Oxime derivatives, hydrazone derivatives and use thereof

This application is a 371 of PCT/JP97/03585 filed on Oct. 7, 1997.
TECHNICAL FIELD
The present invention relates to a novel oxime derivative and a novel hydrazone derivative as well as the use of the same.
BACKGROUND ART
While as oxime derivatives and hydrazone derivatives analogous to the present invention Japanese Patent Application Laid-Open Nos. 3-215464 and 7-309825, and WO 95/21153, WO 95/21154, WO 95/18789 and WO 96/11183 disclose compounds having fungicidal activities, a compound disclosed in the present invention is not included in these publications. In addition, none of these publications mentioned the tachykinin receptor antagonism of the compounds disclosed therein.
Tachykinin is a name which is used commonly in a group of the neuropeptides having 10 to 11 amino acids, and includes substance P, neurokinin A and neurokinin B which are known. Each of these substances binds to three receptors, namely NK1, NK2 and NK3, and is known to be involved in pain transmission, vasodilation, saliva secretion, increase in capillary vessel permeability, immunoregulation, nerve cell regulation and the like. Accordingly, a compound having a tachykinin receptor antagonistic effect is considered to have various biological activities, and each of EP 394989, EP 428434, EP 429366, EP 436334, EP 443132, EP 474561, EP 482 539, EP 499313, EP 512901, EP 512902, EP 514273, EP 514275, EP 515240, EP 517589, EP 520555, EP 522808, EP 528495, EP 532456, EP 533280, EP 536817, EP 545478, EP 559538, EP 585913, WO 90/05525, WO 90/05729, WO 91/09844, WO 91/18899, WO 92/01688, WO 92/06079, WO 92/12151, WO 95/15585, WO 92/19254, WO 92/20661, WO 92/20667, WO 93/00330, WO 93/00331, WO 93/01159, WO 93/01165, WO 93101169, WO 93/01170, WO 93/06099, WO 93/09116, WO 93/10073, WO 93/14084, WO 93/18023, WO 93/19064, WO 93/21155, WO 93/21181, WO 93/23380, WO 94/16697, WO 94/17045, WO 94/19323, WO 94/20500, WO 94/26740, WO 94/29309, WO 95/02595, WO 95/04040, WO 95/04042, WO 95/18124, WO 95/18129, WO 95/28389, WO 96/29326, WO 96/30367, Japanese Patent Application Laid-Open Nos. 8-239323, 8-295667, 8-2301849 and 8-5301871 discloses a compound having a tachykinin receptor antagonistic effect.
However, none of these publications describes an oxime derivative or a hydrazone derivative disclosed in the present invention.
DISCLOSURE OF INVENTION
An objective of the present invention is to provide a compound having a higher fungicidal effect and a higher tachykinin receptor antagonistic effect.
The present inventors made an effort to achieve the objective described above and finally found that a novel oxime derivative and a novel hydrazone derivative described below have a higher fungicidal effect and a higher tachykinin receptor antagonistic effect, whereby accomplishing the present invention.
Thus, the present invention is a compound represented by Formula (I): ##STR2## wherein R.sup.1 is an optionally substituted aryl, an optionally substituted allyl or an optionally substituted cycloalkyl; R.sup.2 is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R.sup.3 is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted alkylsulfonyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or an optionally substituted heterocyclic group; R.sup.4 and R.sup.5 are the same or different from each other and each is a hydrogen atom, an optionally substituted alkyl an optionally substituted cycloalkyl or an optionally substituted alkoxy, or R.sup.4 and R.sup.5 may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring or polycyclic ring; X and Y are the same or different from each other and each is an oxygen atom or an NR.sup.6 wherein R.sup.6 is a hydrogen atom, an optionally substituted alkyl, an optionally substituted aryl, an optionally substituted alkanoyl or an optionally substituted aroyl; Z is an oxygen atom or a sulfur atom; a wave-shaped line (.about.) represents the configuration of a E form or a Z form or a mixture thereof,
provided that when R.sup.2 is an optionally substituted benzyl, then the substituent is not a group represented by formula: ##STR3## wherein (R.sup.12).sub.2 is H.sub.2, .dbd.O, .dbd.CH.OH, .dbd.CHOCH.sub.3, .dbd.N.OH or .dbd.N.OCH.sub.3 ; and R.sup.13 represents an alkoxy or a monoalkylamino;
and a salt or a hydrate thereof, preferably a compound or a salt or a hydrate thereof described above wherein R.sup.1 is an aryl or an alkyl; R.sup.2 is an optionally substituted alkyl, alkenyl, alkynyl, aryl or heterocyclic group; R.sup.3 is an optionally substituted alkyl alkenyl, alkynyl, an optionally substituted aryl, an optionally substituted arylsulfonyl or heterocyclic group; R.sup.4 and R.sup.5 are the same or different from each other and each is a hydrogen atom, an alkyl or an alkoxy, or R.sup.4 and R.sup.5 may be taken together with their adjacent nitrogen atom to form an optionally substituted monocyclic ring; X and Y are the same or different from each other and each is an oxygen atom or a NR.sup.6 wherein R.sup.6 is a hydrogen atom, alkyl, aryl, alkanoyl or aroyl.
BEST MODE FOR CARRYING OUT THE INVENTION
In this specification, the term "lower" means a straight or branched chain group having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, unless otherwise specified.
The aryl in an optionally substituted aryl represented by R.sup.1 may be an aryl having 6 to 14 carbon atoms, such as phenyl, naphthyl (e.g., 1-naphthyl, 2-naphthyl) and the like.
The substituent on an optionally substituted aryl represented by R.sup.1 may for example be a lower alkyl (e.g., methyl, ethyl, propyl, butyl and the like), a lower alkenyl (e.g., vinyl, allyl, 2-butenyl and the like), a lower alkynyl (e.g., ethynyl, 2-propynyl 3-butynyl and the like), a cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl and the like), a cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl and the like), a halogenated lower alkyl (e.g., trifluoromethyl, trichloromethyl, difluoromethyl, chloromethyl, 2-bromoethyl, 1,2-dichloropropyl and the like), a halogen atom (e.g., fluorine atom, chlorine atom, bromine atom, iodine atom), nitro, cyano, a lower alkylthio (e.g., methylthio, ethylthio, propylthio and the like), --NR.sup.8 R.sup.9 wherein R.sup.8 and R.sup.9 are the same or different from each other and each is a hydrogen atom, an optionally substituted lower allyl (e.g., methyl ethyl, propyl, 2-chloroethyl, methoxymethyl, 2-ethoxyethyl, benzyl, 4-chlorobenzyl, 2-oxopropyl, methoxycarbonylmethyl, ethoxycarbonylmethyl carbamoylmethyl and the like), formyl, a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted aryl (e.g., phenyl, 2-chlorophenyl, 3-chlorophenyL 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 1-naphthyl, 2-naphthyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl and the like), an optionally substituted lower alkylsulfonyl (e.g., methanesulfonyl, ethanesulfonyl, trifluoromethanesulfonyl and the like), an optionally substituted arylsulfonyl (e.g., benzenesulfonyl, 4-chlorobenzenesulfonyl, 4-methylbenzenesulfonyl and the like); or alternatively R.sup.8 and R.sup.9 may be taken together to form a cyclic system such as pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine and the like, --OR.sup.10 wherein R.sup.10 is a hydrogen atom, a lower alkyl (e.g., methyl, ethyl, propyl and the like), a lower alkenyl (e.g., vinyl, allyl 2-butenyl and the like), a lower alkynyl (e.g., ethynyl 2-propynyl, 3-butynyl and the like), an optionally substituted aryl (e.g., phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-methoxyphenyl 3-methoxyphenyl 4-methoxyphenyl, 1-naphthyl, 2-naphthyl and the like), an alkoxyalkyl (e.g., methoxymethyl, ethoxymethyl, 2-methoxyethyl and the like), or a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkanoyl (e.g., acetyl, propionyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyL 4-methylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl and the like), a lower alkylsulfonyl (e.g., mesyl and the like), phenyl, a phenyl(lower)alkyl (e.g., benzyl, phenethyl and the like), a phenyl(lower)alkenyl (e.g., styryl, cinnamyl and the like) and the like. Each of these substituents may be in any possible position on the respective aryl group, and may occur one to four times.
The alkyl in an optionally substituted alkyl represented by R.sup.1 may be a straight or branched chain alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and is typically methyl, ethyl, propyl, isopropyl butyl, isobutyl, sec-butyl, tertbutyl and the like.
The substituent on an optionally substituted alkyl may for example be nitro, cyano, a halogen atom (e.g., fluorine atom, chlorine atom, bromine atom, iodine atom), a cycloalkyl (e.g., cyclopropyl cyclobutyl, cyclopentyl, cyclohexyl and the like), hydroxy, a lower alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), --NR.sup.8 R.sup.9 wherein R.sup.8 and R.sup.9 are defined as described above, a lower alkylthio (e.g., methylthio, ethylthio, propylthio and the like), a lower alkylsulfonyl (e.g., methanesulfonyl, ethanesulfonyl and the like), an optionally substituted aryl (similar to those exemplified as an optionally substituted aryl represented by R.sup.1 described above), an optionally substituted heterocyclic group (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, isoxazol-3-yl, isoxazol-5-yl, pyrrol-2-yl, pyrazol-3-yl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, imidazol-2-yl oxazol-2-yl, thiazol-2-yl and the like), .dbd.O, .dbd.NOR.sup.11 wherein R.sup.11 is the same or different from each other and a hydrogen atom, a lower alkyl (e.g., methyl, ethyl, propyl and the like), a lower alkenyl (e.g., allyl, 2-butenyl and the like), a lower alkynyl (e.g., 2-propynyL 3-butynyl and the like), or a lower alkanoyl (e.g., acetyl, propionyl and the like), an optionally substituted aroyl (e.g., benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-methoxybenzoyl 3-methoxybenzoyl, 4-methoxybenzoyl and the like), a lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl and the like), an optionally substituted arylsulfonyl (e.g., benzenesulfonyl, 4-chlorobenzenesulfonyl, 4-methylbenzenesulfonyl and the like) and the like.
The cycloalkyl in an optionally substituted cycloalkyl represented by R.sup.1 may be a cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms. Typically, cyclopropyl, cyclopentyl and cyclohexyl may be mentioned.
The substituent on an optionally substituted cycloalkyl represented by R.sup.1 may be similar to those exemplified as the substituent on an optionally substituted alkyl represented by R.sup.1 described above.
R.sup.1 is preferably methyl, ethyl, propyl, isopropyl, optionally substituted phenyl and the like.
Examples of an optionally substituted alkyl represented by R.sup.2 may be those exemplified as an optionally substituted alkyl represented by R.sup.1 described above.
Examples of an optionally substituted cycloalkyl represented by R.sup.2 may be those exemplified as an optionally substituted cycloalkyl represented by R.sup.1 described above.
The alkenyl in an optionally substituted alkenyl represented by R.sup.2 may be an alkenyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and is typically 1-propenyl, isopropenyl, allyl, 2-butenyl and the like.
The alkynyl in an optionally substituted alkynyl represented by R.sup.2 may be an alkynyl having 3 to 6 carbon atoms, preferably 3 to 4 carbon atoms, and is typically 2-propynyl, 3-butynyl and the like.
The alkyl in an optionally substituted alkylsulfonyl represented by R.sup.2 may be those exemplified as an alkyl represented by R.sup.1 described above.
The substituent on a substituted alkenyl, a substituted alkynyl and a substituted alkylsulfonyl represented by R.sup.2 may be similar to those exemplified as the substituent on a substituted alkyl represented by R.sup.1 described above.
Examples of an optionally substituted aryl represented by R.sup.2 may be those exemplified as an optionally substituted aryl represented by R.sup.1 described above.
Examples of an optionally substituted aryl on an optionally substituted arylsulfonyl represented by R.sup.2 may be those exemplified as an optionally substituted aryl represented by R.sup.1 described above.
An optionally substituted heterocyclic group represented by R.sup.2 includes a nonsubstituted heterocyclic group as well as a substituted heterocyclic group. Examples of these heterocyclic groups are a 5- to 7-membered heterocyclic group containing 1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfuir and oxygen atoms, and typically, pyridyl (e.g., pyridin-2-yl, pyridin-3-yL pyridin-4-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl), isoxazolyl (e.g., isoxazol-3-yl, isoxazol5-yl and the like), thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-4-yl and the like), pyridazinyl (e.g., pyridazin-3-yl, pyridazin-4-yl and the like), pyrrolyl (e.g., pyrrol-1-yl, pyrrol-2-yl and the like), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl and the like), furyl (e.g., furan-2-yl, furan-3-yl), thienyl (e.g., thiophen-2-yl, thiophen-3-yl), imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl and the like), oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl and the like), thiazolyl (e.g., thiazol-2-yl and the like), oxadiazolyl (e.g., 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-5-yl and the like), pyrazinyl (e.g., pyrazin-2-yl and the like), quinolyl (e.g., quinolin-2-yl and the like) and indolyl (e.g., indolin-1-yl, indolin-2-yl and the like) and the like.
Each of these heterocyclic groups may have a bond in any possible position.
The substituent on a substituted heterocyclic group represented by R.sup.2 may be similar to those exemplified as the substituent on a substituted aryl represented by R.sup.1 described above. Each of these substituents may be in any possible position on the respective heterocyclic group, and may occur one to three times.
R.sup.2 is preferably methyl, methoxymethyl, ethyl, allyl, cinnamyl, 2-propynyl 2-butynyl, 2-pyridyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted 2-pyridylmethyl, optionally substituted 3-pyxidylmethyl, optionally substituted 4-pyridylmethyl, optionally substituted 1-naphthyl, optionally substituted 2-naphthyl, optionally substituted 2-thenyl, optionally substituted 3-thenyl and the like. In the case R.sup.2 is an optionally substituted benzyl, the substituent is not a group represented by formula: ##STR4## wherein (R.sup.12).sub.2 is H.sub.2, .dbd.O, .dbd.CH.OH, .dbd.CHOCH.sub.3, .dbd.N.OH or .dbd.N.OCH.sub.3 ; and R.sup.13 represents an alkoxy or a monoalkylamino.
The alkoxy represented by R.sup.13 may be an alkoxy having 1 to 4 carbon atoms, and is typically methoxy, ethoxy, propoxy, butoxy and the like.
The monoalkylamino represented by R.sup.13 may be a monoalkylamino containing an alkyl having 1 to 4 carbon atoms, and is typically monomethylamino, monoethylamino and the like.
Examples of an optionally substituted alkyl represented by R.sup.3 may be those exemplified as an optionally substituted alkyl represented by R.sup.1 described above.
Examples of an optionally substituted cycloalkyl represented by R.sup.3 may be those exemplified as an optionally substituted cycloalkyl represented by R.sup.1 described above.
Examples of an optionally substituted alkenyl represented by R.sup.3 may be those exemplified as an optionally substituted alkenyl represented by R.sup.2 described above.
Examples of an optionally substituted alkvnyl represented by R.sup.3 may be those exemplified as an optionally substituted alkyi represented by R.sup.2 described above.
Examples of an optionally substituted alkylsulfonyl represented by R.sup.3 may be those exemplified as an optionally substituted alkylsulfonyl represented by R.sup.2 described above.
Examples of an optionally substituted aryl represented by R.sup.3 may be those exemplified as an optionally substituted aryl represented by R.sup.1 described above.
Examples of an optionally substituted arylsulfonyl represented by R.sup.3 may be those exemplified as an optionally substituted arylsulfonyl represented by R.sup.2 described above.
Examples of an optionally substituted heterocyclic group represented by R.sup.3 may be those exemplified as an optionally substituted heterocyclic group represented by R.sup.2 described above.
R.sup.3 is preferably methyl, ethyl, propyl, isopropyl, allyl, cinnamyl, 2-propynyl, 2-butynyl, 2-pyridyl, optionally substituted benzyl, optionally substituted 2-phenylethyl, optionally substituted 2-pyridylmethyl, optionally substituted 3-pyridylmethyl, optionally substituted 4-pyridylmethyl, optionally substituted benzenesulfonyl and the like.
Examples of an optionally substituted alkyl represented by each of R.sup.4 and R.sup.5 may be those exemplified as an optionally substituted alkyl represented by R.sup.1 described above.
Examples of an optionally substituted cycloalkyl represented by each of R.sup.4 and R.sup.5 may be those exemplified as an optionally substituted cycloalkyl represented by R.sup.1 described above.
Examples of the alkoxy in an optionally substituted alkoxy represented by each of R.sup.4 and R.sup.5 may for example be an alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and is typically, methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like.
Examples of the substituent on an optionally substituted alkoxy represented by each of R.sup.4 and R.sup.5 may be similar to those exemplified as the substituent on a substituted alkyl represented by R.sup.1 described above.
R.sup.4 and R.sup.5 may be the same or different from each other. Alternatively, R.sup.4 and R.sup.5 may be taken together to form an optionally substituted monocyclic ring or polycyclic ring. Such monocyclic ring or polycyclic ring means a 4- to 8-membered cyclic system formed together with the nitrogen atom to which the two substituents are bound and optionally containing a hetero atom (e.g., oxygen, nitrogen, sulfur and the like), as well as the polycyclic ring formed as a result of condensation of these rings with other rings. Examples of such monocyclic ring and polycyclic ring are pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine, hexamethyleneimine, oxazolane, diazepane, tetrahydroquinoline, tetrahydroisoquinoline and the like. The substituent on each of these cyclic systems may be those exemplified as the substituent on an optionally substituted alkyl represented by R.sup.1 described above, as well as an optionally substituted lower alkyl (e.g., methyl, ethyl, propyl, 2-chloroethyl, methoxymethyl 2-ethoxyethyl, benzyl, 4-chlorobenzyl, 2-oxopropyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, carbamoylmethyl and the like), formyl, a lower alkanoyl (e.g., acetyl, propionyl and the like) and the like. Each of these substituents may be in any possible position on the respective cyclic system, and may occur one to four times.
The group --NR.sup.4 R.sup.5 is preferably --NH.sub.2, --NHMe, --NMe.sub.2, --NEt.sub.2, --N(Me)Et, --N(OMe)Me, optionally substituted 1-pyrrolidinyl, optionally substituted piperidino, optionally substituted morpholino, optionally substituted 4-thiomorpholinyl, optionally substituted 1-piperazinyl, optionally substituted 2-oxazolanyl, optionally substituted diazepan-1-yl.
Examples of an optionally substituted alkyl represented by R.sup.6 may be those exemplified as an optionally substituted alkyl represented by R.sup.1 described above.
Examples of an optionally substituted aryl represented by R.sup.6 may be those exemplified as an optionally substituted aryl represented by R.sup.1 described above.
The optionally substituted alkanoyl represented by R.sup.6 may be an optionally substituted alkanoyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and is typically acetyl, propionyl, trifluoroacetyl and the like.
The optionally substituted aroyl represented by R.sup.6 may be an optionally substituted aroyl having 7 to 16 carbon atoms, preferably 7 to 12 carbon atoms, and is typically benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl and the like.
Preferred examples of X are an oxygen atom, --NH--, --N(Me)--, --N(Ph)-- and the like.
Preferred examples of Y are an oxygen atom, --NH--, --N(Me)--, --N(Et)--, --N(Ph)--, --N(Ac)--, --N(Bz)-- and the like.
Examples of an alkyl represented by R.sup.7 may be those exemplified as an alkyl represented by R.sup.1 described above.
R.sup.7 is preferably a hydrogen atom, methyl and ethyl.
While a compound according to the present invention occurs as any of the two isomers, i.e., an E form and a Z form, with respect to its imino moiety, the present invention encompasses these isomers as well as a mixture of these isomers in any ratio. Such isomerism is designated in the present invention using a wave-shaped line (.about.) in a formula.
A compound according to the present invention may also form a salt in its amino group when its hydrazone moiety or its primary to tertiary amino group is substituted, and such salt may be a mineral acid salt (e.g., hydrochlorides, sulfates, nitrates and the like) as well as an organic acid salt (e.g., acetates, maleates and the like).
A compound according to the present invention may be in a form of a hydrate.
Compound (I) according to the present invention (i.e., a compound represented by Formula (I); Hereinafter the same abbreviation may apply analogously to a compound represented by another formula) and Compound (II) may for example be produced via a synthetic route shown below.
Route 1 ##STR5## wherein each radical is defined as described above.
Thus, a compound according to the present invention represented by Formula (Ia) can be prepared by reacting a hydroxylamine derivative or a hydrazine derivative represented by Formula (IV) or its salt (e.g., hydrochloride, sulfate) with Compound (III) in a suitable solvent (a single solvent or a solvent mixture).
When a salt is employed, the reaction may be performed after neutralization with a base. Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like), metal acetates (sodium acetate, potassium acetate and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide and the like), pyridine and the like, and the amount to be used is 1 to 3 equivalents, relative to a salt of Compound an, preferably 1 to 2 equivalents.
In this reaction, Compound (V) can be used in an amount of 1 equivalent or more, relative to Compound (III), preferably 1 to 3 equivalents.
Examples of a solvent which can be employed are aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), alcohols (e.g., methanol ethanol, propanol and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), acetic acid, water as well as a mixture thereof.
The reaction temperature may be 0 to 160.degree. C., preferably 20 to 130.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 90 hours may be sufficient.
A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Compound (III) employed as a starting material in this reaction may be prepared by a method described in Reference Example 1 discussed later in this specification or an analogous method.
A hydroxylamine derivative or a hydrazine derivative represented by Formula (IV) is known per se, or, may be prepared by a known method similar to that described in Methoden der Organischen Chemie, Vol.X/1 and X/2 by Houben-Weyl.
Route 2 ##STR6## wherein L represents a halogen atom (e.g., chlorine atom, bromine atom and the like), an alkylsulfonyloxy (e.g., methylsulfonyloxy, ethylsulfonyloxy and the like) or an arylsulfonyloxy which may be substituted by a halogen atom or a lower alkyl (e.g., benzensulfonyloxy, p-toluenesulfonyloxy, m-toluenesulfonyloxy, o-toluenesulfonyloxy and the like), and other radicals are defined as described above.
Thus, a compound according to the present invention represented by Formula (Ia') can be prepared by reacting Compound (V) and Compound (VI) in the presence of a base in a suitable solvent (a single solvent or a solvent mixture).
In this reaction, Compound (VI) can be used in an amount of 1 equivalent or more, relative to Compound (V), preferably 1 to 2 equivalents.
Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal hydrides (e.g., sodium hydride, potassium hydride and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like) and the like, and the amount to be used is 1 equivalent or more, relative to Compound (V), preferably 1 to 2 equivalents.
Examples of a solvent which can be employed are N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), ketones (e.g., acetone, methylethylketone and the like), water as well as a mixture thereof.
The reaction temperature may be -30 to 150.degree. C., preferably -10 to 100.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 90 hours may be sufficient.
A desired Compound (Ia') thus obtained may be purified by a standard method e.g., column chromatography, recrystallization and the like).
Compound (V) employed as a starting material in this reaction may be repared by a method described in WO 96/11183 or an analogous method.
Route 3 ##STR7## wherein R.sup.7' represents an allyl and other radicals are defined as described above.
Thus, a compound according to the present invention represented by Formula (Ia) can be prepared by reacting Compound (IIa) and Compound (VII) in the presence or absence of a suitable solvent (a single solvent or a solvent mixture).
In this reaction, Compound (VII) can be used in an amount of 1 equivalent or more, relative to Compound (IIa), preferably 1 to 30 equivalents.
Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuiran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), nitrites (e.g., acetonitrile and the like), water as well as a mixture thereof.
The reaction temperature may be -30 to 160.degree. C., preferably -10 to 120.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 120 hours may be sufficient.
A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Compound (IIa) employed as a starting material in this reaction may be prepared via Route 4 and Route 5 shown below.
Route 4 ##STR8## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (IIa) can be prepared by reacting Compound (VII) and Compound (IV) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.
A desired Compound (IIa) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Compound (VIII) employed as a starting material in this reaction may be prepared by a method described in Reference Example 2 discussed later in this specification or an analogous method.
Route 5 ##STR9## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (IIa') can be prepared by reacting Compound (IX) and Compound (VI) in the presence of a base in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 2 described above.
A desired Compound (IIa') thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Compound (IX) employed as a starting material in this reaction may be prepared by a method described in W096/11183 or an analogous method.
Route 6 ##STR10## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (IIb) can be prepared by reacting an acid or a base with Compound (IIa) in a suitable solvent.
Example of an acid which may be employed are hydrochloric acid, hydrobromic acid, trifluoroacetic acid, p-toluenesulfonic acid and the like, and each may be used in an amount of 0.1 equivalent or more, relative to Compound (IIa), preferably 0.1 to 3 equivalents.
Examples of a base which may be employed are sodium hydroxide, potassium hydroxide, and the like, and each may be used in an amount of 1 equivalent or more, preferably 1 to 3 equivalents.
Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), water as well as a mixture thereof.
The reaction temperature may be 0 to 150.degree. C., preferably 20 to 100.degree. C. The reaction time is generally 15 minutes to 100 hours.
A desired Compound (IIb) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
A compound represented by Formula (II): ##STR11## wherein the radicals are defined as described above, consisting of Compound (IIa) and Compound (IIb) obtained in Scheme 4, Scheme 5 and Scheme 6 described above, is a novel compound, and encompassed in the present invention. ##STR12## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (Ia) can be prepared by reacting Compound (IIb) and Compound (VII) in the presence of a suitable condensing agent in a suitable solvent (a single solvent or a solvent mixture).
In this reaction, Compound (VII) may be used in an amount of 1 equivalent or more, relative to Compound (IIb), preferably 1 to 5 equivalents.
Examples of a condensing agent are N,N'-dicyclohexylcarbodiimide, 1,1'-carbonyldidazole, diphenylphosphoric acid azide, diethylphosphoric acid cyanide, ethyl chlorocarbonate, isopropyl chlorocarbonate and the like, and each may be used in an amount of 1 equivalent or more, relative to Compound (IIb) preferably 1 to 3 equivalents.
An organic base such as triethylamine, diisopropylethylamine, pyridine and the like, or an inorganic base such as sodium hydroxide, potassium hydroxide may be used in an amount of 1 to 5 equivalents or more, relative to Compound (IIb), preferably 1 to 2 equivalents.
Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol and the like), N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), nitrites (e.g., acetonitrile and the like) as well as a mixture thereof.
The reaction temperature may be -30 to 100.degree. C., preferably -20 to 80.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 120 hours may be sufficient.
A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Route 7 ##STR13## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (X) can be prepared by chlorinating Compound (IIb) in a suitable solvent (a single solvent or a solvent mixture).
Examples of a chlorinating agent are thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride, carbon tetrachloridetriphenylphosphine and the like, and each may be used in an amount of 1 to 5 equivalents, relative to Compound (IIb), preferably 1 to 2 equivalents.
A small amount of N,N-dimethylformamide (DMF) may be used as a reaction catalyst.
Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), nitrites (e.g., acetonitrile and the like) as well as a mixture thereof.
The reaction temperature may be -20 to 120.degree. C., preferably 0 to 100.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 60 hours may be sufficient.
A desired Compound (X) thus obtained may be used in the subsequent step as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like). ##STR14## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (Ia) can be prepared by reacting Compound (X) and Compound (VII) in a suitable solvent (a single solvent or a solvent mixture).
In this reaction, Compound (VI) may be used in an amount of 1 equivalent or more, relative to Compound (X), preferably 1 to 5 equivalents.
An organic base such as triethylamine, diisopropylethylamine, pyridine and the like, or an inorganic base such as sodium hydroxide, potassium hydroxide may be used in an amount of 1 to 5 equivalents or more, relative to Compound (X), preferably 1 to 2 equivalents.
Examples of a solvent which can be employed are hydrocarbons (e.g., benzene, toluene, xylene and the like), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), nitrites (e.g., acetonitrile and the like), water as well as a mixture thereof
The reaction temperature may be -30 to 100.degree. C., preferably -10 to 80.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 24 hours may be sufficient.
A desired Compound (Ia) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Route 8 ##STR15## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (XII) can be prepared by reacting Compound (IV) with Compound (XI) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.
A desired Compound (XII) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like).
Compound (XI) employed as a starting material in this reaction is known per se, or may be prepared by a known method similar to that described in Synthesis, page 290 (1993). ##STR16## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (XIII) can be prepared by reacting Compound (XII) with selenium dioxide in a suitable solvent (a single solvent or a solvent mixture).
In this reaction, selenium dioxide may be used in an amount of 1 equivalent or more, relative to Compound (XII), preferably 1 to 3 equivalents.
Examples of a solvent which can be employed are aromatic hydrocarbons (toluene, benzene, xylene and the like), halogenated aromatic hydrocarbons (e.g., chlorobenzene, dichlorobenzene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), alcohols (e.g., methanol, ethanol, propanol and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), acetic acid, water as well as a mixture thereof.
The reaction temperature may be 30 to 180.degree. C., preferably 50 to 160.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 50 hours may be sufficient.
A desired Compound (XIII) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like). ##STR17## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (XIV) can be prepared by reacting Compound (XIII) and Compound (VII) in the presence or absence of a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 3 described above.
A desired Compound (XIV) thus obtained may be used in the subsequent step, as a reaction solution or a crude product, or after being purified by a standard method (e.g., distillation, crystallization and the like). ##STR18## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (Ib) can be prepared by reacting a hydroxylamine derivative or a hydrazine derivative represented by Formula (XV) or its salt (e.g., hydrochloride, sulfate) and Compound (XIV) in a suitable solvent (a single solvent or a solvent mixture) similarly as in Scheme 1 described above.
A desired Compound (Ib) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
A hydroxylamine derivative or a hydrazine derivative represented by Formula (XV) is known per se, or, may be prepared by a known method similar to that described in Methoden der Organischen Chemie, Vol.X/1 and X/2 by Houben-Weyl.
Route 9 ##STR19## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (Ic) can be prepared by reacting Compound (Ib') and Compound X in the presence of a base in a suitable solvent (a single solvent or a solvent mixture).
In this reaction, Compound (XVI) may be used in an amount of 1 equivalent or more, relative to Compound (Ib'), preferably 1 to 10 equivalents.
Examples of a base which may be employed are metal hydroxides (e.g., sodium hydroxide, potassium hydroxide and the like), metal hydrides (e.g., sodium hydride, potassium hydride and the like), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide and the like), metal carbonates (e.g., sodium carbonate, potassium carbonate and the like), pyridine, triethylamine and the like, and the amount to be used is 1 equivalent or more, relative to Compound (Ib'), preferably 1 to 20 equivalents.
Examples of a solvent which can be employed are N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), aromatic hydrocarbons (toluene, benzene, xylene and the like), saturated hydrocarbons (e.g., cyclohexane, hexane and the like), ethers (e.g., tetrahydrofuran, dioxane and the like), ketones (e.g., acetone, methylethylketone and the like), water as well as a mixture thereof.
The reaction temperature may be -30 to 150.degree. C., preferably -10 to 100.degree. C. While the reaction time varies depending on reactants, a time of 0.1 to 90 hours may be sufficient.
A desired Compound (Ic) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Route 10 ##STR20## wherein the radicals are defined as described above.
Thus, a compound represented by Formula (Id) can be prepared by reacting Compound (Ib) with a sulfurizing agent in a suitable solvent (a single solvent or a solvent mixture).
As a sulfurizing agent, phosphorus pentasulfide or Lawson's reagent may be mentioned, and each is used in an amount of 1 to 5 equivalents, relative to Compound (Ib), preferably 1 to 2 equivalents.
Examples of a solvent which can be employed are hydrocarbons (benzene toluene, xylene and the like), pyridine as well as a mixture thereof.
The reaction temperature may be 10 to 200.degree. C., preferably 60 to 150.degree. C. While the reaction time varies depending on reactants, a time of 0.5 to 48 hours may be sufficient.
A desired Compound (Id) thus obtained may be purified by a standard method (e.g., column chromatography, recrystallization and the like).
Compound (I) according to the present invention or its salt or hydrate is effective against pathogenic microbes (fungi) and soil fungi on crop plants or their seeds such as rice, wheat, barley, rye, corn, millet, foxtail millet, buckwheat, soybean, redbean, peanut, and the like, fruit trees such as citrus fruits, grape, apple, pear, peach and the like, or vegetables such as cucumber, eggplant, tomato, pumpkin, kidney bean and the like. The compound of this invention shows a potent fungicidal activity particularly against a rice blight microorganism (Pyricularia oryzae), a sheath blight microorganism (Rhizoctonia solani), a wheat powdery mildew microorganism (Erysiphe graminis), a cucumber mildew microorganism (Sphaerotheca fuliginea), a tobacco mildew microorganism (Erysiphe cichoracearum), a potato late blight microorganism (Phylophthora infestans), a cucumber downy mildew microorganism (Pseudoperonospora cubensis), a soybean downey mildew microorganism (Peronospora manshurica), a grape downy mildew microorganism (Plasaopara viticola), a grey mold microorganism (Botrytis cinerea) of vegetables, grape and the like, a cucumber seedle damping off microorganism (Pythium aphanidermatum), a sclerotium disease microorganism (Sclerotinia sclerotiorum) of buckwheat, soybean, rape and the like, a stem rot microrganism (Corticium rolfsii) of soybean, redbean, potato, peanut and the like, a wheat eyespot disease microorganism (Pseudocercosporella herpotrichoides) and the like. Therefore, Compound (I) according to the present invention or its salt or hydrate is useful as a fungicide, particularly as an agricultural fungicide.
Application of Compound (I) according to the present invention or a salt or a hydrate thereof as agrochemicals may be to a plant may be performed by any conventional procedure such as atomizing, scattering or spreading of an active compound, or, alternatively, the application may be performed by mans of a treatment of a seed of a plant, a soil where a plant grows, a soil for seeding, a paddy field or a water for perfusion with an active compound. Application may be performed before or after an infection with a phytopathogenic microorganism.
A compound according to the present invention can be used as an agrochemical formulation suitable for an agricultural fungicide, such as a solution, a wettable powder, an emulsion, a suspension, a concentrated liquid preparation, a tablet, a granule, an aerosol, a powder, a paste, a fumigant and the like.
Such formulation can be prepared in a conventional manner by mixing at least one compound according to the present invention with an appropriate solid or liquid carrier and, if necessary, an appropriate adjuvant (e.g., surfactant, spreader, dispersant, stabilizer and the like) for improving the dispersibility and other properties of an active ingredient.
Examples of a solid carrier or a diluent are a botanical material (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue and the like), a fibrous material (e.g., paper, corrugated cardboard, old rag and the like), an artificial plastic powder, a clay (e.g., kaolin, bentonite, fuller's earth and the like), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfuir powder, activated carbon and the like), a chemical fertilizer (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride and the like) and the like.
Examples of a liquid carrier or a diluent are water, alcohols (e.g., methanol, ethanol and the like), ketones (e.g., acetone, methyl ethyl ketone and the like), ethers (e.g., diethylether, dioxane, cellosolve, tetrahydrofuran), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnahthalene and the like), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil and the like), esters, nitrites, acid amides (e.g. dimethylformamide, dimethylacetamide and the like), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride and the like) and the like.
Examples of a surfactant are an alkyl sulfiric, an alyl ester, an alkylaryl sulfuric ester, a polyethylene glycol ether, a polyhydric alcohol ester and the like. Examples of a spreader or a dispersant are casein, gelatin, starch powder, carboxymethylcellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar and the like. Examples of a stabilizer are PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tall oil, an epoxidized oil, a surfactant, a fatty acid and its ester and the like.
A composition according to the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the ingredients listed above.
In general, a composition described above contains at least one compound of Formula (I) of the present invention or its salt or hydrate in a concentration of 0.1 to 95% by weight, preferably 1.0 to 80% by weight. The composition can be used as it is or in a diluted form, and about 1.0 g to 5 kg/ha, preferably about 10 g to 1.0 kg/ha, of a compound according to the present invention is used in a concentration of normally about 1 to 5,000 ppm, preferably about 10 to 1,000 ppm.
A compound of Formula (I) according to the present invention or its salt or hydrate is useful as a prophylactic or therapeutic agent in mammals including human against tachykinin receptor antagonism-related inflammatory diseases, gastrointestinal diseases, vomiting, dysuria, pain, migraine, neuralgia, Alzheimer's disease, immunopotentiation or immunosuppression-related diseases, rheumatoid diseases, allergic diseases and the like.
A compound of Formula (I) according to the present invention or its salt or hydrate may be administered as a pharmaceutical via any route such as oral, topical and parenteral routes.
A compound according to the present invention may be used as a pharmaceutical formulation for a medical use such as a powder, a fine granule, a granule, a tablet, a capsule, a solution for injection and the like.
Such formulation may be obtained by an ordinary process in which at least one of the compounds according to the present invention is mixed with a suitable solid or liquid carrier, and, if desired, an excipient (e.g., starch, lactose, sugar, potassium carbonate, calcium phosphate and the like), a binder (e.g., starch, gum arabic, carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, alginic acid, gelatin, polyvinylpyrrolidone and the like), a glidant (e.g., stearic acid, magnesium stearate, calcium stearate, talc and the like), a disintegrant (e.g., potassium carboxymethylcellulose, talc and the like), a diluent (e.g., physiological saline and the like).
In general, a pharmaceutical described above may be given in a dose which may vary depending on the administration route as well as the symptoms and the ages of the subjects, and the daily dose, as at least one Compound (I) according to the present invention or its salt or hydrate, may be about 0.001 mg to 50 mg, preferably about 0.01 mg to 10 mg, per kg body weight, which may be given as being divided to 3 dosages or less a day.

EXAMPLES
The following Examples and Test Examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof The .sup.1 H-NMR (CDCl.sub.3) data in Examples and Tables shown later were determined at 270 MHz in CDC13 using tetramethylsilane as an internal standard and indicated in .delta. values (ppm). The coupling constants (J) are indicated in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, q is a quartet, AB is a ABq type quartet, sept is a septet and m is a multiplet.
Reference Example 1
Synthesis of 2-methoxyimino-N,N-dimethylacetoacetamide
18.04 g (0.2 mol) of a 50% aqueous solution of dimethylamine in 10 ml toluene was cooled in an ice bath and combined with 8.41 g (0.1 mol) of a diketene in 20 ml of toluene and stirred for 1 hour at room temperature. After distilling water off azeotropically, 200 ml of ethyl acetate was added and the mixture was dried over with anhydrous sodium sulfate to distill the solvent off. To the residue thus obtained, 7.63 g (0.105 mol) of sodium nitrite was added and the mixture was cooled in an ice bath and then 10 ml (0.12 mol) of a concentrated hydrochloric acid was added dropwise. After stirring for 0.5 hour at room temperature, the reaction mixture was cooled again in an ice bath, and 5.42 g (0.13 mol) of sodium hydroxide was added. The solution thus obtained was added to a solution of 18.92 g (0.15 mol) of dimethyl sulfate and 1.61 g (0.05 mol) of tetrabutylammonium bromide in 50 ml of toluene dropwise while cooling with an ice, and the mixture was stirred for 4 hours at room temperature. The reaction mixture was extracted four times with 150 ml of ethyl acetate and dried over with anhydrous magnesium sulfate, and then the solvent was distilled ofE and finally the residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 13.46 g (yield: 78%) of 2-methoxyimino-N,N-dimethylacetoacetamide as a colorless crystal.
(Melting point: 73.5 to 75.degree. C.)
Example 1
Synthesis of 2-methoxyimino-N,N-dimethyl-3-(N-methyl-N-phenylhydrazono)butyramide (Compound No.1-1)
1.0 g (5.8 mmol) of 2-methoxyimino-N,N-dimethylacetoacetamide was dissolved in 15 ml of ethanol and 0.5 ml of acetic acid, and 0.78 g (6.4 mmol) of N-methyl-N-phenylhydrazine was added and the mixture was stirred for 24 hours at room temperature. After distilling the solvent of water was added and the mixture was extracted three times with 20 ml of diethylether. After washing with a dilute hydrochloric acid, water and a saturated aqueous sodium chloride, the mixture was dried over with anhydrous magnesium sulfate, and the solvent was distilled of, and finally the residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 1.38 g (yield: 86%) of 2-methoxyimino-N,N-dimethy-3-(N-methyl-N-phenylhydrazono)butyramide as a yellow oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:2.13(3H, s), 2.90(3H,s), 3.07(3H, s), 3.29(3H, s), 3.99(3H, s), 6.90-7.02(3H, m), 7.33-7.29(2H, m)
Example 2
Synthesis of 3-(4-methylbenzyloxyimino)-2-methoxyimino-N,N-dimethylbutyramide (Compound No.C-376)
To a solution of 600 mg (3.2 mmol) of 3-hydroxyimino-2-methoxyimino-N,N-dimethylbutyramide in 20 ml of acetone, 500 mg (3.5 mmol) of 4-methylbenzylchloride and 660 mg (4.8 mmol) of potassium carbonate were added and the mixture was heated under reflux for 16 hours. The reaction mixture was combined with 30 ml of water and extracted three times with 30 ml of diethylether. After washing with water and a saturated aqueous sodium chloride, the mixture was dried over with aanhydrous magnesium sulfate and then the solvent was distilled off. The residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 900 mg (yield: 96%) of 3-(4-methylbenzyloxyimino)-2-methoxyimino-N,N-dimethylbutyramide as a colorless crystal.
(Melting point: 68 to 69.degree. C.)
Reference Example 2
Synthesis of methyl 2-benzyloxyiminoacetoacetate
(1) Synthesis of methyl 2-hydroxyiminoacetoacetate
To a solution of 46.45 g (0.4 mol) of methyl acetoacetate in 200 ml of diethylether, 30.4 g (0.44 mol) of sodium nitrite was added and the mixture was cooled in an ice bath and treated dropwise with 40 ml (0.48 mol) of a concentrated hydrochloric acid. After stirring for 1 hour at room temperature, 200 ml of water was added and the mixture was extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off to obtain 50.09 g (yield: 86%) of a crude methyl 2-hydroxyiminoacetoacetate as a pale yellow oil.
(2) Synthesis of methyl 2-benzyloxyiminoacetoacetate
To a solution of 15.0 g (103 mmol) of methyl 2-hydroxyiminoacetoacetate in 200 ml of acetone, 14.4 g (113 mmol) of benzyl chloride and 21.4 g (155 mmol) of potassium carbonate were added and the mixture was heated under reflux for 15 hours. The reaction mixture was combined with 200 ml of water and extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off. The residue thus obtained was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 18.7 g (yield: 77%) of methyl 2-benzyloxyiminoacetoacetate as a colorless crystal.
(Melting point: 35 to 36.degree. C.)
Example 3
Synthesis of methyl 2-benzyloxyimino-3-methoxyiminobutyrate (Compound No.x-10)
To a solution of 4.0 g (17 mol) of methyl 2-benzyloxyiminoacetoacetate in 50 ml of methanol, 1.56 g (18.7 mmol) of methoxyamine hydrochloride was added and the mixture was heated under reflux for 3 hours. After distilling the solvent off under reduced pressure, 50 ml of water was added and the mixture was extracted twice with 50 ml of diethylether and then washed with water and a saturated aqueous sodium chloride. The organic layer was dried over with anhydrous magnesium sufate and the solvent was distilled off to obtain a residue, which was then purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 4.11 g yield:91%) of methyl 2-benzyloxyimino-3-methoxyiminobutyrate as a colorless oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:1.99(3H, s), 3.86(3H, s), 3.94(3H, s), 5.21(2H, s), 7.33(5H, m)
Example 4
Synthesis of 2-benzyloxyimino-3-methoxyiminobutyric acid (Compound No. z-10)
To a solution of 3.2 g (12.1 mmol) of methyl 2-benzyloxyimino-3-methoxyiminobutyrate in 50 ml of methanol, 1.01 g (24.2 mmol) of sodium hydroxide and 10 ml of water were added and the mixture was heated under reflux for 24 hours. After distilling the solvent off under reduced pressure and adding 50 ml of water, the mixture was washed with 50 ml of diethylether. The aqueous layer was made acidic by adding a concentrated hydrochloric acid, and then the mixture was extracted three times with 50 ml of diethylether. After washing with water and with a saturated aqueous sodium chloride, the organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain 3.02 g (yeld:100%) of 2-benzyloxyimino-3-methoxyiminobutyric acid as a white solid.
(Melting point: 88 to 89.degree. C.)
Example 5
Synthesis of 2-benzyoxyimino-3-methoxyimino-N,N-dimethylbutyramide (Compound No.C-10)
To a solution of 0.9 g (3.6 mmol) of 2-benzyloxyimino-3-methoxyiminobutyric acid in 15 ml of toluene, 0.5 g (4.0 mmol) of thionyl chloride and one drop of N,N-dimethylformamide were added and the mixture was stirred for 1 hour at 60.degree. C. After cooling with an ice, 5 ml of 50% dimethylamine solution was added and the mixture was stirred for 0.5 hour at room temperature. 30 ml of water was added and the mixture was extracted three times with 50 ml of diethylether. After washing with water and a saturated aqueous sodium chloride, the organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain a residue, which was then purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 0.53 g yield: 53%) of 2-benzyloxyimino-3-methoxyimino-N,N-dimethylbutyramide as a colorless oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:2.02(3H, s), 2.74(3H, s), 3.00(3H, s), 3.92(3H, s), 5.19(2H, s), 7.33(5H,m)
Example 6
Synthesis of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine (Compound No. n-794)
(1) Synthesis of methyl 3-benzyloxyiminovalerate
To a solution of 26.03 g (0.2 mol) of methyl propionylacetate in 300 ml of methanol, 100 ml of water and 35.12 g (0.22 mol) of benzyloxyamine hydrochloride, 19.69 g (0.24 mol) of potassium acetate were added and the mixture was stirred for 15 hours at room temperature. After distilling methanol off under reduced pressure, followed by adding 200 ml of water and extracting three times with 200 ml of ethyl acetate, the mixture was washed with water and a saturated aqueous sodium chloride and then dried over with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 47.06 g yield: 100%) of a crude methyl 3-benzyloxyiminovalerate as a colorless oil.
(2) Synthesis of methyl 3-benzyloxyimino-2-oxovalerate
To a solution of 47.06 g (0.2 mol) of methyl 3-benzyloxyiminovalerate in 150 ml of chlorbenzene, 24.41 g (0.22 mol) of selenium dioxide was added and the mixture was stirred for 8 hours at 120.degree. C. After adding 200 ml of water and filtering through Celite, the filtrate was extracted three times with 200 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexanelethyl acetate) to obtain 31.15 g (yield 62%) of methyl 3-benzyloxyimino-2-oxovalerate as a colorless oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:1.04(3H, t, J=7.6), 2.52(2H, d, J=7.6), 3.86(3H, s), 5.29(2H, s), 7.36(5H, m)
(3) Synthesis of 4-(3-benzyloxyimino-2-oxyvaleryl)morpholine
10.0 g (0.04 mol) of methyl 3-benzyloxyimino-2-oxovalerate and 20 ml of morpholine were combined and the mixture was stirred for 3 hours at 100.degree. C. After distilling the morpholine off under reduced pressure, 100 ml of water was added and the mixture was extracted three times with 100 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexanelethyl acetate) to obtain 6.78 g (yield: 56%) of 4-(3-benzyloxyimino-2-oxovaleryl)morpholine as a white solid.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:1.07(3H, t, J=7.6), 2.56(2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.39(2H,t, J=4.9), 3.60-3.70(4H, m), 5.29(2H, s), 7.36(5H, m)
(4) Synthesis of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine
1.0 g (3.3 mmol) of 4-(3-benzyloxyimino-2-oxovaleryl)morpholine was dissolved in 20 ml of 2-propanol and 1.24 g (6.6 mmol) of 4-methoxybenzylhydrazine hydrochloride, 1.08 g (13.2 mmol) of sodium acetate and 1 ml of acetic acid were added and the mixture was refluxed for 15 hours. After distilling the solvent off under reduced pressure, 20 ml of water was added and the mixture was extracted three times with 30 ml of diethylether. After washing with 1N aqueous hydrochloric acid, water, a saturated aqueous sodium bicarbonate, water and then a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 1.19 g (yield: 83%) of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine as a yellow oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:1.08(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H,t, J=4.9), 3.59(4H, brs), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10(2H, s), 6.15(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.19(2H, d, J=8.5), 7.32(5H, m)
Example 7
Synthesis of 4-(3-benzyloxyimino-2-((4-methoxybenzyl)methylhydrazono)valeryl)moxpholine (Compound No. o-794)
0.04 g (1.0 mmol) of 60% sodium hydride was suspended in 10 ml of N,N-dimethylformamide, and to this a solution of 0.40 g (0.91 mmol) of 4-(3-benzyloxyimino-2-(4-methoxybenzylhydrazono)valeryl)morpholine in 5 ml of N,N-dimethylformamide and 0.19 g (0.13 mmol) of methyl iodide were added and the mixture was stirred for 1 hour at room temperature. 20 ml of water was added and the mixture was extracted three times with 20 ml of diethylether. After washing with water and a saturated aqueous sodium chloride followed by drying over with anhydrous magnesium sulfate, the solvent was distilled off to obtain a residue, which was purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 0.35 g (yield: 85%) of 4-(3-benzyloxyimino-2-((4-methoxybenzyl)methylhydrazono)valeryl) as a yellow oil.
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm:1.07(3H, t, J=7.6), 2.65(2H, q, J=7.6), 2.84(3H, s), 2.92-2.98(2H, m), 3.23-3.69(6H, m), 3.79(3H, s), 4.32(1H, d, J=14.3), 4.36(1H, d, J=14.3), 5.05(1H, d, J=12.5), 5.15(1H, d, J=12.5), 6.84(2H, d, J=8.5), 7.18(2H, d, J=8.5), 7.33(5H, m).
Examples of the compounds represented by Formula (I) and (II) obtainable by the same manner as that in Examples described above are the following compound group A to Z, and a to w and x to z, and examples of combination of the substituents R.sup.1, R.sup.2 and R.sup.3 of the compound groups A to Z and a to z are shown in Tables 1 to 70. The physical data of the compounds are shown in Tables 71 to 83. The physical data of the compound obtained in the above Examples are also listed in the Tables. "No." in each Table represents a compound number, and, for example, "A-176" means a compound which is included in compound group A and which has the combination of the substituent designated by No.176. ##STR21##
TABLE 1______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________ 1 Me Me Me 2 Me Me Et 3 Me Me n-Pr 4 Me Me i-Pr 5 Me Me allyl 6 Me Me cinnamyl 7 Me Me 2-propynyl 8 Me Me 2-butynyl 9 Me Me 2-pyridyl10 Me Me benzyl11 Me Me 2-Cl-benzyl12 Me Me 3-Cl-benzyl13 Me Me 4-Cl-benzyl14 Me Me 2-Me-benzyl15 Me Me 3-Me-benzyl16 Me Me 4-Me-benzyl17 Me Me 2-MeO-benzyl18 Me Me 3-MeO-benzyl19 Me Me 4-MeO-benzyl20 Me Me 2-Cl-4-MeO-benzyl21 Me Me 3,4-(Cl).sub.2 -benzyl22 Me Me 2-Me-4-MeO-benzyl23 Me Me .alpha.-Me-4-MeO-benzyl24 Me Me 4-MeO-PhSO.sub.225 Me Me 4-pyridylCH.sub.2______________________________________
TABLE 2______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________26 Me MeOCH.sub.2 Me27 Me MeOCH.sub.2 Et28 Me MeOCH.sub.2 n-Pr29 Me MeOCH.sub.2 i-Pr30 Me MeOCH.sub.2 allyl31 Me MeOCH.sub.2 cinnamyl32 Me MeOCH.sub.2 2-propynyl33 Me MeOCH.sub.2 2-butynyl34 Me MeOCH.sub.2 2-pyridyl35 Me MeOCH.sub.2 benzyl36 Me MeOCH.sub.2 2-Cl-benzyl37 Me MeOCH.sub.2 3-Cl-benzyl38 Me MeOCH.sub.2 4-Cl-benzyl39 Me MeOCH.sub.2 2-Me-benzyl40 Me MeOCH.sub.2 3-Me-benzyl41 Me MeOCH.sub.2 4-Me-benzyl42 Me MeOCH.sub.2 2-MeO-benzyl43 Me MeOCH.sub.2 3-MeO-benzyl44 Me MeOCH.sub.2 4-MeO-benzyl45 Me MeOCH.sub.2 2-Cl-4-MeO-benzyl46 Me MeOCH.sub.2 3,4-(Cl).sub.2 -benzyl47 Me MeOCH.sub.2 2-Me-4-MeO-benzyl48 Me MeOCH.sub.2 .alpha.-Me-4-MeO-benzyl49 Me MeOCH.sub.2 4-MeO-PhSO.sub.250 Me MeOCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 3______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________51 Me Et Me52 Me Et Et53 Me Et n-Pr54 Me Et i-Pr55 Me Et allyl56 Me Et cinnamyl57 Me Et 2-propynyl58 Me Et 2-butynyl59 Me Et 2-pyridyl60 Me Et benzyl61 Me Et 2-Cl-benzyl62 Me Et 3-Cl-benzyl63 Me Et 4-Cl-benzyl64 Me Et 2-Me-benzyl65 Me Et 3-Me-benzyl66 Me Et 4-Me-benzyl67 Me Et 2-MeO-benzyl68 Me Et 3-MeO-benzyl69 Me Et 4-MeO-benzyl70 Me Et 2-Cl-4-MeO-benzyl71 Me Et 3,4-(Cl).sub.2 -benzyl72 Me Et 2-Me-4-MeO-benzyl73 Me Et .alpha.-Me-4-Meo-benzyl74 Me Et 4-MeO-PhSO.sub.275 Me Et 4-pyridylCH.sub.2______________________________________
TABLE 4______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________76 Me allyl Me77 Me allyl Et78 Me allyl n-Pr79 Me allyl i-Pr80 Me allyl allyl81 Me allyl cinnamyl82 Me allyl 2-propynyl83 Me allyl 2-butynyl84 Me allyl 2-pyridyl85 Me allyl benzyl86 Me allyl 2-Cl-benzyl87 Me allyl 3-Cl-benzyl88 Me allyl 4-Cl-benzyl89 Me allyl 2-Me-benzyl90 Me allyl 3-Me-benzyl91 Me allyl 4-Me-benzyl92 Me allyl 2-MeO-benzyl93 Me allyl 3-MeO-benzyl94 Me allyl 4-MeO-benzyl95 Me allyl 2-Cl-4-MeO-benzyl96 Me allyl 3,4-(Cl).sub.2 -benzyl97 Me allyl 2-Me-4-MeO-benzyl98 Me allyl .alpha.-Me-4-MeO-benzyl99 Me allyl 4-MeO-PhSO.sub.2100 Me allyl 4-pyridylCH.sub.2______________________________________
TABLE 5______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________101 Me cinnamyl Me102 Me cinnamyl Et103 Me cinnamyl n-Pr104 Me cinnamyl i-Pr105 Me cinnamyl allyl106 Me cinnamyl cinnamyl107 Me cinnamyl 2-propynyl108 Me cinnamyl 2-butynyl109 Me cinnamyl 2-pyridyl110 Me cinnamyl benzyl111 Me cinnamyl 2-Cl-benzyl112 Me cinnamyl 3-Cl-benzyl113 Me cinnamyl 4-Cl-benzyl114 Me cinnamyl 2-Me-benzyl115 Me cinnamyl 3-Me-benzyl116 Me cinnamyl 4-Me-benzyl117 Me cinnamyl 2-MeO-benzyl118 Me cinnamyl 3-MeO-benzyl119 Me cinnamyl 4-MeO-benzyl120 Me cinnamyl 2-Cl-4-MeO-benzyl121 Me cinnamyl 3,4-(Cl).sub.2 -benzyl122 Me cinnamyl 2-Me-4-MeO-benzyl123 Me cinnamyl .alpha.-Me-4-MeO-benzyl124 Me cinnamyl 4-MeO-PhSO.sub.2125 Me cinnamyl 4-pyridylCH.sub.2______________________________________
TABLE 6______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________126 Me 2-propynyl Me127 Me 2-propynyl Et128 Me 2-propynyl n-Pr129 Me 2-propynyl i-Pr130 Me 2-propynyl allyl131 Me 2-propynyl cinnamyl132 Me 2-propynyl 2-propynyl133 Me 2-propynyl 2-butynyl134 Me 2-propynyl 2-pyridyl135 Me 2-propynyl benzyl136 Me 2-propynyl 2-Cl-benzyl137 Me 2-propynyl 3-Cl-benzyl138 Me 2-propynyl 4-Cl-benzyl139 Me 2-propynyl 2-Me-benzyl140 Me 2-propynyl 3-Me-benzyl141 Me 2-propynyl 4-Me-benzyl142 Me 2-propynyl 2-MeO-benzyl143 Me 2-propynyl 3-MeO-benzyl144 Me 2-propynyl 4-MeO-benzyl145 Me 2-propynyl 2-Cl-4-MeO-benzyl146 Me 2-propynyl 3,4-(Cl).sub.2 -benzyl147 Me 2-propynyl 2-Me-4-MeO-benzyl148 Me 2-propynyl .alpha.-Me-4-MeO-benzyl149 Me 2-propynyl 4-MeO-PhSO.sub.2150 Me 2-propynyl 4-pyridylCH.sub.2______________________________________
TABLE 7______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________151 Me 2-pyridyl Me152 Me 2-pyridyl Et153 Me 2-pyridyl n-Pr154 Me 2-pyridyl i-Pr155 Me 2-pyridyl allyl156 Me 2-pyridyl cinnamyl157 Me 2-pyridyl 2-propynyl158 Me 2-pyridyl 2-butynyl159 Me 2-pyridyl 2-pyridyl160 Me 2-pyridyl benzyl161 Me 2-pyridyl 2-Cl-benzyl162 Me 2-pyridyl 3-Cl-benzyl163 Me 2-pyridyl 4-Cl-benzyl164 Me 2-pyridyl 2-Me-benzyl165 Me 2-pyridyl 3-Me-benzyl166 Me 2-pyridyl 4-Me-benzyl167 Me 2-pyridyl 2-MeO-benzyl168 Me 2-pyridyl 3-MeO-benzyl169 Me 2-pyridyl 4-MeO-benzyl170 Me 2-pyridyl 2-Cl-4-MeO-benzyl171 Me 2-pyridyl 3,4-(Cl).sub.2 -benzyl172 Me 2-pyridyl 2-Me-4-MeO-benzyl173 Me 2-pyridyl .alpha.-Me-4-MeO-benzyl174 Me 2-pyridyl 4-MeO-PhSO.sub.2175 Me 2-pyridyl 4-pyridylCH.sub.2______________________________________
TABLE 8______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________176 Me benzyl Me177 Me benzyl Et178 Me benzyl n-Pr179 Me benzyl i-Pr180 Me benzyl allyl181 Me benzyl cinnamyl182 Me benzyl 2-propynyl183 Me benzyl 2-butynyl184 Me benzyl 2-pyridyl185 Me benzyl benzyl186 Me benzyl 2-Cl-benzyl187 Me benzyl 3-Cl-benzyl188 Me benzyl 4-Cl-benzyl189 Me benzyl 2-Me-benzyl190 Me benzyl 3-Me-benzyl191 Me benzyl 4-Me-benzyl192 Me benzyl 2-MeO-benzyl193 Me benzyl 3-MeO-benzyl194 Me benzyl 4-MeO-benzyl195 Me benzyl 2-Cl-4-MeO-benzyl196 Me benzyl 3,4-(Cl).sub.2 -benzyl197 Me benzyl 2-Me-4-MeO-benzyl198 Me benzyl .alpha.-Me-4-MeO-benzyl199 Me benzyl 4-MeO-PhSO.sub.2200 Me benzyl 4-pyridylCH.sub.2______________________________________
TABLE 9______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________201 Me 2-butynyl Me202 Me 2-butynyl Et203 Me 2-butynyl n-Pr204 Me 2-butynyl i-Pr205 Me 2-butynyl allyl206 Me 2-butynyl cinnamyl207 Me 2-butynyl 2-propynyl208 Me 2-butynyl 2-butynyl209 Me 2-butynyl 2-pyridyl210 Me 2-butynyl benzyl211 Me 2-butynyl 2-Cl-benzyl212 Me 2-butynyl 3-Cl-benzyl213 Me 2-butynyl 4-Cl-benzyl214 Me 2-butynyl 2-Me-benzyl215 Me 2-butynyl 3-Me-benzyl216 Me 2-butynyl 4-Me-benzyl217 Me 2-butynyl 2-MeO-benzyl218 Me 2-butynyl 3-MeO-benzyl219 Me 2-butynyl 4-MeO-benzyl220 Me 2-butynyl 2-Cl-4-MeO-benzyl221 Me 2-butynyl 3,4-(Cl).sub.2 -benzyl222 Me 2-butynyl 2-Me-4-MeO-benzyl223 Me 2-butynyl .alpha.-Me-4-MeO-benzyl224 Me 2-butynyl 4-MeO-PhSO.sub.2225 Me 2-butynyl 4-pyridylCH.sub.2______________________________________
TABLE 10______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________226 Me Ph Me227 Me Ph Et228 Me Ph n-Pr229 Me Ph i-Pr230 Me Ph allyl231 Me Ph cinnamyl232 Me Ph 2-propynyl233 Me Ph 2-butynyl234 Me Ph 2-pyridyl235 Me Ph benzyl236 Me Ph 2-Cl-benzyl237 Me Ph 3-Cl-benzyl238 Me Ph 4-Cl-benzyl239 Me Ph 2-Me-benzyl240 Me Ph 3-Me-benzyl241 Me Ph 4-Me-benzyl242 Me Ph 2-MeO-benzyl243 Me Ph 3-MeO-benzyl244 Me Ph 4-MeO-benzyl245 Me Ph 2-Cl-4-MeO-benzyl246 Me Ph 3,4-(Cl).sub.2 -benzyl247 Me Ph 2-Me-4-MeO-benzyl248 Me Ph .alpha.-Me-4-MeO-benzyl249 Me Ph 4-MeO-PhSO.sub.2250 Me Ph 4-pyridylCH.sub.2______________________________________
TABLE 11______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________251 Me 2-Cl-benzyl Me252 Me 2-Cl-benzyl Et253 Me 2-Cl-benzyl n-Pr254 Me 2-Cl-benzyl i-Pr255 Me 2-Cl-benzyl allyl256 Me 2-Cl-benzyl cinnamyl257 Me 2-Cl-benzyl 2-propynyl258 Me 2-Cl-benzyl 2-butynyl259 Me 2-Cl-benzyl 2-pyridyl260 Me 2-Cl-benzyl benzyl261 Me 2-Cl-benzyl 2-Cl-benzyl262 Me 2-Cl-benzyl 3-Cl-benzyl263 Me 2-Cl-benzyl 4-Cl-benzyl264 Me 2-Cl-benzyl 2-Me-benzyl265 Me 2-Cl-benzyl 3-Me-benzyl266 Me 2-Cl-benzyl 4-Me-benzyl267 Me 2-Cl-benzyl 2-MeO-benzyl268 Me 2-Cl-benzyl 3-MeO-benzyl269 Me 2-Cl-benzyl 4-MeO-benzyl270 Me 2-Cl-benzyl 2-Cl-4-MeO-benzyl271 Me 2-Cl-benzyl 3,4-(Cl).sub.2 -benzyl272 Me 2-Cl-benzyl 2-Me-4-MeO-benzyl273 Me 2-Cl-benzyl .alpha.-Me-4-MeO-benzyl274 Me 2-Cl-benzyl 4-MeO-PhSO.sub.2275 Me 2-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 12______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________276 Me 3-Cl-benzyl Me277 Me 3-Cl-benzyl Et278 Me 3-Cl-benzyl n-Pr279 Me 3-Cl-benzyl i-Pr280 Me 3-Cl-benzyl allyl281 Me 3-Cl-benzyl cinnamyl282 Me 3-Cl-benzyl 2-propynyl283 Me 3-Cl-benzyl 2-butynyl284 Me 3-Cl-benzyl 2-pyridyl285 Me 3-Cl-benzyl benzyl286 Me 3-Cl-benzyl 2-Cl-benzyl287 Me 3-Cl-benzyl 3-Cl-benzyl288 Me 3-Cl-benzyl 4-Cl-benzyl289 Me 3-Cl-benzyl 2-Me-benzyl290 Me 3-Cl-benzyl 3-Me-benzyl291 Me 3-Cl-benzyl 4-Me-benzyl292 Me 3-Cl-benzyl 2-MeO-benzyl293 Me 3-Cl-benzyl 3-MeO-benzyl294 Me 3-Cl-benzyl 4-MeO-benzyl295 Me 3-Cl-benzyl 2-Cl-4-MeO-benzyl296 Me 3-Cl-benzyl 3,4-(Cl).sub.2 -benzyl297 Me 3-Cl-benzyl 2-Me-4-MeO-benzyl298 Me 3-Cl-benzyl .alpha.-Me-4-MeO-benzyl299 Me 3-Cl-benzyl 4-MeO-PhSO.sub.2300 Me 3-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 13______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________301 Me 4-Cl-benzyl Me302 Me 4-Cl-benzyl Et303 Me 4-Cl-benzyl n-Pr304 Me 4-Cl-benzyl i-Pr305 Me 4-Cl-benzyl allyl306 Me 4-Cl-benzyl cinnamyl307 Me 4-Cl-benzyl 2-propynyl308 Me 4-Cl-benzyl 2-butynyl309 Me 4-Cl-benzyl 2-pyridyl310 Me 4-Cl-benzyl benzyl311 Me 4-Cl-benzyl 2-Cl-benzyl312 Me 4-Cl-benzyl 3-Cl-benzyl313 Me 4-Cl-benzyl 4-Cl-benzyl314 Me 4-Cl-benzyl 2-Me-benzyl315 Me 4-Cl-benzyl 3-Me-benzyl316 Me 4-Cl-benzyl 4-Me-benzyl317 Me 4-Cl-benzyl 2-MeO-benzyl318 Me 4-Cl-benzyl 3-MeO-benzyl319 Me 4-Cl-benzyl 4-MeO-benzyl320 Me 4-Cl-benzyl 2-Cl-4-MeO-benzyl321 Me 4-Cl-benzyl 3,4-(Cl).sub.2 -benzyl322 Me 4-Cl-benzyl 2-Me-4-MeO-benzyl323 Me 4-Cl-benzyl .alpha.-Me-4-MeO-benzyl324 Me 4-Cl-benzyl 4-MeO-PhSO.sub.2325 Me 4-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 14______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________326 Me 2-Me-benzyl Me327 Me 2-Me-benzyl Et328 Me 2-Me-benzyl n-Pr329 Me 2-Me-benzyl i-Pr330 Me 2-Me-benzyl allyl331 Me 2-Me-benzyl cinnamyl332 Me 2-Me-benzyl 2-propynyl333 Me 2-Me-benzyl 2-butynyl334 Me 2-Me-benzyl 2-pyridyl335 Me 2-Me-benzyl benzyl336 Me 2-Me-benzyl 2-Cl-benzyl337 Me 2-Me-benzyl 3-Cl-benzyl338 Me 2-Me-benzyl 4-Cl-benzyl339 Me 2-Me-benzyl 2-Me-benzyl340 Me 2-Me-benzyl 3-Me-benzyl341 Me 2-Me-benzyl 4-Me-benzyl342 Me 2-Me-benzyl 2-MeO-benzyl343 Me 2-Me-benzyl 3-MeO-benzyl344 Me 2-Me-benzyl 4-MeO-benzyl345 Me 2-Me-benzyl 2-Cl-4-MeO-benzyl346 Me 2-Me-benzyl 3,4-(Cl).sub.2 -benzyl347 Me 2-Me-benzyl 2-Me-4-MeO-benzyl348 Me 2-Me-benzyl .alpha.-Me-4-MeO-benzyl349 Me 2-Me-benzyl 4-MeO-PhSO.sub.2350 Me 2-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 15______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________351 Me 3-Me-benzyl Me352 Me 3-Me-benzyl Et353 Me 3-Me-benzyl n-Pr354 Me 3-Me-benzyl i-Pr355 Me 3-Me-benzyl allyl356 Me 3-Me-benzyl cinnamyl357 Me 3-Me-benzyl 2-propynyl358 Me 3-Me-benzyl 2-butynyl359 Me 3-Me-benzyl 2-pyridyl360 Me 3-Me-benzyl benzyl361 Me 3-Me-benzyl 2-Cl-benzyl362 Me 3-Me-benzyl 3-Cl-benzyl363 Me 3-Me-benzyl 4-Cl-benzyl364 Me 3-Me-benzyl 2-Me-benzyl365 Me 3-Me-benzyll 3-Me-benzyl366 Me 3-Me-benzyl 4-Me-benzyl367 Me 3-Me-benzyl 2-MeO-benzyl368 Me 3-Me-benzyl 3-MeO-benzyl369 Me 3-Me-benzyl 4-MeO-benzyl370 Me 3-Me-benzyl 2-Cl-4-MeO-benzyl371 Me 3-Me-benzyl 3,4-(Cl).sub.2 -benzyl372 Me 3-Me-benzyl 2-Me-4-MeO-benzyl373 Me 3-Me-benzyl .alpha.-Me-4-MeO-benzyl374 Me 3-Me-benzyl 4-MeO-PhSO.sub.2375 Me 3-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 16______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________376 Me 4-Me-benzyl Me377 Me 4-Me-benzyl Et378 Me 4-Me-benzyl n-Pr379 Me 4-Me-benzyl i-Pr380 Me 4-Me-benzyl allyl381 Me 4-Me-benzyl cinnamyl382 Me 4-Me-benzyl 2-propynyl383 Me 4-Me-benzyl 2-butynyl384 Me 4-Me-benzyl 2-pyridyl385 Me 4-Me-benzyl benzyl386 Me 4-Me-benzyl 2-Cl-benzyl387 Me 4-Me-benzyl 3-Cl-benzyl388 Me 4-Me-benzyl 4-Cl-benzyl389 Me 4-Me-benzyl 2-Me-benzyl390 Me 4-Me-benzyl 3-Me-benzyl391 Me 4-Me-benzyl 4-Me-benzyl392 Me 4-Me-benzyl 2-MeO-benzyl393 Me 4-Me-benzyl 3-MeO-benzyl394 Me 4-Me-benzyl 4-MeO-benzyl395 Me 4-Me-benzyl 2-Cl-4-MeO-benzyl396 Me 4-Me-benzyl 3,4-(Cl).sub.2 -benzyl397 Me 4-Me-benzyl 2-Me-4-MeO-benzyl398 Me 4-Me-benzyl .alpha.-Me-4-MeO-benzyl399 Me 4-Me-benzyl 4-MeO-PhSO.sub.2400 Me 4-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 17______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________401 Me 2-MeO-benzyl Me402 Me 2-MeO-benzyl Et403 Me 2-MeO-benzyl n-Pr404 Me 2-MeO-benzyl i-Pr405 Me 2-MeO-benzyl allyl406 Me 2-MeO-benzyl cinnamyl407 Me 2-MeO-benzyl 2-propynyl408 Me 2-MeO-benzyl 2-butynyl409 Me 2-MeO-benzyl 2-pyridyl410 Me 2-MeO-benzyl benzyl411 Me 2-MeO-benzyl 2-Cl-benzyl412 Me 2-MeO-benzyl 3-Cl-benzyl413 Me 2-MeO-benzyl 4-Cl-benzyl414 Me 2-MeO-benzyl 2-Me-benzyl415 Me 2-MeO-benzyl 3-Me-benzyl416 Me 2-MeO-benzyl 4-Me-benzyl417 Me 2-MeO-benzyl 2-MeO-benzyl418 Me 2-MeO-benzyl 3-MeO-benzyl419 Me 2-MeO-benzyl 4-MeO-benzyl420 Me 2-MeO-benzyl 2-Cl-4-MeO-benzyl421 Me 2-MeO-benzyl 3,4-(Cl).sub.2 -benzyl422 Me 2-MeO-benzyl 2-Me-4-MeO-benzyl423 Me 2-MeO-benzyl .alpha.-Me-4-MeO-benzyl424 Me 2-MeO-benzyl 4-MeO-PhSO.sub.2425 Me 2-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 18______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________426 Me 3-MeO-benzyl Me427 Me 3-MeO-benzyl Et428 Me 3-MeO-benzyl n-Pr429 Me 3-MeO-benzyl i-Pr430 Me 3-MeO-benzyl allyl431 Me 3-MeO-benzyl cinnamyl432 Me 3-MeO-benzyl 2-propynyl433 Me 3-MeO-benzyl 2-butynyl434 Me 3-MeO-benzyl 2-pyridyl435 Me 3-MeO-benzyl benzyl436 Me 3-MeO-benzyl 2-Cl-benzyl437 Me 3-MeO-benzyl 3-Cl-benzyl438 Me 3-MeO-benzyl 4-Cl-benzyl439 Me 3-MeO-benzyl 2-Me-benzyl440 Me 3-MeO-benzyl 3-Me-benzyl441 Me 3-MeO-benzyl 4-Me-benzyl442 Me 3-MeO-benzyl 2-MeO-benzyl443 Me 3-MeO-benzyl 3-MeO-benzyl444 Me 3-MeO-benzyl 4-MeO-benzyl445 Me 3-MeO-benzyl 2-Cl-4-MeO-benzyl446 Me 3-MeO-benzyl 3,4-(Cl).sub.2 -benzyl447 Me 3-MeO-benzyl 2-Me-4-MeO-benzyl448 Me 3-MeO-benzyl .alpha.-Me-4-MeO-benzyl449 Me 3-MeO-benzyl 4-MeO-PhSO.sub.2450 Me 3-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 19______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________451 Me 4-MeO-benzyl Me452 Me 4-MeO-benzyl Et453 Me 4-MeO-benzyl n-Pr454 Me 4-MeO-benzyl i-Pr455 Me 4-MeO-benzyl allyl456 Me 4-MeO-benzyl cinnamyl457 Me 4-MeO-benzyl 2-propynyl458 Me 4-MeO-benzyl 2-butynyl459 Me 4-MeO-benzyl 2-pyridyl460 Me 4-MeO-benzyl benzyl461 Me 4-MeO-benzyl 2-Cl-benzyl462 Me 4-MeO-benzyl 3-Cl-benzyl463 Me 4-MeO-benzyl 4-Cl-benzyl464 Me 4-MeO-benzyl 2-Me-benzyl465 Me 4-MeO-benzyl 3-Me-benzyl466 Me 4-MeO-benzyl 4-Me-benzyl467 Me 4-MeO-benzyl 2-MeO-benzyl468 Me 4-MeO-benzyl 3-MeO-benzyl469 Me 4-MeO-benzyl 4-MeO-benzyl470 Me 4-MeO-benzyl 2-Cl-4-MeO-benzyl471 Me 4-MeO-benzyl 3,4-(Cl).sub.2 -benzyl472 Me 4-MeO-benzyl 2-Me-4-MeO-benzyl473 Me 4-MeO-benzyl .alpha.-Me-4-MeO-benzyl474 Me 4-MeO-benzyl 4-MeO-PhSO.sub.2475 Me 4-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 20______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________476 Me 3,4-(Cl).sub.2 -benzyl Me477 Me 3,4-(Cl).sub.2 -benzyl Et478 Me 3,4-(Cl).sub.2 -benzyl n-Pr479 Me 3,4-(Cl).sub.2 -benzyl i-Pr480 Me 3,4-(Cl).sub.2 -benzyl allyl481 Me 3,4-(Cl).sub.2 -benzyl cinnamyl482 Me 3,4-(Cl).sub.2 -benzyl 2-propynyl483 Me 3,4-(Cl).sub.2 -benzyl 2-butynyl484 Me 3,4-(Cl).sub.2 -benzyl 2-pyridyl485 Me 3,4-(Cl).sub.2 -benzyl benzyl486 Me 3,4-(Cl).sub.2 -benzyl 2-Cl-benzyl487 Me 3,4-(Cl).sub.2 -benzyl 3-Cl-benzyl488 Me 3,4-(Cl).sub.2 -benzyl 4-Cl-benzyl489 Me 3,4-(Cl).sub.2 -benzyl 2-Me-benzyl490 Me 3,4-(Cl).sub.2 -benzyl 3-Me-benzyl491 Me 3,4-(Cl).sub.2 -benzyl 4-Me-benzyl492 Me 3,4-(Cl).sub.2 -benzyl 2-MeO-benzyl493 Me 3,4-(Cl).sub.2 -benzyl 3-MeO-benzyl494 Me 3,4-(Cl).sub.2 -benzyl 4-MeO-benzyl495 Me 3,4-(Cl).sub.2 -benzyl 2-Cl-4-MeO-benzyl496 Me 3,4-(Cl).sub.2 -benzyl 3,4-(Cl).sub.2 -benzyl497 Me 3,4-(Cl).sub.2 benzyl 2-Me-4-MeO-benzyl498 Me 3,4-(Cl).sub.2 -benzyl .alpha.-Me-4-MeO-benzyl499 Me 3,4-(Cl).sub.2 -benzyl 4-MeO-PhSO.sub.2500 Me 3,4-(Cl).sub.2 -benzyl 4-pyridylCH.sub.2______________________________________
TABLE 21______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________501 Me 2-Cl-4-MeO-benzyl Me502 Me 2-Cl-4-MeO-benzyl Et503 Me 2-Cl-4-MeO-benzyl n-Pr504 Me 2-Cl-4-MeO-benzyl i-Pr505 Me 2-Cl-4-MeO-benzyl allyl506 Me 2-Cl-4-MeO-benzyl cinnamyl507 Me 2-Cl-4-MeO-benzyl 2-propynyl508 Me 2-Cl-4-MeO-benzyl 2-butynyl509 Me 2-Cl-4-MeO-benzyl 2-pyridyl510 Me 2-Cl-4-MeO-benzyl benzyl511 Me 2-Cl-4-MeO-benzyl 2-Cl-benzyl512 Me 2-Cl-4-MeO-benzyl 3-Cl-benzyl513 Me 2-Cl-4-MeO-benzyl 4-Cl-benzyl514 Me 2-Cl-4-MeO-benzyl 2-Me-benzyl515 Me 2-Cl-4-MeO-benzyl 3-Me-benzyl516 Me 2-Cl-4-MeO-benzyl 4-Me-benzyl517 Me 2-Cl-4-MeO-benzyl 2-MeO-benzyl518 Me 2-Cl-4-MeO-benzyl 3-MeO-benzyl519 Me 2-Cl-4-MeO-benzyl 4-MeO-benzyl520 Me 2-Cl-4-MeO-benzyl 2-Cl-4-MeO-benzyl521 Me 2-Cl-4-MeO-benzyl 3,4-(Cl).sub.2 -benzyl522 Me 2-Cl-4-MeO-benzyl 2-Me-4-MeO-benzyl523 Me 2-Cl-4-MeO-benzyl .alpha.-Me-4-MeO-benzyl524 Me 2-Cl-4-MeO-benzyl 4-MeO-PhSO.sub.2525 Me 2-Cl-4-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 22______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________526 Me 2-pyridylCH.sub.2 Me527 Me 2-pyridylCH.sub.2 Et528 Me 2-pyridylCH.sub.2 n-Pr529 Me 2-pyridylCH.sub.2 i-Pr530 Me 2-pyridylCH.sub.2 allyl531 Me 2-pyridylCH.sub.2 cinnamyl532 Me 2-pyridylCH.sub.2 2-propynyl533 Me 2-pyridylCH.sub.2 2-butynyl534 Me 2-pyridylCH.sub.2 2-pyridyl535 Me 2-pyridylCH.sub.2 benzyl536 Me 2-pyridylCH.sub.2 2-Cl-benzyl537 Me 2-pyridylCH.sub.2 3-Cl-benzyl538 Me 2-pyridylCH.sub.2 4-Cl-benzyl539 Me 2-pyridylCH.sub.2 2-Me-benzyl540 Me 2-pyridylCH.sub.2 3-Me-benzyl541 Me 2-pyridylCH.sub.2 4-Me-benzyl542 Me 2-pyridylCH.sub.2 2-MeO-benzyl543 Me 2-pyridylCH.sub.2 3-MeO-benzyl544 Me 2-pyridylCH.sub.2 4-MeO-benzyl545 Me 2-pyridylCH.sub.2 2-Cl-4-MeO-benzyl546 Me 2-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl547 Me 2-pyridylCH.sub.2 2-Me-4-MeO-benzyl548 Me 2-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl549 Me 2-pyridylCH.sub.2 4-MeO-PhSO.sub.2550 Me 2-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 23______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________551 Me 3-pyridylCH.sub.2 Me552 Me 3-pyridylCH.sub.2 Et553 Me 3-pyridylCH.sub.2 n-Pr554 Me 3-pyridylCH.sub.2 i-Pr555 Me 3-pyridylCH.sub.2 allyl556 Me 3-pyridylCH.sub.2 cinnamyl557 Me 3-pyridylCH.sub.2 2-propynyl558 Me 3-pyridylCH.sub.2 2-butynyl559 Me 3-pyridylCH.sub.2 2-pyridyl560 Me 3-pyridylCH.sub.2 benzyl561 Me 3-pyridylCH.sub.2 2-Cl-benzyl562 Me 3-pyridylCH.sub.2 3-Cl-benzyl563 Me 3-pyridylCH.sub.2 4-Cl-benzyl564 Me 3-pyridylCH.sub.2 2-Me-benzyl565 Me 3-pyridylCH.sub.2 3-Me-benzyl566 Me 3-pyridylCH.sub.2 4-Me-benzyl567 Me 3-pyridylCH.sub.2 2-MeO-benzyl568 Me 3-pyridylCH.sub.2 3-MeO-benzyl569 Me 3-pyridylCH.sub.2 4-MeO-benzyl570 Me 3-pyridylCH.sub.2 2-Cl-4-MeO-benzyl571 Me 3-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl572 Me 3-pyridylCH.sub.2 2-Me-4-MeO-benzyl573 Me 3-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl574 Me 3-pyridylCH.sub.2 4-MeO-PhSO.sub.2575 Me 3-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 24______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________576 Me 4-pyridylCH.sub.2 Me577 Me 4-pyridylCH.sub.2 Et578 Me 4-pyridylCH.sub.2 n-Pr579 Me 4-pyridylCH.sub.2 i-Pr580 Me 4-pyridylCH.sub.2 allyl581 Me 4-pyridylCH.sub.2 cinnamyl582 Me 4-pyridylCH.sub.2 2-propynyl583 Me 4-pyridylCH.sub.2 2-butynyl584 Me 4-pyridylCH.sub.2 2-pyridyl585 Me 4-pyridylCH.sub.2 benzyl586 Me 4-pyridylCH.sub.2 2-Cl-benzyl587 Me 4-pyridylCH.sub.2 3-Cl-benzyl588 Me 4-pyridylCH.sub.2 4-Cl-benzyl589 Me 4-pyridylCH.sub.2 2-Me-benzyl590 Me 4-pyridylCH.sub.2 3-Me-benzyl591 Me 4-pyridylCH.sub.2 4-Me-benzyl592 Me 4-pyridylCH.sub.2 2-MeO-benzyl593 Me 4-pyridylCH.sub.2 3-MeO-benzyl594 Me 4-pyridylCH.sub.2 4-MeO-benzyl595 Me 4-pyridylCH.sub.2 2-Cl-4-MeO-benzyl596 Me 4-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl597 Me 4-pyridylCH.sub.2 2-Me-4-MeO-benzyl598 Me 4-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl599 Me 4-pyridylCH.sub.2 4-MeO-PhSO.sub.2600 Me 4-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 25______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________601 Et Me Me602 Et Me Et603 Et Me n-Pr604 Et Me i-Pr605 Et Me allyl606 Et Me cinnamyl607 Et Me 2-propynyl608 Et Me 2-butynyl609 Et Me 2-pyridyl610 Et Me benzyl611 Et Me 2-Cl-benzyl612 Et Me 3-Cl-benzyl613 Et Me 4-Cl-benzyl614 Et Me 2-Me-benzyl615 Et Me 3-Me-benzyl616 Et Me 4-Me-benzyl617 Et Me 2-MeO-benzyl618 Et Me 3-MeO-benzyl619 Et Me 4-MeO-benzyl620 Et Me 2-Cl-4-MeO-benzyl621 Et Me 3,4-(Cl).sub.2 -benzyl622 Et Me 2-Me-4-MeO-benzyl623 Et Me .alpha.-Me-4-MeO-benzyl624 Et Me 4-MeO-PhSO.sub.2625 Et Me 4-pyridylCH.sub.2______________________________________
TABLE 26______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________626 Et MeOCH.sub.2 Me627 Et MeOCH.sub.2 Et628 Et MeOCH.sub.2 n-Pr629 Et MeOCH.sub.2 i-Pr630 Et MeOCH.sub.2 allyl631 Et MeOCH.sub.2 cinnamyl632 Et MeOCH.sub.2 2-propynyl633 Et MeOCH.sub.2 2-butynyl634 Et MeOCH.sub.2 2-pyridyl635 Et MeOCH.sub.2 benzyl636 Et MeOCH.sub.2 2-Cl-benzyl637 Et MeOCH.sub.2 3-Cl-benzyl638 Et MeOCH.sub.2 4-Cl-benzyl639 Et MeOCH.sub.2 2-Me-benzyl640 Et MeOCH.sub.2 3-Me-benzyl641 Et MeOCH.sub.2 4-Me-benzyl642 Et MeOCH.sub.2 2-MeO-benzyl643 Et MeOCH.sub.2 3-MeO-benzyl644 Et MeOCH.sub.2 4-MeO-benzyl645 Et MeOCH.sub.2 2-Cl-4-MeO-benzyl646 Et MeOCH.sub.2 3,4-(Cl).sub.2 -benzyl647 Et MeOCH.sub.2 2-Me-4-MeO-benzyl648 Et MeOCH.sub.2 .alpha.-Me-4-MeO-benzyl649 Et MeOCH.sub.2 4-MeO-PhSO.sub.2650 Et MeOCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 27______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________651 Et Et Me652 Et Et Et653 Et Et n-Pr654 Et Et i-Pr655 Et Et allyl656 Et Et cinnamyl657 Et Et 2-propynyl658 Et Et 2-butynyl659 Et Et 2-pyridyl660 Et Et benzyl661 Et Et 2-Cl-benzyl662 Et Et 3-Cl-benzyl663 Et Et 4-Cl-benzyl664 Et Et 2-Me-benzyl665 Et Et 3-Me-benzyl666 Et Et 4-Me-benzyl667 Et Et 2-MeO-benzyl668 Et Et 3-MeO-benzyl669 Et Et 4-MeO-benzyl670 Et Et 2-Cl-4-MeO-benzyl671 Et Et 3,4-(Cl).sub.2 -benzyl672 Et Et 2-Me-4-MeO-benzyl673 Et Et .alpha.-Me-4-MeO-benzyl674 Et Et 4-MeO-PhSO.sub.2675 Et Et 4-pyridylCH.sub.2______________________________________
TABLE 28______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________676 Et allyl Me677 Et allyl Et678 Et allyl n-Pr679 Et allyl i-Pr680 Et allyl allyl681 Et allyl cinnamyl682 Et allyl 2-propynyl683 Et allyl 2-butynyl684 Et allyl 2-pyridyl685 Et allyl benzyl686 Et allyl 2-Cl-benzyl687 Et allyl 3-Cl-benzyl688 Et allyl 4-Cl-benzyl689 Et allyl 2-Me-benzyl690 Et allyl 3-Me-benzyl691 Et allyl 4-Me-benzyl692 Et allyl 2-MeO-benzyl693 Et allyl 3-MeO-benzyl694 Et allyl 4-MeO-benzyl695 Et allyl 2-Cl-4-MeO-benzyl696 Et allyl 3,4-(Cl).sub.2 -benzyl697 Et allyl 2-Me-4-MeO-benzyl698 Et allyl .alpha.-Me-4-MeO-benzyl699 Et allyl 4-MeO-PhSO.sub.2700 Et allyl 4-pyridylCH.sub.2______________________________________
TABLE 29______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________701 Et cinnamyl Me702 Et cinnamyl Et703 Et cinnamyl n-Pr704 Et cinnamyl i-Pr705 Et cinnamyl allyl706 Et cinnamyl cinnamyl707 Et cinnamyl 2-propynyl708 Et cinnamyl 2-butynyl709 Et cinnamyl 2-pyridyl710 Et cinnamyl benzyl711 Et cinnamyl 2-Cl-benzyl712 Et cinnamyl 3-Cl-benzyl713 Et cinnamyl 4-Cl-benzyl714 Et cinnamyl 2-Me-benzyl715 Et cinnamyl 3-Me-benzyl716 Et cinnamyl 4-Me-benzyl717 Et cinnamyl 2-MeO-benzyl718 Et cinnamyl 3-MeO-benzyl719 Et cinnamyl 4-MeO-benzyl720 Et cinnamyl 2-Cl-4-MeO-benzyl721 Et cinnamyl 3,4-(Cl).sub.2 -benzyl722 Et cinnamyl 2-Me-4-MeO-benzyl723 Et cinnamyl .alpha.-Me-4-MeO-benzyl724 Et cinnamyl 4-MeO-PhSO.sub.2725 Et cinnamyl 4-pyridylCH.sub.2______________________________________
TABLE 30______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________726 Et 2-propynyl Me727 Et 2-propynyl Et728 Et 2-propynyl n-Pr729 Et 2-propynyl i-Pr730 Et 2-propynyl allyl731 Et 2-propynyl cinnamyl732 Et 2-propynyl 2-propynyl733 Et 2-propynyl 2-butynyl734 Et 2-propynyl 2-pyridyl735 Et 2-propynyl benzyl736 Et 2-propynyl 2-Cl-benzyl737 Et 2-propynyl 3-Cl-benzyl738 Et 2-propynyl 4-Cl-benzyl739 Et 2-propynyl 2-Me-benzyl740 Et 2-propynyl 3-Me-benzyl741 Et 2-propynyl 4-Me-benzyl742 Et 2-propynyl 2-MeO-benzyl743 Et 2-propynyl 3-MeO-benzyl744 Et 2-propynyl 4-MeO-benzyl745 Et 2-propynyl 2-Cl-4-MeO-benzyl746 Et 2-propynyl 3,4-(Cl).sub.2 -benzyl747 Et 2-propynyl 2-Me-4-MeO-benzyl748 Et 2-propynyl .alpha.-Me-4-MeO-benzyl749 Et 2-propynyl 4-MeO-PhSO.sub.2750 Et 2-propynyl 4-pyridylCH.sub.2______________________________________
TABLE 31______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________751 Et 2-pyridyl Me752 Et 2-pyridyl Et753 Et 2-pyridyl n-Pr754 Et 2-pyridyl i-Pr755 Et 2-pyridyl allyl756 Et 2-pyridyl cinnamyl757 Et 2-pyridyl 2-propynyl758 Et 2-pyridyl 2-butynyl759 Et 2-pyridyl 2-pyridyl760 Et 2-pyridyl benzyl761 Et 2-pyridyl 2-Cl-benzyl762 Et 2-pyridyl 3-Cl-benzyl763 Et 2-pyridyl 4-Cl-benzyl764 Et 2-pyridyl 2-Me-benzyl765 Et 2-pyridyl 3-Me-benzyl766 Et 2-pyridyl 4-Me-benzyl767 Et 2-pyridyl 2-MeO-benzyl768 Et 2-pyridyl 3-MeO-benzyl769 Et 2-pyridyl 4-MeO-benzyl770 Et 2-pyridyl 2-Cl-4-MeO-benzyl771 Et 2-pyridyl 3,4-(Cl).sub.2 -benzyl772 Et 2-pyridyl 2-Me-4-MeO-benzyl773 Et 2-pyridyl .alpha.-Me-4-MeO-benzyl774 Et 2-pyridyl 4-MeO-PhSO.sub.2775 Et 2-pyridyl 4-pyridylCH.sub.2______________________________________
TABLE 32______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________776 Et benzyl Me777 Et benzyl Et778 Et benzyl n-Pr779 Et benzyl i-Pr780 Et benzyl allyl781 Et benzyl cinnamyl782 Et benzyl 2-propynyl783 Et benzyl 2-butynyl784 Et benzyl 2-pyridyl785 Et benzyl benzyl786 Et benzyl 2-Cl-benzyl787 Et benzyl 3-Cl-benzyl788 Et benzyl 4-Cl-benzyl789 Et benzyl 2-Me-benzyl790 Et benzyl 3-Me-benzyl791 Et benzyl 4-Me-benzyl792 Et benzyl 2-MeO-benzyl793 Et benzyl 3-MeO-benzyl794 Et benzyl 4-MeO-benzyl795 Et benzyl 2-Cl-4-MeO-benzyl796 Et benzyl 3,4-(Cl).sub.2 -benzyl797 Et benzyl 2-Me-4-MeO-benzyl798 Et benzyl .alpha.-Me-4-MeO-benzyl799 Et benzyl 4-MeO-PhSO.sub.2800 Et benzyl 4-pyridylCH.sub.2______________________________________
TABLE 33______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________801 Et 2-butynyl Me802 Et 2-butynyl Et803 Et 2-butynyl n-Pr804 Et 2-butynyl i-Pr805 Et 2-butynyl allyl806 Et 2-butynyl cinnamyl807 Et 2-butynyl 2-propynyl808 Et 2-butynyl 2-butynyl809 Et 2-butynyl 2-pyridyl810 Et 2-butynyl benzyl811 Et 2-butynyl 2-Cl-benzyl812 Et 2-butynyl 3-Cl-benzyl813 Et 2-butynyl 4-Cl-benzyl814 Et 2-butynyl 2-Me-benzyl815 Et 2-butynyl 3-Me-benzyl816 Et 2-butynyl 4-Me-benzyl817 Et 2-butynyl 2-MeO-benzyl818 Et 2-butynyl 3-MeO-benzyl819 Et 2-butynyl 4-MeO-benzyl820 Et 2-butynyl 2-Cl-4-MeO-benzyl821 Et 2-butynyl 3,4-(Cl).sub.2 -benzyl822 Et 2-butynyl 2-Me-4-MeO-benzyl823 Et 2-butynyl .alpha.-Me-4-MeO-benzyl824 Et 2-butynyl 4-MeO-PhSO.sub.2825 Et 2-butynyl 4-pyridylCH.sub.2______________________________________
TABLE 34______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________826 Et Ph Me827 Et Ph Et828 Et Ph n-Pr829 Et Ph i-Pr830 Et Ph allyl831 Et Ph cinnamyl832 Et Ph 2-propynyl833 Et Ph 2-butynyl834 Et Ph 2-pyridyl835 Et Ph benzyl836 Et Ph 2-Cl-benzyl837 Et Ph 3-Cl-benzyl838 Et Ph 4-Cl-benzyl839 Et Ph 2-Me-benzyl840 Et Ph 3-Me-benzyl841 Et Ph 4-Me-benzyl842 Et Ph 2-MeO-benzyl843 Et Ph 3-MeO-benzyl844 Et Ph 4-MeO-benzyl845 Et Ph 2-Cl-4-MeO-benzyl846 Et Ph 3,4-(Cl).sub.2 -benzyl847 Et Ph 2-Me-4-MeO-benzyl848 Et Ph .alpha.-Me-4-MeO-benzyl849 Et Ph 4-MeO-PhSO.sub.2850 Et Ph 4-pyridylCH.sub.2______________________________________
TABLE 35______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________851 Et 2-Cl-benzyl Me852 Et 2-Cl-benzyl Et853 Et 2-Cl-benzyl n-Pr854 Et 2-Cl-benzyl i-Pr855 Et 2-Cl-benzyl allyl856 Et 2-Cl-benzyl cinnamyl857 Et 2-Cl-benzyl 2-propynyl858 Et 2-Cl-benzyl 2-butynyl859 Et 2-Cl-benzyl 2-pyridyl860 Et 2-Cl-benzyl benzyl861 Et 2-Cl-benzyl 2-Cl-benzyl862 Et 2-Cl-benzyl 3-Cl-benzyl863 Et 2-Cl-benzyl 4-Cl-benzyl864 Et 2-Cl-benzyl 2-Me-benzyl865 Et 2-Cl-benzyl 3-Me-benzyl866 Et 2-Cl-benzyl 4-Me-benzyl867 Et 2-Cl-benzyl 2-MeO-benzyl868 Et 2-Cl-benzyl 3-MeO-benzyl869 Et 2-Cl-benzyl 4-MeO-benzyl870 Et 2-Cl-benzyl 2-Cl-4-MeO-benzyl871 Et 2-Cl-benzyl 3,4-(Cl).sub.2 -benzyl872 Et 2-Cl-benzyl 2-Me-4-MeO-benzyl873 Et 2-Cl-benzyl .alpha.-Me-4-MeO-benzyl874 Et 2-Cl-benzyl 4-MeO-PhSO.sub.2875 Et 2-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 36______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________876 Et 3-Cl-benzyl Me877 Et 3-Cl-benzyl Et878 Et 3-Cl-benzyl n-Pr879 Et 3-Cl-benzyl i-Pr880 Et 3-Cl-benzyl allyl881 Et 3-Cl-benzyl cinnamyl882 Et 3-Cl-benzyl 2-propynyl883 Et 3-Cl-benzyl 2-butynyl884 Et 3-Cl-benzyl 2-pyridyl885 Et 3-Cl-benzyl benzyl886 Et 3-Cl-benzyl 2-Cl-benzyl887 Et 3-Cl-benzyl 3-Cl-benzyl888 Et 3-Cl-benzyl 4-Cl-benzyl889 Et 3-Cl-benzyl 2-Me-benzyl890 Et 3-Cl-benzyl 3-Me-benzyl891 Et 3-Cl-benzyl 4-Me-benzyl892 Et 3-Cl-benzyl 2-MeO-benzyl893 Et 3-Cl-benzyl 3-MeO-benzyl894 Et 3-Cl-benzyl 4-MeO-benzyl895 Et 3-Cl-benzyl 2-Cl-4-MeO-benzyl896 Et 3-Cl-benzyl 3,4-(Cl).sub.2 -benzyl897 Et 3-Cl-benzyl 2-Me-4-MeO-benzyl898 Et 3-Cl-benzyl .alpha.-Me-4-MeO-benzyl899 Et 3-Cl-benzyl 4-MeO-PhSO.sub.2900 Et 3-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 37______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________901 Et 4-Cl-benzyl Me902 Et 4-Cl-benzyl Et903 Et 4-Cl-benzyl n-Pr904 Et 4-Cl-benzyl i-Pr905 Et 4-Cl-benzyl allyl906 Et 4-Cl-benzyl cinnamyl907 Et 4-Cl-benzyl 2-propynyl908 Et 4-Cl-benzyl 2-butynyl909 Et 4-Cl-benzyl 2-pyridyl910 Et 4-Cl-benzyl benzyl911 Et 4-Cl-benzyl 2-Cl-benzyl912 Et 4-Cl-benzyl 3-Cl-benzyl913 Et 4-Cl-benzyl 4-Cl-benzyl914 Et 4-Cl-benzyl 2-Me-benzyl915 Et 4-Cl-benzyl 3-Me-benzyl916 Et 4-Cl-benzyl 4-Me-benzyl917 Et 4-Cl-benzyl 2-MeO-benzyl918 Et 4-Cl-benzyl 3-MeO-benzyl919 Et 4-Cl-benzyl 4-MeO-benzyl920 Et 4-Cl-benzyl 2-Cl-4-MeO-benzyl921 Et 4-Cl-benzyl 3,4-(Cl).sub.2 -benzyl922 Et 4-Cl-benzyl 2-Me-4-MeO-benzyl923 Et 4-Cl-benzyl .alpha.-Me-4-MeO-benzyl924 Et 4-Cl-benzyl 4-MeO-PhSO.sub.2925 Et 4-Cl-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 38______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________926 Et 2-Me-benzyl Me927 Et 2-Me-benzyl Et928 Et 2-Me-benzyl n-Pr929 Et 2-Me-benzyl i-Pr930 Et 2-Me-benzyl allyl931 Et 2-Me-benzyl cinnamyl932 Et 2-Me-benzyl 2-propynyl933 Et 2-Me-benzyl 2-butynyl934 Et 2-Me-benzyl 2-pyridyl935 Et 2-Me-benzyl benzyl936 Et 2-Me-benzyl 2-Cl-benzyl937 Et 2-Me-benzyl 3-Cl-benzyl938 Et 2-Me-benzyl 4-Cl-benzyl939 Et 2-Me-benzyl 2-Me-benzyl940 Et 2-Me-benzyl 3-Me-benzyl941 Et 2-Me-benzyl 4-Me-benzyl942 Et 2-Me-benzyl 2-MeO-benzyl943 Et 2-Me-benzyl 3-MeO-benzyl944 Et 2-Me-benzyl 4-MeO-benzyl945 Et 2-Me-benzyl 2-Cl-4-MeO-benzyl946 Et 2-Me-benzyl 3,4-(Cl).sub.2 -benzyl947 Et 2-Me-benzyl 2-Me-4-MeO-benzyl948 Et 2-Me-benzyl .alpha.-Me-4-MeO-benzyl949 Et 2-Me-benzyl 4-MeO-PhSO.sub.2950 Et 2-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 39______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________951 Et 3-Me-benzyl Me952 Et 3-Me-benzyl Et953 Et 3-Me-benzyl n-Pr954 Et 3-Me-benzyl i-Pr955 Et 3-Me-benzyl allyl956 Et 3-Me-benzyl cinnamyl957 Et 3-Me-benzyl 2-propynyl958 Et 3-Me-benzyl 2-butynyl959 Et 3-Me-benzyl 2-pyridyl960 Et 3-Me-benzyl benzyl961 Et 3-Me-benzyl 2-Cl-benzyl962 Et 3-Me-benzyl 3-Cl-benzyl963 Et 3-Me-benzyl 4-Cl-benzyl964 Et 3-Me-benzyl 2-Me-benzyl965 Et 3-Me-benzyl 3-Me-benzyl966 Et 3-Me-benzyl 4-Me-benzyl967 Et 3-Me-benzyl 2-MeO-benzyl968 Et 3-Me-benzyl 3-MeO-benzyl969 Et 3-Me-benzyl 4-MeO-benzyl970 Et 3-Me-benzyl 2-Cl-4-MeO-benzyl971 Et 3-Me-benzyl 3,4-(Cl).sub.2 -benzyl972 Et 3-Me-benzyl 2-Me-4-MeO-benzyl973 Et 3-Me-benzyl .alpha.-Me-4-MeO-benzyl974 Et 3-Me-benzyl 4-MeO-PhSO.sub.2975 Et 3-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 40______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________976 Et 4-Me-benzyl Me977 Et 4-Me-benzyl Et978 Et 4-Me-benzyl n-Pr979 Et 4-Me-benzyl i-Pr980 Et 4-Me-benzyl allyl981 Et 4-Me-benzyl cinnamyl982 Et 4-Me-benzyl 2-propynyl983 Et 4-Me-benzyl 2-butynyl984 Et 4-Me-benzyl 2-pyridyl985 Et 4-Me-benzyl benzyl986 Et 4-Me-benzyl 2-Cl-benzyl987 Et 4-Me-benzyl 3-Cl-benzyl988 Et 4-Me-benzyl 4-Cl-benzyl989 Et 4-Me-benzyl 2-Me-benzyl990 Et 4-Me-benzyl 3-Me-benzyl991 Et 4-Me-benzyl 4-Me-benzyl992 Et 4-Me-benzyl 2-MeO-benzyl993 Et 4-Me-benzyl 3-MeO-benzyl994 Et 4-Me-benzyl 4-MeO-benzyl995 Et 4-Me-benzyl 2-Cl-4-MeO-benzyl996 Et 4-Me-benzyl 3,4-(Cl).sub.2 -benzyl997 Et 4-Me-benzyl 2-Me-4-MeO-benzyl998 Et 4-Me-benzyl .alpha.-Me-4-MeO-benzyl999 Et 4-Me-benzyl 4-MeO-PhSO.sub.21000 Et 4-Me-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 41______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1001 Et 2-MeO-benzyl Me1002 Et 2-MeO-benzyl Et1003 Et 2-MeO-benzyl n-Pr1004 Et 2-MeO-benzyl i-Pr1005 Et 2-MeO-benzyl allyl1006 Et 2-MeO-benzyl cinnamyl1007 Et 2-MeO-benzyl 2-propynyl1008 Et 2-MeO-benzyl 2-butynyl1009 Et 2-MeO-benzyl 2-pyridyl1010 Et 2-MeO-benzyl benzyl1011 Et 2-MeO-benzyl 2-Cl-benzyl1012 Et 2-MeO-benzyl 3-Cl-benzyl1013 Et 2-MeO-benzyl 4-Cl-benzyl1014 Et 2-MeO-benzyl 2-Me-benzyl1015 Et 2-MeO-benzyl 3-Me-benzyl1016 Et 2-MeO-benzyl 4-Me-benzyl1017 Et 2-MeO-benzyl 2-MeO-benzyl1018 Et 2-MeO-benzyl 3-MeO-benzyl1019 Et 2-MeO-benzyl 4-MeO-benzyl1020 Et 2-MeO-benzyl 2-Cl-4-MeO-benzyl1021 Et 2-MeO-benzyl 3,4-(Cl).sub.2 -benzyl1022 Et 2-MeO-benzyl 2-Me-4-MeO-benzyl1023 Et 2-MeO-benzyl .alpha.-Me-4-MeO-benzyl1024 Et 2-MeO-benzyl 4-MeO-PhSO.sub.21025 Et 2-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 42______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1026 Et 3-MeO-benzyl Me1027 Et 3-MeO-benzyl Et1028 Et 3-MeO-benzyl n-Pr1029 Et 3-MeO-benzyl i-Pr1030 Et 3-MeO-benzyl allyl1031 Et 3-MeO-benzyl cinnamyl1032 Et 3-MeO-benzyl 2-propynyl1033 Et 3-MeO-benzyl 2-butynyl1034 Et 3-MeO-benzyl 2-pyridyl1035 Et 3-MeO-benzyl benzyl1036 Et 3-MeO-benzyl 2-Cl-benzyl1037 Et 3-MeO-benzyl 3-Cl-benzyl1038 Et 3-MeO-benzyl 4-Cl-benzyl1039 Et 3-MeO-benzyl 2-Me-benzyl1040 Et 3-MeO-benzyl 3-Me-benzyl1041 Et 3-MeO-benzyl 4-Me-benzyl1042 Et 3-MeO-benzyl 2-MeO-benzyl1043 Et 3-MeO-benzyl 3-MeO-benzyl1044 Et 3-MeO-benzyl 4-MeO-benzyl1045 Et 3-MeO-benzyl 2-Cl-4-MeO-benzyl1046 Et 3-MeO-benzyl 3,4-(Cl).sub.2 -benzyl1047 Et 3-MeO-benzyl 2-Me-4-MeO-benzyl1048 Et 3-MeO-benzyl .alpha.-Me-4-MeO-benzyl1049 Et 3-MeO-benzyl 4-MeO-PhSO.sub.21050 Et 3-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 43______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1051 Et 4-MeO-benzyl Me1052 Et 4-MeO-benzyl Et1053 Et 4-MeO-benzyl n-Pr1054 Et 4-MeO-benzyl i-Pr1055 Et 4-MeO-benzyl allyl1056 Et 4-MeO-benzyl cinnamyl1057 Et 4-MeO-benzyl 2-propynyl1058 Et 4-MeO-benzyl 2-butynyl1059 Et 4-MeO-benzyl 2-pyridyl1060 Et 4-MeO-benzyl benzyl1061 Et 4-MeO-benzyl 2-Cl-benzyl1062 Et 4-MeO-benzyl 3-Cl-benzyl1063 Et 4-MeO-benzyl 4-Cl-benzyl1064 Et 4-MeO-benzyl 2-Me-benzyl1065 Et 4-MeO-benzyl 3-Me-benzyl1066 Et 4-MeO-benzyl 4-Me-benzyl1067 Et 4-MeO-benzyl 2-MeO-benzyl1068 Et 4-MeO-benzyl 3-MeO-benzyl1069 Et 4-MeO-benzyl 4-MeO-benzyl1070 Et 4-MeO-benzyl 2-Cl-4-MeO-benzyl1071 Et 4-MeO-benzyl 3,4-(Cl).sub.2 -benzyl1072 Et 4-MeO-benzyl 2-Me-4-MeO-benzyl1073 Et 4-MeO-benzyl .alpha.-Me-4-MeO-benzyl1074 Et 4-MeO-benzyl 4-MeO-PhSO.sub.21075 Et 4-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 44______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1076 Et 3,4-(Cl).sub.2 -benzyl Me1077 Et 3,4-(Cl).sub.2 -benzyl Et1078 Et 3,4-(Cl).sub.2 -benzyl n-Pr1079 Et 3,4-(Cl).sub.2 -benzyl i-Pr1080 Et 3,4-(Cl).sub.2 -benzyl allyl1081 Et 3,4-(Cl).sub.2 -benzyl cinnamyl1082 Et 3,4-(Cl).sub.2 -benzyl 2-propynyl1083 Et 3,4-(Cl).sub.2 -benzyl 2-butynyl1084 Et 3,4-(Cl).sub.2 -benzyl 2-pyridyl1085 Et 3,4-(Cl).sub.2 -benzyl benzyl1086 Et 3,4-(Cl).sub.2 -benzyl 2-Cl-benzyl1087 Et 3,4-(Cl).sub.2 -benzyl 3-Cl-benzyl1088 Et 3,4-(Cl).sub.2 -benzyl 4-Cl-benzyl1089 Et 3,4-(Cl).sub.2 -benzyl 2-Me-benzyl1090 Et 3,4-(Cl).sub.2 -benzyl 3-Me-benzyl1091 Et 3,4-(Cl).sub.2 -benzyl 4-Me-benzyl1092 Et 3,4-(Cl).sub.2 -benzyl 2-MeO-benzyl1093 Et 3,4-(Cl).sub.2 -benzyl 3-MeO-benzyl1094 Et 3,4-(Cl).sub.2 -benzyl 4-MeO-benzyl1095 Et 3,4-(Cl).sub.2 -benzyl 2-Cl-4-MeO-benzyl1096 Et 3,4-(Cl).sub.2 -benzyl 3,4-(Cl).sub.2 -benzyl1097 Et 3,4-(Cl).sub.2 -benzyl 2-Me-4-MeO-benzyl1098 Et 3,4-(Cl).sub.2 -benzyl .alpha.-Me-4-MeO-benzyl1099 Et 3,4-(Cl).sub.2 -benzyl 4-MeO-PhSO.sub.21100 Et 3,4-(Cl).sub.2 -benzyl 4-pyridylCH.sub.2______________________________________
TABLE 45______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1101 Et 2-Cl-4-MeO-benzyl Me1102 Et 2-Cl-4-MeO-benzyl Et1103 Et 2-Cl-4-MeO-benzyl n-Pr1104 Et 2-Cl-4-MeO-benzyl i-Pr1105 Et 2-Cl-4-MeO-benzyl allyl1106 Et 2-Cl-4-MeO-benzyl cinnamyl1107 Et 2-Cl-4-MeO-benzyl 2-propynyl1108 Et 2-Cl-4-MeO-benzyl 2-butynyl1109 Et 2-Cl-4-MeO-benzyl 2-pyridyl1110 Et 2-Cl-4-MeO-benzyl benzyl1111 Et 2-Cl-4-MeO-benzyl 2-Cl-benzyl1112 Et 2-Cl-4-MeO-benzyl 3-Cl-benzyl1113 Et 2-Cl-4-MeO-benzyl 4-Cl-benzyl1114 Et 2-Cl-4-MeO-benzyl 2-Me-benzyl1115 Et 2-Cl-4-MeO-benzyl 3-Me-benzyl1116 Et 2-Cl-4-MeO-benzyl 4-Me-benzyl1117 Et 2-Cl-4-MeO-benzyl 2-MeO-benzyl1118 Et 2-Cl-4-MeO-benzyl 3-MeO-benzyl1119 Et 2-Cl-4-MeO-benzyl 4-MeO-benzyl1120 Et 2-Cl-4-MeO-benzyl 2-Cl-4-MeO-benzyl1121 Et 2-Cl-4-MeO-benzyl 3,4-(Cl).sub.2 -benzyl1122 Et 2-Cl-4-MeO-benzyl 2-Me-4-MeO-benzyl1123 Et 2-Cl-4-MeO-benzyl .alpha.-Me-4-MeO-benzyl1124 Et 2-Cl-4-MeO-benzyl 4-MeO-PhSO.sub.21125 Et 2-Cl-4-MeO-benzyl 4-pyridylCH.sub.2______________________________________
TABLE 46______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1126 Et 2-pyridylCH.sub.2 Me1127 Et 2-pyridylCH.sub.2 Et1128 Et 2-pyridylCH.sub.2 n-Pr1129 Et 2-pyridylCH.sub.2 i-Pr1130 Et 2-pyridylCH.sub.2 allyl1131 Et 2-pyridylCH.sub.2 cinnamyl1132 Et 2-pyridylCH.sub.2 2-propynyl1133 Et 2-pyridylCH.sub.2 2-butynyl1134 Et 2-pyridylCH.sub.2 2-pyridyl1135 Et 2-pyridylCH.sub.2 benzyl1136 Et 2-pyridylCH.sub.2 2-Cl-benzyl1137 Et 2-pyridylCH.sub.2 3-Cl-benzyl1138 Et 2-pyridylCH.sub.2 4-Cl-benzyl1139 Et 2-pyridylCH.sub.2 2-Me-benzyl1140 Et 2-pyridylCH.sub.2 3-Me-benzyl1141 Et 2-pyridylCH.sub.2 4-Me-benzyl1142 Et 2-pyridylCH.sub.2 2-MeO-benzyl1143 Et 2-pyridylCH.sub.2 3-MeO-benzyl1144 Et 2-pyridylCH.sub.2 4-MeO-benzyl1145 Et 2-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1146 Et 2-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl1147 Et 2-pyridylCH.sub.2 2-Me-4-MeO-benzyl1148 Et 2-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl1149 Et 2-pyridylCH.sub.2 4-MeO-PhSO.sub.21150 Et 2-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 47______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1151 Et 3-pyridylCH.sub.2 Me1152 Et 3-pyridylCH.sub.2 Et1153 Et 3-pyridylCH.sub.2 n-Pr1154 Et 3-pyridylCH.sub.2 i-Pr1155 Et 3-pyridylCH.sub.2 allyl1156 Et 3-pyridylCH.sub.2 cinnamyl1157 Et 3-pyridylCH.sub.2 2-propynyl1158 Et 3-pyridylCH.sub.2 2-butynyl1159 Et 3-pyridylCH.sub.2 2-pyridyl1160 Et 3-pyridylCH.sub.2 benzyl1161 Et 3-pyridylCH.sub.2 2-Cl-benzyl1162 Et 3-pyridylCH.sub.2 3-Cl-benzyl1163 Et 3-pyridylCH.sub.2 4-Cl-benzyl1164 Et 3-pyridylCH.sub.2 2-Me-benzyl1165 Et 3-pyridylCH.sub.2 3-Me-benzyl1166 Et 3-pyridylCH.sub.2 4-Me-benzyl1167 Et 3-pyridylCH.sub.2 2-MeO-benzyl1168 Et 3-pyridylCH.sub.2 3-MeO-benzyl1169 Et 3-pyridylCH.sub.2 4-MeO-benzyl1170 Et 3-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1171 Et 3-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl1172 Et 3-pyridylCH.sub.2 2-Me-4-MeO-benzyl1173 Et 3-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl1174 Et 3-pyridylCH.sub.2 4-MeO-PhSO.sub.21175 Et 3-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 48______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1176 Et 4-pyridylCH.sub.2 Me1177 Et 4-pyridylCH.sub.2 Et1178 Et 4-pyridylCH.sub.2 n-Pr1179 Et 4-pyridylCH.sub.2 i-Pr1180 Et 4-pyridylCH.sub.2 allyl1181 Et 4-pyridylCH.sub.2 cinnamyl1182 Et 4-pyridylCH.sub.2 2-propynyl1183 Et 4-pyridylCH.sub.2 2-butynyl1184 Et 4-pyridylCH.sub.2 2-pyridyl1185 Et 4-pyridylCH.sub.2 benzyl1186 Et 4-pyridylCH.sub.2 2-Cl-benzyl1187 Et 4-pyridylCH.sub.2 3-Cl-benzyl1188 Et 4-pyridylCH.sub.2 4-Cl-benzyl1189 Et 4-pyridylCH.sub.2 2-Me-benzyl1190 Et 4-pyridylCH.sub.2 3-Me-benzyl1191 Et 4-pyridylCH.sub.2 4-Me-benzyl1192 Et 4-pyridylCH.sub.2 2-MeO-benzyl1193 Et 4-pyridylCH.sub.2 3-MeO-benzyl1194 Et 4-pyridylCH.sub.2 4-MeO-benzyl1195 Et 4-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1196 Et 4-pyridylCH.sub.2 3,4-(Cl).sub.2 -benzyl1197 Et 4-pyridylCH.sub.2 2-Me-4-MeO-benzyl1198 Et 4-pyridylCH.sub.2 .alpha.-Me-4-MeO-benzyl1199 Et 4-pyridylCH.sub.2 4-MeO-PhSO.sub.21200 Et 4-pyridylCH.sub.2 4-pyridylCH.sub.2______________________________________
TABLE 49______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1201 Pr Me Me1202 Pr Me allyl1203 Pr Me benzyl1204 Pr Me 2-Cl-benzyl1205 Pr Me 4-Cl-benzyl1206 Pr Me 2-Me-benzyl1207 Pr Me 4-Me-benzyl1208 Pr Me 2-Cl-4-MeO-benzyl1209 Pr Me 2-MeO-benzyl1210 Pr Me 4-MeO-benzyl1211 Pr allyl Me1212 Pr allyl allyl1213 Pr allyl benzyl1214 Pr allyl 2-Cl-benzyl1215 Pr allyl 4-Cl-benzyl1216 Pr allyl 2-Me-benzyl1217 Pr allyl 4-Me-benzyl1218 Pr allyl 2-Cl-4-MeO-benzyl1219 Pr allyl 2-MeO-benzyl1220 Pr allyl 4-MeO-benzyl1221 Pr 2-propynyl Me1222 Pr 2-propynyl allyl1223 Pr 2-propynyl benzyl1224 Pr 2-propynyl 2-Cl-benzy1225 Pr 2-propynyl 4-Cl-benzyl______________________________________
TABLE 50______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1226 Pr 2-propynyl 2-Me-benzyl1227 Pr 2-propynyl 4-Me-benzyl1228 Pr 2-propynyl 2-Cl-4-MeO-benzyl1229 Pr 2-propynyl 2-MeO-benzyl1230 Pr 2-propynyl 4-MeO-benzyl1231 Pr benzyl Me1232 Pr benzyl allyl1233 Pr benzyl benzyl1234 Pr benzyl 2-Cl-benzyl1235 Pr benzyl 4-Cl-benzyl1236 Pr benzyl 2-Me-benzyl1237 Pr benzyl 4-Me-benzyl1238 Pr benzyl 2-Cl-4-MeO-benzyl1239 Pr benzyl 2-MeO-benzyl1240 Pr benzyl 4-MeO-benzyl1241 Pr 4-Me-benzyl Me1242 Pr 4-Me-benzyl allyl1243 Pr 4-Me-benzyl benzyl1244 Pr 4-Me-benzyl 2-Cl-benzyl1245 Pr 4-Me-benzyl 4-Cl-benzyl1246 Pr 4-Me-benzyl 2-Me-benzyl1247 Pr 4-Me-benzyl 4-Me-benzyl1248 Pr 4-Me-benzyl 2-Cl-4-MeO-benzyl1249 Pr 4-Me-benzyl 2-MeO-benzyl1250 Pr 4-Me-benzyl 4-MeO-benzyl______________________________________
TABLE 51______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1251 Pr 4-Cl-benzyl Me1252 Pr 4-Cl-benzyl allyl1253 Pr 4-Cl-benzyl benzyl1254 Pr 4-Cl-benzyl 2-Cl-benzyl1255 Pr 4-Cl-benzyl 4-Cl-benzyl1256 Pr 4-Cl-benzyl 2-Me-benzyl1257 Pr 4-Cl-benzyl 4-Me-benzyl1258 Pr 4-Cl-benzyl 2-Cl-4-MeO-benzyl1259 Pr 4-Cl-benzyl 2-MeO-benzyl1260 Pr 4-Cl-benzyl 4-MeO-benzyl1261 Pr 4-MeO-benzyl Me1262 Pr 4-MeO-benzyl allyl1263 Pr 4-MeO-benzyl benzyl1264 Pr 4-MeO-benzyl 2-Cl-benzyl1265 Pr 4-MeO-benzyl 4-Cl-benzyl1266 Pr 4-MeO-benzyl 2-Me-benzyl1267 Pr 4-MeO-benzyl 4-Me-benzyl1268 Pr 4-MeO-benzyl 2-Cl-4-MeO-benzyl1269 Pr 4-MeO-benzyl 2-MeO-benzyl1270 Pr 4-MeO-benzyl 4-MeO-benzyl1271 Pr 2-pyridylCH.sub.2 Me1272 Pr 2-pyridylCH.sub.2 allyl1273 Pr 2-pyridylCH.sub.2 benzyl1274 Pr 2-pyridylCH.sub.2 2-Cl-benzyl1275 Pr 2-pyridylCH.sub.2 4-Cl-benzyl______________________________________
TABLE 52______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1276 Pr 2-pyridylCH.sub.2 2-Me-benzyl1277 Pr 2-pyridylCH.sub.2 4-Me-benzyl1278 Pr 2-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1279 Pr 2-pyridylCH.sub.2 2-MeO-benzyl1280 Pr 2-pyridylCH.sub.2 4-MeO-benzyl1281 Pr 3-pyridylCH.sub.2 Me1282 Pr 3-pyridylCH.sub.2 allyl1283 Pr 3-pyridylCH.sub.2 benzyl1284 Pr 3-pyridylCH.sub.2 2-Cl-benzyl1285 Pr 3-pyridylCH.sub.2 4-Cl-benzyl1286 Pr 3-pyridylCH.sub.2 2-Me-benzyl1287 Pr 3-pyridylCH.sub.2 4-Me-benzyl1288 Pr 3-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1289 Pr 3-pyridylCH.sub.2 2-MeO-benzyl1290 Pr 3-pyridylCH.sub.2 4-MeO-benzyl1291 Pr 4-pyridylCH.sub.2 Me1292 Pr 4-pyridylCH.sub.2 allyl1293 Pr 4-pyridylCH.sub.2 benzyl1294 Pr 4-pyridylCH.sub.2 2-Cl-benzyl1295 Pr 4-pyridylCH.sub.2 4-Cl-benzyl1296 Pr 4-pyridylCH.sub.2 2-Me-benzyl1297 Pr 4-pyridylCH.sub.2 4-Me-benzyl1298 Pr 4-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1299 Pr 4-pyridylCH.sub.2 2-MeO-benzyl1300 Pr 4-pyridylCH.sub.2 4-MeO-benzyl______________________________________
TABLE 53______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1301 Ph Me Me1302 Ph Me allyl1303 Ph Me benzyl1304 Ph Me 2-Cl-benzyl1305 Ph Me 4-Cl-benzyl1306 Ph Me 2-Me-benzyl1307 Ph Me 4-Me-benzyl1308 Ph Me 2-Cl-4-MeO-benzyl1309 Ph Me 2-MeO-benzyl1310 Ph Me 4-MeO-benzyl1311 Ph allyl Me1312 Ph allyl allyl1313 Ph allyl benzyl1314 Ph allyl 2-Cl-benzyl1315 Ph allyl 4-Cl-benzyl1316 Ph allyl 2-Me-benzyl1317 Ph allyl 4-Me-benzyl1318 Ph allyl 2-Cl-4-MeO-benzyl1319 Ph allyl 2-MeO-benzyl1320 Ph allyl 4-MeO-benzyl1321 Ph 2-propynyl Me1322 Ph 2-propynyl allyl1323 Ph 2-propynyl benzyl1324 Ph 2-propynyl 2-Cl-benzy1325 Ph 2-propynyl 4-Cl-benzyl______________________________________
TABLE 54______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1326 Ph 2-propynyl 2-Me-benzyl1327 Ph 2-propynyl 4-Me-benzyl1328 Ph 2-propynyl 2-Cl-4-MeO-benzyl1329 Ph 2-propynyl 2-MeO-benzyl1330 Ph 2-propynyl 4-MeO-benzyl1331 Ph benzyl Me1332 Ph benzyl allyl1333 Ph benzyl benzyl1334 Ph benzyl 2-Cl-benzyl1335 Ph benzyl 4-Cl-benzyl1336 Ph benzyl 2-Me-benzyl1337 Ph benzyl 4-Me-benzyl1338 Ph benzyl 2-Cl-4-MeO-benzyl1339 Ph benzyl 2-MeO-benzyl1340 Ph benzyl 4-MeO-benzyl1341 Ph 4-Me-benzyl Me1342 Ph 4-Me-benzyl allyl1343 Ph 4-Me-benzyl benzyl1344 Ph 4-Me-benzyl 2-Cl-benzyl1345 Ph 4-Me-benzyl 4-Cl-benzyl1346 Ph 4-Me-benzyl 2-Me-benzyl1347 Ph 4-Me-benzyl 4-Me-benzyl1348 Ph 4-Me-benzyl 2-Cl-4-MeO-benzyl1349 Ph 4-Me-benzyl 2-MeO-benzyl1350 Ph 4-Me-benzyl 4-MeO-benzyl______________________________________
TABLE 55______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1351 Ph 4-Cl-benzyl Me1352 Ph 4-Cl-benzyl allyl1353 Ph 4-Cl-benzyl benzyl1354 Ph 4-Cl-benzyl 2-Cl-benzyl1355 Ph 4-Cl-benzyl 4-Cl-benzyl1356 Ph 4-Cl-benzyl 2-Me-benzyl1357 Ph 4-Cl-benzyl 4-Me-benzyl1358 Ph 4-Cl-benzyl 2-Cl-4-MeO-benzyl1359 Ph 4-Cl-benzyl 2-MeO-benzyl1360 Ph 4-Cl-benzyl 4-MeO-benzyl1361 Ph 4-MeO-benzyl Me1362 Ph 4-MeO-benzyl allyl1363 Ph 4-MeO-benzyl benzyl1364 Ph 4-MeO-benzyl 2-Cl-benzyl1365 Ph 4-MeO-benzyl 4-Cl-benzyl1366 Ph 4-MeO-benzyl 2-Me-benzyl1367 Ph 4-MeO-benzyl 4-Me-benzyl1368 Ph 4-MeO-benzyl 2-Cl-4-MeO-benzyl1369 Ph 4-MeO-benzyl 2-MeO-benzyl1370 Ph 4-MeO-benzyl 4-MeO-benzyl1371 Ph 2-pyridylCH.sub.2 Me1372 Ph 2-pyridylCH.sub.2 allyl1373 Ph 2-pyridylCH.sub.2 benzyl1374 Ph 2-pyridylCH.sub.2 2-Cl-benzyl1375 Ph 2-pyridylCH.sub.2 4-Cl-benzyl______________________________________
TABLE 56______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1376 Ph 2-pyridylCH.sub.2 2-Me-benzyl1377 Ph 2-pyridylCH.sub.2 4-Me-benzyl1378 Ph 2-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1379 Ph 2-pyridylCH.sub.2 2-MeO-benzyl1380 Ph 2-pyridylCH.sub.2 4-MeO-benzyl1381 Ph 3-pyridylCH.sub.2 Me1382 Ph 3-pyridylCH.sub.2 allyl1383 Ph 3-pyridylCH.sub.2 benzyl1384 Ph 3-pyridylCH.sub.2 2-Cl-benzyl1385 Ph 3-pyridylCH.sub.2 4-Cl-benzyl1386 Ph 3-pyridylCH.sub.2 2-Me-benzyl1387 Ph 3-pyridylCH.sub.2 4-Me-benzyl1388 Ph 3-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1389 Ph 3-pyridylCH.sub.2 2-MeO-benzyl1390 Ph 3-pyridylCH.sub.2 4-MeO-benzyl1391 Ph 4-pyridylCH.sub.2 Me1392 Ph 4-pyridylCH.sub.2 allyl1393 Ph 4-pyridylCH.sub.2 benzyl1394 Ph 4-pyridylCH.sub.2 2-Cl-benzyl1395 Ph 4-pyridylCH.sub.2 4-Cl-benzyl1396 Ph 4-pyridylCH.sub.2 2-Me-benzyl1397 Ph 4-pyridylCH.sub.2 4-Me-benzyl1398 Ph 4-pyridylCH.sub.2 2-Cl-4-MeO-benzyl1399 Ph 4-pyridylCH.sub.2 2-MeO-benzyl1400 Ph 4-pyridylCH.sub.2 4-MeO-benzyl______________________________________
TABLE 57______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1401 Pr .sup.i benzyl benzyl1402 Pr .sup.i benzyl 4-Cl-benzyl1403 Pr .sup.i benzyl 4-Me-benzyl1404 Pr .sup.i benzyl 4-MeO-benzyl1405 Pr .sup.i 4-Cl-benzyl benzyl1406 Pr .sup.i 4-Cl-benzyl 4-Cl-benzyl1407 Pr .sup.i 4-Cl-benzyl 4-Me-benzyl1408 Pr .sup.i 4-Cl-benzyl 4-MeO-benzyl1409 Pr .sup.i 4-Me-benzyl benzyl1410 Pr .sup.i 4-Me-benzyl 4-Cl-benzyl1411 Pr .sup.i 4-Me-benzyl 4-Me-benzyl1412 Pr .sup.i 4-Me-benzyl 4-MeO-benzyl1413 Pr .sup.i 4-MeO-benzyl benzyl1414 Pr .sup.i 4-MeO-benzyl 4-Cl-benzyl1415 Pr .sup.i 4-MeO-benzyl 4-Me-benzyl1416 Pr .sup.i 4-MeO-benzyl 4-MeO-benzyl1417 Pr .sup.i 4-pyridylCH.sub.2 benzyl1418 Pr .sup.i 4-pyridylCH.sub.2 4-Cl-benzyl1419 Pr .sup.i 4-pyridylCH.sub.2 4-Me-benzyl1420 Pr .sup.i 4-pyridylCH.sub.2 4-MeO-benzyl1421 Me benzyl Ph1422 Me 4-Cl-benzyl Ph1423 Me 4-Me-benzyl Ph1424 Me 4-MeO-benzyl Ph1425 Me 4-pyridylCH.sub.2 Ph______________________________________
TABLE 58______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1426 Me benzyl 3-Cl-Ph1427 Me 4-Cl-benzyl 3-Cl-Ph1428 Me 4-Me-benzyl 3-Cl-Ph1429 Me 4-MeO-benzyl 3-Cl-Ph1430 Me 4-pyridylCH.sub.2 3-Cl-Ph1431 Me benzyl 4-Cl-Ph1432 Me 4-Cl-benzyl 4-Cl-Ph1433 Me 4-Me-benzyl 4-Cl-Ph1434 Me 4-MeO-benzyl 4-Cl-Ph1435 Me 4-pyridylCH.sub.2 4-Cl-Ph1436 Me benzyl 3-Me-Ph1437 Me 4-Cl-benzyl 3-Me-Ph1438 Me 4-Me-benzyl 3-Me-Ph1439 Me 4-MeO-benzyl 3-Me-Ph1440 Me 4-pyridylCH.sub.2 3-Me-Ph1441 Me benzyl 4-Me-Ph1442 Me 4-Cl-benzyl 4-Me-Ph1443 Me 4-Me-benzyl 4-Me-Ph1444 Me 4-MeO-benzyl 4-Me-Ph1445 Me 4-pyridylCH.sub.2 4-Me-Ph1446 Me benzyl 3-MeO-Ph1447 Me 4-Cl-benzyl 3-MeO-Ph1448 Me 4-Me-benzyl 3-MeO-Ph1449 Me 4-MeO-benzyl 3-MeO-Ph1450 Me 4-pyridylCH.sub.2 3-MeO-Ph______________________________________
TABLE 59______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1451 Me benzyl 4-MeO-Ph1452 Me 4-Cl-benzyl 4-MeO-Ph1453 Me 4-Me-benzyl 4-MeO-Ph1454 Me 4-MeO-benzyl 4-MeO-Ph1455 Me 4-pyridylCH.sub.2 4-MeO-Ph1456 Et benzyl Ph1457 Et 4-Cl-benzyl Ph1458 Et 4-Me-benzyl Ph1459 Et 4-MeO-benzyl Ph1460 Et 4-pyridylCH.sub.2 Ph1461 Et benzyl 3-Cl-Ph1462 Et 4-Cl-benzyl 3-Cl-Ph1463 Et 4-Me-benzyl 3-Cl-Ph1464 Et 4-MeO-benzyl 3-Cl-Ph1465 Et 4-pyridylCH.sub.2 3-Cl-Ph1466 Et benzyl 4-Cl-Ph1467 Et 4-Cl-benzyl 4-Cl-Ph1468 Et 4-Me-benzyl 4-Cl-Ph1469 Et 4-MeO-benzyl 4-Cl-Ph1470 Et 4-pyridylCH.sub.2 4-Cl-Ph1471 Et benzyl 3-Me-Ph1472 Et 4-Cl-benzyl 3-Me-Ph1473 Et 4-Me-benzyl 3-Me-Ph1474 Et 4-MeO-benzyl 3-Me-Ph1475 Et 4-pyridylCH.sub.2 3-Me-Ph______________________________________
TABLE 60______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1476 Et benzyl 4-Me-Ph1477 Et 4-Cl-benzyl 4-Me-Ph1478 Et 4-Me-benzyl 4-Me-Ph1479 Et 4-MeO-benzyl 4-Me-Ph1480 Et 4-pyridylCH.sub.2 4-Me-Ph1481 Et benzyl 3-MeO-Ph1482 Et 4-Cl-benzyl 3-MeO-Ph1483 Et 4-Me-benzyl 3-MeO-Ph1484 Et 4-MeO-benzyl 3-MeO-Ph1485 Et 4-pyridylCH.sub.2 3-MeO-Ph1486 Et benzyl 4-MeO-Ph1487 Et 4-Cl-benzyl 4-MeO-Ph1488 Et 4-Me-benzyl 4-MeO-Ph1489 Et 4-MeO-benzyl 4-MeO-Ph1490 Et 4-pyridylCH.sub.2 4-MeO-Ph1491 Me 4-H.sub.2 N-benzyl benzyl1492 Me 4-H.sub.2 N-benzyl 4-Cl-benzyl1493 Me 4-H.sub.2 N-benzyl 4-HO-benzyl1494 Me 4-H.sub.2 N-benzyl 4-MeO-benzyl1495 Me 4-H.sub.2 N-benzyl .alpha.-Me-4-MeO-benzyl1496 Me 4-H.sub.2 N-benzyl 4-EtO-benzyl1497 Me 4-H.sub.2 N-benzyl 4-PrO-benzyl1498 Me 4-H.sub.2 N-benzyl 4-AcO-benzyl1499 Me 4-H.sub.2 N-benzyl 4-MOMO-benzyl1500 Me 4-H.sub.2 N-benzyl 4-MeO-Ph(CH.sub.2).sub.2______________________________________
TABLE 61______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1501 Me 4-AcNH-benzyl benzyl1502 Me 4-AcNH-benzyl 4-Cl-benzyl1503 Me 4-AcNH-benzyl 4-HO-benzyl1504 Me 4-AcNH-benzyl 4-MeO-benzyl1505 Me 4-AcNH-benzyl .alpha.-Me-4-MeO-benzyl1506 Me 4-AcNH-benzyl 4-EtO-benzyl1507 Me 4-AcNH-benzyl 4-PrO-benzyl1508 Me 4-AcNH-benzyl 4-AcO-benzyl1509 Me 4-AcNH-benzyl 4-MOMO-benzyl1510 Me 4-AcNH-benzyl 4-MeO-Ph(CH.sub.2).sub.21511 Me 4-CF.sub.3 -benzyl benzyl1512 Me 4-CF.sub.3 -benzyl 4-Cl-benzyl1513 Me 4-CF.sub.3 -benzyl 4-HO-benzyl1514 Me 4-CF.sub.3 -benzyl 4-MeO-benzyl1515 Me 4-CF.sub.3 -benzyl .alpha.-Me-4-MeO-benzyl1516 Me 4-CF.sub.3 -benzyl 4-EtO-benzyl1517 Me 4-CF.sub.3 -benzyl 4-PrO-benzyl1518 Me 4-CF.sub.3 -benzyl 4-AcO-benzyl1519 Me 4-CF.sub.3 -benzyl 4-MOMO-benzyl1520 Me 4-CF.sub.3 -benzyl 4-MeO-Ph(CH.sub.2).sub.21521 Me 2,5-(Me).sub.2 -benzyl benzyl1522 Me 2,5-(Me).sub.2 -benzyl 4-Cl-benzyl1523 Me 2,5-(Me).sub.2 -benzyl 4-HO-benzyl1524 Me 2,5-(Me).sub.2 -benzyl 4-MeO-benzyl1525 Me 2,5-(Me).sub.2 -benzyl .alpha.-Me-4-MeO-benzyl______________________________________
TABLE 62______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1526 Me 2,5-(Me).sub.2 -benzyl 4-EtO-benzyl1527 Me 2,5-(Me).sub.2 -benzyl 4-PrO-benzyl1528 Me 2,5-(Me).sub.2 -benzyl 4-AcO-benzyl1529 Me 2,5-(Me).sub.2 -benzyl 4-MOMO-benzyl1530 Me 2,5-(Me).sub.2 -benzyl 4-MeO-Ph(CH.sub.2).sub.21531 Me 1-naphthylmethyl benzyl1532 Me 1-naphthylmethyl 4-Cl-benzyl1533 Me 1-naphthylmethyl 4-HO-benzyl1534 Me 1-naphthylmethyl 4-MeO-benzyl1535 Me 1-naphthylmethyl .alpha.-Me-4-MeO-benzyl1536 Me 1-naphthylmethyl 4-EtO-benzyl1537 Me 1-naphthylmethyl 4-PrO-benzyl1538 Me 1-naphthylmethyl 4-AcO-benzyl1539 Me 1-naphthylmethyl 4-MOMO-benzyl1540 Me 1-naphthylmethyl 4-MeO-Ph(CH.sub.2).sub.21541 Me 2-naphthylmethyl benzyl1542 Me 2-naphthylmethyl 4-Cl-benzyl1543 Me 2-naphthylmethyl 4-HO-benzyl1544 Me 2-naphthylmethyl 4-MeO-benzyl1545 Me 2-naphthylmethyl .alpha.-Me-4-MeO-benzyl1546 Me 2-naphthylmethyl 4-EtO-benzyl1547 Me 2-naphthylmethyl 4-PrO-benzyl1548 Me 2-naphthylmethyl 4-AcO-benzyl1549 Me 2-naphthylmethyl 4-MOMO-benzyl1550 Me 2-naphthylmethyl 4-MeO-Ph(CH.sub.2).sub.2______________________________________
TABLE 63______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1551 Me 2-thenyl benzyl1552 Me 2-thenyl 4-Cl-benzyl1553 Me 2-thenyl 4-HO-benzyl1554 Me 2-thenyl 4-MeO-benzyl1555 Me 2-thenyl .alpha.-Me-4-MeO-benzyl1556 Me 2-thenyl 4-EtO-benzyl1557 Me 2-thenyl 4-PrO-benzyl1558 Me 2-thenyl 4-AcO-benzyl1559 Me 2-thenyl 4-MOMO-benzyl1560 Me 2-thenyl 4-MeO-Ph(CH.sub.2).sub.21561 Me 3-thenyl benzyl1562 Me 3-thenyl 4-Cl-benzyl1563 Me 3-thenyl 4-HO-benzyl1564 Me 3-thenyl 4-MeO-benzyl1565 Me 3-thenyl .alpha.-Me-4-MeO-benzyl1566 Me 3-thenyl 4-EtO-benzyl1567 Me 3-thenyl 4-PrO-benzyl1568 Me 3-thenyl 4-AcO-benzyl1569 Me 3-thenyl 4-MOMO-benzyl1570 Me 3-thenyl 4-MeO-Ph(CH.sub.2).sub.21571 Me benzyl 4-HO-benzyl1572 Me benzyl 4-EtO-benzyl1573 Me benzyl 4-PrO-benzyl1574 Me benzyl 4-AcO-benzyl1575 Me benzyl 4-MOMO-benzyl______________________________________
TABLE 64______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1576 Me benzyl 4-MeO-Ph(CH.sub.2).sub.21577 Me benzyl 4-AllylO-benzyl1578 Me benzyl 4-PhO-benzyl1579 Me 2-propynyl 4-HO-benzyl1580 Me 2-propynyl 4-EtO-benzyl1581 Me 2-propynyl 4-PrO-benzyl1582 Me 2-propynyl 4-AcO-benzyl1583 Me 2-propynyl 4-MOMO-benzyl1584 Me 2-propynyl 4-MeO-Ph(CH.sub.2).sub.21585 Me 2-Cl-benzyl 4-HO-benzyl1586 Me 2-Cl-benzyl 4-EtO-benzyl1587 Me 2-Cl-benzyl 4-PrO-benzyl1588 Me 2-Cl-benzyl 4-AcO-benzyl1589 Me 2-Cl-benzyl 4-MOMO-benzyl1590 Me 2-Cl-benzyl 4-MeO-Ph(CH.sub.2).sub.21591 Me 4-Cl-benzyl 4-HO-benzyl1592 Me 4-Cl-benzyl 4-EtO-benzyl1593 Me 4-Cl-benzyl 4-PrO-benzyl1594 Me 4-Cl-benzyl 4-AcO-benzyl1595 Me 4-Cl-benzyl 4-MOMO-benzyl1596 Me 4-Cl-benzyl 4-MeO-Ph(CH.sub.2).sub.21597 Me 2-MeO-benzyl 4-HO-benzyl1598 Me 2-MeO-benzyl 4-EtO-benzyl1599 Me 2-MeO-benzyl 4-PrO-benzyl1600 Me 2-MeO-benzyl 4-AcO-benzyl______________________________________
TABLE 65______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1601 Me 2-MeO-benzyl 4-MOMO-benzyl1602 Me 2-MeO-benzyl 4-MeO-Ph(CH.sub.2).sub.21603 Me 4-MeO-benzyl 4-HO-benzyl1604 Me 4-MeO-benzyl 4-EtO-benzyl1605 Me 4-MeO-benzyl 4-Pr-benzyl1606 Me 4-MeO-benzyl 4-AcO-benzyl1607 Me 4-MeO-benzyl 4-MOMO-benzyl1608 Me 4-MeO-benzyl 4-MeO-Ph(CH.sub.2).sub.21609 Me 2-pyridylCH.sub.2 4-HO-benzyl1610 Me 2-pyridylCH.sub.2 4-EtO-benzyl1611 Me 2-pyridylCH.sub.2 4-PrO-benzyl1612 Me 2-pyridylCH.sub.2 4-AcO-benzyl1613 Me 2-pyridylCH.sub.2 4-MOMO-benzyl1614 Me 2-pyridylCH.sub.2 4-MeO-Ph(CH.sub.2).sub.21615 Me 4-pyridylCH.sub.2 4-HO-benzyl1616 Me 4-pyridylCH.sub.2 4-EtO-benzyl1617 Me 4-pyridylCH.sub.2 4-PrO-benzyl1618 Me 4-pyridylCH.sub.2 4-AcO-benzyl1619 Me 4-pyridylCH.sub.2 4-MOMO-benzyl1620 Me 4-pyridylCH.sub.2 4-MeO-Ph(CH.sub.2).sub.21621 Et 4-H.sub.2 N-benzyl benzyl1622 Et 4-H.sub.2 N-benzyl 4-Cl-benzyl1623 Et 4-H.sub.2 N-benzyl 4-HO-benzyl1624 Et 4-H.sub.2 N-benzyl 4-MeO-benzyl1625 Et 4-H.sub.2 N-benzyl .alpha.-Me-4-MeO-benzyl______________________________________
TABLE 66______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1626 Et 4-H.sub.2 N-benzyl 4-EtO-benzyl1627 Et 4-H.sub.2 N-benzyl 4-PrO-benzyl1628 Et 4-H.sub.2 N-benzyl 4-AcO-benzyl1629 Et 4-H.sub.2 N-benzyl 4-MOMO-benzyl1630 Et 4-H.sub.2 N-benzyl 4-MeO-Ph(CH.sub.2).sub.21631 Et 4-AcNH-benzyl benzyl1632 Et 4-AcNH-benzyl 4-Cl-benzyl1633 Et 4-AcNH-benzyl 4-HO-benzyl1634 Et 4-AcNH-benzyl 4-MeO-benzyl1635 Et 4-AcNH-benzyl .alpha.-Me-4-MeO-benzyl1636 Et 4-AcNH-benzyl 4-EtO-benzyl1637 Et 4-AcNH-benzyl 4-PrO-benzyl1638 Et 4-AcNH-benzyl 4-AcO-benzyl1639 Et 4-AcNH-benzyl 4-MOMO-benzyl1640 Et 4-AcNH-benzyl 4-MeO-Ph(CH.sub.2).sub.21641 Et 4-CF.sub.3 -benzyl benzyl1642 Et 4-CF.sub.3 -benzyl 4-Cl-benzyl1643 Et 4-CF.sub.3 -benzyl 4-HO-benzyl1644 Et 4-CF.sub.3 -benzyl 4-MeO-benzyl1645 Et 4-CF.sub.3 -benzyl .alpha.-Me-4-MeO-benzyl1646 Et 4-CF.sub.3 -benzyl 4-EtO-benzyl1647 Et 4-CF.sub.3 -benzyl 4-PrO-benzyl1648 Et 4-CF.sub.3 -benzyl 4-AcO-benzyl1649 Et 4-CF.sub.3 -benzyl 4-MOMO-benzyl1650 Et 4-CF.sub.3 -benzyl 4-MeO-Ph(CH.sub.2).sub.2______________________________________
TABLE 67______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1651 Et 2,5-(Me).sub.2 -benzyl benzyl1652 Et 2,5-(Me).sub.2 -benzyl 4-Cl-benzyl1653 Et 2,5-(Me).sub.2 -benzyl 4-HO-benzyl1654 Et 2,5-(Me).sub.2 -benzyl 4-MeO-benzyl1655 Et 2,5-(Me).sub.2 -benzyl .alpha.-Me-4-MeO-benzyl1656 Et 2,5-(Me).sub.2 -benzyl 4-EtO-benzyl1657 Et 2,5-(Me).sub.2 -benzyl 4-PrO-benzyl1658 Et 2,5-(Me).sub.2 -benzyl 4-AcO-benzyl1659 Et 2,5-(Me).sub.2 -benzyl 4-MOMO-benzyl1660 Et 2,5-(Me).sub.2 -benzyl 4-MeO-Ph(CH.sub.2).sub.21661 Et 1-naphthylmethyl benzyl1662 Et 1-naphthylmethyl 4-Cl-benzyl1663 Et 1-naphthylmethyl 4-HO-benzyl1664 Et 1-naphthylmethyl 4-MeO-benzyl1665 Et 1-naphthylmethyl .alpha.-Me-4-MeO-benzyl1666 Et 1-naphthylmethyl 4-EtO-benzyl1667 Et 1-naphthylmethyl 4-PrO-benzyl1668 Et 1-naphthylmethyl 4-AcO-benzyl1669 Et 1-naphthylmethyl 4-MOMO-benzyl1670 Et 1-naphthylmethyl 4-MeO-Ph(CH.sub.2).sub.21671 Et 2-naphthylmethyl benzyl1672 Et 2-naphthylmethyl 4-Cl-benzyl1673 Et 2-naphthylmethyl 4-HO-benzyl1674 Et 2-naphthylmethyl 4-MeO-benzyl1675 Et 2-naphthylmethyl .alpha.-Me-4-MeO-benzyl______________________________________
TABLE 68______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1676 Et 2-naphthylmethyl 4-EtO-benzyl1677 Et 2-naphthylmethyl 4-PrO-benzyl1678 Et 2-naphthylmethyl 4-AcO-benzyl1679 Et 2-naphthylmethyl 4-MOMO-benzyl1680 Et 2-naphthylmethyl 4-MeO-Ph(CH.sub.2).sub.21681 Et 2-thenyl benzyl1682 Et 2-thenyl 4-Cl-benzyl1683 Et 2-thenyl 4-HO-benzyl1684 Et 2-thenyl 4-MeO-benzyl1685 Et 2-thenyl .alpha.-Me-4-MeO-benzyl1686 Et 2-thenyl 4-EtO-benzyl1687 Et 2-thenyl 4-PrO-benzyl1688 Et 2-thenyl 4-AcO-benzyl1689 Et 2-thenyl 4-MOMO-benzyl1690 Et 2-thenyl 4-MeO-Ph(CH.sub.2).sub.21691 Et 3-thenyl benzyl1692 Et 3-thenyl 4-Cl-benzyl1693 Et 3-thenyl 4-HO-benzyl1694 Et 3-thenyl 4-MeO-benzyl1695 Et 3-thenyl .alpha.-Me-4-MeO-benzyl1696 Et 3-thenyl 4-EtO-benzyl1697 Et 3-thenyl 4-PrO-benzyl1698 Et 3-thenyl 4-AcO-benzyl1699 Et 3-thenyl 4-MOMO-benzyl1700 Et 3-thenyl 4-MeO-Ph(CH.sub.2).sub.2______________________________________
TABLE 69______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1701 Et benzyl 4-HO-benzyl1702 Et benzyl 4-EtO-benzyl1703 Et benzyl 4-PrO-benzyl1704 Et benzyl 4-AcO-benzyl1705 Et benzyl 4-MOMO-benzyl1706 Et benzyl 4-MeO-Ph(CH.sub.2).sub.21707 Et benzyl 4-AllylO-benzyl1708 Et benzyl 4-PhO-benzyl1709 Et 2-propynyl 4-HO-benzyl1710 Et 2-propynyl 4-EtO-benzyl1711 Et 2-propynyl 4-PrO-benzyl1712 Et 2-propynyl 4-AcO-benzyl1713 Et 2-propynyl 4-MOMO-benzyl1714 Et 2-propynyl 4-MeO-Ph(CH.sub.2).sub.21715 Et 2-Cl-benzyl 4-HO-benzyl1716 Et 2-Cl-benzyl 4-EtO-benzyl1717 Et 2-Cl-benzyl 4-PrO-benzyl1718 Et 2-Cl-benzyl 4-AcO-benzyl1719 Et 2-Cl-benzyl 4-MOMO-benzyl1720 Et 2-Cl-benzyl 4-MeO-Ph(CH.sub.2).sub.21721 Et 4-Cl-benzyl 4-HO-benzyl1722 Et 4-Cl-benzyl 4-EtO-benzyl1723 Et 4-Cl-benzyl 4-PrO-benzyl1724 Et 4-Cl-benzyl 4-AcO-benzyl1725 Et 4-Cl-benzyl 4-MOMO-benzyl______________________________________
TABLE 70______________________________________No R.sup.1 R.sup.2 R.sup.3______________________________________1726 Et 4-Cl-benzyl 4-MeO-Ph(CH.sub.2).sub.21727 Et 2-MeO-benzyl 4-HO-benzyl1728 Et 2-MeO-benzyl 4-EtO-benzyl1729 Et 2-MeO-benzyl 4-PrO-benzyl1730 Et 2-MeO-benzyl 4-AcO-benzyl1731 Et 2-MeO-benzyl 4-MOMO-benzyl1732 Et 2-MeO-benzyl 4-MeO-Ph(CH.sub.2).sub.21733 Et 4-MeO-benzyl 4-HO-benzyl1734 Et 4-MeO-benzyl 4-EtO-benzyl1735 Et 4-MeO-benzyl 4-PrO-benzyl1736 Et 4-MeO-benzyl 4-AcO-benzyl1737 Et 4-MeO-benzyl 4-MOMO-benzyl1738 Et 4-MeO-benzyl 4-MeO-Ph(CH.sub.2).sub.21739 Et 2-pyridylCH.sub.2 4-HO-benzyl1740 Et 2-pyridylCH.sub.2 4-EtO-benzyl1741 Et 2-pyridylCH.sub.2 4-PrO-benzyl1742 Et 2-pyridylCH.sub.2 4-AcO-benzyl1743 Et 2-pyridylCH.sub.2 4-MOMO-benzyl1744 Et 2-pyridylCH.sub.2 4-MeO-Ph(CH.sub.2).sub.21745 Et 4-pyridylCH.sub.2 4-HO-benzyl1746 Et 4-pyridylCH.sub.2 4-EtO-benzyl1747 Et 4-pyridylCH.sub.2 4-PrO-benzyl1748 Et 4-pyridylCH.sub.2 4-AcO-benzyl1749 Et 4-pyridylCH.sub.2 4-MOMO-benzyl1750 Et 4-pyridylCH.sub.2 4-MeO-Ph(CH.sub.2).sub.2______________________________________
TABLE 71______________________________________No Physical Data______________________________________A-176 mp 89-97.degree. C.A-1301 mp 83-92.degree. C.A-1310 Isomer A: mp 84-86.degree. C. Isomer B: mp 173-174.degree. C.B-476 mp 112-114.degree. C.B-480 mp 78-89.degree. C.B-1301 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.97(3H, d, J=4.9), 3.91(3H, s), 3.94 (3H, s), 5.90(1H, br), 7.40(5H, m)B-1310 mp 136-137.degree. C.B-1331 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.89(3H, d, J=4.9), 3.91(3H, s), 5.25 (1H, s), 6.58(1H, br), 7.25-7.40(8H, m), 7.51-7.55(2H, m)C-1 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.85(3H, s), 3.03(3H, s), 3.93(3H, s), 3.97(3H, s)C-10 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.02(3H, s), 2.74(3H, s), 3.00(3H, s), 3.92(3H, s), 5.19(2H, s), 7.33(5H, m)C-11 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.01(3H, s), 2.80(3H, s), 3.03(3H, s), 3.93(3H, s), 5.30(1H, d, J=13.4), 5.33(1H, d, J=13.4), 7.20- 7.43(4H, m)C-12 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.77(3H, s), 3.03(3H, s), 3.92(3H, s), 5.16(2H, s), 7.20-7.32(4H, m)C-13 mp 83-85.degree. C.C-19 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.02(3H, s), 2.71(3H, s), 2.99(3H, s), 3.80(3H, s), 3.91(3H, s), 5.11(2H, s), 6.86(2H, d, J=8.5), 7.27 (2H, d, J=8.5)C-20 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.99(3H, s), 2.75(3H, s), 2.99(3H, s), 3.92(3H, s), 5.30(2H, s), 6.86-7.47(9H, m)C-21 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.00(3H, s), 2.79(3H, s), 3.03(3H, s), 3.93(3H, s), 5.12(2H, s), 7.18(1H, dd, J=8.5, 1.8), 7.43(2H, m)C-86 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.78(3H, s), 3.01(3H, s), 4.62(2H, d, J=5.5), 5.15-5.38(4H, m), 5.87-6.02(1H, m), 7.20- 7.47(4H, m)______________________________________
TABLE 72______________________________________No Physical Data______________________________________C-87 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.76(3H, s), 3.01(3H, s), 4.61(2H, d, J=5.5), 5.16(2H, s), 5.16-5.29(2H, m), 5.87-6.02 (1H, m), 7.20-7.32(4H, m)C-94 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.05(3H, s), 2.70(3H, s), 2.98(3H, s), 3.80(3H, s), 4.61(2H, d, J=5.5), 5.12(2H, s), 5.16-5.28(2H, m), 5.87-6.01(1H, m), 6.86(2H, d, J=8.5), 7.28(2H, d, J=8.5)C-95 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.02(3H, s), 2.73(3H, s), 2.98(3H, s), 4.61(2H, d, J=5.5), 5.16-5.29(2H, m), 5.30(2H, s), 5.87-6.02 1H, m), 6.87-7.47(9H, m)C-96 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.03(3H, s), 2.77(3H, s), 3.01(3H, s), 4.62(2H, d, J=5.5), 5.12(2H, s), 5.12-5.29(2H, m), 5.87-6.02 (1H, m), 7.18(1H, dd, J=8.5, 1.8), 7.26-7.43(2H, m)C-101 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.09(3H, s), 2.79(3H, s), 2.98(3H, s), 3.97(3H, s), 4.74-4.84(2H, m), 6.27-6.37(1H, m), 6.57-6.63 (1H, m), 7.21-7.46(4H, m)C-144 mp 96-99.degree. C.C-146 mp 82-83.5.degree. C.C-176 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.63(3H, s), 2.98(3H, s), 3.95(3H, s), 5.12(1H, d, J=12.2), 5.15(1H, d, J=12.2), 7.32(5H, m)C-180 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.64(3H, s), 2.99(3H, s), 4.64(2H, d, J=5.9), 5.13-5.32(4H, m), 5.88-6.03(1H, m), 7.37 (5H, m)C-185 mp 102-104.degree. C.C-194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.50(3H, s), 2.95(3H, s), 3.80(3H, s), 5.09and 5.15(each 1H, ABq, J=12.2), 5.10(2H, s), 6.84(2H, d, J=8.7), 7.26(2H, d, J=8.8), 7.31(5H, m)C-219 mp 93-93.5.degree. C.C-251 mp 82.5-83.5.degree. C.C-276 mp 49.5-51.degree. C.C-301 mp 92-93.degree. C.C-326 mp 54.5-56.degree. C.C-376 mp 68-69.degree. C.______________________________________
TABLE 73______________________________________No Physical Data______________________________________C-451 mp 93-94.degree. C.C-476 mp 77-79.degree. C.C-480 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.70(3H, s), 3.01(3H, s), 4.65(2H, m), 5.07(2H, s), 5.19-5.32(2H, m), 5.88-6.03(1H, m), 7.16(1H, dd, J=8.5, 1.8), 7.40-7.44(2H, m)C-619 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.05(3H, t, J=7.3), 2.50-2.63(2H, m), 2.68(3H, s), 2.98(3H, s), 3.80(3H, s), 3.89(3H, s), 5.11(2H, s), 6.86(2H, d, J=9.2), 7.28(2H, d, J=9.2)C-780 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.3), 2.53-2.66(2H, m), 2.60(3H, s), 2.97(3H, s), 4.64(2H, d, J=6.1), 5.12(1H, d, J=11.6), 5.14(1H, d, J=11.6), 5.18-5.31(2H, m), 5.88-6.02 (1H, m), 7.33(5H, m)C-1310 mp 111-113.degree. C.C-1331 mp 78-96.degree. C.F-176 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.08(3H, s), 3.23(3H, s), 3.44(3H, s), 3.97(3H, s), 5.16(2H, s), 7.26-7.34(5H, m)F-180 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.07(3H, s), 3.23(3H, s), 3.45(3H, s), 4.66(2H, d, J=5.5), 5.16(2H, s), 5.16-5.33(2H, m), 5.92-6.02 (1H, m), 7.26-7.32(5H, m)G-194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.59-1.82(4H, m), 2.03(3H, m), 2.84 (2H, m), 3.49(2H, m), 3.79(3H, s), 5.10-5.13(4H, m), 6.84 (2H, d, J=8.8), 7.25(2H, d, J=8.8), 7.30(5H, m)H-176 mp 121-123.degree. C.H-194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.10-1.28(2H, m), 1.47(4H, m), 2.05 (3H, s), 2.80-2.96(2H, m), 3.45(1H, m), 3.64(1H, m), 3.80 (3H, s), 5.09(2H, s), 5.10and 5.16(each 1H, ABq, J=12.2), 6.84 (2H, d, J=8.5), 7.25(2H, d, J=8.5), 7.31(5H, m)L-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.46-1.01(2H, m), 1.08and 1.12(total 3H, t, J=7.6), 1.36-1.90(2H, m), 1.92and 1.95(total 3H, s), 2.51-2.81(4H, m), 3.07(1H, m), 3.75(1H, m), 3.80(3H, s), 4.46(1H, m), 4.79and 4.92(total 1H, br d), 5.05-5.25(4H, m), 6.83-6.89(2H, m), 7.27-7.36(7H, m)______________________________________
TABLE 74______________________________________No Physical Data______________________________________M-1194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 023-1.10(2H, m), 1.11and 1.12(total 3H, t, J=7.6), 1.41-1.83(2H, m), 1.92and 2.03(total 3H, s), 2.57-2.74(4H, m), 2.95and 3.19(total 1H, m), 3.76(1H, m), 3.80and 3.81(total 3H, s), 4.40(1H, m), 5.04-5.18(4H, m), 6.83-6.90(2H, m), 7.17-7.32(4H, m), 7.56-7.58(2H, m)N-794 mp 136-137.degree. C.O-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.51and 0.96(total 1H, m), 1.08and 1.11(total 3H, t, J=7.6), 1.37-1.56(1H, m), 1.81(1H, m), 2.50- 2.78(4H, m), 3.03(1H, m), 3.66and 3.67(total 3H, s), 3.79and 3.80(total 3H, s), 4.10-4.22(2H, m), 5.05-5.21(4H, m), 6.85 (2H, br d, J=8.8), 7.24-7.34(7H, m)P-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.47-1.20(2H, m), 1.09and 1.12(total 3H, t, J=7.6), 1.42-1.58(1H, m), 1.83(1H, m), 2.51-2.78(4H, m), 2.90and 2.92(total 3H, s), 3.03-3.36(2H, m), 3.62-3.79 (1H, m), 3.80and 3.81(total 3H, s), 4.40(1H, m), 5.05-5.22 4H, m), 6.85and 6.86total 2H, d, J=8.5), 7.23-7.36 7H, m)R-194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.25-1.81(4H, m), 2.05and 2.06(total 3H, s), 2.64-2.89(1H, m), 3.30and 3.31(total 3H, s), 3.79and 3.80(total 3H, s), 3.10-3.95(4H, m), 5.05-5.18(4H, m), 6.85 (2H, br d, J=8.5), 7.24-7.33(7H, m)T-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.3), 1.75-2.76(4H, m), 2.62(2H, q, J=7.3), 2.91-3.01(2H, m), 3.44-3.55(1H, m), 3.79 (3H, s), 3.80-3.96(1H, m), 5.05(1H, d, J=12.2), 5.10(2H, s), 5.16(1H, d, J=12.2), 6.85(2H, dd, J=1.2, 8.6), 7.12(1H, br), 7.28(7H, m)U-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.3), 1.78-2.68(4H, m), 2.61(2H, q, J=7.3), 2.89-3.01(2H, m), 3.43-3.53(1H, m), 3.79 (3H, s), 3.82and 3.83(total 3H, s), 3.80-3.95(1H, m), 5.05(1H, d, J=12.2), 5.09(2H, s), 5.15(1H, d, J=12.2), 6.84(2H, d, J=8.9), 7.27(7H, m)V-794 mp 92-93 .degree. C.W-10 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.02(3H, s), 3.10-3.14(2H, m), 3.43- 3.58(2H, m), 3.62-3.75(4H, m), 3.93(3H, s), 5.20(2H, s), 7.34 (5H, m)______________________________________
TABLE 75______________________________________No Physical Data______________________________________W-144 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.07(3H, s), 2.44(1H, t, J=2.5), 3.10 (2H. m), 3.46(1H, m), 3.57-3.78(5H, m), 3.81(3H, s), 4.72 (2H, d, J=2.5), 5.13(2H, s), 6.86(2H, d, J=8.7), 7.27(2H, d, J= 8.7)W-176 mp 111-113.degree. C.W-194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.84(1H, ddd, J=3.2, 6.4, 13.4), 2.93(1H, ddd, J=3.2, 6.6, 13.4), 3.17(1H, ddd, J=3.2, 6.6, 11.5), 3.29(1H, ddd, 3.2, 6.4, 11.5), 3.57-3.62(4H. m), 3.80 (3H, s), 5.10(2H, s), 5.11and 5.17(each 1H, ABq, J=12.2), 6.85 (2H, d, J=8.5), 7.25(2H, d, J=8.5), 7.31(5H, m)W-199 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.01(3H, s), 2.91(1H, m), 3.13(1H, m), 3.29(1H, m), 3.52-3.72(5H, m), 3.88(3H, s), 5.13and 5.22 (each 1H, ABq, J=12.2), 6.99(2H, d, J=9.0), 7.27-7.35(5H, m), 7.89(2H, d, J=9.0))W-319 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.85-3.03(2H, m), 3.21- 3.38(2H. m), 3.58-3.63(4H, m), 3.80(3H, s), 5.06and 5.13 (each 1H, ABq, J=12.5), 5.11(2H, s), 6.86(2H, d, J=8.8), 7.22-7.33(6H, m)W-469 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.03(3H, s), 2.86-3.01(2H, m), 3.23- 3.35(2H, m), 3.59-3.65(4H, m), 3.78(6H, s), 5.03and 5.11 (each 1H, ABq, J=12.0), 5.09(2H, s), 6.85(2H, d, J=8.8), 6.86 (2H, d, J=8.8), 7.25(2H, d, J=8.8), 7.26(2H, d, J=8.8)W-569 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.13(3H, s), 2.86-3.04(2H, m), 3.19- 3.37(2H, m), 3.52-3.63(4H, m), 3.80(3H, s), 5.12(2H, s), 5.12 and 5.29(each 1H, ABq, J=12.0), 6.86(2H, d, J=8.8), 7.18- 7.31(2H, m), 7.26(2H, d, J=8.8), 7.67(1H, dt, J=1.7, 7.6), 8.57(2H, br d, J=4.2)W-594 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.91-2.99(2H, m), 3.10- 3.17(2H, m), 3.58-3.67(4H, m), 3.80(3H, s), 5.11(2H, s), 5.13 and 5.18(each 1H, ABq, J=12.5), 6.86(2H, d, J=8.5), 7.25 (2H, d, J=8.5), 7.26(1H, m), 7.63(1H, br d, J=7.8), 8.55-8.58 (2H, m)W-785 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.2), 2.60(2H, q, J=7.2), 2.75-2.96(2H, m), 3.12-3.31(2H, m), 3.54-3.64(4H, m), 5.10 (1H, d, J=12.2), 5.18(1H, d, J=12.2), 7.32(10H, m)______________________________________
TABLE 76______________________________________No Physical Data______________________________________W-788 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.05(3H, t, J=7.3), 2.58(2H, q, J=7.3), 2.77-2.98(2H, m), 3.13-3.35(2H, m), 3.51-3.65(4H, m), 5.09 (1H, d, J=12.2), 5.13(2H, s), 5.19(1H, d, J=12.2), 7.24-7.38 9H, m)W-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 2.60(2H, q, J=7.6), 2.76(1H, ddd, J=3.2, 6.3, 13.5), 2.89(1H, ddd, J=3.2, 6.3, 13.5), 3.15(1H, ddd, J=3.2, 6.3, 11.5), 3.27(1H, ddd, J=3.2, 6.3, 11.5), 3.54-3.62(4H, m), 3.79(3H, s), 5.09and 5.17(each 1H, ABq, J=12.2), 5.10(2H, s), 6.84(2H, d, J=8.3), 7.24-7.35(7H, m)W-869 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.09(3H, t, J=7.3), 2.63(2H, q, J=7.3), 2.79-2.95(2H, m), 3.20-3.30(2H, m), 3.54-3.70(4H, m), 3.80 (3H, s), 5.11(2H, s), 5.25(2H, s), 6.86(2H, d, J=8.6), 7.22-7.38 6H, m)W-919 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.3), 2.59(2H, q, J=7.3), 2.84-2.93(2H, m), 3.20-3.34(2H, m), 3.53-3.67(4H, m), 3.80 (3H, s), 5.05(1H, d, J=12.2), 5.11(2H, s), 5.13(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.21-7.33(6H, m)W-944 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.3), 2.34(3H, s), 2.59 (2H, q, J=7.3), 2.75-2.93(2H, m), 3.19-3.31(2H, m), 3.54- 3.71(4H, m), 3.79(3H, s), 5.10(2H, s), 5.11(1H, d, J=12.2), 5.19(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.14-7.28(6H, m)W-994 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.05(3H, t, J=7.3), 2.33(3H, s), 2.58 (2H, q, J=7.3), 2.76-2.95(2H, m), 3.15-3.33(2H, m), 3.52- 3.77(4H, m), 3.79(3H, s), 5.04(1H, d, J=12.2), 5.10(2H, s), 5.13(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.13(2H, d, J=7.9), 7.20(2H, d, J=7.9), 7.26(2H, d, J=8.6)W-1019 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.81-2.98(2H, m), 3.22-3.34(2H, m), 3.52-3.65(4H, m), 3.80 (3H, s), 3.81(3H, s), 5.11(2H, s), 5.17(1H, d, J=12.2), 5.23(1H, d, J=12.2), 6.82-6.95(4H, m), 7.23-7.30(4H, m)W-1069 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.04(3H, t, J=7.3), 2.57(2H, q, J=7.3), 2.83-2.91(2H, m), 3.24-3.31(2H, m), 3.56-3.68(4H, m), 3.80 (3H, s), 5.02(1H, d, J=12.2), 5.10(2H, s), 5.10(1H, d, J=12.2), 6.83-6.88(4H, m), 7.22-7.28(4H, m)______________________________________
TABLE 77______________________________________No Physical Data______________________________________W-1094 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.86-2.94(2H, m), 3.24-3.33(2H, m), 3.52-3.69(4H, m), 3.79 (3H, s), 5.03(1H, d, J=12.8), 5.07(2H, s), 5.10(1H, d, J=12.8), 6.86(2H, d, J=8.6), 7.14(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.41 (2H, d, J=8.6)W-1144 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.12(3H, t, J=7.6), 2.66(2H, q, J=7.6), 2.91(2H, m), 3.28(2H, m), 3.57(4H, m), 3.80(3H, s), 5.12(2H, s), 5.26and 5.28(each 1H, ABq, J=13.7), 6.86(2H, d, J=8.8), 7.18-7.30(4H, m), 7.67(1H, dt, J=1.7, 7.6), 8.56(1H, d, J=4.2)W-1169 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.6), 2.59(2H, q, J=7.6), 2.83(2H, m), 3.24(2H, m), 3.51-3.70(4H, m), 3.80(3H, s), 5.11(2H, s), 5.12and 5.17(each ABq, J=12.2), 6.85(2H, d, J=8.8), 7.24-7.30(3H, m), 7.63(1H, br d, J=7.8), 8.54-8.57 (2H, m)W-1194 mp 69.5-70.5.degree. C.W-1240 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.92(3H, t, J=7.6), 1.53(2H, m), 2.57 (2H, t, J=8.1), 2.78(1H, m), 2.86(1H, m), 3.15(1H, m), 3.26 (1H, m), 3.57(4H, m), 3.80(3H, s), 5.08and 5.16(each 1H, ABq, J=12.4), 5.09(2H, s), 6.84(2H, d, J=8.8), 7.24-7.34(7H, m)W-1300 mp 73-74.degree. C.W-1404 Isomer A: .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.20(6H, d, J=6.8), 2.70- 2.90(3H, br), 3.00(1H, sept, J=6.8), 3.22(2H, m), 3.33(2H, m), 3.61(1H, br), 3.80(3H, s), 5.02(2H, br s), 5.07(2H, s), 6.85 (2H, d, J=8.6), 7.24(2H, d, J=8.6), 7.29-7.37(5H, m) Isomer B: .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.22(6H, d, J=7.1), 2.69- 2.90(2H, m), 3.13-3.27(2H, m), 3.40(1H, sept, J=7.1), 3.50- 3.68(4H, m), 3.80(3H, s), 5.06and 5.15(each 1H, ABq, J= 12.2), 5.09(2H, s), 6.85(2H, d, J=8.8), 7.26(2H, d, J=8.8), 7.28-7.36(5H, m)W-1494 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.02(3H, s), 2.92-2.97(2H, m), 3.31- 3.35(2H, m), 3.62-3.68(6H, m), 3.80(3H, s), 4.97(1H, d, J=11.6), 5.05(1H, d, J=11.6), 5.10(2H, s), 6.63(2H, d, J=8.6), 6.85(2H, d, J=8.6), 7.12(2H, d, J=8.6), 7.26(2H, d,______________________________________ J=8.6)
TABLE 78______________________________________No Physical Data______________________________________W-1504 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.16(3H, s), 2.78-2.95 (2H, m), 3.21-3.34(2H, m), 3.57-3.66(4H, m), 3.80(3H, s), 5.05(1H, d, J=12.2), 5.13(1H, d, J=12.2), 5.10(2H, s), 6.85(2H, d, J=8.6), 7.19(1H, s), 7.23-7.28(4H, m)7.46(2H, d, J=7.9),W-1534 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.03(3H, s), 2.68-2.90(2H, m), 3.07- 3.25(2H, m), 3.56-3.63(4H, m), 3.79(3H, s), 5.09(2H, s), 5.50 (1H, d, J=12.2), 5.70(1H, d, J=12.2), 6.84(2H, d, J=8.5), 7.23(2H, d, J=8.5), 7.40-7.56(4H, m), 7.77-7.88(2H, m), 8.09(1H, m)W-1554 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.04(3H, s), 2.98-3.02(2H, m), 3.31- 3.40(2H, m), 3.57-3.78(4H, m), 3.80(3H, s), 5.12(2H, s), 5.17 (2H, s), 6.77(1H, d, J=3.7), 6.84-6.98(3H, m), 7.24-7.29(3H, m)W-1564 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.05(3H, s), 2.90-3.05(2H, m), 3.25- 3.42(2H, m), 3.55-3.75(4H, m), 3.80(3H, s), 5.11(2H, s), 5.14 (2H, s), 6.86(2H, d, J=8.8), 7.05(1H, dd, J=1.2J=4.9), 7.22- 7.30(4H, m)W-1571 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.83-3.02(2H, m), 3.15- 3.36(2H, m), 3.55-3.62(4H, m), 5.07(2H, s), 5.10and 5.17 (each 1H, ABq, J=12.5), 6.74(2H, d, J=8.5), 7.12(2H, d, J= 8.5), 7.29-7.33(5H, m)W-1575 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.06(3H, s), 2.80-2.99(2H, m), 3.13- 3.31(2H, m), 3.47(3H, s), 3.56-3.63(4H, m), 5.11(2H, s), 5.16 (2H, s), 5.11and 5.17(each 1H, ABq, J=12.2), 6.98(2H, d, J= 8.5), 7.25(2H, d, J=8.5), 7.26-7.33(5H, m)W-1576 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.07(3H, s), 2.85-2.96(4H, m), 3.13- 3.30(2H, m), 3.52-3.70(4H, m), 3.77(3H, s), 4.30-4.36(2H, m), 5.11and 5.20(each 1H, ABq, J=12.2), 6.82(2H, d, J=8.5), 7.11(2H, d, J=8.5), 7.33(5H, m)W-1644 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.3), 2.62(2H, q, J=7.3), 2.76-2.97(2H, m), 3.12-3.34(2H, m), 3.51-3.66(4H, m), 3.80 (3H, s), 5.11(2H, s), 5.14(1H, d, J=12.8), 5.23(1H, d, J=12.8), 6.86(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.42(2H, d, J=7.9), 7.60 (2H, d, J=7.9)______________________________________
TABLE 79______________________________________No Physical Data______________________________________W-1645 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.05(3H, t, J=7.3), 2.29(3H, s), 2.30 (3H, s), 2.58(2H, q, J=7.3), 2.76-2.94(2H, m), 3.20-3.29(2H, m), 3.32-3.70(4H, m), 3.79(3H, s), 5.06(1H, d, J=12.2), 5.10 (2H, s), 5.16(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.26(2H, d, J=8.6), 7.00-7.06(3H, m)W-1694 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.3), 2.59(2H, q, J=7.3), 2.86-2.94(2H, m), 3.27-3.33(2H, m), 3.60-3.68(4H, m), 3.80 (3H, s), 5.05-5.13(4H, m), 6.85(2H, d, J=8.6), 7.04(1H, d, J=4.9), 7.20-7.29(4H, m)W-1702 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.3), 1.41(3H, t, J=7.3), 2.60(2H, q, J=7.3), 2.70-2.95(2H, m), 3.10-3.32(2H, m), 3.56- 3.70(4H, m), 4.02(2H, q, J=7.3), 5.08(1H, d, J=12.2), 5.10 (2H, s), 5.18(1H, d, J=12.2), 6.84(2H, d, J=9.1), 7.22-7.33(7H, m)W-1703 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.90-1.13(6H, m), 1.60-1.85(2H, m), 2.58-2.63(2H, m), 2.70-3.35(4H, m), 3.40-3.70(4H, m), 3.85- 4.12(2H, m), 5.05-5.25(4H, m), 6.80-6.93(2H, m), 7.21- 7.40(7H, m)W-1704 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06(3H, t, J=7.3), 2.29(3H, s), 2.59 (2H, q, J=7.3), 2.74-2.95(2H, m), 3.11-3.33(2H, m), 3.54- 3.64(4H, m), 5.09(1H, d, J=12.2), 5.16(2H, s), 5.19(1H, d, J=12.2), 7.05(2H, d, J=8.6), 7.28-7.36(7H, m)Y-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 2.15(2H, m), 2.54 (2H, m), 2.60(2H, q, J=7.6), 3.13(2H, m), 3.75(1H, m), 3.80 (3H, s), 3.96(1H, m), 5.08and 5.17(each 1H, ABq, J=12.2), 5.10(2H, s), 6.85(2H, d, J=8.8), 7.24-7.34(7H, m)Z-794 mp 105-110.degree. C.b-594 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.83-1.95(1H, m), 2.12(3H, s), 2.16 (3H, s), 2.10-2.25(2H, m), 2.27-2.40(1H, m), 2.95-3.02(2H, m), 3.50-3.83(2H, m), 3.80(3H s)5.11(2H, s), 5.16(2H, d, J=3.7), 6.86(2H, d, J=8.6), 7.20(2H, d, J=6.1), 7.26(2H, d, J=8.6), 8.57(2H, d, J=6.1)______________________________________
TABLE 80______________________________________No Physical Data______________________________________b-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 1.94-2.37(4H, m), 2.18(3H, s), 2.60(2H, q, J=7.6), 2.96(2H, m), 3.63(2H, m), 3.80(3H, s), 5.10(2H, s), 5.11and 5.16(each 1H, ABq, J=12.5), 6.85(2H, d, J=8.6), 7.24-7.34(7H, m)b-1194 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.12(3H, t, J=7.6), 1.87(1H, m), 2.15 (3H, s), 2.05-2.36(3H, m), 2.65(2H, q, J=7.6), 2.95(2H, m), 3.50-3.70(2H, m), 3.80(3H, s), 5.11(2H, s), 5.12and 5.17 (each 1H, ABq, J=12.2) 6.85(2H, d, J=8.8), 7.19(2H, d, J=5.9), 7.25(2H, d, J=8.8), 8.56(2H, d, J=5.9)e-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.3), 1.28(3H, t, J=7.3), 2.61(2H, q, J=7.3), 2.67-3.81(8H, m), 3.79(3H, s), 4.15(2H, q, J=7.3), 5.04(1H, d, J=12.2), 5.09(2H, s), 5.17(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.22-7.30(7H, m)f-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.3), 2.03-2.70(4H, m), 2.60(2H, q, J=7.3), 2.90-3.10(2H, m), 3.06(2H, s), 3.50-3.80 (2H, m), 3.71(3H, s), 3.80(3H, s), 5.10(2H, s), 5.10(1H, d, J=12.8), 5.18(1H, d, J=12.8), 6.85(2H, d, J=9.2), 7.24-7.33 (7H, m)g-794 mp 107-112.degree. C.h-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.10(3H, t, J=7.3); 2.55(3H, s), 2.56- 3.90(8H, m), 2.63(2H, q, J=7.3), 3.79(3H, s), 5.08(1H, d, J=12.2), 5.11(2H, s), 5.18(1H, d, J=12.2), 6.85(2H, d, J=8.6), 7.23-7.33(7H, m)i-794 mp 89.5-91.degree. C.j-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 2.08(2H, m), 2.61 (2H, q, J=7.6), 3.45(2H, br s), 3.68(2H, m), 3.79(3H, s), 5.12 (2H, s), 5.14(2H, s), 6.85(2H, d, J=8.5), 7.27(2H, d, J=8.5), 7.29-7.32(5H, m)k-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.06and 1.07(total 3H, t, J=7.6), 1.49-1.89(2H, m), 2.19and 2.25(total 3H, s), 2.23-2.31(2H, m), 2.45-2.53(4H, m), 2.84-3.08(2H, m), 3.55-3.74(2H, m), 3.79(3H, s), 5.08-5.20(4H, m), 6.85(2H, d, J=8.6), 7.25- 7.30(7H, m)______________________________________
TABLE 81______________________________________No Physical Data______________________________________l-1 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.13(3H, s), 2.90(3H, s), 3.07(3H, s), 3.29(3H, s), 3.99(3H, s), 6.90-7.02(3H, m), 7.23-7.29(2H, m)n-776 mp 89-92.degree. C.n-785 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H, t, J=4.9), 3.59(4H, brs), 4.45(2H, d, J=4.9), 5.10(2H, s), 6.24(1H, t, J=4.9), 7.22-7.40(10H, m)n-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.94(2H, t, J=4.9), 3.29(2H, t, J=4.9), 3.59(4H, brs), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10(2H, s), 6.15(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.19(2H, d, J=8.5), 7.32(5H, m)n-1456 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.18(3H, t, J=7.6), 2.77(2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.60-3.75(4H, m), 5.15 (2H, s), 6.93(1H, t, J=7.3), 7.08(2H, d, J=7.9), 7.25-7.40(7H, m), 8.28(1H, s)n-1461 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.17(3H, t, J=7.6), 2.74(2H, q, J=7.6), 2.99(2H, t, J=4.9), 3.34(2H, t, J=4.9), 3.60-3.72(4H, m), 5.15 (2H, s), 6.87-6.92(2H, m), 7.12-7.20(2H, m), 7.27-7.44 (5H, m), 8.34(1H, s)n-1466 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.16(3H, t, J=7.6), 2.74(2H, q, J=7.6), 3.00(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.67(4H, brs), 5.15(2H, s), 7.10(2H, d, J=8.5), 7.22(2H, d, J=8.5), 7.35(5H, m), 8.30 (1H, s)n-1476 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.17(3H, t, J=7.6), 2.29(3H, s), 2.76 (2H, q, J=7.6), 3.01(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.60-3.72 (4H, m), 5.14(2H, s), 6.98(2H, d, J=8.5), 7.07(2H, d, J=8.5), 7.27-7.42(5H, m), 8.21(1H, s)n-1486 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.17(3H, t, J=7.6), 2.75(2H, q, J=7.6), 3.02(2H, t, J=4.9), 3.35(2H, t, J=4.9), 3.64-3.75(4H, m), 3.78 (3H, s), 5.14(2H, s), 6.85(2H, d, J=9.2), 7.02(2H, d, J=9.2), 7.25-7.42(5H, m), 8.21(1H, s)______________________________________
TABLE 82______________________________________No Physical Data______________________________________o-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.07(3H, t, J=7.6), 2.65(2H, q, J=7.6), 2.84(3H, s), 2.92-2.98(2H, m), 3.23-3.69(6H, m), 3.79(3H, s), 4.32(1H, d, J=14.3), 4.36(1H, d, J=14.3), 5.05(1H, d, J=12.5), 5.15(1H, d, J=12.5), 6.84(2H, d, J=8.5), 7.18(2H, d, J=8.5), 7.33(5H, m)o-799 mp 97-98.degree. C.o-1486 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.15(3H, t, J=7.3), 2.74(2H, q, J=7.3), 2.97-3.20(2H, m), 3.24-3.36(1H, m), 3.38-3.52(2H, m), 3.45 (3H, s), 3.57-3.64(2H, m), 3.67-3.80(1H, m), 3.79(3H, s), 5.08(1H, d, J=12.2), 5.19(1H, d, J=12.2), 6.86(2H, d, J=9.2), 7.17(2H, d, J=9.2), 7.27-7.42(5H, m)p-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.11(3H, t, J=7.3), 1.90-2.05(1H, m), 2.49(3H, s), 2.50-3.02(6H, m), 3.30-3.46(2H, m), 3.68-3.82 (1H, m), 3.77(3H, s), 4.90(1H, d, J=17.4), 5.08(1H, d, J=12.5), 5.22(1H, d, J=12.5), 5.57(1H, d, J=17.4), 6.80-6.93(4H, m), 7.25-7.40(5H, m)q-776 mp 105-106.degree. C.q-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 0.80(3H, t, J=7.3), 2.23-2.42(3H, m), 2.52-2.65(1H, m), 2.95-3.15(3H, m), 3.42(2H, t, J=4.9), 3.62- 3.75(1H, m), 3.78(3H, s), 5.02-5.50(4H, m), 6.86(2H, d, J=8.5), 7.06(2H, d, J=8.5), 7.25-7.45(9H, m), 7.57(2H, dd, J=1.8, 7.9)t-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.08(3H, t, J=7.3), 2.11(2H, t, J=4.9), 2.20(3H, s), 2.32(2H, t, J=4.9), 2.63(2H, q, J=7.3), 3.07(2H, t, J=4.9), 3.64(2H, t, J=4.9), 3.79(3H, s), 4.38(2H, d, J=4.9), 5.10 (2H, s), 6.11(1H, t, J=4.9), 6.84(2H, d, J=8.5), 7.27-7.40(5H, m)v-794 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.09(3H, t, J=7.6), 2.63(2H, q, J=7.6), 2.95-3.30(4H, m), 3.66(2H, m), 3.80(3H, s), 4.16(2H, m), 5.06and 5.16(each 1H, ABq, J=12.2), 5.12(2H, s), 6.84(2H, d, J=8.8), 7.25-7.33(7H, m)x-10 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.99(3H, s), 3.86(3H, s), 3.94(3H, s), 5.21(2H, s), 7.33(5H, m)______________________________________
TABLE 83______________________________________No Physical Data______________________________________x-185 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 2.01(3H, s), 3.83(3H, s), 5.15(2H, s), 5.21(2H, s), 7.33(10H, m)x-480 mp 53-54.degree. C.y-476 .sup.1 H-NMR(CDCl.sub.3).delta.ppm: 1.28(3H, t, J=7.3), 2.05(3H, s), 3.98 (3H, s), 4.31(2H, q, J=7.3), 5.08(2H, s), 7.15(1H, dd, J=8.8, 2.0), 7.40-7.42(4H, m)z-10 mp 88-89.degree. C.z-185 mp 79-80.degree. C.z-476 mp 134-136.degree. C.z-480 mp 111-112.degree. C.______________________________________ Agrochemical Formulations
Formulation 1
A mixture of 2 parts by weight of Compound C-180 and 98 parts by weight of talc was pulverized to obtain a powder formulation.
Formulation 2
40 Parts by weight of Compound C-180, 10 parts by weight of sodium lignosulfonate and 50 parts by weight of water were mixed to obtain a suspension formulation.
Pharmaceutical Formulations
Formulation for Injection
5 g of Compound b-251 was dissolved in 10 L of distilled water for injection to form a solution for injection, which was then dispensed into 100 ampoules.
The following Test Examles illustrate the fungicidal effects of the compound according to the present invention.
Controlling effects on various plant diseases by foliage application (pot experiment)
Experimental method
A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to a given concentration with distilled water containing a spreader, whereby preparing a liquid sample. The liquid sample was sprayed to each test plant, and after 24 hours each pathogens was inoculated by the method described below.
A % control was calculated according to the following equation. ##EQU1## Test Example 1 Controlling Effect on Rice Blight (Pyricularia oryzae)
A two-week rice seedling (cv.: AICHIASAHI) was transplanted in a plastic cup which was 9 cm in diameter and cultivated for 2 weeks, and then the test compound in the form of a solution or a suspension was sprayed to the foliage of the rice seedling. A conidia suspension of a rice blight microorganism (Pyricularia oryzae) cultured in an oatmeal medium was inoculated by spraying, and after the inoculation the test plant was kept in a moist chamber (28.degree. C., 100% RH) for 24 hours, and subsequently cultivated in a green house for 5 days. Six days after the inoculation, the number of the lesions on the leaves of the inoculated plant was measured to calculate the % control.
The results are shown below.
______________________________________ Controlling effect on rice blight (Pyricularia oryzae) by foliageCompound No. application at 500 ppm (% control)______________________________________C-11 90C-86 90C-95 90C-96 90Reference agent:Fthalide 97______________________________________
Test Example 2
Controlling Effect on Cucumber Mildew Microorganism (Sphaerotheca fulginea)
A seed of a cucumber (cv.: TSUKUBASHIROIBO) was sown in a plastic cup which was 9 cm in diameter, and cultivated for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of the first leaf. The pathogen was inoculated to the leaf by spraying a conidia suspension of a cucumber mildew microorganism (Sphaerotheca fuliginea) which had been cultured on a cucumber leaf. After the inoculation, the plant was kept in a greenhouse at 20.degree. C. for 10 days. Then, the infected area on the leaf was observed, and the % control was calculated.
The results are shown below.
______________________________________ Controlling effect on cucumber mildew microorganism (Sphaerotheca fuliginea)Compound No. by foliage application at 500 ppm (% control)______________________________________B-476 100C-180 100C-780 97F-180 100Reference agent:Fenarimol 100______________________________________
Test Example 3
Controlling effect on wheat powdery mildew microorganism (Erysiphe graminis f.sp.tritici)
A seed of a wheat (cv.: NORIN No.61) was sown in a plastic cup which was 9 cm in diameter and cultivated for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to a seedling, and conidia of a wheat powdery mildew microorganism (Erysiphe graminis fsp.tritici) cultured on a wheat leaf was dropped on the test plant to inoculate the plant with the pathogen. After the inoculation, the plant was kept in a green house at 20.degree. C. for 10 days. The infected area on the leaf was observed, and the % control was calculated.
The results are shown below.
______________________________________ Controlling effect on wheat powdery mildew microorganism (Erysiphe graminis f.sp.tritici)Compound No. by foliage application at 500 ppm (% control)______________________________________C-11 90C-86 90C-96 90C-176 90C-180 90C-251 90C-276 90C-780 90F-180 90Reference agent:Fenarimol 97______________________________________
The tachykinin receptor antagonistic effect of a compound according to the present invention was investigated by the method described below.
Effect of Compound on Capsaicin-Induced Increase in Blood Vessel Permeability
Method
5 Minutes after giving Evans Blue (30 mg/kg, i.v) to a guinea pig anesthetized with pentobarbital (30 mg/kg, i.p.), a test compound dissolved in dimethylsulfide was injected intravenously. After further 5 minutes, capsaicin (0.15 mg/kg, iv.) was given to induce the plasma transudation. 5 Minutes after administration of capsaicin, the guinea pig was sacrificed to isolate the trachea and the urinary bladder. After extraction with formamide for 24 hours, the dye content in each tissue was quantified on the basis of the absorbance at 620 nm, and the amount of the dye transudated into the tissue was calculated from the calibration curve.
By the method described above, the amount of the compound required to obtain 50% suppression (ED.sub.50) was determined and represented in units (mg/kg).
______________________________________ ED.sub.50 (mg/kg)Compound No. Guinea pig trachea Guinea pig urinary bladder______________________________________M-11 0.024M-86 0.085W-96 0.040W-176 0.145 0.075b-180 0.054 0.087b-251 0.017 0.017______________________________________
Industrial Applicability
A compound according to the present invention is usefull as a fungicide, especially as an agricultural fungicide. It also has a tachykinin receptor antagonistic effect, and thus is useful as a pharmaceutical.

Oxime derivatives, hydrazone derivatives and use thereof

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