embedded image


H


embedded image







YA0151
CH3—


embedded image


H


embedded image







YA0152
CH3—


embedded image


H


embedded image







YA0153
CH3—


embedded image


H


embedded image







YA0154
CH3—


embedded image


H


embedded image







YA0155
CH3—


embedded image


H


embedded image







YA0156
CH3—


embedded image


H


embedded image







YA0157
CH3—


embedded image


H


embedded image







YA0158
CH3—


embedded image


H


embedded image







YA0159
CH3—


embedded image


H


embedded image







YA0160
CH3—


embedded image


H


embedded image







YA0161
CH3—


embedded image


H


embedded image







YA0162
CH3—


embedded image


H


embedded image







YA0163
CH3—


embedded image


H


embedded image







YA0164
CH3—


embedded image


H


embedded image







YA0165
CH3—


embedded image


H


embedded image







YA0166
CH3—


embedded image


H


embedded image







YA0167
CH3—


embedded image


H


embedded image







YA0168
CH3—


embedded image


H


embedded image







YA0169
CH3—


embedded image


H


embedded image







YA0170
CH3—


embedded image


H


embedded image







YA0171
CH3—


embedded image


H


embedded image







YA0172
CH3—


embedded image


H


embedded image







YA0173
CH3—


embedded image


H


embedded image







YA0174
CH3—


embedded image


H


embedded image







YA0175
CH3—


embedded image


H


embedded image







YA0176
CH3—


embedded image


H


embedded image







YA0177
CH3—


embedded image


H


embedded image







YA0178
CH3—


embedded image


H
H





YA0179
CH3—


embedded image


H
CH3—





YA0180
CH3—


embedded image


H
CH3CH2—





YA0181
CH3—


embedded image


H


embedded image







YA0182
CH3—


embedded image


H


embedded image







YA0183
CH3—


embedded image


H


embedded image







YA0184
CH3—


embedded image


H


embedded image







YA0185
CH3—


embedded image


H


embedded image







YA0186
CH3—


embedded image


H


embedded image







YA0187
CH3—


embedded image


H


embedded image







YA0188
CH3—


embedded image


H


embedded image







YA0189
CH3—


embedded image


H


embedded image







YA0190
CH3—


embedded image


H


embedded image







YA0191
CH3—


embedded image


H


embedded image







YA0192
CH3—


embedded image


H


embedded image







YA0193
CH3—


embedded image


H


embedded image







YA0194
CH3—


embedded image


H


embedded image







YA0195
CH3—


embedded image


H


embedded image







YA0196
CH3—


embedded image


H


embedded image







YA0197
CH3—


embedded image


H


embedded image







YA0198
CH3—


embedded image


H


embedded image







YA0199
CH3—


embedded image


H


embedded image







YA0200
CH3—


embedded image


H


embedded image







YA0201
CH3—


embedded image


H


embedded image







YA0202
CH3—


embedded image


H


embedded image







YA0203
CH3—


embedded image


H


embedded image







YA0204
CH3—


embedded image


H


embedded image







YA0205
CH3—


embedded image


H


embedded image







YA0206
CH3—


embedded image


H


embedded image







YA0207
CH3—


embedded image


H


embedded image







YA0208
CH3—


embedded image


H


embedded image







YA0209
CH3—


embedded image


H


embedded image







YA0210
CH3—


embedded image


H


embedded image







YA0211
CH3—


embedded image


H


embedded image







YA0212
CH3—


embedded image


H


embedded image







YA0213
CH3—


embedded image


H


embedded image







YA0214
CH3—


embedded image


H


embedded image







YA0215
CH3—


embedded image


H


embedded image







YA0216
CH3—


embedded image


H


embedded image







YA0217
CH3—


embedded image


H


embedded image







YA0218
CH3—


embedded image


H


embedded image







YA0219
CH3—


embedded image


H


embedded image







YA0220
CH3—


embedded image


H


embedded image







YA0221
CH3—


embedded image


H


embedded image







YA0222
CH3—


embedded image


H


embedded image







YA0223
CH3—


embedded image


H


embedded image







YA0224
CH3—


embedded image


H


embedded image







YA0225
CH3—


embedded image


H


embedded image







YA0226
CH3—


embedded image


H


embedded image







YA0227
CH3—


embedded image


H


embedded image







YA0228
CH3—


embedded image


H


embedded image







YA0229
CH3—


embedded image


H


embedded image







YA0230
CH3—


embedded image


H


embedded image







YA0231
CH3—


embedded image


H


embedded image







YA0232
CH3—


embedded image


H


embedded image







YA0233
CH3—
CH3—
H
H


YA0234
CH3—
CH3CH2—
H
H





YA0235
CH3—


embedded image


H
H





YA0236
CH3—


embedded image


H
H





YA0237
CH3—


embedded image


H
H





YA0238
CH3—


embedded image


H
H





YA0239
CH3—


embedded image


H
H





YA0240
CH3—


embedded image


H
H





YA0241
CH3—


embedded image


H
H





YA0242
CH3—


embedded image


H
H





YA0243
CH3—


embedded image


H
H





YA0244
CH3—


embedded image


H
H





YA0245
CH3—


embedded image


H
H





YA0246
CH3—


embedded image


H
H





YA0247
CH3—


embedded image


H
H





YA0248
CH3—


embedded image


H
H





YA0249
CH3—


embedded image


H
H





YA0250
CH3—


embedded image


H
H





YA0251
CH3—


embedded image


H
H





YA0252
CH3—


embedded image


H
H





YA0253
CH3—


embedded image


H
H





YA0254
CH3—


embedded image


H
H





YA0255
CH3—


embedded image


H
H





YA0256
CH3—


embedded image


H
H





YA0257
CH3—


embedded image


H
H





YA0258
CH3—


embedded image


H
H





YA0259
CH3—


embedded image


H
H





YA0260
CH3—


embedded image


H
H





YA0261
CH3—


embedded image


H
H





YA0262
CH3—


embedded image


H
H





YA0263
CH3—


embedded image


H
H





YA0264
CH3—


embedded image


H
H





YA0265
CH3—


embedded image


H
H





YA0266
CH3—


embedded image


H
H





YA0267
CH3—


embedded image


H
H





YA0268
CH3—


embedded image


H
H





YA0269
CH3—


embedded image


H
H





YA0270
CH3—


embedded image


H
H





YA0271
CH3—


embedded image


H
H





YA0272
CH3—


embedded image


H
H





YA0273
CH3—


embedded image


H
H





YA0274
CH3—


embedded image


H
H





YA0275
CH3—


embedded image


H
H





YA0276
CH3—


embedded image


H
H





YA0277
CH3—


embedded image


H
H





YA0278
CH3—


embedded image


H
H





YA0279
CH3—


embedded image


H
H





YA0280
CH3—


embedded image


H
H





YA0281
CH3—


embedded image


H
H





YA0282
CH3—


embedded image


H
H





YA0283
CH3—


embedded image


H
H





YA0284
CH3—


embedded image


H
H





YA0285
CH3—


embedded image


H
H





YA0286
CH3—


embedded image


H
H





YA0287
CH3—


embedded image


H
H





YA0288
CH3—


embedded image


H
H





YA0289
CH3—


embedded image


H
H





YA0290
CH3—


embedded image


H
H





YA0291
CH3—


embedded image


H
H





YA0292
CH3—


embedded image


H
H





YA0293
CH3—


embedded image


H
H





YA0294
CH3—


embedded image


H
H





YA0295
CH3—


embedded image


H
H





YA0296
CH3—


embedded image


H
H





YA0297
CH3—


embedded image


H
H





YA0298
CH3—


embedded image


H
H





YA0299
CH3—


embedded image


H
H





YA0300
CH3—


embedded image


H
H





YA0301
CH3—


embedded image


H
H





YA0302
CH3—


embedded image


H
H





YA0303
CH3—


embedded image


H
H





YA0304
CH3—


embedded image


H
H





YA0305
CH3—


embedded image


H
H





YA0306
CH3—


embedded image


H
H





YA0307
CH3—


embedded image


H
H





YA0308
CH3—


embedded image


H
H





YA0309
CH3—


embedded image


H
H





YA0310
CH3—


embedded image


H
H





YA0311
CH3—


embedded image


H
H





YA0312
CH3—


embedded image


H
H





YA0313
CH3—


embedded image


H
H





YA0314
CH3—


embedded image


H
H





YA0315
CH3—


embedded image


H
H





YA0316
CH3—


embedded image


H
H





YA0317
CH3—


embedded image


H
H





YA0318
CH3—


embedded image


H
H





YA0319
CH3—


embedded image


H
H





YA0320
CH3—


embedded image


H
H





YA0321
CH3—


embedded image


H
H





YA0322
CH3—


embedded image


H
H





YA0323
CH3—


embedded image


H
H





YA0324
CH3—


embedded image


H
H





YA0325
CH3—


embedded image


H
H





YA0326
CH3—


embedded image


H
H





YA0327
CH3—


embedded image


H
H





YA0328
CH3—


embedded image


H
H





YA0329
CH3—


embedded image


H
H





YA0330
CH3—


embedded image


H
H





YA0331
CH3—


embedded image


H
H





YA0332
CH3—


embedded image


H
H





YA0333
CH3—


embedded image


H
H





YA0334
CH3—


embedded image


H
H





YA0335
CH3—


embedded image


H
H





YA0336
CH3—


embedded image


H
H





YA0337
CH3—


embedded image


H
H





YA0338
CH3—


embedded image


H
H





YA0339
CH3—


embedded image


H
H





YA0340
CH3—


embedded image


H
H





YA0341
CH3—


embedded image


H
H





YA0342
CH3—


embedded image


H
H





YA0343
CH3—


embedded image


H
H





YA0344
CH3—


embedded image


H
H





YA0345
CH3—


embedded image


H
H





YA0346
CH3—


embedded image


H
H





YA0347
CH3—


embedded image


H
H





YA0348
CH3—


embedded image


H
H





YA0349
CH3—


embedded image


H
H





YA0350
CH3—


embedded image


H
H





YA0351
CH3—


embedded image


H
H





YA0352
CH3—


embedded image


H
H





YA0353
CH3—


embedded image


H
H





YA0354
CH3—


embedded image


H
H





YA0355
CH3—


embedded image


H
H





YA0356
CH3—


embedded image


H
H





YA0357
CH3—


embedded image


H
H





YA0358
CH3—


embedded image


H
H





YA0359
CH3—


embedded image


H
H





YA0360
CH3—


embedded image


H
H





YA0361
CH3—


embedded image


H
H





YA0362
CH3—


embedded image


H
H





YA0363
CH3—


embedded image


H
H





YA0364
CH3—


embedded image


H
H





YA0365
CH3—


embedded image


H
H





YA0366
CH3—


embedded image


H
H





YA0367
CH3—


embedded image


H
H





YA0368
CH3—


embedded image


H
H





YA0369
CH3—


embedded image


H
H





YA0370
CH3—


embedded image


H
H





YA0371
CH3—


embedded image


H
H





YA0372
CH3—


embedded image


H
H





YA0373
CH3—


embedded image


H
H





YA0374
CH3—


embedded image


H
H





YA0375
CH3—


embedded image


H
H





YA0376
CH3—


embedded image


H
H





YA0377
CH3—


embedded image


H
H





YA0378
CH3—


embedded image


H
H





YA0379
CH3—


embedded image


H
H





YA0380
CH3—


embedded image


H
H





YA0381
CH3—


embedded image


H
H





YA0382
CH3—


embedded image


H
H





YA0383
CH3—


embedded image


H
H





YA0384
CH3—


embedded image


H
H





YA0385
CH3—


embedded image


H
H





YA0386
CH3—


embedded image


H
H





YA0387
CH3—


embedded image


H
H





YA0388
CH3—


embedded image


H
H





YA0389
CH3—


embedded image


H
H





YA0390
CH3—


embedded image


H
H





YA0391
CH3—


embedded image


H
H





YA0392
CH3—


embedded image


H
H





YA0393
CH3—


embedded image


H
H





YA0394
CH3—


embedded image


H
H





YA0395
CH3—


embedded image


H
H





YA0396
CH3—


embedded image


H
H





YA0397
CH3—


embedded image


H
H





YA0398
CH3—


embedded image


H
H





YA0399
CH3—


embedded image


H
H





YA0400
CH3—


embedded image


H
H





YA0401
CH3—


embedded image


H
H





YA0402
CH3—


embedded image


H
H





YA0403
CH3—


embedded image


H
H





YA0404
CH3—


embedded image


H
H





YA0405
CH3—


embedded image


H
H





YA0406
CH3—


embedded image


H
H





YA0407
CH3—


embedded image


H
H





YA0408
CH3—


embedded image


H
H





YA0409
CH3—


embedded image


H
H





YA0410
CH3—


embedded image


H
H





YA0411
CH3—


embedded image


H
H





YA0412
CH3—


embedded image


H
H





YA0413
CH3—


embedded image


H
H





YA0414
CH3—


embedded image


H
H





YA0415
CH3—


embedded image


H
H





YA0416
CH3—


embedded image


H
H





YA0417
CH3—


embedded image


H
H





YA0418
CH3—


embedded image


H
H





YA0419
CH3—


embedded image


H
H





YA0420
CH3—


embedded image


H
H

























YA0421
CH3—


embedded image


H
H





YA0422
CH3—


embedded image


H
H





YA0423
CH3—


embedded image


H
H





YA0424
CH3—


embedded image


H
H





YA0425
CH3—


embedded image


H
H





YA0426
CH3—


embedded image


H
H





YA0427
CH3—


embedded image


H
H





YA0428
CH3—


embedded image


H
H





YA0429
CH3—


embedded image


H
H





YA0430
CH3—


embedded image


H
H





YA0431
CH3—


embedded image


H
H





YA0432
CH3—


embedded image


H
H





YA0433
CH3—


embedded image


H
H





YA0434
CH3—


embedded image


H
H





YA0435
CH3—


embedded image


H
H





YA0436
CH3—


embedded image


H
H





YA0437
CH3—


embedded image


H
H





YA0438
CH3—


embedded image


H
H





YA0439
CH3—


embedded image


H
H





YA0440
CH3—


embedded image


H
H





YA0441
CH3—


embedded image


H
H





YA0442
CH3—


embedded image


H
H





YA0443
CH3—


embedded image


H
H





YA0444
CH3—


embedded image


H
H





YA0445
CH3—


embedded image


H
H





YA0446
CH3—


embedded image


H
H





YA0447
CH3—


embedded image


H
H





YA0448
CH3—


embedded image


H
H





YA0449
CH3—


embedded image


H
H





YA0450
CH3—


embedded image


H
H





YA0451
CH3—


embedded image


H
H





YA0452
CH3—


embedded image


H
H





YA0453
CH3—


embedded image


H
H





YA0454
CH3—


embedded image


H
H





YA0455
CH3—


embedded image


H
H





YA0456
CH3—


embedded image


H
H





YA0457
CH3—


embedded image


H
H





YA0458
CH3—


embedded image


H
H





YA0459
CH3—


embedded image


H
H





YA0460
CH3—


embedded image


H
H





YA0461
CH3—


embedded image


H
H





YA0462
CH3—


embedded image


H
H





YA0463
CH3—


embedded image


H
H





YA0464
CH3—


embedded image


H
H





YA0465
CH3—


embedded image


H
H





YA0466
CH3—


embedded image


H
H





YA0467
CH3—


embedded image


H
H





YA0468
CH3—


embedded image


H
H





YA0469
CH3—


embedded image


H
H





YA0470
CH3—


embedded image


H
H





YA0471
CH3—


embedded image


H
H





YA0472
CH3—


embedded image


H
H





YA0473
CH3—


embedded image


H
H





YA0474
CH3—


embedded image


H
H





YA0475
CH3—


embedded image


H
H





YA0476
CH3—


embedded image


H
H





YA0477
CH3—


embedded image


H
H





YA0478
CH3—


embedded image


H
H





YA0479
CH3—


embedded image


H
H





YA0480
CH3—


embedded image


H
H





YA0481
CH3—


embedded image


H
H





YA0482
CH3—


embedded image


H
H





YA0483
CH3—


embedded image


H
H





YA0484
CH3—


embedded image


H
H





YA0485
CH3—


embedded image


H
H





YA0486
CH3—


embedded image


H
H





YA0487
CH3—


embedded image


H
H





YA0488
CH3—


embedded image


H
H





YA0489
CH3—


embedded image


H
H





YA0490
CH3—


embedded image


H
H





YA0491
CH3—


embedded image


H
H





YA0492
CH3—


embedded image


H
H





YA0493
CH3—


embedded image


H
H





YA0494
CH3—


embedded image


H
H





YA0495
CH3—


embedded image


H
H





YA0496
CH3—


embedded image


H
H





YA0497
CH3—


embedded image


H
H





YA0498
CH3—


embedded image


H
H





YA0499
CH3—


embedded image


H
H





YA0500
CH3—


embedded image


H
H





YA0501
CH3—


embedded image


H
H





YA0502
CH3—


embedded image


H
H





YA0503
CH3—


embedded image


H
H





YA0504
CH3—


embedded image


H
H





YA0505
CH3—


embedded image


H
H





YA0506
CH3—


embedded image


H
H





YA0507
CH3—


embedded image


H
H





YA0508
CH3—


embedded image


H
H





YA0509
CH3—


embedded image


H
H





YA0510
CH3—


embedded image


H
H





YA0511
CH3—


embedded image


H
H





YA0512
CH3—


embedded image


H
H





YA0513
CH3—


embedded image


H
H





YA0514
CH3—


embedded image


H
H





YA0515
CH3—


embedded image


H
H





YA0516
CH3—


embedded image


H
H





YA0517
CH3—


embedded image


H
H





YA0518
CH3—


embedded image


H
H





YA0519
CH3—


embedded image


H
H





YA0520
CH3—


embedded image


H
H





YA0521
CH3—
CH3—
H
CH3


YA0522
CH3—
CH3CH2—
H
CH3





YA0523
CH3—


embedded image


H
CH3





YA0524
CH3—


embedded image


H
CH3





YA0525
CH3—


embedded image


H
CH3





YA0526
CH3—


embedded image


H
CH3





YA0527
CH3—


embedded image


H
CH3





YA0528
CH3—


embedded image


H
CH3





YA0529
CH3—


embedded image


H
CH3





YA0530
CH3—


embedded image


H
CH3





YA0531
CH3—


embedded image


H
CH3





YA0532
CH3—


embedded image


H
CH3





YA0533
CH3—


embedded image


H
CH3





YA0534
CH3—


embedded image


H
CH3





YA0535
CH3—


embedded image


H
CH3





YA0536
CH3—


embedded image


H
CH3





YA0537
CH3—


embedded image


H
CH3





YA0538
CH3—


embedded image


H
CH3





YA0539
CH3—


embedded image


H
CH3





YA0540
CH3—


embedded image


H
CH3





YA0541
CH3—


embedded image


H
CH3





YA0542
CH3—


embedded image


H
CH3





YA0543
CH3—


embedded image


H
CH3





YA0544
CH3—


embedded image


H
CH3





YA0545
CH3—


embedded image


H
CH3





YA0546
CH3—


embedded image


H
CH3





YA0547
CH3—


embedded image


H
CH3





YA0548
CH3—


embedded image


H
CH3





YA0549
CH3—


embedded image


H
CH3





YA0550
CH3—


embedded image


H
CH3





YA0551
CH3—


embedded image


H
CH3





YA0552
CH3—


embedded image


H
CH3





YA0553
CH3—


embedded image


H
CH3





YA0554
CH3—


embedded image


H
CH3





YA0555
CH3—


embedded image


H
CH3





YA0556
CH3—


embedded image


H
CH3





YA0557
CH3—


embedded image


H
CH3





YA0558
CH3—


embedded image


H
CH3





YA0559
CH3—


embedded image


H
CH3





YA0560
CH3—


embedded image


H
CH3





YA0561
CH3—


embedded image


H
CH3





YA0562
CH3—


embedded image


H
CH3





YA0563
CH3—


embedded image


H
CH3





YA0564
CH3—


embedded image


H
CH3





YA0565
CH3—


embedded image


H
CH3





YA0566
CH3—


embedded image


H
CH3





YA0567
CH3—


embedded image


H
CH3





YA0568
CH3—


embedded image


H
CH3





YA0569
CH3—


embedded image


H
CH3





YA0570
CH3—


embedded image


H
CH3





YA0571
CH3—


embedded image


H
CH3





YA0572
CH3—


embedded image


H
CH3





YA0573
CH3—


embedded image


H
CH3





YA0574
CH3—


embedded image


H
CH3





YA0575
CH3—


embedded image


H
CH3





YA0576
CH3—


embedded image


H
CH3





YA0577
CH3—


embedded image


H
CH3





YA0578
CH3—


embedded image


H
CH3





YA0579
CH3—


embedded image


H
CH3





YA0580
CH3—


embedded image


H
CH3





YA0581
CH3—


embedded image


H
CH3





YA0582
CH3—


embedded image


H
CH3





YA0583
CH3—


embedded image


H
CH3





YA0584
CH3—


embedded image


H
CH3





YA0585
CH3—


embedded image


H
CH3





YA0586
CH3—


embedded image


H
CH3





YA0587
CH3—


embedded image


H
CH3





YA0588
CH3—


embedded image


H
CH3





YA0589
CH3—


embedded image


H
CH3





YA0590
CH3—


embedded image


H
CH3





YA0591
CH3—


embedded image


H
CH3





YA0592
CH3—


embedded image


H
CH3





YA0593
CH3—


embedded image


H
CH3





YA0594
CH3—


embedded image


H
CH3





YA0595
CH3—


embedded image


H
CH3





YA0596
CH3—


embedded image


H
CH3





YA0597
CH3—


embedded image


H
CH3





YA0598
CH3—


embedded image


H
CH3





YA0599
CH3—


embedded image


H
CH3





YA0600
CH3—


embedded image


H
CH3





YA0601
CH3—


embedded image


H
CH3





YA0602
CH3—


embedded image


H
CH3





YA0603
CH3—


embedded image


H
CH3





YA0604
CH3—


embedded image


H
CH3





YA0605
CH3—


embedded image


H
CH3





YA0606
CH3—


embedded image


H
CH3





YA0607
CH3—


embedded image


H
CH3





YA0608
CH3—


embedded image


H
CH3





YA0609
CH3—


embedded image


H
CH3





YA0610
CH3—


embedded image


H
CH3





YA0611
CH3—


embedded image


H
CH3





YA0612
CH3—


embedded image


H
CH3





YA0613
CH3—


embedded image


H
CH3





YA0614
CH3—


embedded image


H
CH3





YA0615
CH3—


embedded image


H
CH3





YA0616
CH3—


embedded image


H
CH3





YA0617
CH3—


embedded image


H
CH3





YA0618
CH3—


embedded image


H
CH3





YA0619
CH3—


embedded image


H
CH3





YA0620
CH3—


embedded image


H
CH3





YA0621
CH3—


embedded image


H
CH3





YA0622
CH3—


embedded image


H
CH3





YA0623
CH3—


embedded image


H
CH3





YA0624
CH3—


embedded image


H
CH3





YA0625
CH3—


embedded image


H
CH3





YA0626
CH3—


embedded image


H
CH3





YA0627
CH3—


embedded image


H
CH3





YA0628
CH3—


embedded image


H
CH3





YA0629
CH3—


embedded image


H
CH3





YA0630
CH3—


embedded image


H
CH3





YA0631
CH3—


embedded image


H
CH3





YA0632
CH3—


embedded image


H
CH3





YA0633
CH3—


embedded image


H
CH3





YA0634
CH3—


embedded image


H
CH3





YA0635
CH3—


embedded image


H
CH3





YA0636
CH3—


embedded image


H
CH3





YA0637
CH3—


embedded image


H
CH3





YA0638
CH3—


embedded image


H
CH3





YA0639
CH3—


embedded image


H
CH3





YA0640
CH3—


embedded image


H
CH3





YA0641
CH3—


embedded image


H
CH3





YA0642
CH3—


embedded image


H
CH3





YA0643
CH3—


embedded image


H
CH3





YA0644
CH3—


embedded image


H
CH3





YA0645
CH3—


embedded image


H
CH3





YA0646
CH3—


embedded image


H
CH3





YA0647
CH3—


embedded image


H
CH3





YA0648
CH3—


embedded image


H
CH3





YA0649
CH3—


embedded image


H
CH3





YA0650
CH3—


embedded image


H
CH3





YA0651
CH3—


embedded image


H
CH3





YA0652
CH3—


embedded image


H
CH3





YA0653
CH3—


embedded image


H
CH3





YA0654
CH3—


embedded image


H
CH3





YA0655
CH3—


embedded image


H
CH3





YA0656
CH3—


embedded image


H
CH3





YA0657
CH3—


embedded image


H
CH3





YA0658
CH3—


embedded image


H
CH3





YA0659
CH3—


embedded image


H
CH3





YA0660
CH3—


embedded image


H
CH3





YA0661
CH3—


embedded image


H
CH3





YA0662
CH3—


embedded image


H
CH3





YA0663
CH3—


embedded image


H
CH3





YA0664
CH3—


embedded image


H
CH3





YA0665
CH3—


embedded image


H
CH3





YA0666
CH3—


embedded image


H
CH3





YA0667
CH3—


embedded image


H
CH3





YA0668
CH3—


embedded image


H
CH3





YA0669
CH3—


embedded image


H
CH3





YA0670
CH3—


embedded image


H
CH3





YA0671
CH3—


embedded image


H
CH3





YA0672
CH3—


embedded image


H
CH3





YA0673
CH3—


embedded image


H
CH3





YA0674
CH3—


embedded image


H
CH3





YA0675
CH3—


embedded image


H
CH3





YA0676
CH3—


embedded image


H
CH3





YA0677
CH3—


embedded image


H
CH3





YA0678
CH3—


embedded image


H
CH3





YA0679
CH3—


embedded image


H
CH3





YA0680
CH3—


embedded image


H
CH3





YA0681
CH3—


embedded image


H
CH3





YA0682
CH3—


embedded image


H
CH3





YA0683
CH3—


embedded image


H
CH3





YA0684
CH3—


embedded image


H
CH3





YA0685
CH3—


embedded image


H
CH3





YA0686
CH3—


embedded image


H
CH3





YA0687
CH3—


embedded image


H
CH3





YA0688
CH3—


embedded image


H
CH3





YA0689
CH3—


embedded image


H
CH3





YA0690
CH3—


embedded image


H
CH3





YA0691
CH3—


embedded image


H
CH3





YA0692
CH3—


embedded image


H
CH3





YA0693
CH3—


embedded image


H
CH3





YA0694
CH3—


embedded image


H
CH3





YA0695
CH3—


embedded image


H
CH3





YA0696
CH3—


embedded image


H
CH3





YA0697
CH3—


embedded image


H
CH3





YA0698
CH3—


embedded image


H
CH3





YA0699
CH3—


embedded image


H
CH3





YA0700
CH3—


embedded image


H
CH3





YA0701
CH3—


embedded image


H
CH3





YA0702
CH3—


embedded image


H
CH3





YA0703
CH3—


embedded image


H
CH3





YA0704
CH3—


embedded image


H
CH3





YA0705
CH3—


embedded image


H
CH3





YA0706
CH3—


embedded image


H
CH3





YA0707
CH3—


embedded image


H
CH3





YA0708
CH3—


embedded image


H
CH3





YA0709
CH3—


embedded image


H
CH3





YA0710
CH3—


embedded image


H
CH3





YA0711
CH3—


embedded image


H
CH3





YA0712
CH3—


embedded image


H
CH3





YA0713
CH3—


embedded image


H
CH3





YA0714
CH3—


embedded image


H
CH3





YA0715
CH3—


embedded image


H
CH3





YA0716
CH3—


embedded image


H
CH3





YA0717
CH3—


embedded image


H
CH3





YA0718
CH3—


embedded image


H
CH3





YA0719
CH3—


embedded image


H
CH3





YA0720
CH3—


embedded image


H
CH3





YA0721
CH3—


embedded image


H
CH3





YA0722
CH3—


embedded image


H
CH3





YA0723
CH3—


embedded image


H
CH3





YA0724
CH3—


embedded image


H
CH3





YA0725
CH3—


embedded image


H
CH3





YA0726
CH3—


embedded image


H
CH3





YA0727
CH3—


embedded image


H
CH3





YA0728
CH3—


embedded image


H
CH3





YA0729
CH3—


embedded image


H
CH3





YA0730
CH3—


embedded image


H
CH3





YA0731
CH3—
CH3—
H


embedded image







YA0732
CH3—
CH3CH2—
H


embedded image







YA0733
CH3—


embedded image


H


embedded image







YA0734
CH3—


embedded image


H


embedded image







YA0735
CH3—


embedded image


H


embedded image







YA0736
CH3—


embedded image


H


embedded image







YA0737
CH3—


embedded image


H


embedded image







YA0738
CH3—


embedded image


H


embedded image







YA0739
CH3—


embedded image


H


embedded image







YA0740
CH3—


embedded image


H


embedded image







YA0741
CH3—


embedded image


H


embedded image







YA0742
CH3—


embedded image


H


embedded image







YA0743
CH3—


embedded image


H


embedded image







YA0744
CH3—


embedded image


H


embedded image







YA0745
CH3—


embedded image


H


embedded image







YA0746
CH3—


embedded image


H


embedded image







YA0747
CH3—


embedded image


H


embedded image







YA0748
CH3—


embedded image


H


embedded image







YA0749
CH3—


embedded image


H


embedded image







YA0750
CH3—


embedded image


H


embedded image







YA0751
CH3—


embedded image


H


embedded image







YA0752
CH3—


embedded image


H


embedded image







YA0753
CH3—


embedded image


H


embedded image







YA0754
CH3—


embedded image


H


embedded image







YA0755
CH3—


embedded image


H


embedded image







YA0756
CH3—


embedded image


H


embedded image







YA0757
CH3—


embedded image


H


embedded image







YA0758
CH3—


embedded image


H


embedded image







YA0759
CH3—


embedded image


H


embedded image







YA0760
CH3—


embedded image


H


embedded image







YA0761
CH3—


embedded image


H


embedded image







YA0762
CH3—


embedded image


H


embedded image







YA0763
CH3—


embedded image


H


embedded image







YA0764
CH3—


embedded image


H


embedded image







YA0765
CH3—


embedded image


H


embedded image







YA0766
CH3—


embedded image


H


embedded image







YA0767
CH3—


embedded image


H


embedded image







YA0768
CH3—


embedded image


H


embedded image







YA0769
CH3—


embedded image


H


embedded image







YA0770
CH3—


embedded image


H


embedded image







YA0771
CH3—


embedded image


H


embedded image







YA0772
CH3—


embedded image


H


embedded image







YA0773
CH3—


embedded image


H


embedded image







YA0774
CH3—


embedded image


H


embedded image







YA0775
CH3—


embedded image


H


embedded image







YA0776
CH3—


embedded image


H


embedded image







YA0777
CH3—


embedded image


H


embedded image







YA0778
CH3—


embedded image


H


embedded image







YA0779
CH3—


embedded image


H


embedded image







YA0780
CH3—


embedded image


H


embedded image







YA0781
CH3—


embedded image


H


embedded image







YA0782
CH3—


embedded image


H


embedded image







YA0783
CH3—


embedded image


H


embedded image







YA0784
CH3—


embedded image


H


embedded image







YA0785
CH3—


embedded image


H


embedded image







YA0786
CH3—


embedded image


H


embedded image







YA0787
CH3—


embedded image


H


embedded image







YA0788
CH3—


embedded image


H


embedded image







YA0789
CH3—


embedded image


H


embedded image







YA0790
CH3—


embedded image


H


embedded image







YA0791
CH3—


embedded image


H


embedded image







YA0792
CH3—


embedded image


H


embedded image







YA0793
CH3—


embedded image


H


embedded image







YA0794
CH3—


embedded image


H


embedded image







YA0795
CH3—


embedded image


H


embedded image







YA0796
CH3—


embedded image


H


embedded image







YA0797
CH3—


embedded image


H


embedded image







YA0798
CH3—


embedded image


H


embedded image







YA0799
CH3—


embedded image


H


embedded image







YA0800
CH3—


embedded image


H


embedded image







YA0801
CH3—


embedded image


H


embedded image







YA0802
CH3—


embedded image


H


embedded image







YA0803
CH3—


embedded image


H


embedded image







YA0804
CH3—


embedded image


H


embedded image







YA0805
CH3—


embedded image


H


embedded image







YA0806
CH3—


embedded image


H


embedded image







YA0807
CH3—


embedded image


H


embedded image







YA0808
CH3—


embedded image


H


embedded image







YA0809
CH3—


embedded image


H


embedded image







YA0810
CH3—


embedded image


H


embedded image







YA0811
CH3—


embedded image


H


embedded image







YA0812
CH3—


embedded image


H


embedded image







YA0813
CH3—


embedded image


H


embedded image







YA0814
CH3—


embedded image


H


embedded image







YA0815
CH3—


embedded image


H


embedded image







YA0816
CH3—


embedded image


H


embedded image







YA0817
CH3—


embedded image


H


embedded image







YA0818
CH3—


embedded image


H


embedded image







YA0819
CH3—


embedded image


H


embedded image







YA0820
CH3—


embedded image


H


embedded image







YA0821
CH3—


embedded image


H


embedded image







YA0822
CH3—


embedded image


H


embedded image







YA0823
CH3—


embedded image


H


embedded image







YA0824
CH3—


embedded image


H


embedded image







YA0825
CH3—


embedded image


H


embedded image







YA0826
CH3—


embedded image


H


embedded image







YA0827
CH3—


embedded image


H


embedded image







YA0828
CH3—


embedded image


H


embedded image







YA0829
CH3—


embedded image


H


embedded image







YA0830
CH3—


embedded image


H


embedded image







YA0831
CH3—


embedded image


H


embedded image







YA0832
CH3—


embedded image


H


embedded image







YA0833
CH3—


embedded image


H


embedded image







YA0834
CH3—


embedded image


H


embedded image







YA0835
CH3—


embedded image


H


embedded image







YA0836
CH3—


embedded image


H


embedded image







YA0837
CH3—


embedded image


H


embedded image







YA0838
CH3—


embedded image


H


embedded image







YA0839
CH3—


embedded image


H


embedded image







YA0840
CH3—


embedded image


H


embedded image







YA0841
CH3—


embedded image


H


embedded image







YA0842
CH3—


embedded image


H


embedded image







YA0843
CH3—


embedded image


H


embedded image







YA0844
CH3—


embedded image


H


embedded image







YA0845
CH3—


embedded image


H


embedded image







YA0846
CH3—


embedded image


H


embedded image







YA0847
CH3—


embedded image


H


embedded image







YA0848
CH3—


embedded image


H


embedded image







YA0849
CH3—


embedded image


H


embedded image







YA0850
CH3—


embedded image


H


embedded image







YA0851
CH3—


embedded image


H


embedded image







YA0852
CH3—


embedded image


H


embedded image







YA0853
CH3—


embedded image


H


embedded image







YA0854
CH3—


embedded image


H


embedded image







YA0855
CH3—


embedded image


H


embedded image



























YA0856
CH3—


embedded image


H


embedded image







YA0857
CH3—


embedded image


H


embedded image







YA0858
CH3—


embedded image


H


embedded image







YA0859
CH3—


embedded image


H


embedded image







YA0860
CH3—


embedded image


H


embedded image







YA0861
CH3—


embedded image


H


embedded image







YA0862
CH3—


embedded image


H


embedded image







YA0863
CH3—


embedded image


H


embedded image







YA0864
CH3—


embedded image


H


embedded image







YA0865
CH3—


embedded image


H


embedded image







YA0866
CH3—


embedded image


H


embedded image







YA0867
CH3—


embedded image


H


embedded image







YA0868
CH3—


embedded image


H


embedded image







YA0869
CH3—


embedded image


H


embedded image







YA0870
CH3—


embedded image


H


embedded image







YA0871
CH3—


embedded image


H


embedded image







YA0872
CH3—


embedded image


H


embedded image







YA0873
CH3—


embedded image


H


embedded image







YA0874
CH3—


embedded image


H


embedded image







YA0875
CH3—


embedded image


H


embedded image







YA0876
CH3—


embedded image


H


embedded image







YA0877
CH3—


embedded image


H


embedded image







YA0878
CH3—


embedded image


H


embedded image







YA0879
CH3—


embedded image


H


embedded image







YA0880
CH3—


embedded image


H


embedded image







YA0881
CH3—


embedded image


H


embedded image







YA0882
CH3—


embedded image


H


embedded image







YA0883
CH3—


embedded image


H


embedded image







YA0884
CH3—


embedded image


H


embedded image







YA0885
CH3—


embedded image


H


embedded image







YA0886
CH3—


embedded image


H


embedded image







YA0887
CH3—


embedded image


H


embedded image







YA0888
CH3—


embedded image


H


embedded image







YA0889
CH3—


embedded image


H


embedded image







YA0890
CH3—


embedded image


H


embedded image







YA0891
CH3—


embedded image


H


embedded image







YA0892
CH3—


embedded image


H


embedded image







YA0893
CH3—


embedded image


H


embedded image







YA0894
CH3—


embedded image


H


embedded image







YA0895
CH3—


embedded image


H


embedded image







YA0896
CH3—


embedded image


H


embedded image







YA0897
CH3—


embedded image


H


embedded image







YA0898
CH3—


embedded image


H


embedded image







YA0899
CH3—


embedded image


H


embedded image







YA0900
CH3—


embedded image


H


embedded image







YA0901
CH3—


embedded image


H


embedded image







YA0902
CH3—


embedded image


H


embedded image







YA0903
CH3—


embedded image


H


embedded image







YA0904
CH3—


embedded image


H


embedded image







YA0905
CH3—


embedded image


H


embedded image







YA0906
CH3—


embedded image


H


embedded image







YA0907
CH3—


embedded image


H


embedded image







YA0908
CH3—


embedded image


H


embedded image







YA0909
CH3—


embedded image


H


embedded image







YA0910
CH3—


embedded image


H


embedded image







YA0911
CH3—


embedded image


H


embedded image







YA0912
CH3—


embedded image


H


embedded image







YA0913
CH3—


embedded image


H


embedded image







YA0914
CH3—


embedded image


H


embedded image







YA0915
CH3—


embedded image


H


embedded image







YA0916
CH3—


embedded image


H


embedded image







YA0917
CH3—


embedded image


H


embedded image







YA0918
CH3—


embedded image


H


embedded image







YA0919
CH3—


embedded image


H


embedded image







YA0920
CH3—


embedded image


H


embedded image







YA0921
CH3—


embedded image


H


embedded image







YA0922
CH3—


embedded image


H


embedded image







YA0923
CH3—


embedded image


H


embedded image







YA0924
CH3—


embedded image


H


embedded image







YA0925
CH3—


embedded image


H


embedded image







YA0926
CH3—


embedded image


H


embedded image







YA0927
CH3—


embedded image


H


embedded image







YA0928
CH3—


embedded image


H


embedded image







YA0929
CH3—


embedded image


H


embedded image







YA0930
CH3—


embedded image


H


embedded image







YA0931
CH3—


embedded image


H


embedded image







YA0932
CH3—


embedded image


H


embedded image







YA0933
CH3—


embedded image


H


embedded image







YA0934
CH3—


embedded image


H


embedded image







YA0935
CH3—


embedded image


H


embedded image







YA0936
CH3—


embedded image


H


embedded image







YA0937
CH3—


embedded image


H


embedded image







YA0938
CH3—


embedded image


H


embedded image







YA0939
CH3—


embedded image


H


embedded image







YA0940
CH3—


embedded image


H


embedded image







YA0941
CH3—
CH3—
H


embedded image




YA0942
CH3—
CH3CH2—
H


embedded image







YA0943
CH3—


embedded image


H


embedded image







YA0944
CH3—


embedded image


H


embedded image







YA0945
CH3—


embedded image


H


embedded image







YA0946
CH3—


embedded image


H


embedded image







YA0947
CH3—


embedded image


H


embedded image







YA0948
CH3—


embedded image


H


embedded image







YA0949
CH3—


embedded image


H


embedded image







YA0950
CH3—


embedded image


H


embedded image







YA0951
CH3—


embedded image


H


embedded image







YA0952
CH3—


embedded image


H


embedded image







YA0953
CH3—


embedded image


H


embedded image







YA0954
CH3—


embedded image


H


embedded image







YA0955
CH3—


embedded image


H


embedded image







YA0956
CH3—


embedded image


H


embedded image







YA0957
CH3—


embedded image


H


embedded image







YA0958
CH3—


embedded image


H


embedded image







YA0959
CH3—


embedded image


H


embedded image







YA0960
CH3—


embedded image


H


embedded image







YA0961
CH3—


embedded image


H


embedded image







YA0962
CH3—


embedded image


H


embedded image







YA0963
CH3—


embedded image


H


embedded image







YA0964
CH3—


embedded image


H


embedded image







YA0965
CH3—


embedded image


H


embedded image







YA0966
CH3—


embedded image


H


embedded image







YA0967
CH3—


embedded image


H


embedded image







YA0968
CH3—


embedded image


H


embedded image







YA0969
CH3—


embedded image


H


embedded image







YA0970
CH3—


embedded image


H


embedded image







YA0971
CH3—


embedded image


H


embedded image







YA0972
CH3—


embedded image


H


embedded image







YA0973
CH3—


embedded image


H


embedded image







YA0974
CH3—


embedded image


H


embedded image







YA0975
CH3—


embedded image


H


embedded image







YA0976
CH3—


embedded image


H


embedded image







YA0977
CH3—


embedded image


H


embedded image







YA0978
CH3—


embedded image


H


embedded image







YA0979
CH3—


embedded image


H


embedded image







YA0980
CH3—


embedded image


H


embedded image







YA0981
CH3—


embedded image


H


embedded image







YA0982
CH3—


embedded image


H


embedded image







YA0983
CH3—


embedded image


H


embedded image







YA0984
CH3—


embedded image


H


embedded image







YA0985
CH3—


embedded image


H


embedded image







YA0986
CH3—


embedded image


H


embedded image







YA0987
CH3—


embedded image


H


embedded image







YA0988
CH3—


embedded image


H


embedded image







YA0989
CH3—


embedded image


H


embedded image







YA0990
CH3—


embedded image


H


embedded image







YA0991
CH3—


embedded image


H


embedded image







YA0992
CH3—


embedded image


H


embedded image







YA0993
CH3—


embedded image


H


embedded image







YA0994
CH3—


embedded image


H


embedded image







YA0995
CH3—


embedded image


H


embedded image







YA0996
CH3—


embedded image


H


embedded image







YA0997
CH3—


embedded image


H


embedded image







YA0998
CH3—


embedded image


H


embedded image







YA0999
CH3—


embedded image


H


embedded image







YA1000
CH3—


embedded image


H


embedded image







YA1001
CH3—


embedded image


H


embedded image







YA1002
CH3—


embedded image


H


embedded image







YA1003
CH3—


embedded image


H


embedded image







YA1004
CH3—


embedded image


H


embedded image







YA1005
CH3—


embedded image


H


embedded image







YA1006
CH3—


embedded image


H


embedded image







YA1007
CH3—


embedded image


H


embedded image







YA1008
CH3—


embedded image


H


embedded image







YA1009
CH3—


embedded image


H


embedded image







YA1010
CH3—


embedded image


H


embedded image







YA1011
CH3—


embedded image


H


embedded image







YA1012
CH3—


embedded image


H


embedded image







YA1013
CH3—


embedded image


H


embedded image







YA1014
CH3—


embedded image


H


embedded image







YA1015
CH3—


embedded image


H


embedded image







YA1016
CH3—


embedded image


H


embedded image







YA1017
CH3—


embedded image


H


embedded image







YA1018
CH3—


embedded image


H


embedded image







YA1019
CH3—


embedded image


H


embedded image







YA1020
CH3—


embedded image


H


embedded image







YA1021
CH3—


embedded image


H


embedded image







YA1022
CH3—


embedded image


H


embedded image







YA1023
CH3—


embedded image


H


embedded image







YA1024
CH3—


embedded image


H


embedded image







YA1025
CH3—


embedded image


H


embedded image







YA1026
CH3—


embedded image


H


embedded image







YA1027
CH3—


embedded image


H


embedded image







YA1028
CH3—


embedded image


H


embedded image







YA1029
CH3—


embedded image


H


embedded image







YA1030
CH3—


embedded image


H


embedded image







YA1031
CH3—


embedded image


H


embedded image







YA1032
CH3—


embedded image


H


embedded image







YA1033
CH3—


embedded image


H


embedded image







YA1034
CH3—


embedded image


H


embedded image







YA1035
CH3—


embedded image


H


embedded image







YA1036
CH3—


embedded image


H


embedded image







YA1037
CH3—


embedded image


H


embedded image







YA1038
CH3—


embedded image


H


embedded image







YA1039
CH3—


embedded image


H


embedded image







YA1040
CH3—


embedded image


H


embedded image







YA1041
CH3—


embedded image


H


embedded image







YA1042
CH3—


embedded image


H


embedded image







YA1043
CH3—


embedded image


H


embedded image







YA1044
CH3—


embedded image


H


embedded image







YA1045
CH3—


embedded image


H


embedded image







YA1046
CH3—


embedded image


H


embedded image







YA1047
CH3—


embedded image


H


embedded image







YA1048
CH3—


embedded image


H


embedded image







YA1049
CH3—


embedded image


H


embedded image







YA1050
CH3—


embedded image


H


embedded image







YA1051
CH3—


embedded image


H


embedded image







YA1052
CH3—


embedded image


H


embedded image







YA1053
CH3—


embedded image


H


embedded image







YA1054
CH3—


embedded image


H


embedded image







YA1055
CH3—


embedded image


H


embedded image







YA1056
CH3—


embedded image


H


embedded image







YA1057
CH3—


embedded image


H


embedded image







YA1058
CH3—


embedded image


H


embedded image







YA1059
CH3—


embedded image


H


embedded image







YA1060
CH3—


embedded image


H


embedded image







YA1061
CH3—


embedded image


H


embedded image







YA1062
CH3—


embedded image


H


embedded image







YA1063
CH3—


embedded image


H


embedded image







YA1064
CH3—


embedded image


H


embedded image







YA1065
CH3—


embedded image


H


embedded image







YA1066
CH3—


embedded image


H


embedded image







YA1067
CH3—


embedded image


H


embedded image







YA1068
CH3—


embedded image


H


embedded image







YA1069
CH3—


embedded image


H


embedded image







YA1070
CH3—


embedded image


H


embedded image







YA1071
CH3—


embedded image


H


embedded image







YA1072
CH3—


embedded image


H


embedded image







YA1073
CH3—


embedded image


H


embedded image







YA1074
CH3—


embedded image


H


embedded image







YA1075
CH3—


embedded image


H


embedded image







YA1076
CH3—


embedded image


H


embedded image







YA1077
CH3—


embedded image


H


embedded image







YA1078
CH3—


embedded image


H


embedded image







YA1079
CH3—


embedded image


H


embedded image







YA1080
CH3—


embedded image


H


embedded image







YA1081
CH3—


embedded image


H


embedded image







YA1082
CH3—


embedded image


H


embedded image







YA1083
CH3—


embedded image


H


embedded image







YA1084
CH3—


embedded image


H


embedded image







YA1085
CH3—


embedded image


H


embedded image







YA1086
CH3—


embedded image


H


embedded image







YA1087
CH3—


embedded image


H


embedded image







YA1088
CH3—


embedded image


H


embedded image







YA1089
CH3—


embedded image


H


embedded image







YA1090
CH3—


embedded image


H


embedded image







YA1091
CH3—


embedded image


H


embedded image







YA1092
CH3—


embedded image


H


embedded image







YA1093
CH3—


embedded image


H


embedded image







YA1094
CH3—


embedded image


H


embedded image







YA1095
CH3—


embedded image


H


embedded image







YA1096
CH3—


embedded image


H


embedded image







YA1097
CH3—


embedded image


H


embedded image







YA1098
CH3—


embedded image


H


embedded image







YA1099
CH3—


embedded image


H


embedded image







YA1100
CH3—


embedded image


H


embedded image







YA1101
CH3—


embedded image


H


embedded image







YA1102
CH3—


embedded image


H


embedded image







YA1103
CH3—


embedded image


H


embedded image







YA1104
CH3—


embedded image


H


embedded image







YA1105
CH3—


embedded image


H


embedded image







YA1106
CH3—


embedded image


H


embedded image







YA1107
CH3—


embedded image


H


embedded image







YA1108
CH3—


embedded image


H


embedded image







YA1109
CH3—


embedded image


H


embedded image







YA1110
CH3—


embedded image


H


embedded image







YA1111
CH3—


embedded image


H


embedded image







YA1112
CH3—


embedded image


H


embedded image







YA1113
CH3—


embedded image


H


embedded image







YA1114
CH3—


embedded image


H


embedded image







YA1115
CH3—


embedded image


H


embedded image







YA1116
CH3—


embedded image


H


embedded image







YA1117
CH3—


embedded image


H


embedded image







YA1118
CH3—


embedded image


H


embedded image







YA1119
CH3—


embedded image


H


embedded image







YA1120
CH3—


embedded image


H


embedded image







YA1121
CH3—


embedded image


H


embedded image







YA1122
CH3—


embedded image


H


embedded image







YA1123
CH3—


embedded image


H


embedded image







YA1124
CH3—


embedded image


H


embedded image







YA1125
CH3—


embedded image


H


embedded image







YA1126
CH3—


embedded image


H


embedded image







YA1127
CH3—


embedded image


H


embedded image







YA1128
CH3—


embedded image


H


embedded image







YA1129
CH3—


embedded image


H


embedded image







YA1130
CH3—


embedded image


H


embedded image







YA1131
CH3—


embedded image


H


embedded image







YA1132
CH3—


embedded image


H


embedded image







YA1133
CH3—


embedded image


H


embedded image







YA1134
CH3—


embedded image


H


embedded image







YA1135
CH3—


embedded image


H


embedded image







YA1136
CH3—


embedded image


H


embedded image







YA1137
CH3—


embedded image


H


embedded image







YA1138
CH3—


embedded image


H


embedded image







YA1139
CH3—


embedded image


H


embedded image







YA1140
CH3—


embedded image


H


embedded image







YA1141
CH3—


embedded image


H


embedded image







YA1142
CH3—


embedded image


H


embedded image







YA1143
CH3—


embedded image


H


embedded image







YA1144
CH3—


embedded image


H


embedded image







YA1145
CH3—


embedded image


H


embedded image







YA1146
CH3—


embedded image


H


embedded image







YA1147
CH3—


embedded image


H


embedded image







YA1148
CH3—


embedded image


H


embedded image







YA1149
CH3—


embedded image


H


embedded image







YA1150
CH3—


embedded image


H


embedded image







YA1151
CH3—


embedded image


H


embedded image







YA1152
CH3—


embedded image


H


embedded image







YA1153
CH3—


embedded image


H


embedded image







YA1154
CH3—
CH3—
CH3—
H


YA1155
CH3—
CH3CH2—
CH3—
H





YA1156
CH3—


embedded image


CH3—
H





YA1157
CH3—


embedded image


CH3—
H





YA1158
CH3—


embedded image


CH3—
H





YA1159
CH3—


embedded image


CH3—
H





YA1160
CH3—


embedded image


CH3—
H





YA1161
CH3—


embedded image


CH3—
H





YA1162
CH3—


embedded image


CH3—
H





YA1163
CH3—


embedded image


CH3—
H





YA1164
CH3—


embedded image


CH3—
H





YA1165
CH3—


embedded image


CH3—
H





YA1166
CH3—


embedded image


CH3—
H





YA1167
CH3—


embedded image


CH3—
H





YA1168
CH3—


embedded image


CH3—
H





YA1169
CH3—


embedded image


CH3—
H





YA1170
CH3—


embedded image


CH3—
H





YA1171
CH3—


embedded image


CH3—
H





YA1172
CH3—


embedded image


CH3—
H





YA1173
CH3—


embedded image


CH3—
H





YA1174
CH3—


embedded image


CH3—
H





YA1175
CH3—


embedded image


CH3—
H





YA1176
CH3—


embedded image


CH3—
H





YA1177
CH3—


embedded image


CH3—
H





YA1178
CH3—


embedded image


CH3—
H





YA1179
CH3—


embedded image


CH3—
H





YA1180
CH3—


embedded image


CH3—
H





YA1181
CH3—


embedded image


CH3—
H





YA1182
CH3—


embedded image


CH3—
H





YA1183
CH3—


embedded image


CH3—
H





YA1184
CH3—


embedded image


CH3—
H





YA1185
CH3—


embedded image


CH3—
H





YA1186
CH3—


embedded image


CH3—
H





YA1187
CH3—


embedded image


CH3—
H





YA1188
CH3—


embedded image


CH3—
H





YA1189
CH3—


embedded image


CH3—
H





YA1190
CH3—


embedded image


CH3—
H





YA1191
CH3—


embedded image


CH3—
H





YA1192
CH3—


embedded image


CH3—
H





YA1193
CH3—


embedded image


CH3—
H





YA1194
CH3—


embedded image


CH3—
H





YA1195
CH3—


embedded image


CH3—
H





YA1196
CH3—


embedded image


CH3—
H





YA1197
CH3—


embedded image


CH3—
H





YA1198
CH3—


embedded image


CH3—
H





YA1199
CH3—


embedded image


CH3—
H





YA1200
CH3—


embedded image


CH3—
H





YA1201
CH3—


embedded image


CH3—
H





YA1202
CH3—


embedded image


CH3—
H





YA1203
CH3—


embedded image


CH3—
H





YA1204
CH3—


embedded image


CH3—
H





YA1205
CH3—


embedded image


CH3—
H





YA1206
CH3—


embedded image


CH3—
H





YA1207
CH3—


embedded image


CH3—
H





YA1208
CH3—


embedded image


CH3—
H





YA1209
CH3—


embedded image


CH3—
H





YA1210
CH3—


embedded image


CH3—
H





YA1211
CH3—


embedded image


CH3—
H





YA1212
CH3—


embedded image


CH3—
H





YA1213
CH3—


embedded image


CH3—
H





YA1214
CH3—


embedded image


CH3—
H





YA1215
CH3—


embedded image


CH3—
H





YA1216
CH3—


embedded image


CH3—
H





YA1217
CH3—


embedded image


CH3—
H





YA1218
CH3—


embedded image


CH3—
H





YA1219
CH3—


embedded image


CH3—
H





YA1220
CH3—


embedded image


CH3—
H





YA1221
CH3—


embedded image


CH3—
H





YA1222
CH3—


embedded image


CH3—
H





YA1223
CH3—


embedded image


CH3—
H





YA1224
CH3—


embedded image


CH3—
H





YA1225
CH3—


embedded image


CH3—
H





YA1226
CH3—


embedded image


CH3—
H





YA1227
CH3—


embedded image


CH3—
H





YA1228
CH3—


embedded image


CH3—
H





YA1229
CH3—


embedded image


CH3—
H





YA1230
CH3—


embedded image


CH3—
H





YA1231
CH3—


embedded image


CH3—
H





YA1232
CH3—


embedded image


CH3—
H





YA1233
CH3—


embedded image


CH3—
H





YA1234
CH3—


embedded image


CH3—
H





YA1235
CH3—


embedded image


CH3—
H





YA1236
CH3—


embedded image


CH3—
H





YA1237
CH3—


embedded image


CH3—
H





YA1238
CH3—


embedded image


CH3—
H





YA1239
CH3—


embedded image


CH3—
H





YA1240
CH3—


embedded image


CH3—
H





YA1241
CH3—


embedded image


CH3—
H





YA1242
CH3—


embedded image


CH3—
H





YA1243
CH3—


embedded image


CH3—
H





YA1244
CH3—


embedded image


CH3—
H





YA1245
CH3—


embedded image


CH3—
H





YA1246
CH3—


embedded image


CH3—
H





YA1247
CH3—


embedded image


CH3—
H





YA1248
CH3—


embedded image


CH3—
H





YA1249
CH3—
CH3—
H
CH3—


YA1250
CH3—
CH3CH2—
H
CH3—





YA1251
CH3—


embedded image


H
CH3—





YA1252
CH3—


embedded image


H
CH3—





YA1253
CH3—


embedded image


H
CH3—





YA1254
CH3—


embedded image


H
CH3—





YA1255
CH3—


embedded image


H
CH3—





YA1256
CH3—


embedded image


H
CH3—





YA1257
CH3—


embedded image


H
CH3—





YA1258
CH3—


embedded image


H
CH3—





YA1259
CH3—


embedded image


H
CH3—





YA1260
CH3—


embedded image


H
CH3—





YA1261
CH3—


embedded image


H
CH3—





YA1262
CH3—


embedded image


H
CH3—





YA1263
CH3—


embedded image


H
CH3—





YA1264
CH3—


embedded image


H
CH3—





YA1265
CH3—


embedded image


H
CH3—





YA1266
CH3—


embedded image


H
CH3—





YA1267
CH3—


embedded image


H
CH3—





YA1268
CH3—


embedded image


H
CH3—





YA1269
CH3—


embedded image


H
CH3—





YA1270
CH3—


embedded image


H
CH3—





YA1271
CH3—


embedded image


H
CH3—





YA1272
CH3—


embedded image


H
CH3—





YA1273
CH3—


embedded image


H
CH3—





YA1274
CH3—


embedded image


H
CH3—





YA1275
CH3—


embedded image


H
CH3—





YA1276
CH3—


embedded image


H
CH3—





YA1277
CH3—


embedded image


H
CH3—





YA1278
CH3—


embedded image


H
CH3—





YA1279
CH3—


embedded image


H
CH3—





YA1280
CH3—


embedded image


H
CH3—





YA1281
CH3—


embedded image


H
CH3—





YA1282
CH3—


embedded image


H
CH3—





YA1283
CH3—


embedded image


H
CH3—





YA1284
CH3—


embedded image


H
CH3—





YA1285
CH3—


embedded image


H
CH3—





YA1286
CH3—


embedded image


H
CH3—





YA1287
CH3—


embedded image


H
CH3—





YA1288
CH3—


embedded image


H
CH3—





YA1289
CH3—


embedded image


H
CH3—





YA1290
CH3—


embedded image


H
CH3—





YA1291
CH3—


embedded image


H
CH3—





YA1292
CH3—


embedded image


H
CH3—





YA1293
CH3—


embedded image


H
CH3—





YA1294
CH3—


embedded image


H
CH3—





YA1295
CH3—


embedded image


H
CH3—





YA1296
CH3—


embedded image


H
CH3—





YA1297
CH3—


embedded image


H
CH3—





YA1298
CH3—


embedded image


H
CH3—





YA1299
CH3—


embedded image


H
CH3—





YA1300
CH3—


embedded image


H
CH3—





YA1301
CH3—


embedded image


H
CH3—





YA1302
CH3—


embedded image


H
CH3—





YA1303
CH3—


embedded image


H
CH3—





YA1304
CH3—


embedded image


H
CH3—





YA1305
CH3—


embedded image


H
CH3—





YA1306
CH3—


embedded image


H
CH3—





YA1307
CH3—


embedded image


H
CH3—





YA1308
CH3—


embedded image


H
CH3—





YA1309
CH3—


embedded image


H
CH3—





YA1310
CH3—


embedded image


H
CH3—





YA1311
CH3—


embedded image


H
CH3—





YA1312
CH3—


embedded image


H
CH3—





YA1313
CH3—


embedded image


H
CH3—





YA1314
CH3—


embedded image


H
CH3—





YA1315
CH3—


embedded image


H
CH3—





YA1316
CH3—


embedded image


H
CH3—





YA1317
CH3—


embedded image


H
CH3—





YA1318
CH3—


embedded image


H
CH3—





YA1319
CH3—


embedded image


H
CH3—





YA1320
CH3—


embedded image


H
CH3—





YA1321
CH3—


embedded image


H
CH3—





YA1322
CH3—


embedded image


H
CH3—





YA1323
CH3—


embedded image


H
CH3—





YA1324
CH3—


embedded image


H
CH3—





YA1325
CH3—


embedded image


H
CH3—





YA1326
CH3—


embedded image


H
CH3—





YA1327
CH3—


embedded image


H
CH3—





YA1328
CH3—


embedded image


H
CH3—





YA1329
CH3—


embedded image


H
CH3—





YA1330
CH3—


embedded image


H
CH3—





YA1331
CH3—


embedded image


H
CH3—





YA1332
CH3—


embedded image


H
CH3—





YA1333
CH3—


embedded image


H
CH3—





YA1334
CH3—


embedded image


H
CH3—





YA1335
CH3—


embedded image


H
CH3—





YA1336
CH3—


embedded image


H
CH3—





YA1337
CH3—


embedded image


H
CH3—





YA1338
CH3—


embedded image


H
CH3—





YA1339
CH3—


embedded image


H
CH3—





YA1340
CH3—


embedded image


H
CH3—





YA1341
CH3—


embedded image


H
CH3—





YA1342
CH3—


embedded image


H
CH3—





YA1343
CH3—


embedded image


H
CH3—





YA1344
CH3CH2—
CH3—
H
H


YA1345
CH3CH2—
CH3CH2—
H
H





YA1346
CH3CH2—


embedded image


H
H





YA1347
CH3CH2—


embedded image


H
H





YA1348
CH3CH2—


embedded image


H
H





YA1349
CH3CH2—


embedded image


H
H





YA1350
CH3CH2—


embedded image


H
H





YA1351
CH3CH2—


embedded image


H
H





YA1352
CH3CH2—


embedded image


H
H





YA1353
CH3CH2—


embedded image


H
H





YA1354
CH3CH2—


embedded image


H
H





YA1355
CH3CH2—


embedded image


H
H





YA1356
CH3CH2—


embedded image


H
H





YA1357
CH3CH2—


embedded image


H
H





YA1358
CH3CH2—


embedded image


H
H





YA1359
CH3CH2—


embedded image


H
H





YA1360
CH3CH2—


embedded image


H
H





YA1361
CH3CH2—


embedded image


H
H





YA1362
CH3CH2—


embedded image


H
H





YA1363
CH3CH2—


embedded image


H
H





YA1364
CH3CH2—


embedded image


H
H





YA1365
CH3CH2—


embedded image


H
H





YA1366
CH3CH2—


embedded image


H
H





YA1367
CH3CH2—


embedded image


H
H





YA1368
CH3CH2—


embedded image


H
H





YA1369
CH3CH2—


embedded image


H
H





YA1370
CH3CH2—


embedded image


H
H





YA1371
CH3CH2—


embedded image


H
H





YA1372
CH3CH2—


embedded image


H
H





YA1373
CH3CH2—


embedded image


H
H





YA1374
CH3CH2—


embedded image


H
H





YA1375
CH3CH2—


embedded image


H
H





YA1376
CH3CH2—


embedded image


H
H





YA1377
CH3CH2—


embedded image


H
H





YA1378
CH3CH2—


embedded image


H
H





YA1379
CH3CH2—


embedded image


H
H





YA1380
CH3CH2—


embedded image


H
H





YA1381
CH3CH2—


embedded image


H
H





YA1382
CH3CH2—


embedded image


H
H





YA1383
CH3CH2—


embedded image


H
H





YA1384
CH3CH2—


embedded image


H
H





YA1385
CH3CH2—


embedded image


H
H





YA1386
CH3CH2—


embedded image


H
H





YA1387
CH3CH2—


embedded image


H
H





YA1388
CH3CH2—


embedded image


H
H





YA1389
CH3CH2—


embedded image


H
H





YA1390
CH3CH2—


embedded image


H
H





YA1391
CH3CH2—


embedded image


H
H





YA1392
CH3CH2—


embedded image


H
H





YA1393
CH3CH2—


embedded image


H
H





YA1394
CH3CH2—


embedded image


H
H





YA1395
CH3CH2—


embedded image


H
H





YA1396
CH3CH2—


embedded image


H
H





YA1397
CH3CH2—


embedded image


H
H





YA1398
CH3CH2—


embedded image


H
H





YA1399
CH3CH2—


embedded image


H
H





YA1400
CH3CH2—


embedded image


H
H





YA1401
CH3CH2—


embedded image


H
H





YA1402
CH3CH2—


embedded image


H
H





YA1403
CH3CH2—


embedded image


H
H





YA1404
CH3CH2—


embedded image


H
H





YA1405
CH3CH2—


embedded image


H
H





YA1406
CH3CH2—


embedded image


H
H





YA1407
CH3CH2—


embedded image


H
H





YA1408
CH3CH2—


embedded image


H
H





YA1409
CH3CH2—


embedded image


H
H





YA1410
CH3CH2—


embedded image


H
H





YA1411
CH3CH2—


embedded image


H
H





YA1412
CH3CH2—


embedded image


H
H





YA1413
CH3CH2—


embedded image


H
H





YA1414
CH3CH2—


embedded image


H
H





YA1415
CH3CH2—


embedded image


H
H





YA1416
CH3CH2—


embedded image


H
H





YA1417
CH3CH2—


embedded image


H
H





YA1418
CH3CH2—


embedded image


H
H





YA1419
CH3CH2—


embedded image


H
H





YA1420
CH3CH2—


embedded image


H
H





YA1421
CH3CH2—


embedded image


H
H





YA1422
CH3CH2—


embedded image


H
H





YA1423
CH3CH2—


embedded image


H
H





YA1424
CH3CH2—


embedded image


H
H





YA1425
CH3CH2—


embedded image


H
H





YA1426
CH3CH2—


embedded image


H
H





YA1427
CH3CH2—


embedded image


H
H





YA1428
CH3CH2—


embedded image


H
H





YA1429
CH3CH2—


embedded image


H
H





YA1430
CH3CH2—


embedded image


H
H





YA1431
CH3CH2—


embedded image


H
H





YA1432
CH3CH2—


embedded image


H
H





YA1433
CH3CH2—


embedded image


H
H





YA1434
CH3CH2—


embedded image


H
H





YA1435
CH3CH2—


embedded image


H
H





YA1436
CH3CH2—


embedded image


H
H





YA1437
CH3CH2—


embedded image


H
H





YA1438
CH3CH2—


embedded image


H
H





YA1439
CH3CH2—
CH3—
H
CH3—


YA1440
CH3CH2—
CH3CH2—
H
CH3—





YA1441
CH3CH2—


embedded image


H
CH3—





YA1442
CH3CH2—


embedded image


H
CH3—





YA1443
CH3CH2—


embedded image


H
CH3—





YA1444
CH3CH2—


embedded image


H
CH3—





YA1445
CH3CH2—


embedded image


H
CH3—





YA1446
CH3CH2—


embedded image


H
CH3—





YA1447
CH3CH2—


embedded image


H
CH3—





YA1448
CH3CH2—


embedded image


H
CH3—





YA1449
CH3CH2—


embedded image


H
CH3—





YA1450
CH3CH2—


embedded image


H
CH3—





YA1451
CH3CH2—


embedded image


H
CH3—





YA1452
CH3CH2—


embedded image


H
CH3—





YA1453
CH3CH2—


embedded image


H
CH3—





YA1454
CH3CH2—


embedded image


H
CH3—





YA1455
CH3CH2—


embedded image


H
CH3—





YA1456
CH3CH2—


embedded image


H
CH3—





YA1457
CH3CH2—


embedded image


H
CH3—





YA1458
CH3CH2—


embedded image


H
CH3—





YA1459
CH3CH2—


embedded image


H
CH3—





YA1460
CH3CH2—


embedded image


H
CH3—





YA1461
CH3CH2—


embedded image


H
CH3—





YA1462
CH3CH2—


embedded image


H
CH3—





YA1463
CH3CH2—


embedded image


H
CH3—





YA1464
CH3CH2—


embedded image


H
CH3—





YA1465
CH3CH2—


embedded image


H
CH3—





YA1466
CH3CH2—


embedded image


H
CH3—





YA1467
CH3CH2—


embedded image


H
CH3—





YA1468
CH3CH2—


embedded image


H
CH3—





YA1469
CH3CH2—


embedded image


H
CH3—





YA1470
CH3CH2—


embedded image


H
CH3—





YA1471
CH3CH2—


embedded image


H
CH3—





YA1472
CH3CH2—


embedded image


H
CH3—





YA1473
CH3CH2—


embedded image


H
CH3—





YA1474
CH3CH2—


embedded image


H
CH3—





YA1475
CH3CH2—


embedded image


H
CH3—





YA1476
CH3CH2—


embedded image


H
CH3—





YA1477
CH3CH2—


embedded image


H
CH3—





YA1478
CH3CH2—


embedded image


H
CH3—





YA1479
CH3CH2—


embedded image


H
CH3—





YA1480
CH3CH2—


embedded image


H
CH3—





YA1481
CH3CH2—


embedded image


H
CH3—





YA1482
CH3CH2—


embedded image


H
CH3—





YA1483
CH3CH2—


embedded image


H
CH3—





YA1484
CH3CH2—


embedded image


H
CH3—





YA1485
CH3CH2—


embedded image


H
CH3—





YA1486
CH3CH2—


embedded image


H
CH3—





YA1487
CH3CH2—


embedded image


H
CH3—





YA1488
CH3CH2—


embedded image


H
CH3—





YA1489
CH3CH2—


embedded image


H
CH3—





YA1490
CH3CH2—


embedded image


H
CH3—





YA1491
CH3CH2—


embedded image


H
CH3—





YA1492
CH3CH2—


embedded image


H
CH3—





YA1493
CH3CH2—


embedded image


H
CH3—





YA1494
CH3CH2—


embedded image


H
CH3—





YA1495
CH3CH2—


embedded image


H
CH3—





YA1496
CH3CH2—


embedded image


H
CH3—





YA1497
CH3CH2—


embedded image


H
CH3—





YA1498
CH3CH2—


embedded image


H
CH3—





YA1499
CH3CH2—


embedded image


H
CH3—





YA1500
CH3CH2—


embedded image


H
CH3—





YA1501
CH3CH2—


embedded image


H
CH3—





YA1502
CH3CH2—


embedded image


H
CH3—





YA1503
CH3CH2—


embedded image


H
CH3—





YA1504
CH3CH2—


embedded image


H
CH3—





YA1505
CH3CH2—


embedded image


H
CH3—





YA1506
CH3CH2—


embedded image


H
CH3—





YA1507
CH3CH2—


embedded image


H
CH3—





YA1508
CH3CH2—


embedded image


H
CH3—





YA1509
CH3CH2—


embedded image


H
CH3—





YA1510
CH3CH2—


embedded image


H
CH3—





YA1511
CH3CH2—


embedded image


H
CH3—





YA1512
CH3CH2—


embedded image


H
CH3—





YA1513
CH3CH2—


embedded image


H
CH3—





YA1514
CH3CH2—


embedded image


H
CH3—





YA1515
CH3CH2—


embedded image


H
CH3—





YA1516
CH3CH2—


embedded image


H
CH3—





YA1517
CH3CH2—


embedded image


H
CH3—





YA1518
CH3CH2—


embedded image


H
CH3—





YA1519
CH3CH2—


embedded image


H
CH3—





YA1520
CH3CH2—


embedded image


H
CH3—





YA1521
CH3CH2—


embedded image


H
CH3—





YA1522
CH3CH2—


embedded image


H
CH3—





YA1523
CH3CH2—


embedded image


H
CH3—





YA1524
CH3CH2—


embedded image


H
CH3—





YA1525
CH3CH2—


embedded image


H
CH3—





YA1526
CH3CH2—


embedded image


H
CH3—





YA1527
CH3CH2—


embedded image


H
CH3—





YA1528
CH3CH2—


embedded image


H
CH3—





YA1529
CH3CH2—


embedded image


H
CH3—





YA1530
CH3CH2—


embedded image


H
CH3—





YA1531
CH3CH2—


embedded image


H
CH3—





YA1532
CH3CH2—


embedded image


H
CH3—





YA1533
CH3CH2—


embedded image


H
CH3—






















No.
STRUCTURE





YA1534


embedded image







YA1535


embedded image







YA1536


embedded image







YA1537


embedded image







YA1538


embedded image







YA1539


embedded image







YA1540


embedded image







YA1541


embedded image







YA1542


embedded image







YA1543


embedded image







YA1544


embedded image







YA1545


embedded image







YA1546


embedded image







YA1547


embedded image







YA1548


embedded image







YA1549


embedded image







YA1550


embedded image







YA1551


embedded image







YA1552


embedded image







YA1553


embedded image







YA1554


embedded image







YA1555


embedded image







YA1556


embedded image







YA1557


embedded image







YA1558


embedded image







YA1559


embedded image







YA1560


embedded image







YA1561


embedded image







YA1562


embedded image







YA1563


embedded image







YA1564


embedded image







YA1565


embedded image







YA1566


embedded image







YA1567


embedded image







YA1568


embedded image







YA1569


embedded image







YA1570


embedded image







YA1571


embedded image







YA1572


embedded image







YA1573


embedded image







YA1574


embedded image







YA1575


embedded image







YA1576


embedded image







YA1577


embedded image







YA1578


embedded image







YA1579


embedded image







YA1580


embedded image







YA1581


embedded image







YA1582


embedded image







YA1583


embedded image







YA1584


embedded image







YA1585


embedded image







YA1586


embedded image







YA1587


embedded image







YA1588


embedded image







YA1589


embedded image







YA1590


embedded image























TABLE 4




embedded image

















No.
R1
R2
R3
R4
R5





YB1
CH3—
CH3—
H
H
H


YB2
CH3—
CH3CH2—
H
H
H





YB3
CH3—


embedded image


H
H
H





YB4
CH3—


embedded image


H
H
H





YB5
CH3—


embedded image


H
H
H





YB6
CH3—


embedded image


H
H
H





YB7
CH3—


embedded image


H
H
H





YB8
CH3—


embedded image


H
H
H





YB9
CH3—


embedded image


H
H
H





YB10
CH3—


embedded image


H
H
H





YB11
CH3—


embedded image


H
H
H





YB12
CH3—


embedded image


H
H
H





YB13
CH3—


embedded image


H
H
H





YB14
CH3—


embedded image


H
H
H





YB15
CH3—


embedded image


H
H
H





YB16
CH3—


embedded image


H
H
H





YB17
CH3—


embedded image


H
H
H





YB18
CH3—


embedded image


H
H
H





YB19
CH3—


embedded image


H
H
H





YB20
CH3—


embedded image


H
H
H





YB21
CH3—


embedded image


H
H
H





YB22
CH3—


embedded image


H
H
H





YB23
CH3—


embedded image


H
H
H





YB24
CH3—


embedded image


H
H
H





YB25
CH3—


embedded image


H
H
H





YB26
CH3—


embedded image


H
H
H





YB27
CH3—


embedded image


H
H
H





YB28
CH3—


embedded image


H
H
H





YB29
CH3—


embedded image


H
H
H





YB30
CH3—


embedded image


H
H
H





YB31
CH3—


embedded image


H
H
H





YB32
CH3—


embedded image


H
H
H





YB33
CH3—


embedded image


H
H
H





YB34
CH3—


embedded image


H
H
H





YB35
CH3—


embedded image


H
H
H





YB36
CH3—


embedded image


H
H
H





YB37
CH3—


embedded image


H
H
H





YB38
CH3—


embedded image


H
H
H





YB39
CH3—


embedded image


H
H
H





YB40
CH3—


embedded image


H
H
H





YB41
CH3—


embedded image


H
H
H





YB42
CH3—


embedded image


H
H
H





YB43
CH3—


embedded image


H
H
H





YB44
CH3—


embedded image


H
H
H





YB45
CH3—


embedded image


H
H
H





YB46
CH3—


embedded image


H
H
H





YB47
CH3—


embedded image


H
H
H





YB48
CH3—


embedded image


H
H
H





YB49
CH3—


embedded image


H
H
H





YB50
CH3—


embedded image


H
H
H





YB51
CH3—


embedded image


H
H
H





YB52
CH3—


embedded image


OH
H
H





YB53
CH3—


embedded image


OH
H
H





YB54
CH3—


embedded image


OH
H
H





YB55
CH3—


embedded image


OH
H
H





YB56
CH3—


embedded image


OH
H
H





YB57
CH3—


embedded image


OH
H
H





YB58
CH3—


embedded image


OH
H
H





YB59
CH3—


embedded image


OH
H
H





YB60
CH3—


embedded image


OH
H
H





YB61
CH3—


embedded image


OH
H
H





YB62
CH3—


embedded image


OH
H
H





YB63
CH3—


embedded image


OH
H
H





YB64
CH3—


embedded image


OH
H
H





YB65
CH3—


embedded image


OH
H
H





YB66
CH3—


embedded image


OH
H
H





YB67
CH3—


embedded image


OH
H
H





YB68
CH3—


embedded image


OH
H
H





YB69
CH3—


embedded image


OH
H
H





YB70
CH3—


embedded image


OH
H
H





YB71
CH3—


embedded image


OH
H
H





YB72
CH3—


embedded image


OH
H
H





YB73
CH3—


embedded image


OH
H
H





YB74
CH3—


embedded image


OH
H
H





YB75
CH3—


embedded image


OH
H
H





YB76
CH3—


embedded image


OH
H
H





YB77
CH3—


embedded image


OH
H
H





YB78
CH3—


embedded image


OH
H
H





YB79
CH3—


embedded image


OH
H
H





YB80
CH3—


embedded image


OH
H
H





YB81
CH3—


embedded image


OH
H
H





YB82
CH3—


embedded image


CN
H
H





YB83
CH3—


embedded image


CN
H
H





YB84
CH3—


embedded image


CN
H
H





YB85
CH3—


embedded image


CN
H
H





YB86
CH3—


embedded image


CN
H
H





YB87
CH3—


embedded image


CN
H
H





YB88
CH3—


embedded image


CN
H
H





YB89
CH3—


embedded image


CN
H
H





YB90
CH3—


embedded image


CN
H
H





YB91
CH3—


embedded image


CN
H
H





YB92
CH3—


embedded image


CN
H
H





YB93
CH3—


embedded image


CN
H
H





YB94
CH3—


embedded image


CN
H
H





YB95
CH3—


embedded image


CN
H
H





YB96
CH3—


embedded image


CN
H
H





YB97
CH3—


embedded image


CN
H
H





YB98
CH3—


embedded image


CN
H
H





YB99
CH3—


embedded image


CN
H
H





YB100
CH3—


embedded image


CN
H
H





YB101
CH3—


embedded image


CN
H
H





YB102
CH3—


embedded image


CN
H
H





YB103
CH3—


embedded image


CN
H
H





YB104
CH3—


embedded image


CN
H
H





YB105
CH3—


embedded image


CN
H
H





YB106
CH3—


embedded image


CN
H
H





YB107
CH3—


embedded image


CN
H
H





YB108
CH3—


embedded image


CN
H
H





YB109
CH3—


embedded image


CN
H
H





YB110
CH3—


embedded image


CN
H
H





YB111
CH3—


embedded image


CN
H
H





YB112
CH3—
H
H
CH3—
H


YB113
CH3—
H
H
CH3CH2—
H





YB114
CH3—
H
H


embedded image


H





YB115
CH3—
H
H


embedded image


H





YB116
CH3—
H
H


embedded image


H





YB117
CH3—
H
H


embedded image


H





YB118
CH3—
H
H


embedded image


H





YB119
CH3—
H
H


embedded image


H





YB120
CH3—
H
H


embedded image


H





YB121
CH3—
H
H


embedded image


H





YB122
CH3—
H
H


embedded image


H





YB123
CH3—
H
H


embedded image


H





YB124
CH3—
H
H


embedded image


H





YB125
CH3—
H
H


embedded image


H





YB126
CH3—
H
H


embedded image


H





YB127
CH3—
H
H


embedded image


H





YB128
CH3—
H
H


embedded image


H





YB129
CH3—
H
H


embedded image


H





YB130
CH3—
H
H


embedded image


H





YB131
CH3—
H
H


embedded image


H





YB132
CH3—
H
H


embedded image


H





YB133
CH3—
H
H


embedded image


H





YB134
CH3—
H
H


embedded image


H





YB135
CH3—
H
H


embedded image


H





YB136
CH3—
H
H


embedded image


H





YB137
CH3—
H
H


embedded image


H





YB138
CH3—
H
H


embedded image


H





YB139
CH3—
H
H


embedded image


H





YB140
CH3—
H
H


embedded image


H





YB141
CH3—
H
H


embedded image


H





YB142
CH3—
H
H


embedded image


H





YB143
CH3—
H
H


embedded image


H





YB144
CH3—
H
H


embedded image


H





YB145
CH3—
H
H


embedded image


H





YB146
CH3—
H
H


embedded image


H





YB147
CH3—
H
H


embedded image


H





YB148
CH3—
H
H


embedded image


H





YB149
CH3—
H
H


embedded image


H





YB150
CH3—
H
H


embedded image


H





YB151
CH3—
H
H


embedded image


H





YB152
CH3—
H
H


embedded image


H





YB153
CH3—
H
H


embedded image


H





YB154
CH3—
H
H


embedded image


H





YB155
CH3—
H
H


embedded image


H





YB156
CH3—
H
H


embedded image


H





YB157
CH3—
H
H


embedded image


H





YB158
CH3—
H
H


embedded image


H





YB159
CH3—
H
H


embedded image


H





YB160
CH3—
H
H


embedded image


H





YB161
CH3—
H
H


embedded image


H





YB162
CH3—
H
H


embedded image


H





YB163
CH3—
H
H


embedded image


H





YB164
CH3—
H
H


embedded image


OH





YB165
CH3—
H
H


embedded image


OH





YB166
CH3—
H
H


embedded image


OH





YB167
CH3—
H
H


embedded image


OH





YB168
CH3—
H
H


embedded image


OH





YB169
CH3—
H
H


embedded image


OH





YB170
CH3—
H
H


embedded image


OH





YB171
CH3—
H
H


embedded image


OH





YB172
CH3—
H
H


embedded image


OH





YB173
CH3—
H
H


embedded image


OH





YB174
CH3—
H
H


embedded image


OH





YB175
CH3—
H
H


embedded image


OH





YB176
CH3—
H
H


embedded image


OH





YB177
CH3—
H
H


embedded image


OH





YB178
CH3—
H
H


embedded image


OH





YB179
CH3—
H
H


embedded image


OH





YB180
CH3—
H
H


embedded image


OH





YB181
CH3—
H
H


embedded image


OH





YB182
CH3—
H
H


embedded image


OH





YB183
CH3—
H
H


embedded image


OH





YB184
CH3—
H
H


embedded image


OH





YB185
CH3—
H
H


embedded image


OH





YB186
CH3—
H
H


embedded image


OH





YB187
CH3—
H
H


embedded image


OH





YB188
CH3—
H
H


embedded image


OH





YB189
CH3—
H
H


embedded image


OH





YB190
CH3—
H
H


embedded image


OH





YB191
CH3—
H
H


embedded image


OH





YB192
CH3—
H
H


embedded image


OH





YB193
CH3—
H
H


embedded image


CN





YB194
CH3—
H
H


embedded image


CN





YB195
CH3—
H
H


embedded image


CN





YB196
CH3—
H
H


embedded image


CN





YB197
CH3—
H
H


embedded image


CN





YB198
CH3—
H
H


embedded image


CN





YB199
CH3—
H
H


embedded image


CN





YB200
CH3—
H
H


embedded image


CN





YB201
CH3—
H
H


embedded image


CN





YB202
CH3—
H
H


embedded image


CN





YB203
CH3—
H
H


embedded image


CN





YB204
CH3—
H
H


embedded image


CN





YB205
CH3—
H
H


embedded image


CN





YB206
CH3—
H
H


embedded image


CN





YB207
CH3—
H
H


embedded image


CN





YB208
CH3—
H
H


embedded image


CN





YB209
CH3—
H
H


embedded image


CN





YB210
CH3—
H
H


embedded image


CN





YB211
CH3—
H
H


embedded image


CN





YB212
CH3—
H
H


embedded image


CN





YB213
CH3—
H
H


embedded image


CN





YB214
CH3—
H
H


embedded image


CN





YB215
CH3—
H
H


embedded image


CN





YB216
CH3—
H
H


embedded image


CN





YB217
CH3—
H
H


embedded image


CN





YB218
CH3—
H
H


embedded image


CN





YB219
CH3—
H
H


embedded image


CN





YB220
CH3—
H
H


embedded image


CN





YB221
CH3—
H
H


embedded image


CN





YB222
CH3—
H
H


embedded image




embedded image







YB223
CH3—
H
H


embedded image




embedded image







YB224
CH3—
H
H


embedded image




embedded image







YB225
CH3—
H
H


embedded image




embedded image







YB226
CH3—
H
H


embedded image




embedded image







YB227
CH3—
H
H


embedded image




embedded image







YB228
CH3—
H
H


embedded image




embedded image







YB229
CH3—
H
H


embedded image




embedded image







YB230
CH3—
H
H


embedded image




embedded image







YB231
CH3—
H
H


embedded image




embedded image







YB232
CH3—
H
H


embedded image




embedded image







YB233
CH3—
H
H


embedded image




embedded image







YB234
CH3—
H
H


embedded image




embedded image







YB235
CH3—
H
H


embedded image




embedded image







YB236
CH3—
H
H


embedded image




embedded image







YB237
CH3—
H
H


embedded image




embedded image







YB238
CH3—
H
H


embedded image




embedded image







YB239
CH3—
H
H


embedded image




embedded image







YB240
CH3—
H
H


embedded image




embedded image







YB241
CH3—
H
H


embedded image




embedded image







YB242
CH3—
H
H


embedded image




embedded image







YB243
CH3—
H
H


embedded image




embedded image







YB244
CH3—
H
H


embedded image




embedded image







YB245
CH3—
H
H


embedded image




embedded image







YB246
CH3—
H
H


embedded image




embedded image







YB247
CH3—
H
H


embedded image




embedded image







YB248
CH3—
H
H


embedded image




embedded image







YB249
CH3—
H
H


embedded image




embedded image







YB250
CH3—
H
H


embedded image




embedded image
























No.
STRUCTURE





YB251


embedded image







YB252


embedded image







YB253


embedded image







YB254


embedded image







YB255


embedded image







YB256


embedded image







YB257


embedded image







YB258


embedded image







YB259


embedded image







YB260


embedded image







YB261


embedded image







YB262


embedded image







YB263


embedded image







YB264


embedded image







YB265


embedded image







YB266


embedded image







YB267


embedded image







YB268


embedded image







YB269


embedded image







YB270


embedded image







YB271


embedded image







YB272


embedded image







YB273


embedded image







YB274


embedded image







YB275


embedded image







YB276


embedded image







YB277


embedded image







YB278


embedded image











Particularly preferred compounds of the present invention represented by formula (I) include:

  • 2-(3-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Ethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(5-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-3-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Chloro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-2-methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Fluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(5-Bromo-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Bromo-4-fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Chloro-6-fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,4-Difluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,6-Difluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,6-Dichlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,5-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,6-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,4-Difluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(5-Cyano-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Cyano-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(1-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,3-Dihydrobenzofuran-7-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-methoxy-5-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Phenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Fluorophenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(2-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Morpholin-4-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Benzylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Benzoylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-(1,2-Benzisothiazol-3-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Methyl-3-phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Acetyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Benzyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-Benzyl-3-(ethoxycarbonyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(4-methyl-3-(1-naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(5,5-Dimethyl-3-(2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-Phenylpiperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Chlorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Bromophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-((Pyrrolidin-1-yl)methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-Hydroxy-3-phenylpiperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(3-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Ethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(6-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(5-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Chloro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(5-Bromo-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,6-Dichlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;
  • 2-(3-(3,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,5-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,6-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,4-Difluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(1-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2,3-Dihydrobenzofuran-7-yl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H pyrimidin-4-one;
  • 2-(3-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(2-methoxy-5-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Phenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Fluorophenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(2-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(Morpholin-4-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-Acetyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-Benzyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-(4-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-Cyano-4-phenylpiperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-(6-Fluorobenofuran-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(Benzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (S)-2-(3-(Benzoisoazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • (R)-2-(3-(Benzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(3-(6-Fluorobenzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-(6-Fluorobenzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;
  • 2-(4-(5-Methylbenzofuran-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one; and
  • 2-(4-(6-Fluorobenzothiophene-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one.


Salts of the aforementioned preferred compound, and solvates or hydrates of the aforementioned compounds and salts thereof are also preferred.


The 3-substituted-4-pyrimidone compounds represented by the aforementioned formula (I) can be prepared, for example, according to the method explained below.




embedded image



(In the above scheme, definitions of Q, R, X and Y are the same as those already described.)


The 2-thiopyrimidone represented by the above formula (III) is prepared easily by a modification of the method described in EP 354,179. The reaction may be carried out in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, triethylamine, diisopropylethylamine, and 1,8-diazabicyclo[5,4,0]undec-7-en for 1 to 100 hours at a suitable temperature ranging from 0° C. to 200° C. under nitrogen or argon atmosphere or under ordinary air to afford the desired compound (III). Examples of a solvent for the reactions include, for example, alcoholic solvent such as methanol, ethanol, 1-propanol, isopropanol, tert-butanol, ethylene glycol, propylene glycol; etheric solvents such as diethyl ether, tert-butyl methyl ether, tetrahydrofuran, isopropyl ether; hydrocarbonic solvents such as benzene, toluene, xylene; halogenated hydrocarbonic solvents such as dichloromethane, chloroform, dichloroethane; aprotic polar solvents such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, hexamethylphosphoric triamide, water and the like. Generally, a single solvent or a mixture of two or more solvents may be used so as to be suitable to a base used.


Then the 2-thiopyrimidone derivative (III) is transformed into the 2-chloropyrimidone (IV) by a chlorinating agent. The reaction time and temperature depend on the chlorinating agent used. Examples of a chlorinating agent for the reactions include, for example, thionyl chloride, thionyl chloride and dimethylformamide, phosphorus oxychloride, phosphorus oxychloride and dimethylformamide, oxalyl chloride, phosphorous oxychloride and dimethylformamide, and phosphorus pentachloride.


The amine represented by the above formula (V) may be prepared by a modification of the method described in Japanese Patent Unexamined Publication [Kokai] No. 52-139085/1977 or according to well-known methods of one skilled in the art.


Then the chloride derivative (IV) is allowed to react with the amine (V) or salts thereof in the presence of a base such as sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, triethylamine, diisopropylethylamine, and 1,8-diazabicyclo[5,4,0]undec-7-en for 0.1 to 100 hours at a suitable temperature ranging from 0° C. to 200° C. under nitrogen or argon atmosphere or under ordinary air to afford the desired compound (II).


Examples of a solvent for the reactions include, for example, alcoholic solvent such as methanol, ethanol, 1-propanol, isopropanol, tert-butanol, ethylene glycol, propylene glycol; etheric solvents such as diethyl ether, tert-butyl methyl ether, tetrahydrofuran, isopropyl ether; hydrocarbonic solvents such as benzene, toluene, xylene; halogenated hydrocarbonic solvents such as dichloromethane, chloroform, dichloroethane; aprotic polar solvents such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, sulfolane, hexamethylphosphoric triamide, water and the like. Generally, a single solvent or a mixture of two or more solvents may be used so as to be suitable to a base used.


The compounds of the present invention have inhibitory activity against TPK1, and they inhibit TPK1 activity in neurodegenerative diseases like Alzheimer disease, thereby suppress the neurotoxicity of A β and the formation of PHF and inhibit the nerve cell death. Accordingly, the compounds of the present invention are useful as an active ingredient of a medicament which radically enables preventive and/or therapeutic treatment of Alzheimer disease. In addition, the compounds of the present invention are also useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of ischemic cerebrovascular accidents, Down syndrome, cerebral bleeding due to solitary cerebral amyloid angiopathy, progressive supranuclear palsy, subacute sclerosing panencephalitis, postencephalitic parkinsonism, pugilistic encephalosis, Guam parkinsonism-dementia complex, Lewy body disease, Pick's disease, corticobasal degeneration frontotemporal dementia, vascular dementia, acute stroke and traumatic injuries, brain and spinal cord trauma, peripheral neuropathies, retinopathies and glaucoma, non-insulin dependent diabetes (such as diabetes type II), and obesity, manic depressive illness, schizophrenia, alopecia, cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus-induced tumors.


As the active ingredient of the medicament of the present invention, a substance may be used which is selected from the group consisting of the compound represented by the aforementioned formula (I) and pharmacologically acceptable salts thereof, and solvates thereof and hydrates thereof. The substance, per se, may be administered as the medicament of the present invention, however, it is desirable to administer the medicament in a form of a pharmaceutical composition which comprises the aforementioned substance as an active ingredient and one or more of pharmaceutical additives. As the active ingredient of the medicament of the present invention, two or more of the aforementioned substance may be used in combination. The above pharmaceutical composition may be supplemented with an active ingredient of other medicament for the treatment of, for example, Alzheimer disease, vascular dementia, acute stroke and traumatic injuries, brain and spinal cord trauma, peripheral neuropathies, retinopathies and glaucoma, non-insulin dependent diabetes (such as diabetes type II), and obesity, manic depressive illness, schizophrenia, alopecia, cancers such as breast cancer, non-small cell lung carcinoma, thyroid cancer, T or B-cell leukemia and several virus-induced tumors.


A type of the pharmaceutical composition is not particularly limited, and the composition may be provided as any formulation for oral or parenteral administration. For example, the pharmaceutical composition may be formulated, for example, in the form of pharmaceutical compositions for oral administration such as granules, fine granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, solutions and the like, or in the form of pharmaceutical compositions for parenteral administrations such as injections for intravenous, intramuscular, or subcutaneous administration, drip infusions, transdermal preparations, transmucosal preparations, nasal drops, inhalants, suppositories and the like. Injections or drip infusions may be prepared as powdery preparations such as in the form of lyophilized preparations, and may be used by dissolving just before use in an appropriate aqueous medium such as physiological saline. Sustained-release preparations such as those coated with a polymer may be directly administered intracerebrally.


Types of pharmaceutical additives used for the manufacture of the pharmaceutical composition, content rations of the pharmaceutical additives relative to the active ingredient, and methods for preparing the pharmaceutical composition may be appropriately chosen by those skilled in the art. Inorganic or organic substances, or solid or liquid substances may be used as pharmaceutical additives. Generally, the pharmaceutical additives may be incorporated in a ratio ranging from 1% by weight to 90% by weight based on the weight of an active ingredient.


Examples of excipients used for the preparation of solid pharmaceutical compositions include, for example, lactose, sucrose, starch, talc, cellulose, dextrin, kaolin, calcium carbonate and the like. For the preparation of liquid compositions for oral administration, a conventional inert diluent such as water or a vegetable oil may be used. The liquid composition may contain, in addition to the inert diluent, auxiliaries such as moistening agents, suspension aids, sweeteners, aromatics, colorants, and preservatives. The liquid composition may be filled in capsules made of an absorbable material such as gelatin. Examples of solvents or suspension mediums used for the preparation of compositions for parenteral administration, e.g. injections, suppositories, include water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin and the like. Examples of base materials used for suppositories include, for example, cacao butter, emulsified cacao butter, lauric lipid, witepsol.


Dose and frequency of administration of the medicament of the present invention are not particularly limited, and they may be appropriately chosen depending on conditions such as a purpose of preventive and/or therapeutic treatment, a type of a disease, the body weight or age of a patient, severity of a disease and the like. Generally, a daily dose for oral administration to an adult may be 0.01 to 1,000 mg (the weight of an active ingredient), and the dose may be administered once a day or several times a day as divided portions, or once in several days. When the medicament is used as an injection, administrations may preferably be performed continuously or intermittently in a daily dose of 0.001 to 100 mg (the weight of an active ingredient) to an adult.


EXAMPLES

The present invention will be explained more specifically with reference to examples. However, the scope of the present invention is not limited to the following examples. The compound numbers in the examples correspond to those in the table above.


Reference Example 1
Synthesis of 2-mercapto-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one

A solution of ethyl 3-oxo-3-(4-pyridyl)propionate (29.0 g, 150 mmol), N-methyl thiourea (40.6 g, 450 mmol) and 1,8-diazabicyclo[5,4,0]-7-undecene (22.4 ml, 150 mmol) was refluxed for 4 hours and the solution of methanesulfonic acid (14.4 g, 150 mmol) in water (50 ml) was added after cooling by ice-water. The precipitate was washed with water, filtered and dried to give the title compound (23.7 g, 72%).



1H-NMR (DMSO-d6) δ: 3.58(s, 3H), 6.40(s, 1H), 7.72(dd, J=1.8, 4.5 Hz, 2H), 8.73(dd, J=1.5, 4.8 Hz, 2H), 12.92(brd, 1H).


Reference Example 2
Synthesis of 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one

Phosphorous oxychloride (26.11 g, 170 mmol) was added to dimethyl-formamide (180 ml) and stirred 20 min. 2-Mercapto-3-methyl-6-(4-pyridyl)-pyrimidine-4-one (24.15 g, 110 mmol) was added to the solution and stirred 5 min and then stirred at 70° C. for 2 hours. Ethyl acetate (630 ml) was added to the ice-cooled solution and precipitate was collected by filtration after stirring for 20 minutes. After drying, the precipitate was dissolved in water (400 ml) and pH was adjusted to 10 by using aqueous sodium hydroxide. The precipitate was washed with water, filtered and dried to give the title compound (18.82 g, 77%).



1H-NMR (CDCl3) δ: 3.72(s, 3H), 6.90(s, 1H), 7.78(dd, J=1.7, 4.5 Hz, 2H), 8.75(dd, J=1.6, 4.5 Hz, 2H).


Reference Example 3
Synthesis of 2-mercapto-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one

A solution of ethyl 3-oxo-3-(4-pyrimidyl)propionate (34.1 g, 176 mmol), N-methyl thiourea (47.5 g, 527 mmol) and 1,8-diazabicyclo[5,4,0]-7-undecene (26.3 ml, 176 mmol) in ethanol (340 ml) was refluxed for 2 hours and the solution of methanesulfonic acid (16.9 g, 176 mmol) in water (70 ml) was added after cooling by ice-water. The precipitate was washed with water, filtered and dried to give the title compound (30.2 g, 78%).



1H-NMR (DMSO-d6) δ: 3.56(s, 3H), 6.88(s, 1H), 8.24(dd, J=1.2, 5.4 Hz, 2H), 9.05 (dd, J=5.4 Hz, 1H), 11.94(s, 1H).


Reference Example 4
Synthesis of 2-chloro-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one

Phosphorous oxychloride (4.60 g, 30 mmol) was added to dimethyl-formamide (32 ml) and stirred for 20 min at 0° C. 2-Mercapto-3-methyl-6-(4-pyrimidyl)-3H-pyrimidine-4-one (4.40 g, 20 mmol) was added to the solution and stirred 5 min and then stirred at 70° C. for 2 hours. The reaction mixture was poured into ice water, neutralized by solid potassium carbonate, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated under reduced pressure. Purification of the residue by silica gel chromatography (ethyl acetate) gave the title compound (1.20 g, 27%).



1H-NMR (CDCl3) δ: 3.74(s, 3H), 7.56(s, 1H), 8.18(d, J=5.1 Hz, 1H), 8.92(d, J=5.1 Hz, 1H), 9.30(s, 1H).


MS[M+H]+: 223.


Example 1
Synthesis of 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one dihydrochloride (No. XA468)

A solution of 2-bromo-5-fluoroanisole (11.8 g, 57.6 mmol) in tetrahydrofuran (60 ml) was dropped into the magnesium (1.40 g, 57.6 mmol) in refluxed tetrahydrofuran (32 ml) containing small amount of 1,2-dibromoethane and refluxed for 15 min. After addition of tetrehydrofuran (50 ml), the solution was cooled to −78° C. and diethyl oxalate (7.41 g, 50.7 mmol) in diethyl ether (50 ml) was dropped into the solution. After stirring at same temperature for 30 min, the solution was warmed to −10° C. and 1N aqueous hydrogen chloride (50 ml) and water were added. Organic layer was extracted with diethyl ether, washed with brine and dried over magnesium sulfate. After removal of the solvent under reduced pressure, purification of the residue by silica gel column chromatography (eluent: hexane/ethyl acetate=5/2) gave ethyl 2-(4-fluoro-2-methoxyphenyl)-2-ozoacetate (6.80 g, 59%)



1H-NMR (CDCl3) δ: 1.40(3H, t, J=7.1 Hz), 3.87(3H, s), 4.89(2H, q, J=7.1 Hz), 6.68(1H, d, J=10.5 Hz), 6.77-6.81(1H, m), 7.91-7.95(1H, m).


Ethylenediamine (0.60 g, 10.0 mmol) was added to a solution of ethyl 2-(4-fluoro-2-methoxyphenyl)-2-oxoacetate (2.26 g, 10.0 mmol) in ethanol (30 ml) and refluxed 4 hr. After removal of the solvent under reduced pressure, residue was washed with ethanol-diethyl ether to give 5,6-dihydro-3-(4-fluoro-2-methoxyphenyl)pyrazinone (1.76 g, 79%).



1H-NMR (CDCl3) δ: 3.50-3.56 (2H, m), 3.81 (3H, s), 3.88-3.92 (2H, m), 6.65(1H, d, J=11.0 Hz), 6.70-6.76 (1H, m), 6.89(1H, bs), 7.36-7.40(1H, m).


5,6-Dihydro-3-(4-fluoro-2-methoxyphenyl)pyrazinone was added to the solution of lithium aluminium hydride (0.46 g, 12 mmol) in diethyl ether (25 ml) and refluxed for 6 hr. Water (0.48 ml), 15% sodium hydroxide solution (0.48 ml) and again water (1.21 ml) were added to the ice-cooled solution and the precipitate was filtered and washed with dichloromethane. Combined organic layer was evaporated to give 2-(4-fluoro-2-methoxyphenyl)piperazine (0.83 g, 99%).



1H-NMR (CDCl3) δ: 2.02(2H, s), 2.57-2.63 (1H, m), 2.80-2.89 (1H, m), 2.92-2.99 (2H, m), 3.06-3.12 (2H, m), 3.80(3H, s), 4.06 (1H, d, J=10.0 Hz), 6.56-6.65 (2H, m), 7.40 (1H, t, J=7.8 Hz).


2-Chloro-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (222 mg, 1.0 mmol) was added to an ice-cooled solution of 2-(4-fluoro-2-methoxyphenyl)piperazine (210 mg, 1.0 mmol), triethylamine (0.15 ml, 1.1 mmol) in N,N-dimethylformamide (10 ml) and stirred at that temperature for 1 hr and then at room temperature for 2 hr. Next day, reaction was quenched by ice-water and the filtrate was washed with water and dried to give 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (246 mg, 62%).



1H-NMR (CDCl3) δ: 2.89-2.96 (1H, m), 3.19-3.31 (3H, m), 3.59 (3H, s), 3.62-3.74 (2H, m), 3.85 (3H, s), 4.39-4.44 (1H, m), 6.63-6.71 (2H, m), 6.67 (1H, s), 7.51-7.55 (1H, m), 7.81 (2H, dd, J=1.7, 4.6 Hz), 8.71 (2H, dd, J=1.7, 4.6 Hz).


4N Hydrogen chloride in 1,4-dioxane (0.4 ml) was added to the solution of 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (217 mg, 0.6 mmol) in dichloromethane (5 ml) and stirred for 15 min. After addition of diethyl ether, filtration and wash with diethyl ether and dryness gave the title compound (260 mg, quant.).


Example 2
Synthesis of 2-(2-(4-methoxyphenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one dihydrochloride (No. XA393)

Dimethylslufoxide (50 ml) solution of 4-methyoxyphenacylbromide (9.94 g, 43.4 mmol) and water (1.6 ml, 88.8 mmol) were stirred at 50° C. for 2.5 hr. Water was added and the solution was extracted with ethyl acetate 3 times and washed with brine and then dried over sodium sulfate. Removal of the solvent gave 4-methoxyphenylglyoxal (8.30 g, quant.).



1H-NMR (DMSO) δ: 3.84 (3H, s), 6.60-6.69 (1H, m), 7.04 (2H, d, J=8.8 Hz), 8.05 (2H, d, J=9.1 Hz).


Methanol (5 ml) solution of ethylenediamine (3.74 g, 62.29 mmol) was added to the ice-cooled solution of 4-methoxyphenylglyoxal (8.30 g, 45.5 mmol) in methanol (100 ml) and tetrahydrofuran (50 ml) and stirred for 10 min. After cooling to 0° C., sodium tetrahydroborate (6.14 g, 162.2 mmol) and additional methanol (50 ml) was added and stirred overnight. After removal of the solvent, aqueous sodium hydroxide was added and was extracted with dichloromethane three times and washed with brine and dried over sodium sulfate. After removal of the solvent, purification of the residue by silica gel column chromatography (eluent; dichloromethane/ethanol/diethylamine=20/2/1) gave 2-(4-methoxypheny)-piperazine (3.96 g, 45%).



1H-NMR (CDCl3) δ: 2.69(1H, dd, J=10.3, 11.9 Hz), 2.80-3.01(4H, m), 3.07-3.11 (1H, m), 3.68-3.73(1H, m), 3.79(3H, s), 6.84-6.88 (2H, m), 7.27-7.32 (2H, m).


A solution of triethylamine (697 mg, 6.9 mmol), 2-(4-methoxyphenyl)-piperazine (430 mg, tetrahydrofuran (10 ml) was stirred at room temperature for 30 min and at 50° C. for 3 hr. Solvent was removed under reduced pressure, and 1N aqueous sodium hydroxide solution was added to the residue and extracted by dichloromethane three times and washed with brine and dried over sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent; dichloromethane/ethanol=10/1) to give 2-(2-(4-methoxyphenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (594 mg, 76%)



1H-NMR (CDCl3) δ: 3.02 (1H, dd, J=10.8, 12.7 Hz), 3.18-3.25 (3H, m), 3.55 (3H, s), 3.57-3.67 (2H, m), 3.82 (3H, s), 3.98(1H, dd, J=2.7, 10.8 Hz), 6.67 (1H, s), 6.92 (2H, d, J=8.7 Hz), 7.37 (2H, d, J=8.7 Hz), 7.80 (2H, d, J=6.0 Hz), 8.71 (2H, d, J=6.0 Hz).


4N Hydrogen chloride in ethyl acetate (5 ml) was added to the solution of 2-(2-(4-methoxyphenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (594 mg, 1.6 mmol) in dichloromethane (5 ml) and stirred for 1 hr. Wash with ethyl acetate after removal of the solvent and dryness gave the title compound (683 mg, 96%).


Example 3
Synthesis of 2-(2-(4-chlorophenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one hydrochloride (No. XA371)

Mixture of methyl(4-chlorophenyl)acetate (5.10 g, 27.6 mmol) and N-bromosuccinimide (5.16 g, 29 mmol) in carbon tetrachloride was treated by Hg lamp. After filtration, solvent was removed under reduced pressure and the residue was dissolved in methanol. Ethylenediamine (2.03 ml, 30.4 mmol) and triethylamine (2.06 ml, 14.8 mmol) and di-tert-butyldicarbonate (3.10 ml, 13.5 mmol) were added to the solution of 3-(4-chlorophenyl)piperazin-2-one (2.60 g, 12.3 mmol) in dichloromethane (100 ml) and stirred. The reaction mixture was washed with 1N aqueous hydrogen chloride, water, brine and then dried. After removal of the solvent under reduced pressure, residue was purified by silica gel column chromatography to give 4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)-piperazin-2-one.



1H-NMR (CDCl3) δ: 1.44 (9H, s), 3.21-3.32 (2H, m), 3.48 (1H, m), 4.04 (1H, brs), 5.66 (1H, brs), 7.10 (1H, brs), 7.30-7.38 (4H, m).


Solution of 4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)-piperazin-2-one (500 mg, 1.6 mmol) and acetic acid (929 μl, 16 mmol) were added to a refluxed solution of sodium borohydride (608 mg, 16 mmol) in 1,4-dioxane (5 ml) and reflux was continued. The reaction was quenched by water and extracted with dichloromethane and washed with brine and dried. After removal of the solvent, residue was purified by silica gel column chromatography to give 4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)piperazine (330 mg, 69%).



1H-NMR (CDCl3) δ: 1.46(9H, s), 2.76-2.99(3H, m), 3.13(1H, dd, J=13.0 Hz, 4.3 Hz), 3.45-3.49(2H, m), 3.92(1H, m), 5.15(1H, s), 7.27-7.33(4H, m).


A solution of 4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)piperazine (330 mg, 1.1 mmol), 2-chloro-3-methyl-6-(4-pyridyl)pyrimidin-4-one (246 mg, 1.1 mmol) and triethylamine (170 μl, 1.22 mmol) in tetrahydrofuran were refluxed. Usual workup and purification by silica gel column chromatography gave 2-(1-(tert-butoxy-carbonyl)-2-(4-chlorophenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (500 mg, 93%).



1H-NMR (CDCl3) δ: 1.45(9H, s), 3.09(1H, m), 3.35(3H, s), 3.40-3.63(4H, m), 3.96-4.19(2H, m), 5.43(1H, s), 6.68(1H, s), 7.23(2H, d, J=8.3 Hz), 7.32(2H, d, J=8.3 Hz), 7.78(2H, d, J=5.9 Hz), 8.72(2H, d, J=5.9 Hz).


4N Hydrogen chloride in ethyl acetate was added to the solution of 2-(1-(tert-butoxycarbonyl)-2-(4-chlorophenyl)-piperazine-4-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (500 mg, 1.0 mmol) in ethyl acetate and stirred. Filtration and successive dryness gave the title compound (373 mg, 79%).


Example 4
Synthesis of 3-methyl-2-(3-(4-((1-pyrrolidinyl)methyl)phenyl)piperidine-1-yl)-6-(4-pyridyl)pyrimidin-4-one fumarate (No. XB43)

Tetrakis(triphenylphosphine)palladium (0.65 g, 0.56 mmol), 4-formylphenylboric acid (2.81 g, 18.7 mmol), 2M aqueous sodium carbonate (18.7 ml, 37.4 mmol) and ethanol were added to the nitrogen-saturated solution of 3-bromopyridine (2.66 g, 16.8 mmol) in toluene and refluxed under nitrogen for 8 hrs. Water was added to the solution and extracted with ethyl acetate, washed with water and brine and dried. Solvents were removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1.5) to give 4-(3-pyridyl)benzaldehyde (0.78 g, 25%).


Methyl iodide (0.8 ml, 12.9 mmol) was added to a solution of 4-(3-pyridyl)benzaldehyde (0.78 g, 4.3 mmol) in dichloromethane and stirred 2 days. Additional methyl iodide (0.8 ml, 12.9 mmol) was added and stirred for 3 hr. After removal of the solvent, methanol was added to the residue and ice-cooled. Sodium tetrahydroborate (6.4 g, 17.0 mmol) was added to the solution and stirred for 1.5 hr with warming to room temperature. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. After removal of the solvent under reduced pressure, residue was purified by silica gel chromatography (eluent ethyl acetate to methanol) to give 3-(4-hydroxymethylphenyl)-1-methyl-1,2,5,6-tetrahydropyridine (0.63 g, 72%).


Triethylamine (1.29 ml, 9.2 mmol), acetic anhydride (0.35 ml, 3.7 mmol) were added to a solution of 4-(hydroxymethyl)phenyl-1-methyl-1,2,5,6-tetrahydropyridine (0.63 g, 3.1 mmol) in dichloromethane and stirred overnight. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave 3-(4-acetozymethylphenyl)-1-methyl-1,2,5,6-tetrahydropyridine (0.67 g, 89%).


A solution of 3-(4-acetoxymethylphenyl)-1-methyl-1,2,5,6-tetrahydropyridine (0.67 g, 2.7 mmol) and 1-chloroethyl chloroformate (0.36 ml, 3.3 mmol) in dichloroethane was refluxed for 2 hr. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. After removal of the solvent, methanol was added and refluxed for 1.5 hr. Tetrahydrofuran and water were added to the residue after removal of the solvent under reduced pressure and triethylamine (1.9 ml, 13.6 mmol) and di-tert-butyl dicarbonate (0.66 g, 3.0 mmol) were added and stirred. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure and the residue was purified by silica gel chromatography to give 3-(4-acetoxymethylphenyl)-1-(tert-butoxycarbonyl)-1,2,5,6-tetrahydropyridine (0.71 g, 78%).


Palladium on charcoal was added to the solution of 3-(4-acetoxymethylphenyl)-1-(tert-butoxycarbonyl)-1,2,5,6-tetrahydropyridine (0.71 g, 2.1 mmol) in ethyl acetate and stirred under hydrogen atmosphere. After filtration with celite and removal of the solvent under reduced pressure, methanol and 1N aqueous sodium hydroxide were added and stirred. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure and the residue was purified by silica gel chromatography (eluent; hexane/ethyl acetate=3/1) to give 3-(4-hydroxymethylphenyl)-1-(tert-butoxycarbonyl)piperidine (0.39 g, 62%).


Triethylamine (0.47 g, 3.4 mmol) and methanesulfonyl chloride (0.12 ml, 1.6 mmol) were added to an ice-cooled solution of 3-(4-hydroxymethylphenyl)-1-(tert-butoxycarbonyl)piperidine (0.39 g, 1.34 mmol) in dichloromethane and stirred for 7.5 hr. Pyrrolidine (1.0 ml, 12 mmol) was added to the solution and stirred overnight. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure and the residue was purified by silica gel chromatography (eluent; ethyl acetate to ethyl acetate/methanol=1/1, then methanol only) to give 3-(4-(1-pyrrolidinyl)methylphenyl)-1-(tert-butoxycarbonyl)piperidine (0.26 g, 56%).


4N Hydrogen chloride in ethyl acetate was added to 3-(4-(1-pyrrolidinyl)-methylphenyl)-1-(tert-butoxycarbonyl)piperidine (0.26 g, 0.75 mmol) and stirred overnight. After filtration and dryness, triethylamine (0.5 ml, 3.6 mmol), 2-chloro-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (0.14 g, 0.63 mmol) and tetrahydrofuran were added and stirred at 70° C. Organic solvents were removed under reduced pressure after addition of water and extracted with ethyl acetate, washed with water and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure and the residue was dissolved into ethyl acetate. A solution of fumaric acid (0.095 g, 0.82 mmol) in acetone was added and the resulting precipitate was filtered and dried to give the title compound (0.29 g, 76%).


Example 5
Synthesis of (R)-2-(2-(4-chlorophenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (No. XA372)

To a solution of (S)-2-methyl-CBS-oxazaborolidine (27.6 mL, 1.0 M solution in toluene, 27.6 mmol) was added borane-tetrahydrofuran complex (166 ml, 1.0 M solution in tetrahydrofuran, 166 mmol) at −40° C. To the resulting solution was added a solution of 4′-chlorophenacyl bromide (32.25 g, 138.1 mmol) in tetrahydrofuran (200 ml) through dropping funnel over 1 h at −40° C. After stirring for 3 hours below 0° C., methanol (ca. 50 ml) was added dropwise. After stirring the resulting solution for additional 30 min at room temperature, solvent was removed under reduced pressure. The residue, dissolved in ethyl acetate, was treated with 1 N hydrochloric acid to form white precipitate, which was filtered off. The layers of the filtrate was separated, and the organic layer was washed with hydrochloric acid and brine successively, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was used for the next reaction without further purification.


The residue was dissolved in ether (250 ml), and stirred with potassium hydroxide (15.5 g, 276 mmol) in water (250 ml) vigorously. After consumption of the starting material, the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was used for the next reaction without further purification.


The residue was heated with benzylamine (37.7 ml, 345 mmol) at 80° C. for 4.5 h. After cooling at room temperature, the resulting white crystals was washed with ether/hexane and collected to afford (S)-2-benzylamino-1-(4-chlorophenyl)ethanol (23.8 g, 65.8%). The excess benzylamine in the filtrate was distilled off at 120° C. under reduced pressure. From the residue, another (S)-2-benzylamino-1-(4-chlorophenyl)ethanol (2.41 g, 6.7%) was obtained.



1H NMR (CDCl3)™: 2.68(1H, dd, J=12.3, 8.9 Hz), 2.92(1H, dd, J=12.3, 3.7 Hz), 3.80(1H, d, J=11.9 Hz), 3.86(1H, d, J=11.9 Hz), 4.68(1H, dd, J=8.9, 3.7 Hz), 7.30(9H, m).


To a suspension of (S)-2-benzylamino-1-(4-chlorophenyl)ethanol (15.76 g, 60.21 mmol) and triethylamine (33.6 ml, 241 mmol) in dichloromethane (300 ml) was added a solution of thionyl chloride (4.83 ml, 66.2 mmol) in dichloromethane (20 ml) at −78° C. over 20 min. The resulting suspension was stirred at −78° C. for 20 min and at 0° C. for additional 20 min. The reaction mixture was partitioned between ether and water, and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 10-20% ethyl acetate-hexane) to afford (2RS,5S)-3-benzyl-5-(4-chlorophenyl)-1,2,3-oxathiazolidine 2-oxide (16.2 g 87.4%) as a pale yellow solid.


The resulting product was obtained as a mixture of two diastereomers due to the S-oxide.


major isomer: 1H NMR (CDCl3) δ: 3.31(1H, dd, J=10.5, 9.9 Hz), 3.55(1H, dd, J=9.0, 6.3 Hz), 3.88(1H, d, J=13.2 Hz), 4.37(1H, d, J=13.2 Hz), 5.49(1H, dd, J=10.5, 6.3 Hz), 7.22-7.43(9H, m).


minor isomer: 1H NMR (CDCl3) δ: 3.21(1H, dd, J=13.5, 4.5 Hz), 3.77(1H, dd, J=13.5, 11.4 Hz), 4.05(1H, d, J=13.5 Hz), 4.38(1H, d, J=13.5 Hz), 5.99(1H, dd, J=11.4, 4.5 Hz), 7.22-7.43(9H, m).


A solution of (2RS,5S)-3-benzyl-5-(4-chlorophenyl)-1,2,3-oxathiazolidine 2-oxide (16.2 g, 52.6 mmol) and sodium azide (17.11 g, 263.2 mmol) in N,N-dimethylformamide (100 ml) was heated at 70° C. for 24 hours. The reaction mixture was partitioned between ether and water, and the organic layer was washed with water and brine successively, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 10-20% ethyl acetate-hexane) to afford (R)-N-benzyl-2-azido-2-(4-chlorophenyl)ethylamine (12.7 g, 83.8%) as a yellow oil.



1H NMR (CDCl3) δ: 2.81(1H, dd, J=12.5, 5.1 Hz), 2.89(1H, dd, J=12.5, 8.5 Hz), 3.82(2H, s), 4.64(1H, dd, J=8.5, 5.1 Hz), 7.23-7.36(9H, m).


A solution of (R)-N-benzyl-2-azido-2-(4-chlorophenyl)ethylamine (12.7 g, 44.1 mmol) in tetrahydrofuran (176 mL) was treated with triphenylphosphine (13.9 g, 52.9 mmol) at room temperature. After addition of water (20 ml), the reaction mixture was heated at 60° C. for 1 h. The reaction mixture was condensed, and partitioned between ether and 1 N hydrochloric acid. The aqueous layer was treated with 1 N aqueous sodium hydroxide solution until the solution became basic. The resulting solution was extracted with dichlromethane thoroughly. The combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was used for the next reaction without further purification.


The residue was heated with diethyl oxalate (18 ml, 132 mmol) at 120° C. for 1.5 h. The resulting white precipitate was washed with ether and collected to afford (R)-1-benzyl-5-(4-chlorophenyl)-2,3-dioxopiperazine (11.4 g, 82.2%).



1H NMR (CDCl3) δ: 3.46(1H, dd, J=12.9, 8.1 Hz), 3.60(1H, dd, J=12.9, 3.8 Hz), 4.48(1H, d, J=14.7 Hz), 4.79(1H, d, J=14.7 Hz), 4.80(1H, dd, J=8.9, 3.8 Hz), 6.83(1H, s), 7.13(4H, m), 7.27(5H, m).


To a suspension of (R)-1-benzyl-5-(4-chlorophenyl)-2,3-dioxopiperazine (11.4 g, 36.3 mmol) in tetrahydrofuran (300 ml) was added borane-tetrahydrofuran complex (181 mL, 1.0 M solution in tetrahydrofuran, 181 mmol) at room temperature. After stirring for 24 hours, the reaction mixture was quenched with methanol (50 ml) at 0° C., and concentrated under reduced pressure. The residue was treated with 10% aqueous sodium hydroxide solution (300 ml) and heated at 100° C. for 2 hours. After cooling at room temperature, the mixture was extracted with dichloromethane thoroughly. The combined organic layer was dried over anhydrous sodium sulfated, filtered, and concentrated under reduced pressure. The residue was used for the next reaction without further purification.


To a solution of the residue and triethylamine (7.58 ml, 54.4 mmol) in dichloromethane (150 ml) was added di-tert-butyl dicarbonate (9.49 g, 43.5 mmol) at room temperature. After stirring for 45 min, the resulting mixture was partitioned between dichloromethane and water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 10-20% ethyl acetate-hexane) to afford (R)-1-benzyl-4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)piperazine (11.6 g, 82.8%) as an oil.



1H NMR (CDCl3) δ: 1.43(9H, s), 2.16(1H, dt, J=4.4, 11.7 Hz), 2.40(1H, dd, J=4.4, 11.7 Hz), 2.78(1H, dd, J=4.4, 11.7 Hz), 2.98(1H, dt, J=4.4, 11.7 Hz), 3.20(1H, d, J=12.8 Hz), 3.42(1H, d, J=12.9 Hz), 3.57(1H, d, J=12.9 Hz), 3.89(1H, d, J=12.8 Hz), 5.17(1H, s), 7.24-7.36(9H, m).


To a solution of (R)-1-benzyl-4-(tert-butoxycarbonyl)-3-(4-chlorophenyl)piperazine (11.6 g, 30.1 mmol) in 1,2-dichloroethane (80 ml) was added 1-chloroethyl chloroformate (4.91 ml, 45.1 mmol) at room temperature. Upon disappearance of the starting material, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in methanol (100 ml) and refluxed for 30 min. The resulting white precipitate was filtered and washed with methanol to afford (R)-2-(4-chlorophenyl)piperazine dihydrochloride, which was liberated with aqueous sodium hydroxide solution, and extracted with dichloromethane to afford (R)-2-(4-chlorophenyl)piperazine (3.04 g, 51.4%) as white solid.



1H NMR (CDCl3) δ: 2.65(1H, dd, J=12.0, 10.5 Hz), 2.82-3.04(4H, m), 3.09(1H, d, J=12.6 Hz), 3.73(1H, dd, J=10.1, 2.7 Hz), 7.29(4H, m)


The filtrate was concentrated under reduced pressure and partitioned between ether and 1 N hydrochloric acid. The aqueous layer was neutralized with 1 N aqueous sodium hydroxide solution, and extracted with dichloromethane thoroughly. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified after Boc-protection (Boc2O, Et3N, CH2Cl2) to furnish (R)-1,4-di(tert-butoxycarbonyl)-2-(4-chlorophenyl)piperazine (2.70 g, 22.6%) as pale yellow solid.



1H NMR (CDCl3) δ: 1.43(9H, s), 1.46(9H, s), 2.96(2H, m), 3.32(1H, dd, J=13.8, 4.2 Hz), 3.74(1H, m), 3.94(1H, d, J=11.4 Hz), 4.40(1H, d, J=13.2 Hz), 5.23(1H, s), 7.25(2H, m)


To a suspension of (R)-2-(4-chlorophenyl)piperazine dihydrochloride (1.09 g, 4.05 mmol) in tetrahydrofuran (24 ml) was added triethylamine (2.82 ml, 20.3 mmol). After stirring for 15 min at room temperature, 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (748 mg, 3.38 mmol) was added portionwise. Upon disappearance of the chloropyrimidone, the reaction mixture was condensed under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give pale yellow solid, which was recrystallized from ethanol to afford (R)-2-(2-(4-chlorophenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (998 mg, 77.4%) as white crystals. The enantiomer excess was determined by HPLC (>99% ee). The crystals were converted into its dihydrochloride salt.



1H NMR (DMSO-d6) δ: 3.40(3H, m), 3.46(3H, s), 3.62(1H, dd, J=12.0, 13.2 Hz), 3.72(1H, m), 3.92(1H, t, J=15.5 Hz), 4.68(1H, t, J=10.1 Hz), 7.18(1H, s), 7.58(2H, d, J=8.6 Hz), 7.83(2H, d, J=8.6 Hz), 8.57(2H, d, J=6.6 Hz), 9.01(2H, d, J=6.6 Hz), 10.20(1H, d, J=7.8 Hz), 10.76(1H, br s) MS: 382(M+H)


[α]D24=+62.2° (c 1.00, H2O)


Example 6
Synthesis of (S)-2-(2-(4-chlorophenyl)piperazin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (No. XA373)

(S)-isomer was prepared same as above by using (R)-2-methyl-CBS-oxazaborolidine instead of (S)-2-methyl-CBS-oxazaborolidine.



1H NMR (DMSO-d6) δ: 3.40 (3H, m), 3.45 (3H, s), 3.53-3.96 (3H, m), 4.68 (1H, t, J=13.5 Hz), 7.10 (1H, s), 7.60 (2H, d, J=8.3 Hz), 7.76 (2H, d, J=8.3 Hz), 8.38 (1H, br s), 8.91 (1H, d, J=4.8 Hz), 9.88 (1H, br s), 10.31 (1H, br s)


MS: 382(M+H)


[α]D24=−63.3° (c 1.00, H2O)


Example 7
Synthesis of 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyrimidyl)-pyrimidin-4-one (No. YA0366)

A solution of 2-bromo-5-fluoroanisole (11.8 g, 57.6 mmol) in tetrahydrofuran (60 ml) was dropped into the magnesium (1.40 g, 57.6 mmol) in refluxed tetrahydrofuran (32 ml) containing small amount of 1,2-dibromoethane and refluxed for 15 min. After addition of tetrahydrofuran (50 ml), the solution was cooled to −78° C. and diethyl oxalate (7.41 g; 50.7 mmol) in diethyl ether (50 ml) was dropped into the solution. After stirring at the same temperature for 30 min, the solution was warmed to −10° C. and 1N aqueous hydrogen chloride (50 ml) and water were added. Organic layer was extracted with diethyl ether, washed with brine and dried over magnesium sulfate. After removal of the solvent under reduced pressure, purification of the residue by silica gel column chromatography (eluent: hexane/ethyl acetate=5/2) gave ethyl 2-(4-fluoro-2-methoxyphenyl)-2-oxoacetate (6.80 g, 59%)



1H-NMR (CDCl3) δ: 1.40(3H, t, J=7.1 Hz), 3.87(3H, s), 4.89(2H, q, J=7.1 Hz), 6.68(1H, d, J=10.5 Hz), 6.77-6.81(1H, m), 7.91-7.95(1H, m).


Ethylenediamine (0.60 g, 10.0 mmol) was added to a solution of ethyl 2-(4-fluoro-2-methoxyphenyl)-2-oxoacetate (2.26 g, 10.0 mmol) in ethanol (30 ml) and refluxed 4 hr; After removal of the solvent under reduced pressure, residue was washed with ethanol-diethyl ether to give 5,6-dihydro-3-(4-fluoro-2-methoxyphenyl)pyrazinone (1.76 g, 79%).



1H-NMR (CDCl3) δ: 3.50-3.56 (2H, m), 3.81 (3H, s), 3.88-3.92 (2H, m), 6.65(1H, d, J=11.0 Hz), 6.70-6.76 (1H, m), 6.89(1H, bs), 7.36-7.40(1H, m).


5,6-Dihydro-3-(4-fluoro-2-methoxyphenyl)pyrazinone was added to the solution of lithium aluminium hydride (0.46 g, 12 mmol) in diethyl ether (25 ml) and refluxed for 6 hr. Water (0.48 ml), 15% sodium hydroxide solution (0.48 ml) and again water (1.21 ml) were added to the ice-cooled solution and the precipitate was filtered and washed with dichloromethane. Combined organic layer was evaporated to give 2-(4-fluoro-2-methoxyphenyl)piperazine (0.83 g, 99%).



1H-NMR (CDCl3) δ: 2.02(2H, s), 2.57-2.63 (1H, m), 2.80-2.89 (1H, m), 2.92-2.99 (2H, m), 3.06-3.12 (2H, m), 3.80(3H, s), 4.06 (1H, d, J=10.0 Hz), 6.56-6.65 (2H, m), 7.40 (1H, t, J=7.8 Hz).


2-Chloro-3-methyl-6-(4-pyrimidyl)-pyrimidin-4-one (223 mg, 1:0 mmol) was added to an ice-cooled solution of 2-(4-fluoro-2-methoxyphenyl)piperazine (210 mg, 1.0 mmol), triethylamine (0.15 ml, 1.1 mmol) in N,N-dimethylformamide (10 ml) and stirred at that temperature for 0.5 hr and then at room temperature for 3 hours. Reaction was quenched by ice-water and the filtrate was washed with water and dried to give 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyrimidyl)-pyrimidin-4-one (262 mg, 66%).



1H-NMR (CDCl3) δ: 2.89-2.98 (1H, m), 3.22-3.31 (3H, m), 3.60 (3H, s), 3.62-3.71 (2H, m), 3.86 (3H, s), 4.39-4.44 (1H, m), 6.43-6.73 (2H, m), 7.33 (1H, s), 7.52-7.56 (1H, m), 8.19 (1H, d, J=5.1 Hz), 8.87 (1H, d, J=5.2 Hz), 9.28 (1H, d, J=1.2 Hz).


4N Hydrogen chloride in 1,4-dioxane (0.2 ml) was added to the solution of 2-(2-(4-fluoro-2-methoxyphenyl)piperazin-4-yl)-3-methyl-6-(4-pyrimidyl)-pyrimidin-4-one (238 mg, 0.6 mmol) in dichloromethane (5 ml) and stirred for 15 min. Wash with methanol and ethyl acetate after removal of the solvent and dryness gave the title compound (223 mg, 86%).


Example 8
Synthesis of 2-(2-(4-chlorophenyl)-piperazine-4-yl)-3-methyl-6-(4-pyrimidyl)pyrimidin-4-one (No. YA0269)

Dimethyl sulfoxide (60 ml) solution of 4-chlorophenacylbromide (11.11 g, 65.9 mmol) and water (1.7 ml) were stirred. The solution was extracted with ethyl acetate 3 times and washed with water twice and brine and then dried over sodium sulfate. After removal of the solvent, the residue was washed with hexane-ethyl acetate and dried to give 4-chlorophenylglyoxal (4.43 g, 50%).



1H-NMR (CDCl3) δ: 4.02-4.16(2H, m), 5.90-5.95(1H, m), 7.45-7.53(2H, m), 8.05-8.11(2H, m).


A methanol (10 ml) solution of ethylenediamine (1.90 g, 31.6 mmol) was added to the ice-cooled solution of 4-chlorophenylglyozal (4.43 g, 26.3 mmol) in methanol (100 ml) and tetrahydrofuran (30 ml) and stirred for 10 min. After addition of sodium tetrahydroborate (3.26 g, 86.3 mmol), additional methanol (50 ml) was added and stirred overnight. After removal of the solvent, diluted hydrochloric acid was added and extracted with ether twice. After addition of sodium hydroxide, basic aqueous layer was extracted with dichloromethane three times and washed with brine and dried over sodium sulfate. After removal of the solvent by filtration, purification of the residue by silica gel column chromatography (eluent; dichloromethane/ethanol=10/1 to dichloromethane/ethanol/diethylamine=20/2/1) to give 2-(4-chlorophenyl)-piperazine (0.43 g, 9%)



1H-NMR (CDCl3) δ: 2.67(1H, dd, J=10.5, 12.0 Hz), 2.87-3.03(4H, m), 3.07-3.13(1H, m), 3.77(1H, dd, J=2.7, 10.2 Hz), 7.27-7.36(4H, m).


Triethylamine (528 mg, 5.2 mmol) was added to a solution of 4-(chlorophenyl)piperazine (216 mg, 1.1 mmol) and 2-chloro-3-methyl-6-(4-pyrimidyl)pyrimidin-4-one and stirred at 50° C. for 2 hr. Solvent was removed under reduced pressure, and 1N aqueous sodium hydroxide solution was added to the residue and extracted by dichloromethane. After washing with brine and dryness by sodium sulfate, solvent was removed under reduced pressure, and the residue was purified using ISOLUTE(registered trade mark) SI (International Sorvent Technology, UK) (eluent; dichloromethane/ethanol=10/1) to give the title compound (396 mg, 95%).


Example 9
Synthesis of 2-(2-(4-chlorophenyl)-6,6-dimethyl-piperazin-4-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride (No. XA1986)

A solution of 4′-chloro-2-bromoacetophenone (25.0 g, 107 mmol), water (1.92 mL, 107 mmol) and 47% hydrobromic acid (0.20 mL) in dimethylsulfoxide (160 mL) was stirred at 80° C. for 5 h. After the reaction mixture was poured into water, the precipitate was filtered, washed with diethylether and dried, affording 4′-chloro-2,2-dihydroxyacetophenone (14.0 g, 70%). 1H NMR (300 MHz, CDCl3), δ 5.92(1H, s), 7.45-7.52(2H, m), 8.05-8.20(2H, m).


2,2-dimethly-ethylenediamine (2.10 mL, 20.0 mmol) was added to a solution of 4′-chloro-2,2-dihydroxyacetophenone (3.70 g, 20.0 mmol) in methanol (120 mL) and tetrahydrofuran (30 mL) at room temperature. After 2 h, sodium borohydride (1.50 g, 40.0 mmol) was added to the reaction mixture at 0° C. The reaction mixture was stirred overnight, then quenched with 1N hydrochloric acid and evaporated in vacuo. The acidic solution was extracted with ethyl acetate, then basified to pH 11 using 15% aqueous sodium hydroxide, and extracted with dichloromethane. The extract was dried over sodium sulfate and concentrated in vacuo. Di-t-butyldicarbonate (6.40 mL, 27.9 mmol) was added to the solution of the residue in 1N aqueous sodium hydroxide (40 mL) and tetrahydrofuran (60 mL). The resulting suspension was heated at 40° C. for 8 h, then diluted with ethyl acetate and water. The organic layer was extracted with additional ethyl acetate, dried and concentrated in vacuo. The crude product was purified by flash column chromatography, affording 2-(4-chlorophenyl)-4-t-butoxycarbonyl-6,6-dimethylpiperazine (1.69 g, 28%, 2 steps). 1H NMR (300 MHz, CDCl3), δ 1.15(3H, s), 1.21(3H, s), 2.47-2.70(2H, m), 3.72-4.16(3H, m), 7.26-7.37(4H, m).


4 M Hydrogen chloride in ethyl acetate (5.0 mL, 20.0 mmol) was added to a solution of 2-(4-chlorophenyl)-4-t-butoxycarbonyl-6,6-dimethyl-piperazine (1.69 g, 5.2 mmol). After 12 h, removing the solvent, filtrating and washing the precipitate with ethyl acetate gave 2-(4-chlorophenyl)-6,6-dimethyl-piperazine dihydrochloride (1.43 g, 95%). 1H NMR (300 MHz, DMSO-d6), δ 1.40 (3H, s), 1.58(3H, s), 3.24-3.99(4H, m), 4.73(1H, m), 7.69(2H, d, J=8.4 Hz), 7.79(2H, m), 9.99-10.12(2H, m).


A solution of 2-(4-chlorophenyl)-6,6-dimethyl-piperazine hydrochloride (155 mg, 0.52 mmol), 2-chloro-3-methyl-6-(4-pyridyl)-pyrimidine-4-one (111 mg, 0.50 mmol) and triethylamine (0.42 mL, 2.50 mmol) in tetrahydrofuran (5 mL) was stirred at room temperature for 6 h. The whole was evaporated in vacuo and the residue was extracted with dichloromethane. The organic layer was washed with water, dried and concentrated in vacuo. The residue was dissolved in methanol (5 mL) and treated with 4M hydrogen chloride in ethyl acetate (0.50 mL, 2.0 mmol) for 20 min. After removing the solvent, filtrating and washing the precipitate with ethanol gave 2-(2-(4-chlorophenyl)-6,6-dimethyl-piperazin-4-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride (235 mg, 97%).


Example 10
Synthesis of 2-(2S-(4-bromophenyl)-piperazin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (No. XA2051)

Benzyl chloroformate (2.40 mL, 15.0 mmol) was added to a solution of 2S-(4-bromophenyl)-piperazine dihydrochloride in 1N aqueous sodium hydroxide (30 mL) and dichloromethane (60 mL). The resulting suspension was stirred at room temperature for 1.5 h. After partitioned between ethyl-acetate, the organic layer was extracted with additional ethyl acetate, dried and concentrated in vacuo. The precipitate was washed with ether, affording 2S-(4-bromophenyl)-4-benzyloxycarbonyl-piperazine (2.92 g, 57%). 1H NMR (300 MHz, CDCl3), δ 2.87-3.01(2H, m), 3.47(2H, m), 3.93-3.97(1H, m), 4.20(2H, m), 5.16(2H, s), 7.36(5H, m), 7.42-7.61(4H, m).


A solution of 2S-(4-bromophenyl)-4-benzyloxycarbonyl-piperazine (788 mg, 2.10 mmol), 2-chloro-3-methyl-6-(4-pyridyl)-pyrimidine-4-one (444 mg, 2.00 mmol) and diisopropylethylamine (0.70 mL, 4.00 mmol) in dimethylformamide (20 mL) was stirred at 80° C. for 3 h. The reaction mixture was poured into water and the whole was extracted with ethyl acetate. The organic layer was washed with brine, dried and concentrated in vacuo. Chromatographic purification of the residue provided 2-(2S-(4-bromophenyl)-4-benzyloxycarbonyl-piperazin-1-yl)}-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (601 mg, 54%). 1H NMR (300 MHz, CDCl3), δ 3.05(1H, m), 3.30-3.48(3H, m), 3.64(3H, s), 4.08-4.22(2H, m), 4.68(1H, m), 5.15(1H, d, J=12.3 Hz), 5.21(1H, d, J=12.6 Hz), 6.63(1H, s), 7.21(2H, d, J=8.4 Hz), 7.28-7.39(7H, m), 7.59(2H, d, J=6.3 Hz), 8.68(2H, d, J=6.3 Hz).


Potassium hydroxide (168 mg, 3.0 mmol) was added to a solution of 2-{2S-(4-bromophenyl)-4-benzyloxycarbonyl-piperazin-1-yl}-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one in ethanol (2.0 mL). After stirring for 8 h at room temperature, purifying by preparative HPLC gave 2-(2S-(4-bromophenyl)-piperazin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (40 mg, 26%).


Example 11
Synthesis of (S)-3-methyl-6-(4-pyridyl)-2-(3-(4-(3-(pyrrolidin-1-yl) pyrrolidin-1-yl)phenyl)piperazin-1-yl)pyrimidin-4-one (No. XA2032)

A suspension of (S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl) piperazine (1.33 g, 3.00 mmol), (R)-3-pyrrolidinol (520 mg, 4.20 mmol), palladium acetate (27 mg, 0.12 mmol), 2-(di-t-butylphosphino)biphenyl (72 mg, 0.24 mmol), and sodium t-butoxide (808 mg, 8.41 mmol) in tert-butanol (20 mL) was heated at 90° C. for 3.5 h. After dilution with ethyl acetate, the resulting mixture was passed through a Celite column. The filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography eluting 10-50% ethyl acetate-hexane to afford (S)-1,4-di-(t-butoxycarbonyl)-2-(4-((R)-3-hydroxypyrrolidino) phenyl)piperazine (733 mg, 54.5%) as a yellow foam.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-hydroxy pyrrolidino)phenyl)piperazine (733 mg, 1.64 mmol) and triethylamine (0.34 mL, 2.46 mmol) in dichloromethane (20 mL) was added methanesulfonyl chloride (0.152 mL, 1.97 mmol) at 0° C. After stirring for 20 min, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-(methansulfonyloxy)pyrrolidin-1-yl) phenyl)piperazine (877 mg, quant.) as a brown solid.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-((R)-3-methansulfonyloxy-pyrrolidino)phenyl)piperazine (877 mg, 1.64 mmol) in toluene (10 mL) was added pyrrolidine (0.64 mL, 8.19 mmol), and the resulting solution was heated at 90° C. for 8 h. After checking consumption of the starting material with TLC, the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate aqueous solution. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 30-100% ethyl acetate-hexane and then 3-10% methanol-ethyl acetate to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4-((S)-3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl)piperazine (479 mg, 58%) as a pale yellow powder.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-((S)-3-(pyrrolidin-1-yl) pyrrolidin-1-yl)phenyl)piperazine (479 mg, 0.957 mmol) in dichloromethane (4 mL) was added 4 N hydrogen chloride in ethyl acetate (4 mL) at room temperature. After stirring for 3 h, the resulting precipitate was collected and dried in vacuo to afford (S)-2-(4-((S)-3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl)piperazine tetrahydrochloride (370 mg, 87%) as a white solid.


To a suspension of (S)-2-(4-((S)-3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl) piperazine tetrahydrochloride (98 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.20 mL, 1.40 mmol) and 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (44 mg, 0.20 mmol) at room temperature. After stirring for 24 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane and sodium bicarbonate aqueous solution, and the solution was passed through CHEM ELUT CE1010 (manufactured by VARIAN). The filtrate was concentrated, and the resulting crystals were washed in a mixture of diisopropyl ether and ethanol to afford (S)-2-(3-(4-(3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (80 mg, 82%) as a pale yellow solid.


Example 12
Synthesis of (S)-3-methyl-6-(4-pyrimidinyl)-2-(3-(4-(3-(pyrrolidin-1-yl) pyrrolidin-1-yl)phenyl)piperazin-1-yl)pyrimidin-4-one (No. YA1577)

To a suspension of (S)-2-(4-((S)-3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl) piperazine tetrahydrochloride (99 mg, 0.22 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.20 mL, 1.40 mmol) and 2-chloro-3-methyl-6-(4-pyrimidinyl)-3H-pyrimidin-4-one (45 mg, 0.20 mmol) at room temperature. After stirring for 24 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane and sodium bicarbonate aqueous solution, and the solution was passed through CHEM ELUT CE1010 (manufactured by VARIAN). The filtrate was concentrated, and the resulting crystals were washed in a mixture of diisopropyl ether and ethanol to afford (S)-3-methyl-6-(4-pyrimidinyl)-2-(3-(4-(3-(pyrrolidin-1-yl)pyrrolidin-1-yl)phenyl)piperazin-1-yl)-pyrimidin-4-one (65 mg, 66%) as a pale yellow solid.


Example 13
Synthesis of (S)-2-(3-(4-(N-cyclohexyl-N-methylamino)phenyl) piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (No. XA1999)

A suspension of (S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl) piperazine (1.21 g, 2.75 mmol), N-methylcyclohexylamine (0.43 mL, 3.30 mmol), palladium acetate (25 mg, 0.11 mmol), 2-(di-t-butylphosphino)biphenyl (66 mg, 0.22 mmol), and sodium t-butoxide (370 mg, 3.85 mmol) in t-butanol (15 mL) was heated at 80° C. for 8 h. The resulting solution was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 10-15% ethyl acetate-hexane to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazine (917 mg) as white crystals.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazine in dichloromethane (4 mL) was added 4 N hydrogen chloride in ethyl acetate (4 mL). After stirring for 40 min, the white precipitate was collected, which included impurities. The mixture was purified by a reverse phase chromatography eluting 0.05% TFA in water-acetonitrile to afford (S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazine (59 mg 8% in 2 steps) as a clear oil.


To a solution of (S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl) piperazine (50 mg, 0.183 mmol) and triethylamine (0.077 mL, 0.55 mmol) was added 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (37 mg, 0.17 mmol) at room temperature. After stirring for 4.5 h, the reaction mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by a reverse phase chromatography eluting 0.05% TFA in water-acetonitrile to afford (S)-2-(3-(4-(N-cyclohexyl-N-methylamino)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (67 mg, 88%) as a oil, which was dissolved in ethyl acetate and treated with 4 N hydrogen chloride in ethyl acetate to yield its trihydrochloride.


Example 14
Synthesis of (S)-2-(3-(4-(N,N-dimethylamino)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one trihydrochloride (No. XA2017)

A suspension of (S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl) piperazine (1.14 g, 2.59 mmol), N,N-dimethylamine hydrochloride (422 mg, 5.17 mmol), palladium acetate (23 mg, 0.10 mmol), 2-(di-t-butylphosphino)biphenyl(62 mg, 0.21 mmol), and sodium t-butoxide (845 mg, 8.80 mmol) in t-butanol (15 mL) was heated at 90° C. for 3 h. After dilution with ethyl acetate, the resulting solution was passed through a Celite column. The filtrate was concentrated, and the residue was purified by silica gel column chromatography eluting 10-20% ethyl acetate-hexane to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4-(N,N-dimethylamino) phenyl)piperazine (556 mg, 53%) as white crystals.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4-(N,N-dimethylamino) phenyl)piperazine (556 mg, 1.37 mmol) in dichloromethane (4 mL) was added 4 N hydrogen chloride in ethyl acetate (4 mL). After stirring for 8.5 h, the white precipitate was collected and dried in vacuo to afford (S)-2-(4-(N,N-dimethylamino) phenyl)piperazine trihydrochloride (413 mg, 96%) as white crystals.


To a suspension of (S)-2-(4-(N,N-dimethylamino)phenyl)piperazine trihydrochloride (115 mg, 0.365 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.28 mL, 2.0 mmol) and then 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (74 mg, 0.33 mmol) at room temperature. After stirring for 10 h, the resulting mixture was concentrated in vacuo. The residue was dissolved in dichloromethane and saturated sodium bicarbonate aqueous solution, and the solution was passed through CHEM ELUT CE1010 (manufactured by VARIAN). The filtrate was concentrated in vacuo to yield crystals, which were washed with diisopropyl ether. After the crystals were dissolved in ethyl acetate, the solution was treated with 4 N hydrogen chloride in ethyl acetate. White precipitate was collected and dried in vacuo to afford (S)-2-(3-(4-(N,N-dimethylamino)phenyl) piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one trihydrochloride (135 mg, 81%).


Example 15
Synthesis of (S)-2-(3-(4-methoxybiphen-4-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (No. XA1991)

A mixture of (S)-2-(4-bromophenyl)-1,4-di(t-butoxycarbonyl)piperazine (1.82 g, 4.11 mmol), 4-methoxyphenylboronic acid (937 mg, 6.17 mmol), sodium carbonate (2.18 g, 20.6 mmol), and tetrakis(triphenylphosphine)palladium(0) (238 mg, 0.206 mmol) was dissolved in dimethoxyethane (20 mL) and water (20 mL), and the resulting solution was refluxed for 3 h. After cooling to room temperature, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting solid was washed with ethyl acetate to afford (S)-1,4-di(t-butoxycarbonyl)-2-(4′-methoxybiphen-4-yl)piperazine (1.46 g, 75.9%) as a white solid.


To a solution of (S)-1,4-di(t-butoxycarbonyl)-2-(4′-methoxybiphen-4-yl)-piperazine (1.46 g, 3.12 mmol) in dichloromethane (8 mL) was added 4 N hydrogen chloride in ethyl acetate (8 mL) at room temperature. After stirring for 1 h, the precipitate was collected and dried in vacuo to afford (S)-2-(4′-methoxybiphen-4-yl) piperazine dihydrochloride (1.00 g, 94%) as white solid.


To a suspension of (S)-2-(4′-methoxybiphen-4-yl)-piperazine dihydrochloride (237 mg, 0.694 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.40 mL, 2.9 mmol) and then 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (128 mg, 0.579 mmol) at room temperature. After stirring for 28 h, the resulting mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution, and the organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting solid was washed with hot ethanol to afford (S)-2-(3-(4-methoxybiphen-4-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (252 mg, 96%), which was treated with 4 N hydrogen chloride in ethyl acetate to yield its dihydrochloride salt (252 mg) as pale yellow crystals.


Example 16
Synthesis of (S)-2-(3-benzylpiperazin-1-yl)-3-methyl-6-(4-pyridyl) pyrimidin-4-one (No. XA2004)

To a solution of L-phenylalanine ethyl ester hydrochloride (3.875 g, 16.87 mmol), Boc-glycine (2.815 g, 16.07 mmol) in dichloromethane (100 mL) was added triethylamine (2.35 mL, 16.87 mmol) and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.23 g, 16.87 mmol) at room temperature. After the resulting mixture was stirred for 2.5 h, it was partitioned between ethyl acetate and water. The organic layer was washed with 1 N hydrochloric acid, brine, and then saturated sodium bicarbonate aqueous solution, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford Boc-glyclylphenylalanine ethyl ester (5.96 g).


To a solution of Boc-glycylphenylalanine ethyl ester (5.96 g) in dichloromethane (20 ml) was added trifluoroacetic acid (20 mL) at room temperature. After stirring 1.5 h, the resulting solution was concentrated in vacuo. The residue was dissolved in water, into which sodium bicarbonate was added until the pH was 9. After the solution was stirred for several hours, the resulting white crystals were collected and dried in vacuo to afford (S)-3-benzyl-2,5-dioxopiperazine (2.29 g, 70% in 2 steps) as a white powder.


To a suspension of (S)-3-benzyl-2,5-dioxopiperazine (2.284 g, 11.18 mmol) in tetrahydrofuran (20 mL) was added borane-tetrahydrofuran complex (49 mL, 1.0 M solution in THF, 49 mmol) at room temperature. The resulting mixture was refluxed for several hours before it was quenched with methanol at 0° C. After concentration in vacuo, the residue was treated with 10% sodium hydroxide aqueous solution, which was extracted with dichloromethane thoroughly. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford white crystals, which were washed with ether to yield (S)-2-benzylpiperazine (795 mg, 40.3%).


To a solution of (S)-2-benzylpiperazine (48 mg, 0.27 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.10 mL, 0.74 mmol) and then 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (55 mg, 0.248 mmol) at room temperature. After refluxing for 24 h, the resulting mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution, and the organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The residue was purified by a reverse phase chromatography eluting 0.05% TFA in water-acetonitrile to afford (S)-2-(3-benzylpiperazin-1-yl)-3-methyl-6-(4-pyridyl) pyrimidin-4-one (73 mg 81%), which was treated with 4 N hydrogen chloride in ethyl acetate to yield its dihydrochloride salt as a yellow powder.


Example 17
Synthesis of (S)-3-methyl-2-(3-(4-(1,2,4-oxadiazol-3-yl)phenyl) piperazin-1-yl)-6-(4-pyridyl)pyrimidin-4-one (No. XA2039)

To a solution of 4-cyanoacetophenone (11.32 g, 77.98 mmol) in dichloromethane (200 mL) was added bromine (4.00 mL, 78.0 mmol) dropwise at room temperature. After stirring several minutes, the reaction mixture was washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to afford 4-cyanophenacyl bromide (17.73 g) as a white solid.


A solution of 4-cyanophenacyl bromide (11.20 g, 49.99 mmol) in dimethylsulfoxide (83 mL) was treated with water (0.90 mL, 49.99 mmol). After stirring for 24 h at room temperature, it was poured into ice-water, and extracted with ether. The organic layer was washed with water and then brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by a silica gel column chromatography eluting 20-50% ethyl acetate in hexane to afford 4-cyanophenylglyoxal (5.10 g, 64.1%) as a yellow solid.


To a solution of 4-cyanophenylglyoxal (2.21 g, 12.5 mmol) in methanol (30 mL) and tetrahydrofuran (10 mL) was added ethylenediamine (1.00 mL, 14.96 mmol) at room temperature. After the mixture was stirred at room temperature for 1 h, sodium borohydride (943 mg, 24.92 mmol) was added at 0° C. The solution was warmed up to room temperature and stirred for another 2 h before it was quenched with 1 N hydrochloric acid. After concentration in vacuo, the mixture was partitioned between ether and water. The aqueous layer was alkalized with sodium hydroxide, and extracted with dichloromethane. The extract was dried over anhydrous sodium sulfate, and then concentrated in vacuo to afford reddish oil (1.69 g). The oil was dissolved in dichloromethane (30 mL), into which triethylamine (3.82 mL, 27.41 mmol) and di-tert-butyl dicarbonate (5.98 g, 27.41 mmol) at room temperature. The reaction mixture was stirred for several hours before it was partitioned between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate, and then concentrated in vacuo. The residue was purified by a silica gel column chromatography eluting 5-20% ethyl acetate in hexane to afford 1,4-di(t-butoxycarbonyl)-2-(4-cyanophenyl)piperazine (2.46 g, 50.9%) as white crystals.


A solution of 1,4-di(t-butoxycarbonyl)-2-(4-cyanophenyl)piperazine (558 mg, 1.44 mmol), hydroxylamine hydrochloride (300 mg, 4.23 mmol), and sodium carbonate (763 mg, 7.20 mmol) in ethanol (3 mL) and water (3 mL) was heated at 80° C. for 2.5 h before it was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane. The combined organic layer was dried over sodium sulfate, and concentrated in vacuo to afford white foam (680 mg), which was dissolved in toluene (5 mL) and treated with triethyl orthoformate (2.4 mL, 14.4 mmol) and p-toluenesulfonic acid (27 mg, 0.14 mmol). The solution was heated at 90° C. for 1 h before it was partitioned between dichloromethane and saturated sodium bicarbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting white crystals were washed with ethyl acetate, and dried in vacuo to afford 1,4-di(t-butoxycarbonyl)-2-(4-(1,2,4-oxadiazol-3-yl)phenyl)piperazine (464 mg, 75% in 2 steps).


To a solution of 1,4-di(t-butoxycarbonyl)-2-(4-(1,2,4-oxadiazol-3-yl) phenyl)piperazine (464 mg, 1.08 mmol) in dichloromethane (2 mL) was added 4 N hydrogen chloride in ethyl acetate (3 mL) at room temperature. After stirring for 1.5 h, the precipitate was collected and dried in vacuo to afford 2-(4-(1,2,4-oxadiazol-3-yl)phenyl)piperazine dihydrochloride (321 mg, 98%) as a white powder.


To a suspension of 2-(4-(1,2,4-oxadiazol-3-yl)phenyl)piperazine dihydrochloride (102 mg, 0.34 mmol) in tetrahydrofuran (6 mL) was added triethylamine (0.23 mL, 1.65 mmol) and then 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (73 mg, 0.33 mmol) at room temperature. After stirring for 24 h, the resulting mixture was concentrated in vacuo. The residue was dissolved in dichloromethane and saturated sodium bicarbonate aqueous solution, and the solution was passed through CHEM ELUT CE1010 (manufactured by VARIAN). The filtrate was concentrated in vacuo to yield crystals, which were washed with diisopropyl ether and ethanol to afford (S)-2-(3-(4-(1,2,4-oxadiazol-3-yl)phenyl) piperazin-1-yl)-3-methyl-6-(4-pyridyl)pyrimidin-4-one (102 mg 74%) as a white powder.


Example 18
Synthesis of 2-[4-(2-Methoxyphenylamino)-piperidin-1-yl]-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (No. XB276)

To a solution of anisidine (3.1 g, 25.2 mmol) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5.0 g, 25.1 mmol) in methanol (100 mL) was added sodium triacetoxyborohydride (13.4 g, 63.2 mmol) at room temperature. After stirring for 6 h, the resulting suspension was partitioned between ethyl acetate and 1N sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 10-20% ethyl acetate in hexane to furnish 4-(2-methoxyphenylamino)-piperidine-1-carboxylic acid tert-butyl ester (2.7 g, 8.8 mmol, 35%) as a pale yellow oil.


To a solution of 4-(2-methoxyphenylamino)-piperidine-1-carboxylic acid tert-butyl ester (2.7 g, 8.8 mmol) in methanol (30 mL) was added 4N hydrochloric acid in ethyl acetate (20 mL) at room temperature. After stirring for 1 h, the resulting suspension was concentrated in vacuo. The residue was partitioned between chloroform and 1N sodium hydroxide. The aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 10-20% methanol in chloroform to furnish 4-(2-methoxyphenylamino)-piperidine (1.8 g, 8.7 mmol, 99%) as white crystals.


To a solution of 4-(2-methoxyphenylamino)-piperidine (0.8 g, 3.87 mmol) and triethylamine (1.3 g, 12.8 mmol) in tetrahydrofuran (20 mL) was added 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (0.8 g, 3.61 mmol) portionwise. After stirring for 12 h, the resulting suspension was partitioned between chloroform and 1N sodium hydroxide. The aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish 2-(4-(2-methoxyphenylamino)-piperidin-1-yl)-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (1.2 g, 3.07 mmol, 85%) as white crystals.


Example 19
Synthesis of 3-Methyl-2-(3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidin-1-yl)-6-(pyridin-4-yl)-3H-pyrimidin-4-one (No. XB278)

A solution of (4-bromo-phenyl)-acetic acid ethyl ester (2.31 g, 9.50 mmol) in dimethylsulfoxide (6 mL) was added to the suspension of sodium hydride (407 mg, 60% in oil, 10.17 mmol) and stirred 3 min. A solution of (3-bromo-propyl)-carbamic acid tert-butyl ester (2.03 g, 8.52 mmol) in dimethylsulfoxide (6 mL) was added to the solution and stirred at 50° C. for 30 min. The resulting solution was partitioned between ethyl acetate and saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried by passing through Celite column, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting ethyl acetate/hexane (4/1 to 3/1, v/v) to afford 3-(4-Bromo-phenyl)-6-tert-butoxycarbonylamino-hexanoic acid ethyl ester (2.43 g, 74%).


To a solution of 3-(4-Bromo-phenyl)-6-tert-butoxycarbonylamino-hexanoic acid ethyl ester (2.43 g, 6.32 mmol) in ethyl acetate (3 mL) was added 4 N hydrogen chloride in ethyl acetate (6 mL) at room temperature. Removal of the solvent in vacuo after stirring for 30 min afforded 6-Amino-3-(4-bromo-phenyl)-hexanoic acid ethyl ester hydrochloride that was used in the next step without further purification.


A solution of 6-amino-3-(4-bromo-phenyl)-hexanoic acid ethyl ester hydrochloride, potassium carbonate (1039 mg, 7.52 mmol) in ethanol (50 ml) was refluxed for 20 hr. Solvent was removed in vacuo after addition of dilute hydrochloric acid and water was added to the residue. Filtration, wash with water and dryness afforded 3-(4-Bromo-phenyl)-piperidin-2-one (1387 mg, 86%, 2 steps).


To an ice-cooled solution of 3-(4-bromo-phenyl)-piperidin-2-one (37.97 g, 149 mmol) in tetrahydrofuran (250 ml) was added borane-tetrahydrofuran complex (335 ml, 1.0 M solution in THF, 335 mmol). The solution was stirred overnight at room temperature, and then refluxed 1.5 hr after addition of 10% aqueous hydrochloric acid. Solvents was removed in vacuo, and the residue was partitioned between dichloromethane and 1N sodium hydroxide. The aqueous layer was extracted with dichlorometane. The combined organic layer was washed with water and brine, dried over sodium sulfate, and concentrated in vacuo. The residue was dissolved in water (100 mL) and concentrated hydrochloric acid (100 mL) and refluxed for 3 hr. Sodium hydroxide was added to the solution and the resulting solution was extracted with dichlorometane. The organic layer was washed with water and brine, dried over sodium sulfate Concentration in vacuo afforded 3-(4-bromo-phenyl)-piperidine (32 18 g, 90%).


To a suspension of 3-(4-bromophenyl)-piperidine (25.2 g, 105 mmol), and triethylamine (13 g, 128 mmol) in tetrahydrofuran (250 mL) was added di-tert-butyl-dicarbonate (25.2 g, 105 mmol) at room temperature. After stirring for 1 h, the resulting suspension was partitioned between ethyl acetate and 1N sodium hydroxide. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was washed by hexane to furnish 3-(4-bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (35.7 g, 105 mmol, 100%) as white crystals.


To a suspension of 3-(4-bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (3.0 g, 8.8 mmol), palladium acetate (80 mg, 0.36 mmol), 2-(di-t-butyl phosphino)biphenyl (210 mg, 0.70 mmol), and sodium t-butoxide (1.2 g, 125 mmol) in toluene (30 mL) was added N-methylpiperazine (1.3 g, 13.0 mmol) at room temperature. After heating at 90° C. for 5 h, the resulting suspension was passed through a Celite column. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography eluting 5-25% of ethyl acetate in hexane to afford 3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 5.56 mmol, 63%) as white crystals.


To a solution of 3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 5.56 mmol) in methanol (20 mL) was added 4N hydrochloric acid in ethyl acetate (20 mL) at room temperature. After stirring for 1 h, the resulting suspension was concentrated in vacuo. The residue was washed with ethyl acetate to furnish 3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidine trihydrochloride (1.84 g, 4.99 mmol, 90%) as white crystals.


To a solution of 3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidine trihydrochloride salt (0.4 g, 1.08 mmol) and triethylamine (0.6 g, 5.93 mmol) in tetrahydrofuran (10 mL) was added 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (0.22 g, 0.99 mmol) portionwise. After stirring for 12 h, the resulting suspension was partitioned between chloroform and 1N sodium hydroxide. The aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish 3-methyl-2-(3-(4-(4-methylpiperazin-1-yl)-phenyl)-piperidin-1-yl)-6-(piridin-4-yl)-3H-pyrimidin-4-one (0.31 g, 0.70 mmol; 71%) as white crystals.


Example 20
Synthesis of 2-(3-(4-cyclohexylaminophenyl)-piperidin-1-yl)-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (No. XB301)

To a suspension of 3-(4-bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (8.0 g, 23.5 mmol), palladium acetate (210 mg, 0.94 mmol), 2-(di-t-butyl phosphino)biphenyl (560 mg, 1.88 mmol), and sodium t-butoxide (3.2 g, 33.3 mmol) in toluene (80 mL) was added cyclohexylamine (2.8 g, 28.2 mmol) at room temperature. After heating at 90° C. for 5 h, the resulting suspension was passed through a Celite column. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography eluting 5-25% of ethyl acetate in hexane to afford 3-(4-cyclohexylaminophenyl)-piperidine-1-carboxylic acid tert-butyl ester (6.74 g, 18.8 mmol, 80%) as white crystals.


To a solution of 3-(4-cyclohexylaminophenyl)-piperidine-1-carboxylic acid tert-butyl ester (6.74 g, 18.8 mmol) in methanol (50 mL) was added 4N hydrochloric acid in ethyl acetate (40 mL) at room temperature. After stirring for 1 h, the resulting suspension was concentrated in vacuo. The residue was washed with ethyl acetate to furnish 3-(4-cyclohexylaminophenyl)-piperidine dihydrochloride (5.84 g, 17.6 mmol, 94%) as white crystals.


To a solution of 3-(4-cyclohexylaminophenyl)-piperidine dihydrochloride salt (1.0 g, 3.02 mmol) and triethylamine (1.5 g, 14.8 mmol) in tetrahydrofuran (20 mL) was added 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (0.64 g, 2.89 mmol) portionwise. After stirring for 12 h, the resulting suspension was partitioned between chloroform and 1N sodium hydroxide. The aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish 2-(3-(4-cyclohexylaminophenyl)-piperidin-1-yl)-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (1.23 g, 2.77 mmol, 96%) as white crystals.


Example 21
Synthesis of 2-(4-(4-Bromo-phenyl)-piperidin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (No. XB267)

Mixture of 4-bromobenzaldehyde (22.40 g, 121.1 mmol), dimethyl malonate (19.37 g, 146.6 mmol), cat. acetic acid and cat. piperidine in toluene (100 ml) were refluxed for 6 h with azeotropically removal of water. Resulting solution was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water, saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate. Concentration of the organic solvent in vacuo afforded 2-(4-bromo-benzylidene)-malonic acid diethyl ester as an oil that was used in the next step without further purification.


To an ice-cooled solution of dimethyl malonate (19.35 g, 146.5 mmol) and sodium methoxide (30.12 g in 28% methanol solution, 156.1 mmol) in methanol (300 ml) was added 2-(4-bromo-benzylidene)-malonic acid diethyl ester in methanol (50 ml). After stirring for 3 h, the solvent was removed in vacuo and the residue was partitioned between ethyl acetate and dilute hydrochloric acid. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate. Concentration of the organic solvent in vacuo afforded 3-(4-bromo-phenyl)-2,4-bis-ethoxycarbonyl-pentanedioic acid diethyl ester as an oil that was used in the next step without further purification.


A solution of 3-(4-bromo-phenyl)-2,4-bis-ethoxycarbonyl-pentanedioic acid diethyl ester in concentrated hydrochloric acid (100 ml) and acetic acid (100 ml) was refluxed for 8 h. Removal of the solvent in vacuo and recrystallization of the residue from acetonitrile yielded 3-(4-bromo-phenyl)-pentanedioic acid (22.84 g in 1st crop, 65%, 3.84 g in 2nd crop, 11.05% from 4-bromobenzaldehyde).


A solution 3-(4-bromo-phenyl)-pentanedioic acid (26.68 g, 92.9 mmol) in acetic anhydride (100 ml) was refluxed for 1.5 hr. Removal of the solvent in vacuo, and remaining solvent were azeotropically removed using toluene. Teterahydrofuran (200 ml) and aqueous ammonia (28%, 50 ml) was added to the residue and stirred overnight. After removal of the solvent in vacuo, acetic anhydride (100 ml) was added and refluxed for 4 hr. After removal of the solvent in vacuo and succeeding azeotropic distillation with toluene, residue was partitioned between ethyl ether and water. Filtration of the suspension and dryness afforded the 4-(4-bromo-phenyl)-piperidine-2,6-dione (12.53 g, 50%) as a solid.


To an ice-cooled solution of lithium tetrahydroborate (4.13 g, 189.6 mmol) in tetrahydrofuran (200 ml) was added chlorotrimethylsilane (41.52 g, 382.2 mmol). After stirring 5 min, a solution of 4-(4-bromo-phenyl)-piperidine-2,6-dione (12.53 g, 46.7 mmol) was added and stirred overnight. The resulting solution was concentrated in vacuo after addition of 10% aqueous hydrochloric acid. The residue was dissolved in aqueous sodium hydroxide solution and methanol, and a solution of di-tert-butyl dicarbonate (11.45 g, 52.5 mmol) in methanol (10 ml) was added and stirred for 6 h. After removal of the solvent in vacuo, concentrated hydrochloric acid wad added and stirred overnight. After extraction of the solution by diethyl ether, sodium hydroxide was added to the aqueous layer to turn basic, and extracted with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate. The residue of the diethyl ether and dichloromethane after removal of the solvents under reduced pressure was mixed and dissolved in tetrahydrofuran (200 ml). A solution of di-tert-butyl dicarbonate (7.45 g, 34.1 mmol) in tetrahydrofuran (10 ml) and triethylamine were added and stirred overnight. The resulting solution was concentrated in vacuo. Purification of the residue by silica gel chromatography eluting hexane/ethyl acetate (5/1, v/v) furnished 4-(4-bromo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (14.4 g, 91%) as a solid.


To a solution of furnished 4-(4-bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (1114 mg, 3.27 mmol) in ethyl acetate (1 mL) was added 4 N hydrogen chloride in ethyl acetate (2 mL) at room temperature. After stirring for 5 h, solvent was removed in vacuo, and the resulting solid was washed with ethyl acetate and dried in vacuo to afford (4-(4-bromophenyl)-piperidine hydrochloride (884 mg, 98%) as a white solid.


A solution of (4-(4-bromophenyl)-piperidine hydrochloride (279 mg, 1.01 mmol) and triethylamine (554 mg, 5.47 mmol), 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (206 mg, 0.929 mmol) in tetrahydrofuran (20 mL) was stirred for 3 hr. The resulting solution was diluted with tetrahydrofuran and filtrated. After removal of the solvents under reduced pressure and the purification of the resulting residue by CHEM ELUT CE1010 (manufactured by VARIAN) eluting dichloromethane/ethanol (15/1, v/v) and wash with ethyl acetate afforded 2-(4-(4-Bromophenyl)-piperidin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (368 mg, 93%) as a solid.


Example 22
Synthesis of 3-Methyl-6-pyridin-4-yl-2-[4-(4-pyrrolidin-1-yl-phenyl)-piperidin-1-yl]-3H-pyrimidin-4-one (No. XB269)

A suspension of 4-(4-Bromophenyl)-piperidine-1-carboxylic acid tert-butyl ester (1.97 g, 5.79 mmol), palladium acetate (54 mg, 0.24 mmol), 2-(di-t-butylphosphino)biphenyl (154 mg, 0.52 mmol), and sodium t-butoxide (846 mg, 8.80 mmol), pyrrolidine (587 mg, 8.25 mmol) in toluene (80 mL) was heated at 90° C. for 3 h under nitrogen atmosphere. The resulting suspension was passed through a Celite column and partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. Purification of the residue by HPLC afforded 4-(4-pyrrolidin-1-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a solid that was used in the next step without further purification.


To a solution of furnished 4-(4-Pyrrolidin-1-yl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester in ethyl acetate (5 mL) was added 4 N hydrogen chloride in ethyl acetate (10 mL) at room temperature. After stirring for 3 h, solvent was removed in vacuo, and the resulting solid was purified by HPLC. Sodium hydroxide was added to the resulting fractions and the aqueous layer was extracted by dichloromethane. Organic layer was washed with brine, and passed through Cerite. Removal of the solvent under reduced pressure afforded 4-(4-pyrrolidin-1-yl-phenyl)-piperidine (1.01 g, 76%).


A solution of 4-(4-pyrrolidin-1-yl-phenyl)-piperidine (215 mg, 0.933 mmol) and triethylamine (391 mg, 3.86 mmol), 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (187 mg, 0.844 mmol) in tetrahydrofuran (10 mL) was refluxed for 5 hr. The resulting solution was diluted with tetrahydrofuran and filtrated. After removal of the solvents under reduced pressure and the purification of the resulting residue by CHEM ELUT CE1010 (manufactured by VARIAN) eluting dichloromethane/ethanol (15/1, v/v) and wash with ethyl acetate afforded 3-methyl-6-pyridin-4-yl-2-(4-(4-pyrrolidin-1-yl-phenyl)-piperidin-1-yl)-3H-pyrimidin-4-one (284 mg, 81%) as a solid.


Example 23
Synthesis of 2-(4-(6-Fluorobenzo[b]thiophen-3-yl)piperidin-1-yl)-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (No. YB253)

The key intermediate 4-(6-fluorobenzo[b]thiophen-3-yl)piperidine hydrochloride of 2-[4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one was synthesized from 1-acetylpipridine-4-carboxylic acid which was prepared according to the method reported by Watanabe (J. Heterocyclic Chem., 30, 445 (1993)).


To a solution of 1-benzoylpiperidine-4-carboxylic acid (66 g, 285 mmol) in dichloromethane (160 mL) was added thionyl chloride (26 mL, 388 mmol). After stirring at 60° C. for 1 h, the mixture was added portionwise to a stirred suspension of 2,4-difluorobenzene (45 g, 397 mmol) and anhydrous aluminum chloride (88 g, 666 mmol) in dichloromethane (245 mL), and the reaction mixture was refluxed for 5 h. The reaction mixture was poured into a mixture of ice and concentrated hydrochloric acid and extracted with chloroform. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. Recrystallization from hexane gave 1-benzoyl-4-(2,4-difluorobenzoyl)piperidine (46 g, 50%) as colorless crystals.


A solution of 1-benzoyl-4-(2,4-difluorobenzoyl)piperidine (40 g, 120 mmol), methyl thioglycolate (12 mL, 130 mmol) in dimethylformamide (500 mL) was stirred at room temperatute for 12 h. The solvent was evaporated off in vacuo and the residue treated with water and ethyl acetate. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography eluting hexane/ethyl acetate to give 3-(1-benzoylpiperidin-4-yl)-6-fluorobenzo[b]thiophene-2-carboxylic acid (11.8 g, 26%) as an oil.


3-(1-Benzoylpiperidin-4-yl)-6-fluorobenzo[b]thiophene-2-carboxylic acid (10 g, 26 mmol) was suspended in quinoline (100 mL) and cupper powder (0.5 g) was added. After stirring at 200° C. for 1 h, the mixture was cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate and evaporated. The obtained residue was purified by silica gel column chromatography eluting hexane/ethyl acetate to give (4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl)phenylmethanone (5.0 g, 48%) as yellow crystals.


A solution of (4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl) phenylmethanone (6.5 g, 19 mmol) in acetic acid (100 mL) and concentrated hydrochloric acid (100 mL) was stirred at 90° C. for 10 h. To a solution of reaction mixture was added ethyl acetate. The precipitated crystals were collected by filtration and washed with ethyl acetate to give 4-(6-fluorobenzo[b]thiophen-3-yl)piperidine hydrochloride (4.8 g, 89%) as yellow crystals.


To a solution of 4-(6-fluorobenzo[b]thiophen-3-yl)piperidine hydrochloride (200 mg, 0.74 mmol) and 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (160 mg, 0.70 mmol) in tetrahydrofuran (10 mL) was added triethylamine (212 mg, 2.1 mmol). The mixture was stirred at 90° C. for 6 h. The solvent was evaporated off in vacuo and the residue was treated with water and chloroform. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. Recrystallization from ethyl acetate gave 2-[4-(6-fluorobenzo[b]thiophen-3-yl)piperidin-1-yl]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (220 mg, 96%) as colorless crystals.


Example 24
Synthesis of 2-(4-(Biphenyl-2-yl)piperazin-1-yl)-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (No. YA1552)

To a solution of 1-biphenyl-2-yl-piperazine dihydrochloride (311 mg, 1.0 mmol) and 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (202 mg, 0.91 mmol) in tetrahydrofuran (20 mL) was added triethylamine (404 mg, 4.0 mmol). The mixture was stirred at 90° C. for 4 h. The solvent was evaporated off in vacuo and the residue treated with water and chloroform. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. Recrystallization from ethyl acetate gave 2-[4-(biphenyl-2-yl)piperazin-1-yl]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (250 mg, 65%) as colorless crystals.


The compounds in the following table were prepared in the same manner as the methods described above. The compound numbers in the following table correspond to those shown in the above-described table of preferred compounds.











TABLE 5









Exact-


NO
NMR
MS





XA19
2.51-2.89(4H, m), 3.31-3.34(4H, m),
362



3.39(3H, s), 3.56(2H, s), 6.80(1H, s),



7.25-7.31(1H, m), 7.31-7.36(4H, m),



7.98(2H, dd, J=1.5, 4.8Hz), 8.68(2H, dd,



J=1.5, 4.5Hz) (DMSO-d6)


XA25
3.32-3.34(4H, m), 3.46(3H, s), 3.48-3.51(4H,
348



m), 6.80-6.85(1H, m), 6.84(1H, s), 7.01(2H,



d, J=8.0Hz), 7.23-7.28(2H, m), 8.00(2H, dd,



J=1.3, 4.6Hz), 8.70(2H, dd, J=1.5, 4.5Hz)



(DMSO-d6)


XA156
3.47(3H, s), 3.51-3.60(4H, m), 3.62-3.71(4H,
405



m), 6.85(1H, s), 7.41-7.49(1H, m),



7.56-7.61(1H, m), 8.02(2H, dd, J=1.5, 4.5Hz),



8.09(1H, d, J=8.1Hz), 8.16(1H, d, J=8.1Hz),



8.70(2H, dd, J=1.5, 4.8Hz) (DMSO-d6)


XA289
1.11-1.28(3H, m), 2.98-3.16(1H, m),
434



3.28-3.41(1H, m), 3.39(3H, s), 3.54-3.80(3H,



m), 3.88-3.99(1H, m), 4.08-4.26(4H, m),



4.32-4.45(1H, m), 7.13(1H, s), 7.37-7.53(5H,



m), 8.45(2H, d, J=5.8Hz), 8.96(2H, d,



J=6.0Hz) (DMSO-d6)


XA361
3.44(3H, s), 3.54-3.95(6H, m), 4.64(1H, brs),
348



7.11(1H, s), 7.42-7.51(3H, m),



7.74(2H, d, J=6.6Hz), 8.46(2H, d, J=5.7Hz),



8.94(2H, d, J=5.7Hz), 9.98(1H, brs), 10.46(1H,



brs) (DMSO-d6).


XA364
(DMSO-d6): 3.41-3.76(4H, m), 3.48(3H, s),
366



3.89-4.01(2H, m), 4.96(1H, m), 7.16(1H, s),



7.33-7.58(3H, m), 8.11(1H, dd, J=7.2,



7.2Hz), 8.52(2H, d, J=6.6Hz), 8.97(2H, d,



J=6.6Hz), 10.04(1H, m), 10.66(1H, m).


XA365
3.43(s, 3H), 3.51-3.96(m, 6H), 4.70(m, 1H),
366



7.00(s, 1H), 7.25(m, 1H), 7.54(m, 2H),



7.60(m, 1H), 8.20(d, J=5.7Hz, 2H), 8.80(d,



J=5.7Hz, 2H) (CDCl3)


XA366
2.27-2.85(1H, m), 2.94-3.08(3H, m),
366



3.43(3H, s), 3.59-3.67(2H, m), 3.94-3.97(1H,



m), 6.81(1H, s), 7.19(2H, t, J=8.9Hz),



7.50-7.55(2H, m), 7.96(2H, dd, J=1.6, 4.5Hz),



8.68(2H, dd, J=1.5, 4.6Hz) (DMSO-d6)


XA366
3.35-3.50(2H, m), 3.46(3H, s), 3.58-3.75(2H,
366


(HCl)
m), 3.86-3.97(2H, m), 4.68(1H, t, J=9.3Hz),



7.15(1H, s), 7.35(2H, t, J=9.0Hz),



7.82-7.87(2H, m), 8.48(2H, d, J=6.6Hz),



8.96(2H, d, J=6.3Hz), 9.55-10.08(1H, m),



10.54-10.70(1H, m) (DMSO-d6)


XA369
(CDCl3): 2.81(1H, dd, J=10.4, 12.5Hz),
382



3.18-3.40(3H, m), 3.50-3.80(5H, m),



4.50(1H, dd, J=2.5, 10.1Hz), 6.67(1H, s),



7.20-7.45(3H, m), 7.74(1H, dd, J=1.9, 7.6Hz),



7.81(2H, dd, J=1.4, 4.6Hz),



8.70(2H, dd, J=1.4, 4.6Hz).


XA370
(CDCl3): 3.01(1H, dd, J=10.4, 12.5Hz),
382



3.10-3.30(3H, m), 3.50-3.80(5H, m),



4.04(1H, dd, J=2.7, 10.8Hz), 6.67(1H, s),



7.20-7.45(4H, m), 7.50(1H, s),



7.80(2H, dd, J=1.5, 4.8Hz),



8.71(2H, dd, J=1.5, 5.1Hz).


XA371
3.44(3H, s), 3.44-3.71(7H, m), 3.90(2H, m),
382



4.66(1H, brs), 7.11(1H, s),



7.55(2H, d, J=8.4Hz), 7.78(2H, d, J=8.4Hz),



8.50(2H, d, J=5.7Hz), 8.95(2H, d, J=5.7Hz),



10.13(1H, brs), 10.60(1H, brs) (DMSO-d6)


XA376
(DMSO-d6): 3.45(3H, s), 3.50-4.20(6H, m),
426



4.66(1H, br s), 7.12(1H, s), 7.72(4H, s),



8.44(2H, d, J=6.6Hz), 8.94(2H, d, J=6.6Hz),



10.00(1H, br s), 10.05(1H, br s)


XA391
3.37-3.93(6H, m), 3.48(3H, s), 3.87(3H, s),
378



4.89-4.95(1H, m), 7.04-7.12(2H, m),



7.17(1H, d, J=8.5Hz), 7.45-7.51(1H, m),



7.75-7.81(1H, m), 8.29-8.38(2H, m),



8.83-8.91(2H, m), 9.66-9.77(1H, m),



9.91-10.10(1H, m) (DMSO)


XA392
(DMSO-d6): 3.30-3.58(5H, m),
378



3.58-3.80(2H, m), 3.81(3H, s),



3.85-4.00(2H, m), 4.58-4.75(1H, m),



7.03(1H, dd, J=1.8, 8.1Hz), 7.11(1H, s),



7.26(1H, d, J=7.8Hz), 7.35-7.50(2H, m),



8.41(2H, d, J=5.7Hz), 8.92(2H, d, J=6.0Hz),



9.80-10.00(1H, brd), 10.30-10.60(1H, brd).


XA393
3.40-3.43(5H, m), 3.51-3.63(2H, m),
378



3.78(3H, s), 3.93(2H, m), 4.58(1H, br),



7.02-7.06(3H, m), 7.64(2H, d, J=8.7Hz),



8.34(2H, d, J=6.3Hz), 8.88(2H, d, J=8.7Hz),



9.76(1H, br), 10.16(1H, br) (DMSO-d6)


XA396
1.30(3H, t, J=6.9Hz), 3.38-3.54(1H, m),
392



3.49(3H, s), 3.65-3.79(1H, m), 3.84-3.98(2H,



m), 4.02-4.18(2H, m), 4.84(1H, t, J=10.5Hz),



7.04-7.16(2H, m), 7.15(1H, s), 7.39-7.45(1H,



m), 7.89(1H, d, J=6.6Hz), 8.49(2H, d, J=6.3Hz),



8.95(2H, d, J=6.6Hz), 9.92(1H, d, J=9.3Hz),



10.51-10.64(1H, m) (DMSO-d6)


XA406
(DMSO-d6): 3.64(2H, m),
373



3.94(2H, t, J=11.4Hz), 4.02-4.40(5H, m),



4.78(1H, t, J=10.4Hz), 7.06(1H, s),



7.98(2H, d, J=8.3Hz), 8.01(2H, d, J=8.3Hz),



8.23(1H, dd, J=1.2, 5.1Hz),



9.02(1H, d, J=5.1Hz), 9.31(1H, d, J=1.2Hz),



10.03(1H, d, J=8.7Hz), 10.57(1H, s).


XA433
(CDCl3): 2.00(4H, m),
417



3.03(1H, dd, J=10.8, 12.0Hz), 3.21(3H, m),



3.29(4H, m), 3.57(3H, s), 3.62(2H, m),



3.90(1H, dd, J=2.7, 10.8Hz),



6.57(2H, d, J=8.7Hz), 6.66(1H, s),



7.29(2H, d, J=8.7Hz), 7.80(2H, d, J=4.8Hz),



8.70(2H, d, J=4.8Hz).


XA439
(CDCl3): 3.02(1H, dd, J=10.7, 12.4Hz),
434



3.18(7H, m), 3.55(3H, s), 3.62(2H, m),



3.87(4H, m), 3.96(1H, dd, J=2.5, 11.1Hz),



6.66(1H, S), 6.93(2H, d, J=8.7Hz),



7.36(2H, d, J=8.7Hz), 7.79(2H, d, J=4.5Hz),



8.70(2H, d, J=4.5Hz).


XA442
(CDCl3): 2.36(3H, s), 2.59(4H, m),
446



3.02(1H, t, J=11.6Hz), 3.22(7H, m),



3.55(3H, s), 3.63(2H, m),



3.94(1H, d, J=10.5Hz), 6.66(1H, s),



6.93(2H, d, J=8.7Hz), 7.34(2H, d, J=8.7Hz),



7.80(2H, d, J=4.5Hz), 8.70(2H, d, J=4.5Hz).


XA463
3.41-3.54(3H, m), 3.48(3H, s), 3.69-3.73(1H,
408



m), 3.78(3H, s), 3.82(3H, s), 3.86-3.93(2H,



m), 4.89(1H, t, J=10.5Hz), 6.97-7.01(1H, m),



7.08(1H, d, J=9.0Hz), 7.15(1H, s), 7.66(1H,



d, J=3.0Hz), 8.51(2H, d, J=6.3Hz), 8.96(2H,



d, J=6.3Hz), 9.93(1H, d, J=9.0Hz),



10.60-10.73(1H, m) (DMSO-d6)


XA464
(DMSO-d6): 3.45(3H, s), 3.38-3.81(6H, m),
408



3.88(6H, s), 5.06(1H, m), 6.82(2H, d,



J=8.7Hz), 7.04(1H, s), 7.44(1H, t, J=8.4Hz),



8.20(1H, m), 8.30(2H, d, J=6.3Hz), 8.87(2H,



d, J=6.3Hz), 10.07(1H, m).


XA468
3.40-3.50(4H, m), 3.47(3H, s), 3.83-3.94(2H,
396



m), 3.88(3H, s), 4.81-4.91(1H, m),



6.92-6.99(1H, m), 7.07-7.10(1H, m),



7.12(1H, s), 7.79-7.91(1H, m), 8.30-8.40(2H,



m), 8.85-8.92(2H, m), 9.70-9.79(1H, m),



10.02-10.23(1H, m) (DMSO)


XA469/
(DMSO-d6): 3.38-3.60(6H, m),
396


XA470
3.60-3.80(1H, m) 3.80-4.00(5H, m),



4.80-4.97(1H, m), 6.85-7.00(1H, m),



7.09(1H, dd, J=2.4, 11.4Hz), 7.13(1H, s),



7.95(1H, dd, J=6.9, 8.7Hz),



8.46(2H, d, J=6.6Hz), 8.94(2H, d, J=6.3Hz),



9.80-10.00(1H, brd), 10.35-10.60(1H, brd).


XA472
3.36-4.00(6H, m), 3.46(3H, s), 3.94(3H, s),
396



4.94-5.02(1H, m), 6.96-7.01(1H, m),



7.05(1H, d, J=8.6Hz), 7.14(1H, s),



7.49-7.58(1H, m), 8.44-8.50(2H, m),



8.52-8.64(1H, m), 8.96(2H, d, J=6.6Hz),



10.49-10.60(1H, m) (DMSO)


XA480
2.78(1H, dd, J=10.0, 12.1Hz), 3.18-3.27(3H,
412



m), 3.59(3H, s), 3.64-3.74(2H, m), 3.86(3H,



s), 4.37(1H, dd, J=2.4, 10.1Hz), 6.67(1H, s),



6.89(1H, d, J=2.1Hz), 6.99(1H, dd, J=1.7,



8.0Hz), 7.50(1H, d, J=8.2Hz), 7.82(2H, dd,



J=1.5, 4.8Hz), 8.71(2H, dd, J=1.8, 4.5Hz)



(CDCl3)


XA490
3.35-3.94(6H, m), 3.49(3H, s), 4.71-4.80(1H,
380


(2HCl)
m), 7.02-7.11(1H, m), 7.18-7.28(2H, m),



7.98-8.10(1H, m), 8.31-8.48(2H, m),



8.87-8.97(2H, m), 9.79-9.92(1H, m),



10.18-10.39(1H, m) (DMSO)


XA501
(CDCl3): 2.77(1H, dd, J=10.2, 12.0Hz),
456



3.15-3.35(3H, m), 3.50-3.80(5H, m),



3.84(3H, s), 4.39(1H, d, J=7.8Hz), 6.67(1H, s),



6.78(1H, d, J=8.8Hz),



7.39(1H, dd, J=2.4, 8.7Hz),



7.71(1H, d, J=2.3Hz), 7.82(2H, d, J=6.0Hz),



8.71(2H, d, J=6.0Hz).


XA510
(CDCl3): 1.98-2.05(4H, m), 2.85(1H, dd,
447



J=12, 10.5Hz), 3.17-3.24(7H, m), 3.58(3H,



s), 3.65-3.72(2H, m), 3.85(3H, s), 4.28(1H,



dd, 10.5, 2.7Hz), 6.10(1H, d, J=2.1Hz),



6.18(1H, dd, J=8.7, 2.1Hz), 6.65(1H, s),



7.33(1H, d, J=8.4Hz), 7.83(2H, dd, J=4.5,



1.8Hz), 8.70(2H, dd, J=4.5, 1.5Hz).


XA511
(CDCl3): 1.90-2.05(4H, m),
447



2.93(1H, t, J=12.0Hz), 3.15-3.40(7H, m),



3.59(3H, s), 3.65-3.85(5H, m),



4.11(1H, dd, J=2.1, 10.2Hz),



6.49(1H, dd, J=3.0, 9.0Hz), 6.66(1H, s),



7.83(2H, dd, J=1.8, 4.5Hz),



8.70(2H, dd, J=1.5, 4.5Hz).


XA516
(DMSO-d6): 3.20-3.70(4H, m), 3.70(1H, m),
414



3.98(3H, s), 3.99(3H, s), 4.00(1H, m),



4.96(1H, d, J=10.2Hz), 7.01(1H, s),



7.03(2H, m), 8.26(2H, d, J=6.1Hz), 8.53(1H, s),



8.84(2H, d, J=6.1Hz), 10.25(1H, d, J=10.7Hz)


XA525
(DMSO-d6): 3.30-3.50(2H, m), 3.48(3H, s),
454



3.55-3.78(2H, m), 3.78(3H, s),



3.96(2H, d, J=13.5Hz), 4.69(1H, t, J=10.4Hz),



7.06(1H, t, J=7.4Hz), 7.12(1H, s),



7.14(1H, d, J=7.4Hz), 7.31(1H, d, J=7.4Hz),



7.39(1H, t, J=7.4Hz), 7.59(2H, d, J=8.3Hz),



7.77(2H, d, J=8.3Hz), 8.43(2H, d, J=6.5Hz),



8.93(2H, d, J=6.5Hz), 9.89(1H, d, J=8.7Hz),



10.34(1H, s).


XA527
(DMSO-d6): 3.40-4.10(9H, m), 3.81(3H, s),
454



4.69(1H, m), 7.05(1H, s), 7.05(2H, d, J=9.0Hz),



7.67(2H, d, J=9.0Hz) 7.75(4H, s),



8.27(2H, d, J=5.7Hz), 8.85(2H, d, J=5.7Hz),



9.75(1H, s), 10.04(1H, s).


XA536
(DMSO-d6): 3.40-3.60(2H, m), 3.47(3H, s),
443



3.68(2H, m), 3.95(2H, m),



4.71(1H, t, J=9.9Hz), 7.16(1H, s),



7.33(2H, t, J=8.85Hz), 7.78(6H, m),



8.50(2H, d, J=6.3Hz), 8.97(2H, d, J=6.3Hz),



10.02(1H, s), 10.50(1H, s).


XA543
3.52(s, 3H), 3.57-4.10(m, 6H), 5.57(m, 1H),
398



7.02(s, 1H), 7.53-7.70(m, 2H), 8.06(d,



J=7.2Hz, 2H), 8.21-8.34(m, 3H), 8.82(d,



J=6.3Hz, 2H), 9.88-9.92(m, 1H),



10.58-10.61(m, 1H) (DMSO d6)


XA544
3.41-3.59(2H, m), 3.49(3H, s), 3.68-3.76(2H,
398



m), 3.97-4.02(2H, m), 4.78-4.89(1H, m),



7.15(1H, s), 7.58-7.63(2H, m), 7.89-8.07(4H,



m), 8.30(1H, s), 8.49(2H, d, J=6.3Hz),



8.95(2H, d, J=6.3Hz), 10.17(1H, d, J=8.4Hz),



10.57-10.70(1H, m) (DMSO-d6)


XA619
(CDCl3): 2.98(1H, dd, J=12.6, 10.8Hz),
390



3.17-3.28(5H, m), 3.58(3H, s), 3.62(1H, m),



3.79(1H, m), 4.26(1H, dd, 10.5, 2.7Hz),



4.62(2H, m), 6.66(1H, s), 6.88(1H, t,



J=7.5Hz), 7.16(1H, d, J=7.2Hz), 7.27(1H,



m), 7.84(2H, d, J=6.0), 8.70(2H, dd, J=4.8, 1.2Hz).


XA626
3.33-3.41(4H, m), 3.42(3H, s), 3.47-3.87(4H,
376



m), 6.84(1H, s), 7.44-7.49(5H, m), 7.99(2H,



dd, J=1.5, 4.5Hz), 8.69(2H, dd, J=1.4, 4.8Hz)



(DMSO-d6)


XA649
3.44(3H, s), 3.37-4.04(9H, m), 4.67(1H,
362



d, J=9.6Hz), 7.10(1H, s), 7.45-7.55(3H,



m), 7.83(2H, d, J=6.0Hz), 8.47(2H



d, J=6.6Hz), 8.95(2H, d, J=6.6Hz), 12.15(1H,



brs) (DMSO-d6)


XA756
(CDCl3): 2.50-2.61(1H, m), 2.80-2.95(1H, m),
410



3.05-3.20(1H, m), 3.25-3.40(1H, m),



3.50-3.60(1H, m), 3.57(3H, s),



3.65-3.75(1H, m), 3.75-3.80(1H, m),



3.85(3H, s), 6.60-6.80(3H, m),



7.47(1H, dd, J=7.2, 8.4Hz),



7.82(2H, dd, J=1.5, 4.5Hz),



8.71(2H, dd, J=1.5, 4.5Hz).


XA757/
(DMSO-d6): 2.54(3H, s), 3.40-3.79(3H, m),
410


XA758
3.46(3H, s), 3.80-4.10(6H, m),



4.83-5.10(1H, m), 6.90-7.05(1H, m),



7.08(1H, s), 7.13(1H, dd, J=2.7, 11.4Hz),



8.00-8.25(1H, brd), 8.37(2H, d, J=6.3Hz),



8.91(2H, d, J=6.6Hz), 11.80-12.20(1H, brd).


XA831
2.55(s, 3H), 3.51(s, 3H), 3.67-3.82(m, 4H),
412



4.04-4.08(m, 2H), 5.64(m, 1H), 7.05(s, 1H),



7.59-7.72(m, 3H), 8.06-8.11(m, 2H), 8.35(d,



J=6.6Hz, 2H), 8.41(d, J=7.8Hz, 1H), 8.49(d,



J=6.9Hz, 1H), 8.84(d, J=6.6Hz, 2H) (DMSO d6)


XA1016
(DMSO-d6): 3.15-3.35(1H, m),
486



3.38-3.60(4H, m), 3.75-4.15(8H, m),



4.18-4.25(1H, m), 4.90-5.20(1H, m),



7.00-7.20(3H, m), 7.30-7.55(6H, m),



8.50-8.70(3H, m), 9.00(2H, d, J=6.3Hz).


XA1276
(CDCl3): 1.80-2.42(3H, m), 3.08-3.39(4H,
438



m), 3.40-3.62(1H, m), 3.65-4.23(6.8H, m),



4.63-4.90(0.6H, m), 5.40-5.62(0.7H, m),



5.80-6.00(0.1H, m), 6.52-6.78(3H, m),



6.90-7.2(1H, m), 7.68-7.90(2H, m),



8.64-8.80(2H, m)


XA1649
1.48(3H, s), 1.57(3H, s), 3.50(3H, s),
406



3.51-3.66(2H, m), 3.72-3.76(1H, m),



3.90(3H, s), 3.99(1H, d, J=13.4Hz),



5.15-5.23(1H, m), 7.08-7.12(2H, m),



7.18(1H, d, J=8.6Hz), 7.46-7.49(1H, m),



8.04-8.11(1H, m), 8.37-8.45(2H, m),



8.89-8.97(2H, m), 9.49-9.60(1H, m),



9.95-10.11(1H, m) (DMSO)


XA1973
3.01(1H, dd, J=10.8, 12.9Hz),
382



3.10-3.30(3H, m), 3.50-3.75(5H, m), 4.04(1H,



dd, J=2.7, 10.8Hz), 6.67(1H, s), 7.20-7.40(4H,



m), 7.50(1H, s), 7.80(2H, dd, J=1.5, 4.8Hz),



8.71(2H, dd, J=1.5, 5.1Hz) (CDCl3)


XA1974
2.80(1H, dd, J=10.3, 12.2Hz),
426



3.15-3.30(3H, m), 3.50-3.80(5H, m), 4.44(1H,



dd, J=2.6, 10.3Hz), 6.67(1H, s),



7.10-7.20(1H, m), 7.25-7.40(1H, m),



7.58(1H, dd, J=1.0, 8.1Hz),



7.73(1H, dd, J=1.6, 7.8Hz),



7.81(2H, dd, J=1.6, 4.5Hz), 8.70(2H, dd,



J=1.6, 4.5Hz) (CDCl3)


XA1975
2.95-3.10(1H, m), 3.10-3.35(3H, m),
407



3.56(3H, s), 3.60-3.70(2H, m), 3.80-4.05(7H, m),



6.67(1H, s), 6.87(1H, d, J=8.1Hz),



6.90-7.10(2H, m), 7.80(2H, dd, J=1.8, 6.3Hz),



8.71(2H, dd, J=1.5, 4.8Hz) (CDCl3)


XA1976
3.40(3H, m), 3.45(3H, s), 3.53-3.96(3H, m),
382



4.68(1H, t, J=13.5Hz), 7.10(1H, s),



7.60(2H, d, J=8.3Hz), 7.76(2H, d, J=8.3Hz),



8.38(1H, br s), 8.91(1H, d, J=4.8Hz), 9.88(1H, br



s), 10.31(1H, br s) (DMSO-d6)


XA1977
3.40(3H, m), 3.46(3H, s), 3.62(1H, dd,
382



J=12.0, 13.2Hz), 3.72(1H, m), 3.92(1H, t,



J=15.5Hz), 4.68(1H, t, J=10.1Hz), 7.18(1H,



s), 7.58(2H, d, J=8.6Hz), 7.83(2H, d,



J=8.6Hz), 8.57(2H, d, J=6.6Hz), 9.01(2H, d,



J=6.6Hz), 10.20(1H, d, J=7.8Hz), 10.76(1H,



br s) (DMSO-d6)


XA1978
2.98(1H, t, J=10.9Hz), 3.22(m, 3H),



3.56(3H, s), 3.60(2H, m), 4.03(1H, d, J=8.7Hz),



6.68(1H, s), 7.28(1H, d, J=8.2Hz),



7.46(1H, d, J=8.2Hz), 7.61(1H, s), 7.79(2H, d,



J=5.6Hz), 8.71(2H, d, J=5.6Hz) (CDCl3)


XA1979
3.31(1H, dd, J=13.8, 8.9Hz), 3.46(3H, s),
396



3.85(1H, dd, J=13.8, 3.6Hz), 4.10(1H, d,



J=17.7Hz), 4.19(1H, d, J=17.7Hz),



4.91(1H, dd, J=8.9, 3.6Hz), 6.11(1H, s),



6.74(1H, s), 7.32(2H, d, J=8.4Hz), 7.42(2H, d,



J=8.4Hz), 7.79(2H, dd, J=4.8, 1.5Hz),



8.74(2H, dd, J=4.8, 1.5Hz) (CDCl3)


XA1980
1.97(4H, m), 3.26(4H, m), 3.38(2H, m),
417



3.45(3H, s), 3.60(2H, m), 3.80(1H, d, J=13.8Hz),



3.92(1H, d, J=14.1Hz), 4.48(1H, t, J=10.4Hz),



6.65(2H, d, J=8.7Hz), 7.16(1H,



s), 7.54(2H, d, J=8.7Hz), 8.57(2H, d, J=6.6Hz),



9.00(2H, d, J=6.6Hz), 9.83(1H, d,



J=9.3Hz), 10.32(1H, br s) (DMSO-d6)


XA1981
3.21(4H, m), 3.40(2H, m), 3.46(3H, s),
433



3.65(2H, m), 3.78(4H, m), 3.91(2H, t, J=13.7Hz),



4.55(1H, t, J=10.1Hz), 7.14(2H, d, J=8.7Hz),



7.20(1H, s), 7.64(2H, d, J=8.7Hz),



8.60(2H, d, J=6.6Hz), 9.02(2H, d, J=6.6Hz),



9.93(1H, d, J=9.0Hz), 10.47(1H, br s)



(DMSO-d6)


XA1982
2.80(3H, d, J=4.5Hz), 3.15(4H, m),
446



3.44(4H, m), 3.45(3H, s), 3.60(2H, m), 3.82(1H,



d, J=13.5Hz), 3.90(3H, m), 4.54(1H, t, J=10.5),



7.10(2H, d, J=8.7Hz), 7.17(1H, s),



7.64(2H, d, J=8.7Hz), 8.54(2H, d, J=6.3Hz),



8.99(2H, d, J=6.3Hz), 9.94(1H, d, J=8.7Hz),



10.47(1H, br s), 11.26(1H, br s)



(DMSO-d6)


XA1983
1.27(3H, t, J=6.6Hz), 3.46-4.14(8H, m),
396



4.70(1H, m), 7.11(1H, s), 7.60(2H, d, J=8.4Hz),



7.76(2H, d, J=8.4Hz), 8.32(2H, d, J=6Hz),



8.89(2H, d, J=6.0Hz), 9.87(1H, m),



10.23(1H, m), (DMSO-d6)


XA1984
1.27(6H, dd, J=6.9, 6.9Hz), 3.37-4.36(6H,
410



m), 4.66-4.79(2H, m), 7.03(1H, s), 7.62(2H,



d, J=8.7Hz), 7.78(2H, d, J=8.7Hz), 8.33(2H,



d, J=6Hz), 8.90(2H, d, J=6.0Hz), 9.93(1H,



m), 10.25(1H, m), (DMSO-d6)


XA1985
1.40(3H, d, J=6.3Hz), 3.44-4.04(5H, m),
396



3.48(3H, s), 4.69(1H, m), 7.08(1H, s),



7.60(2H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz),



8.33(2H, d, J=6.3Hz), 8.90(2H, d, J=6.3Hz),



9.83(1H, m), 10.00(1H, m), (DMSO-d6)


XA1986
1.57(6H, s), 3.50(3H, s), 3.51-3.93(4H, m),
410



4.98(1H, m), 7.11(1H, s), 7.60(2H, d, J=7.4Hz),



7.94(2H, d, J=7.4Hz), 8.41(2H, d, J=6.0Hz),



8.93(2H, d, J=6.0Hz), 9.88(1H, m),



10.05(1H, m), (DMSO-d6)


XA1987
1.43(3H, d, J=6.6Hz), 3.38-3.93(5H, m),
396



3.48(3H, s), 4.72(1H, m), 7.12(1H, s),



7.59(2H, d, J=8.4Hz), 7.84(2H, d, J=8.4Hz),



8.43(2H, d, J=6.6Hz), 8.95(2H, d, J=6.6Hz),



9.65(1H, m), 10.23(1H, m), (DMSO-d6)


XA1988
2.34(1H, m), 2.42(1H, m), 2.80(3H, d, J=5.6Hz),
460



2.81(3H, d, J=5.6Hz), 3.28(1H, q,



J=8.8Hz), 3.43(2H, m), 3.45(3H, s),



3.57(5H, m), 3.80(1H, d, J=11.4Hz), 3.96(2H,



m), 4.50(1H, t, J=10.4Hz), 6.69(2H, d, J=8.4Hz),



7.14(1H, s), 7.55(2H, d, J=8.4Hz),



8.47(2H, d, J=5.6Hz), 8.96(2H, d, J=5.6Hz),



9.75(1H, d, J=8.0Hz), 10.16(1H, br s),



11.40(1H, br s) (DMSO-d6)


XA1989
1.65(2H, br s), 1.91(4H, br s), 3.46(9H, s),
431



3.70(2H, m), 3.92(2H, t, J=16.6Hz),



4.66(1H, br s), 7.16(1H, s), 7.85(4H, br s),



8.50(2H, d, J=6.4Hz), 8.97(2H, d, J=6.4Hz),



10.01(1H, br s), 10.59(1H, br s) (DMSO-d6)


XA1990
2.32(1H, m), 2.42(1H, m), 2.79(3H, d, J=5.2Hz),
460



2.81(3H, d, J=5.2Hz), 3.27(1H,



m), 3.39(2H, m), 3.45(3H, s), 3.59(5H, m),



3.79(1H, d, J=13.3Hz), 3.95(2H, m),



4.50(1H, t, J=11.6Hz), 6.69(2H, d, J=8.4Hz),



7.16(1H, s), 7.56(2H, d, J=8.4Hz),



8.50(2H, s), 8.98(2H, d, J=5.6Hz), 9.78(1H, br



s), 10.19(1H, br s), 11.44(1H, br s)



(DMSO-d6)


XA1991
3.47(3H, s), 3.61(3H, m), 3.81(3H, s),
454



4.02(3H, m), 4.69(1H, t, J=10.6Hz), 7.05(2H, d,



J=8.8Hz), 7.10(1H, s), 7.67(2H, d, J=8.8Hz),



7.77(4H, s), 8.38(2H, br s), 8.91(2H, d,



J=5.2Hz), 9.90(1H, br s), 10.28(1H, br s)



(DMSO-d6)


XA1992
1.26(3H, t, J=6.9Hz), 1.41(3H, d, J=6.3Hz),
410



3.43-4.06(7H, m), 4.74(1H, m), 7.09(1H, s),



7.58(2H, d, J=8.4Hz), 7.84(2H, d, J=8.4Hz),



8.32(2H, d, J=6.6Hz), 8.90(2H, d, J=6.6Hz),



9.90(1H, m), 10.03(1H, m), (DMSO-d6)


XA1993
1.41(3H, t, J=6.3Hz), 1.55(6H, dd, J=6.6, 6.6Hz),
424



3.49-3.73(5H, m), 4.64(1H, m),



4.78(1H, m), 6.99(1H, s), 7.58(2H, d, J=8.7Hz),



7.81(2H, d, J=8.7Hz), 8.28(2H, d, J=6.3Hz),



8.87(2H, d, J=6.3Hz), 9.91(2H,



m) (DMSO-d6)


XA1994
1.27(3H, t, J=6.9Hz), 1.55(3H, s), 1.60(3H,
424



s), 3.42-4.14(6H, m), 5.04(1H, m), 7.13(1H,



s), 7.60(2H, d, J=8.4Hz), 7.91(2H, d, J=8.4Hz),



8.32(2H, d, J=6.3Hz), 8.89(2H, d, J=6.3Hz),



9.80-9.84(2H, m) (DMSO-d6)


XA1995
1.52(3H, d, J=6.6Hz), 1.58(6H, s), 1.59(3H,
438



d, J=6.6Hz), 3.40-3.68(4H, m), 4.75(1H, m),



5.09(1H, m), 7.03(1H, s), 7.60(2H, d, J=8.4Hz),



7.93(2H, d, J=8.4Hz), 8.33(2H, d, J=6.0Hz),



8.89(2H, d, J=6.0Hz), 9.89(2H,



m) (DMSO-d6)


XA1996
1.29(3H, t, J=6.8Hz), 3.47(2H, br s),
468



3.66(3H, m), 3.81(3H, s), 3.83(1H, m), 4.04(2H,



m), 4.71(1H, d, J=10.6Hz), 7.05(2H, d, J=8.8Hz),



7.12(1H, s), 7.67(2H, d, J=8.8Hz),



7.75(2H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz),



8.36(2H, d, J=6.4Hz), 8.91(2H, d, J=6.4Hz),



9.92(1H, d, J=8.8Hz), 10.29(1H,



br s) (DMSO-d6)


XA1997
1.56(3H, d, J=6.4Hz), 1.58(3H, d, J=6.4Hz),
482



3.47(2H, br s), 3.60(1H, m), 3.77(2H,



m), 3.81(3H, s), 4.72(3H, m), 7.05(2H, d, J=8.8Hz),



7.06(1H, s), 7.68(2H, d, J=8.8Hz),



7.76(2H, d, J=8.4Hz), 7.80(2H, d, J=8.4Hz),



8.42(2H, d, J=6.4Hz), 8.94(2H, d,



J=6.4Hz), 10.02(1H, d, J=9.6Hz),



10.39(1H, br s) (DMSO-d6)


XA1998
1.24(1H, m), 1.39(4H, m), 1.72(1H, m),
430



1.79(4H, m), 2.55(1H, m), 3.45(3H, s),



4.00-3.45(6H, m), 4.61(1H, t, J=11.2Hz), 7.09(1H,



s), 7.35(2H, d, J=8.4Hz), 7.62(2H, d, J=8.4Hz),



8.37(2H, d, J=4.0Hz), 8.90(2H, d,



J=4.0Hz), 9.75(1H, d, J=9.6Hz),



10.17(1H, br s), (DMSO-d6)


XA1999
1.04(1H, m), 1.17(2H, m), 1.43(2H, m),
459



1.60(1H, m), 1.79(4H, m), 2.96(3H, br s),



3.45(3H, s), 4.18-3.44(6H, m), 4.62(1H, br s),



7.13(1H, s), 7.75(4H, br s), 8.46(1H, br s),



8.95(1H, br s), 9.87(1H, br s), 10.40(1H, br



s) (DMSO-d6)


XA2000
1.40(3H, d, J=6.6Hz), 3.44-4.04(5H, m),
396



3.48(3H, s), 4.72(1H, m), 7.05(1H, s),



7.61(2H, d, J=8.4Hz), 7.78(2H, d, J=8.4Hz),



8.29(2H, d, J=6.0Hz), 8.90(2H, d, J=6.0Hz),



9.78-10.00(2H, m), (DMSO-d6)


XA2001
1.26(3H, t, J=6.9Hz), 1.41(3H, d, J=6.0Hz),
410



3.43-4.06(7H, m), 4.74(1H, m), 7.08(1H, s),



7.58(2H, d, J=8.4Hz), 7.81(2H, d, J=8.4Hz),



8.29(2H, d, J=6.3Hz), 8.88(2H, d, J=6.3Hz),



9.84-10.00(2H, m), (DMSO-d6)


XA2002
1.41(3H, t, J=6.0Hz), 1.56(6H, dd, J=6.6, 6.6Hz),
424



3.49-3.73(5H, m), 4.62(1H, m),



4.78(1H, m), 7.00(1H, s), 7.59(2H, d, J=8.4Hz),



7.81(2H, d, J=8.4Hz), 8.30(2H, d, J=6.3Hz),



8.88(2H, d, J=6.3Hz), 9.91(2H,



m) (DMSO-d6)


XA2003
3.03(4H, td, J=4.6Hz), 3.26(4H, t, J=4.5Hz),
425



3.48(3H, s), 6.65(1H, s), 7.10(2H, m),



7.20-7.45(5H, m), 7.65(2H, d, J=8.5Hz),



7.79(2H, d, J=6.3Hz), 8.71(2H, d, J=1.5,



4.8Hz) (CDCl3),


XA2004
2.93(1H, m), 3.20(2H, m), 3.30(3H, s),
362



3.36(1H, d, J=12.8Hz), 3.46(1H, t, J=12.0Hz),



3.73(4H, m), 7.03(1H, s), 7.33(2H, m),



7.42(3H, m), 8.16(2H, d, J=6.4Hz), 8.86(2H, d,



J=6.4Hz), 9.61(1H, d, J=10.0Hz),



9.95(1H, d, J=8.4Hz) (DMSO-d6)


XA2005
2.93(1H, dd, J=14.8, 8.4Hz), 3.07(1H, m),
396



3.19(1H, m), 3.33(3H, s), 3.41(3H, s),



3.69(1H, m), 3.80(2H, d, J=14.0Hz), 6.96(1H,



br s), 7.39(2H, d, J=8.0Hz), 7.49(2H, d, J=8.0Hz),



8.00(2H, br s), 8.77(2H, br s),



9.24(1H, s), 9.54(1H, s) (DMSO-d6)


XA2006
3.39(2H, m), 3.46(3H, s), 3.56(2H, m),
508



3.85(1H, d, J=13.2Hz), 3.93(1H, d, J=13.6Hz),



4.55(1H, t, J=10.4Hz), 6.94(1H, br s),



7.13(1H, s), 7.14(4H, m), 7.30(2H, m), 7.59(2H,



d, J=8.0Hz), 8.45(2H, s), 8.95(2H, s),



9.73(1H, br s), 10.10(1H, br s) (DMSO-d6)


XA2007
1.39(1H, m), 1.80(8H, m), 2.18(2H, d, J=11.2Hz),
514



2.76(2H, t, J=11.4Hz), 3.90(2H,



m), 3.33(1H, m), 3.40(3H, m), 3.45(3H, s),



3.58(2H, m), 3.82(1H, d, J=13.3Hz),



3.93(3H, m), 4.53(1H, t, J=10.4Hz), 7.09(2H, d,



J=8.8Hz), 7.11(1H, s), 7.56(2H, d, J=8.8Hz),



8.40(2H, d, J=6.0Hz), 8.92(2H, d, J=6.0Hz),



9.75(1H, d, J=8.8Hz), 10.14(1H,



br s), 10.39(1H, br s) (DMSO-d6)


XA2008
2.82-2.90(1H, m), 3.01-3.05(4H, m),
426



3.22(3H, s), 3.44(3H, s), 3.58-3.66(2H, m),



4.08(1H, dd, J=1.2, 10.2Hz), 6.81(1H, s),



7.77(2H, d, J=7.2Hz), 7.92-7.98(4H, m),



8.69(2H, d, J=4.2Hz) (DMSO-d6)


XA2009
1.21(3H, d, J=6.6Hz), 3.17-3.45(4H, m),
396



3.52(3H, s), 4.02(1H, m), 4.69(1H, m),



7.20(1H, s), 7.54(2H, d, J=8.4Hz), 7.70(2H,



d, J=8.4Hz), 8.26(2H, d, J=6.3Hz), 8.88(2H,



d, J=6.3Hz), 9.90(1H, m), 10.16(1H, m),



(DMSO-d6)


XA2010
1.21(3H, d, J=6.0Hz), 3.17-3.45(4H, m),
396



3.53(3H, s), 4.02(1H, m), 4.70(1H, m),



7.24(1H, s), 7.54(2H, d, J=8.7Hz), 7.73(2H,



d, J=8.7Hz), 8.33(2H, d, J=5.7Hz), 8.93(2H,



d, J=5.7Hz), 10.04(1H, m), 1037(1H, m),



(DMSO-d6)


XA2011
3.02(1H, t, J=11.9Hz), 3.17(6H, m),
433



3.55(3H, s), 3.63(2H, m), 3.86(4H, m), 3.96(1H,



d, J=10.2Hz), 6.66(1H, s), 6.92(2H, d, J=8.4Hz),



7.35(2H, d, J=8.4Hz), 7.80(2H, d,



J=5.1Hz), 8.70(2H, d, J=5.1Hz) (CDCl3)


XA2012
2.31(3.6H, s), 3.16(4H, t, J=4.8Hz),
433



3.44(3H, s), 3.45(4H, m), 3.75(4H, t, J=4.8Hz),



3.86(1H, d, J=14.0Hz), 3.92(1H, d, J=12.4Hz),



4.56(1H, d, J=10.4Hz), 6.95(1H,



s), 7.06(2H, d, J=8.8Hz), 7.43(2H, d, J=8.8Hz),



8.06(2H, d, J=6.0Hz), 8.75(2H, d,



J=6.0Hz), 9.03(1H, s), 9.33(1H, d, J=10.0Hz)



(DMSO-d6)


XA2013
1.82(4H, m), 1.97(2H, m), 2.12(2H, m),
500



2.77(2H, t, J=11.6Hz), 3.01(2H, m), 3.27(1H,



m), 3.40(2H, m), 3.45(3H, s), 3.49(2H, m),



3.57(1H, m), 3.63(1H, m), 3.84(1H, d, J=13.6Hz),



3.92(3H, d, J=12.8Hz), 4.53(1H,



t, J=11.2Hz), 7.12(2H, d, J=8.4Hz),



7.14(1H, s), 7.58(2H, d, J=8.9Hz), 8.49(2H, d,



J=5.2Hz), 8.97(2H, d, J=5.2Hz), 9.82(1H,



br s), 10.24(1H, br s), 11.12(1H, br s)



(DMSO-d6)


XA2014
1.75(2H, m), 2.14(2H, m), 2.72(6H, d, J=4.5Hz),
474



2.74-2.80(3H, m), 3.30-3.95(8H, m),



3.45(3H, s), 4.54(1H, m), 7.10(2H, d, J=9.0Hz),



7.15(1H, s), 7.60(2H, d, J=9.0Hz),



8.51(2H, d, J=6.6Hz), 8.98(2H, d, J=6.6Hz),



9.86(1H, m), 10.32(1H, m), 10.93(1H, m),



(DMSO-d6)


XA2015
1.68(2H, m), 2.09(2H, m), 3.16-3.90(10H,
447



m), 3.45(3H, s), 4.60(1H, m), 7.13(1H, s),



7.45-7.71(4H, m), 8.45(2H, d, J=6.0Hz),



8.94(2H, d, J=6.0Hz), 9.83(1H, m),



10.22(1H, m) (DMSO-d6)


XA2016
1.91-2.03(2H, m), 3.09(1H, m),
433



3.28-3.57(7H, m), 3.40(3H, s), 4.41(2H, m),



6.58(2H, d, J=8.7Hz), 7.13(1H, s), 7.46(2H,



d, J=8.7Hz), 8.44(2H, d, J=6.3Hz), 8.94(2H,



d, J=6.3Hz), 9.61(1H, m), 9.89(1H, m)



(DMSO-d6)


XA2017
2.97(6H, s), 3.45(3H, s), 4.20-3.30(6H, m),
391



4.53(1H, t, J=9.8Hz), 6.69(2H, br s),



7.14(1H, s), 7.57(2H, br s), 8.48(2H, br s),



8.96(2H, br s), 9.72(1H, br s), 10.09(1H, br s)



(DMSO-d6)


XA2018
3.18-3.22(1H, m), 3.44-3.80(15H, m),
566



4.51-4.55(1H, m), 5.11(2H, s), 7.04-7.07(3H,



m), 7.32-7.39(5H, m), 7.52-7.55(2H, m),



8.33-8.35(2H, m), 8.82-8.87(2H, m),



9.65-9.75(2H, br) (DMSO-d6)


XA2019
1.32(6H, d, J=6.8Hz), 3.04-3.88(18H, m),
474



4.52-4.55(1H, m), 7.09-7.12(3H, m),



7.62(2H, d, J=7.2Hz), 8.45(2H, d, J=4.2Hz),



8.94(2H, d, J=4.2Hz), 9.83-10.34(3H, br),



11.00-11.04(1H, br) (DMSO-d6)


XA2020
1.32(6H, d, J=6.8Hz), 3.04-3.88(18H, m),
476



4.52-4.55(1H, m), 7.09-7.12(3H, m),



7.62(2H, d, J=7.2Hz), 8.45(2H, d, J=4.2Hz),



8.94(2H, d, J=4.2Hz), 9.83-10.34(3H, br),



11.00-11.04(1H, br) (DMSO-d6)


XA2021
2.09(3H, s), 3.19-4.00(20H, m),
518



4.43-4.54(3H, m), 7.06-7.19(3H, m),



7.62(2H, d, J=7.2Hz), 8.44(2H, d, J=4.2Hz),



8.94(2H, d, J=4.2Hz), 9.82-9.85(1H, br),



10.26-10.30(1H, br), 11.30-11.40(1H,



br) (DMSO-d6)


XA2022
3.17-3.21(4H, m), 3.38-4.16(14H, m),
432



4.51-4.54(1H, m), 7.08-7.18(3H, m),



7.60(2H, d, J=7.2Hz), 8.43(2H, d, J=4.2Hz),



8.93(2H, d, J=4.2Hz), 9.26-9.34(2H, br),



9.81-84(1H, br), 10.25-10.30(1H,



br) (DMSO-d6)


XA2023
1.82(3H, m), 3.29(3H, m), 3.40-3.96(9H, m),
445



3.48(3H, s), 4.55(1H, m), 7.10(1H, s),



7.13(2H, d, J=8.4Hz), 7.56(2H, d, J=8.4Hz),



8.39(2H, d, J=6.0Hz), 8.91(2H, d, J=6.0Hz),



9.67(1H, m), 9.97(1H, m) (DMSO-d6)


XA2024
1.89-2.03(2H, m), 2.95-3.07(5H, m),
433



3.29-3.83(5H, m), 3.40(3H, s), 4.40(1H, m),



4.94(1H, m), 6.49(2H, d, J=8.4Hz), 7.13(1H,



s), 7.25(2H, d, J=8.4Hz), 7.95(2H, d, J=6.0Hz),



8.69(2H, d, J=6.0Hz) (DMSO-d6)


XA2025
1.16(6H, d, J=6.3Hz), 2.28-2.36(2H, m),
460



2.97-3.21(6H, m), 3.54(3H, s), 3.55-3.62(4H,



m), 3.95(1H, m), 6.66(1H, s), 6.93(2H, d, J=8.7Hz),



7.32(2H, d, J=8.7Hz), 7.80(2H, d,



J=6.3Hz), 8.70(2H, d, J=6.3Hz) (CDCl3)


XA2026
1.26(6H, d, J=6.3Hz), 2.42(2H, dd, J=11.1,
461



11.1Hz), 3.02(1H, dd, J=12.3, 10.8Hz),



3.17-3.22(3H, m), 3.45-3.63(4H, m),



3.55(3H, s), 3.81(1H, m), 3.95(1H, dd, J=13.2,



2.1Hz), 6.66(1H, s), 6.92(2H, d, J=8.4Hz),



7.34(2H, d, J=8.4Hz), 7.80(2H, d, J=6.0Hz),



8.70(2H, d, J=6.0Hz) (CDCl3)


XA2027
2.91-3.09(5H, m), 3.26(3H, s), 3.46(3H, s),
502



3.69-3.73(2H, m), 4.07-4.11(1H, m),



6.81(1H, s), 7.64(2H, d, J=7.2Hz), 7.77(2H,



d, J=7.2Hz), 7.94-8.02(6H, m), 8.68(1H, d,



J=4.2Hz) (DMSO-d6)


XA2028
3.28-3.32(4H, m), 3.46(3H, s), 3.86-3.91(2H,
449



m), 4.59-4.61(1H, m), 6.90(1H, s),



7.77-8.06(10H, m), 8.70(2H, d, J=4.2Hz),



9.36-9.44(1H, br) (DMSO-d6)


XA2029
3.08(1H, dd, J=12.4, 10.4Hz), 3.25(3H,
508



m), 3.58(3H, s), 3.68(2H, m), 4.09(1H, dd, J=10.4,



2.4Hz), 6.68(1H, s), 7.29(2H, d, J=8.4Hz),



7.54(2H, d, J=8.4Hz), 7.56(2H, d,



J=8.4Hz), 7.59(2H, d, J=8.4Hz), 7.81(2H,



dd, J=4.4, 1.6Hz), 8.71(2H, dd, J=4.4, 1.6Hz)



(CDCl3)


XA2030
3.08(1H, dd, J=12.4, 10.4Hz), 3.27(3H,
492



m), 3.58(3H, s), 3.70(2H, m), 4.11(1H, dd, J=10.4,



2.4Hz), 6.68(1H, s), 7.57(2H, d, J=8.0Hz),



7.63(2H, d, J=8.0Hz), 7.70(4H, s),



7.81(2H, dd, J=4.8, 1.2Hz), 8.71(2H, dd, J=4.8,



1.2Hz) (CDCl3)


XA2031
1.45(3H, t, J=12.4Hz), 3.08(1H, dd, J=12.4,
468



10.8Hz), 3.24(3H, m), 3.57(3H, s),



3.67(2H, m), 4.07(1H, m), 4.09(2H, q, J=7.0Hz),



6.67(1H, s), 6.97(2H, d, J=8.4Hz),



7.51(2H, d, J=8.4Hz), 7.51(2H, d, J=8.4Hz),



7.54(2H, d, J=8.4Hz), 7.57(2H, d, J=8.4Hz),



7.81(2H, dd, J=4.8, 1.2Hz),



8.71(2H, dd, J=4.8, 1.2Hz) (CDCl3)


XA2032
1.94(4H, m), 2.02(1H, m), 2.21(1H, m),
468



2.62(4H, m), 2.91(1H, m), 3.03(1H, dd, J=12.4,



10.4Hz), 3.20(4H, m), 3.33(1H, m),



3.48(2H, m), 3.54(3H, s), 3.62(2H, m), 3.91(1H,



dd, J=10.4, 2.4Hz), 6.55(2H, d, J=8.4Hz),



6.66(1H, s), 7.29(2H, d, J=8.4Hz),



7.81(2H, dd, J=4.4, 0.8Hz), 8.70(2H, dd, J=4.4,



0.8Hz) (CDCl3)


XA2033
2.29(3H, s), 3.06(4H, t, J=4.8Hz), 3.38(4H, t,
427



J=4.8Hz), 3.51(3H, s), 5.70(1H, s), 6.67(1H,



s), 7.24-7.29(5H, m), 7.83(2H, dd, J=1.6,



4.3Hz), 8.72(2H, dd, J=1.3, 4.5Hz) (CDCl3)


XA2034
3.09(1H, dd, J=12.0, 10.8Hz), 3.23(3H,
484



m), 3.57(3H, s), 3.66(2H, m), 3.82(3H, s),



3.86(3H, s), 4.06(1H, dd, J=10.8, 2.4Hz),



6.58(2H, m), 6.67(1H, s), 7.24(2H, m),



7.47(2H, d, J=8.0Hz), 7.53(2H, d, J=8.0Hz),



7.82(2H, dd, J=4.8, 1.2Hz), 8.71(2H, dd, J=4.8,



1.2Hz) (CDCl3)


XA2035
3.08(3H, dd, J=12.4, 10.8Hz), 3.25(3H,
484



m), 3.57(3H, s), 3.67(2H, m), 3.93(3H, s),



3.96(3H, s), 4.08(1H, dd, J=10.0, 2.0Hz),



6.68(1H, s), 6.95(1H, d, J=8.4Hz),



7.11(1H, d, J=2.4Hz), 7.16(1H, dd, J=8.4, 2.4Hz),



7.51(2H, d, J=8.0Hz), 7.58(2H, d, J=8.0Hz),



7.81(2H, dd, J=4.8, 1.2Hz),



8.71(2H, dd, J=4.8, 1.2Hz) (CDCl3)


XA2036
3.08(1H, dd, J=12.4, 10.8Hz), 3.26(3H,
458



m), 3.57(3H, s), 3.67(2H, m), 4.09(1H, dd, J=10.0,



2.0Hz), 6.68(1H, s), 7.42(2H, d, J=8.4Hz),



7.53(4H, d, J=8.4Hz), 7.58(2H, d,



J=8.4Hz), 7.80(2H, dd, J=4.8, 1.6Hz),



8.71(2H, dd, J=4.8, 1.6Hz) (CDCl3)


XA2037
3.09(1H, dd, J=12.4, 10.8Hz), 3.25(3H,
492



m), 3.58(3H, s), 3.69(2H, m), 4.11(1H, dd, J=10.4,



2.4Hz), 6.68(1H, s), 7.28(2H, m),



7.44(2H, d, J=8.0Hz), 7.51(3H, m),



8.81(2H, dd, J=4.0, 1.2Hz), 8.72(2H, dd, J=4.0,



1.2Hz) (CDCl3)


XA2038
3.07(1H, dd, J=12.3, 11.0Hz), 3.26(3H,
492



m), 3.57(3H, s), 3.67(2H, m), 4.10(1H, dd, J=10.2,



2.1Hz), 6.68(1H, s), 7.42(1H, dd, J=8.1,



2.2Hz), 7.55(5H, m), 7.68(1H, d, J=2.2Hz),



7.80(2H, dd, J=4.8, 1.3Hz),



8.71(2H, dd, J=4.8, 1.3Hz) (CDCl3)


XA2039
3.06(1H, dd, J=12.0, 10.8Hz), 3.24(3H,
416



m), 3.58(3H, s), 3.67(2H, m), 4.13(1H, dd, J=10.4,



2.4Hz), 6.68(1H, s), 7.61(2H, d, J=8.4Hz),



7.80(2H, d, J=4.4Hz), 8.15(2H, d,



J=8.4Hz), 8.71(2H, d, J=4.4Hz), 8.77(1H,



s) (CDCl3)


XA2040
3.04-3.26(4H, m), 3.57(3H, s), 3.66-3.71(2H,
530



m), 4.07(1H, m), 5.12(2H, s), 6.68(1H, s),



7.06(2H, d, J=8.7Hz), 7.40-7.59(11H, m),



7.81(2H, d, J=6.0Hz), 8.71(2H, d, J=6.0Hz)



(CDCl3)


XA2041
0.38(2H, m), 0.67(2H, m), 1.32(1H, m),
494



3.09(1H, dd, J=12.6, 11.1Hz), 3.22-3.28(3H,



m), 3.58(3H, s), 3.67-3.71(2H, m), 3.86(2H,



d, J=6.9Hz), 4.08(1H, m), 6.68(1H, s),



7.06(2H, d, J=9.0Hz), 7.49-7.60(6H, m),



7.82(2H, d, J=6.0Hz), 8.72(2H, d, J=6.0Hz)



(CDCl3)


XA2042
1.37(6H, d, J=6.0Hz), 3.08(1H, dd, J=12.3,
482



11.1Hz), 3.20-3.28(3H, m), 3.57(3H, s),



3.65-3.70(2H, m), 4.06(1H, m), 4.59(1H, m),



6.67(1H, s), 7.06(2H, d, J=9.0Hz),



7.48-7.59(6H, m), 7.81(2H, d, J=6.0Hz),



8.71(2H, d, J=6.0Hz) (CDCl3)


XA2043
0.99(3H, t, J=7.5Hz), 1.40-1.85(4H, m),
496



3.05-3.30(4H, m), 3.57(3H, s), 3.65-3.70(2H,



m), 4.00-4.10(3H, m), 6.67(1H, s), 6.97(2H,



d, J=8.7Hz), 7.50-7.56(6H, m), 7.81(2H, d,



J=6.0Hz), 8.71(2H, d, J=6.0Hz) (CDCl3)


XA2044
1.66(1H, br.s), 2.52(3H, s), 3.05(1H, dd,
469



J=10.5, 12.6Hz), 3.20-3.26(3H, m), 3.57(3H,



s), 3.62-3.72(2H, m), 4.07(1H, dd, J=2.1,



10.5Hz), 6.67(1H, s), 7.33(2H, d, J=8.4Hz),



7.50-7.61(6H, m), 7.81(2H, dd, J=1.6,



4.3Hz), 8.70(2H, dd, J=1.3, 4.5Hz) (CDCl3)


XA2045
1.72(1H, br.s), 2.40(3H, s), 2.98-3.26(5H,
437



m), 3.57(3H, s), 3.57-3.67(1H, m), 4.07(1H,



dd, J=2.1, 10.5Hz), 6.67(1H, s), 7.24(2H, d,



J=8.1Hz), 7.49-7.52(4H, m), 7.60(2H, d,



J=8.1Hz), 7.81(2H, dd, J=1.6, 4.3Hz),



8.70(2H, dd, J=1.3, 4.5Hz) (CDCl3)


XA2046
1.36(9H, s), 1.72(1H, br.s), 3.06(1H, dd,
479



J=10.5, 12.4Hz), 3.20-3.28(3H, m), 3.57(3H,



s), 3.57-3.67(2H, m), 4.07(1H, dd, J=2.1,



10.5Hz), 6.67(1H, s), 7.24(2H, d, J=8.1Hz),



7.43-7.56(6H, m), 7.81(2H, dd, J=1.6,



4.3Hz), 8.71(2H, dd, J=1.3, 4.5Hz) (CDCl3)


XA2047
1.29(6H, d, J=6.9Hz), 1.73(1H, br.s),
465



2.96(1H, m), 3.06(1H, dd, J=10.5, 12.4Hz),



3.21-3.29(3H, m), 3.57(3H, s), 3.62-3.71(2H,



m), 4.07(1H, dd, J=2.1, 10.5Hz), 6.67(1H, s),



7.31(2H, d, J=8.1Hz), 7.45-7.54(4H, m),



7.63(2H, d, J=8.1Hz), 7.81(2H, dd, J=1.6,



4.3Hz), 8.71(2H, dd, J=1.3, 4.5Hz), (CDCl3)


XA2048
1.68(2H, br.s), 2.98(1H, dd, J=10.5, 12.6Hz),
438



3.20-3.27(2H, m), 3.56(3H, s), 3.64-3.74(1H,



m), 4.04(1H, dd, J=3.3, 11.1Hz), 4.80(3H, s),



6.66(1H, s), 6.72(2H, d, J=8.5Hz),



7.49-7.52(4H, m), 7.63(2H, d, J=8.1Hz),



7.81(2H, dd, J=1.6, 4.3Hz), 8.70(2H, dd,



J=1.3, 4.5Hz) (DMSO-d6)


XA2049
2.67(3H, s), 3.06(1H, dd, J=12.4, 10.8Hz),
430



3.25(3H, m), 3.57(3H, s), 3.62(2H, m),



4.12(1H, dd, J=10.0, 2.0Hz), 6.68(1H, s),



7.59(2H, d, J=8.0Hz), 7.80(1H, dd, J=4.8, 1.2Hz),



8.09(1H, d, J=8.0Hz), 8.71(1H, dd, J=4.8,



1.2Hz) (CDCl3)


XA2050
3.05(1H, m), 3.30-3.48(3H, m), 3.64(3H, s),
560



4.08-4.22(2H, m), 4.68(1H, m), 5.15(1H, d,



J=12.3Hz), 5.21(1H, d, J=12.6Hz),



6.63(1H, s), 7.21(2H, d, J=8.4Hz),



7.28-7.39(7H, m), 7.59(2H, d, J=6.3Hz),



8.68(2H, d, J=6.3Hz) (CDCl3)


XA2051
2.88-3.34(6H, m), 3.67(3H, s), 4.56(1H, dd,
426



J=9.9, 3.3Hz), 6.62(1H, s), 7.19(2H, d, J=10.8Hz),



7.36(2H, d, J=10.8Hz), 7.58(2H,



dd, J=4.5, 1.5Hz), 8.67(2H, dd, J=4.5, 1.5Hz)



(CDCl3)


XA2052
3.04(1H, m), 3.29-3.48(3H, m), 3.64(3H, s),
560



4.10-4.15(2H, m), 4.68(1H, m), 5.15(1H, d,



J=12.3Hz), 5.21(1H, d, J=12.6Hz),



6.63(1H, s), 7.21(2H, d, J=8.1Hz),



7.32-7.39(7H, m), 7.59(2H, d, J=6.0Hz),



8.68(2H, d, J=6.0Hz) (CDCl3)


XA2053
3.01(1H, m), 3.29-3.41(3H, m), 3.66(3H, s),
527



4.05-4.13(2H, m), 4.67(1H, m), 6.64(1H, s),



7.23(2H, d, J=8.4Hz), 7.41(2H, d, J=8.4Hz),



7.60(2H, dd, J=4.5, 1.5Hz), 8.69(2H,



dd, J=4.5, 1.5Hz) (CDCl3)


XA2054
2.28(3H, s), 3.07(4H, m), 3.59(4H, m),
445



3.73(3H, s), 5.78(1H, s), 6.70(1H, s),



6.98(1H, m), 7.40(1H, m), 7.60-7.66(2H, m),



7.81(2H, dd, J=1.6, 4.3Hz), 8.72(2H, dd,



J=1.3, 4.5Hz) (CDCl3)


XA2055
2.31(3H, s), 3.19(4H, m), 3.46(4H, m),
428



3.54(3H, s), 5.79(1H, s), 6.69(1H, s),



7.18-7.23(1H, m), 7.79(2H, d, J=5.4Hz),



7.79-7.87(2H, m), 8.54(1H, d, J=5.2Hz),



8.72(2H, d, J=4.5Hz) (CDCl3)


XB13
1.16-1.28(1H, m), 1.50-1.64(1H, m),
361



1.70-1.82(2H, m), 1.90-2.01(1H, m),



2.58(2H, d, J=7.3Hz), 2.64-2.72(1H, m),



2.89-2.97(1H, m), 3.28(3H, s), 3.57-3.67(2H,



m), 6.93(1H, s), 7.20-7.35(5H, m), 8.26(2H,



d, J=5.7Hz), 8.87(2H, d, J=5.9Hz)



(DMSO-d6)


XB16
1.75-2.16(4H, m), 2.96-3.08(3H, m, 3.55(3H,
347



s), 3.69-3.79(2H, m), 6.66(1H, s),



7.26-7.40(5H, m), 7.81(2H, d, J=6.0Hz),



8.70(2H, d, J=6.0Hz) (CDCl3)


XB17
1.76-1.99(5H, m), 2.97-3.10(2H, m),
365



3.75(1H, d, J=12.4Hz), 6.81(1H, s),



7.18-7.24(2H, m), 7.28-7.35(1H, m),



7.47(1H, t, J=7.1Hz), 7.98(2H, d, J=5.8Hz),



8.68(2H, d, J=5.8Hz) (DMSO-d6)


XB19
1.86-2.14(4H, m), 2.94-3.03(3H, m),
365



3.55(3H, s), 3.68-3.75(2H, m), 6.66(1H, s),



7.05(2H, m), 7.23(2H, m), 7.80(2H, d, J=6.3Hz),



8.70(2H, d, J=6.3Hz) (CDCl3)


XB33
1.75-2.08(4H, m), 2.80(1H, m), 3.03(1H, m),
377



3.42(3H, s), 3.77(2H, m), 3.85(3H, s),



6.65(1H, s), 6.89-7.00(2H, m), 7.22-7.28(2H,



m), 7.82(2H, d, J=6.0Hz), 8.70(2H, d, J=6.0Hz)



(CDCl3)


XB35
1.73-1.83(4H, m), 2.90-3.02(3H, m),
377



3.42(3H, s), 3.67-3.81(2H, m), 3.74(3H, s),



6.80(1H, s), 6.91(2H, d, J=8.7Hz), 7.27(2H,



d, J=8.5Hz), 7.97(2H, d, J=5.9Hz), 8.69(2H,



d, J=5.7Hz) (DMSO-d6)


XB43
1.69-1.90(7H, m), 1.94-2.00(1H, m),
430



2.59-2.68(4H, m), 2.92-3.02(3H, m),



3.43(3H, s), 3.69-3.80(4H, m), 6.59(3H, s),



6.79(1H, s), 7.29-7.36(4H, m), 7.96(2H, d,



J=5.9Hz), 8.68(2H, d, J=5.1Hz) (DMSO-d6)


XB46
(CDCl3): 1.95-2.09(3H, m), 2.39(1H, m),
388



3.15(1H, m), 3.45(1H, dd, J=12.9, 10.8Hz),



3.57(3H, s), 3.61-3.72(2H, m), 4.08(1H, m),



6.67(1H, s), 7.32(1H, m), 7.58-7.60(2H, m),



7.74(1H, d, J=7.8Hz), 7.80(2H, dd, J=4.5,



1.5Hz), 8.69(2H, dd, J=4.5, 1.5Hz).


XB47
(CDCl3): 1.90-2.06(3H, m), 2.36(1H, m),
406



3.14(1H, m), 3.42(1H, m), 3.57(3H, s),



3.61-3.71(2H, m), 4.06(1H, m), 6.68(1H, s),



7.09(1H, m), 7.28(1H, m), 7.68(1H, dd,



J=8.8, 5.1Hz), 7.79(2H, d, J=4.7Hz),



8.69(2H, d, J=5.9Hz).


XB48
1.90-2.10(3H, m), 2.32-2.44(1H, m),
388



3.11-3.20(1H, m), 3.45(1H, dd, J=10.5, 12.6Hz),



3.57(3H, s), 3.61-3.72(2H, m), 4.08(1H,



d, J=11.1Hz), 6.67(1H, s), 7.30-7.35(1H, m),



7.56-7.62(2H, m), 7.74(1H, d, J=13.8Hz),



7.80(2H, dd, J=1.8, 4.5Hz), 8.70(2H, dd,



J=1.8, 4.8Hz) (CDCl3)


XB49
1.91-2.09(3H, m), 2.37-2.42(1H, m),
388



3.12-3.19(1H, m), 3.45(1H, dd, J=10.8, 12.9Hz),



3.57(3H, s), 3.60-3.72(2H, m), 4.08(1H,



d, J=11.1Hz), 6.67(1H, s), 7.30-7.35(1H, m),



7.54-7.62(2H, m), 7.75(1H, d, J=8.1Hz),



7.80(2H, dd, J=1.5, 4.5Hz), 8.70(2H, dd,



J=1.8, 4.5Hz) (CDCl3)


XB50
1.59-1.67(1H, m), 1.72-1.81(1H, m),
363



2.08(1H, dt, J=3.4, 12.7Hz), 2.23-2.40(1H,



m), 3.06-3.14(1H, m), 3.41-3.54(2H, m),



3.42(3H, s), 3.93(1H, d, J=14.0Hz), 7.02(1H,



s), 7.24-7.29(1H, m), 7.34-7.39(2H, m),



7.56-7.59(2H, m), 8.55(2H, d, J=6.6Hz),



8.98(2H, d, J=6.5Hz) (DMSO-d6)


XB80
2.21-2.36(4H, m), 3.19-3.31(2H, m),
372



3.46(3H, s), 3.88(2H, d, J=13.2Hz), 6.86(1H,



s), 7.38-7.42(1H, m), 7.46-7.51(2H, m),



7.58-7.64(2H, m), 8.01(2H, d, J=5.1Hz),



8.70(2H, d, J=5.1Hz) (DMSO-d6)


XB122
1.44(2H, m), 1.75-1.83(3H, m), 2.63(2H, d,
361



J=6.9Hz), 2.90(2H, m), 3.51(3H, s), 3.64(2H,



m), 6.65(1H, s), 7.17-7.34(5H, m), 7.80(2H,



d, J=6.3Hz), 8.70(2H, d, J=6.3Hz)



(CDCl3)


XB123
1.44-2.16(5H, m), 2.86-2.97(2H, m),
395



3.49(3H, s), 3.62(1H, m), 3.72(1H, m),



4.48(1H, d, J=7.2Hz), 6.64(1H, s), 7.07(2H,



m), 7.32(2H, m), 7.79(2H, d, J=6.3Hz),



8.69(2H, d, J=6.3Hz) (CDCl3)


XB124
1.38-1.60(3H, m), 1.78(1H, m), 2.16(1H, m),
409



2.79-2.94(2H, m), 3.20(3H, s), 3.49(3H, s),



3.59(1H, m), 3.69(1H, m), 3.88(1H, d, J=7.5Hz,



1H), 6.64(1H, s), 7.08(2H, m), 7.25(2H,



m), 7.79(2H, d, J=6.0Hz), 8.70(2H, d, J=6.0Hz)



(CDCl3)


XB127
1.87-2.06(4H, m), 2.79(1H, m), 3.10(2H, m),
347



3.57(3H, s), 3.78(2H, m), 6.68(1H, s),



7.23-7.29(3H, m), 7.34(2H, m), 7.84(2H, d,



J=6.0Hz), 8.72(2H, d, J=6.0Hz) (CDCl3)


XB130
1.81-2.03(4H, m), 2.78(1H, m), 3.09(2H, m),
365



3.57(3H, s), 3.79(2H, m), 6.69(1H, s),



7.03(2H, m), 7.23(2H, m), 7.84(2H, d, J=5.4Hz),



8.72(2H, br s) (CDCl3)


XB134
1.78-1.95(4H, m), 2.80-2.91(1H, m),
415



2.96-3.09(2H, m), 3.45(3H, s), 3.81(2H, d,



J=13.1Hz), 6.80(1H, s), 7.33(1H, dd, J=2.0,



8.3Hz), 7.56-7.60(2H, m), 7.99(2H, dd,



J=1.6, 4.5Hz), 8.69(2H, dd, J=1.5, 4.5Hz)



(DMSO-d6)


XB145
1.82-2.02(4H, m), 3.09-3.27(3H, m),
377



3.57(3H, s), 3.79(2H, m), 3.86(3H, s),



6.67(1H, s), 6.89-6.99(2H, m), 7.21-7.26(2H,



m), 7.84(2H, d, J=6.0Hz), 8.72(2H, d, J=6.0Hz)



(CDCl3)


XB157
1.85-2.07(2H, m), 2.17-2.30(2H, m),
405



2.91-3.10(1H, m), 3.10-3.24(2H, m),



3.57(3H, s), 3.71-3.88(2H, m), 6.69(1H, s),



6.99-7.06(1H, m), 7.21(1H, dd, J=2.1, 8.7Hz),



7.45(1H, s), 7.49-7.65(1H, m),



7.83(2H, dd, J=1.8, 4.5Hz),



8.72(2H, dd, J=1.2, 4.8Hz) (CDCl3)


XB158
2.22-2.32(4H, m), 3.22(2H, m), 3.37(1H, m),
406



3.58(3H, s), 3.82(2H, m, 6.71(1H, s),



7.10(1H, m), 7.29(1H, m), 7.67(1H, m),



7.83(2H, d, J=6.3Hz), 8.72(2H, d, J=6.3Hz)



(CDCl3)


XB159
2.19-2.26(4H, m), 3.21(2H, m), 3.35(1H, m),
405



3.59(3H, s), 3.82(2H, m), 6.70(1H, s),



6.95(1H, dt, J=9.0, 2.1Hz), 7.13(1H, dd, J=9.0,



2.1Hz), 7.71(1H, m), 7.85(2H, d, J=6.3Hz),



8.72(2H, d, J=6.3Hz) (CDCl3)


XB160
2.13-2.34(2H, m), 2.34-2.43(2H, m),
388



3.10-3.38(3H, m), 3.57(3H, s),



3.68-3.83(2H, m), 6.69(1H, s),



7.29-7.40(2H, m), 7.46-7.59(1H, m),



7.64-7.78(1H, m), 7.80-7.78(2H, m),



8.72(2H, d, J=6.0Hz) (CDCl3)


XB161
2.19(2H, m), 2.38(2H, m), 3.18(2H, m),
404



3.39(1H, m), 3.58(3H, s), 3.80(2H, m),



6.70(1H, s), 7.39(1H, m), 7.50(1H, m),



7.83(2H, d, J=6.0Hz), 7.89(1H, d, J=7.2Hz),



8.01(1H, d, J=7.8Hz), 8.73(2H, d, J=6.0Hz)



(CDCl3)


XB162
1.96(2H, m), 2.88(2H, m), 3.15(2H, m),
420



3.60(3H, s), 3.85(2H, m), 4.63(1H, m),



6.73(1H, s), 7.13-7.23(3H, m), 7.46(1H, d,



J=7.5Hz), 7.84(2H, d, J=6.3Hz), 8.73(2H,



d, J=6.3Hz) (CDCl3)


XB164
1.64(2H, m), 2.23(2H, m), 3.13(2H, m),
380



3.50(1H, m), 3.53(3H, s), 3.68(2H, m),



6.58(2H, m), 6.68(1H, s), 6.91(2H, m),



7.81(2H, d, J=6.0Hz), 8.72(2H, d, J=6.0Hz)



(CDCl3)


XB165
1.91-1.99(4H, m), 2.84(3H, s), 3.07(2H, m),
376



3.55(3H, s), 3.77(2H, m), 3.84(1H, m),



6.69(1H, s), 6.75-6.87(3H, m), 7.27(2H, m),



7.82(2H, d, J=6.3Hz), 8.72(2H, d, J=6.3Hz)



(CDCl3)


XB168
1.52(2H, m), 1.79(3H, s), 1.96(2H, m),
422



3.09(2H, m), 3.42(3H, s), 3.64(2H, m),



4.86(1H, m), 6.63(1H, s), 7.09-7.19(4H, m),



7.74(2H, d, J=6.0Hz), 8.70(2H, d, J=6.0Hz)



(CDCl3)


XB169
1.86(1H, br s), 1.95(2H, m), 2.30(2H, m),
363



3.47-3.63(7H, m), 6.68(1H, s), 7.30-7.44(3H,



m), 7.54(2H, d, J=7.5Hz), 7.84(2H, d, J=6.0Hz),



8.71(2H, d, J=6.0Hz) (CDCl3)


XB201
2.20-2.31(4H, m), 3.20-3.29(2H, m),
390



3.46(3H, s), 3.87(2H, d, J=13.8Hz), 6.86(1H,



s), 7.29-7.35(2H, m), 7.64-7.69(2H, m),



8.01(2H, dd, J=1.5, 4.5Hz), 8.70(2H, dd,



J=1.5, 4.5Hz) (DMSO-d6)


XB227
2.16-2.25(2H, m), 2.48-2.58(2H, m),
389



3.14-3.21(2H, m), 3.40(3H, s), 3.41-3.50(2H,



m), 6.79(1H, s), 7.28-7.33(1H, m),



7.39-7.46(4H, m), 7.97(2H, dd, J=1.5, 4.5Hz),



8.68(2H, dd, J=1.5, 4.5Hz) (DMSO-d6)


XB256
1.77-1.85(8H, m), 2.10(1H, m), 2.51(4H, m),
430



2.97-3.02(3H, m), 3.58(3H, s), 3.55(3H, s),



3.62(2H, s), 3.74(1H, m), 6.66(1H, s),



7.16(2H, d, J=7.8Hz), 7.32(1H, d, J=7.8Hz),



7.80(2H, dd, J=1.5, 4.8Hz), 8.70(2H, dd,



J=1.5, 4.8Hz) (CDCl3)


XB257
1.77-1.85(8H, m), 2.10(1H, m), 2.51(4H, m),
430



2.97-3.02(3H, m), 3.58(3H, s), 3.55(3H, s),



3.62(2H, s), 3.74(1H, m), 6.66(1H, s),



7.16(2H, d, J=7.8Hz), 7.32(1H, d, J=7.8Hz),



7.80(2H, dd, J=1.5, 4.8Hz), 8.70(2H, dd,



J=1.5, 4.8Hz) (CDCl3)


XB258
1.86(4H, m), 1.99(4H, m), 3.03(5H, m),
429



3.35(4H, m), 3.43(3H, s), 3.73(2H, m), 4.30(2H,



s), 6.81(1H, s), 7.43(2H, d, J=8.1Hz),



7.69(2H, d, J=8.1Hz), 7.97(2H, d, J=6.0Hz),



8.69(2H, d, J=6.0Hz), 11.01(1H, br s)



(DMSO-d6)


XB259
1.75(1H, m), 1.89(3H, m), 1.97(3H, m),
443



2.13(1H, d, J=13.6Hz), 3.02(3H, m), 3.46(2H, t,



J=7.0Hz), 3.55(3H, s), 3.66(2H, t, J=7.0Hz),



3.75(2H, m), 6.66(1H, s), 7.30(2H, d, J=8.0Hz),



7.52(2H, d, J=8.0Hz), 7.80(2H,



dd, J=6.0, 1.2Hz), 8.71(2H, dd, J=6.0, 1.2Hz)


XB260
1.77-1.86(8H, m), 2.94-3.06(5H, m),
430



3.43(3H, s), 3.73-3.78(2H, m), 4.28-4.31(2H,



m), 6.81(1H, s), 7.44(2H, d, J=7.3Hz),



7.57(2H, d, J=7.3Hz), 7.96(2H, d, J=4.2Hz),



8.63(2H, d, J=4.2Hz), 10.75-10.80(1H,



br) (DMSO-d6)


XB261
1.45-1.59(6H, m), 1.73-1.94(4H, m),
444



2.10-2.15(4H, m), 2.98-3.05(3H, m),



3.49(2H, m), 3.55(3H, s), 3.74-3.77(2H, m),



6.65(1H, s), 7.22(2H, d, J=8.4Hz), 7.33(2H,



d, J=8.4Hz), 7.80(2H, d, J=6.0Hz), 8.70(2H,



d, J=6.0Hz) (CDCl3)


XB262
1.19-1.31(6H, m), 1.80-1.94(7H, m),
472



2.10(1H, m), 2.32(3H, s), 2.45(1H, m),



2.97-3.02(3H, m), 3.54(3H, s), 3.55(2H, m),



3.69-3.74(2H, m), 6.66(1H, s), 7.22(2H, d,



J=8.4Hz), 7.33(2H, d, J=8.4Hz), 7.81(2H, d,



J=6.0Hz), 8.71(2H, d, J=6.0Hz) (CDCl3)


XB263
1.77-1.86(4H, m), 2.44(1H, m), 2.80(6H, s),
473



2.98-3.16(4H, m), 3.42(3H, s), 3.62-3.79(6H,



m), 4.42(3H, m), 6.93(1H, s), 7.45(2H, d,



J=8.4Hz), 7.58(2H, d, J=8.4Hz), 8.21(2H, d,



J=6.0Hz), 8.82(2H, d, J=6.0Hz) (DMSO-d6)


XB264
0.99(3H, t, J=7.2Hz), 1.20-1.24(6H, m),
486



1.80-1.93(7H, m), 2.10(1H, m),



2.50-2.55(2H, m), 2.97-3.00(3H, m),



3.55(3H, s), 3.60(2H, s), 3.69-3.74(2H, m),



6.65(1H, s), 7.18(2H, d, J=8.4Hz), 7.34(2H,



d, J=8.4Hz), 7.80(2H, d, J=6.0Hz), 8.70(2H,



d, J=6.0Hz) (CDCl3)


XB265
1.02(6H, d, J=6.6Hz), 1.23-1.28(5H, m),
500



1.72-2.15(9H, m), 2.51(1H, m),



2 97-3.08(4H, m), 3.55(3H, s), 3.70(2H, s),



3.74-3.78(2H, m), 6.65(1H, s), 7.18(2H, d,



J=7.8Hz), 7.34(2H, d, J=7.8Hz), 7.81(2H, d,



J=6.0Hz), 8.70(2H, d, J=6.0Hz) (CDCl3)


XB266
1.77-1.87(4H, m), 2.44(1H, m), 2.80(6H, s),
473



2.99-3.09(4H, m), 3.42(3H, s), 3.62-3.79(6H,



m), 4.42(3H, m), 6.95(1H, s), 7.45(2H, d,



J=8.1Hz), 7.58(2H, d, J=8.1Hz), 8.29(2H, d,



J=6.0Hz), 8.86(2H, d, J=6.0Hz) (DMSO-d6)


XB267
1.85-1.88(4H, m), 2.81(1H, m),
425



2.99-3.07(2H, m), 3.44(3H, s), 3.79-3.84(2H,



m), 6.82(1H, s), 7.29(2H, d, J=8.4Hz),



7.51(2H, d, J=8.4Hz), 8.01(2H, d, J=6.0Hz),



8.70(2H, d, J=6.0Hz) (DMSO-d6)


XB268
1.83-1.99(4H, m), 2.83(1H, m),
425



2.98-3.06(2H, m), 3.45(3H, s), 3.79-3.84(2H,



m), 6.82(1H, s), 7.29-7.43(3H, m), 7.53(1H,



s), 8.01(2H, d, J=6.0Hz), 8.70(2H, d, J=6.0Hz)



(DMSO-d6)


XB269
1.74-1.96(8H, m), 2.51(1H, m),
416



2.65-3.01(2H, m), 3.04-3.18(4H, m),



3.44(3H, s), 3.77-3.81(2H, m), 6.49(2H, d,



J=8.4Hz), 6.80(1H, s), 7.09(2H, d, J=8.4Hz),



8.00(2H, dd, J=4.5, 1.8Hz), 8.69(2H,



dd, J=4.5, 1.8Hz) (DMSO-d6)


XB270
1.83-1.99(8H, m), 2.72(1H, m),
416



2.97-3.07(2H, m), 3.19-3.23(4H, m),



3.45(3H, s), 3.78-3.83(2H, m), 6.38(1H, d,



J=7.8Hz) 6.44(1H, s), 6.53(1H, d, J=7.5Hz),



6.81(1H, s), 7.09(1H, dd, J=7.8, 7.8Hz),



8.00(2H, d, J=5.4Hz), 8.70(2H, d, J=5.7Hz)



(DMSO-d6)


XB271
1.81-1.92(2H, m), 2.07-2.15(2H, m),
404



3.02-3.21(3H, m), 3.51(3H, s), 3.79-3.83(2H,



m), 6.80-6.86(2H, m), 7.10-7.17(2H, m),



7.58-7.63(1H, m), 8.00(2H, d, J=4.2Hz),



8.69(2H, d, J=4.2Hz), 10.90(1H,



brs) (DMSO-d6)


XB272
1.53-1.63(2H, m), 2.02-2.07(2H, m),
430



3.11-3.19(2H, m), 3.41(3H, s), 3.60-3.72(3H,



m), 6.12(1H, d, J=8.2Hz), 6.79-6.80(2H, m),



6.88-6.91(2H, m), 7.25-7.31(1H, m),



8.00(2H, d, J=4.2Hz), 8.70(2H, d,



J=4.2Hz) (DMSO-d6)


XB273
1.47-1.57(2H, m), 2.00-2.07(2H, m),
405



2.71(6H, s), 3.04-3.12(2H, m), 3.37-3.42(4H,



m), 3.67-3.71(2H, m), 4.87(1H, d, J=8.2Hz),



6.56-6.65(4H, m), 6.79(1H, s), 7.99(2H, d,



J=4.2Hz), 8.69(2H, d, J=4.2Hz) (DMSO-d6)


XB274
1.51-1.61(2H, m), 2.01-2.07(2H, m),
392



3.08-3.16(2H, m), 3.43(3H, s), 3.50-3.53(1H,



m), 3.67(3H, s), 3.70-3.73(2H, m), 5.56(1H,



d, J=8.2Hz), 6.09-6.24(3H, m), 6.78(1H, s),



6.96(1H, dd, J=7.2Hz, 7.3Hz), 7.99(2H, d,



J=4.2Hz), 8.69(2H, d, J=4.2Hz) (DMSO-d6)


XB275
1.48-1.59(2H, m), 2.00-2.07(2H, m),
392



3.06-3.13(2H, m), 3.40(3H, s), 3.44-3.46(1H,



m), 3.64(3H, s), 3.66-3.71(2H, m), 5.07(1H,



d, J=8.2Hz), 6.59(2H, d, J=7.2Hz), 6.70(2H,



d, J=7.2Hz), 6.79(1H, s), 7.98(2H, d,



J=4.2Hz), 8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB276
1.57-1.68(2H, m), 2.03-2.07(2H, m),
392



3.05-3.09(2H, m), 3.41(3H, s), 3.51-3.77(6H,



m), 4.57(1H, d, J=8.2Hz), 6.53-6.58(1H, m),



6.66-6.69(1H, m), 6.74-6.82(3H, m),



7.99(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB277
1.78-1.92(4H, m), 2.94-3.07(5H, m),
406



3.41-3.86(10H, m), 6.88-6.92(1H, m),



7.04(1H, s), 7.21-7.24(2H, m), 7.39-7.44(1H,



m), 8.48(2H, d, J=4.2Hz), 8.95(2H, d,



J=4.2Hz) (DMSO-d6)


XB278
1.68-2.08(4H, m), 2.90-2.96(2H, m),
406



3.15(3H, s), 3.38(3H, s), 3.81-4.04(7H, m),



7.03(1H, s), 7.13(2H, d, J=7.2Hz), 7.81(2H,



d, J=7.2Hz), 8.45(2H, d, J=4.2Hz), 8.94(2H,



d, J=4.2Hz) (DMSO-d6)


XB279
1.76-1.85(4H, m), 2.65(3H, s), 2.85-2.94(2H,
406



m), 3.41-3.42(1H, m), 3.44(3H, s),



3.74-3.79(2H, m), 4.02(3H, s), 6.78(1H, s),



6.83-6.99(4H, m), 7.97(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB280
1.86-1.98(4H, m), 2.98(6H, s), 3.01-3.10(2H,
419



m), 3.40-3.92(11H, m), 7.00-7.13(2H, m),



7.42-7.50(2H, m), 8.51(2H, d, J=4.2Hz),



8.97(2H, d, J=4.2Hz) (DMSO-d6)


XB281
1.69-1.88(3H, m), 1.92-2.00(1H, m),
425



2.92-3.06(3H, m), 3.42(3H, s), 3.63-3.88(2H,



m), 6.79(1H, s), 7.33(2H, d, J=8.4Hz),



7.54(2H, d, J=8.4Hz), 7.96(2H, d, J=5.7Hz),



8.68(2H, d, J=6.0Hz) (DMSO-d6)


XB282
2.51-2.60(4H, m), 3.47(3H, s), 3.65-3.68(4H,
285



m), 6.54(1H, s), 8.00(2H, d, J=4.2Hz),



8.70(1H, d, J=4.2Hz) (DMSO-d6)


XB283
1.71-1.82(4H, m), 2.40-2.49(2H, m),
475



2.50-2.53(4H, m), 2.86-2.94(3H, m),



3.06-3.09(4H, m), 3.41(3H, s), 3.50-3.68(4H,



m), 4.43-4.46(1H, m), 6.78(1H, s), 6.89(2H,



d, J=7.2Hz), 7.17(2H, d, J=7.2Hz), 7.95(2H,



d, J=4.2Hz), 8.67(2H, d,



J=4.2Hz) (DMSO-d6)


XB284
1.71-1.93(4H, m), 2.86(6H, s), 2.88-2.97(3H,
390



m), 3.41(3H, s), 3.65-3.75(2H, m), 6.73(2H,



d, J=7.2Hz), 6.78(1H, s), 7.15(2H, d,



J=7.2Hz), 7.96(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB285
1.72-1.83(4H, m), 2.89-2.96(3H, m),
432



3.05-3.09(4H, m), 3.42(3H, s), 3.71-3.75(4H,



m), 6.78(1H, s), 6.91(2H, d, J=7.2Hz),



7.20(2H, d, J=7.2Hz), 7.96(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB286
1.52-1.91(10H, m), 2.86-2.94(3H, m),
430



3.07-3.10(4H, m), 3.41(3H, s), 3.66-3.75(2H,



m), 6.78(1H, s), 6.89(2H, d, J=7.2Hz),



7.16(2H, d, J=7.2Hz), 7.95(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB287
1.64-1.88(4H, m), 2.21(3H, s), 2.42-2.45(4H,
445



m), 2.89-2.94(3H, m), 3.07-3.11(4H, m),



3.41(3H, s), 3.69-3.75(2H, m), 6.78(1H, s),



6.90(2H, d, J=7.2Hz), 7.18(2H, d, J=7.2Hz),



7.96(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB288
1.43-1.47(2H, m), 1.71-1.90(6H, m),
473



2.19(6H, s), 2.58-2.66(2H, m), 2.87-2.95(2H,



m), 2.87-2.98(3H, m), 3.30-3.32(1H, m),



3.41(3H, s), 3.64-3.75(4H, m), 6.78(1H, s),



6.90(2H, d, J=7.2Hz), 7.16(2H, d, J=7.2Hz),



7.96(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB289
1.72-1.94(4H, m), 2.92-2.99(3H, m),
565



3.08-3.11(4H, m), 3.41(3H, s), 3.52-3.56(4H,



m), 3.66-3.75(2H, m), 5.11(2H, s), 6.78(1H,



s), 6.93(2H, d, J=7.2Hz), 7.20(2H, d,



J=7.2Hz), 7.28-7.39(5H, m), 7.95(2H, d,



J=4.2Hz), 8.69(2H, d, J=4.2Hz) (DMSO-d6)


XB290
1.53-1.63(2H, m), 1.85-1.89(2H, m),
369



2.14(3H, s), 2.31-2.46(8H, m), 2.86-2.94(2H,



m), 3.34-3.35(1H, m), 3.39(3H, s),



3.70-3.74(2H, m), 6.79(1H, s), 7.98(2H, d,



J=4.2Hz), 8.69(2H, d, J=4.2Hz) (DMSO-d6)


XB291
1.52-1.63(2H, m), 1.85-1.90(2H, m),
399



2.34-2.42(11H, m), 2.86-2.94(2H, m),



3.39(3H, s), 3.45-3.50(2H, m), 3.70-3.74(2H,



m), 4.38-4.40(1H, m), 6.80(1H, s), 7.98(2H,



d, J=4.2Hz), 8.69(2H, d,



J=4.2Hz) (DMSO-d6)


XB292
1.71-1.83(4H, m), 2.81-3.00(11H, m),
431



3.28-3.30(1H, m), 3.41(3H, s), 3.66-3.75(2H,



m), 6.78(1H, s), 6.89(2H, d, J=7.2Hz),



7.17(2H, d, J=7.2Hz), 7.96(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB293
1.43-1.53(2H, m), 1.93-1.98(3H, m),
406



2.63-2.66(1H, m), 2.92-3.00(2H, m),



3.39(3H, s), 3.62-3.79(7H, m), 6.78(1H, s),



6.88-6.97(2H, m), 7.18-7.22(1H, m),



7.35(1H, d, J=7.3Hz), 7.98(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB294
1.42-1.53(2H, m), 1.96-2.08(3H, m),
406



2.61-2.67(1H, m), 2.91-2.99(2H, m),



3.39(3H, s), 3.62-3.80(7H, m), 6.77(1H, s),



6.86(2H, d, J=7.2Hz), 7.25(2H, d, J=7.2Hz),



7.97(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB295
1.81-1.91(2H, m), 2.61-2.20(2H, m),
420



2.96-3.17(6H, m), 3.41-3.47(5H, m),



3.74-3.86(4H, m), 6.90-7.03(3H, m),



7.21-7.29(2H, m), 8.44(2H, d, J=4.2Hz),



8.93(2H, d, J=4.2Hz), 9.30-9.38(2H,



br) (DMSO-d6)


XB296
1.80-1.91(2H, m), 2.07-2.21(2H, m),
420



2.96-3.11(6H, m), 3.34-3.41(5H, m),



3.69-3.86(4H, m), 6.91(2H, d, J=7.2Hz),



7.05(1H, s), 7.20(2H, d, J=7.2Hz), 8.49(2H,



d, J=4.2Hz), 8.96(2H, d, J=4.2Hz),



9.44-9.50(2H, br) (DMSO-d6)


XB297
1.41-1.51(2H, m), 1.91-1.96(3H, m),
419



2.61-2.65(1H, m), 2.86(6H, s), 2.91-2.98(2H,



m), 3.38(3H, s), 3.61-3.67(4H, m), 6.70(2H,



d, J=7.2Hz), 6.77(1H, s), 7.20(2H, d,



J=7.2Hz), 7.97(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)


XB298
2.04(2H, d, J=13.1Hz), 2.34(3H, s), 2.53(2H,
426



m), 2.91(2H, m), 3.55(3H, s), 3.70(2H, d,



J=13.1Hz), 4.27(1H, m), 6.08(1H, s),



6.86(1H, s), 7.36-7.48(5H, m), 7.80(2H, dd,



J=1.6, 4.3Hz), 8.69(2H, dd, J=1.3,



4.5Hz) (CDCl3)


XB299
2.06(2H, d, J=13.1Hz), 2.22(2H, m), 2.99(2H,
413



m), 3.13(1H, m), 3.54(3H, s), 3.70(2H, d,



J=13.1Hz), 6.68(1H, s), 7.25(1H, s),



7.44-7.48(2H, m), 7.64-7.67(3H, m),



7.78(2H, dd, J=1.6, 4.3Hz), 8.69(2H, dd,



J=1.3, 4.5Hz) (CDCl3)


XB300
1.75-1.85(4H, m), 2.97-3.10(5H, m),
464



3.43(3H, s), 3.71-3.76(2H, m), 3.88-3.93(2H,



m), 6.70(1H, dd, J=7.2, 7.3Hz), 6.79(1H, s),



7.02-7.06(2H, m), 7.15-7.23(3H, m),



7.31-7.35(2H, m), 7.97(2H, d, J=4.2Hz),



8.69(2H, d, J=4.2Hz) (DMSO-d6)


XB301
1.09-1.34(5H, m), 1.57-1.88(9H, m),
444



2.78-2.93(3H, m), 3.08-3.18(1H, m),



3.41(3H, s), 3.62-3.74(2H, m), 5.27(1H, d,



J=8.2Hz), 6.52(2H, d, J=7.2Hz), 6.79(1H, s),



7.01(2H, d, J=7.2Hz), 7.96(2H, d, J=4.2Hz),



8.68(2H, d, J=4.2Hz) (DMSO-d6)


XB302
1.10-1.16(1H, m), 1.32-1.46(4H, m),
458



1.64-1.82(9H, m), 2.68(3H, s), 2.82-2.93(3H,



m), 3.41(3H, s), 3.54-3.74(3H, m), 6.72(2H,



d, J=7.2Hz), 6.78(1H, s), 7.12(2H, d,



J=7.2Hz), 7.95(2H, d, J=4.2Hz), 8.68(2H, d,



J=4.2Hz) (DMSO-d6)







MS


No.
NMR
[M+1]





YA0262
(DMSO-d6): 3.47(3H, s), 3.48-3.66(4H, m),
367



3.89-4.02(2H, m), 4.98(1H, m), 7.06(1H, s),



7.35-7.59(3H, m), 7.99(1H, dd, J=7.2, 6.9Hz),



8.25(1H, dd, J=5.4, 1.2Hz), 9.01(1H, d,



J=5.1Hz), 9.31(1H, s), 9.84(1H, m), 10.19(1H,



m).


YA0263
(CDCl3): 3.01(1H, dd, J=10.5, 12.4Hz),
367



3.10-3.35(3H, m), 3.57(3H, s), 3.55-3.65(2H, m),



4.05(1H, dd, J=2.4, 10.4Hz), 7.00-7.10(1H, m),



7.30(1H, s), 7.22(2H, m), 7.30-7.42(2H, m),



8.15(1H, dd, J=1.3, 5.2Hz), 8.86(1H, d, J=5.2Hz),



9.27(1H, d, J=1.0Hz).


YA0264
2.83(1H, dd, J=11.0, 11.9Hz), 2.93(1H, s),
367



2.99-3.10(3H, m), 3.45(3H, s), 3.61-3.69(2H, m),



3.95(1H, dd, J=2.1, 10.3Hz), 6.97(1H, s),



7.19(2H, t, J=8.8Hz), 7.48-7.56(2H, m), 8.17(1H,



dd, J=1.0, 5.0Hz), 8.99(1H, d, J=5.1Hz),



9.29(1H, d, J=1.0Hz) (DMSO-d6)


YA0264
3.39-3.47(2H, m), 3.45(3H, s), 3.55-3.66(2H, m),
367


(HCl)
3.86-3.96(2H, m), 4.64-4.71(1H, m), 7.05(1H, s),



7.36(2H, t, J=8.7Hz), 7.77-7.81(2H, m), 8.23(1H,



dd, J=1.2, 5.1Hz), 9.02(1H, d, J=5.1Hz),



9.32(1H, d, J=1.2Hz), 9.79(1H, d, J=10.2Hz),



10.13-10.28(1H, m) (DMSO-d6)


YA0267
(CDCl3): 2.81(1H, dd, J=10.5, 12.6Hz),
383



3.15-3.40(3H, m),



3.50-3.65(4H, m), 3.65-3.80(1H, m),



4.51(1H, dd, J=2.7, 10.5Hz), 7.20-7.45(4H, m),



7.74(1H, dd, J=1.5, 7.5Hz), 8.15-8.20(1H, m),



8.85(1H, d, J=5.1Hz), 9.27(1H, s).


YA0268
(CDCl3): 3.00(1H, dd, J=10.5, 12.6Hz),
383



3.10-3.35(3H, m), 3.50-3.70(5H, m),



4.03(1H, dd, J=2.4, 10.5Hz), 7.32(4H, m),



7.50(1H, s), 8.15(1H, dd, J=1.2, 5.1Hz),



8.87(1H, d, J=5.1Hz), 9.27(1H, d, J=1.5Hz).


YA0269
3.40-3.50(2H, m), 3.45(3H, s), 3.53-3.65(2H, m),
383



3.87-3.97(2H, m), 4.68(1H, t, J=10.2Hz),



7.05(1H, s), 7.59(2H, d, J=11.1Hz), 7.75(2H, d,



J=11.1Hz), 8.22(1H, dd, J=1.5, 5.4Hz), 9.02(1H,



d, J=5.1Hz), 9.31(1H, s), 9.83(1H, d, J=9.6Hz),



10.11-10.25(1H, m) (DMSO-d6)


YA0274
(DMSO-d6): 3.45(3H, s), 3.40-3.70(4H, m),
427



3.92(2H, t, J=14.1Hz), 4.67(1H, br s), 7.06(1H, s),



7.68(2H, d, J=10.0Hz), 7.72(2H, d, J=10.0Hz),



8.22(1H, d, J=4.8Hz), 9.03(1H, d, J=4.8Hz),



9.31(1H, s), 9.88(1H, br s), 10.22(1H, br s).


YA0289
3.38-3.57(4H, m), 3.35(3H, s), 3.89(3H, s),
379



3.91-3.97(2H, m), 4.84-4.94(1H, m), 7.06(1H, s),



7.08-7.15(1H, m), 7.18(1H, d, J=8.4Hz),



7.41-7.49(1H, m), 7.68(1H, d, J=7.6Hz),



8.25(1H, d, J=4.9Hz), 9.04(1H, d, J=5.1Hz),



9.32(1H, s) (DMSO)


YA0290
(DMSO-d6): 3.40-3.75(7H, m),
379



3.92(2H, t, J=13.2Hz), 4.64(1H, t, J=9.1Hz),



7.00-7.10(2H, m), 7.23(1H, d, J=7.6Hz),



7.35(1H, s), 7.42(1H, t, J=7.8Hz),



8.23(1H, d, J=5.6Hz), 9.02(1H, d, J=5.2Hz),



9.32(1H, s), 9.65-9.80(1H, brd),



9.90-10.15(1H, brd).


YA0291
(DMSO-d6): 3.42(3H, s), 3.36-3.58(4H, m),
379



3.79(3H, s), 3.83-3.95(2H, m), 4.61(1H, m),



7.05(1H, s), 7.07(2H, d, J=8.1Hz), 7.60(2H, d,



J=8.7Hz), 8.22(1H, dd, J=5.1, 1.2Hz), 9.02(1H,



d, J=5.4Hz), 9.31(1H, s), 9.58-9.74(2H, m).


YA0294
1.31(3H, t, J=6.8Hz), 3.44-3.59(2H, m), 3.48(3H,
393



s), 3.87-3.97(2H, m), 4.09-4.20(2H, m),



4.80-4.91(1H, m), 7.06(1H, s), 7.09-7.17(2H, m),



7.44(1H, t, J=7.4Hz), 7.64(1H, d, J=7.5Hz),



8.23(1H, d, J=5.3Hz), 9.03(1H, d, J=5.2Hz),



9.32(1H, s), 9.49-9.60(2H, m) (DMSO-d6)


YA0304
(DMSO-d6): 3.45(3H, s), 3.64(3H, m),
374



3.93(3H, m), 4.78(1H, t, J=9.6Hz), 7.13(1H, s),



7.97(2H, d, J=8.7Hz), 8.01(2H, d, J=8.7Hz),



8.43(2H, d, J=6.2Hz), 8.93(2H, d, J=6.2Hz),



10.12(1H, s), 10.70(1H, s).


YA0331
(CDCl3): 2.00(4H, m), 3.05(1H, t, J=11.7Hz),
418



3.18-3.30(3H, m), 3.29(4H, m), 3.56(3H, s),



3.62(2H, m), 3.91(1H, d, J=8.4Hz),



6.57(2H, d, J=8.7Hz), 7.31(3H, m),



8.17(1H, dd, J=1.2, 5.1Hz), 8.85(1H, d, J=5.1Hz),



9.27(1H, d, J=1.2Hz).


YA0337
(CDCl3): 3.02(1H, dd, J=10.8, 12.6Hz),
434



3.18(8H, m), 3.56(3H, s), 3.61(1H, t, J=9.0Hz),



3.87(4H, m), 3.95(1H, dd, J=2.7, 10.8Hz),



6.93(2H, d, J=8.9Hz), 7.31(1H, s),



7.36(2H, d, J=8.9Hz), 8.16(1H, dd, J=1.5, 5.4Hz),



8.85(1H, d, J=5.4Hz), 9.27(1H, d, J=1.5Hz).


YA0340
(CDCl3): 2.36(3H, s), 2.59(4H, m),
447



3.02(1H, t, J=11.4Hz), 3.16-3.29(7H, m),



3.26(3H, s), 3.61(2H, m), 3.94(1H, d, J=8.0Hz),



6.94(2H, d, J=8.7Hz), 7.31(1H, s),



7.34(2H, d, J=8.7Hz), 8.16(1H, d, J=5.1Hz),



8.85(1H, d, J=5.1Hz), 9.27(1H, s).


YA0361
3.39-3.50(2H, m), 3.47(3H, s), 3.61-3.73(1H, m),
409



3.78(3H, s), 3.83(3H, s), 3.87-3.92(3H, m),



4.92(1H, t, J=10.5Hz), 6.99-7.11(3H, m),



7.57(1H, d, J=2.7Hz), 8.25(1H, dd, J=1.2, 5.1Hz),



9.03(1H, d, J=4.8Hz), 9.31(1H, d, J=0.9Hz),



9.78(1H, d, J=9.0Hz), 10.21-10.38(1H,



m) (DMSO-d6)


YA0362
(DMSO-d6): 3.47(3H, s), 3.37-4.04(6H, m),
409



3.94(6H, s), 5.09(1H, m), 6.82(2H, d, J=8.4Hz),



7.05(1H, s), 7.45(1H, t, J=8.4Hz), 8.22(1H, m),



8.24(1H, dd, J=5.4, 1.5Hz), 9.05(1H, d,



J=5.1Hz), 9.32(1H, s), 10.06(1H, m).


YA0366
3.38-3.60(4H, m), 3.47(3H, s), 3.88-3.95(2H, m),
397



3.90(3H, s), 4.86-4.92(1H, m), 6.96-7.01(1H, m),



7.06(1H, s), 7.12(1H, d, J=8.8Hz), 7.71-7.79(1H,



m), 8.23-8.24(1H, m), 9.03(1H, d, J=5.1Hz),



9.32(1H, d, J=1.2Hz), 9.55-9.72(2H, m) (DMSO)


YA0367/
(DMSO-d6): 3.30-3.75(7H, m), 3.80-4.00(5H, m),
397


YA0368
4.80-5.00(1H, m), 6.93-7.00(1H, m), 7.05(1H, s),



7.11(1H, dd, J=2.4, 11.4Hz), 7.84(1H, m),



8.23(1H, d, J=5.1Hz), 9.03(1H, d, J=5.1Hz),



9.31(1H, s), 9.60-9.80(1H, brd),



9.90-10.15(1H, brd).


YA0370
3.31-3.56(3H, m), 3.45(3H, s), 3.69-3.78(1H, m),
397



3.90-3.99(2H, m), 3.94(3H, s), 4.95-5.03(1H, m),



6.96-7.02(1H, m), 7.03-7.09(2H, m),



7.49-7.56(1H, m), 8.24(1H, d, J=4.4Hz),



8.51-8.69(1H, m), 9.03(1H, d, J=5.1Hz),



9.32(1H, s), 10.55-10.67(1H, m) (DMSO)


YA0378
2.77(1H, dd, J=10.5, 12.0Hz), 3.18-3.30(3H, m),
413



3.61(3H, s), 3.64-3.71(2H, m), 3.86(3H, s),



4.37(1H, dd, J=2.1, 10.1Hz), 6.89(1H, d, J=1.7Hz),



6.99(1H, dd, J=1.6, 8.2Hz), 7.32(1H, s),



7.50(1H, d, J=8.2Hz), 8.19(1H, d, J=5.2Hz),



8.86(1H, d, J=5.2Hz), 9.27(1H, s) (CDCl3)


YA0399
(CDCl3): 2.76(1H, dd, J=10.2, 12.3Hz),
457



3.10-3.40(3H, m), 3.55-3.80(5H, m), 3.85(3H, s),



4.39(1H, dd, J=2.4, 10.2Hz), 6.78(1H, d, J=8.7Hz),



7.32(1H, s), 7.39(1H, dd, J=2.7, 8.7Hz),



7.72(1H, d, J=2.4Hz), 8.20(1H, dd, J=1.2, 5.1Hz),



8.87(1H, d, J=5.1Hz), 9.27(1H, d, J=1.2Hz).


YA0408
(CDCl3): 1.98-2.03(4H, m), 2.84(1H, m),
448



3.17-3.32(7H, m), 3.60(3H, s), 3.59-3.71(2H, m),



3.85(3H, s), 4.28(1H, d, 8.4Hz), 6.10(1H, d,



J=1.8Hz), 6.18(1H, d, J=8.3Hz), 7.29(1H, s),



7.33(1H, d, J=8.4Hz), 8.21(1H, d, J=5.2Hz),



8.85(1H, d, J=5.2Hz), 9.27(1H, s).


YA0409
(CDCl3): 1.95-2.10(4H, m), 2.95-3.10(1H, m),
448



3.19-3.45(7H, m), 3.59(3H, s), 3.50-3.80(2H, m),



3.80(3H, s), 4.48(1H, dd, J=2.2, 10.2Hz),



6.49(1H, dd, J=3.0, 8.9Hz), 6.63-6.87(2H, m),



7.32(1H, s), 8.20(1H, dd, J=1.4, 5.2Hz),



8.86(2H, d, J=5.2Hz), 9.27(1H, d, J=1.1Hz).


YA0414
(CDCl3): 3.14(2H, m), 3.22(1H, t, J=11.6Hz),
415



3.41(1H, t, J=11.6Hz), 3.82(2H, m), 3.83(3H, s),



3.88(3H, s), 4.58(1H, dd, J=3.1, 11.0Hz),



6.51(2H, m), 7.32(1H, s),



8.19(1H, dd, J=1.5, 5.3Hz), 8.86(1H, d, J=5.3Hz),



9.27(1H, d, J=1.5Hz).


YA0423
(DMSO-d6): 3.35-3.70(4H, m), 3.48(3H, s),
455



3.78(3H, s), 3.97(2H, m), 4.70(1H, m),



7.06(1H, t, J=7.7Hz), 7.07(1H, s),



7.15(1H, d, J=7.7Hz), 7.31(1H, d, J=7.7Hz),



7.39(1H, t, J=7.7Hz), 7.61(2H, d, J=8.1Hz),



7.70(2H, d, J=8.1Hz), 8.25(1H, d, J=4.5Hz),



9.07(1H, d, J=4.5Hz), 9.33(1H, s), 9.66(1H, br s).


YA0425
(DMSO-d6): 3.61(3H, m), 3.76(3H, s), 3.81(3H, s),
455



4.01(3H, m), 4.69(1H, t, J=9.9Hz),



7.05(2H, d, J=9.0Hz), 7.07(1H, s),



7.67(2H, d, J=9.0Hz), 7.76(4H, s),



8.24(1H, dd, J=1.2, 5.1Hz), 9.03(1H, d, J=5.1Hz),



9.32(1H, d, J=1.2Hz), 9.79(1H, d, J=10.2Hz),



10.07(1H, s).


YA0434
(DMSO-d6): 3.30-3.70(4H, m), 3.42(3H, s),
443



3.96(2H, d, J=13.8Hz), 4.71(1H, t, J=11.3Hz),



7.06(1H, s), 7.33(2H, t, J=8.0Hz), 7.77(6H, m),



8.24(1H, d, J=5.4Hz), 9.03(1H, d, J=5.4Hz),



9.32(1H, s), 9.80(1H, d, J=8.7Hz), 10.03(1H, s).


YA0442
3.43-3.59(2H, m), 3.48(3H, s), 3.63-3.75(2H, m),
399



3.97-4.01(2H, m), 4.80-4.86(1H, m), 7.06(1H, s),



7.60-7.64(2H, m), 7.86-7.88(1H, m),



7.95-8.00(2H, m), 8.05-8.07(1H, m),



8.24-8.27(2H, m), 9.02(1H, d, J=5.4Hz),



9.32(1H, s), 10.01(1H, d, J=10.2Hz),



10.30-10.41(1H, m) (DMSO-d6)


YA0517
(CDCl3): 2.97(1H, dd, J=12.3, 10.5Hz),
391



3.18-3.28(5H, m), 3.58(3H, s), 3.59(1H, m),



3.77(1H, m), 4.27(1H, dd, 10.2, 2.7Hz),



4.62(2H, m), 6.89(1H, t, J=7.5Hz), 7.16(1H, m),



7.27(1H, m), 7.28(1H, s), 8.26(1H, dd, J=5.4,



1.5Hz), 8.86(1H, d, J=5.4Hz), 9.26(1H, s).


YA0864
(DMSO-d6): 3.15-3.35(1H, m), 3.38-3.50(4H, m),
487



3.70-4.30(9H, m), 5.00-5.20(1H, m),



7.00-7.10(2H, m), 7.10-7.20(1H, m),



7.30-7.50(6H, m), 8.15-8.20(1H, m),



8.30-8.40(1H, brd), 9.05(1H, d, J=5.1Hz),



9.31(1H, d, J=0.9Hz).


YA1074
(CDCl3): 1.80-2.40(3H, m), 3.12-3.34(4H, m),
439



3.39-4.20(7.6H, m), 4.50-5.07(0.6H, m),



5.30-5.60(0.7H, m), 5.72-6.05(0.1H, m),



6.52-6.80(2H, m), 6.82-7.22(1H, m), 7.28(1H, s),



8.18(1H, d, J=4.8Hz), 8.89(1H, d, J=5.1Hz),



9.28(1H, d, J=1.2Hz)


YA1339
(CDCl3): 2.50-2.62(1H, m), 2.80-2.95(1H, m),
411



3.02-3.20(1H, m), 3.25-3.40(1H, m),



3.50-3.74(5H, m), 3.75-3.80(1H, m), 3.85(3H, s),



6.60-6.80(2H, m), 7.30(1H, s),



7.48(1H, t, J=8.4Hz), 8.19(1H, dd, J=1.2, 5.1Hz),



8.86(1H, d, J=5.1Hz), 9.27(1H, d, J=1.5Hz).


YA1340/
(DMSO-d6): 2.55(3H, d, J=3.9Hz),
411


YA1341
3.40-3.80(3H, m), 3.45(3H, s), 3.80-4.15(6H, m),



4.85-5.15(1H, m), 6.90-7.05(1H, m), 7.05(1H, s),



7.13(1H, dd, J=2.4, 11.4Hz),



8.21(1H, dd, J=1.2, 5.1Hz), 9.04(1H, d, J=5.1Hz),



9.31(1H, d, J=1.2Hz), 11.50-12.20(1H, brd).


YA1534
2.90-3.10(1H, m), 3.15-3.35(3H, m),
408



3.50-3.70(5H, m), 3.80-4.05(7H, m), 6.87(1H, d,



J=8.1Hz), 6.90-7.10(2H, m), 7.31(1H, s),



8.16(1H, d, J=4.6Hz), 8.85(1H, d, J=5.0Hz),



9.27(1H, s) (CDCl3)


YA1535
3.45(3H, s), 3.46(2H, m), 3.64(m, 2H), 3.91(2H,
383



t, J=16.1Hz), 4.68(1H, t, J=10.5Hz), 7.05(1H,



s), 7.59(2H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz),



8.23(1H, dd, J=5.1, 1.2Hz), 9.02(1H, d, J=5.1Hz),



9.31(1H, d, J=1.2Hz), 10.00(1H, d,



J=8.7Hz), 10.49(1H, br s) (DMSO-6)


YA1536
3.45(3H, s), 3.46(2H, m), 3.64(m, 2H), 3.91(2H,
383



t, J=16.1Hz), 4.68(1H, t, J=10.5Hz), 7.05(1H,



s), 7.59(2H, d, J=8.4Hz), 7.79(2H, d, J=8.4Hz),



8.23(1H, dd, J=5.1, 1.2Hz), 9.02(1H, d, J=5.1Hz),



9.31(1H, d, J=1.2Hz), 10.00(1H, d,



J=8.7Hz), 10.49(1H, br s) (DMSO-6)


YA1537
2.39(3H, s), 2.60(4H, t, J=4.6Hz), 3.37(4H, t,
286



J=4.8Hz), 3.53(3H, s), 7.27(1H, s), 8.18(1H, dd,



J=1.2, 5.4Hz), 8.87(1H, d, J=5.1Hz), 9.28(1H,



s) (CDCl3)


YA1538
2.64-2.74(1H, br.s), 2.66(2H, t, J=5.3Hz),
316



2.73(4H, t, J=4.4Hz), 3.39(4H, t, J=4.0Hz),



3.54(3H, s), 3.69-3.70(2H, m), 7.26(1H, s),



8.18(1H, d, J=5.0Hz), 8.88(1H, t, J=5.0Hz),



9.28(1H, s) (CDCl3)


YA1539
1.10(6H, t, J=6.6Hz), 2.71(4H, t, J=4.9Hz),
314



2.77(1H, m), 3.36(4H, t, J=4.9Hz), 3.54(3H, s),



7.27(1H, s), 8.18(1H, dd, J=1.1, 5.2Hz), 8.87(2H,



d, J=5.1Hz), 9.27(1H, s) (CDCl3)


YA1540
1.15(6H, d, J=6.2Hz), 1.50(1H, br.s), 2.61(2H,
300



dd, J=1.6, 12.4Hz), 3.06-3.16(2H, m), 3.49(2H, d,



J=13.0Hz), 3.52(3H, s), 7.27(1H, s), 8.16(1H, dd,



J=1.3, 5.0Hz), 8.88(1H, d, J=5.0Hz), 9.27(1H, d,



J=1.3Hz) (CDCl3)


YA1541
2.98(1H, t, J=11.5Hz), 3.20(3H, m), 3.57(3H,
417



s), 3.58(2H, m), 4.02(1H, dd, J=10.5, 2.2Hz),



7.27(1H, s), 7.29(1H, d, J=8.3Hz), 7.46(1H, d,



J=8.3Hz), 7.61(1H, s), 8.13(1H, d, J=5.2Hz),



8.86(1H, d, J=5.2Hz), 9.27(1H, s) (CDCl3)


YA1542
3.44(3H, s), 3.62-3.73(2H, m), 3.86-3.93(2H, m),
427



4.66(1H, m), 7.05(1H, s), 7.45(1H, dd, J=8.4,



8.4Hz), 7.67(1H, d, J=8.4Hz), 7.81(1H, d,



J=8.4Hz), 8.04(1H, s), 8.25(1H, dd, J=5.4,



1.5Hz), 9.02(1H, d, J=5.4Hz), 8.18(1H, dd,



J=5.4, 1.2Hz), 8.99(1H, d, J=5.1Hz), 9.32(1H, d,



J=1.5Hz), 10.13(1H, m), 10.67(1H, m) (DMSO)


YA1543
3.33(1H, dd, J=13.5, 8.9Hz), 3.47(3H, s),
397



3.79(1H, dd, J=13.5, 3.9Hz), 4.73(1H, d,



J=17.1Hz), 4.22(1H, d, J=17.1Hz), 4.82(1H,



dd, J=8.9, 3.9Hz), 6.08(1H, s), 7.31(2H, d,



J=8.4Hz), 7.42(2H, d, J=8.4Hz), 8.14(1H,



d, J=5.1, 1.5Hz), 8.90(1H, d, J=5.1Hz),



9.29(1H, d, J=1.5Hz) (CDCl3)


YA1544
1.97(4H, m), 3.26(4H, m), 3.39(2H, m),
418



3.44(3H, s), 3.60(2H, m), 3.79(1H, d, J=13.5Hz),



3.91(1H, d, J=13.8Hz), 4.48(1H, t, J=10.1Hz),



6.66(2H, d, J=8.4Hz), 7.04(1H, s), 7.51(2H, d,



J=8.4Hz), 8.21(1H, d, J=5.1Hz), 9.02(1H, d,



J=5.1Hz), 9.31(1H, s), 9.70(1H, d, J=10.8Hz),



10.07(1H, br s) (DMSO-d6)


YA1545
3.21(4H, m), 3.42(2H, m), 3.44(3H, s), 3.62(2H,
434



m), 3.79(4H, m), 3.90(2H, t, J=14.6Hz),



4.54(1H, t, J=10.5Hz), 7.05(1H, s), 7.13(2H, d,



J=8.7Hz), 7.62(2H, d, J=8.7Hz), 8.22(1H,



d, J=4.8Hz), 9.02(1H, d, J=4.8Hz), 9.31(1H, s),



9.80(1H, d, J=9.3Hz), 10.23(1H, br s)



(DMSO-d6)


YA1546
2.80(3H, d, J=4.5Hz), 3.26(4H, m), 3.44(3H,
447



s), 3.45(4H, m), 3.60(2H, m), 3.80(1H, d, J=3.5Hz),



3.90(3H, m), 4.54(1H, t, J=10.5Hz),



7.04(1H, s), 7.10(2H, d, J=8.7Hz), 7.62(2H, d,



J=8.7Hz), 8.20(1H, dd, J=5.1, 1.2Hz), 9.02(1H,



d, J=5.1Hz), 9.32(1H, d, J=1.2Hz), 9.86(1H,



d, J=10.2Hz), 10.33(1H, br s), 11.15(1H, br s)



(DMSO-d6)


YA1547
2.28(3H, s), 3.07(4H, t, J=4.7Hz), 3.37(4H, t,
428



J=4.8Hz), 3.75(3H, s), 5.76(1H, s), 7.26-7.33(2H,



m), 7.45(2H, dd, J=7.8, 7.8Hz), 7.79(2H, d,



J=7.8Hz), 8.14(1H, d, J=5.4Hz), 8.87(1H, dd,



J=7.8, 7.8Hz), 9.28(1H, d, J=1.2Hz) (CDCl3)


YA1548
2.37(1H, m), 2.43(1H, m), 2.80(3H, d, J=5.2Hz),
461



2.81(3H, d, J=5.2Hz), 3.28(1H, q, J=8.8Hz),



3.40(2H, m), 3.44(3H, s), 3.57(5H, m),



3.79(1H, d, J=11.4Hz), 3.97(2H, m), 4.50(1H, t,



J=10.0Hz), 6.69(2H, d, J=8.4Hz), 7.05(1H, s),



7.54(2H, d, J=8.4Hz), 8.20(1H, dd, J=4.8,



1.2Hz), 9.03(1H, d, J=4.8Hz), 9.32(1H, d,



J=1.2Hz), 9.71(1H, br s), 10.06(1H, br s),



11.35(1H, br s) (DMSO-d6)


YA1549
2.33(1H, m), 2.41(1H, m), 2.79(3H, d, J=4.8Hz),
461



2.81(3H, d, J=4.8Hz), 3.28(1H, d, J=8.4Hz),



3.39(2H, m), 3.44(3H, s), 3.57(5H, m),



3.79(1H, d, J=13.3Hz), 3.97(2H, m), 4.50(1H, t,



J=11.6Hz), 6.69(2H, d, J=8.4Hz), 7.04(1H, s),



7.55(2H, d, J=8.4Hz), 8.21(2H, d, J=5.2Hz),



9.02(2H, d, J=5.2Hz), 9.32(1H, s), 9.75(1H,



br s), 10.14(1H, br s), 11.45(1H, br s) (DMSO-d6)


YA1550
3.47(3H, s), 3.60(2H, m), 3.76(2H, m), 3.81(3H,
455



s), 3.94(2H, m), 4.68(1H, m), 7.05(2H, d, J=8.6Hz),



7.06(1H, s), 7.67(2H, d, J=8.6Hz),



7.76(4H, s), 8.25(1H, d, J=5.0Hz), 9.03(1H, d,



J=5.0Hz), 9.32(1H, s) (DMSO-d6)


YA1551
1.18(1H, m), 1.40(4H, m), 1.70(1H, m),
431



1.80(4H, m), 2.55(1H, m), 3.43(2H, m), 3.45(3H,



s), 3.60(2H, m), 3.91(2H, m), 4.60(1H, t,



J=10.8Hz), 7.05(1H, s), 7.35(2H, d, J=8.0Hz),



7.64(2H, d, J=8.0Hz), 9.03(1H, d, J=4.8Hz),



9.31(1H, s), 9.80(1H, d, J=8.8Hz), 10.24(1H, m)



(DMSO-d6)


YA1552
3.02(4H, m), 3.23(4H, m), 3.49(3H, s),
424



7.08-7.67(10H, m), 8.15(1H, d, J=5.1Hz),



8.87(1H, d, J=5.1Hz), 9.27(1H, s) (CDCl3)


YA1553
2.90(1H, dd, J=13.2, 9.6Hz), 3.16(2H, m),
363



3.24(1H, d, 14.4Hz), 3.31(3H, s), 3.34(1H, d,



J=13.6Hz), 3.47(1H, t, J=13.2Hz), 3.80(3H, m),



6.97(1H, s), 7.38(2H, m), 7.45(3H, m), 7.64(1H,



dd, J=5.2, 1.2Hz), 8.94(1H, d, J=5.2Hz),



9.28(1H, d, J=1.2Hz), 9.54(1H, br s), 9.78(1H, br s)



(DMSO-d6)


YA1554
2.95(1H, m), 3.29-3.05(3H, m), 3.34(3H, s),
397



3.35(1H, m), 3.44(1H, t, J=12.4Hz), 3.79(3H,



m), 6.99(1H, s), 7.40(2H, d, J=8.4Hz),



7.51(2H, d, J=8.4Hz), 7.76(1H, dd, J=4.8, 1.2Hz),



8.96(1H, d, J=4.8Hz), 9.29(1H, d, J=1.2Hz),



9.38(1H, br s), 9.71(1H, br s) (DMSO-d6)


YA1555
1.65(2H, br s), 1.90(4H, br s), 3.44(6H, m),
432



3.45(3H, s), 3.61(2H, m), 3.88(1H, d, J=13.6Hz),



3.94(1H, d, J=13.6Hz), 4.66(1H, t, J=8.8Hz),



7.05(1H, s), 7.82(4H, br s), 8.23(1H, dd, J=5.2,



1.2Hz), 9.02(1H, d, J=5.2Hz), 9.31(1H, d,



J=1.2Hz), 9.89(1H, br s), 10.37(1H, br s)



(DMSO-d6)


YA1556
3.42(2H, m), 3.45(3H, s), 3.56(2H, m), 3.85(1H,
509



d, J=13.2Hz), 3.93(1H, d, J=14.0Hz),



4.55(1H, t, J=10.8Hz), 6.94(1H, br s), 7.05(1H, s),



7.15(4H, br s), 7.31(2H, br s), 7.57(2H, br s),



8.22(1H, d, J=4.8Hz), 9.03(1H, d, J=4.8Hz),



9.32(1H, s), 9.66(1H, br s), 9.90(1H, br s)



(DMSO-d6)


YA1557
1.40(1H, m), 1.78(8H, m), 2.18(2H, d, J=11.2Hz),
515



2.78(2H, m), 2.91(2H, m), 3.30(1H, m),



3.40(3H, m), 3.44(3H, s), 3.58(2H, m), 3.82(1H,



d, J=13.3Hz), 3.93(3H, m), 4.53(1H, m),



7.05(1H, s), 7.11(2H, d, J=8.8Hz), 7.57(2H, d,



J=8.8Hz), 8.21(1H, d, J=5.2Hz), 9.02(1H, d,



J=5.2Hz), 9.32(1H, s), 9.73(1H, d, J=8.4Hz),



10.09(1H, br s), 10.39(1H, br s) (DMSO-d6)


YA1558
2.84-2.91(1H, m), 3.01-3.05(4H, m), 3.22(3H, s),
427



3.46(3H, s), 3.68-3.72(2H, m), 4.07-4.11(1H, m),



6.95(1H, s), 7.78(2H, d, J=7.2Hz), 7.93(2H, d,



J=7.2Hz), 8.31(1H, d, J=4.2Hz), 8.99(1H, d,



J=4.2Hz), 9.28(1H, s) (DMSO-d6)


YA1559
1.84(4H, m), 1.97(2H, m), 2.13(2H, m),
501



2.79(2H, t, J=11.6Hz), 3.04(2H, m), 3.24(1H, m),



3.40(2H, m), 3.44(3H, s), 3.59(2H, m), 3.80(1H,



d, J=14.0Hz), 3.91(3H, m), 4.53(1H, t, J=11.2Hz),



7.05(1H, s), 7.13(2H, d, J=8.4Hz),



7.58(2H, d, J=8.4Hz), 8.22(1H, d, J=5.2Hz),



9.02(1H, d, J=5.2Hz), 9.31(1H, s), 9.75(1H, d,



J=8.4Hz), 10.10(1H, br s), 11.04(1H, br s)



(DMSO-d6)


YA1560
1.71(2H, m), 2.12(2H, m), 2.74(6H, d, J=4.8Hz),
475



2.74-2.80(3H, m), 3.30-3.96(8H, m), 3.40(3H, s),



4.54(1H, m), 7.05(1H, s), 7.10(2H, d, J=9.0Hz),



7.54(2H, d, J=9.0Hz), 8.21(1H, dd, J=5.1, 1.2Hz),



9.03(1H, d, J=5.4Hz), 9.32(1H, s), 9.68(1H,



m), 9.92(1H, m), 10.54(1H, m), (DMSO-d6)


YA1561
1.51(2H, m), 1.84(2H, m), 3.00-3.20(3H, m),
448



3.38(3H, s), 3.38-3.91(8H, m), 4.55(1H, m),



7.05(1H, s), 7.18(2H, d, J=9.0Hz), 7.51(2H, d,



J=9.0Hz), 8.21(1H, d, J=6.0Hz), 9.02(1H, d,



J=5.1Hz), 9.31(1H, s), 9.54-9.62(3H, m),



(DMSO-d6)


YA1562
1.89-2.05(2H, m), 2.65-3.20(5H, m),
434



3.25-3.82(5H, m), 3.41(3H, s), 4.39(1H, m),



4.91(1H, m), 6.49(2H, d, J=8.4Hz), 6.96(1H, s),



7.25(2H, d, J=8.4Hz), 8.18(1H, dd, J=4.2, 0.9Hz),



8.99(1H, d, J=5.1Hz), 9.28(1H, s),



(DMSO-d6)


YA1563
1.06(1H, m), 1.30(2H, m), 1.43(2H, m),
460



1.60(2H, m), 1.79(3H, m), 2.97(3H, m), 3.45(3H,



s), 3.60(2H, m), 3.80(3H, s), 3.90(2H, m), 4.63(1H,



m), 7.05(1H, s), 7.70(4H, br s), 8.23(1H, d,



J=5.2Hz), 9.03(1H, d, J=5.2Hz), 9.32(1H, s),



9.75(1H, br s) (DMSO-d6)


YA1564
2.99(6H, m), 3.44(1H, m), 3.45(3H, s), 3.57(3H,
392



m), 3.82(1H, d, J=13.2Hz), 4.92(1H, d, J=14.4Hz),



4.55(1H, t, J=10.0Hz), 7.05(1H, s),



7.06(2H, br s), 7.61(2H, br s), 8.22(1H, d,



J=5.2Hz), 9.03(1H, d, J=5.2Hz), 9.32(1H, s),



9.73(1H, br s), 10.11(1H, br s) (DMSO-d6)


YA1565
3.20-3.22(4H, m), 3.44-3.89(15H, m),
567



4.51-4.55(1H, m), 5.11(2H, s), 7.04-7.07(3H, m),



7.35-7.39(5H, m), 7.53(2H, d, J=7.2Hz), 8.20(1H,



d, J=4.2Hz), 9.01(1H, d, J=4.2Hz), 9.31(1H, s),



9.78-9.92(2H, br) (DMSO-d6)


YA1566
1.33(6H, d, J=6.8Hz), 3.02-3.55(13H, m),
475



3.89-3.93(5H, m), 4.52-4.55(1H, m),



6.99-7.13(3H, m), 7.60(2H, d, J=7.2Hz), 8.21(1H,



d, J=4.2Hz), 9.02(1H, d, J=4.2Hz), 9.32(1H, s),



9.67-10.15(3H, br), 10.84-10.88(1H,



br) (DMSO-d6)


YA1567
3.17-3.26(8H, m), 3.44-3.55(6H, m),
477



3.80-3.94(9H, m), 4.50-4.57(1H, m),



7.05-7.12(3H, m), 7.60(2H, d, J=7.2Hz), 8.21(1H,



d, J=4.2Hz), 9.02(1H, d, J=4.2Hz), 9.32(1H, s),



9.77-9.80(1H, br), 10.16-10.20(1H, br),



10.49-10.52(1H, br) (DMSO-d6)


YA1568
3.18-3.24(3H, m), 3.40-3.59(13H, m),
433



4.02-4.06(2H, m), 4.51-4.55(1H, m),



7.03-7.11(3H, m), 7.52(2H, d, J=7.2Hz), 8.21(1H,



d, J=4.2Hz), 9.02(1H, d, J=4.2Hz), 9.18-9.22(1H,



br), 9.38(1H, s), 9.72-9.78(1H, br),



10.04-10.10(1H, br) (DMSO-d6)


YA1569
1.90-2.02(2H, m), 2.80-3.06(5H, m),
434



3.25-3.82(5H, m), 3.65(3H, s), 4.39(1H, m),



4.94(1H, m), 6.49(2H, d, J=8.4Hz), 6.96(1H, s),



7.25(2H, d, J=8.4Hz), 8.16(1H, dd, J=5.4, 0.9Hz),



8.99(1H, d, J=5.1Hz), 9.29(1H, s)



(DMSO-d6)


YA1570
1.15(6H, d, J=6.3Hz), 2.31(2H, dd, J=11.1Hz),
461



2.98-3.23(6H, m), 3.48-3.62(4H, m), 3.56(3H, s),



3.94(1H, dd, J=10.2, 2.1Hz), 6.94(2H, d, J=8.7Hz),



7.31(1H, s), 7.34(2H, d, J=8.7Hz), 8.16(1H,



dd, J=5.1, 1.2Hz), 8.86(1H, d, J=5.1Hz),



9.26(1H, s) (CDCl3)


YA1571
1.27(6H, d, J=6.0Hz), 2.43(2H, dd, J=11.1,
462



11.1Hz), 3.02(1H, dd, J=12.0, 10.5Hz),



3.17-3.23(3H, m), 3.45-3.61(4H, m), 3.56(3H, s),



3.81(1H, m), 3.95(1H, m), 6.92(2H, d, J=8.7Hz),



7.32(1H, s), 7.35(2H, d, J=8.7Hz), 8.17(1H, m),



8.86(1H, d, J=5.1Hz), 9.26(1H, d, J=1.2Hz)



(CDCl3)


YA1572
3.27-3.32(8H, m), 3.47(3H, s), 3.82-3.86(2H, m),
503



4.36-4.39(1H, m), 7.02(1H, s), 7.72(2H, d,



J=7.2Hz), 7.84(2H, d, J=7.2Hz), 7.96-8.04(4H,



m), 8.22(1H, d, J=4.2Hz), 9.01(1H, d, J=4.2Hz),



9.30(1H, s) (DMSO-d6)


YA1573
2.93-3.10(5H, m), 3.46(3H, s), 3.69-3.71(1H, m),
450



4.01-4.04(1H, m), 6.99(1H, s), 7.63(2H, d,



J=7.2Hz), 7.77(2H, d, J=7.2Hz), 7.88-7.95(4H,



m), 8.18(1H, d, J=4.2Hz), 8.99(1H, d, J=4.2Hz),



9.29(1H, s) (DMSO-d6)


YA1574
3.08(1H, dd, J=12.5, 10.4Hz), 3.24(3H, m),
509



3.59(3H, s), 3.66(2H, m), 4.09(1H, dd, J=10.4,



2.4Hz), 7.29(2H, d, J=8.3Hz), 7.33(1H, s),



7.54(2H, d, J=8.3Hz), 7.56(2H, d, J=8.3Hz),



7.59(2H, d, J=8.3Hz), 8.17(1H, d, J=4.9Hz),



8.86(1H, d, J=4.9Hz), 9.27(1H, s) (CDCl3)


YA1575
3.08(1H, dd, J=12.4, 10.0Hz), 3.25(3H, m),
493



3.59(3H, s), 3.67(2H, m), 4.11(1H, dd, J=10.0,



2.0Hz), 7.33(1H, s), 7.57(2H, d, J=8.0Hz),



7.63(2H, d, J=8.0Hz), 7.71(4H, s), 8.16(1H,



dd, J=5.2, 1.2Hz), 8.16(1H, dd, J=5.2, 1.2Hz),



8.86(1H, d, J=5.2Hz), 9.27(1H, d, J=1.2Hz)



(CDCl3)


YA1576
1.45(3H, t, J=7.0Hz), 3.08(1H, dd, J=12.5,
469



10.6Hz), 3.22(3H, m), 3.58(3H, s), 3.62(2H, m),



4.05(1H, m), 4.08(2H, q, J=7.0Hz), 6.98(2H, d,



J=8.0Hz), 7.32(1H, s), 7.49(2H, d, J=8.0Hz),



7.52(2H, d, J=8.0Hz), 7.58(2H, d, J=8.0Hz),



8.17(1H, d, J=5.3Hz), 8.86(1H, d, J=5.3Hz),



9.27(1H, s), (CDCl3)


YA1577
1.83(4H, m), 1.99(1H, m), 2.21(1H, m),
487



2.61(4H, m), 2.87(1H, m), 3.03(1H, dd, J=12.0,



10.0Hz), 3.20(4H, m), 3.33(1H, m), 3.42(1H, m),



3.49(1H, m), 3.56(3H, s), 3.61(2H, m), 3.90(1H,



dd, J=10.0, 2.0Hz), 6.55(2H, d, J=8.8Hz),



7.29(2H, d, J=8.8Hz), 7.30(1H, s), 8.16(1H, d,



J=5.2Hz), 8.85(1H, d, J=5.2Hz), 9.26(1H, s)



(CDCl3)


YA1578
3.09(1H, dd, J=12.4, 10.8Hz), 3.20(3H, m),
485



3.58(3H, s), 3.64(2H, m), 3.82(3H, s), 3.86(3H,



s), 4.05(1H, dd, J=10.4, 2.8Hz), 6.58(2H, m),



7.24(2H, m), 7.32(1H, s), 7.47(2H, d, J=8.4Hz),



7.53(2H, d, J=8.4Hz), 8.17(1H, dd, J=5.2,



1.2Hz), 8.86(1H, d, J=5.2Hz), 9.27(1H, d,



J=1.2Hz) (CDCl3)


YA1579
3.08(1H, dd, J=12.5, 10.6Hz), 3.23(3H, m),
485



3.59(3H, s), 3.66(2H, m), 3.93(3H, s), 3.96(3H,



s), 4.07(1H, dd, J=10.3, 2.2Hz), 6.95(1H, d,



J=8.3Hz), 7.11(1H, d, J=2.0Hz), 7.16(1H, dd,



J=8.3, 2.0Hz), 7.33(1H, s), 7.52(1H, d, J=8.1Hz),



7.59(1H, d, J=8.1Hz), 8.17(1H, dd, J=5.3,



1.2Hz), 8.85(1H, d, J=5.3Hz), 9.27(1H, d,



J=1.2Hz) (CDCl3)


YA1580
3.07(1H, dd, J=12.4, 10.4Hz), 3.23(3H, m),
459



3.59(3H, s), 3.65(2H, m), 4.08(1H, dd, J=10.4,



2.0Hz), 7.32(1H, s), 7.41(2H, d, J=8.4Hz),



7.52(2H, d, J=8.4Hz), 7.53(2H, d, J=8.4Hz),



7.58(2H, d, J=8.4Hz), 8.16(1H, d, J=4.8Hz),



8.86(1H, d, J=4.8Hz), 9.27(1H, s) (CDCl3)


YA1581
3.09(1H, dd, J=12.2, 11.0Hz), 3.24(3H, m),
493



3.59(3H, s), 3.66(2H, m), 4.10(1H, dd, J=10.4,



2.4Hz), 7.29(2H, m), 7.33(1H, s), 7.44(2H, d,



J=8.0Hz), 7.52(3H, m), 8.18(1H, dd, J=5.3, 1.0Hz),



8.87(1H, d, J=5.3Hz), 9.27(1H, d, J=1.0Hz)



(CDCl3)


YA1582
3.06(1H, dd, J=12.4, 10.4Hz), 3.25(3H, m),
493



3.58(3H, s), 3.65(2H, m), 4.09(1H, dd, J=10.0,



2.0Hz), 7.33(1H, s), 7.42(1H, dd, J=8.0, 2.0Hz),



7.56(5H, m), 7.68(1H, d, J=2.0Hz),



8.16(1H, dd, J=5.2, 1.2Hz), 8.85(1H, d, J=5.2Hz),



9.27(1H, d, J=1.2Hz) (CDCl3)


YA1583
3.06(1H, dd, J=12.3, 10.8Hz), 3.23(3H, m),
417



3.59(3H, s), 3.65(2H, m), 4.13(1H, dd, J=10.2,



2.2Hz), 7.33(1H, s), 8.14(1H, d, J=5.3Hz),



8.15(2H, d, J=8.4Hz), 8.78(1H, s), 8.86(1H, d,



J=5.3Hz), 9.27(1H, s) (CDCl3)


YA1584
1.37(6H, d, J=6.0Hz), 3.07(1H, dd, J=12.6,
483



10.8Hz), 3.20-3.26(3H, m), 3.58(3H, s),



3.65-3.68(2H, m), 4.07(1H, m), 4.59(1H, m),



6.98(2H, d, J=8.7Hz), 7.48(1H, s),



7.50-7.61(6H, m), 8.17(1H, d, J=4.8Hz),



8.86(1H, d, J=5.1Hz), 9.26(1H, d, J=1.2Hz)



(CDCl3)


YA1585
0.99(3H, t, J=7.5Hz), 1.47-1.82(4H, m),
497



3.07(1H, dd, J=12.3, 10.5Hz), 3.22-3.27(3H, m),



3.58(3H, s), 3.62-3.65(2H, m), 4.03(2H, t,



J=6.3Hz), 4.04(1H, m), 6.98(2H, d, J=8.7Hz),



7.48(1H, s), 7.50-7.59(6H, m), 8.17(1H, dd,



J=5.1, 1.2Hz), 8.86(1H, d, J=5.1Hz), 9.26(1H, d,



J=1.2Hz) (CDCl3)


YA1586
1.28(1H, br.s), 2.51(3H, s), 3.07(1H, dd, J=10.8,
470



12.6Hz), 3.21-3.28(3H, m), 3.58(3H, s), 3.64(2H,



m), 4.08(1H, dd, J=2.5, 19.5Hz), 7.34(2H, d,



J=7.8Hz), 7.45-7.67(7H, m), 8.17(1H, d,



J=5.4Hz), 8.86(1H, d, J=5.1Hz), 9.27(1H, d,



J=1.2Hz) (CDCl3)


YA1587
1.86(1H, br.s), 2.40(3H, s), 3.07(1H, dd, J=10.8,
438



12.6Hz), 3.20-3.27(2H, m), 3.58(3H, s),



3.62-3.68(3H, m), 4.06(1H, dd, J=2.5, 19.5Hz),



7.24-7.27(2H, m), 7.49-7.52(5H, m), 7.60(2H, d,



J=8.2Hz), 8.17(1H, d, J=5.4Hz), 8.85(1H, d,



J=5.2Hz), 9.27(1H, s) (CDCl3)


YA1588
1.29(6H, s), 1.85(1H, br.s), 2.94-2.96(1H, m),
466



3.08(1H, dd, J=10.8, 12.6Hz), 3.21-3.27(3H, m),



3.59(3H, s), 3.65(2H, m), 4.07(1H, dd, J=2.5,



19.5Hz), 7.28-7.62(9H, m), 8.17(1H, dd, J=1.2,



5.7Hz), 8.86(1H, d, J=5.1Hz), 9.27(1H, d,



J=1.2Hz) (CDCl3)


YA1589
1.72(1H, br.s), 3.10(1H, m), 3.21-3.24(3H, m),
439



3.58(3H, s), 3.58-3.73(4H, m), 4.09(1H, dd,



J=2.5, 19.5Hz), 6.75(2H, dd, J=2.1, 6.6Hz),



7.23-7.57(7H, m), 8.16(1H, d, J=5.4Hz), 8.86(1H,



d, J=5.1Hz), 9.27(1H, d, J=1.2Hz) (CDCl3)


YA1590
2.79(1H, dd, J=10.5, 12.6Hz), 3.20-3.40(3H,
427



m), 3.50-3.80(5H, m), 4.45(1H, dd, J=3.0, 10.2Hz),



7.10-7.20(1H, m), 7.30-7.40(2H, m),



7.58(1H, dd, J=0.9, 7.8Hz), 7.73(1H, dd, J=1.5,



7.8Hz), 8.19(1H, dd, J=0.9, 4.8Hz), 8.85(1H, d,



J=5.1Hz), 9.26(1H, d, J=0.9Hz) (CDCl3)


YB013
1.31-1.46(1H, m), 1.60-1.96(3H, m),
378



2.17-2.30(1H, m), 2.89-3.02(2H, m), 3.41(3H, s),



3.61(1H, d, J=12.4Hz), 3.80(1H, d, J=13.5Hz),



3.90-4.01(2H, m), 6.89-7.01(3H, m), 6.96(1H, s),



7.27-7.32(2H, m), 8.18(1H, d, J=4.4Hz),



8.96(1H, d, J=5.0Hz), 9.28(1H, s) (DMSO-d6)


YB014
1.33-1.49(1H, m), 1.60-1.93(3H, m),
406



2.20-2.32(1H, m), 2.89-3.04(2H, m), 3.41(3H, s),



3.63(1H, d, J=13.3Hz), 3.82(1H, d, J=11.1Hz),



4.22-4.37(2H, m), 6.95(1H, s), 7.51-7.56(2H, m),



7.65-7.70(1H, m), 8.00-8.03(2H, m), 8.17(1H, dd,



J=1.1, 5.1Hz), 8.87(1H, d, J=5.1Hz), 9.28(1H, d,



J=1.0Hz) (DMSO-d6)


YB048
(CDCl3): 1.93-2.07(3H, m), 2.38(1H, m),
389



3.09(1H, m), 3.46(1H, m), 3.57(3H, s),



3.61-3.70(2H, m), 4.05(1H, m), 7.26-7.34(2H, m),



7.59-7.61(2H, m), 7.76(1H, m), 8.16(1H, m),



8.83(1H, m), 9.27(1H, s).


YB049
(CDCl3): 1.92-2.08(3H, m), 2.36(1H, m),
407



3.11(1H, m), 3.44(1H, dd, J=12.9, 10.8Hz),



3.58(3H, s), 3.61-3.70(2H, m), 4.06(1H, m),



7.11(1H, m), 7.28-7.33(2H, m), 7.70(1H, dd,



J=8.7, 4.8Hz), 8.15(1H, m), 8.86(1H, d,



J=5.4Hz), 9.28(1H, s).


YB050
1.93-2.11(3H, m), 2.33-2.45(1H, m),
389



3.08-3.16(1H, m), 3.46(1H, dd, J=11.4, 12.9Hz),



3.59(3H, s), 3.62-3.71(2H, m), 4.06(1H, d,



J=12.6Hz), 7.32-7.37(1H, m), 7.32(1H, s),



7.57-7.64(2H, m), 7.75(1H, d, J=8.1Hz),



8.16(1H, dd, J=1.2, 5.4Hz), 8.84(1H, d, J=4.8Hz),



9.28(1H, d, J=0.9Hz) (CDCl3)


YB051
1.91-2.11(3H, m), 2.35-2.43(1H, m),
389



3.08-3.16(1H, m), 3.42-3.50(1H, m), 3.59(3H, s),



3.62-3.71(2H, m), 4.05(1H, d, J=11.1Hz),



7.32(1H, s), 7.33-7.37(1H, m), 7.57-7.65(2H, m),



7.75(1H, d, J=7.8Hz), 8.16(1H, d, J=5.7Hz),



8.84(1H, d, J=5.4Hz), 9.28(1H, d, J=1.2Hz)



(CDCl3)


YB130
1.78-1.96(4H, m), 2.73-2.90(1H, m),
366



3.02-3.09(2H, m), 3.46(3H, s), 3.84(2H, d,



J=12.6Hz), 6.98(1H, s), 7.11-7.17(2H, m),



7.33-7.38(2H, m), 8.25(1H, d, J=5.1Hz),



9.01(1H, d, J=4.8Hz), 9.30(1H, s) (DMSO-d6)


YB157
1.90-2.05(2H, m), 2.18-2.35(2H, m),
406



2.92-3.09(1H, m), 3.10-3.23(2H, m), 3.58(3H, s),



3.72-3.83(2H, m), 6.95-7.07(1H, m),



7.22(1H, dd, J=2.2, 9.0Hz), 7.34(1H, s),



7.46(1H, s), 7.48-7.55(1H, m),



8.20(1H, d, J=5.3Hz), 8.88(1H, d, J=5.2Hz),



9.29(1H, s) (CDCl3)


YB158
1.91-2.04(2H, m), 2.23(2H, d, J=8.9Hz), 2.44(3H,
402



s), 2.97-3.11(1H, m), 3.16(2H, dd, J=11.1,



12.4Hz), 3.58(3H, s), 3.77(2H, d, J=13.0Hz),



7.12(1H, d, J=8.5Hz), 7.36-7.41(4H, m), 8.20(1H,



d, J=5.3Hz), 8.87(1H, d, J=4.8Hz), 9.28(1H, s)



(CDCl3)


YB159
1.93-2.05(2H, m), 2.23(2H, d, J=12.6Hz),
422



3.19(3H, m), 3.58(3H, s), 3.81(2H, d, J=13.2Hz),



7.12-7.16(1H, m), 7.26(1H, s), 7.34(1H, s),



7.56(1H, dd, J=2.4, 8.7Hz), 7.77-7.76(1H, m),



8.20(1H, dd, J=1.2, 5.1Hz), 8.87(1H, d,



J=5.1Hz), 9.29(1H, s) (CDCl3)


YB160
2.01-2.22(5H, m), 3.20(2H, dd, J=1.4, 11.7Hz),
407



3.47(3H, s), 3.84(2H, d, J=13.2Hz), 6.99(1H, s),



7.32(1H, m), 7.72(1H, dd, J=2.1, 9.0Hz),



8.09(1H, dd, J=2.7, 9.1Hz), 8.27(1H, m),



9.01(1H, d, J=5.1Hz), 9.31(1H, d, J=1.5Hz)



(DMSO-d6)


YB162
2.13-2.43(4H, m), 3.10-3.38(3H, m), 3.57(3H, s),
389



3.65-3.83(2H, m), 7.30-7.40(3H, m),



7.45-7.59(1H, m), 7.62-7.80(1H, m),



8.10-8.22(1H, m), 8.88(1H, d, J=5.1Hz),



9.28(1H, s) (CDCl3)


YB193
2.22-2.39(4H, m), 3.21-3.35(2H, m), 3.48(3H, s),
373



3.90(2H, d, J=13.5Hz), 7.03(1H, s),



7.38-7.43(1H, m), 7.46-7.51(2H, m),



7.59-7.66(2H, m), 8.28(1H, d, J=5.0Hz),



9.01(1H, d, J=5.0Hz), 9.30(1H, s) (DMSO-d6)


YB251
2.01-2.22(5H, m), 3.20(2H, dd, J=11.4, 11.7Hz),
406



3.47(3H, s), 3.82(2H, d, J=13.2Hz), 7.32(1H, m),



6.70(1H, s), 7.72(1H, dd, J=2.1, 9.0Hz), 8.09(1H,



dd, J=2.7, 9.1Hz), 8.27(1H, m), 9.01(1H, d,



J=5.1Hz), 9.31(1H, d, J=1.5Hz) (DMSO-d6)


YB252
1.64(2H, m), 2.23(2H, d, J=8.9Hz), 2.44(3H, s),
401



2.97-3.11(1H, m), 3.16(2H, dd, J=11.1, 11.4Hz),



3.58(3H, s), 3.77(2H, d, J=13.0Hz) 7.12(1H, d,



J=8.5Hz), 7.36-7.41(4H, m), 8.20(1H, d,



J=5.3Hz), 8.87(1H, d, J=4.8Hz), 9.28(1H,



s) (CDCl3)


YB253
1.93-2.05(2H, m), 2.23(2H, d, J=12.6Hz),
421



3.19(3H, m), 3.58(3H, s), 3.81(2H, d, J=13.2Hz),



7.12-7.16(1H, m), 7.26(1H, s) 7.34(1H, s),



7.56(1H, dd, J=2.4, 8.7Hz), 7.11-7.76(1H, m),



8.20(1H, dd, J=1.2, 5.1Hz), 8.87(1H, d,



J=5.1Hz), 9.29(1H, s) (CDCl3)


YB254
1.72-1.94(8H, m), 2.52(4H, m), 2.97-3.05(3H,
431



m), 3.56(3H, s), 3.61(2H, s), 3.67-3.73(2H, m),



7.21-7.34(4H, m), 8.17(1H, d, J=5.4Hz),



8.86(1H, d, J=5.1Hz), 9.27(1H, s) (CDCl3)


YB255
1.78(1H, m), 1.89(3H, m), 1.96(3H, m),
444



2.13(1H, d, J=13.6Hz), 3.46(2H, m), 3.56(3H, s),



3.66(2H, t, J=6.8Hz), 3.73(2H, m), 7.30(2H, d,



J=8.0Hz), 7.31(1H, s), 7.52(2H, d, J=5.2Hz),



8.15(1H, d, J=5.2Hz), 8.86(1H, d, J=5.2Hz),



9.27(1H, s)


YB256
1.46-1.73(9H, m), 2.01(2H, d, J=12.1Hz),
354



2.56(4H, t, J=5.0Hz), 2.94(2H, td, J=1.3,



12.7Hz), 3.52(3H, s), 3.70(2H, d, J=13.8Hz),



7.27(1H, s), 8.18(1H, dd, J=1.3, 5.3Hz), 8.86(1H,



d, J=5.3Hz), 9.27(1H, d, J=1.3Hz) (CDCl3)


YB257
1.81-1.88(4H, m), 2.80(1H, m), 2.99-3.08(2H, m),
425



3.46(3H, s), 3.82-3.86(2H, m), 6.98(1H, s),



7.26-7.43(3H, m), 7.53(1H, s), 8.26(1H, d,



J=4.8Hz), 9.01(1H, d, J=4.8Hz), 9.30(1H, s)



(DMSO-d6)


YB258
1.80-1.90(4H, m), 2.83(1H, m), 2.99-3.08(2H, m),
425



3.46(3H, s), 3.81-3.86(2H, m), 6.98(1H, s),



7.26-7.43(3H, m), 7.53(1H, s), 8.26(1H, d,



J=4.8Hz), 9.01(1H, d, J=4.8Hz), 9.30(1H, s)



(DMSO-d6)


YB259
1.76-1.96(8H, m), 2.67(1H, m), 2.99-3.07(2H, m),
417



3.16-3.21(4H, m), 3.45(3H, s), 3.79-3.84(2H, m),



6.49(2H, d, J=8.4Hz) 6.97(1H, s), 7.09(2H, d,



J=8.4Hz), 8.24(1H, d, J=5.1Hz), 9.01(1H, d,



J=5.1Hz), 9.30(1H, s) (DMSO-d6)


YB260
1.87-1.99(8H, m), 2.72(1H, m), 2.99-3.09(2H, m),
417



3.19-3.23(4H, m), 3.46(3H, s), 3.80-3.85(2H, m),



6.38(1H, d, J=7.8Hz) 6.44(1H, s), 6.53(1H, d,



J=7.8Hz), 6.98(1H, s), 7.09(1H, dd, J=7.8,



7.8Hz), 8.25(1H, d, J=5.1Hz), 9.01(1H, d,



J=5.1Hz), 9.30(1H, s) (DMSO-d6)


YB261
1.48-1.58(2H, m), 2.00-2.07(2H, m), 2.71(6H, s),
406



3.07-3.14(2H, m), 3.34-3.36(1H, m), 3.48(3H, s),



3.69-3.73(2H, m), 4.87(1H, d, J=8.2Hz),



6.56-6.66(4H, m), 6.96(1H, s), 8.24(1H, d,



J=4.2Hz), 9.00(1H, d, J=4.2Hz), 9.30(1H,



s) (DMSO-d6)


YB262
1.51-1.62(2H, m), 2.02-2.08(2H, m),
393



3.10-3.18(2H, m), 3.42(3H, s), 3.46-3.50(1H, m),



3.67(3H, s), 3.69-3.73(2H, m), 5.56(1H, d,



J=8.2Hz), 6.10-6.24(3H, m), 6.94-6.99(2H, m),



8.24(1H, d, J=4.2Hz), 9.00(1H, d, J=4.2Hz),



9.29(1H, s) (DMSO-d6)


YB263
1.48-1.58(2H, m), 2.01-2.08(2H, m),
393



3.08-3.17(2H, m), 3.40(3H, s), 3.41-3.43(1H, m),



3.63(3H, s), 3.69-3.73(2H, m), 5.09(1H, d,



J=8.2Hz), 6.59(2H, d, J=7.2Hz), 6.72(2H, d,



J=7.2Hz), 6.96(1H, s), 8.24(1H, d, J=4.2Hz),



9.01(1H, d, J=4.2Hz), 9.29(1H, s) (DMSO-d6)


YB264
1.58-1.69(2H, m), 2.04-2.08(2H, m),
393



3.08-3.15(2H, m), 3.42(3H, s), 3.55-3.83(6H, m),



4.57(1H, d, J=8.2Hz), 6.53-6.90(4H, m), 7.03(1H,



s), 8.25(1H, d, J=4.2Hz), 9.00(1H, d, J=4.2Hz),



9.30(1H, s) (DMSO-d6)


YB265
1.66-1.87(3H, m), 1.91-1.99(1H, m),
426



2.93-3.08(3H, m), 3.43(3H, s), 3.72-3.78(2H, m),



6.97(1H, s), 7.34(2H, d, J=5.7Hz), 7.54(2H, d,



J=5.4Hz), 8.18(1H, dd, J=5.4, 1.2Hz), 8.99(1H,



d, J=5.1Hz), 9.29(1H, d, J=0.9Hz) (DMSO)


YB266
1.71-1.91(4H, m), 2.41-2.45(2H, m),
476



2.53-2.56(4H, m), 2.93-3.00(3H, m),



3.08-3.10(4H, m), 3.43(3H, s), 3.50-3.54(2H, m),



3.67-3.71(2H, m), 4.42-4.46(1H, m), 6.90(2H, d,



J=7.2Hz), 6.96(1H, s), 7.19(2H, d, J=7.2Hz),



8.17(1H, dd, J=1.2, 4.2Hz), 8.99(1H, d,



J=4.2Hz), 9.29(1H, d, J=1.2Hz) (DMSO-d6)


YB267
1.70-1.94(4H, m), 2.86(6H, s), 2.89-2.90(3H, m),
391



3.43(3H, s), 3.66-3.77(2H, m), 6.71(2H, d,



J=7.2Hz), 6.96(1H, s), 7.15(2H, d, J=7.2Hz),



8.17(1H, d, J=4.2Hz), 8.99(1H, d, J=4.2Hz),



9.28(1H, s) (DMSO-d6)


YB268
1.72-1.84(4H, m), 2.89-3.08(7H, m), 3.43(3H, s),
433



3.67-3.77(6H, m), 6.90-6.96(3H, m), 7.21(2H, d,



J=7.2Hz), 8.17(1H, d, J=4.2Hz), 8.99(1H, d,



J=4.2Hz), 9.29(1H, s) (DMSO-d6)


YB269
1.51-1.83(10H, m), 2.87-3.00(3H, m),
431



3.07-3.10(4H, m), 3.43(3H, s), 3/68-3.77(2H, m),



6.89(2H, d, J=7.2Hz), 6.96(1H, s), 7.17(2H, d,



J=7.2Hz), 8.18(1H, d, J=4.2Hz), 8.99(1H, d,



J=4.2Hz), 9.29(1H, s) (DMSO-d6)


YB270
1.72-1.90(4H, m), 2.21(3H, s), 2.42-2.45(4H, m),
446



2.87-2.97(3H, m), 3.08-3.10(4H, m), 3.43(3H, s),



3.67-3.77(2H, m), 6.90(2H, d, J=7.2Hz), 6.96(1H,



s), 7.19(2H, d, J=7.2Hz), 8.17(1H, d, J=4.2Hz),



8.98(1H, d, J=4.2Hz), 9.29(1H, s) (DMSO-d6)


YB271
1.63-1.95(6H, m), 2.04-2.08(2H, m),
474



2.61-2.65(2H, m), 2.69(6H, s), 2.86-3.00(3H, m),



3.13-3.16(1H, m), 3.43(3H, s), 3.67-3.81(4H, m)



6.92-6.96(3H, m), 7.20(2H, d, J=7.2Hz), 8.17(1H,



d, J=4.2Hz), 9.00(1H, d, J=4.2Hz), 9.29(1H,



s) (DMSO-d6)


YB272
1.72-1.83(4H, m), 2.89-3.09(7H, m), 3.42(3H, s),
566



3.54-3.57(4H, m), 3.67-3.77(2H, m), 5.11(2H, s),



6.91-6.96(3H, m), 7.21(2H, d, J=7.2Hz),



7.26-7.44(5H, m), 8.17(1H, d, J=4.2Hz), 8.99(1H,



d, J=4.2Hz), 9.29(1H, s) (DMSO-d6)


YB273
1.57-1.63(2H, m), 1.82-1.89(2H, m),
370



2.51-2.98(13H, m), 3.41(3H, s), 3.76-3.80(3H,



m), 6.70(1H, s), 8.22(1H, d, J=4.2Hz), 9.01(1H,



d, J=4.2Hz), 9.30(1H, s) (DMSO-d6)


YB274
1.52-1.63(2H, m), 1.84-1.90(2H, m),
400



2.36-2.42(11H, m), 2.86-2.94(2H, m), 3.40(3H,



s), 3.49-3.53(2H, m), 3.73-3.77(2H, m),



4.40-4.43(1H, m), 6.96(1H, s), 8.22(1H, d,



J=4.2Hz), 9.01(1H, d, J=4.2Hz), 9.30(1H,



s) (DMSO-d6)


YB275
1.72-1.92(4H, m), 2.80-3.02(11H, m),
432



3.28-3.30(1H, m), 3.43(3H, s), 6.88(2H, d,



J=7.2Hz), 6.96(1H, s), 7.18(2H, d, J=7.2Hz),



8.18(1H, d, J=4.2Hz), 8.99(1H, d, J=4.2Hz),



9.29(1H, s) (DMSO-d6)


YB276
1.06-1.38(5H, m), 1.61-1.92(9H, m),
445



2.77-2.91(3H, m), 3.03-3.12(1H, m), 3.42(3H, s),



3.64-3.75(2H, m), 5.27(1H, d, J=8.2Hz), 6.52(2H,



d, J=7.2Hz), 6.96(1H, s), 7.02(2H, d, J=7.2Hz),



8.17(1H, d, J=4.2Hz), 8.99(1H, d, J=4.2Hz),



9.28(1H, s) (DMSO-d6)


YB277
1.76-1.97(4H, m), 2.97-3.10(5H, m), 3.47(3H, s),
465



3.73-3.76(2H, m), 3.88-3.93(2H, m), 6.71(1H, dd,



J=7.2, 7.3Hz), 6.96-7.34(8H, m), 8.19(1H, d,



J=4.2Hz), 9.00(1H, d, J=4.2Hz), 9.29(1H,



s) (DMSO-d6)


YB278
1.10-1.15(1H, m), 1.32-1.47(4H, m),
459



1.64-1.82(9H, m), 2.69(3H, s), 2.82-2.97(3H, m),



3.42(3H, s), 3.54-3.75(3H, m), 6.73(2H, d,



J=7.2Hz), 6.95(1H, s), 7.13(2H, d, J=7.2Hz),



8.16(1H, d, J=4.2Hz), 8.98(1H, d, J=4.2Hz),



9.28(1H, s) (DMSO-d6)









Test Example
Inhibitory Activity of the Medicament of the Present Invention against P-GS1 Phosphorylation by Bovine Cerebral TPK1

A mixture containing 100 mM MES-sodium hydroxide (pH 6.5), 1 mM magnesium acetate, 0.5 mM EGTA, 5 mM β-mercaptoethanol, 0.02% Tween 20, 10% glycerol, 12 μg/ml P-GS1, 41.7 μM [γ-32P] ATP (68 kBq/ml), bovine cerebral TPK1 and a compound shown in Table (a final mixture contained 1.7% DMSO deriving from a solution of a test compound prepared in the presence of 10% DMSO) was used as a reaction system. The phosphorylation was started by adding ATP, and the reaction was conducted at 25° C. for 2 hours, and then stopped by adding 21% perchloric acid on ice cooling. The reaction mixture was centrifuged at 12,000 rpm for 5 minutes and adsorbed on P81 paper (Whatmann), and then the paper was washed four times with 75 mM phosphoric acid, three times with water and once with acetone. The paper was dried, and the residual radioactivity was measured using a liquid scintillation counter. The results are shown in the table below. The test compound markedly inhibited the P-GS1 phosphorylation by TPK1. The results strongly suggest that the medicaments of the present invention inhibit the TPK1 activity, thereby suppress the A β neurotoxicity and the PHF formation, and that the medicaments of the present invention are effective for preventive and/or therapeutic treatment of Alzheimer disease and the above-mentioned diseases.












TABLE 6







Compound No.
IC50









XA361
0.018 μM



XB80
 0.23 μM



YA0864
0.216 μM



YB257
0.014 μM










Formulation Example

(1) Tablets


The ingredients below were mixed by an ordinary method and compressed by using a conventional apparatus.



















Compound of Example 1
30
mg



Crystalline cellulose
60
mg



Corn starch
100
mg



Lactose
200
mg



Magnesium stearate
4
mg











(2) Soft Capsules


The ingredients below were mixed by an ordinary method and filled in soft capsules.



















Compound of Example 1
30
mg



Olive oil
300
mg



Lecithin
20
mg










INDUSTRIAL APPLICABILITY

The compounds of the present invention have TPK1 inhibitory activity and are useful as an active ingredient of a medicament for preventive and/or therapeutic treatment of diseases caused by abnormal advance of TPK1 such as neurodegenerative diseases (e.g. Alzheimer disease) and the above-mentioned diseases.

Claims
  • 1. A pyrimidone derivative represented by formula (I) or a salt thereof:
  • 2. The pyrimidone derivative or the salt thereof according to claim 1 having the following fonnula(II)
  • 3. The pyrimidone derivative or the salt thereof according to claim 2, wherein R is a C1-C3 alkyl group.
  • 4. The pyrimidone derivative or the salt thereof according to claim 3, wherein R is methyl group or ethyl group; Y is in 3-, 4- or 5-position of the piperazine ring or the piperidine ring; p+q is 1; and r is an integer of 0 to 3.
  • 5. The pyrimidone derivative or the salt thereof according to claim 4, wherein X is a C1-C8 alkyl group which may be substituted or a C6-C10 aryl ring which may be substituted; Y is a C1-C6 alkyl group; p is 1; q is 0; r is an integer of 0 to 3; and Z is N or CH.
  • 6. The pyrimidone derivative or the salt thereof according to claim 5, wherein X is a benzene ring which may be substituted, a benzyl group which may be substituted; Y is a methyl group; Z is N and r is 0 or 1.
  • 7. The pyrimidone derivative or the salt thereof according to claim 4, wherein X is a benzene ring which may be substituted, or a benzyl group which may be substituted; Y is a methyl group which may be substituted; Z is N and p is 0.
  • 8. The pyrimidone derivative or the salt thereof according to claim 4, wherein X is a C1-C8 alkyl group substituted by a benzene ring which may be substituted or a benzene ring which may be substituted; Y is a hydroxy group; Z is CH or C-Y and r is 0 or 1.
  • 9. The pyrimidone derivative or the salt thereof according to claim 8, wherein X is a benzyl group which may be substituted or a benzene ring which may be substituted; Y is a hydroxy group; Z is CH or C-Y and r is 0 or 1.
  • 10. A pyrimidone derivative which is selected from the group consisting of: 2-(3-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one; (S)-2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Ethoxyphenyl)piperazin-1-yl)-13-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(5-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-3-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(S)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-13-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Chloro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-2-methylphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Fluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(5-Bromo-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Bromo-4-fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Chloro-6-fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,4-Difluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,6-Difluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,6-Dichlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,5-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,6-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,4-Difluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(1034)2-(3-(5-Cyano-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Cyano-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(1-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,3-Dihydrobenzofuran-7-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(S)-2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(Pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-methoxy-5-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(Phenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Fluorophenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(2-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(Morpholin-4-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Benzylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Benzoylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-(1,2-Benzisothiazol-3-yl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Methyl-3-phenylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(S)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Acetyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Benzyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-Benzyl-3-(ethoxycarbonyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(4-methyl-3-(1-naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(5,5-Dimethyl-3-(2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-Phenylpiperidin-1-yl)-13-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Chlorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Bromophenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2-Methoxyphenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(4-((Pyrrolidin-1-yl)methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(S)-2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-Hydroxy-3-phenylpiperidin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-Phenylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(3-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Fluorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(3-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Chlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(3-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Bromophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(3-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Cyanophenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(3-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Ethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(6-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(5-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(S)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-Fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Chloro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(5-Bromo-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2,6-Dichlorophenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(2,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one;2-(3-(3,4-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2,5-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2,6-Dimethoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2,4-Difluoro-6-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(1-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-Naphthyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2,3-Dihydrobenzofuran-7-yl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(Benzofuran-2-yl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(Pyrrolidin-1-yl-methyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(Pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(2-methoxy-5-(pyrrolidin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(Phenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Fluorophenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(2-Methoxyphenyl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(Morpholin-4-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(S)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(R)-2-(3-(4-Fluoro-2-methoxyphenyl)-4-methylpiperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-Acetyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-Benzyl-3-(4-fluoro-2-methoxyphenyl)piperazin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-(4-Fluorophenyl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-Cyano-4-phenylpiperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-(6-Fluorobenofiuran-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(Benzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(S)-2-(3-(Benzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;(R)-2-(3-(Benzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(3-(6-Fluorobenzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-(6-Fluorobenzoisoxazol-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one;2-(4-(5-Methylbenzofuran-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one; and2-(4-(6-Fluorobenzothiophene-3-yl)piperidin-1-yl)-3-methyl-6-(4-pyrimidyl)-3H-pyrimidin-4-one
  • 11. A medicament composition comprising as an active ingredient at least one pyrimidone derivative represented by formula (I) or a salt thereof according to claim 1.
  • 12. A method for therapeutic treatment of a disease selected from Alzheimer disease and non-insulin dependent diabetes comprising administering to a patient a therapeutically effective amount of the composition according to claim 11.
Priority Claims (2)
Number Date Country Kind
2003-126021 Mar 2003 JP national
2003-126022 Mar 2003 JP national
PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/JP2004/004320 3/26/2004 WO 00 5/31/2006
Publishing Document Publishing Date Country Kind
WO2004/085408 10/7/2004 WO A
US Referenced Citations (15)
Number Name Date Kind
4166180 Kato et al. Aug 1979 A
4507302 Fast et al. Mar 1985 A
4619933 Stringfellow et al. Oct 1986 A
4725600 Takaya et al. Feb 1988 A
5612286 Mayer et al. Mar 1997 A
6096753 Spohr et al. Aug 2000 A
6107301 Aldrich et al. Aug 2000 A
6410729 Spohr et al. Jun 2002 B1
6420385 Spohr et al. Jul 2002 B1
6586441 Borroni et al. Jul 2003 B2
6844335 Almario Garcia et al. Jan 2005 B2
20030187004 Almario Garcio et al. Oct 2003 A1
20050090490 Uehara et al. Apr 2005 A1
20050130967 Uehara et al. Jun 2005 A1
20050130998 Almario Garcia et al. Jun 2005 A1
Foreign Referenced Citations (23)
Number Date Country
0168262 Jan 1986 EP
0354179 Jul 1989 EP
1 136 482 Sep 2001 EP
1136482 Sep 2001 EP
218974 Aug 1995 HU
P0001698 Apr 2001 HU
49-035631 Apr 1974 JP
49-35632 Apr 1974 JP
49-035633 Apr 1974 JP
49-35634 Apr 1974 JP
52-071481 Jun 1977 JP
52-139085 Nov 1977 JP
6-239893 Aug 1994 JP
6-329551 Nov 1994 JP
9311231 Jun 1998 WO
9824780 Jun 1998 WO
9824782 Jun 1998 WO
0018758 Apr 2000 WO
0170728 Sep 2001 WO
0170729 Sep 2001 WO
03027080 Apr 2003 WO
03037888 May 2003 WO
2004055007 Jul 2004 WO
Related Publications (1)
Number Date Country
20060252768 A1 Nov 2006 US