Calcium receptor modulating compound and use thereof

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to heterocyclic compounds having calcium-sensing receptor (CaSR, hereinafter simply referred to as Ca receptor) modulating (agonistic or antagonistic) activity, pharmaceutical compositions containing them and intermediate compounds useful for synthesizing them.

2. Background Art

Calcium ion (hereinafter simply referred to as Ca) plays an essential role to maintain and modulate functions of various cells such as endocrine and exocrine cells, etc., in addition to nerve and muscle. For this reason, the blood Ca level is strictly maintained in a narrow range. Parathyroid hormone (PTH) plays a central role in maintaining this blood Ca level. Therefore, secretion of PTH from parathyroid gland responds sharply to change in the blood Ca level and is must be modulated according to this. In fact, when the blood Ca level is changed, the blood PTH level is rapidly changed in response to this. The possibility of a mechanism by which the extracellular Ca concentration is sensed by parathyroid gland cells and the information transmitted into cells has been pointed out early by Brown et al. In 1993, they succeeded in the cloning and characterization of a Ca-sensing receptor (CaSR; hereinafter, simply referred to as Ca receptor) from bovine parathyroid (Nature, 366, 575-580(1993)).

The Ca receptor is composed of a large terminal extracellular region spanning 600 amino acids at the N-terminal, having seven transmembrane spanning domains like other G protein coupled receptors, and an intracellular region consisting of 200 or less amino acids at the caboxyl C-terminal.

It is considered that, when the extracellular Ca concentration is increased, phospholipase (PL)-C is activated, leading to increase in the intracellular Ca concentration and inhibition of PTH secretion due to increase in inositol triphosphate (IP₃). Since when a high value of the extracellular Ca concentration is maintained, the intracellular Ca concentration is thereafter increased continuously, it is considered that influx of Ca from the outside of a cell is also promoted. PL-A₂and D are activated due to increase in extracellular Ca, but there is a possibility that these are via protein kinase (PK)-C and the like which are activated at the same time via Ca receptor. The Ca receptor also inhibits adenylyl cyclase via Gi protein or via arachidonic acid production due to activation of PL-A₂and decreases intracellular cyclic AMP (Bone, 20, 303-309 (1997)).

Ca receptor mRNA is expressed in many tissues, and the expression amount is high, in parathyroid gland, thyroid gland C cell, medulla and cortex thick ascending limb (MTAL and CTAL) of kidney uriniferous tubule, intramedullary collecting tubule (IMCD) and encephalic subfornical organ (SFO) and hippocampus (Bone, 20, 303-309 (1997)). In addition, expression is recognized in many tissues such as encephalic hypothalamus, cerebellum and olfactory nucleus, regions other than TAL of renal uriniferous tubule, lung, stomach, pancreas, intestine and skin. Since the Ca receptor is present in various tissues, its physiological function has yet to be fully understood. However, it is expected that the Ca receptor modulating (agonistic or antagonistic) drug would provide for a novel treatment of various disease states which include the following:

1. Drugs for Treating Bone Diseases

Since the anabolic activity is manifested by intermittent administration of PTH, Ca receptor modulating drugs which are considered to be able to regulate secretion of PTH are promising as a drug for treating osteoporosis. In addition, Ca receptor modulating drugs which are selectable for thyroid gland C cell may be also effective for treating osteoporosis by stimulation of calcitonin secretion. Whether the same Ca receptor as that of parathyroid gland is present in osteoblast, osteoclast and bone cell or not is disputable. However, some Ca-sensing mechanism is assuredly present therein and, therefore, drugs which directly act on them can be expected as a drug for treating bone diseases.

2. Kidney-Acting Drugs

Handling of water and mineral in kidney is not only based on the results of function as a target organ for hormones, such as PTH, vitamin D etc., but also the Ca receptor in kidney is presumed to function in a response to the Ca concentration and the magnesium ion concentration in the extracellular fluid (Kidney Int, 50, 2129-2139 (1996)). Further, it is also considered that Ca receptor modulating drugs may modulate the blood amount in kidney, the amount of glomerulus filtration, renin secretion and activation of vitamin D in addition to control of influx and efflux of water and mineral.

3. Central Nervous System and Endocrine-Acting Drugs

Ca receptor is present in almost all areas in the central nervous system, and is remarkably expressed, in particular, in the hippocampus, cerebellum and subfornical organ (Brain Res, 744. 47-56 (1997)). Although the details of the function are still unclear, the term of Ca receptor expression after birth in the hippocampus is consistent with the term of acquisition of LTP (Long Tightening Phenomenon) (Develop Brain Res, 100, 13-21 (1997)) and, therefore, the relationship with memory and learning can be presumed. Therefore, Ca receptor modulating drugs which are high in brain-blood barrier permeability and selective for the central nerve system may be utilized for treating Alzheimer's disease. In addition, since dry mouth occurs in hypercalcemic patient, Ca receptor modulating drugs may control them. The presence of Ca receptor in mouse pituitary gland cells which secreteACTH has been reported (Mol Endocrinol, 10, 555-565 (1996)). It is also considered that Ca receptor modulating drugs can be applied to Sheehann's syndrome and hypopituitarism or hyperpituitarism.

4. Digestive System-Acting Drugs

It is considered that a Ca receptor is present in the Auerbach nerve plexus of the digestive tract and controls intestinal tract motion. Constipation is known in hypercalcemic patients and stimulation of digestive tract motion is known in hypocalcemic patients in clinical tests. The existence of a Ca receptor in the gastrin secreting cell (G cell) of the stomach has been reported (J. Clin Invest, 99, 2328-2333 (1997)), and intestinal tract absorption, constipation, diarrhea, defecation and secretion of acid in the stomach may be controlled by drugs which act on a Ca receptor in the digestive tract. Further, it has been found that a Ca receptor is present in human colon cancer cell strains and it controls c-myc expression and proliferation (Biochem Biophys Res Commum, 232, 80-83 (1997)), this is better consistent with the fact that the Ca uptake and sideration of colon and rectum cancers exhibit the negative correlation and, therefore, Ca receptor regulating drugs can be expected also as a drug for preventing and treating such cancers.

Various heterocyclic compounds have been disclosed in the prior art. For example, WO 01/53266 discloses a compound of the formula:
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where in R, R¹and R²are independently H, hydroxyl, etc. This compound has a phosphoinositide 3-kinase inhibitory activity and is useful for treating coronary obstruction, etc. Indian J. Chem., Sect. B (1993), 32B(5), 586-9 discloses the synthesis of a compound of the formula:

wherein R is hydrogen, chlorine, methyl or methoxy. However, no utility is disclosed. U.S. Pat. No. 4,746,656 (JP 63-33380 A) discloses a compound of the formula:
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wherein R₁is aryl or heterocyclic group, R₂is aryl, etc., R₃and R₄are independently H, alkyl, etc. This compound is a Ca channel blocker.

EP 217142 discloses a compound of the formula:

wherein R is hydrogen, alkyl, etc., R₁is hydrogen, nitro, cyano, etc., R₂is phenyl, cycloalkyl, etc., R₃is hydrogen, acyl etc., and R₈is carboxyl, carbamoyl, etc. This compound is also a Ca channel blocker.

However, a heterocyclic compound having Ca receptor modulating activity is not found in the prior art.

OBJECTS OF THE INVENTION

One object of the present invention is to provide compounds having Ca receptor modulating activity including novel compounds.

Another object of the present invention is to provide pharmaceutical compositions containing the compounds of the present invention.

These objects as well as other objects and advantages of the present invention will become apparent to those skilled in the art from the following description.

SUMMARY OF THE INVENTION

The present inventors have intensively investigated compounds having Ca receptor modulating activity. As a result, it has been found that compounds represented by formula (I) as shown hereinafter have Ca receptor modulating activity useful for medicine and, among them, compounds represented by the formulas (II), (III) and (IIIa) as shown hereinafter are novel compounds.

According to the present invention, there is provided:

1. A compound of the formula (II):
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wherein ring A is an optionally substituted 5- to 7-membered ring;

Q is C, CR⁵(wherein R⁵is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group)), or N;
X¹is CR¹(wherein R¹is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)), CR¹R²(wherein R¹is as defined above, and R²is H, or an optionally substituted hydrocarbon group), N, or NR¹³(wherein R¹³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above));
R³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above);
Y is C, CR⁴(wherein R⁴is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)), or N;
Ar is an optionally substituted cyclic group;
R⁹and R¹⁰are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above); and R¹¹and R¹²are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z^1′-Z²(wherein -Z^1′- is —CS—, —SO— or —SO₂—, and Z²is as defined above); or R⁹and R¹⁰, or R¹¹and R¹²may be combined to form an oxo group, methylene group or a ring; or R¹⁰and R¹¹may be combined to form a ring; and is a single bond or a double bond; provided that
(1) when ring A is a 6-membered ring and Q is C or CR⁵, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and both R⁹and R¹⁰are not H, or R⁹and R¹⁰are not combined to form an oxo group, or R¹⁰and R¹¹are not combined to form a 5-membered ring,
(2) when ring A is a 6-membered ring and Q is N, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and R⁹and R¹⁰are not combined to form an oxo group,
(3) when ring A is a 5-membered ring and Q is C or CR⁵, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and Z²is an optionally substituted amino group, and
(4) when ring A is a 5-membered ring and Q is N, at least one of R⁹and R¹⁰is CHR¹⁵R¹⁶(wherein at least one of R¹⁵and R¹⁶are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) and the other is other than an optionally substituted phenyl group; or a salt thereof;

2. A compound of the formula (III):
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wherein R¹is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group);

R³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above);
Y is C, CR⁴(wherein R⁴is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) or N;
R⁸is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above);
Ar is an optionally substituted cyclic group;
R⁹and R¹⁰are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above), or R⁹and R¹⁰may be combined to form an oxo group, methylene group or a ring;
X³is a bond, oxygen atom, an optionally oxidized sulfur atom, N, NR^7′ (wherein R^7′ is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula -Z^1′-Z²(wherein -Z^1′- is —CS—, —SO— or —SO₂—, and Z²is as defined above)), or an optionally substituted bivalent C_1-2hydrocarbon group; and
is a single bond or a double bond;
provided that at least one of R⁹and R¹⁰is CHR¹⁵R¹⁶(wherein R¹⁵and R¹⁶are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) and the other is other than an optionally substituted phenyl group; or a salt thereof;

3. The compound according to the above 1 or 2, wherein R¹is (1) an optionally substituted heterocyclic group, or (2) a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group);

4. The compound according to the above 3, wherein Z¹is —CO— and Z²is an optionally substituted hydroxyl group or an optionally substituted amino group;

5. The compound according to the above 2, wherein R³is H, a C_1-6alkyl group or a C_7-14aralkyl group;

6. The compound according to the above 2, wherein Re is H, a C_1-6alkyl group, a C_1-6alkylthio group or a C_1-6alkoxy group which may be substituted with hydroxyl group;

7. The compound according to the above 1 or 2, wherein R⁹and R¹⁰are the same or different and are a C_1-6alkyl group or R⁹and R¹⁰are combined each other to form a ring;

8. The compound according to the above 2, wherein R¹is a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group); R³is H; Ar is an optionally substituted aromatic ring group; X³is CR¹¹R¹²(wherein R¹¹and R¹²are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z are as defined above), or R¹¹and R¹²may be combined to form an oxo group, methylene group or a ring); and R⁹and R¹⁰are the same or different and a C_1-6alkyl group, or R⁹and R¹⁰may be combined to form a ring;

9. The compound according to the above 8, wherein R¹is an optionally substituted carbamoyl group;

10. The compound according to the above 9, wherein R¹is a group of the formula: —CONR²⁰(CR²¹R²²R²³) (wherein R²⁰is H or an optionally substituted hydrocarbon group, and R²¹, R²², and R²³are the same or different and are an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, or R²⁰and R²¹may be combined to form a ring);

11. A compound of the formula (IIIa):
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wherein R^1ais (1) an optionally substituted heterocyclic group, or (2) a group of the formula: -Z^1a-Z^2a(wherein -Z^1a- is —CO—, —CS—, —SO— or —SO₂—, and Z^2ais (i) an optionally substituted heterocyclic group, (ii) —NR^20a(CR^21aR^22aR^23a) (wherein (a) R^20ais H or an optionally substituted hydrocarbon group; and R^21ais an optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring and R^22aand R^23aare the same or different and are an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group or R^22aand R^23amay be combined to form a ring, or (b) R^20ais H or an optionally substituted hydrocarbon group; and R^21a, R^22aand R^23aare the same or different and are an optionally substituted C_1-8aliphatic hydrocarbon group, provided that the sum total of the number of carbon atoms is 7 or more), (iii) —NR^20aR^25a(wherein R^20ais as defined above and R^25ais an optionally substituted C_6-10aryl-C_2-4alkyl, C_6-10aryloxy-C_2-4alkyl, C_6-10arylamino-C_2-4alkyl, C_7-14aralkylamino-C_2-4alkyl, heterocyclic ring-C_2-4alkyl or heterocyclic group), (iv) a substituted 5- to 7-membered cyclic amino group, or (v) —OR^24a(wherein R²⁴is (a) an optionally substituted C_7-14aralkyl group, (b) an optionally substituted C_3-7alicyclic hydrocarbon group, (c) an optionally substituted C_7-24aliphatic hydrocarbon group, or (d) an optionally substituted heterocyclic group); R³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group);

Y is C, CR⁴(wherein R⁴is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) or N;
R⁸is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above);
Ar is an optionally substituted cyclic group;
R⁹and R¹⁰are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above), or R⁹and R¹⁰may be combined to form an oxo group, methylene group or a ring;
X³is a bond, oxygen atom, an optionally oxidized sulfur atom, N, NR^7′(wherein R^7′ is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula -Z^1′-Z²(wherein -Z^1′- is —CS—, —SO— or —SO₂—, and Z²is as defined above)), or an optionally substituted bivalent C_1-2hydrocarbon group; and
is a single bond or a double bond;
provided that at least one of R⁹and R¹⁰is CHR¹⁵R¹⁶(wherein R¹⁵and R¹⁶are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) and the other is other than an optionally substituted phenyl group; or a salt thereof;

12. The compound according to the above 11, wherein R^1ais a group of the formula: —CONR^20a(CR^21bR^22bR^23b) (wherein R^20ais as defined above and at least one of R^21b, R^22b, and R^23bis an optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring);

13. The compound according to the above 11, wherein R^1ais (1) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, or (2) a group of the formula: —CO-Z^2c(wherein Z^2cis (i) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, (ii) —NR^20c(CR^21cR^22cR^23c) (wherein (a) R^20cis H or an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group; and R^21cis 1) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, which may be fused with an optionally substituted benzene ring, or 2) an optionally substituted C_6-10aryl group which may be fused with an optionally substituted 5- to 7-membered aromatic heterocyclic ring having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom; and R^22cand R^23care the same or different and are an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group or an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, or R^22cand R^23cmay be combined to form a C_3-7carbon ring, or

(b) R^20cis H or an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group; and R^21c, R^22cand R^23care the same or different and are an optionally substituted C_1-8aliphatic hydrocarbon group, provided that the sum total of the number of carbon atoms is 7 or more),
(iii) —NR^20cR^25c(wherein R^20cis as defined above and R^25cis an optionally substituted C_6-10aryl-C_2-4alkyl, C_6-10aryloxy-C_2-4alkyl, C_6-10arylamino-C_2-4alkyl, C_7-14aralkylamino-C_2-4alkyl, 5- to 7-membered heterocyclic ring (having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom)-C_2-4alkyl or 5- to 7-membered heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom),
(iv) a substituted 5- to 7-membered cyclic amino group, or
(v) —OR^24c(wherein R^24cis (a) an optionally substituted C_7-14aralkyl group, (b) an optionally substituted C_3-7alicyclic hydrocarbon group, (c) an optionally substituted C_7-24aliphatic hydrocarbon group, or (d) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom;
wherein said substituents for R^1a, Z^2c, R^20c, R^21c, R^22c, R^23c, R^24cand R^25care 1 to 3 substituents selected from the group consisting of
1) C_1-6alkyl,
2) C_2-6alkenyl,
3) C_2-6alkynyl,
4) C_3-7cycloalkyl,
5) C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group consisting of C_1-6alkyl, amino, N-(C_1-6alkyl)amino, N,N-di-(C_1-6alkyl)amino, amidino, carbamoyl, N-(C_1-6alkyl)carbamoyl, N,N-di-(C_1-6alkyl)carbamoyl, sulfamoyl, N-(C_1-6alkyl)sulfamoyl, N,N-di-(C_1-6alkyl)sulfamoyl, carboxyl, C_2-7alkoxycarbonyl, hydroxyl, C_1-6alkoxy, mercapto, C_1-6alkylthio, sulfo, cyano, azido, halogen, nitro, nitroso, phosphono, C_1-6alkoxyphosphoryl, di-(C_1-6alkoxy)phosphoryl and C_1-6alkyl substituted with phosphono, C_1-6alkoxyphosphoryl and di-(C_1-6alkoxy)phosphoryl (hereinafter the group of 5) is referred to as group “C”),
6) aromatic heterocyclic group selected from (a) aromatic 5- or 6-membered heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, (b) fused bicyclic heterocyclic group formed by condensation of an aromatic 5- or 6-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom with benzene ring or an aromatic 5- or 6-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom and (c) fused tricyclic heterocyclic group formed by condensation of [1] an aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, [2] benzene ring, and [3] an aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom or benzene ring,
7) heterocyclic-oxy group formed by combining each of the above aromatic heterocyclic groups (a), (b) and (c) with oxy group,
8) non-aromatic 4- or 7-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom,
9) C_7-14aralkyl which may be substituted with 1 to 3 substituents selected from the group “C”,
10) amino group,
11) N-mono-substituted amino selected from N-(C_1-6alkyl)amino, N-(C_2-6alkenyl)amino, N-(C_3-7cycloalkyl)amino group and N-(C_6-10aryl)amino which may be substituted with 1 to 3 substituents selected from the group “C”,
12) amino substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkenyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
13) amidino,
14) acyl selected from C_2-8alkanoyl, C_3-8alkenoyl, C_3-7cycloalkyl-carbonyl, C_3-7cycloalkenyl-carbonyl, C_6-10aryl-carbonyl which may be substituted with 1 to 3 substituents selected from the group “C”, and heterocyclic-carbonyl formed by binding of an aromatic or non-aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom with carbonyl,
15) carbamoyl,
16) mono-substituted carbamoyl group selected from N-(C_1-6alkyl)carbamoyl, N-(C_2-6alkenyl) carbamoyl, N-(C_3-7cycloalkyl)carbamoyl and N-(C_6-10aryl)carbamoyl which may be substituted with 1 to 3 substituents selected from the group “C”,
17) carbamoyl substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
18) sulfamoyl,
19) N-mono-substituted sulfamoyl selected from N-(C_1-6alkyl)sulfamoyl, N-(C_2-6alkenyl)sulfamoyl, N-(C_3-7cycloalkyl)sulfamoyl and N-(C_6-10aryl)sulfamoyl which may be substituted with 1 to 3 substituents selected from the group “C”,
20) sulfamoyl substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
21) carboxyl,
22) C_1-6alkoxy-carbonyl,
23) hydroxyl,
24) C_1-6alkoxy,
25) C_2-10alkenyloxy,
26) C_3-7cycloalkyloxy,
27) C_6-10aryloxy which may be substituted with 1 to 3 substituents selected from the group “C”,
28) C_7-14aralkyloxy which may be substituted with 1 to 3 substituents selected from the group “C”,
29) mercapto,
30) C_1-6alkylthio,
31) C_7-14aralkylthio which may be substituted with 1 to 3 substituents selected from the group “C”,
32) C_6-10arylthio which may be substituted with 1 to 3 substituents selected from the group “C”,
33) C_1-6alkylsulfinyl,
34) C_7-14aralkylsulfinyl which may be substituted with 1 to 3 substituents selected from the group “C”,
35) C_6-10arylsulfinyl which may be substituted with 1 to 3 substituents selected from the group “C”,
36) C_1-6alkylsulfonyl,
38) C_7-14aralkylsulfonyl which may be substituted with 1 to 3 substituents selected from the group “C”,
39) C_6-10arylsulfonyl which may be substituted with 1 to 3 substituents selected from the group “C”,
40) sulfo,
41) cyano,
42) azido,
43) halogen,
44) nitro,
45) nitroso,
46) phosphono,
47) C_1-6alkoxy-phosphoryl
48) di-C_1-6alkoxy-phosphoryl,
49) C_1-6alkyl substituted with phosphono, C_1-6alkoxyphosphoryl or di-(C_1-6alkoxy)phosphoryl
50) C_1-6alkyl substituted with 1 to 4 halogen atoms
51) C_1-6alkoxy substituted with 1 to 4 halogen atoms and
52) C_1-6alkylenedioxy (hereinafter the group of above 1) to 52) is referred to as group “B”);
R³is H, a C_2-6alkyl group or a C_7-14aralkyl group;
Y is CH;
R⁸is H, a C_1-6alkyl group, a C_1-6alkylthio group or a C_1-6alkoxy group which may be substituted with hydroxyl group; Ar is (1) a C_6-10aryl group, (2) a 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, or (3) a C_3-7saturated or unsaturated alicyclic hydrocarbon group, each of which may be substituted with 1 to 3 substituents selected from the group “B”;
one of R⁹and R¹⁰is a hydrogen atom or C_1-6alkyl group which may be substituted with 1 to 3 substituents selected from the group “B” and the other is (1) a hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group, each of which may be substituted with 1 to 3 substituents selected from the group “B” or (2) a 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, which may be substituted with 1 to 3 substituents selected from the group “B”, or
R⁹and R¹⁰may be combined to form a C_5-7carbon ring; and X³is CH₂;

14. The compound according to the above 8, wherein R¹is a group of the formula: —CONR²⁰(CR²¹R²²R²³) (wherein R²⁰is H, and R²¹, R²², and R²³are the same or different and are an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group); R³is H; Ar is an optionally substituted aromatic ring group; X³is CH₂; Y is CH; R⁸is H or an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, an optionally substituted sulfanyl group, an optionally substituted sulfinyl group, or an optionally substituted sulfonyl group, C_1-6alkoxy-carbonyl; and R⁹and R¹⁰are the same or different and are an optionally substituted hydrocarbon group;

15. The compound according to the above 14, wherein at least one of R²¹, R²², and R²³is an optionally substituted heterocyclic group or an optionally substituted phenyl group;

16. The compound according to the above 14, wherein R²⁰and R²¹are combined to form an optionally substituted 5- to 7-membered ring, and R²²and R²³are the same or different and are an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted phenyl group;

17. The compound according to the above 14, wherein R²¹and R²²are the same or different and are a C_1-8hydrocarbon group, and R²³is an optionally substituted 5-membered heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted phenyl group;

18. The compound according to the above 16, wherein R²⁰and R²¹are combined to form a 5- or 6-membered ring which may be fused with benzene ring and/or substituted with 1 to 3 substituents selected from the group consisting of (1) halogen, (2) hydrogen, (3) a phenoxy which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl,

(4) C_1-6alkoxy which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl, N,N-di-C_1-6alkyl-carbamoyl and phenyl which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, halogeno C_1-6alkyl, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl,
and (5) a C_1-8hydrocarbon group which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl, N,N-di-C_1-6alkyl-carbamoyl and phenyl which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, halogeno C_1-6alkyl, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl,
and R²²and R²³are the same or different and C_1-8hydrocarbon group which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl, N,N-di-C_1-6alkyl-carbamoyl and phenyl which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, halogeno C_1-6alkyl, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl;

19. N-(1-ethyl-1-(4-methylphenyl)propyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,

N-(1-ethyl-1-(4-methylphenyl)propyl)-5-(2-fluorophenyl)-7,7-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-ethyl-1-(4-methylphenyl)propyl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-ethyl-1-(4-ethylphenyl)propyl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-ethyl-1-(4-methylphenyl)propyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-ethyl-1-(4-ethylphenyl)propyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
5-(2-chlorophenyl)-N-(1-ethyl-1-(4-methylphenyl)propyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-(4-(dimethylamino)phenyl)-1-ethylpropyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1,1-diethylbutyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
N-(1-ethyl-1-phenylpropyl)-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide or a salt thereof,
3-(5-(1-ethyl-1-(4-methylphenyl)propyl)-1,3,4-oxadiazol-2-yl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
3-(5-(1-ethyl-1-(4-methylphenyl)propyl)-1,3,4-thiadiazol-2-yl)-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
3-((4-(benzyloxy)-2,2-diethyl-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof,
3-((2,2-diethyl-4-methoxy-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof, or
3-((2,2-diethyl-4-fluoro-1-pyrrolidinyl)carbonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine or a salt thereof;

20. The compound according to the above 19, which is an optically active compound;

21. A prodrug of the compound according to the above 1, 2 or 13;

22. A pharmaceutical composition which comprises the compound according to the above 1, 2 or 13 or a prodrug thereof;

23. A composition for modulating calcium receptor which comprises a compound of the formula (I):
embedded image

wherein ring A is an optionally substituted 5- to 7-membered ring;

ring B is an optionally substituted 5- to 7-membered heterocyclic ring;
X¹is CR¹(wherein R¹is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group)), CR¹R²(wherein R¹is as defined above, R²is H or an optionally substituted hydrocarbon group), N or NR¹³(wherein R¹³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above));
X²is N or NR³(wherein R³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above);
Y is C, CR⁴(wherein R⁴is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)) or N;
Z is CR⁵(wherein R⁵is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)), CR⁵R⁶(wherein R⁵and R⁶are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)), N or NR⁷(wherein R⁷is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above));
Ar is an optionally substituted cyclic group;
R is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, an optionally substituted sulfonyl group or an optionally substituted sulfinyl group, or R and Z may be combined to form a ring B; and
is a single bond or a double bond;
or a salt thereof or a prodrug thereof;

24. The composition according to the above 23, which is a calcium receptor antagonist;

25. The composition according to the above 23, which is an agent for preventing or treating diseases caused by abnormality of calcium concentration in a living body or a calcium receptor;

26. The composition according to the above 23, which is an agent for preventing or treating bone diseases;

27. The composition according to the above 23, which is an agent for preventing or treating osteoporosis or fracture;

28. A method for modulating a calcium receptor which comprises administering to a mammal an effective amount of a compound of the formula (I) or a salt thereof or a prodrug thereof according to the above 23;

29. A method for preventing or treating bone diseases, which comprises administering to a mammal an effective amount of a compound of the formula (I) or a salt thereof or a prodrug thereof according to the above 23;

30. Use of the compound of the formula (I) or a salt thereof or a prodrug thereof according to the above 23 for producing a calcium receptor modulator; and

31. Use of the compound of the formula (I) or a salt thereof or a prodrug thereof according to the above 23 for producing a composition for preventing or treating bone diseases.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The above formula (I) includes a monocyclic heterocyclic compound containing ring A and a condensed heterocyclic compound containing rings A and B.

In the above formulas, ring A of the formulas (I) and (II) is an optionally substituted 5- to 7-membered ring.

Examples of the “5- to 7-membered ring” of “an optionally substituted 5- to 7-membered ring” includes an aromatic or non-aromatic 5- to 7-membered hydrocarbon ring or 5- to 7-membered heterocyclic ring which may contain 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur atoms as the ring constituting atoms in addition to carbon atoms. Specific examples thereof include a hydrocarbon ring such as benzene, tropilidene, cyclopentane, cyclohexane, cycloheptane, 1-cyclopentene, 2-cyclopentene, 3-cyclopentene, 1-cyclohexene, 2-cyclohexene, 3-cyclohexene, 1-cycloheptene, 2-cycloheptene, 3-cycloheptene, 2,4-cycloheptadiene, etc.; a heterocyclic ring such as pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethylenimine, heptamethylenimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, pyrrole, pyrazole, 1,2,3-triazole, oxazole, oxazolidine, thiazole, thiazolidine, isoxazole, imidazoline, triazole, thiadiazole, oxadiazole, oxathiadiazole, triazine, etc.; and the like.

Examples of the substituent(s) of “an optionally substituted 5- to 7-membered ring group” include halogen, nitro, cyano, oxo, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted sulfinyl group, an optionally substituted sulfonyl group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted amino group, an optionally substituted acyl group, an optionally esterified or amidated carboxyl group, an optionally substituted phosphoryl group, or the like.

Examples of halogen include fluorine, chlorine, bromine, iodine, and the like, preferably, fluorine and chlorine.

Examples of the hydrocarbon group in an optionally substituted hydrocarbon group as the substituent of the 5- to 7-membered ring group include an optionally substituted aliphatic hydrocarbon group, an optionally substituted alicyclic hydrocarbon group, an optionally substituted alicyclic-aliphatic hydrocarbon group, an optionally substituted aromatic hydrocarbon group, an optionally substituted aromatic-aliphatic hydrocarbon group (an aralkyl group), and the like.

Examples of said aliphatic hydrocarbon group include a saturated aliphatic hydrocarbon group having 1-8 carbon atoms (e.g., alkyl group) such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.; and an unsaturated aliphatic hydrocarbon group having 2-8 carbon atoms (e.g., alkenyl group, alkynyl group, alkadienyl group, alkadiynyl group, etc.) such as vinyl, allyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2,4-hexadienyl, 1-heptenyl, 1-octenyl, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 2,4-hexadiynyl, 1-heptynyl, 1-octynyl, etc.

Examples of said alicyclic hydrocarbon group include a saturated alicyclic hydrocarbon group having 3-7 carbon atoms (e.g., cycloalkyl group, etc.) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like; an unsaturated alicyclic hydrocarbon group having 3-7 carbon atoms (e.g., cycloalkenyl group, cycloalkadienyl group, etc.) such as 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1-cycloheptenyl, 2-cycloheptenyl, 3-cycloheptenyl, 2,4-cycloheptadienyl, etc.; a partly saturated and fused bicyclic hydrocarbon group [preferably, C_9-10(partly saturated and fused bicyclic hydrocarbon group, etc. (including those where the benzene ring is combined to 5- or 6-membered non-aromatic cyclic hydrocarbon group)] such as 1-indenyl, 2-indenyl, 1-indanyl, 2-indanyl, 1,2,3,4-tetrahydro-1-naphthyl, 1,2,3,4-tetrahydro-2-naphthyl, 1,2-dihydro-1-naphthyl, 1,2-dihydro-2-naphthyl, 1,4-dihydro-1-naphthyl, 1,4-dihydro-2-naphthyl, 3,4-dihydro-1-naphthyl, 3,4-dihydro-2-naphthyl, etc.; and the like. Said alicyclic hydrocarbon group may be cross-linked.

Examples of said alicyclic-aliphatic hydrocarbon group include those where the above-mentioned alicyclic hydrocarbon group and the above-mentioned aliphatic hydrocarbon group are combined, for example, those having 4-14 carbon atoms such as cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, 2-cyclopentenylmethyl, 3-cyclopentenylmethyl, cyclopentylethyl, cyclohexylmethyl, 2-cyclohexenylmethyl, 3-cyclohexenylmethyl, cyclohexylethyl, cycloheptylmethyl, cycloheptylethyl, 2-(3,4-dihydro-2-naphtyl)ethyl, 2-(1,2,3,4-tetrahydro-2-naphtyl)ethyl, 2-(3,4-dihydro-2-naphtyl)ethenyl, etc. (e.g., C_3-7cycloalkyl-C_1-4alkyl group, C_3-7cycloalkenyl-C_1-4alkyl group, C_3-7cycloalkyl-C_2-4alkenyl group, C_3-7cycloalkenyl-C_2-4alkenyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl groups, etc.).

Examples of said aromatic hydrocarbon group include an aryl group having 6-10 carbon atoms (including that where a 5- to 6-membered non-aromatic hydrocarbon ring is fused with phenyl group) such as phenyl, α-naphthyl, β-naphthyl, 4-indenyl, 5-indenyl, 4-indanyl, 5-indanyl, 5,6,7,8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 5,6-dihydro-1-naphthyl, 5,6-dihydro-2-naphthyl, 5,6-dihydro-3-naphthyl, 5,6-dihydro-4-naphthyl, etc.; and the like.

Examples of said aromatic-aliphatic hydrocarbon group include an aralkyl group having 7-14 carbon atoms (C_6-10aryl-C_1-4alkyl group) such as phenyl-C_1-4alkyl group, e.g., benzyl, phenethyl, 1-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, etc.; naphthyl-C_1-4alkyl group such as α-naphthylmethyl, α-naphthylethyl, β-naphthylmethyl, β-naphthylethyl, etc.; C_6-10aryl-C_2-4alkenyl group such as phenyl-C_2-4alkenyl group, e.g., styryl, cinnamyl, etc.; and the like.

Examples of the heterocyclic group in an optionally substituted heterocyclic group as the substituent of the 5- to 7-membered ring include (i) a 5- to 7-membered heterocyclic group containing one sulfur atom, one nitrogen atom, or one oxygen atom, (ii) a 5- to 6-membered heterocyclic group containing 2-4 nitrogen atoms, (iii) a 5- to 6-membered heterocyclic group containing 1-2 nitrogen atoms and one sulfur or oxygen atom, or the like; and (iv) these heterocyclic groups may be fused with a 5- to 6-membered ring containing 2 or less nitrogen atoms, benzene ring, or a 5-membered ring containing one sulfur atom. In addition, each of the heterocyclic groups exemplified in (i) to (iv) may be a saturated or unsaturated heterocyclic group and the unsaturated heterocyclic group may be either aromatic or non-aromatic.

Examples of the heterocyclic group in an optionally substituted heterocyclic group as the substituent of the 5- to 7-membered ring include an aromatic monocyclic heterocyclic group, an aromatic fused heterocyclic group, and a non-aromatic heterocyclic group.

Specific examples of the heterocyclic group in an optionally substituted heterocyclic group as the substituent of the 5- to 7-membered ring include (i) an aromatic monocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, etc.); (ii) an aromatic fused heterocyclic group (e.g., benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benztriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.); and (iii) a non-aromatic, heterocyclic group (e.g., oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.).

Examples of sulfinyl group in an optionally substituted sulfinyl group as the substituent of the 5- to 7-membered ring include that where —SO— is combined with “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring.

Preferred examples include a C_1-8alkylsulfinyl group where sulfinyl group is combined with a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.; a C_6-10arylsulfinyl group where sulfinyl group is combined with a C_6-10aryl group such as phenyl, α-naphthyl, β-naphthyl, 4-indenyl, 5-indenyl, 4-indanyl, 5-indanyl, 5,6,7,8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 5,6-dihydro-1-naphthyl, 5,6-dihydro-2-naphthyl, 5,6-dihydro-3-naphthyl, 5,6-dihydro-4-naphthyl, etc.; a group where sulfinyl group is combined with an aromatic monocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, etc.); and a group where sulfinyl group is combined with an aromatic fused heterocyclic group (e.g., benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benztriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.).

More preferred examples include a C_1-8alkylsulfinyl group where sulfinyl group is combined with a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.

Examples of sulfonyl group in an optionally substituted sulfonyl group as the substituent of the 5- to 7-membered ring include a group where —SO₂— is combined with “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring.

Preferred examples include a C_1-8alkylsulfonyl group where sulfonyl group is combined with a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.; a C_6-10arylsulfonyl group where sulfonyl group is combined with a C_6-10aryl group such as phenyl, α-naphthyl, β-naphthyl, 4-indenyl, 5-indenyl, 4-indanyl, 5-indanyl, 5,6,7,8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 5,6-dihydro-1-naphthyl, 5,6-dihydro-2-naphthyl, 5,6-dihydro-3-naphthyl, 5,6-dihydro-4-naphthyl, etc.; a group where sulfonyl group is combined with an aromatic monocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, or the like); and a group where the sulfonyl group is combined with an aromatic, fused heterocyclic group (e.g., benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benztriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.).

More preferred examples include a C_1-8alkylsulfonyl group where sulfonyl group is combined with a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.

Examples of an optionally substituted hydroxyl group as the substituent of the 5- to 7-membered ring include hydroxyl group and that having an appropriate substituent, for example, “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the above substituent of the 5- to 7-membered ring.

Preferred examples include a C_1-8alkyloxy group whose substituent is a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.; a C_6-10aryloxy group whose substituent is a C_6-10aryl group such as phenyl, α-naphthyl, β-naphthyl, 4-indenyl, 5-indenyl, 4-indanyl, 5-indanyl, 5,6,7,8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 5,6-dihydro-1-naphthyl, 5,6-dihydro-2-naphthyl, 5,6-dihydro-3-naphthyl, 5,6-dihydro-4-naphthyl, etc.; a hydroxyl group substituted with an aromatic monocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, etc.); a hydroxyl group substituted with an aromatic fused heterocyclic group (e.g., benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benztriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.).

More preferred examples include a C_6-10aryloxy group (in particular, phenyloxy) or a hydroxyl group substituted with an aromatic monocyclic heterocyclic group (in particular, pyridyl) or an aromatic fused heterocyclic group (in particular, quinolyl).

“The hydrocarbon group” or “the heterocyclic group” as the substituent of the substituted hydroxyl group exemplified above may have the same substituent as that of “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring.

Examples of an optionally substituted thiol group as the substituent of the 5- to 7-membered ring include thiol group and that substituted with an appropriate group such as “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring.

Preferred examples include a C_1-8alkylthio group, whose substituent is a C_1-8alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, etc.; a C_6-10arylthio group, whose substituent is a C_6-10aryl group such as phenyl, α-naphthyl, β-naphthyl, 4-indenyl, 5-indenyl, 4-indanyl, 5-indanyl, 5,6,7,8-tetrahydro-1-naphthyl, 5,6,7,8-tetrahydro-2-naphthyl, 5,6-dihydro-1-naphthyl, 5,6-dihydro-2-naphthyl, 5,6-dihydro-3-naphthyl, 5,6-dihydro-4-naphthyl, etc.; a thiol group substituted with an aromatic monocyclic heterocyclic group (e.g., furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, etc.); and a thiol group substituted with an aromatic fused heterocyclic groups (e.g., benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benzotriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.).

“The hydrocarbon group” or “the heterocyclic group” as the substituent of the substituted thiol group exemplified above may have the same substituent as that of “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring.

More preferred examples include a C_1-8alkylthio group substituted with a C_1-8alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, or the like.

Examples of an optionally substituted amino group as the substituent of the 5- to 7-membered ring include amino group, an N-mono-substituted amino group, and an N,N-di-substituted amino group. Examples of said substituted amino groups include that having one or two substituents of an optionally substituted hydrocarbon group (e.g., the same group as an optionally substituted hydrocarbon group of the substituent of the 5- to 7-membered ring, more specifically, a C_1-8alkyl group, a C_3-7cycloalkyl group, a C_2-8alkenyl group, a C_2-8alkynyl group, a C_3-7cycloalkenyl group, a C_6-10aryl group that may have a C_1-4alkyl group, etc.), an optionally substituted heterocyclic group (e.g., the same group as an optionally substituted heterocyclic group of the substituent of the 5- to 7-membered ring), or the formula: —COR′ (wherein R′ represents hydrogen atom or an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group. As for “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of R′ may have the same substituent as that of “the hydrocarbon group” or “the heterocyclic group” in “an optionally substituted hydrocarbon group” or “an optionally substituted heterocyclic group” of the substituent of the 5- to 7-membered ring), preferably a C_1-10acyl group (e.g., a C_2-7alkanoyl, benzoyl, nicotinoyl, etc.). Specific examples thereof include methylamino, dimethylamino, ethylamino, diethylamino, dipropylamino, dibutylamino, diallylamino, cyclohexylamino, phenylamino, N-methyl-N-phenylamino, acetylamino, propionylamino, benzoylamino, nicotinoylamino, and the like.

In addition, the two groups in said substituted amino groups may be combined to form a nitrogen-containing 5- to 7-membered ring (e.g., piperidino, piperadino, morpholino, thiomorpholino, etc.).

Examples of the optionally substituted acyl group as the substituent of the 5- to 7-membered ring include (i) formyl or (ii) a group where the carbonyl group is combined with a C_1-10alkyl group, a C_2-10alkenyl group, a C_2-10alkynyl group, a C_3-7cycloalkyl group, a C_5-7cycloalkenyl group, or an aromatic group (e.g., phenyl group, pyridyl group, etc.) (e.g., acetyl, propionyl, butyryl, isobytyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl, octanoyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, cycloheptanecarbonyl, crotonyl, 2-cyclohexenecarbonyl, benzoyl, etc.) and the like.

Examples of the optionally esterified carboxyl group as the substituent of the 5- to 7-membered ring include, in addition to carboxyl group, an alkyloxycarbonyl group, an alkenyloxycarbonyl, an alkynyloxycarbonyl, an aralkyloxycarbonyl group, an acyoxycarbonyl group, an aryloxycarbonyl group, and the like.

Examples of the alkyl group in said alkyloxycarbonyl group include a C_1-6alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, etc.).

Examples of the alkenyl group in said alkenyloxycarbonyl group include a C_2-6alkenyl group (e.g., vinyl, allyl, isopropenyl, 1-propenyl, 1-butenyl, 2-butenyl, 3-methylallyl, etc.).

Examples of the alkynyl group in said alkynyloxycarbonyl group include a C_2-6alkynyl group (e.g., ethynyl, 2-propynyl, etc.).

The aralkyl group in said aralkyloxycarbonyl group means an aryl-alkyl group (e.g., C_6-10aryl-C_1-6alkyl, etc.). The aryl group in said aryl-alkyl group means a monocyclic or condensed polycyclic aromatic hydrocarbon group, and preferred examples include phenyl, naphthyl, anthryl, phenanthryl, acenaphthenyl, and the like. They may have a substituent such as a C_1-10alkyl group, a C_2-10alkenyl group, a C_2-10alkynyl group, a C_3-8cycloalkyl group, a C_3-8cycloalkenyl group, a C_4-8cycloalkadienyl group, an aryl group (e.g., C_6-14aryl, etc.), an aromatic heterocyclic group (e.g., the same aromatic heterocyclic group as that of the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the above substituent of the 5- to 7-membered ring, etc.), a non-aromatic heterocyclic group (e.g., the same non-aromatic heterocyclic group as that of the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the above substituent of the 5- to 7-membered ring, etc.), an aralkyl group (e.g., a C_6-14aryl-C_1-6alkyl group, etc.), amino group, an N-mono-substituted amino group (e.g., the same N-mono-substituted amino group as that of the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the above substituent of the 5- to 7-membered ring, preferably a N-mono-C_1-4alkylamino group, etc.), a N,N-disubstituted amino group (e.g., the same N,N-disubstituted amino group as that of the substituent in the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the above substituent of the 5- to 7-membered ring, preferably a N,N-di-C_1-4alkylamino group, etc.), amidino group, an acyl group (e.g., the same acyl group as that of the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the above substituent of the 5- to 7-membered ring, etc.), carbamoyl group, a N-mono-substituted carbamoyl group (e.g., a N-mono-C_1-4alkyl-carbamoyl group such as methylcarbamoyl, ethylcarbamoyl, etc.; phenylcarbamoyl; etc.), a N,N-disubstituted carbamoyl group (a N,N-di-C_1-4alkyl-carbamoyl group such as N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, etc.; piperidinocarbamoyl; morpholinocarbamoyl; etc.), sulfamoyl group, a N-mono-substituted sulfamoyl group (e.g., a N-mono-C_1-4alkylsulfamoyl group such as methylsulfamoyl, ethylsulfamoyl, etc.; phenylsulfamoyl; p-toluenesulfamoyl; etc.), a N,N-disubstituted sulfamoyl group (e.g., a N,N-disubstituted C_1-4alkylsulfamoyl group such as N,N-dimethylsulfamoyl, etc.; a N—C_1-4alkyl-N-phenylsulfamoyl group such as N-methyl-N-phenylsulfamoyl, etc.; piperidinosulfamoyl; morpholinosulfamoyl; etc.), carboxyl group, a C_1-10alkoxy-carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, sec-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, etc.), hydroxyl group, a C_1-10alkoxy group, a C_2-10alkenyloxy group, a C_3-7cycloalkyloxy group, an aralkyloxy group (e.g., C_6-14aryl-C_1-6alkyloxy, etc.), an aryloxy group (e.g., C_6-14aryloxy, etc.), mercapto group, a C_1-10alkylthio group, an aralkylthio group (e.g., C_6-14aryl-C_1-6alkylthio, etc.), an arylthio group (e.g., C_6-14arythio, etc.), sulfo group, cyano group, azido group, nitro group, nitroso group, a halogen atom, or the like. As for an alkyl group in said aryl-alkyl group, a C_1-6alkyl group (e.g., methyl, ethyl, propyl, butyl, etc.) is preferred. Preferred examples of said aralkyl group, i.e., an aryl-alkyl group include benzyl, phenethyl, 3-phenylpropyl, (1-naphthyl)methyl, (2-naphthyl)methyl, and the like. Among them, benzyl, phenethyl, and the like are preferred.

As the acyl group in said acyloxycarbonyl group, for example, there are formyl, a C_2-4alkanoyl group, a C_3-4alkenoyl group, a C_3-4alkynoyl group, and the like.

As the aryl group in said aryloxycarbonyl group, for example, there are phenyl, naphthyl, and the like.

Examples of the amidated carboxyl group as the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, the sulfinyl group and the heterocyclic group of the substituent of the 5- to 7-membered ring include the carboxyl group amidated with an optionally substituted amino group as the substituent of the hydrocarbon group, the acyl group, the sulfonyl group, and the heterocyclic group of the above substituent of the 5- to 7-membered ring, each of which may be substituted.

Example of an optionally substituted phosphoryl group of the substituent of the 5- to 7-membered ring include phosphoryl group, a (C_1-6alkoxy)phosphoryl group such as ethoxyphosphoryl, a di-(C_1-6alkoxy)phosphoryl group such as diethoxyphosphoryl, etc.; a lower (C_1-6) alkyl group substituted with an optionally esterified phosphono group such as a phosphono-C_1-6alkyl group, a C_1-6alkoxyphosphoryl-C_1-6alkyl group, a di-(C_1-6alkoxy)phosphoryl-C_1-6alkyl group such as diethoxyphosphorylmethyl, etc.; and the like.

“The hydrocarbon group”, “the heterocyclic group”, “the sulfinyl group”, or “the sulfonyl group” in “an optionally substituted hydrocarbon group”, “an optionally substituted heterocyclic group”, “an optionally substituted sulfinyl group”, or “an optionally substituted sulfonyl group” of the substituent of the 5- to 7-membered ring may be further substituted with 1 to 3 substituents. Examples of said substituents include a lower (C_1-6) alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, etc.); a lower (C_2-6) alkenyl group (e.g., vinyl, allyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, etc.); a lower (C_2-6) alkynyl group (e.g., ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, etc.); a C_3-7cycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.); a C_6-10aryl group (e.g., phenyl, α-naphthyl, β-naphthyl, etc.); an aromatic heterocyclic group [e.g., (i) an aromatic 5- or 6-membered heterocyclic group having 1-4 heteroatoms selected from nitrogen atom, oxygen atom, and sulfur atom; (ii) a fused bicyclic heterocyclic group formed by condensation of an aromatic 5- or 6-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom, and sulfur atom with benzene ring or an aromatic 5- or 6-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom, and sulfur atom; (iii) a fused tricyclic heterocyclic group formed by condensation of [1] an aromatic, 5- or 6-membered heterocyclic group having 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, [2] benzene ring, and [3] an aromatic 5- or 6-membered heterocyclic group having 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom or benzene ring, such as furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, benzofuranyl, isobenzofuranyl, benzo[b]thienyl, indolyl, isoindolyl, 1H-indazolyl, benzimidazolyl, benzoxazolyl, 1,2-benzisothiazolyl, 1H-benztriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, α-carbolinyl, β-carbolinyl, γ-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxatinyl, thianthrenyl, phenanthredinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.]; a heterocyclic-oxy group formed by combining each of the above heterocyclic groups (i), (ii) and (iii) with oxy group; a non-aromatic heterocyclic group (e.g., a non-aromatic, 4- or 7-membered heterocyclic group having 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, such as oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.); a C_7-14aralkyl group (e.g., a C_6-10aryl-C_1-4alkyl group such as benzyl, phenethyl, 1-phenylethyl, 1-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, α-naphthylmethyl, α-naphthylethyl, β-naphthylmethyl, β-naphthylethyl, etc.); amino group; a N-mono-substituted amino group [e.g., a N-(C_1-6alkyl)amino group such as methylamino, ethylamino, allylamino, cyclohexylamino, phenylamino, a N-(C_2-6alkenyl)amino group, a N-(C_3-7cycloalkyl)amino group, a N-(C_6-10aryl)amino group, etc.]; a N,N-disubstituted amino group [e.g., an amino group substituted with two substituents selected from a C_1-6alkyl group, a C_2-6alkenyl group, a C_3-7cycloalkenyl group, and a C_6-10aryl group, such as dimethylamino, diethylamino, dibutylamino, diallylamino, N-methyl-N-phenylamino, etc.]; amidino group; an acyl group (e.g., formyl, a C_2-8alkanoyl group such as acetyl, propionyl, butyryl, isobytyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, heptanoyl, octanoyl, cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, crotonyl, 2-cyclohexenecarbonyl, benzoyl, nicotinoyl, etc.; a C_3-8alkenoyl group; a C_3-7cycloalkyl-carbonyl group; a C_3-7cycloalkenyl-carbonyl group; a C_6-10aryl-carbonyl group; a heterocyclic-carbonyl group formed by binding of an aromatic or non-aromatic 5- or 6-membered heterocyclic group having 1-3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom with carbonyl group, etc.); carbamoyl group; a mono-substituted carbamoyl group [e.g., a N-(C_1-6alkyl)carbamoyl group such as methylcarbamoyl, ethylcarbamoyl, cyclohexylcarbamoyl, phenylcarbamoyl, etc.]; a N-(C_2-6alkenyl)carbamoyl group; a N-(C_3-7cycloalkyl)carbamoyl group; a N-(C_6-10aryl)carbamoyl group; etc.]; a N,N-disubstituted carbamoyl group [e.g., a carbamoyl group substituted with two substituents selected from a C_1-6alkyl group, a C_2-6alkenyl group, a C_3-7cycloalkyl group, and a C_6-10aryl group, such as dimethylcarbamoyl, diethylcarbamoyl, dibutylcarbamoyl, diallylcarbamoyl, N-methyl-N-phenylcarbamoyl, etc.]; sulfamoyl group, a N-mono-substituted sulfamoyl group [e.g., a N-(C_1-6alkyl)sulfamoyl group such as methylsulfamoyl, ethylsulfamoyl, cyclohexylsulfamoyl, phenylsulfamoyl, etc.; a N-(C_2-6alkenyl)sulfamoyl group; a N-(C_3-7cycloalkyl)sulfamoyl group; a N-(C_6-10aryl)sulfamoyl group; etc.], a N,N-disubstituted sulfamoyl group [e.g., sulfamoyl group substituted with two substituents selected from a C_1-6alkyl group, a C_2-6alkenyl group, a C_3-7cycloalkyl group, and a C_6-10aryl group, such as dimethylsulfamoyl, diethylsulfamoyl, dibutylsulfamoyl, diallylsulfamoyl, N-methyl-N-phenylsulfamoyl, etc.]; carboxyl group; a lower (C_1-6) alkoxy-carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc.); hydroxyl group; a lower (C_1-6) alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.); a lower (C_2-10) alkenyloxy group (e.g., allyloxy, 2-butenyloxy, 2-pentenyloxy, 3-hexenyloxy, etc.); a C_3-7cycloalkyloxy group (e.g., cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, etc.); a C_6-10aryloxy group (e.g., phenoxy, naphthyloxy, etc.); a C_7-14aralkyloxy group (e.g., a C_6-10aryl-C_1-4alkyloxy group such as phenyl-C_1-4alkyloxy, naphthyl-C_1-4alkyloxy, etc.); mercapto group; a lower (C_1-6)alkylthio group (e.g., methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio, isopentylthio, neopentylthio, hexylthio, etc.), a C_7-14aralkylthio group (e.g., a C_6-0aryl-C_1-4alkylthio group such as phenyl-C_1-4alkylthio, naphthyl-C_1-4alkylthio, etc.); a C_6-10arylthio group (e.g., phenylthio, naphtylthio, etc.), a lower (C_1-6) alkylsulfinyl group (e.g., methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, pentylsulfinyl, isopentylsulfinyl, neopentylsulfinyl, hexylsulfinyl, etc.); a C_7-14aralkylsulfinyl group (e.g., a C_6-10aryl-C_1-4alkylsulfinyl group such as phenyl-C_1-4alkylsulfinyl, naphthyl-C_1-4alkylsulfinyl, etc.); a C_6-10arylsulfinyl group (e.g., phenylsulfinyl, naphtylsulfinyl, etc.); a lower (C_1-6) alkylsulfonyl group (e.g., methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, hexylsulfonyl, etc.), a C_7-14aralkylsulfonyl group (e.g., a C_6-10aryl-C_1-4alkylsulfonyl group such as phenyl-C_1-4alkylsulfonyl, naphthyl-C_1-4alkylsulfonyl, etc.), a C_6-1arylsulfonyl group (e.g., phenylsulfonyl, naphtylsulfonyl, etc.); sulfo group; cyano group; azido group; a halogen atom (e.g., fluorine, chlorine, bromine, iodine, etc.); nitro group; nitroso group; an optionally esterified phosphono group [e.g., phosphono group, a (C_1-6alkoxy)phosphoryl group such as ethoxyphosphoryl, a di-(C_1-6alkoxy)phosphoryl group such as diethoxyphosphoryl, etc.]; a lower (C_1-6) alkyl group substituted with an optionally esterified phosphono group (e.g., a phosphono-C_1-6alkyl group, a C_1-6alkoxyphosphoryl-C_1-6alkyl group, a di-(C_1-6alkoxy)phosphoryl-C_1-6alkyl group such as diethoxyphosphorylmethyl, etc.); a C_1-6haloalkyl group (e.g., a C_1-6alkyl group substituted with 1 to 4 halogen such as trifluoromethyl, etc.); a C_1-6haloalkoxy group (e.g., a C_1-6alkoxy group substituted with 1 to 4 halogen such as trifluoromethoxy, etc.); and the like.

Among the above substituents, when hydroxyl group is located adjacent to a lower (C_1-6) alkoxy group, they may form C_1-6alkylenedioxy groups such as methylenedioxy, ethylenedioxy, or the like.

The above C_6-10aryl group, the C_6-10aryl group as a substituent of the aromatic heterocyclic group and the N-mono-substituted amino group, the C_6-10aryl group as a substituent of the N,N-di-substituted amino group, the C_6-10aryl group as a substituent of the N-mono-substituted carbamoyl group, the C_6-10aryl group as a substituent of the N,N-di-substituted carbamoyl group, the C_6-10aryl as a substituent of the N-mono-substituted sulfamoyl group, the C_6-10aryl group as a substituent of the N,N-disubstituted sulfamoyl group, the C_6-10aryl group as a substituent of the C_6-10aryloxy group, the C_6-10aryl group of the C_7-14aralkyloxy group, the C_6-10aryl group of the C_7-14aralkylthio groups, the C_6-10aryl group of the C_6-10arylthio groups, the C_6-10aryl group of the C_7-14aralkylsulfinyl groups, the C_6-10aryl group of the C_6-10arylsulfinyl group, the C_6-10aryl group of the C_7-14aralkylsulfonyl groups, and the C_6-10aryl group in the C_6-10arylsulfonyl group may be substituted further with 1 to 3 substituents. Examples of said substituent include a lower (C_1-6) alkyl group, amino group, a N-(C_1-6alkyl)amino group, a N,N-di-(C_1-6alkyl)amino group, amidino group, carbamoyl group, a N-(C_1-6alkyl)carbamoyl group, a N,N-di-(C_1-6alkyl)carbamoyl group, sulfamoyl group, a N-(C_1-6alkyl)sulfamoyl group, a N,N-di-(C_1-6alkyl)sulfamoyl group, carboxyl group, a lower (C_2-7) alkoxycarbonyl group, hydroxyl group, a lower (C_1-6) alkoxy group, mercapto group, a lower (C_1-6) alkylthio group, sulfo group, cyano group, azido group, a halogen atom, nitro group, nitroso group, an optionally substituted phosphono group [e.g., phosphono group, a C_1-6alkoxyphosphoryl group, a di-(C_1-6alkoxy)phosphoryl group, etc.], a lower (C_0-6) alkyl group substituted with an optionally esterified phosphono group [e.g., a phosphono-C_1-6alkyl group, a C_1-6alkoxyphosphoryl-C_1-6alkyl group, a di-(C_1-6alkoxy)phosphoryl-C_1-6alkyl group such as diethoxyphosphorylmethyl, etc.], and the like.

Among the above substituent, when hydroxyl group is located adjacent to a lower (C_1-6) alkoxyl group, they may form a C_1-6alkylenedioxy group such as methylenedioxy, ethylenedioxy, or the like.

The number of the substituents of the 5- to 7-membered ring is 1 to 3, preferably 1 to 2 and the substituents may be the same or different and present at any possible positions of the ring.

Q of the formula (II) is C, CR⁵, or N.

R⁵is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group and an optionally substituted heterocyclic group of R⁵or Z²include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

Examples of halogen and an optionally substituted thiol group of R⁵include the same groups as those exemplified with respect to the above substituent of the 5- to 7-membered ring of ring A.

X¹in the formulas (I) and (II) is CR¹, CR¹R², N or NR¹³.

R¹is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, halogen and an optionally substituted heterocyclic group of R¹include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

R²is H, or an optionally substituted hydrocarbon group, and examples of an optionally substituted hydrocarbon group of R²include the same group as that exemplified with respect to the substituent of the 5- to 7-membered ring of ring A.

R¹³is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group and an optionally substituted heterocyclic group of R¹³include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

R¹of the formula (III) is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group).

In R¹of the formula (III), preferred example of the group of the formula: -Z¹-Z²is a group of the formula: —CONR²⁰(CR²¹R²²R²³), wherein R²⁰is H or an optionally substituted hydrocarbon group, and R²¹, R²², and R²³are the same or different and are an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or R²⁰and R²¹may be combined to form a ring.

Examples of an optionally substituted hydrocarbon group of R¹, R²⁰, R²¹, R²²and R²³, an optionally substituted heterocyclic group of R¹, R²¹, R²²and R²³, and an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group and halogen of R¹include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A of the formulas (I) and (II).

Preferably, at least one of R²¹, R²²and R²³is an optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring.

Examples of the “fused heterocyclic group” of the “optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring” and the “fused phenyl group” of the “optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring” of R²¹, R²²and R²³include the same groups as those exemplified with respect to the aromatic fused heterocyclic group as the substituents of the 5- to 7-membered ring of ring A.

Examples of these substituents include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A of the formulas (I) and (II).

The ring formed in combination with R²⁰and R²¹is preferably an optionally substituted 5- to 7-membered ring, more preferably an optionally substituted 5- or 6-membered ring, and may be fused with an optionally substituted benzene ring. Such rings include the same rings as those exemplified with respect to the “5- to 7-membered ring” of “an optionally substituted 5- to 7-membered ring” in the ring A of the formulas (I) and (II).

These rings may have 1 to 3 substituents selected from the group consisting of (1) halogen, (2) hydrogen, (3) a phenoxy which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl (e.g., formyl, C_2-6alkanoyl, etc.), cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl,

(4) C_1-6alkoxy which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl, N,N-di-C_1-6alkyl-carbamoyl and phenyl which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_0-6alkoxy, C_1-6acyl, cyano, halogeno C_1-6alkyl (e.g., trifluoromethyl, etc.), amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl,
and (5) a C_1-8hydrocarbon group (e.g., C_1-8alkyl, C_3-7cycloalkyl, C_2-8alkenyl, C_2-8alkynyl, C_3-7cycloalkenyl, etc.) which may be substituted with 1 to 3 substituents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl, N,N-di-C_1-6alkyl-carbamoyl and phenyl which may be substituted with 1 to 3 sunstitutents selected from halogen, hydroxyl, C_1-6alkyl, C_1-6alkoxy, C_1-6acyl, cyano, halogeno C_1-6alkyl (e.g., trifluoromethyl, etc.), amino, mono-C_1-6alkyl-amino, di-C_1-6alkyl-amino, C_1-6alkyl-sulfanyl, C_1-6alkyl-sulfinyl, C_1-6alkyl-sulfonyl, C_1-6alkoxy-carbonyl, carbamoyl, N—C_1-6alkyl-carbamoyl and N,N-di-C_1-6alkyl-carbamoyl.

Specific examples of these substituents include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A of the formulas (I) and (II).

R^1aof the formula (IIIa) is (1) an optionally substituted heterocyclic group or (2) a group of the formula: -Z^1a-Z^2a(wherein -Z^1a- is —CO—, —CS—, —SO— or —SO₂—, and Z^2ais (i) an optionally substituted heterocyclic group, (ii)-NR^20a(CR^21aR^22aR^23a) (wherein (a) R^20ais H or an optionally substituted hydrocarbon group; and R^21ais an optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring, or an optionally substituted C_6-10aryl group which may be fused with an optionally substituted aromatic heterocyclic ring and R^22aand R^23aare the same or different and are an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group or R^22aand R^23amay be combined to form a ring, or (b) R^20ais H or an optionally substituted hydrocarbon group; and R^21a, R^22aand R^23aare the same or different and are an optionally substituted C_1-8aliphatic hydrocarbon group, provided that the sum total of the number of carbon atoms is 7 or more),

(iii)-NR^20aR^25awherein R^20ais as defined above and R^25ais an optionally substituted C_6-10aryl-C_2-4alkyl, C_6-10aryloxy-C_2-4alkyl, C_6-10arylamino-C_2-4alkyl, C_7-14aralkylamino-C_2-4alkyl, heterocyclic ring-C_2-4alkyl or heterocyclic group), (iv) a substituted 5- to 7-membered cyclic amino group, or (v) —OR^24a(wherein R^24ais (a) an optionally substituted C_7-14aralkyl group, (b) an optionally substituted C_3-7alicyclic hydrocarbon group, (c) an optionally substituted C_7-24aliphatic hydrocarbon group, or (d) an optionally substituted heterocyclic group)).

Examples of an optionally substituted hydrocarbon group of R^20a, R^22aand R^23aand an optionally substituted heterocyclic group of R^1a, Z^2a, R^21a, R^22aand R^23ainclude the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A of the formulas (I) and (II).

Examples of the “fused heterocyclic group” of the “optionally substituted heterocyclic group which may be fused with an optionally substituted benzene ring” and the “fused phenyl group” of “an optionally substituted phenyl group which may be fused with an optionally substituted aromatic heterocyclic ring” of R^21a, R^22aand R^23ainclude the same groups as those exemplified with respect to the aromatic fused heterocyclic group as the substituents of the 5- to 7-membered ring of ring A.

Examples of the ring formed in combination with R^20aand R^21aand the substituents thereof include the same rings and substituents as those exemplified with respect to the ring formed in combination with R²⁰and R²¹and the substituents thereof.

Examples of the “optionally substituted C_1-8aliphatic hydrocarbon group” of R^20ainclude the same groups as those exemplified with respect to the aliphatic hydrocarbon group as the substituents of the 5- to 7-membered ring of ring A.

Examples of the “optionally substituted C_7-14aralkyl group”, the “optionally substituted C_3-7alicyclic hydrocarbon group” and the “optionally substituted heterocyclic group” of R^24ainclude the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A respectively.

Examples of the “C_7-24aliphatic hydrocarbon group” of the “optionally substituted C_7-24aliphatic hydrocarbon group” in R^24ainclude, for example, C_7-24alkyl, C_7-24alkenyl, C_7-24alkynyl, C_7-24alkadienyl, C_7-24alkadiynyl such as heptyl, octyl, 1-heptenyl, 1-octenyl, 1-heptynyl, 1-octynyl, etc.

Examples of the substituents of the “optionally substituted C_7-24aliphatic hydrocarbon group” in R^24ainclude the same substituents as those exemplified with respect to the substituents of the hydrocarbon group as the substituents of 5- to 7-membered ring of ring A.

In the formula (IIIa), R¹′ is preferably (1) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, or (2) a group of the formula: —CO-Z^2c(wherein Z^2cis (i) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, (ii) —NR^20c(CR^21cR^22cR^23c) (wherein (a) R^20cis H or an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group; and R^21cis 1) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, which may be fused with an optionally substituted benzene ring, or 2) an optionally substituted C_6-10aryl group (e.g., phenyl group, etc.) which may be fused with an optionally substituted 5- to 7-membered aromatic heterocyclic ring having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom; and R^22cand R^23care the same or different and are an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, c_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group, or an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom or R^22cand R^23cmay be combined to form a C_3-7carbon ring, or (b) R^20cis H or an optionally substituted hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group; and R^21c, R^22cand R^23care the same or different and are an optionally substituted C_1-8aliphatic hydrocarbon group, provided that the sum total of the number of carbon atoms is 7 or more),

(iii) —NR^20cR^25c(wherein R^20cis as defined above and R^25cis an optionally substituted C_6-10aryl-C_2-4alkyl, C_6-10aryloxy-C_2-4alkyl, C_6-10arylamino-C_2-4alkyl, C_7-14aralkylamino-C_2-4alkyl, 5- to 7-membered heterocyclic ring (having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom)-C_2-4alkyl or 5- to 7-membered heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom),
(iv) a substituted 5- to 7-membered cyclic amino group (e.g., piperidino, piperadino, morpholino, thiomorpholino, etc.), or
(v) —OR^24c(wherein R^24cis (a) an optionally substituted C_7-14aralkyl group, (b) an optionally substituted C_3-7alicyclic hydrocarbon group, (c) an optionally substituted C_7-24aliphatic hydrocarbon group, or (d) an optionally substituted 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom;
wherein said substituents for R^1a, Z^2c, R^20c, R^21c, R^22c, R^23c, R^24cand R^25care 1 to 3 substituents selected from the group consisting of
- 1) C_1-6alkyl,
- 2) C_2-6alkenyl,
- 3) C_2-6alkynyl,
- 4) C_3-7cycloalkyl,
- 5) C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group consisting of C_1-6alkyl, amino, N-(C_1-6alkyl)amino, N,N-di-(C_1-6alkyl)amino, amidino, carbamoyl, N-(C_1-6alkyl)carbamoyl, N,N-di-(C_1-6alkyl)carbamoyl, sulfamoyl, N-(C_1-6alkyl)sulfamoyl, N,N-di-(C_1-6alkyl)sulfamoyl, carboxyl, C_2-7alkoxycarbonyl, hydroxyl, C_1-6alkoxy, mercapto, C_1-6alkylthio, sulfo, cyano, azido, halogen, nitro, nitroso, phosphono, C_1-6alkoxyphosphoryl, di-(C_1-6alkoxy)phosphoryl and C_1-6alkyl substituted with phosphono, C_1-6alkoxyphosphoryl and di-(C_1-6alkoxy)phosphoryl (hereinafter the group of 5) is referred to as group “C”),
- 6) aromatic heterocyclic group selected from (a) aromatic 5- or 6-membered heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, (b) fused bicyclic heterocyclic group formed by condensation of an aromatic 5- or 6-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom with benzene ring or an aromatic 5- or 6-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom and (c) fused tricyclic heterocyclic group formed by condensation of [1] an aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, [2] benzene ring, and [3] an aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom or benzene ring,
- 7) heterocyclic-oxy group formed by combining each of the above aromatic heterocyclic groups (a), (b) and (c) with oxy group,
- 8) non-aromatic 4- or 7-membered heterocyclic group having 1 to 3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom,
- 9) C_7-14aralkyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 10) amino group,
- 11) N-mono-substituted amino selected from N-(C_1-6alkyl)amino, N-(C_2-6alkenyl)amino, N-(C_3-7cycloalkyl)amino group and N-(C_6-10aryl)amino which may be substituted with 1 to 3 substituents selected from the group “C”,
- 12) amino substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkenyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 13) amidino,
- 14) acyl selected from C_2-8alkanoyl, C_3-8alkenoyl, C_3-7cycloalkyl-carbonyl, C_3-7cycloalkenyl-carbonyl, C_6-10aryl-carbonyl which may be substituted with 1 to 3 substituents selected from the group “C”, and heterocyclic-carbonyl formed by binding of an aromatic or non-aromatic 5- or 6-membered heterocyclic group having 1-3 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom with carbonyl,
- 15) carbamoyl,
- 16) mono-substituted carbamoyl group selected from N-(C_1-6alkyl)carbamoyl, N-(C_2-6alkenyl)carbamoyl, N-(C_3-7cycloalkyl)carbamoyl and N-(C_6-10aryl)carbamoyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 17) carbamoyl substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 18) sulfamoyl,
- 19) N-mono-substituted sulfamoyl selected from N-(C_1-6alkyl)sulfamoyl, N-(C_2-6alkenyl)sulfamoyl, N-(C_3-7cycloalkyl)sulfamoyl and N-(C_6-10aryl)sulfamoyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 20) sulfamoyl substituted with two substituents selected from C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkyl and C_6-10aryl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 21) carboxyl,
- 22) C_1-6alkoxy-carbonyl,
- 23) hydroxyl,
- 24) C_1-6alkoxy,
- 25) C_2-10alkenyloxy,
- 26) C_3-7cycloalkyloxy,
- 27) C_6-10aryloxy which may be substituted with 1 to 3 substituents selected from the group “C”,
- 28) C_7-14aralkyloxy which may be substituted with 1 to 3 substituents selected from the group “C”,
- 29) mercapto,
- 30) C_1-6alkylthio,
- 31) C_7-14aralkylthio which may be substituted with 1 to 3 substituents selected from the group “C”,
- 32) C_6-10arylthio which may be substituted with 1 to 3 substituents selected from the group “C”,
- 33) C_1-6alkylsulfinyl,
- 34) C_7-14aralkylsulfinyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 35) C_6-10arylsulfinyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 36) C_1-6alkylsulfonyl,
- 38) C_7-14aralkylsulfonyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 39) C_6-10arylsulfonyl which may be substituted with 1 to 3 substituents selected from the group “C”,
- 40) sulfo,
- 41) cyano,
- 42) azido,
- 43) halogen,
- 44) nitro,
- 45) nitroso,
- 46) phosphono,
- 47) C_1-6alkoxy-phosphoryl
- 48) di-C_1-6alkoxy-phosphoryl,
- 49) C_1-6alkyl substituted with phosphono, C_1-6alkoxyphosphoryl or di-(C_1-6alkoxy)phosphoryl
- 50) C_1-6alkyl substituted with 1 to 4 halogen atoms
- 51) C_1-6alkoxy substituted with 1 to 4 halogen atoms and
- 52) C_1-6alkylenedioxy
- (hereinafter the group of above 1) to 52) is referred to as group “B”)

Specific examples of these substituents include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

As R^1aof the formula (IIIa), more preferred is the group represented by the formula: —CONR^20c(CR^21cR^22cR^23c)(wherein R^20c, R^21c, R^22cand R^23care as defined above).

Further more preferably, R^1ais (1) a 5- to 7-membered aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom (e.g., 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, etc.) which is substituted with C_1-4alkyl-C_7-14aralkyl (e.g., 1-ethyl-1-(4-methylphenyl)propyl, etc.), or (2) a group represented by the formula: —CO-Z^2c′(wherein Z^2c′is

(i) —NR^20c′(CR^21c′R^22c′R^23c′) (wherein (a) R^20c′ is H or C_1-6alkyl; R^21c′is a C_6-10aryl group or a 5- to 7-membered aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, each of which may be substituted with 1 to 3 substituents selected from the group consisting of halogen, C_1-6alkyl, C_2-6alkenyl, halogeno C_1-6alkyl, hydroxy-C_1-6alkyl, C_1-6alkoxy, carboxyl, C_1-6alkoxy-carbonyl, C_1-6alkyl-carbonyloxy, C_1-6alkyl-carbonyloxy-C_1-6alkyl, carboxy-C_1-6alkoxy, C_1-6alkoxy-carbonyl-C_1-6alkyl, C_1-6alkoxy-carbonyl-C_1-6alkoxy, C_1-6alkoxy-carbonyl-C_1-6alkoxy-C_1-6alkyl, carbonyl, C_1-6alkyl-carbonyl, amino, mono- or di-C_1-6alkylamino, phenyl (said phenyl may be substituted with 1 to 3 substituents selected from halogen, C_1-6alkyl and halogeno C_1-6alkyl) and a 5- to 7-membered aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom; R^22c′ and R^23c′are the same or different and are C_1-6alkyl group, C_5-7cycloalkyl group, phenyl group (said phenyl group may be substituted with 1 to 3 substituents selected from C_1-6alkyl, halogeno C_1-6alkyl and C_1-6alkoxy), C_1-6alkoxy-carbonyl-C_1-6alkyl group or C_1-6alkyl-carbonyl-C_2-6alkenyl group, or R^22cand R^23cmay be combined each other to form a C_3-7carbon ring; or (b) R^20c′and R^21c′are combined each other to form a 5- to 7-membered ring and said ring may be substituted with C_1-6alkoxy or C_7-14aralkyl, and R^22c′and R^23c′are C_1-6alkyl group),
(ii) —NR^20c′R^25c′(wherein R^20c′is H or C_1-6alkyl group; R^25c′ is C_6-10aryl-C_2-4alkyl group, C_6-10aryloxy-C_2-4alkyl group, C_6-10arylamino-C_2-4alkyl group, C_7-14aralkylamino-C_2-4alkyl group, 5- to 7-membered heterocyclic ring-C_2-4alkyl group or 5- to 7-membered heterocyclic group, each of which may be substituted with 1 or 2 substituents selected from the group consisting of halogen, C_1-6alkyl, C_6-10aryl, C_1-6alkoxy, amino, mono- or di-C_1-6alkylamino, 5- to 7-membered cyclic amino, hydroxy, oxo, C_1-6alkoxy-carbonyl and cyano), or
(iii) a 5- to 7-membered cyclic amino group which is substituted with 1 to 3 substituents selected from the group consisting of halogen, C_1-6alkyl, C_2-6alkenyl, C_1-6alkoxy-C_1-6alkyl, C_5-7cycloalkyl, C_6-10aryl (said aryl may have 1 or 2 substituents selected from halogen, C_1-6alkyl, halogeno C_1-6alkyl and C_1-6alkoxy), C_7-14aralkyl (said aralkyl may have 1 or 2 substituents selected from halogen, C_1-6alkyl, halogeno C_1-6alkyl and C_1-6alkoxy), hydroxy, hydroxy-C_1-6alkyl, C_6-10aryloxy (said aryloxy may have 1 or 2 substituents selected from halogen, C_1-6alkyl, halogeno C_1-6alkyl and C_1-6alkoxy), C_7-14aralkyloxy, C_6-10aryl-carbonyl, carboxyl, C_1-6alkoxy-carbonyl, carbamoyl, C_6-10aryl-carbamoyl, amino, C_6-10aryl-carbonylamino, C_1-6alkyl-carbonylamino, C_1-6alkoxy-carbonylamino, C_6-10arylthio, C_6-10arylsulfonyl, cyano, oxo and 5- to 7-membered heterocyclic group.).

R³of the formulas (II), (III) and (IIIa) is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group and an optionally substituted heterocyclic group of R³include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

R³is preferably H, a C_1-6alkyl group or a C_7-14aralkyl group, and more preferably R³is H.

Y in the formulas (I), (II), (III) and (IIIa) is C, CR⁴, or N.

R⁴is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group and halogen of R⁴include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

Y is preferably CH.

R⁸of the formulas (III) and (IIIa) is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, halogen atom and an optionally substituted heterocyclic group of R⁸include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

R⁸is preferably H, a C_1-6alkyl group, a C_1-6alkylthio group or a C_1-6alkoxy group which may be substituted with hydroxyl group, and more preferably R⁸is H or a C_1-6alkyl group.

Ar in the formulas (I), (II), (III) and (IIIa) is an optionally substituted cyclic group.

Examples of the optionally substituted cyclic group of Ar include an optionally substituted aromatic or non-aromatic hydrocarbon ring group or an optionally substituted aromatic or non-aromatic heterocyclic group, and the like.

Examples of the aromatic hydrocarbon ring group and the heterocyclic group of Ar include the same aromatic hydrocarbon group and heterocyclic group as exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

Examples of the non-aromatic hydrocarbon ring group include a saturated alicyclic hydrocarbon group having 3-7 carbon atoms (e.g., cycloalkyl group, etc.) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like; an unsaturated alicyclic hydrocarbon group having 3-7 carbon atoms (e.g., cycloalkenyl group, cycloalkadienyl group, etc.) such as 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1-cycloheptenyl, 2-cycloheptenyl, 3-cycloheptenyl, 2,4-cycloheptadienyl, etc.; a partly saturated and fused bicyclic hydrocarbon group [preferably, c_9-10partly saturated and fused bicyclic hydrocarbon group, etc. (including those where the benzene ring is combined to 5- or 6-membered non-aromatic cyclic hydrocarbon group)] such as 1-indenyl, 2-indenyl, 1-indanyl, 2-indanyl, 1,2,3,4-tetrahydro-1-naphthyl, 1,2,3,4-tetrahydro-2-naphthyl, 1,2-dihydro-1-naphthyl, 1,2-dihydro-2-naphthyl, 1,4-dihydro-1-naphthyl, 1,4-dihydro-2-naphthyl, 3,4-dihydro-1-naphthyl, 3,4-dihydro-2-naphthyl, etc.; and the like.

Examples of the substituent of an optionally substituted aromatic ring group and an optionally substituted heterocyclic group of Ar include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

Ar is preferably (1) a C_6-10aryl group, (2) a 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, or (3) a C_3-7saturated or unsaturated alicyclic hydrocarbon group, each of which may be substituted with 1 to 3 substituents selected from the group “B”.

More preferably, Ar is a C_6-10aryl group which may be substituted with 1 to 3 substituents selected from the group “B”, a 5- to 7-membered aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom which may be substituted with 1 to 3 substituents selected from the group “B”, or a C_3-7saturated or unsaturated alicyclic hydrocarbon group.

Further more preferably, Ar is (1) a C_6-10aryl group (e.g., phenyl, naphthyl, etc.) which may be substituted with 1 or 2 substituents selected from the group consisting of halogen atom, C_1-6alkyl, C_1-6alkoxy, hydroxy, C_7-14aralkyloxy and mono- or di-C_1-4alkylamino, (2) a 5- to 7-membered aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom (e.g., pyridyl, furyl, thiazolyl, thienyl, etc.) which may be substituted with C_1-4alkyl or (3) a C_5-7cycloalkyl group (e.g., cyclohexyl etc.), and most preferably, Ar is an optionally halogenated phenyl group.

R⁹and R¹⁰of the formulas (II), (III) and (IIIa) are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above), or R⁹and R¹⁰may be combined to form an oxo group, methylene group or a ring.

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom and an optionally substituted heterocyclic group of R⁹and R¹⁰include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

One of R⁹and R¹⁰is preferably a hydrogen atom or C_1-6alkyl group which may be substituted with 1 to 3 substituents selected from the group “B” and the other is (1) a hydrocarbon group selected from C_1-8saturated aliphatic hydrocarbon group, C_2-8unsaturated aliphatic hydrocarbon group, C_3-7saturated alicyclic hydrocarbon group, C_3-7unsaturated alicyclic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon group, C_3-7saturated or unsaturated alicyclic-C_1-8saturated or unsaturated aliphatic hydrocarbon group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_1-4alkyl group, C_9-10partly saturated and fused bicyclic hydrocarbon-C_2-4alkenyl group, C_6-10aryl group and C_7-14aralkyl group, each of which may be substituted with 1 to 3 substituents selected from the group “B” or (2) a 5- to 7-membered aromatic or non-aromatic heterocyclic group having 1-4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, which may be substituted with 1 to 3 substituents selected from the group “B”, or R⁹and R¹⁰may be combined to form a C_5-7carbon ring.

More preferably, one of R⁹and R¹⁰is preferably a hydrogen atom or C_1-6alkyl group and the other is an optionally halogenated C_1-6alkyl group, C_6-10aryl group, C_7-10aralkyl group or a 5- to 7-membered aromatic heterocyclic group, or R⁹and R¹⁰are a C_5-7carbon ring formed by combining together.

Examples of R¹¹and R¹²of the forumula (II) are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z^1′-Z²(wherein -Z^1′- is —CS—, —SO— or —SO₂—, and Z²is as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom and an optionally substituted heterocyclic group of R¹¹and R¹²include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

R⁹and R¹⁰, or R¹¹and R¹²may be combined to form an oxo group, methylene group or a ring such as a C_3-6saturated or unsaturated carbon ring (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, etc.); or R¹⁰and R¹¹may be combined to form a ring such as a C_3-6saturated or unsaturated carbon ring (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, etc.).

custom character is a single bond or a double bond.

Z in the formula (I) is CR⁵, CR⁵R⁶, N or NR⁷, and CR⁵is as defined above.

R⁶is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, and an optionally substituted heterocyclic group of R⁶include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

R⁷is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above)).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, a halogen atom and an optionally substituted heterocyclic group of R⁷include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

R⁵, R⁶and R⁷may be the same or different.

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, an optionally substituted sulfonyl group and an optionally substituted sulfinyl group of R include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

R and Z may be combined to form a ring B

Ring B in the formula (I) is an optionally substituted 5- to 7-membered heterocyclic ring and examples thereof include the same group as that exemplified with respect to the 5- to 7-membered ring of ring A.

X²of the formula (I) is N or NR³and R³are as defined above.

X³of the formula (III) and (IIIa) is a bond, oxygen atom, an optionally oxidized sulfur atom, N, NR^7′, or an optionally substituted bivalent C_1-2hydrocarbon group.

R^7′is H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted heterocyclic group, or a group of the formula -Z^1′-Z²(wherein -Z^1′- is —CS—, —SO— or —SO₂—, and Z²is as defined above)).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, and an optionally substituted heterocyclic group of R^7′include the same groups as those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

Examples of an optionally substituted bivalent C_1-2hydrocarbon group include —CH₂—, —(CH₂)₂—, —CH═CH— and the like which may be substituted with one or two substituents selected from those exemplified with respect to the substituents of the 5- to 7-membered ring of ring A.

In the formula (IIIa), X³is preferably CH₂.

Prefered compounds of the formula (I) include not only the compounds of the formula (IIIa) but also the other compounds wherein -Z¹- is —CO— and Z²is an optionally substituted hydroxyl group (e.g., hydroxy, C_1-6alkoxy, etc.) or amino group which is substituted with an optionally substituted phenyl group or an optionally substituted condensed phenyl group (e.g., phenylamino, 3,5-dimethoxyphenylamino, 3-biphenylylamino, 2,3-dihydro-1H-inden-5-yl-amino, quinolin-6-yl-amino, etc.).

In the formula (II),

(1) when ring A is a 6-membered ring and Q is C or CR⁵, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and both R⁹and R¹⁰are not H, or R⁹and R¹⁰are not combined to form an oxo group, or R¹⁰and R¹¹are not combined to form a 5-membered ring;
(2) when ring A is a 6-membered ring and Q is N, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and R⁹and R¹⁰are not combined to form an oxo group;
(3) when ring A is a 5-membered ring and Q is C or CR⁵, X¹is C-Z¹-Z², C(-Z¹-Z²)R²or N-Z¹-Z², and Z²is an optionally substituted amino group; and
(4) when ring A is a 5-membered ring and Q is N, at least one of R⁹and R¹⁰is CHR¹⁵R¹⁶(wherein R¹⁵and R¹⁶are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above).

Examples of an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, a halogen atom and an optionally substituted heterocyclic group include the same groups as those exemplified with respect to the above substituents of the 5- to 7-membered ring of ring A.

In the formulas (II) and (III), preferably, R¹is a group of the formula: -Z¹-Z²; Z¹is —CO— and Z²is an optionally substituted hydroxyl group or an optionally substituted amino group; Ar is an optionally substituted aromatic ring group; and both R⁹and R¹⁰are the same or different and are C_1-6alkyl groups or R⁹and R¹⁰are combined to form a ring such as a saturated or unsaturated C_3-6ring as described above.

In the formula (III), preferably, R³is H. More preferably, in the formula (III), R¹is a group of the formula: -Z¹-Z²(wherein -Z¹- is —CO—, —CS—, —SO— or —SO₂—, and Z²is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxyl group, or an optionally substituted amino group); R³is H; Ar is an optionally substituted aromatic ring group; X³is CR¹¹R¹²(wherein R¹¹and R¹²are the same or different and are H, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted amino group, an optionally substituted thiol group, cyano group, a halogen atom, an optionally substituted heterocyclic group, or a group of the formula: -Z¹-Z²(wherein -Z¹- and Z²are as defined above), or R¹¹and R¹²may be combined to form an oxo group, methylene group or a ring such as a saturated or unsaturated C_3-6ring as described above); and R⁹and R¹⁰are the same or different and are a C_1-6alkyl group, or R⁹and R¹⁰may be combined to form a ring such as a saturated or unsaturated C_3-6ring as described above.

As for a salt of the compound of formula (I), (II), (III) or (IIIa) (hereinafter sometimes referred to as Compound (I), (II), (III) or (IIIa)), a pharmaceutically acceptable salt is preferred. Examples thereof include a salt with an inorganic base, a salt with an organic base, a salt with an inorganic acid, a salt with an organic acid, a salt with a basic or acidic amino acid, or the like. Preferred examples of a salt with an inorganic base include an alkali metal salt such as sodium salt, potassium salt, or the like; an alkaline earth metal salt such as calcium salt, magnesium salt, or the like; and aluminum salt; ammonium salt; or the like. Preferred examples of a salt with an organic base include a salt with trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, N,N′-dibenzylethylenediamine, or the like. Preferred examples of a salt with an inorganic acid include a salt with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, or the like. Preferred examples of a salt with an organic acid include a salt with formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, or the like. Preferred examples of a salt with a basic amino acid include a salt with arginine, lysine, ornithine or the like. Preferred examples of a salt with an acidic amino acid include a salt with aspartic acid, glutamic acid, or the like.

Compound (I), (II), (III) or (IIIa) may be in the form of a prodrug thereof. The prodrug of Compound (I), (II), (III) or (IIIa) refers to a compound that is converted into Compound (I), (II), (III) or (IIIa) by a reaction with an enzyme, gastric acid, or the like under a physiological condition in the living body, namely, (i) a compound that is converted into Compound (I), (II), (III) or (IIIa) by an enzymatic oxidation, reduction, hydrolysis, or the like, and (ii) a compound that is converted into Compound (I), (II), (III) or (IIIa) by hydrolysis with gastric acid or the like. Examples of a prodrug of Compound (I), (II), (III) or (IIIa) to be used include a compound or its salt wherein hydroxyl group in Compound (I), (II), (III) or (IIIa) is acylated, alkylated, phosphorylated, or converted into borate (e.g., a compound or its salt wherein hydroxyl group in Compound (I), (II), (III) or (IIIa) is converted into acetyloxy, palmitoyloxy, propanoyloxy, pivaloyloxy, succinyloxy, fumaryloxy, alanyloxy, dimethylaminomethylcarbonyloxy, etc.), a compound or its salt wherein carboxyl group in Compound (I), (II), (III) or (IIIa) is esterified or amidated (e.g., a compound or its salt wherein carboxyl group in Compound (I), (II), (III) or (IIIa) is subjected to ethyl esterification, phenyl esterification, carboxyoxymethyl esterification, dimethylaminomethyl esterification, pivaloyloxymethyl esterification, ethoxycarbonyloxyethyl esterification, phthalidyl esterification, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl esterification, cyclohexyloxycarbonyl esterification, or conversion into the methyl amide, etc.), or the like. These prodrugs can be produced according to a per se known method or its modified method.

Further, a prodrug of Compound (I), (II), (III) or (IIIa) may be a compound or its salt that is converted into Compound (I), (II), (III) or (IIIa) under physiological conditions as described in “Development of Drugs”, Volume 7, Molecular Design, Hirokawa Shoten, 1990; pages 163-198.

Compound (I), (II), (III) or (IIIa) may be labeled with an isotope (for example, ²H, ³H, ¹⁴C, ³⁵S, ¹²⁵I, or the like) or the like.

When the compound obtained by the present invention or a salt thereof has a double bond in its molecule and a steric configuration of Z or E exsits, each of the stereoisomers and a mixture thereof are included in the present invention.

When a steric configuration exsits due to an asymmetric carbon in the molecule of the compound obtained by the present invention or a salt thereof, each of them and a mixture thereof are included in the present invention.

Hereinafter, production of the compound of the present invention will be illustrated.

A process for preparing Compound (II), Compound (III) and Compound (IIIa) of the present invention will be shown in the following schemes 1 to 13.

A compound wherein Q is N, and Y is C or CR⁴in Compound (II) can be prepared according to the schemes 1 to 3.

A compound wherein Q is C, and Y is C or CR⁴in Compound (II) can be prepared according to the scheme 4.

A compound wherein Q is N, and Y is N in Compound (II) can be prepared according to the scheme 5.

A compound wherein Y is C or CR⁴in Compound (III) and Compound (IIIa) can be prepared by the scheme 6.

A compound wherein Y is N in Compound (III) and Compound (IIIa) can be prepared by the scheme 7.

A compound wherein Q is C, and Y is N in Compound (II) can be prepared by the scheme 13.
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wherein A-1 is the same as A, and the other symbols are as defined above.

In step A, Compound (II-1) is prepared by cyclization reaction of Compound (IV-1) and Compound (X) with an acid or a base. Examples of the acid used in this reaction include: inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid; organic acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such as zinc (II) chloride, tin (IV) chloride, aluminium chloride and the like.

Examples of the base include alkali metal salts such as potassium hydroxide, sodium hydroxide, sodium bicarbonate and potassium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5.4.0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these acids or bases to be used is preferably about 0.1 to about 5 mole equivalent relative to Compound (IV-1).

Examples of a solvent having no adverse effect on the reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran, dimethoxyethane, dioxane and diethyl ether; amides such as N,N-dimethylformamide; alcohol such as ethanol, propanol, tert-butanol and methoxyethanol; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to about 200° C., preferably about −10° C. to about 150° C.

A reaction time is usually about 0.5 to about 60 hours.

The thus obtained compound (II-1) can be isolated and purified by the known separating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

Compound (IV-1) used herein can be prepared, for example, according to the method described in Bilestein, vol. 25, p. 2033. In addition, Compound (X) can be prepared, for example, according to Organometallics, vol. 11, p. 954.

In step B, Compound (II-2) is prepared by a reduction reaction for Compound (II-1).

In the present reaction, a catalytic hydrogenation method using palladium carbon, palladium hydroxide or the like, or reduction using a reducing agent is performed. As the reducing agent, sodium borohydride, aluminium lithium hydride and lithium borohydride are used. In the present reaction, if needed, any solvents can be used as long as they do not inhibit the reaction. Inter alia, alcohols (e.g. C_1-3alcohol such as methanol, ethanol, propanol and the like) or ethers (diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane etc.) are preferable.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (II-2) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein A-1 is the same as A, and the other symbols are as defined above.

In step C, Compound (V) is prepared by a reaction for cyclizing Compound (IV-1) and Compound (XI). The present reaction is carried out in the presence of an acid in a solvent having no adverse effect on the reaction or without a solvent according to the conventional method.

An amount of these acids is preferably about 0.1 to about 5 mole equivalent relative to Compound (IV-1).

Examples of the solvent having no adverse effect on the reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran, dioxane and diethyl ether; halogenated hydrocarbons such as chloroform and dichloromethane; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to 150° C., preferably about −10° C. to about 120° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (V) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

In step B, Compound (II-3) can be prepared according to step B in the scheme 1.
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wherein Y′ is C or CR⁴, and L and L′ is a leaving group, and L is more reactive than L′, and the other symbols are as defined above.

In step D, Compound (VI-1) is prepared from Compound (IV-1). The present method is carried out in the presence of a base in a solvent having no adverse effect on the reaction according to the conventional method. Specific examples of leaving groups L and L′ include halogen atom, sulfonyloxy group such as p-toluenesulfonyloxy group, methanesulfonyloxy group and trifluoromethanesulfonyloxy group, and acyloxy group such as acetyloxy group and benzoyloxy group.

Example of the base include alkali metal salts such as potassium hydroxide, sodium hydroxide, sodium bicarbonate and potassium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5.4.0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these bases to be used is preferably about 1 to about 5 mole equivalent relative to Compound (IV).

Examples of the solvent having no adverse effect on the reaction include: aromatic hydrocarbon such as benzene, toluene and xylene; ethers such as tetrahydrofuran, dioxane and diethyl ether; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50 to about 150° C., preferably about −10° C. to about 120° C.

A reaction time is usually about 0.5 about 20 hours.

The thus obtained Compound (VI-1) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

In step E, Compound (II-4) is prepared by an intramolecular cyclization reaction of Compound (VI-1). The present method is carried out in the presence of an acid or a base in a solvent having no adverse effect on the reaction according to the conventional method. Specific example of a leaving group L′ include halogen atom, p-toluenesulfonyloxy group, methanesulfonyloxy group and trifluoromethanesulfonyloxy group.

Examples of the acid include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid; organic acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid and p-toluenesulfonic acid; and Lewis acids such as zinc (II) chloride, tin (IV) chloride, aluminium chloride and the like. Examples of the base include: alkali metal salts such as potassium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5.4.0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and t-butoxide.

An amount of these acids or bases to be used is preferably about 1 to about 5 mole equivalent relative to Compound (IV-1).

Examples of the solvent having no adverse effect on the reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran, dioxane and diethyl ether; haloganated hydrocarbons such as chloroform and dichloromethane; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to about 150° C., preferably about −10° C. to about 120° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (II-4) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein A-2 is the same as A, and the other symbols are as defined above.

In step F, Compound (VI-2) is prepared from Compound (IV-2) and Compound (XII). The present method is carried out in the presence of a base in a solvent having no adverse effect on the reaction according to the conventional method.

Examples of the base include: alkali metal salts such as potassium carbonate, sodium carbonate and cesium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5.4.0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these bases to be used is preferably about 1 to about 5 mole equivalent relative to Compound (IV-2).

Examples of the solvent having no adverse effect on the reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran; dioxane and diethyl ether; halogenated hydrocarbons such as chloroform and dichloromethane; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to about 200° C., preferably about −10° C. to about 150° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (VI-2) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

In step G, Compound (II-5) is prepared by a reaction for reducing Compound (VI-2).

In the present reaction, a catalytic hydrogenation method using palladium carbon, palladium hydroxide or Raney nickel, or reduction using a reducing agent is carried out. As the reducing agent, sodium borohydride, aluminium lithium hydride and lithium borohydride are used. In the present reaction, if needed, any solvents can be used as long as they do not inhibit the reaction. Inter alia, alcohols (e.g. C_1-3alcohol such as methanol, ethanol, propanol and the like) or ethers (diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane etc.) are preferable.

A reaction time is usually about 0.5 to 20 hours.

The thus obtained Compound (II-5) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein Ar¹is an optionally substituted non-aromatic hydrocarbon ring or an optionally substituent non-aromatic heterocyclic ring, Ar²is an optionally substituted aromatic hydrocarbon ring or an optionally substituted aromatic heterocyclic ring, and A-3 is the same as A, and the other symbols are as defined above.

In step H, an amino group of Compound (IV-3) is converted into a diazonium salt, and ylide is reacted thereon to prepare Compound (VIII-1). Diazotization in the present method is carried out in the presence of an acid in a solvent having no adverse effect on the reaction according to the conventional method. As the acid, for example, acetic acid and hydrochloric acid are used. As a diazotizing agent, sodium nitrite, alkyl nitrite or sulfated nitrosyl is used.

As the solvent, water, dioxane, tetrahydrofuran and the like are used.

A reaction temperature is usually about −50° C. to about 150° C., preferably about −10° C. to about 100° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained diazonium salt of Compound (IV-3) is reacted with ylide produced from Compound (XIII-1) to prepare Compound (VIII-1). The present step is carried out in the presence of a base in a solvent having no adverse effect on the reaction. Examples of the base include: alkali metal salts such as potassium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5,4,0] undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these bases to be used is preferably about 1 to about 3 mole equivalent relative to Compound (XIII-1).

Examples of the solvent having no adverse effect on the reaction include aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahyrdorufan, dioxane and diethyl ether; halogenated hydrocarbons such as chloroform and dichloromethane; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

Since the thus obtained Compound (VIII-1) is unstable depending on a kind of the compound, it is used in the next step without isolation and purification.

In step I, a reduction reaction of Compound (VIII-1) is carried out to prepare Compound (IX-1). In the present reaction, a catalytic hydrogenation method using platinum oxide, Raney nickel, palladium carbon or palladium hydroxide, or reduction using a reducing agent is used. As the reducing agent, sodium borohydride, aluminium lithium hydride and lithium borohydride are used. In the present reaction, if needed, any solvents can be used as long as they do not inhibit the reaction. Inter alia, alcohols (e.g. C_1-3alcohol such as methanol, ethanol, propanol etc.) or ethers (diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane etc.) are preferable.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (IX-1) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

In step J, Compound (II-7) is prepared by a reductive amination reaction between Compound (IX-1) and ketone (XV). The present method is carried out in the presence of a reducing agent in a solvent having no adverse effect on the reaction. Examples of the reducing agent include sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride and lithium borohydride. Although alcohol solvents such as ethanol and methanol, dichloromethane, chloroform and carbon tetrachloride are used as a solvent, any solvents can be used as long as they do not inhibit the reaction.

The thus obtained Compound (II-7) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

In step K, a bismuth regent is acted on Compound (IX-1) to prepare Compound (II-8). The present method is carried out in the presence of a metal catalyst in a solvent having no adverse effect on the reaction. As the metal catalyst, for example, copper catalysts such as copper (II) acetate and copper (II) pivalate are used. Although dichloromethane, chloroform and carbon tetrachloride are used as a solvent, any solvents can be used as long as they do not inhibit the reaction.

A reaction temperature is usually about −80° C. to about 150° C., preferably about −80° C. to about 100° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (II-8) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein X⁴is the same as X³, and the other symbols are as defined above.

Step D and step E can be carried out according to step D and step E of the scheme 3, respectively, to prepare Compound (III-1).
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wherein Ar³is an optionally substituted hydrocarbon ring, an optionally substituted non-aromatic heterocyclic ring, an aromatic hydrocarbon ring or an aromatic heterocyclic ring, X⁵is the same as X³, and other respective symbols have the same meanings as described above.)

Step H, step I, step J and step K can be carried out according to step H, step I, step J, and step K of the scheme 5, respectively, to prepare Compound (III-2).

In Compound (II), when X¹is C—COOR¹⁶, it can be converted as follows:
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wherein A-4 denote the same meaning as that of A, R¹⁶denotes an optionally substituted carbon atom, and the other symbols are as defined above.

In step L, Compound (II-10) is prepared by a reaction for leaving a carboxyl-protecting group.

All conventional methods used in a reaction for leaving a carboxyl-protecting group, for example, hydrolysis, reduction and elimination using a Lewis acid can be applied to the present reaction. It is preferable that hydrolysis is carried out in the presence of a base or an acid. Examples of the suitable base include inorganic bases such as alkali metal hydroxide (e.g. sodium hydroxide and potassium hydroxide), alkaline earth metal hydroxide (e.g. magnesium hydroxide and potassium hydroxide), alkali metal carbonate (e.g. sodium carbonate and potassium carbonate), alkaline earth metal carbonate (e.g. magnesium carbonate and calcium carbonate), alkali metal bicarbonate (e.g. sodium bicarbonate and potassium bicarbonate), alkali metal acetate (e.g. sodium acetate and potassium acetate), alkaline earth metal phosphate (e.g. magnesium phosphate and calcium phosphate) and alkali metal hydrogen phosphate (e.g. disodium hydrogen phosphate and dipotassium hydrogen phosphate), and organic bases such as trialkylamine (e.g. trimethylamine and triethylamine), picoline, N-methylpyrrolidine, N-methylmorpholine, 1,5-diazabicyclo[4.3.2]non-5-ene, 1,4-diazabicyclo[2.2.2]non-5-ene and 1,8-diazabicyclo[4.3.0]-7-undecene. Hydrolysis using a base is carried out in water or a hydrophilic organic solvent or a mixed solvent in many cases. Examples of the suitable acid include formic acid, hydrobromic acid and sulfuric acid.

The present hydrolysis reaction is usually carried out in an organic solvent, water or a mixed solvent thereof. A reaction temperature is not particularly limited, but is appropriately selected depending on a kind of a carboxyl-protecting group and an elimination method. Elimination using a Lewis acid is carried out by reacting Compound (II-9) or a salt thereof with a Lewis acid, for example, trihalogenated boron (e.g. boron trichloride and boron trifluoride), tetrahalogenated titanium (e.g. titanium tetrachloride and titanium tetrabromide), and halogenated aluminium (e.g. aluminium chloride and aluminium bromide), or an organic acid (e.g. trichloroacetic acid and trifluoroacetic acid). This elimination reaction is preferably carried out in the presence of a cation scavenger (e.g. anisole and phenol) and is usually carried out in a solvent such as nitroalkane (e.g. nitromethane and nitroethane), alkylene halide (e.g., methylene chloride and ethylene chloride), diethyl ether, carbon disulfide, and a solvent having no adverse effect on the reaction. These solvents may be used as a mixture thereof.

It is preferable that elimination by reduction is applied to elimination of a protecting group such as halogenated alkyl (e.g. 2-iodoethyl and 2,2,2-trichloroethyl) ester, and aralkyl (e.g. benzyl) ester. Examples of a reduction method using in the present elimination reaction include the conventional catalytic reduction in the presence of a combination of a metal (e.g. zinc and zinc amalgam) or a salt of a chromium compound (e.g. chromate chloride and chromate acetate) and an organic or inorganic acid (e.g. acetic acid, propionic acid and hydrochloric acid); or the conventional metal catalyst (e.g. palladium carbon and Raney nickel). A reaction temperature is not particularly limited, but a reaction is carried out under cooling, at room temperature of under warming.

The thus obtained Compound (II-10) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein R¹⁷and R¹⁸are optionally substituted alkyl group, allyl group or hydroxy group; or R¹⁷and R¹⁸may be combined each other to form a ring, Y″ is the same as Y, and the other symbols are as defined above.

In the present method, Compound (II-12) is prepared by reacting Compound (II-11) or a reactive derivative at a carboxyl group thereof and a salt thereof with the above Compound (XVI) or a reactive derivative at an amino group thereof or a salt thereof. Examples of the suitable reactive derivative at an amino group of Compound (XVI) include: Schiff base type imino produced by a reaction of Compound (XVI) with a carbonyl compound such as aldehyde, ketone and the like; silyl derivative produced by a reaction of Compound (XVI) and a silyl compound such as bis(trimethylsilyl)acetamide, mono(trimethylsilyl) acetamide, bis(trimethylsilyl)urea and the like; derivative produced by a reaction of Compound (XVI) with phosphorus trichloride or phosgene.

Specific examples of the suitable reactive derivative at a carboxyl group of Compound (II-11) include acid halide, acid anhydride, activated amide, activated ester and the like. Examples of the suitable reactive derivative include: acid chloride; acid azide; mixed acid anhydride with an acid such as substituted phosphoric acid such as dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, dibenzylphosphoric acid, halogenated phosphoric acid and the like, dialkylphosphorous acid, sulfurous acid, thiosulfuric acid, sulfuric acid, sulfonic acid such as methanesulfonic acid and the like, aliphatic carboxylic acid such as acetic acid, propionic acid, butyric acid, isobutyric acid, pivalic acid, pentanoic acid, isopentanoic acid, trichloroacetic acid and the like or aromatic carboxylic acid such as benzoic acid and the like; symmetric acid anhydride; activated amide with imidazole; 4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; activated ester such as cyanomethylester, methoxymethyl ester, dimethyliminomethyl ester, vinyl ester, propargyl ester, p-nitrophenyl ester, trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, phenylazophenyl ester, phenyl thioester, p-nitrophenyl ester, p-cresyl thioester, carboxylmethyl thioester, pyranyl ester, pyridyl ester, piperidyl ester, 8-quinolyl thioester and the like, or esters with N-hydroxy compound such as N,N-dimethylhydroxyamine, 1-hydroxy-2-(1H)-pyridone, N-hydroxysuccineimide, N-hydroxyphthalimide, 1-hydroxy-1H-benzotriazole and the like. These reactive derivatives can be arbitrarily selected depending on a kind of Compound (II-11) to be used. Examples of the suitable reactive derivative of Compound (II-12) include alkali metal salts such as sodium salt, potassium salt and the like, alkaline earth metal salts such as calcium salt, magnesium salt and the like, and basic salts such as organic base salts such as ammonium salt, trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N-dibenzylethylenediamine salt and the like. Although the reaction is usually carried out in the conventional solvent such as water, alcohols such as methanol, ethanol and the like, acetone, dioxane, acetonitrile, chloroform, methylene chloride, ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide and pyridine, the reaction may be carried out in any other organic solvents as long as they have no adverse effect on the reaction. These conventional solvents may be used as a mixture with water.

When Compound (II-11) is used as the form of a free acid or a salt thereof in this reaction, it is desirable that the reaction is carried out in the presence of the normally used condensing agent such as so-called Vilsmeier regent and the like prepared by a reaction of N,N′-dicyclohexylcarbodiimide; N-cyclohexyl-N′-morpholinoethylcarbodiimide; N-cyclohexyl-N′-(4-diethylaminocyclohexyl)carbodiimide; N,N′-diethylcarbodiimide, N,N′-diisopropylcarbodiimide, N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide; N,N′-carbonylbis(2-methylimidazole); pentamethyleneketene-N-cyclohexylimine; diphenylketene-N-cyclohexylimine; ethoxyacetylene; 1-alkoxy-1-chloroethylene; trialkyl phosphite; polyethyl phosphate; polyisopropyl phosphate; phosphorus oxychloride; diphenylphosphorylazide; thionyl chloride; oxalyl chloride; lower alkyl haloformate such as ethyl chloroformate; isopropyl chloroformate and the like; triphenylphosphine; 2-ethyl-7-hydroxybenzisooxazolium salt, 2-ethyl-S-(m-sulfopheny)isooxazoliumhydroxide internal salt; N-hydroxybenzotriazole; 1-(p-chlorobenzenesulfonyloxy)-6-chloro-1H-benzotriazole; N—N′-dimethylformamide with thionyl chloride, phosgene, trichloromethyl chloroformate, phosphorus oxychloride or the like. Alternatively, the reaction may be carried out in the presence of an inorganic base or an organic base such as alkali metal bicarbonate salt, tri(lower)alkylamine, pyridine, N-(lower)alkylmorpholine, N,N-di(lower)alkylbenzylamine and the like. A reaction temperature is not particularly limited, but the reaction is carried out under cooling or under warming.

An amount of Compound (XVI) to be used is 1 to 10 mole equivalent, preferably 1 to 3 equivalent relative to Compound (II-11).

A reaction temperature is usually −30° C. to 100° C.

A reaction time is usually 0.5 to 20 hours.

In addition, when a mixed acid anhydride is used, Compound (II-11) and chlorocarbonic ester (e.g. methyl chlorocarbonate, ethyl chlorocarbonate, isobutyl chlorocarbonate etc.) are reacted in the presence of a base (e.g. triethylamine, N-methylmorpholine, N,N-dimethylaniline, sodium bicarbonate, sodium carbonate, potassium carbonate etc.) and is further reacted with Compound (XVI).

An amount of Compound (XVI) to be used is usually 1 to 10 mole equivalent, preferably 1 to 3 mole equivalent relative to Compound (II-11).

A reaction temperature is usually −30° C. to 100° C.

A reaction time is usually 0.5 to 20 hours.

The thus obtained Compound (II-12) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

When X¹is C—COOR¹⁶in Compound (III), the conversion can be carried out as follows:
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wherein the symbols are as defined above.

Step L and step M can be carried out according to step L in the scheme 8 and step M in the scheme 9, respectively, to prepare Compound (III-4) and Compound (III-5).
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wherein R¹⁹is an optionally substituted alkyl group, allyl group, hydroxy group, amino group or sulfanyl group, and the other symbols are as defined above.

In the present method, Compound (II-13) is prepared by a reaction between Compound (V) and a nucleophilic regent.

Examples of the nucleophilic regent include metal phenolate, metal alcoholate, Grignard regent, alkyl metal regent, aryl metal regent and thioalcoholate.

An amount of the nucleophilic regent to be used is preferably about 1 to about 5 mole equivalent relative to Compound (V).

Examples of a solvent having no adverse effect on the reaction include: ethers such as diethyl ether, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene and xylene; amides such as N,N-dimethylformamide and 1-methylpyrrolidone; sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to about 150° C., preferably about −10 to about 100° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (II-13) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.
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wherein the symbols are as defined above.

Step N can be carried out according to step N in the scheme 11 to prepare Compound (III-4).
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wherein A-6 is the same as A, and the other symbols are as defined above.

In step H, an amino group of Compound (IV-5) is converted into a diazonium salt, and ylide is reacted thereon to prepare Compound (VIII-3). Diazotization in this method is carried out in the presence of an acid in a solvent having no adverse effect on the reaction according to the conventional method. As the acid, for example, acetic acid and hydrochloric acid are used. As the diazotizing agent, sodium nitrite, alkyl nitrite or sulfated nitrosyl is used.

As the solvent, water, dioxane, tetrahydrofuran and the like are used.

A reaction temperature is usually about −50° C. to about 150° C., preferably about −10° C. to about 100° C.

A reaction time is about 0.5 to about 20 hours.

The thus obtained diazonium salt of Compound (IV-5) is reacted with ylide produced from Compound (XVII) to prepare Compound (VIII-3). The present step is carried out in the presence of a base in a solvent having no adverse effect on the reaction. Examples of the base include: alkali metal salts such as potassium carbonate; amines such as pyridine, triethylamine, N,N-dimethylaniline and 1,8-diazabicyclo[5.4.0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these bases to be used is preferably about 1 to about 3 mole equivalent relative to Compound (XVII).

Since the thus obtained Compound (VIII-3) is unstable depending on a kind of the compound, it is used in the next step without isolation and purification.

Step I, step J and step K can be carried out according to step I, step J and step K, respectively, to prepare Compound (II-14) and Compound (II-15).

When R³is a hydrogen atom in Compound (II) the following conversion is possible.
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wherein the symbols are as above.

In step O, Compound (II-4) is subjected to alkylation, acylation, carbamoylation, oxycarbonization or thiocarbamoylation to prepare Compound (II-6).

The reaction is carried out according to the conventional method. In alkylation, alkyl halide is reacted, in acylation, acid halide or acid anhydride is reacted, in carbamoylation, isocyanate or carbonylimidazole is reacted and, thereafter, amine is reacted, in oxycarbonization, oxycarbonyl halide or oxycarboic acid anhydride is reacted and, in thiocarbamoylation, thioisocyanate is reacted, respectively, to prepare the compound. The present reaction is generally carried out in the presence of a base in a solvent having no adverse effect on the reaction. Examples of the base include alkali metal salts such as potassium hydroxide, sodium hydroxide, sodium bicarbonate and potassium carbonate; amines such as pyridine, triethyamine, N,N-dimethylaniline and 1,8-diazabicyclo[5,4,0]undec-7-ene; metal hydrides such as potassium hydride and sodium hydride; and alkali metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide.

An amount of these bases to be used is preferably about 1 to about 5 mole equivalent relative to Compound (II-4).

Examples of the solvent having no adverse effect on the reaction include: aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as tetrahydrofuran, dioxane and diethyl ether: halogenated hydrocarbons such as chloroform and dichloromethane; amides such as N,N-dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used by mixing at an appropriate ratio.

A reaction temperature is usually about −50° C. to about 150° C., preferably about −10° C. to about 120° C.

A reaction time is usually about 0.5 to about 20 hours.

The thus obtained Compound (II-6) can be isolated and purified by the known isolating and purifying methods, for example, concentration, concentration under the reduced pressure, extraction with solvent, crystallization, recrystallization, transfer dissolution and chromatography.

When R³is a hydrogen atom in Compound (III), the following conversion is possible.
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wherein the symbols are as above.

Step Or step J and step K can be carried out according to step 0 in the scheme 14, respectively, to prepare Compound (III).

All the compounds used or obtained in the present invention include corresponding salts, even if specifically stated, and they can be exchanged to one another by a per se known method or modified methods thereof.

When the compounds or salts thereof obtained by the present invention are asymmetric molecules, they can be separated into d-form isomer and 1-form isomer according to conventional optical resolution methods.

The compound or its salt obtained by the present invention may be used in a next step as its reaction mixture without sufficient purification.

Compound (I), (II), (III) or (IIIa) of the present invention has an excellent Ca receptor modulating activity and enhances the secretion of PTH, and therefore useful as drugs for treating bone diseases, kidney-acting drugs, central nervous system and endocrine-acting drugs, digestive system-acting drugs, and the like. Further, the toxicity is low. Therefore, Compound (I), (II), (III) or (IIIa) may be safely administered to mammalian animals (for example, human, rat, mouse, dog, rabbit, cat, cow, horse, pig, and the like).

Thus, a pharmaceutical composition containing compound (I), (II), (III) or (IIIa) of the present invention is expected to be useful in the treatment and prevention of diseases, in which Ca receptor modulating activity is required, such as Ca receptor modulating drugs: primary or secondary hyper parathyroidism; hypoparathyroidism; hyperthyroidism; hypothyroidism; Graves' disease; Hashimoto's toxicosis; Paget's disease; hypercalcemia associated with malignant tumor; hypercalcemia; hypocalcemia; postmenopausal osteoporosis; senile osteoporosis; secondary osteoporosis; osteomalacia; renal osteodystrophy; fracture; osteoarthritis; rheumatoid arthritis; osteosarcoma; myeloma; hypertension; diabetes; myocardial infarction; Hachington's diseases; Parkinson's diseases; Alzheimer's disease; dementia; cerebral apoplexy; brain tumor; spinal injury; diabetic renal disease; renal insufficiency; gastric ulcer; duodenal ulcer; Basedow's disease; parathyroid gland tumor; thyride gland tumor; arteriosclerosis; and the like; Ca receptor antagonistic drugs: hyperthyroidism; hypocalcemia; postmenopausal osteoporosis; senile osteoporosis; secondary osteoporosis; osteomalacia; renal osteodystrophy; fracture; osteoarthritis; rheumatoid arthritis; osteosarcoma; myeloma; central nervous system diseases; and the like, in particular osteoporosis.

The dosage of Compound (I), (II), (III) or (IIIa) can be selected in various ways depending on the administration route and the symptom of a patient to be treated. The dosage as Compound (I), (II), (III) or (IIIa) per an adult (a body weight of 50 kg) can be usually selected in a range of about 0.1 mg to about 500 mg, preferably about 1 mg to about 100 mg in the case of oral administration and in a range of about 0.01 mg to about 100 mg, further preferably about 0.1 mg to about 10 mg in the case of parenteral administration. The dosage can be administered with being divided in 1-3 times daily.

Compound (I), (II), (III) or (IIIa) of the present invention can be formulated with a pharmaceutically acceptable carrier and can be orally or parenterally administered as solid formulations such as tablets, capsules, granules, powders, or the like; or liquid formulations such as syrups, injections, or the like. Also, there can be prepared formulations for transdermal administration such as patchings, cataplasms, ointments (including creams), plasters, tapes, lotions, liquids and solutions, suspensions, emulsions, sprays, and the like.

As for a pharmaceutically acceptable carrier, a variety of organic or inorganic carrier substances, which have been conventionally employed as formulation materials, is used and compounded as a bulking agent, a lubricant, a binding agent, and a disintegrator in solid formulations; a vehicle, a solubilizing agent, a suspending agent, an isotonicity agent, a buffering agent, and an analgesic in liquid formulations. If necessary, formulation excipients such as a preservative, an antioxidant, a stabilizer, a coloring agent, a sweetening agent, and the like can be used.

Preferred examples of the bulking agent include lactose, sucrose, D-mannitol, starch, crystalline cellulose, light anhydrous silicic acid, and the like. Preferred examples of the lubricant include magnesium stearate, potassium stearate, talc, colloidal silica, and the like. Preferred examples of the binding agent include crystalline cellulose, α-starch, sucrose, D-mannitol, dextrin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, and the like. Preferred examples of the disintegrator include starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and the like. Preferred examples of the vehicle include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, and the like.

If necessary, for the purpose of taste masking, enteric coating, or prolonged action, oral formulations can be prepared by coating by a per se known method. Examples of this coating agent include hydroxypropylmethyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, polyoxyethylene glycol, Tween 80, Pluronic F68 [polyoxyethylene (160) polyoxypropylene (30) glycol], cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxymethyl cellulose acetate phthalate, Eudragit (manufactured by Rohm Company, methacrylic acid-acrylic acid copolymer), and the like.

Preferred examples of the solubilizing agent include polyethylene glycol, propylene glycol, benzyl benzoate, ethanol, trisamiomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, and the like. Preferred examples of the suspending agent include surface active agents such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, and the like; hydrophilic, high molecular substances such as polyvinyl alcohol, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and the like; and so on. Preferred examples of the isotonicity agent include sodium chloride, glycerin, D-mannitol, and the like. Preferred examples of the buffering agent include buffer solutions of a phosphate, an acetate, a carbonate, a citrate, or the like. Preferable examples of the analgesic include benzyl alcohol and the like. Preferred examples of the preservative include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, and the like. Preferred examples of the antioxidant include sulfites, ascorbic acid, and the like.

The following examples, preparations and experiments describe the manner and process of making and using the present invention and are illustrative rather than limiting. It is to be understood that there may be other embodiments which fall within the spirit and scope of the present invention as defined by the claims appended hereto.

Abbreviations employed herein are defined below.

DCM=dichloromethane
DCE=dichloroethane
DMAP=dimethylaminopyridine
DMF=dimethylformamide
WSC=1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride
M+H=monoisotopic mass plus one proton
Me=methyl
Et=ethyl
Ph=phenyl
h=hours
min=minutes
HPLC=high performance liquid chromatography
HOBt=hydroxybenzotriazole
LC/MS=liquid chromatography/mass spectrometry
MS=mass spectrometry
Rt=retention time
TEA=triethylamine
TFA=trifluoroacetic acid
IPE=diisopropylether
TLC=thin layer chromatography
THF=tetrahydrofuran
TMSCN=trimethylsilyl cyanide
HATU=O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium hexafulorophosphate
DIPEA=diisopropylethylamine

EXAMPLE 1
Ethyl 5-phenyl-7-(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate

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Step A: A mixture of 4,4,4-trifluoro-1-phenyl-1,3-butanedione 1 (6.97 g, 32.24 mmol) and ethyl 3-aminopyrazole-4-carboxylate 2 (5.0 g, 32.22 mmol) in AcOH (100 mL) was refluxed for 4 h. The mixture was cooled to room temperature and concentrated and precipitated crystals were collected by filtration to give 8.63 g (79%) of the title compound as yellow crystals. ¹H NMR (CDCl₃, 200 MHz): 1.47 (3H, t, J=7.0 Hz), 4.47 (2H, q, J=7.0 Hz), 7.54-7.61 (3H, m), 7.80 (1H, s), 8.23-8.28 (2H, m), 8.68 (1H, s)

Step B: To a solution of 3 (3.51 g, 10.3 mmol) in MeOH was added NaBH₄(1.4 g, 3.7 mmol) at room temperature. The whole was stirred at the same temperature for 5 h, quenched with saturated citric acid solution, concentrated in vacuo, and extracted with AcOEt. The extract was successively washed with aq. NaHCO₃, water and brine, dried over MgSO₄and then concentrated to give 1.73 g (49%) of compound 4 as colorless oil. ¹H HMR (CDCl₃, 200 MHz): 1.32 (3H, t, J=6.8 Hz), 2.28-2.46 (1H, m), 2.50-2.61 (1H, m), 4.25 (2H, q, J=6.8 Hz), 4.58 (1H, dd, J=11.4, 3.4 Hz), 4.85 (1H, ddd, J=3.4, 3.0, 2.6 Hz), 6.15 (1H, s)7.34-7.48 (5H, m), 7.74 (1H, s).

Compounds of Examples 2-14, shown in the Table 1, were prepared in a manner similar to that described in Example 1.

TABLE 1PhysiologicalExampleStructureNameData2 embedded image

ethyl 5-(2-naphthyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 120-122° C.3 embedded image

ethyl 5-(4-methoxyphenyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 105-109° C.4 embedded image

ethyl 5-(4-chlorophenyl)-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateIR(KBr) 3376, 2984, 1680, 1597, 1578, 1541 cm⁻¹5 embedded image

ethyl 5-(3-pyridinyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 341 (M + H)+6 embedded image

ethyl 7-benzyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 362 (M + H)+7 embedded image

ethyl 7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 286 (M + H)+8 embedded image

ethyl 5-(4-ethylphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 368 (m + H)+9 embedded image

ethyl 5-(2-methoxyphenyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylate¹H NMR (CDCl₃, 200 MHz): 1.33(3H, t, J=7.2 Hz), 2.16-2.34(1H, m), 2.34-2.61(1H, m)3.88(3H, s), 4.26(2H, q, J=7.2 Hz), 4.80-4.91(1H, m), 5.00(1H, dd, J=11.4, 2.6 Hz), 6.08(1H, s), 6.92-7.08(2H, m), 7.30-7.55(1H, m), 7.74(1H, s)10 embedded image

ethyl 5-(3-methoxyphenyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylate¹H NMR (CDCl₃, 200 MHz): 1.32(3H, t, J=7.0 Hz), 2.27-2.45(1H, m)2.51-2.61(1H, m), 3.84(3H, s), 4.25(2H, q, J=7.0 Hz), 4.55 (1H, dd, J=11.4, 2.8 Hz), 4.76-4.93(1H, m)5.76-4.93(1H, m), 6.15(1H, s), 6.89-7.03(3H, m), 7.30-7.38(1H, m), 7.74(1H, s).11 embedded image

ethyl 5-(2-chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylate¹H NMR (CDCl₃, 200 MHz): 1.34(3H, t, J=7.2 Hz), 2.14-2.32(1H, m), 2.66-2.78(1H, m), 4.27(2H, q, J=7.0 Hz), 4.81-4.97(1H, m), 5.07(1H, dd, J=11.4, 3.0 Hz), 6.11(1H, s), 7.28-7.46(3H, m), 7.66-7.70(1H, m), 7.75(1H, s).12 embedded image

ethyl 5-(3-chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylate¹H NMR (CDCl₃, 200 MHz): 1.37(3H, t, J=7.0 Hz), 2.26-2.44(1H, m), 2.50-2.61(1H, m), 4.26(2H, q, J=7.0 Hz), 4.57(1H, dd, J=11.6, 3.0 Hz), 4.76-4.93(1H, m), 6.16(1H, s), 7.29-7.46(4H, m), 7.74(1H, s).13 embedded image

ethyl 2-methyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 142-143° C.14 embedded image

ethyl 5-(2-furyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 86° C.

EXAMPLE 15
Ethyl 7,7-dimethyl-5-(2-pyridyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate

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Step A: To a stirred solution of compound 1 (7.0 g, 44.3 mmol) in THF (100 mL) was added n-BuLi (1.6 M hexane solution, 28 mL, 44.8 mmol) at −78° C. After the mixture was stirred for 30 min, compound 2(6.34 g, 44.3 mmol) was added thereto. The resulting mixture was stirred at −78—50° C. for 2 h, quenched with saturated citric acid solution and extracted with AcOEt. The extract was successively washed with water and brine, dried over MgSO₄and then concentrated in vacuo. The residue was chromatographed on silica gel with AcOEt/hexane (1:9) as an eluent to give 3.16 g (44% yield) of compound 3 as colorless liquid.

Step B: To a solution of compound 3 and compound 4 in methoxyethanol (60 mL) was added TFA (4.47 g, 39.2 mmol) with ice-water cooling. The mixture was refluxed for 12 h, diluted with AcOEt, and the mixture was washed with saturated NaHCO₃solution, water and brine, dried over MgSO₄, and then concentrated in vacuo. The residue was chromatographed on silica gel with AcOEt/hexane (1:4) as an eluent to give 2.03 g (36% yield) of compound 5 as colorless prisms.

Step C: A mixture of 5 (1.98 g, 6.96 mmol) and 10% Pd—C (1.0 g) in EtOH (100 mL) was stirred for 2 h under the H₂atmosphere (balloon pressure). After the insoluble materials were filtered off, the residue was concentrated in vacuo to give the residue. Crystallization from hexane/IPE gave the title compound 6 (1.00 g, 48%) as colorless solid. ¹H NMR (CDCl₃, 200 MHz): 1.34 (3H, t, J=7.0 Hz), 4.26 (2H, q, J=7.0 Hz), 4.80 (1H, dd, J=11.4, 2.6 Hz), 6.39 (1H, s), 7.24-7.31 (1H, m), 7.51 (1H, d, J=7.6 Hz), 7.76 (1H, td, J=7.6, 1.8 Hz), 8.60-8.63 (1H, m).

Compounds of Examples 16-29, 439-447 and 924-938 shown in the Table 2, were prepared in a manner similar to that described in Example 15.

TABLE 2PhysiologicalExampleStructureNameData16 embedded image

ethyl 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine- 3-carboxylateMS (ESI, m/z) 300 (M + H)+17 embedded image

ethyl 5′-phenyl-5′,6′-dihydro- 4′H-spiro[cyclopentane-1,7′- pyrazolo[1,5-a]pyrimidine]- 3′-carboxylateMS (ESI, m/z) 326 (M + H)+18 embedded image

ethyl 7,7-diethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 300 (M + H)+19 embedded image

ethyl 5′-phenyl-5′,6′-dihydro- 4′H-spiro[cyclohexane-1,7′- pyrazolo[1,5-a]pyrimidine]- 3′-carboxylateMS (ESI, m/z) 328 (M + H)+20 embedded image

ethyl 5-phenyl- 4,5,5a,6,7,8,9,9a- octahydropyrazolo[1,5-a]quinazoline-3-carboxylateMS (ESI, m/z) 326 (M + H)+439 embedded image

ethyl 5-(2-methoxyphenyl)- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]- pyrimidine-3-carboxylateMS (ESI, m/z) 330 (M + H)+440 embedded image

ethyl 2-ethyl-7,7-dimethyl-5- phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 328 (M + H)+441 embedded image

ethyl 2,7,7-trimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 328 (M + H)+442 embedded image

ethyl 7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 301 (M + H)+443 embedded image

ethyl 7,7-dimethyl-5-(5- methyl-1-3-thiazol-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 321 (M + H)+444 embedded image

ethyl 5-(3-methoxyphenyl)- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 330 (M + H)+445 embedded image

ethyl 2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 314 (M + H)+446 embedded image

ethyl 5-(2-fluorophenyl) 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 332 (M + H)+447 embedded image

methyl 7,7-dimethyl-2- (methylthio)-5-phenyl- 4,5,6,7- tetrahydropyrazolo]1,5-a]pyrimidine-3-carboxyalateMS (ESI, m/z) 332 (M + H)+924 embedded image

ethyl 5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 318 (M + H)+925 embedded image

ethyl 5-(2-chlorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 334 (M + H)+926 embedded image

ethyl 7,7-dimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESl, m/z) 314 (M + H)+927 embedded image

ethyl 5-(4-methoxyphenyl)- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 330 (M + H)+928 embedded image

ethyl 5-(2-chlorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 348 (M + H)+929 embedded image

ethy 5-(2-methoxyphenyl)- 2,7,7,-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]- pyrimidine-3-carboxylateMS (ESI, m/z) 344 (M + H)+930 embedded image

ethyl 5-(3-fluorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxyalateMS (ESI, m/z) 332 (M + H)+931 embedded image

ethyl 2,7,7-trimethyl-5-(3- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxyalateMS (ESI, m/z) 328 (M + H)+932 embedded image

ethyl 5-(3-methoxyphenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 344 (M + H)+933 embedded image

ethyl 5-(4-fluorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 332 (M + H)+934 embedded image

ethyl 2,7,7-trimethyl-5-(4- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 328 (M + H)+935 embedded image

ethyl 5-(4-methoxyphenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 344 (M + H)+936 embedded image

ethyl 2,7,7-trimethyl-5-(2- thienyl)-4,5,6,7-tetra- hydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 320 (M + H)+937 embedded image

ethyl 5-(2,4-dimethylphenyl)- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 328 (M + H)+938 embedded image

ethyl 2-(2-hydroxyethoxyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolol[1,5-a]pyrimidine-3-carboxylateMS (ESI, m/z) 360 (M + H)+

EXAMPLE 21
5-Phenyl-7-(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid

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A mixture of 1, 1.5 N KOH solution (14 mL) and EtOH (20 mL) was stirred at 60° C. for 12 h, acidified with saturated citric acid solution, and the precipitated solid was collected by filtration, which was washed with water and IPE to give 1.59 g (76% yield) of the title compound as colorless prisms. mp 184.8-185.0° C., ¹H NMR (CDCl₃, 300 MHz): 2.31-2.44 (1H, m), 2.50-2.59 (1H, m), 4.59 (1H, dd, J=11.4, 3.0 Hz), 4.79 (1H, m), 6.10 (1H, s), 7.20-7.26 (5H, m), 7.78 (1H, s).

Compounds of Examples 22-39, 448-458 and 939-953 shown in the Table 3, were prepared in a manner similar to that described in Example 21.

TABLE 3ExampleStructureNamePhysiological Data22 embedded image

5-(2-naphthyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 143-145° C.23 embedded image

5-(3-pyridinyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 315 (M + H)+24 embedded image

7-benzyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 336 (M + H)+25 embedded image

5-(4-methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 154-155° C.26 embedded image

5-(4-chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 186-187° C.27 embedded image

7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 165-167° C.28 embedded image

5-(4-ethylphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 165-168° C.29 embedded image

5-(2-furyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidmp 156-157° C.30 embedded image

5-(2-methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 189-190° C.31 embedded image

5-(3-methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 169-170° C.32 embedded image

5-(2-chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 177-179° C.33 embedded image

5-(3-chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 194-195° C.34 embedded image

2-methyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidmp 165-166° C.35 embedded image

7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 201-202° C.36 embedded image

5′-pheny-5′,6′-dihydro-4′H- spiro[cyclopentane-1,7′- pyrazolo[1,5-a]pyrimidine]-3′- carboxylic acidMS (ESI, m/z) 298 (M + H)+37 embedded image

7,7-diethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 158-160° C.39 embedded image

5′-phenyl-5′,6′-dihydro-4′H- spiro[cyclohexane-1,7′- pyrazolo[1,5-a]pyrimidine]-3′- carboxylic acidmp 155° C.39 embedded image

5-phenyl-4,5,5a,6,7,8,9,9a- octahydropyrazolo[1,5-a]quinazoline-3-carboxylic acidmp 158-160° C.448 embedded image

5-(2-methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 302 (M + H)+449 embedded image

2-ethyl-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 300 (M + H)+450 embedded image

4-benzyl-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 362 (M + H)+451 embedded image

2,7,7-trimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 300 (M + H)+452 embedded image

7,7-dimethyl-5-(2-pyridinyl)-4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 273 (M + H)+453 embedded image

7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 293 (M + H)+454 embedded image

5-(3-methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 302 (M + H)+455 embedded image

2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 286 (M + H)+456 embedded image

4,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 286 (M + H)+457 embedded image

5-(2-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 304 (M + H)+458 embedded image

7,7-dimethyl-2-(methylthio)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidMS (ESI, m/z) 318 (M + H)+939 embedded image

5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 167-168° C.940 embedded image

5-(2-chlorophenyl)-7,7- dimethyl- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3- carboxylic acidmp 167-168° C.941 embedded image

7,7-dimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid¹H NMR (CDCl₃, 300 MHz) δ 1.59 (3H, s), 1.64 (3H, s), 1.92-2.17 (2H, m), 2.38 (3H, s), 4.89 (1H, dd, J = 10.8, 3.9 Hz), 5.92 (1H, s), 7.16-7.29 (3H, m), 7.53 (1H, dd, J = 7.2, 1.8 Hz), 7.69 (1H, s).942 embedded image

5-(4-methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 196-197° C.943 embedded image

5-(2-chlorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 173-174° C.944 embedded image

5-(2-methoxyphenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 198-199° C.945 embedded image

5-(3-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 153-155° C.946 embedded image

2,7,7-trimethyl-5-(3- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 146-148° C.947 embedded image

5-(3-methoxyphenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 151-152° C.948 embedded image

5-(4-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 173-174° C.949 embedded image

2,7,7-trimethyl-5-(4- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1.5-a]pyrimidine-3-carboxylic acidmp 181-182° C.950 embedded image

5-(4-methoxyphenyl)-2,7,7- trimethyl-4,5,6,7-tetra- hydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 178-179° C.951 embedded image

2,7,7-trimethyl-5-(2-thienyl)- 4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carboxylic acidmp 186-187° C.952 embedded image

5-(2,4-dimethylphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 155-157° C.953 embedded image

2-(2-hydroxyethoxy)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acidmp 137-139° C.

EXAMPLE 40
N-Cyclooctyl-5-phenyl-7-(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

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Cyclooctylamine (24 mg, 0.19 mmol) was added to a suspension of compound 1 (0.05 g, 0.16 mmol), WSC (37 mg, 0.19 mmol), HOBt (29 mg, 0.19 mmol) and DMAP (23 mg, 0.19 mmol) in DMF (1.5 mL). The reaction mixture was stirred at room temperature for 14 h, diluted with DCM (0.5 mL) and saturated NaHCO₃solution (0.5 mL), and then separated using PHASE-SEP filtration syringe. The organic layer was concentrated and loaded onto preparative HPLC (Gilson 215 system). The purest fractions were combined to give 64.6 mg (96% yield) of the title compound as a white solid. Reverse Phase LC/MS: CAPCELLPAKCC18UG120, S-3 μm, 2.0×50 mm, UV detection at 220, 8 min. gradient 10-100% Solvent B/A (Solvent A: CH₃CN with 0.1% TFA, Solvent B: H₂O with 0.1% TFA), 0.5 mL/min. Rt=1.90 min, (96% pure). MS (M+H: 421).

EXAMPLE 41
N-(1-ethyl-1-(4-(trifluoromethyl)phenyl)propyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

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To a solution of 3 (0.5 g, 1.84 mmol) and HATU (0.84 g, 2.21 mmol) in DMF (3 mL) was added DIPEA (0.67 mL, 3.68 mmol) at room temperature. After 30 min, compound 2 (0.59 g, 2.21 mmol) was added thereto. The resulting mixture was stirred at 80° C. for 18 h, concentrated in vacuo, and the residue was chromatographed on silica gel with AcOEt/hexane (1/1) as an eluent to give 0.28 g (31% yield) of compound 4 as colorless prisms. mp 193-194° C.

Compounds of Examples 42-434, 459-867 and 954-1008 shown in the table 4, were prepared in a manner similar to that described in Example 40 or 41.

TABLE 4PhysiologicalExampleStructureNameData42 embedded image

N-(1-adamantyl)-2-methyl-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 162-163° C.43 embedded image

3-(1H-imidazol-1-ylcarbonyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 364 (M + H)+44 embedded image

N-(2,3-dihydro-1H-inden-1-yl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 429 (M + H)+45 embedded image

N-(3,3-diphenylpropyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 508 (M + H)+46 embedded image

N-(3-((2-ethylhexyl)oxy)propyl)- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 484 (M + H)+47 embedded image

N-(4-tert-butylcyclohexyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 452 (M + H)+48 embedded image

N-(2,3-dihydro-1H-inden-2-yl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 429 (M + H)+49 embedded image

N-(sec-butyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 369 (M + H)+50 embedded image

N-(2-(1H-imidazol-4-yl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 407 (M + H)+51 embedded image

5-phenyl-7-(trifluoromethyl)-N- (2-((2-(tritiuoromethyl)-4- quinolinyl)thio)ethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 569 (M + H)+52 embedded image

N-(3-methylbutyl)-5-phenyl-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 383 (M + H)+53 embedded image

N-(3-(3- (acetylamino)phenoxy)propyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 505 (M + H)+54 embedded image

N-(4-(2,4-bis(1,1- dimethylpropyl)phenoxy)butyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 602 (M + H)+55 embedded image

N-(2-(1-methyl-2- pyrrolidinyl)ethyl)-5-phenyl-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 424 (M + H)+56 embedded image

N-(2-(2-oxo-2,3-dihydro-1H- imidazol-1-yl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 423 (M + H)+57 embedded image

5-phenyl-7-(trifluoromethyl)-N- (1,2,2-trimethylpropyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+58 embedded image

N-(1,2-dimethylpropyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 383 (M + H)+59 embedded image

N-(2-adamantyl)-5-phenyl-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 447 (M + H)+60 embedded image

2,2,2-trifluoro-N-((3S)-1-((5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinyl)acetamideMS (ESI, m/z) 478 (M + H)+61 embedded image

N-(3-(1H-imidazol-1-yl)propyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 421 (M + H)+62 embedded image

N-(2-(diisopropylamino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 441 (M + H)+63 embedded image

N-(3-(2-methyl-1- piperidinyl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 453 (M + H)+64 embedded image

N-(2-(ethyl(3- methylphenyl)amino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 475 (M + H)+65 embedded image

5-phenyl-N-(2,2,6,6- tetramethyl-4-piperidinyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 453 (M + H)+66 embedded image

N-butyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- ]pyrimidine-3-carboxamideMS (ESI, m/z) 369 (M + H)+67 embedded image

N-(cyclohexylmethyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 409 (M + H)+68 embedded image

N-cyclopropyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 353 (M + H)+69 embedded image

N-benzyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 403 (M + H)+70 embedded image

N-(1,3-benzodioxol-5-ylmethyl)- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 447 (M + H)+71 embedded image

5-phenyl-N-(2-phenylethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 417 (M + H)+72 embedded image

5-phenyl-N-(3-phenylpropyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 431 (M + H)+73 embedded image

N-benzhydryl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 480 (M + H)+74 embedded image

N-(2-methoxyethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 371 (M + H)+75 embedded image

N-(3-(methylthio)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 401 (M + H)+76 embedded image

N-phenyl-N-(tetrahydro-2- furanylmethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+77 embedded image

N-(2-(1H-indol-3-yl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 456 (M + H)+78 embedded image

N-(1-ethylpropyl)-5-phenyl-7- (trifluoromethy)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 383 (M + H)+79 embedded image

N-(tert-butyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 369 (M + H)+80 embedded image

N-cyclohexyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 395 (M + H)+81 embedded image

5-phenyl-N-2-propynyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 351 (M + H)+82 embedded image

5-phenyl-7-(trifluoromethyl)-N- (4-(trifluoromethyl)benzyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 471 (M + H)+83 embedded image

N-(2-(3,4- dimethoxyphenyl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 477 (M + H)+84 embedded image

5-phenyl-3-(4- thiomorpholinylcarbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 399 (M + H)+85 embedded image

N-(3-isopropoxypropyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 413 (M + H)+86 embedded image

N-(2-oxo-3-azepanyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 424 (M + H)+87 embedded image

N-(2-furylmethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 393 (M + H)+88 embedded image

N-(3-(2-oxo-1- pyrrolidinyl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 438 (M + H)+89 embedded image

3-((1,1-dioxido-4- thiomorpholinyl)carbonyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 431 (M + H)+90 embedded image

N-(2-adamantyl)-5-(2-naphthyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMp 280-282° C.91 embedded image

N-(1-(2-adamantyl)ethyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a[pyrimidine-3-carboxamideMp 94-95° C.92 embedded image

N-(bicyclo[2.2.1]hept-2-yl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 407 (M + H)+93 embedded image

N-(1-adamantyl)-7-tert-butyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 436 (M + H)+94 embedded image

N-(1-adamantyl)-5,7- bis(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+95 embedded image

1,1′-biphenyl-4-yl(5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)methanolMS (ESI, m/z) 452 (M + H)+96 embedded image

N-(1-adamantyl)-5-(2- (benzyloxy)phenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 554 (M + H)+97 embedded image

N-(1-adamantyl)-5,7-diphenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 456 (M + H)+98 embedded image

N-(1-adamantylmethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 462 (M + H)+99 embedded image

N-(2-(4-tert-butylphenyl)ethyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 474 (M + H)+100 embedded image

N-(1-adamantyl)-5-(3-pyridinyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 448 (M + H)+101 embedded image

N-(1-adamantyl)-5-(2- hydroxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 463 (M + H)+102 embedded image

N-(1,1′-biphenyl-4-ylmethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 480 (M + H)+103 embedded image

N-(1,1′-biphenyl-3-ylmethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 480 (M + H)+104 embedded image

N-(1,1′-biphenyl-2-ylmethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 480 (M + H)+105 embedded image

N-(2-(4-tert-butylphenyl)-2- methylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 502 (M + H)+106 embedded image

N-((3′,5′-dichloro-1,1′-biphenyl- 4-yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 548 (M + H)+107 embedded image

N-((3′,5′-bis(trifluoromethyl)- 1,1′-biphenyl-4-yl)methyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 615 (M + H)+108 embedded image

N-(1-naphthylmethyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 453 (M + H)+109 embedded image

5-phenyl-7-(trifluoromethyl)-N- ((1S,2S,5R)-2,6,6- trimethylbicyclo[3.1.1]hept- 3-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 450 (M + H)+110 embedded image

N-(2-(4-fluorophenyl)-1,1- dimethylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 463 (M + H)+111 embedded image

5-phenyl-N-(2-phenyl-2-(1- pyrrolidinyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 487 (M + H)+112 embedded image

5-phenyl-3-((4-(2- (phenylsulfonyl)ethyl)-1- piperazinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 551 (M + H)+113 embedded image

N-(2-(2-chlorophenoxy)propyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tefrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 482 (M + H)+114 embedded image

3-((2-(2-methylphenyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 457 (M + H)+115 embedded image

3-((3-benzyl-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 457 (M + H)+116 embedded image

N-(1-adamantyl)-7- (hydroxymethyl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 410 (M + H)+117 embedded image

N-(1,1-dimethyl-2-(((5-methyl-2- pyrazinyl)methyl)amino)ethyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+118 embedded image

N-(1,1-dimethyl-2-((2-(1-methyl-2- pyrrolidinyl)ethyl)amino)ethyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 496 (M + H)+119 embedded image

N-(1,1-dimethyl-2-((2-(4- morpholinyl)ethyl)amino)ethyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 498 (M + H)+120 embedded image

N-(1,1-dimethyl-2-((2-(1- piperidinyl)ethyl)amino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 496 (M + H)+121 embedded image

N-(2-(3,4-dihydro-2(1H)- isoquinolinyl)-1,1- dimethylethyl)-5-phenyl-7- (trifluoromethyl)-4-5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 501 (M + H)+122 embedded image

N-(1-1-dimethyl-2-(1,2,3,4- tetrahydro-1- naphthalenylamino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 515 (M + H)+123 embedded image

N-(2-(2,3-dihydro-1H-inden-1- ylamino)-1,1-dimethylethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 501 (M + H)+124 embedded image

N-(1,1-dimethyl-2-((1-methyl-1- phenylethyl)amino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 503 (M + H)+125 embedded image

N-(1,1-dimethyl-2-((2-(2- pyridinyl)ethyl)amino)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-telrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 490 (M + H)+126 embedded image

N-(1-adamantyl)-5-(2- (dimethylamino)phenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+127 embedded image

(5R,7R)-N-(1-adamantyl)-7- benzyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 470 (M + H)+128 embedded image

N-(1-adamantyl)-7-methyl-5,7- diphenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 470 (M + H)+129 embedded image

N-(1,1-dimethyl-2-(((4-methyl-2- pyridinyl)(phenyl)methyl)amino) ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 566 (M + H)+130 embedded image

N-(3-((3,5-di-tert- butylphenyl)amino)-2,2- dimethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 587 (M + H)+131 embedded image

N-(3-(benzhydrylamino)-2,2- dimethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 565 (M + H)+132 embedded image

N-(3-((3-cyanophenyl)amino)- 2,2-dimethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 500 (M + H)+133 embedded image

ethyl 3-((2,2-dimethyl-3-(((5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)propyl) amino)benzoateMS (ESI, m/z) 547 (M + H)+134 embedded image

N-(4-phenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazalo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinyl)benzamideMS (ESI, m/z) 563 (M + H)+135 embedded image

N,4-diphenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinecarboxamideMS (ESI, m/z) 563 (M + H)+136 embedded image

tert-butyl 4-phenyl-1-((5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinylcarbamateMS (ESI, m/z) 559 (M + H)+137 embedded image

methyl 4-phenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinecarboxylateMS (ESI, m/z) 502 (M + H)+138 embedded image

4-phenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinecarboxylic acidMS (ESI, m/z) 487 (M + H)+139 embedded image

4-phenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinamineMS (ESI, m/z) 458 (M + H)+140 embedded image

N-(1-adamantyl)-5-(2,3- difluorophenyl)-7-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 492 (M + H)+141 embedded image

N-(1-adamantyl)-5-(4- chlorophenyl)-7-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 490 (M + H)+142 embedded image

N-(1-adamantyl)-5-phenyl-7-(3- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+143 embedded image

N-(1-adamantyl)-5-phenyl-7-(4- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+144 embedded image

ethyl 4-benzyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinecarboxylateMS (ESI, m/z) 544 (M + H)+145 embedded image

N-phenyl-N(-1,2,3,4-tetrahydro- 1-naphthalenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 443 (M + H)+146 embedded image

N-(2-(4-morpholinyl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 426 (M + H)+147 embedded image

N-((5-methyl-2- pyrazinyl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 419 (M + H)+148 embedded image

N-(2-(1,1′-biphenyl-4-yl)ethyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 494 (M + H)+149 embedded image

4-((4-((3,5- dichlorophenyl)(phenyl)methyl)- 1-piperazinyl)carbonyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 617 (M + H)+150 embedded image

5-phenyl-3-((3-(phenylsulfonyl)- 1-pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 508 (M + H)+151 embedded image

5-phenyl-3-((2-phenyl-1- pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 443 (M + H)+152 embedded image

3-((2-(3,5-dichlorophenyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 512 (M + H)+153 embedded image

5-phenyl-3-((2-(2-phenylethyl)- 1-pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 472 (M + H)+154 embedded image

3-((2-cyclohexyl-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 450 (M + H)+155 embedded image

5-phenyl-3-((2-phenyl-4- thiomorpholinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidlneMS (ESI, m/z) 476 (M + H)+156 embedded image

N-(2-(2-chlorophenyl)-2-(1- pyrrolidinyl)ethyl)-5-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 521 (M + H)+157 embedded image

N-(2-(dimethylamino)-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 460 (M + H)+158 embedded image

N-(2-(2-chlorophenyl)-2- (dimethylamino)ethyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 495 (M + H)+159 embedded image

N-(2-(4-morpholinyl)-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 503 (M + H)+160 embedded image

N-(2-(2-chlorophenyl)-2-(4- morpholinyl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 537 (M + H)+161 embedded image

N-methyl-5-phenyl-N-(2- (phenylsulfonyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 496 (M + H)+162 embedded image

N-(4-(dimethylamino)benzyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 446 (M + H)+163 embedded image

N-(1H-benzimidazol-2- ylmethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 443 (M + H)+164 embedded image

N-((3′,4′-dichloro-1,1′-biphenyl- 4-yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 548 (M + H)+165 embedded image

N-(2-(4-methoxyphenoxy)propyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 477 (M + H)+166 embedded image

5-phenyl-N-(2-(3- pyridinyloxy)propyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 448 (M + H)+167 embedded image

N-(2-phenoxypropyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 447 (M + H)+168 embedded image

3-((2-(2-chlorophenyl)-4- thiomorpholinyl)carbonyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 510 (M + H)+169 embedded image

N-(2-(4-methoxyphenyl)-2-(4- morpholinyl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 533 (M + H)+170 embedded image

3-((4-(2-chlorophenoxy)-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 508 (M + H)+171 embedded image

4-(2-chlorophenyl)-N-phenyl-1- ((5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrralidinecarboxamideMS (ESI, m/z) 597 (M + H)+172 embedded image

N-(2-(4′-fluoro-1,1′-biphenyl-4- yl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 512 (M + H)+173 embedded image

N-(1,1′-biphenyl-4-yl)-1-(5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)ethanoneMS (ESI, m/z) 464 (M + H)+174 embedded image

5-phenyl-3-((3-phenyl-1- pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 443 (M + H)+175 embedded image

N-phenyl-3-((3-(2-phenylethyl)- 1-pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 472 (M + H)+176 embedded image

3-((4-phenoxy-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 473 (M + H)+177 embedded image

3-((3-(4-tert-butylbenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 514 (M + H)+178 embedded image

3-((3-(4-methylbenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 472 (M + H)+179 embedded image

5-phenyl-7-(trifluoromethyl)-3- ((3-(4-(trifluoromethyl)benzyl)- 1-pyrrolidinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 525 (M + H)+180 embedded image

3-((3-(4-methoxybenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 488 (M + H)+181 embedded image

3-((3-(4-fluorobenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1 5- a]pyrimidineMS (ESI, m/z) 475 (M + H)+182 embedded image

N-(1-adamantyl)-7-ethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 408 (M + H)+183 embedded image

N-(1-adamantyl)-5′-phenyl-5′,6′- dihydro-4′H-spiro[cyclopentane- 1,7′-pyrazolo[1,5-a]pyrimidine]- 3′-carboxamidemp 259-261° C.184 embedded image

N-(1-adamantyl)-7,7-diethyl-5- phenyl-4,5,6-7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 213-214° C.185 embedded image

7,7-diethyl-N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 174-175° C.186 embedded image

5-phenyl-3-((3-(2- pyridinylmethyl)-1- pyrrolidinyl)carbonyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 458 (M + H)+187 embedded image

3-((3-(3-chlorobenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 492 (M + H)+188 embedded image

3-((3-(3,4-dichlorobenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 526 (M + H)+189 embedded image

3-((3-(3,5-dichlorobenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 526 (M + H)+190 embedded image

3-((3-(2-chlorobenzyl)-1- pyrrolidinyl)carbonyl)-5-phenyl- 7-(trfluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 492 (M + H)+191 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5′-phenyl-5′,6′-dihydro-4′H- spiro[cyclopentane-1,7′- pyrazolo[1,5-a]pyrimidine]- 3′-carboxamideMp 205-207° C.192 embedded image

N-(1-adamantyl)-5′-phenyl-5′,6′- dihydro-4′H-spiro[cyclohexane- 1,7′-pyrazolo[1,5-a]pyrimidine]- 3′-carboxamideMp 274-275° C.193 embedded image

3-(1,3-dihydro-2H-isoindol-2- ylcarbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 375 (M + H)+194 embedded image

7,7-dimethyl-5-phenyl-N-(1- phenylcyclohexyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 432 (M + H)+195 embedded image

7,7-dimethyl-5-phenyl-N-(1- phenylcyclopentyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 418 (M + H)+196 embedded image

7,7-dimethyl-5-phenyl-N-(1- phenylcyclobutyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 404 (M + H)+197 embedded image

7,7-dimethyl-5-phenyl-N-(1- phenylcyclopropyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 389 (M + H)+198 embedded image

7,7-dimethyl-5-phenyl-N-(1-(4- (trifluoromethyl)phenyl) cyclopentyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 486 (M + H)+199 embedded image

N-(1,1-bis(4- methoxyphenyl)ethyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 514 (M + H)+200 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5′-phenyl-5′,6′-dihydro-4′H- spiro[cyclohexane-1,7′- pyrazolo[1,5-a]pyrimidine]-3′- carboxamidemp 274-275° C.201 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5-phenyl-4,5,5a,6,7,8,9,9a- octahydropyrazolo[1,5- a]quinazoline-3-carboxamidemp 213-214° C.202 embedded image

N-(1-adamantyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 241-243° C.203 embedded image

5-(4-methoxyphenyl)-N-(2-(2- naphthyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 495 (M + H)+204 embedded image

5-(4-chlorophenyl)-N-(2-(2- naphthyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 499 (M + H)+205 embedded image

5-(4-ethylphenyl)-N-(2-(2- naphthyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 493 (M + H)+206 embedded image

5-(2-naphthyl)-N-(2-(2- naphthyl)ethyl)-7- trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 515 (M + H)+207 embedded image

7-methyl-N-(2-(2- naphthyl)ethyl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 411 (M + H)+208 embedded image

N-(1,1-dimethyl-2-(2- naphthyl)ethyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 523 (M + H)+209 embedded image

5-(4-chlorophenyl)-N-(1,1- dimethyl-2-(2-naphthyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 527 (M + H)+210 embedded image

N-(1,1-dimethyl-2-(2- naphthyl)ethyl-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 521 (M + H)+211 embedded image

N-(1,1-dimethyl-2-(2- naphthyl)ethyl)-5-(2-naphthyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 543 (M + H)+212 embedded image

N-(1,1-dimethyl-2-(2- naphthyl)ethyl)-7-methyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+213 embedded image

N-(4-chlorophenyl)-N-(2-(4- methoxyphenyl)-1,1- dimethylethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 507 (M + H)+214 embedded image

N-(4-ethylphenyl)-N-(2-(4- methoxyphenyl)-1,1- dimethylethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 501 (M + H)+215 embedded image

N-(1-adamantyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 479 (M + H)+216 embedded image

N-(1-adamantyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 473 (M + H)+217 embedded image

N-(1-adamantyl)-7-methyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 391 (M + H)+218 embedded image

N-(1-(1-adamantyl)ethyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 503 (M + H)+219 embedded image

N-(1-(1-adamantyl)ethyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 507 (M + H)+220 embedded image

N-(1-(1-adamantyl)ethyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 501 (M + H)+221 embedded image

N-(1-(1-adamantyl)ethyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 419 (M + H)+222 embedded image

N-(2-adamantyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 479 (M + H)+223 embedded image

N-(2-adamantyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 473 (M + H)+224 embedded image

N-(2-adamantyl)-7-methyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 391 (M + H)+225 embedded image

N-(cyclohexylmethyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+226 embedded image

5-(4-chlorophenyl)-N- (cyclohexylmethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 441 (M + H)+227 embedded image

N-(cyclohexylmethyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 435 (M + H)+228 embedded image

N-(cyclohexylmethyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+229 embedded image

N-(cyclohexylmethyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 353 (M + H)+230 embedded image

N-(4-(4-fluorophenoxy)benzyl)- 5-(4-methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 541 (M + H)+231 embedded image

5-(4-chlorophenyl)-N-(4-(4- fluorophenoxy)benzyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 545 (M + H)+232 embedded image

5-(4-ethylphenyl)-N-(4-(4- fluorophenoxy)benzyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 539 (M + H)+233 embedded image

N-(4-(4-fluorophenoxy)benzyl)- 5-(2-naphthyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 561 (M + H)+234 embedded image

N-(4-(4-fluorophenoxy)benzyl)- 7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+235 embedded image

N-(4-(benzyloxy)benzyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 537 (M + H)+236 embedded image

N-(4-(benzyloxy)benzyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 537 (M + H)+237 embedded image

N-(4-(benzyloxy)benzyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 535 (M + H)+238 embedded image

N-(4-(benzyloxy)benzyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 557 (M + H)+239 embedded image

N-(4-(benzyloxy)benzyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 453 (M + H)+240 embedded image

N-benzhydryl-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 507 (M + H)+241 embedded image

N-benzhydryl-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 511 (M + H)+242 embedded image

N-benzhydryl-5-(4-ethylphenyl)- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 505 (M + H)+243 embedded image

N-benzhydryl-5-(2-naphthyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 527 (M + H)+244 embedded image

N-benzhydryl-7-methyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 423 (M + H)+245 embedded image

N-(2,2-diphenylethyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- -a]pyrimidrne-3-carboxamideMS (ESI, m/z) 521 (M + H)+246 embedded image

N-(4-chlorophenyl)-N-(2,2- diphenylethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 525 (M + H)+247 embedded image

N-(2,2-diphenylethyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 519 (M + H)+248 embedded image

N-(2,2-diphenylethyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 541 (M + H)+249 embedded image

N-(2,2-diphenylethyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+250 embedded image

5-(4-methoxyphenyl)-N-(2-(4- morpholinyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 454 (M + H)+251 embedded image

5-(4-chlorophenyl)-N-(2-(4- morpholinyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 458 (M + H)+252 embedded image

5-(4-ethylphenyl)-N-(2-(4- morpholinyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 452 (M + H)+253 embedded image

N-(2-(4-morpholinyl)ethyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 474 (M + H)+254 embedded image

N-(1-benzyl-4-piperidinyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 514 (M + H)+255 embedded image

N-(1-benzyl-4-piperidinyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 518 (M + H)+256 embedded image

N-(1-benzyl-4-piperidinyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 512 (M + H)+257 embedded image

N-(1-benzyl-4-piperidinyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 534 (M + H)+258 embedded image

N-(1-benzyl-4-piperidinyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 430 (M + H)+259 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 592 (M + H)+260 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-5-(4- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 596 (M + H)+261 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 590 (M + H)+262 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 611 (M + H)+263 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 507 (M + H)+264 embedded image

N-(4-cyclohexylphenyl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 499 (M + H)+265 embedded image

5-(4-chlorophenyl)-N-(4- cyclohexylphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 503 (M + H)+266 embedded image

N-(4-cyclohexylphenyl)-5-(4- ethylphenyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 497 (M + H)+267 embedded image

N-(4-cyclohexylphenyl)-5-(2- naphthyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 415 (M + H)+268 embedded image

N-(4-cyclohexylphenyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 415 (M + H)+269 embedded image

N-(9H-fluoren-9-yl)-5-(4- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideIR(KBr) 3290, 3067, 2934, 2838, 1622, 1593, 1539, 15161 cm⁻¹270 embedded image

N-(1-adamantyl)-5-(2-furyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 230-231° C.271 embedded image

N-(4-(4-fluorophenoxy)benzyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 169-172° C.272 embedded image

N-(1,1-dimethyl-2-(2- naphthyl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 187-188° C.273 embedded image

3-((4-(benzhydryloxy)-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineIR(KBr) 2934, 2867, 1605, 1532 cm⁻¹274 embedded image

3-((4-benzhydryl-1- piperazinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 181-182° C.275 embedded image

2-(4-chlorophenyl)-5-((5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4,5,6,7-tetrahydro-2H- pyrazolo[4,3-c]pyridinemp 183-184° C.276 embedded image

2-(4-methylphenyl)-5-((5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4,5,6,7-tetrahydro-2H- pyrazolo[4,3-c]pyridinemp 167-168° C.277 embedded image

N-(9H-fluoren-9-yl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideIR(KBr) 3297, 3097, 3042, 1624, 1595, 1534 cm⁻¹278 embedded image

5-phenyl-N-(4-(1,2,3-thiadiazol- 4-yl)benzyl)-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 205-206° C.279 embedded image

N-(1-adamantyl)-5-(2- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMp 238-239° C.280 embedded image

N-(1-adamantyl)-5-(3- methoxyphenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMp 211-212° C.281 embedded image

N-(1-adamantyl)-5-(2- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMp 256-257° C.282 embedded image

N-(1-adamantyl)-5-(3- chlorophenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMp 246-247° C.283 embedded image

N-(1-cyanopropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideless polar mp 180-181° C.284 embedded image

N-(1-cyanopropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidepolar mp 201-202° C.285 embedded image

N-(2-(1-benzofuran-2-yl)-2- oxoethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 244-245° C.286 embedded image

N-(2-(1-naphthyl)-2-oxoethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 141-142° C.287 embedded image

N-(2-hydroxy-2-(1- naphthyl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 490 (M + H)+288 embedded image

N-(2-oxo-2-(2-thienyl)ethyl)-5- phenyl-7-(trilluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 2191-220° C.289 embedded image

N-(2-(2-chlorophenyl)-2- oxoethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 154-155° C.290 embedded image

N-(1-methyl-2-oxo-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 271-272° C.291 embedded image

N-(1-methyl-2-oxo-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 178-179° C.292 embedded image

N-(2-(2,3-dihydro-1H-inden-2- yl)-1,1-dimethylethyli-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 221-222° C.293 embedded image

5-phenyl-7-(trifluoromethyl)-N- (2-(trifluoromethyl)benzyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 469 (M + H)+294 embedded image

N-(3,5- bis(trifluoromethyl)benzyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 537 (M + H)+295 embedded image

N-(4-tert-butylbenzyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+296 embedded image

5-phenyl-N-(2- (trifluoromethoxy)benzyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 485 (M + H)+297 embedded image

N-((4- chlorophenyl)(phenyl)methyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 511 (M + H)+298 embedded image

N-(bis(4- methoxyphenyl)methyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 537 (M + H)+299 embedded image

3-((3,5-dimethyl-1- piperidinyl)carbonyl)-5-Phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 407 (M + H)+300 embedded image

4-phenyl-1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinolMS (ESI, m/z) 471 (M + H)+301 embedded image

3-((4-methyl-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 393 (M + H)+302 embedded image

3-((4-benzyl-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 469 (M + H)+303 embedded image

2-((5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl) decahydroisoquinolineMS (ESI, m/z) 433 (M + H)+304 embedded image

(4-fluorophenyl)(1-((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinyl)methanoneMS (ESI, m/z) 501 (M + H)+305 embedded image

(4-chlorophenyl)(1-((5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinyl)methanoneMS (ESI, m/z) 517 (M + H)+306 embedded image

N,N-dibenzyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+307 embedded image

3-((4-cyclohexyl-1- piperazinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 462 (M + H)+308 embedded image

N-(1-methyl-1-(4- (trifluoromethyl)phenyl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 497 (M + H)+309 embedded image

N-(1-methyl-1-(3- (trifluoromethyl)phenyl)ethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 497 (M + H)+310 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 525 (M + H)+311 embedded image

N-(1-methyl-1-phenylethyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 429 (M + H)+312 embedded image

3-((4-(bis(4- methylphenyl)methoxy)-1- piperidinyl)carbonyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 589 (M + H)+313 embedded image

3-((4-((4-tert- butylphenyl)(phenyl)methoxy)- 1-piperidinyl)carbonyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 617 (M + H)+314 embedded image

N-((2′-chloro-1,1′-biphenyl-4- yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 511 (M + H)+315 embedded image

N-((4′-methyl-1,1′-biphenyl-4- yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+316 embedded image

5-phenyl-7-(trifluoromethyl)-N- ((4′-(trifluoromethyl)-1,1′- biphenyl-4-yl)methyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 545 (M + H)+317 embedded image

N-(2,2-diphenylethyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+318 embedded image

N-(2-(4-methoxyphenyl)-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 521 (M + H)+319 embedded image

N-(2-(4-chlorophenyl)-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 525 (M + H)+320 embedded image

N-(2-(4-methylphenyl)-2- phenylethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 505 (M + H)+321 embedded image

5-phenyl-N-(2-phenyl-2-(4- (trifluoromethyl)phenyl)ethyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 559 (M + H)+322 embedded image

N-((4′-fluoro-1,1′-biphenyl-2- yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 495 (M + H)+323 embedded image

N-((4′-chloro-1,1′-biphenyl-3- yl)methyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 511 (M + H)+324 embedded image

N-(3-phenoxybenzyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 493 (M + H)+325 embedded image

N-(3-(4-chlorophenoxy)benzyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 527 (M + H)+326 embedded image

N-(4-phenoxybenzyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 493 (M + H)+327 embedded image

N-(4-(4-chlorophenoxy)benzyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 527 (M + H)+328 embedded image

N-(4-(4-methylphenoxy)benzyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 507 (M + H)+329 embedded image

N-(4-(3,5- bis(trifluoromethyl)phenoxy) benzyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 629 (M + H)+330 embedded image

7-methyl-5-phenyl-N-(2- (trifluoromethyl)benzyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 415 (M + H)+331 embedded image

N-(3,5- bis(trifluoromethyl)benzyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 483 (M + H)+332 embedded image

N-(4-tert-butylbenzyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 403 (M + H)+333 embedded image

7-methyl-5-phenyl-N-(2- (trifluoromethoxy)benzyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 431 (M + H)+334 embedded image

N-((4- chlorophenyl)(phenyl)methyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+335 embedded image

N-(bis(4- methoxyphenyl)methyl)-7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 483 (M + H)+336 embedded image

3-((3,5-dimethyl-1- piperidinyl)carbonyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 353 (M + H)+337 embedded image

1-((7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- phenyl-4-piperidinolMS (ESI, m/z) 417 (M + H)+338 embedded image

7-methyl-3-((4-methyl-1- piperidinyl)carbonyl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a[pyrimidineMS (ESI, m/z) 339 (M + H)+339 embedded image

3-((4-benzyl-1- piperidinyl)carbonyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 415 (M + H)+340 embedded image

2-((7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidine-3- yl)carbonyl) decahydroisoquinolineMS (ESI, m/z) 379 (M + H)+341 embedded image

(4-fluorophenyl)(1-((7- methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinyl)methanoneMS (ESI, m/z) 447 (M + H)+342 embedded image

(4-chlorophenyl)(1-((7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinyl)methanoneMS (ESI, m/z) 463 (M + H)+343 embedded image

N,N-dibenzyl-7-methyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+344 embedded image

3-((4-cyclohexyl-1- piperazinyl)carbonyl)-7-methyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 408 (M + H)+345 embedded image

7-methyl-N-(1-methyl-1-(4- (trifluoromethyl)phenyl)ethyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 443 (M + H)+346 embedded image

7-methyl-N-(1-methyl-1-(3- (trifluoromethyl)phenyl)ethyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 443 (M + H)+347 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 471 (M + H)+348 embedded image

N-(1-(4-tert-butylphenyl)-1- methylethyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 431 (M + H)+349 embedded image

7-methyl-N-(1-methyl-1- phenylethyl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 375 (M + H)+350 embedded image

3-((4-(bis(4- methylphenyl)methoxy)-1- piperidinyl)carbonyl)-7-methyl- 5-pheny-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 535 (M + H)+351 embedded image

N-((2′-chloro-1,1′-biphenyl-4- yl)methyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+352 embedded image

N-((3′,5′-dichloro-1,1′-biphenyl- 4-yl)methyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 492 (M + H)+353 embedded image

7-methyl-N-((4′-methyl-1,1′- biphenyl-4-yl)methyl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+354 embedded image

7-methyl-5-phenyl-N-((4′- (trifluoromethyl)-1,1′-biphenyl- 4-yl)methyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 491 (M + H)+355 embedded image

N-(2-(4-methoxyphenyl)-2- phenylethyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 467 (M + H)+356 embedded image

N-(2-(4-chlorophenyl)-2- phenylethyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 471 (M + H)+357 embedded image

7-methyl-N-(2-(4- methylpheny-2-phenylethyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 451 (M + H)+358 embedded image

7-methyl-5-phenyl-N-(2-phenyl-2-(4- (trifluoromethyl)phenyl)ethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 505 (M + H)+359 embedded image

N-((4′-fluoro-1,1-biphenyl-2- yl)methyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 441 (M + H)+360 embedded image

N-((4′-chloro-1,1′-biphenyl-3- yl)methyl)-7-methyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+361 embedded image

7-methyl-N-(3-phenoxybenzyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+362 embedded image

N-(3-(4-chlorophenoxy)benzyl)- 7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 473 (M + H)+363 embedded image

7-methyl-N-(4-phenoxybenzyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+364 embedded image

N-(4-(4-chlorophenoxv)benzyl)- 7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 473 (M + H)+365 embedded image

7-methyl-N-(4-(4- methylphenoxy)benzyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 453 (M + H)+366 embedded image

N-(4-(3,5- bis(trifluoromethyl)phenoxy) benzyl)-7-methyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 575 (M + H)+367 embedded image

methyl 1-(((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) cyclohexane carboxylatemp 213-214° C.368 embedded image

N-(1-methyl-1-(1- naphthyl)ethyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 221-222° C.369 embedded image

1-(((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)cyclohexane carboxylic acidmp 236-237° C.370 embedded image

N-(1-(4-morpholinylcarbonyl) cyclohexyl)- 5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 290-291° C.371 embedded image

N-(1-anilinocarbonyl)cyclohexyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 262-263° C.372 embedded image

1-(((5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)oxy)- 1H-1,2,3-benzotriazolemp 216-217° C.373 embedded image

N,N-dicyclohexyl-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 243-244° C.374 embedded image

N-(1-adamantyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 235-236° C.375 embedded image

N-(1-ethyl-1-(2′- (trifluoromethyl)-1,1′-biphenyl- 4-yl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+376 embedded image

N-(1-ethyl-1-(3′- (trifluoromethyl)-1,1′-biphenyl- 4-yl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+377 embedded image

N-(1-ethyl-1-(4′- (trifluoromethyl)-1,1′-biphenyl- 4-yl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+378 embedded image

N-(1-(3′-cyano-1,1′-biphenyl-4- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-caiboxamideMS (ESI, m/z) 558 (M + H)+379 embedded image

N-(1-(4′-cyano-1,1′-biphenyl-4- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 558 (M + H)+380 embedded image

N-(1-ethyl-1-(4′-fluoro-1,1′- biphenyl-4-yl)propyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 551 (M + H)+381 embedded image

N-(1-(4′-chloro-1,1′-biphenyl-4- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 567 (M + H)+382 embedded image

N-(1-ethyl-1-(2′-methyl-1,1′- biphenyl-4-yl)propyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 547 (M + H)+383 embedded image

N-(1-ethyl-1-(4-(6-methoxy-3- pyridinyl)phenyl)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 564 (M + H)+384 embedded image

N-(1-ethyl-1-(4-(2- thienyl)phenyl)propyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 539 (M + H)+385 embedded image

N-(1-(4-butylphenyl)-1- ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 513 (M + H)+386 embedded image

N-(1-ethyl-1-(2′- (trifluoromethyl)-1,1′-biphenyl- 3-yl)propyl)-5-phenyl)-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+387 embedded image

N-(1-ethyl-1-(3′- (trifluoromethyl)-1,1′-biphenyl- 3-yl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+388 embedded image

N-(1-ethyl-1-(4′- (trifluoromethyl)-1,1′-biphenyl- 3-yl)propyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 601 (M + H)+389 embedded image

N-(1-(3′-cyano-1,1′-biphenyl-3- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 558 (M + H)+390 embedded image

N-(1-(4′-cyano-1,1′-biphenyl-3- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 558 (M + H)+391 embedded image

N-(1-ethyl-1-(4′-fluoro-1,1′- biphenyl-3-yl)propyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 551 (M + H)+392 embedded image

N-(1-(4′-chloro-1,1′-biphenyl-3- yl)-1-ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 567 (M + H)+393 embedded image

N-(1-ethyl-1-(3-(6-methoxy-3- pyridinyl)phenyl)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 564 (M + H)+394 embedded image

N-(1-ethyl-1-(3-(2- thienyl)phenyl)propyl)-5-phenyl- 7-(trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 539 (M + H)+395 embedded image

N-(1-(3-butylphenyl)-1- ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 513 (M + H)+396 embedded image

N-(1-ethyl-1-phenylpropyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 165-166° C.397 embedded image

N-(1-(4-bromophenyl)-1- ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 180-181° C.398 embedded image

N-(1-(3-bromophenyl)-1- ethylpropyl)-5-phenyl-7- (trifluoromethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 167-168° C.399 embedded image

N-(1-(2-methylphenyl)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 225-226° C.400 embedded image

N-(1-(2-fluorophenyl)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 204-205° C.401 embedded image

N-(1-(2-bromophenyl)propyl)-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 236-237° C.402 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 193-194° C.403 embedded image

5-phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 277-278° C.404 embedded image

1-propyl-1-(4- (trifluoromethyl)phenyl)butyl 5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS (ESI, m/z) 554 (M + H)+405 embedded image

N-(bis(4-chlorophenyl)methyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 180-181° C.406 embedded image

7,7-dimethyl-5-phenyl-N-(1- propyl-1-(4- (trifluoromethyl)phenyl)butyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 175-1764° C.407 embedded image

N-(bis(4- methoxyphenyl)methyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 184-185° C.408 embedded image

N,N-dibenzyl-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 206-207° C.409 embedded image

7,7-dimethyl-5-phenyl-N,N- bis(4-(trifluoromethyl)benzyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 164-165° C.410 embedded image

N-(4-tert-butylbenzyl)-7,7- dimethyl-5-phenyl-N-(4- (trifluoromethyl)benzyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideIR(KBr) 2965, 1605, 1568, 1528, 1412, 1325, 1246, 1165, 1127 cm⁻¹411 embedded image

N-(1-butyl-1-(4- (trifluoromethyl)phenyl)pentyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 113-114° C.412 embedded image

N-(dicyclohexyl(4- (trifluoromethyl)phenyl)methyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimid:ne-3-carboxamidemp 146-147° C.413 embedded image

N-(1-(4-bromophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 129-130° C.414 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 125-126° C.415 embedded image

N-(1-ethyl-1-(2- fluorophenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 435 (M + H)+416 embedded image

N-(1-(2-bromophenyl)propyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 200-201° C.417 embedded image

N-(1-(4-tert-butylphenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 196-197° C.418 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 155-156° C.419 embedded image

N-(1-ethyl-1-phenylpropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxatnidemp 139-140° C.420 embedded image

N-(1-ethyl-1-(2′-methyl-1,1′- biphenyl-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 507 (M + H)+421 embedded image

N-(1-ethyl-1′-(4′- (trifluoromethyl)-1,1′-biphenyl- 4-yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 561 (M + H)+422 embedded image

N-(1-ethyl-1-(4-(2- thienyl)phenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 499 (M + H)+423 embedded image

N-(1-ethyl-1-(4-(3- thienyl)phenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 499 (M + H)+424 embedded image

N-(1-(4′-tert-butyl-1,1′-biphenyl- 4-yl)-1-ethylpropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 550 (M + H)+425 embedded image

N-(1-(1,1′-biphenyl-4-yl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 493 (M + H)+426 embedded image

N-(1-(4′-chloro-1,1′-biphenyl-4- yl)-1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 527 (M + H)+427 embedded image

7,7-dimethyl-N-(1-methyl-1-(4- (trifluoromethyl)phenyl)ethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 182-183° C.428 embedded image

N-(1-isopropyl-2-methyl-1-(4- (trifluoromethyl)phenyl)propyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 513 (M + H)+429 embedded image

N-(3-hydroxy-1-adamantyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 421 (M + H)+430 embedded image

2-((7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)decahydro- isoquinolineMS (ESI, m/z) 430 (M + H)+431 embedded image

N-(1-ethylcyclohexyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 166-167° C.432 embedded image

N-(1-cyclohexyl-1-ethylpropyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 130-131° C.433 embedded image

N-(dicyclohexylmethyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 187-188° C.434 embedded image

N-(1-ethyl-1-(3- (trifluoromethyl)phenyl)propyl)- 7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 166-167° C.459 embedded image

N-(2-anilinoethyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+460 embedded image

5-cyclohexyl-7,7-dimethyl-N- (2-(4-pyridinyl)ethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 383 (M + H)+461 embedded image

5-cyclohexyl-N-(3-(1H- imidazol-1-yl)propyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 385 (M + H)+462 embedded image

5-cyclohexyl-7,7-dimethyl-N- (3-(4-morpholinyl)propyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 404 (M + H)+463 embedded image

5-cyclohexyl-7,7-dimethyl-N- (2-(1-pyrrolidinyl)ethyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 374 (M + H)+464 embedded image

N-(1-benzyl-3-pyrrolidinyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+465 embedded image

5-cyclohexyl-7,7-dimethyl-N- (3-pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 368 (M + H)+466 embedded image

5-cyclohexyl-N-(2- (dimethylamino)ethyl)-N,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 362 (M + H)+467 embedded image

N-(1-benzyl-3-pyrrolidinyl)-5- cyclohexyl-N,7,7-trimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 451 (M + H)+468 embedded image

5-cyclohexyl-N-ethyl-7,7- dimethyl-N-(4- pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+469 embedded image

5-cyclohexyl-3-((4-ethyl-1- piperazinyl)carbonyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 374 (M + H)+470 embedded image

3-((4-benzyl-1- piperazinyl)carbonyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 437 (M + H)+471 embedded image

5-cyclohexyl-7,7-dimethyl-3- ((4-(2-pyridinyl)-1- piperazinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 424 (M + H)+472 embedded image

3-((4-benzhydryl-1- piperazinyl)carbonyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 513 (M + H)+473 embedded image

5-cyclohexyl-7,7-dimethyl-3- ((4-phenyl-1- piperazinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 423 (M + H)+474 embedded image

1′-((5-cyclohexyl-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,4′-bipiperidineMS (ESI, m/z) 428 (M + H)+475 embedded image

5-cyclohexyl-N,7,7-trimethyl- N-(1-methyl-3-pyrrolidinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 375 (M + H)+476 embedded image

5-cyclohexyl-7,7-dimethyl-3- ((4-methyl-1,4-diazepan-1- yl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 374 (M + H)+477 embedded image

N-benzyl-5-cyclohexyl-N-(2- (dimethylamino)ethyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+478 embedded image

N-(2-(dimethylamino)ethyl)- 7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 363 (M + H)+479 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(2-(1- piperidinyl)ethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 403 (M + H)+480 embedded image

7,7-dimethyl-N-(3-(4-methyl- 1-piperazinyl)propyl)-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 432 (M + H)+481 embedded image

7,7-dimethyl-N-(3- (methyl(phenyl)amino)propyl)- 5-(5-methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 440 (M + H)+482 embedded image

N-(1-benzyl-4-piperidinyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 465 (M + H)+483 embedded image

N-(2-anilinoethyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 411 (M + H)+484 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(2-(4- pyridinyl)ethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+485 embedded image

N-(3-(1H-imidazol-1- yl)propyl)-7,7-dimethyl-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 400 (M + H)+486 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(3-(4- morpholinyl)propyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 419 (M + H)+487 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(2-(1- pyrrolidinyl)ethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 389 (M + H)+488 embedded image

N-(1-benzyl-3-pyrrolidinyl)- 7,7-dimethy-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 451 (M + H)+489 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(3- pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 383 (M + H)+490 embedded image

N-(2-(dimethylamino)ethyl)- N,7,7-trimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 377 (M + H)+491 embedded image

N-(1-benzyl-3-pyrrolidinyl)- N,7,7-trimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 465 (M + H)+492 embedded image

N-ethyl-7,7-dimethyl-5-(5- methyl-1,3-thiazol-2-yl)-N-(4- pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 411 (M + H)+493 embedded image

3-((4-ethyl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 389 (M + H)+494 embedded image

3-((4-benzyl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 451 (M + H)+495 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-3-((4-(2- pyridinyl)-1- piperazinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 439 (M + H)+496 embedded image

3-((4-benzhydryl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 527 (M + H)+497 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-3-((4-phenyl-1- piperazinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 437 (M + H)+498 embedded image

1′-((7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,4′-bipiperidineMS (ESI, m/z) 443 (M + H)+499 embedded image

N,7,7-trimethyl-N-(1-methyl-3- pyrrolidinyl)-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 389 (M + H)+500 embedded image

7,7-dimethyl-3-((4-methyl-1,4- diazepan-1-yl)carbonyl)-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a-]pyrimidineMS (ESI, m/z) 389 (M + H)+501 embedded image

N-benzyl-N-(2- (dimethylamino)ethyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carbaxamideMS (ESI, m/z) 453 (M + H)+502 embedded image

N-cyclopropyl-7,7-dimethyl-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 312 (M + H)+503 embedded image

N-benzyl-7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 362 (M + H)+504 embedded image

7,7-dimethyl-N-(2- phenylethyl)-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 376 (M + H)+505 embedded image

N-benzhydryl-7,7-dimethyl-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 439 (M + H)+506 embedded image

N-(2-methoxyethyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 330 (M + H)+507 embedded image

N-(2-(1H-indol-3-yl)ethyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 416 (M + H)+508 embedded image

N-(1-ethylpropyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 342 (M + H)+509 embedded image

N-cyclohexyl-7,7-dimethyl-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 354 (M + H)+510 embedded image

7,7-dimethyl-5-(2-pyridinyl)-N- (4-(trifluoromethyl)benzyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 430 (M + H)+511 embedded image

N-(2-(3,4- dimethoxyphenyl)ethyl)-7,7- dimethyl-5-(2-pylidinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 437 (M + H)+512 embedded image

N-2,3-dihydro-1H-inden-2-yl- 7,7-dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 388 (M + H)+513 embedded image

7,7-dimethyl-N-(3-(2-oxo-1- pyrrolidinyl)propyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+514 embedded image

7,7-dimethyl-N,N-dipropyl-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 356 (M + H)+515 embedded image

N,7,7-trimethyl-N-(1- naphthylmethyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 427 (M + H)+516 embedded image

7,7-dimethyl-3-(1- piperidinylcarbonyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 340 (M + H)+517 embedded image

2-((7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,2,3,4-tetrahydroisoquinolineMS (ESI, m/z) 388 (M + H)+518 embedded image

1-((7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinecarboxamideMS (ESI, m/z) 383 (M + H)+519 embedded image

3-((4-benzyl-1- piperidinyl)carbonyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 431 (M + H)+520 embedded image

N-(1-((7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinyl)acetamideMS (ESI, m/z) 383 (M + H)+521 embedded image

N-benzyl-N,7,7-trimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 376 (M + H)+522 embedded image

7,7-dimethyl-3-(4- morpholinylcarbonyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 342 (M + H)+523 embedded image

1-((7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- phenyl-4-pipendinolMS (ESI, m/z) 433 (M + H)+524 embedded image

3-(1-azepanylcarbonyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 354 (M + H)+525 embedded image

3-((4-(3-methoxyphenyl)-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 448 (M + H)+526 embedded image

N-cyclohexyl-N-cyclopropyl- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 317 (M + H)+527 embedded image

N-benzyl-5-cyclohexyl-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 368 (M + H)+528 embedded image

5-cyclohexyl-7,7-dimethyl-N- (2-phenylethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 382 (M + H)+529 embedded image

N-benzhydryl-5-cyclohexyl- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 444 (M + H)+530 embedded image

5-cyclohexyl-N-(2- methoxyethyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 335 (M + H)+531 embedded image

5-cyclohexyl-N-(2-(1H-indol- 3-yl)ethyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 421 (M + H)+532 embedded image

N-cyclohexyl-N-(1- ethylpropyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 348 (M + H)+533 embedded image

N,5-dicyclohexyl-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 360 (M + H)+534 embedded image

5-cyclohexyl-7,7-dimethyl-N- (4-(trifluoromethyl)benzyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a-]pyrimidine-3-carboxamideMS (ESI, m/z) 436 (M + H)+535 embedded image

5-cyclohexyl-N-(2-(3,4- dimethoxyphenyl)ethyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 442 (M + H)+536 embedded image

5-cyclohexyl-N-2,3-dihydro- 1H-inden-2-yl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 394 (M + H)+537 embedded image

5-cyclohexyl-7,7-dimethyl-N- (3-(2-oxo-1- pyrrolidinyl)propyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 403 (M + H)+538 embedded image

N-cyclohexyl-7,7-dimethyl- N,N-dipropyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 362 (M + H)+539 embedded image

5-cyclohexyl-N,7,7-trimethyl- N-(1-naphthylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 432 (M + H)+540 embedded image

5-cyclohexyl-7,7-dimethyl-3- (1-piperidinylcarbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 345 (M + H)+541 embedded image

2-((5-cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,2,3,4-tetrahydroisoquinolineMS (ESI, m/z) 394 (M + H)+542 embedded image

1-((5-cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinecarboxamideMS (ESI, m/z) 389 (M + H)+543 embedded image

3-((4-benzyl-1- piperidiny-carbonyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 436 (M + H)+544 embedded image

N-(1-((5-cyclohexyl-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinyl)acetamideMS (ESI, m/z) 389 (M + H)+545 embedded image

N-benzyl-5-cyclohexyl-N,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 382 (M + H)+546 embedded image

5-cyclohexyl-7,7-dimethyl-3- (4-morpholinylcarbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidineMS (ESI, m/z) 347 (M + H)+547 embedded image

1-((5-cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- phenyl-4-pipendinolMS (ESI, m/z) 438 (M + H)+548 embedded image

3-(1-azepanylcarbonyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 360 (M + H)+549 embedded image

5-cyclohexyl-3-((4-(3- methoxyphenyl)-1- piperazinyl)carbonyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 453 (M + H)+550 embedded image

N-cyclopropyl-7,7-dimethyl-5- (5-methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 332 (M + H)+551 embedded image

N-benzyl-7,7-dimethyl-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 382 (M + H)+552 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(2- phenylethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 397 (M + H)+553 embedded image

N-benzhydryl-7,7-dimethyl-5- (5-methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 459 (M + H)+554 embedded image

N-(2-methoxyethyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 350 (M + H)+555 embedded image

N-(2-(1H-indol-3-yl)ethyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 436 (M + H)+556 embedded image

N-(1-ethylpropyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 363 (M + H)+557 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(4- (trifluoromethyl)benzyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 450 (M + H)+558 embedded image

N-(2-(3,4- dimethoxyphenyl)ethyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 457 (M + H)+559 embedded image

N-2,3-dihydro-1H-inden-2-yl- 7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 409 (M + H)+560 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N-(3-(2-oxo-1- pyrrolidinyl)propyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 418 (M + H)+561 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-N,N-dipropyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 377 (M + H)+562 embedded image

N,7,7-trimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-N-(1- naphthylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 447 (M + H)+563 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-3-(1- piperidinylcarbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 360 (M + H)+564 embedded image

2-((7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,2,3,4-tetrahydroisoquinolineMS (ESI, m/z) 409 (M + H)+565 embedded image

1-((7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinecarboxamideMS (ESI, m/z) 404 (M + H)+566 embedded image

3-((4-benzyl-1- piperidinyl)carbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 451 (M + H)+567 embedded image

N-(1-((7,7-dimethyl-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- pyrrolidinyl)acetamideMS (ESI, m/z) 404 (M + H)+568 embedded image

N-benzyl-N,7,7-trimethyl-5-(5- methyl-1,3-thiazol-2-yl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamadeMS (ESI, m/z) 397 (M + H)+569 embedded image

7,7-dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-3-(4- morpholinylcarbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 362 (M + H)+570 embedded image

1-((7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- phenyl-4-piperidinolMS (ESI, m/z) 453 (M + H)+571 embedded image

3-(1-azepanylcarbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 375 (M + H)+572 embedded image

3-((4-(3-methoxyphenyl)-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 468 (M + H)+573 embedded image

N-(1-(6-chloro-3-pyridinyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 223-224° C.574 embedded image

N-(1-(4-cyanophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 237-238° C.575 embedded image

N-(4-ethyltetrahydro-2H- thiopyran-4-yl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 97-98° C.576 embedded image

N-((2,2-diphenyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 477 (M + H)+577 embedded image

7,7-dimethyl-3-((3-(4- methylbenzyl)-1- pyrrolidinyl)carbonyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 429 (M + H)+578 embedded image

3-((3-(2-chlorobenzyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 449 (M + H)+579 embedded image

N-(2,2-bis(4- methoxyphenyl)ethyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 511 (M + H)+580 embedded image

N-(2,2-bis(4- methoxyphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 525 (M + H)+581 embedded image

N-1-adamantyl-5-(2- methoxyphenyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 280-282° C.582 embedded image

N-(4-ethyltetrahydro-2H- pyran-4-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 104-105° C.583 embedded image

N-(1-ethyl-1-(4-(3- pyridinyl)phenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamide2HCl salt mp 168-169° C.584 embedded image

N-(1-ethyl-1-(4-(2- furyl)phenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 167-168° C.585 embedded image

N-(1-ethyl-1-(4-(3- furyl)phenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 185-186° C.586 embedded image

7,7-dimethyl-N-(1- methylcyclohexyl)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 170-171° C.587 embedded image

N-(1-ethynylcyclohexyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 201-202° C.588 embedded image

N-(1-ethylcyclopentyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 140-142° C.589 embedded image

N-(1-(3,4-difluorophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 171-172° C.590 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)propyl)- 5-(2-methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 211-213° C.591 embedded image

1-propyl-1-(4- (trifluoromethyl)phenyl)butyl 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS (ESI, m/z) 514 (M + H)+592 embedded image

N-(1,1-bis(4- methoxyphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS (ESI, m/z) 525 (M + H)+593 embedded image

3-((2-isopropyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 367 (M + H)+594 embedded image

3-((2-isopropyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 367 (M + H)+595 embedded image

3-((2-isobutyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 381 (M + H)+596 embedded image

3-((2-cyclohexyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 407 (M + H)+597 embedded image

ethyl 4-benzyl-1-((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinecarboxylateMS (ESI, m/z) 407 (M + H)+598 embedded image

ethyl 3-benzyl-1-((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-3- piperidinecarboxylateMS (ESI, m/z) 501 (M + H)+599 embedded image

7,7-dimethyl-5-phenyl-3-((3- phenyl-1- pyrrolidinyl)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 501 (M + H)+600 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-5-(2- methoxyphenyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 206.2-206.3° C.601 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 167-169° C.602 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 163.5-163.6° C.603 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-5-(6- methoxy-2-pyridinyl)-7,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 156-157° C.604 embedded image

3-(((2S)-2- (methoxymethyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 369 (M + H)+605 embedded image

3-(((2R)-2- (methoxymethyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 369 (M + H)+606 embedded image

7,7-dimethyl-N-(2-methyl-1- (4-methylphenyl)propyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamideMS (ESI, m/z) 417 (M + H)+607 embedded image

3-((2,5-dimethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 353 (M + H)+608 embedded image

3-((4,4-dimethyl-1,3- oxazolidin-3-yl)carbonyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 355 (M + H)+609 embedded image

3-((4-benzyl-1- piperidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS (ESI, m/z) 429 (M + H)+610 embedded image

4-benzyl-1-((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinecarboxylic acidMS (ESI, m/z) 473 (M + H)+611 embedded image

3-benzyl-1-((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-piperidinecarboxylic acidMS (ESI, m/z) 473 (M + H)+612 embedded image

N-(1-ethyl-4- methylcyclohexyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 160-161° C.613 embedded image

N-(1-(3-bromophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 195-196° C.614 embedded image

N-(1-(3-chlorophenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 195-196° C.615 embedded image

N-(1-ethyl-1-(3- fluorophenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 180-181° C.616 embedded image

N-(1,1-diethylpropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 93-94° C.617 embedded image

N-(4-ethyl-1,1- dioxidotetrahydro-2H- thiopyran-4-yl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamidemp 155-156° C.618 embedded image

N-(1-ethyl-1-methylpropyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 88-89° C.619 embedded image

7,7-dimethyl-5-phenyl-N-(1- propylcyclohexyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 152-153° C.620 embedded image

N-(1,1-diethyl-2- methylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 155-156° C.621 embedded image

N-(1-isopropyl-2- methylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 168-169° C.622 embedded image

N-(1-ethylcycloheptyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 129-130° C.623 embedded image

N-(4-ethyl-1- oxidotetrahydro-2H- thiopyran-4-yl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 172-173° C.624 embedded image

methyl 1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) cyclohexanecarboxylatemp 184-185° C.625 embedded image

1-(((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) cyclohexanecarboxylic acidmp 215-216° C.626 embedded image

N-(1-(aminocarbonyl)cyclohexyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 140-141° C.627 embedded image

N-(1-cyanocyclohexyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp >300° C.628 embedded image

5-(2-(benzyloxy)phenyl)-N- (1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 591 (M + H)+629 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-5-(2-hydroxyphenyl)- 7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 122-124° C.630 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)-4- piperidinyl)(phenyl) methanoneMS(ESI, m/z) 443 (M + H)+631 embedded image

7,7-dimethyl-5-phenyl-3- ((2-(3-pyridinyl)-1- pyrrolidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 402 (M + H)+632 embedded image

(3R)-1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinolMS(ESI, m/z) 341 (M + H)+633 embedded image

1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- N,N-diethyl-3- piperidinecarboxamideMS(ESI, m/z) 438 (M + H)+634 embedded image

7,7-dimethyl-3-((3- phenoxy-1- pyrrolidinyl)carbonyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 417 (M + H)+635 embedded image

7,7-dimethyl-3-((3-(4- methylphenoxy)-1- pyrrolidinyl)carbonyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 545 (M + H)+636 embedded image

3-((3-(4-methoxyphenoxy)- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 447 (M + H)+637 embedded image

7-dimethyl-5-phenyl-3-((3-(4- (trifluoromethyl)phenoxy)- 1-pyrrolidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 485 (M + H)+638 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrroladinyl)methanolMS(ESI, m/z) 355 (M + H)+639 embedded image

(3S)-1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinolMS(ESI, m/z) 341 (M + H)+640 embedded image

methyl 1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- 4-piperidinecarboxylateMS(ESI, m/z) 397 (M + H)+641 embedded image

4-benzyl-1-((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinolMS(ESI, m/z) 445 (M + H)+642 embedded image

N-(1-(3-(4-chlorophenyl)- 1,2,4-oxadiazol-5-yl)-1- methylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 491 (M + H)+643 embedded image

methyl 4-(2-(3-(((1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)amino)carbonyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-5- yl)phenoxy)butanoateMS(ESI, m/z) 602 (M + H)+644 embedded image

N-(1-(hydroxymethyl)cyclohexyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 175-176° C.645 embedded image

N-(1-ethyl-1-(4- vinylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 155-156° C.646 embedded image

N-(1,1-diethylbutyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 76-77° C.647 embedded image

N-(1-ethyl-1-(4- ethylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 156-157° C.648 embedded image

7,7-dimethyl-5-phenyl-N-(4- phenyltetrahydro-2H-pyran- 4-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 431 (M + H)+649 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinyl)methanolMS(ESI, m/z) 369 (M + H)+650 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinyl-4- fluorophenyl)methanolMS(ESI, m/z) 463 (M + H)+651 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 2-piperidinyl)methanolMS(ESI, m/z) 369 (M + H)+652 embedded image

(1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-y)carbonyl)- 3-piperidiny-methanolMS(ESI, m/z) 369 (M + H)+653 embedded image

1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-y-carbonyl)- 3-piperidinolMS(ESI, m/z) 355 (M + H)+654 embedded image

1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-piperidinecarboxamideMS(ESI, m/z) 382 (M + H)+655 embedded image

1-((7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-phenyl-4- pipendinecarbonitrileMS(ESI, m/z) 440 (M + H)+656 embedded image

1-((7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-(trifluoromethyl)-4- piperidinolMS(ESI, m/z) 423 (M + H)+657 embedded image

methyl (2R)-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) (phenyl)acetateMS(ESI, m/z) 419 (M + H)+658 embedded image

methyl (2S)-(((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) (phenyl)acetateMS(ESI, m/z) 419 (M + H)+659 embedded image

N-((1R)-2-hydroxy-1- phenylethyl)-7,7-dimethyl- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 391 (M + H)+660 embedded image

N-((1S)-2-hydroxy-1- phenylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 391 (M + H)+661 embedded image

methyl 4-((1-((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinyl)oxy)benzoateMS(ESI, m/z) 475 (M + H)+662 embedded image

4-((1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinyl)oxy)benzoic acidMS(ESI, m/z) 461 (M + H)+663 embedded image

7,7-dimethyl-5-phenyl-3- ((3-(3-pyridinyloxy)-1- pyrrolidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 418 (M + H)+664 embedded image

N-(1,1-diethyl-3- methoxypropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 129-130° C.665 embedded image

N-(1,1-diethyl-3- (methylthio)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 154-155° C.666 embedded image

N-(1-(3,4-dichlorophenyl)- 1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 156-157° C.667 embedded image

N-(1-ethyl-1-(4- iodophenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 182-183° C.668 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 158-160° C.669 embedded image

7,7-dimethyl-5-phenyl-3- (((3S)-3-phenyl-4- morpholinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 417 (M + H)+670 embedded image

1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-phenyl-4-piperidinolMS(ESI, m/z) 431 (M + H)+671 embedded image

1-(1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-piperidinyl)-2-pyrrolidinoneMS(ESI, m/z) 422 (M + H)+672 embedded image

methyl 2-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-2- methyl-3-phenylpropanoateMS(ESI, m/z) 447 (M + H)+673 embedded image

4-benzyl-N-methoxy-N,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 405 (M + H)+674 embedded image

3-((3-(3,4-dichlorobenzyl)- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 484 (M + H)+675 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 200.9-201.0° C.676 embedded image

5-cyclohexyl-N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 178.7-178.9° C.677 embedded image

N-(1-ethyl-1-(4-(6-methoxy- 3-pyridinyl)phenyl)propyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 172-173° C.678 embedded image

methyl 4-(1-(((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzoatemp 180-181° C.679 embedded image

N-(4-tert-butyl-1- ethylcyclohexyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 437 (M + H)+680 embedded image

N-(1-(2,4-dichlorophenyl)- 1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pylimidine-3-carboxamidemp 220-222° C.681 embedded image

N-(1-ethyl-1-(4-(2- pyridinyl)phenyl)propyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideIR(KBr) 3336, 2975, 1634, 1582, 1532, 1532, 1508, 1456, 1435 cm⁻¹682 embedded image

N-(1-ethyl-1-(4- methoxyphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 140-141° C.683 embedded image

N-(1-benzyl-2-hydroxy-1- methylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrirnidine-3-carboxamideMS(ESI, m/z) 419 (M + H)+684 embedded image

3-((2,2-diallyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 405 (M + H)+685 embedded image

3-((2,2-dipropyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 409 (M + H)+686 embedded image

2-(1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 2-pyrrolidinyl)-2-propanolMS(ESI, m/z) 383 (M + H)+687 embedded image

methyl 1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 4-ethyl-4- piperidinecarboxylateMS(ESI, m/z) 425 (M + H)+688 embedded image

7,7-dimethyl-5-Phenyl-3- ((4-(3-pyridinylmethyl)-1- piperidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 430 (M + H)+689 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-2,7,7- trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideEA Calcd. C; 67.45, H; 6.67, N; 11.24, Found. C; 67.49, H; 6.65, N; 11.08690 embedded image

N-((1R)-2-methoxy-1- phenylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 405 (M + H)+691 embedded image

N-((2-(1-methoxy-1- methylethyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 397 (M + H)+692 embedded image

3-((2,2-dimethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 353 (M + H)+693 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-5-(2-furyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 212-214° C.694 embedded image

5-(2,4-difluorophenyl)-N-(1- ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 198-199° C.695 embedded image

N-(1-ethyl-1-(4- iodophenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 557 (M + H)+696 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 146-148° C.697 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-7,7-dimethyl-5- (2-methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 143-145° C.698 embedded image

N-(1,1-diethyl-4,4,4- trifluorobutyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 84-85° C.699 embedded image

N-(1-(4-Chlorobenzyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 156-157° C.700 embedded image

N-(1-(4-(benzyloxy)phenyl)- 1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 523 (M + H)+701 embedded image

N-(1-ethyl-1-(4- hydroxyphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 152-153° C.702 embedded image

N-(1-ethyl-1-(4- iodophenyl)propyl)-7,7- dimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideEA Calcd. C; 58.27, H; 5.98, N; 10.07. Found. C; 58.47, H; 6.17, N; 9.79703 embedded image

N-(1-ethyl-1-(4- methylbenzyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 150-151° C.704 embedded image

N-(1-ethyl-1-(4- methoxybenzyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 185-186° C.705 embedded image

N-(1-(4-allylphenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 147-148° C.706 embedded image

N-(1-ethyl-1-(4- propylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 177-178° C.707 embedded image

N-(1-ethyl-4-(4- methoxyphenyl)cyclohexyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 487 (M + H)+708 embedded image

3-((2-(1-fluoro-1- methylethyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 385 (M + H)+709 embedded image

(E)-(1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl) carbonyl)-4- piperidinyl)(phenyl) methanone O-methyloximeMS(ESI, m/z) 472 (M + H)+710 embedded image

7,7-dimethyl-5-phenyl-3- ((4-(phenylsulfonyl)-1- piperidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 479 (M + H)+711 embedded image

7,7-dimethyl-5-phenyl-3- ((4-(phenylthio)-1- piperidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 447 (M + H)+712 embedded image

ethyl 1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-(4-pyridinylmethyl)-3- piperidinecarboxylateMS(ESI, m/z) 502 (M + H)+713 embedded image

7,7-dimethyl-5-phenyl-3- ((4-(4-pyridinyloxy)-1- piperidinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 432 (M + H)+714 embedded image

ethyl 1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-(2-pyridinylmethyl)-3- piperidinecarboxylateMS(ESI, m/z) 502 (M + H)+715 embedded image

ethyl 3-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-3- methylbutanoateMS(ESI, m/z) 399 (M + H)+716 embedded image

N-(3-(benzylamino)-1,1- dimethyl-3-oxopropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 460 (M + H)+717 embedded image

N-(1,1-dimethyl-3-(4- methyl-1-piperazinyl)-3- oxopropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 490 (M + H)+718 embedded image

N-((1R)-2-methoxy-1- phenylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 405 (M + H)+719 embedded image

ethyl (2E)-4-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-4- methyl-5-phenyl-2-pentenoateMS(ESI, m/z) 487 (M + H)+720 embedded image

ethyl 4-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-4- phenylbutanoateMS(ESI, m/z) 461 (M + H)+721 embedded image

ethyl 4-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-4- methyl-5-phenylpentanoateMS(ESI, m/z) 489 (M + H)+722 embedded image

N-(1-(4-ethoxyphenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 141-142° C.723 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 180-181° C.724 embedded image

N-(1-ethyl-1-(2- furyl)propyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 407 (M + H)+725 embedded image

7,7-dimethyl-N-(1- (pentafluoroethyl)cyclohexyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 471 (M + H)+726 embedded image

N-(1-ethyl-1-(5-(4- fluorophenyl)-1-methyl-1H- pyrazol-3-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 218-219° C.727 embedded image

N-(1-ethyl-4- (trifluoromethyl)cyclohexyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 449 (M + H)+728 embedded image

4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl acetatemp 171-172° C.729 embedded image

4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl propionatemp 172-173° C.730 embedded image

ethyl (4-(1-(((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy)acetatemp 178-179° C.731 embedded image

(4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy)acetic acidmp 213-214° C.732 embedded image

ethyl 4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzoatemp 181-182° C.733 embedded image

isopropyl 4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- yl)carbonyl)amino-1- ethylpropyl)benzoatemp 205-206° C.734 embedded image

4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzoic acidmp 257-258° C.735 embedded image

3-((2-(4-chlorophenyl)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidineMS(ESI, m/z) 436 (M + H)+736 embedded image

N-(1-ethyl-1-(4- (trifluoromethyl)phenyl) propyl)-7,7-dimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 499 (M + H)+737 embedded image

4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzyl acetatemp 185-186° C.738 embedded image

N-(1-(4-bromophenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 185-187° C.739 embedded image

N-(1-ethyl-1-(4- (hydroxymethyl)phenyl) propyl)-7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 178-179° C.740 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 161-162° C.741 embedded image

methyl (1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) cyclohexyl)acetateMS(ESI, m/z) 425 (M + H)+742 embedded image

N-(1-(2- hydroxyethyl)cyclohexyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 397 (M + H)+743 embedded image

N-(1-ethyl-1-(5-(4- fluorophenyl)-1-methyl-1H- pyrazol-3-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 515 (M + H)+744 embedded image

ethyl 6-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-6- phenylhexanoateMS(ESI, m/z) 489 (M + H)+745 embedded image

ethyl 6-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-6- phenylheptanoateMS(ESI, m/z) 503 (M + H)+746 embedded image

N-(2-(2-(4- chlorobenzoyl)hydrazino)- 1,1-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 510 (M + H)+747 embedded image

N-(1-(5-(4-chlorophenyl)- 1,3,4-oxadiazol-2-yl)-1- methylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 491 (M + H)+748 embedded image

methyl 3-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl) propanoatemp 147-148° C.749 embedded image

3-(4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl) propanoic acidmp 240-241° C.750 embedded image

7,7-dimethyl-N′-(2-methyl-2-(4- methylphenyl)propanoyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carbohydrazideMS(ESI, m/z) 446 (M + H)+751 embedded image

N,N,7,7-tetramethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 299 (M + H)+752 embedded image

ethyl 6-((4- chlorophenyl)((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) hexanoateMS(ESI, m/z) 524 (M + H)+753 embedded image

N-(1-ethyl-1-(3-(4- fluorophenyl)-1-methyl-1H- pyrazol-5-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 515 (M + H)+754 embedded image

N-(1-ethyl-1-(5-methyl-1H- pyrazoI-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 421 (M + H)+755 embedded image

tert-butyl 4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)-3-methyl-1H- pyrazole-1-carboxylateMS(ESI, m/z) 521 (M + H)+756 embedded image

N-(1-(1-((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-isopropyl-1H-pyrazol-4- yl)-1-ethylpropyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 702 (M + H)+757 embedded image

butyl 4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzoatemp 139-140° C.758 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-2-ethyl-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 183-184° C.759 embedded image

ethyl 3-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl) propanoatemp 135-136° C.760 embedded image

4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl butyratemp 148-149° C.761 embedded image

N-(1-ethyl-1-(4- fluorophenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 182-183° C.762 embedded image

propyl 4-(1-(((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzoatemp 162-163° C.763 embedded image

N-(1-ethyl-1-(4-(3- hydroxypropyl)phenyl) propyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 194-195° C.764 embedded image

ethyl 5-((4- chlorophenyl)((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) pentanoateMS(ESI, m/z) 510 (M + H)+765 embedded image

4-benzyl-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 142-143° C.766 embedded image

2-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) cyclohexyl)ethyl acetateMS(ESI, m/z) 439 (M + H)+767 embedded image

N-(1-(1-benzyl-3-methyl- 1H-pyrazol-4-yl)-1- ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 511 (M + H)+768 embedded image

N,7,7-trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 116-117° C.769 embedded image

N-(1-(3,4-dimethylphenyl)- 1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 137-138° C.770 embedded image

ethyl 4-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy) butanoatemp 101-102° C.771 embedded image

4-(4-(1-(((7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy) butanoic acidmp 170-171° C.772 embedded image

3-((4-(benzyloxy)-2,2- diethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 488 (M + H)+773 embedded image

3-((2-tert-butyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 382 (M + H)+774 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-4- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 497 (M + H)+775 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-4- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 497 (M + H)+776 embedded image

N-(1-ethyl-1-(5-methyl-1-(2- pyridinyl)-1H-pyrazol-4- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 498 (M + H)+777 embedded image

N-(1-ethyl-1-(5-methyl-1-(2- pyridinyl)-1H-pyrazol-4- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 498 (M + H)+778 embedded image

N-(1-(4- (dimethylamino)phenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 128-129° C.779 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-2-(methylthio)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 106-107° C.780 embedded image

N-(1-(4-chlorophenyl)-1- ethylpropyl)-7,7-dimethyl-2- (methylthio)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 115-117° C.781 embedded image

2-ethyl-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 182-183° C.782 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-(2- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboxamideHCl salt mp 187-188° C.783 embedded image

N-(1-ethyl-1-(1-(4- methoxyphenyl)-5-methyl- 1H-pyrazol-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 527 (M + H)+784 embedded image

N-(1-(1-benzothien-2-yl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 473 (M + H)+785 embedded image

N-(1-ethyl-1-(4- (methoxymethyl)phenyl) propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 461 (M + H)+786 embedded image

N-(1-ethyl-1-(1-(4- methoxyphenyl)-5-methyl- 1H-pyrazol-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 527 (M + H)+787 embedded image

N-(1-ethyl-1-(1-(4- fluorophenyl)-5-methyl-1H- pyrazol-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrim;dine-3-carboxamideMS(ESI, m/z) 515 (M + H)+788 embedded image

N-(1-ethyl-1-(1-(4- fluorophenyl)-5-methyl-1H- pyrazol-4-yl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 515 (M + H)+789 embedded image

4-benzyl-N-(1-(4- chlorophenyl)-1- ethylpropyl)-N,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 556 (M + H)+790 embedded image

N-(1-ethyl-1-phenylpropyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 185-186° C.791 embedded image

N-(1-(4-chlorophenyl)-1- methylethyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 207-208° C.792 embedded image

N-(1-(4-chlorophenyl)-1- methylethyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 204-205° C.793 embedded image

7,7-dimethyl-N-(1-methyl-1- (4-methylphenyl)ethyl)-5- phenyl-4,5,6,7- tetrahydropyrazine[1,5- a]pyrimidine-3-carboxamideHCl salt mp 150-151° C.794 embedded image

2,7,7-trimethyl-N-(1-methyl- 1-(4-methylphenyl)ethyl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 193-194° C.795 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-3- yl)propyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 497 (M + H)+796 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-3- yl)propyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 497 (M + H)+797 embedded image

3-((2,2-diethyl-4-methoxy- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 412 (M + H)+798 embedded image

N′-ethyl-7,7-dimethyl-N′-(4- methylphenyl)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 404 (M + H)+799 embedded image

3-((2,2-diethyl-4-(4- methoxyphenoxy)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 503 (M + H)+800 embedded image

3-((2,2-diethyl-4-(4- methylphenoxy)-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 487 (M + H)+801 embedded image

methyl 4-((1-((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3- pyrrolidinyl)oxy)benzoateMS(ESI, m/z) 531 (M + H)+802 embedded image

3-((2,2-diethyl-4-fluoro-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 399 (M + H)+803 embedded image

1-((7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3-pyrrolidinoneMS(ESI, m/z) 395 (M + H)+804 embedded image

ethyl ((4-(1-(((7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)benzyl)oxy) acetateMS(ESI, m/z) 533 (M + H)+805 embedded image

7,7-dimethyl-N-(4- methylbenzyl)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 375 (M + H)+806 embedded image

N-(1-(4-chloro-3- methylphenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 465 (M + H)+807 embedded image

N-(1-(3-chloro-4- methylphenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 465 (M + H)+808 embedded image

N-(1-ethyl-1-(3- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 431 (M + H)+809 embedded image

3-((2,2-diethyl-4-((2- methoxyethoxy)methoxy)- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 485 (M + H)+810 embedded image

3-((2,2-diethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 381 (M + H)+811 embedded image

3-((4-(benzyloxy)-2,2- diethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 487 (M + H)+812 embedded image

N-(1-(5-chloro-2-thienyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 457 (M + H)+813 embedded image

N-(1-ethyl-1-(2- thienyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 423 (M + H)+814 embedded image

N-(1-ethyl-1-(1-(4- fluorophenyl)-1H-pyrazol-5- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 501 (M + H)+815 embedded image

butyl 3-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl) propanoateHCl salt mp 143-144° C.816 embedded image

isopropyl 3-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenyl) propanoateHCl salt mp 150-151° C.817 embedded image

ethyl 5-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy)pentanoatemp 120-121° C.818 embedded image

butyl 4-(4-(1-(((7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)-1- ethylpropyl)phenoxy)butanoatemp 133-134° C.819 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 144-145° C.820 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(3- methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 168-169° C.821 embedded image

N-(1-(4- (dimethylamino)phenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamide2HCl salt mp 140-141° C.822 embedded image

N-(1-(1-(4-chlorophenyl)-5- methyl-1H-pyrazol-3-yl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 531 (M + H)+823 embedded image

N-(1-(1-(4-chlorophenyl)-5- methyl-1H-pyrazol-3-yl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 545 (M + H)+824 embedded image

3-((4-((4-chlorobenzyl)oxy)- 2,2-diethyl-1- pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 522 (M + H)+825 embedded image

3-((2,2-diethyl-4-((4- methylbenzyl)oxy)-1- pyrrolidiny-carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 502 (M + H)+826 embedded image

3-((2,2-diethyl-2,3-dihydro- 1H-indol-1-yl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 430 (M + H)+827 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-4,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 120-121° C.828 embedded image

N-(1-(5-chloro-2-thienyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 457 (M + H)+829 embedded image

N-(1-ethyl-1-(2- naphthyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 467 (M + H)+830 embedded image

N-(1-(1-benzothien-2-yl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 487 (M + H)+831 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 152-153° C.832 embedded image

N-(1-ethyl-1-(4- (methylthio)phenyl)propyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 177-178° C.833 embedded image

N-(1-ethyl-1-(4- (methylthio)phenyl)propyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 149-150° C.834 embedded image

N-(1-(4-(4-amino-4- oxobutoxy)phenyl)-1- ethylpropyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 518 (M + H)+835 embedded image

7,7-dimethyl-N-(1-(1- naphthyl)propyl)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 439 (M + H)+: polar836 embedded image

7,7-dimethyl-N-(1-(1- naphthyl)propyl)-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 439 (M + H)+: less polar837 embedded image

N-(1-ethyl-1-(1-methyl-1H- indol-2-yl)propy-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 470 (M + H)+838 embedded image

N-(1,1-diethylbutyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 176-177° C.839 embedded image

N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 163-164° C.840 embedded image

N-(1-ethyl-1-phenylpropyl)- 5-(2-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 160-162° C.841 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-3- yl)propyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 511 (M + H)+842 embedded image

N-(1-ethyl-1-(5-methyl-1- phenyl-1H-pyrazol-3- yl)propyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt MS(ESI, m/z) 511 (M + H)+843 embedded image

N-(1-ethyl-1-(2- fluorophenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideHCl salt mp 180-182° C.844 embedded image

7,7-dimethyl-N-(2-(1- piperidinyl)ethyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 383 (M + H)+845 embedded image

7,7-dimethyl-N-(3- (methyl(phenyl)amino) propyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 419 (M + H)+846 embedded image

N-(1-benzyl-4-piperidinyl)- 7,7-dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 445 (M + H)+847 embedded image

N-(2-anilinoethyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 391 (M + H)+848 embedded image

N-(3-(1H-imidazol-1- yl)propyl)-7,7-dimethyl-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 380 (M + H)+849 embedded image

7,7-dimethyl-N-(3-4- morpholinyl-propyl)-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 399 (M + H)+850 embedded image

7,7-dimethyl-5-(2-pyridinyl)- N-(2-(1-pyrrolidinyl)ethyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 369 (M + H)+851 embedded image

N-(1-benzyl-3-pyrrolidinyl)- 7,7-dimethyl-5-(2-pyridinyl) 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 431 (M + H)+852 embedded image

7,7-dimethyl-5-(2- pyridinyl)-N-(3- pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 363 (M + H)+853 embedded image

N-(1-benzyl-3-pyrrolidinyl)- N,7,7-trimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 445 (M + H)+854 embedded image

N-ethyl-7,7-dimethyl-5-(2- pyridinyl)-N-(4- pyridinylmethyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 391 (M + H)+855 embedded image

3-((4-ethyl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(2-pylidinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 369 (M + H)+856 embedded image

3-((4-benzyl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 431 (M + H)+857 embedded image

7,7-dimethyl-5-(2- pyridinyl)-3-((4-(2- pyridinyl)-1- piperazinyl)carbonyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 417 (M + H)+858 embedded image

3-((4-benzhydryl-1- piperazinyl)carbonyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 507 (M + H)+859 embedded image

7,7-dimethyl-3-((4-phenyl- 1-piperazinyl)carbonyl)-5- (2-pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 417 (M + H)+860 embedded image

1′-((7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 1,4′-bipiperidineMS(ESI, m/z) 423 (M + H)+861 embedded image

7,7-dimethyl-3-((4-methyl- 1,4-diazepan-1- yl)carbonyl)-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 368 (M + H)+862 embedded image

N-benzyl-N-(2- (dimethylamino)ethyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 433 (M + H)+863 embedded image

5-cyclohexyl-N-(2- (dimethylamino)ethyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 348 (M + H)+864 embedded image

5-cyclohexyl-7,7-dimethyl- N-(2-(1-piperidinyl)ethyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 388 (M + H)+865 embedded image

5-cyclohexyl-7,7-dimethyl- N-(3-(4-methyl-1- piperazinyl)propyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 417 (M + H)+866 embedded image

5-cyclohexyl-7,7-dimethyl- N-(3-(methyl(phenyl) amino)propyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 424 (M + H)+867 embedded image

N-(1-benzyl-4-pipendinyl)- 5-cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamideMS(ESI, m/z) 450 (M + H)+954 embedded image

ethyl 4-(1-ethyl-1-(((2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino) propyl)benzoatemp 152-153° C.955 embedded image

N-(1-ethyl-1-(4- (hydroxymethyl)phenyl) propyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 146-147° C.956 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-(2-thienyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 149-150° C. HCl salt957 embedded image

N-(1,1-diethylbutyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 181-182° C. HCl salt958 embedded image

N-(1-ethyl-1-phenylpropyl)- 2,7,7-trimethyl-5-(2- thienyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 171-172° C. HCl salt959 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 159-160° C.960 embedded image

N-[1-ethyl-1-(4- methylphenyl)propyl]-5-(4- methoxyphenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 188-189° C. HCl salt961 embedded image

5-(2-chlorophenyl)-N-[1- ethyl-1-(4- methylphenyl)propyl]-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 128-130° C. HCl salt962 embedded image

N-[1-ethyl-1-(4- methylphenyl)propyl]-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 139-140° C.963 embedded image

N-(1-ethyl-1-phenylpropyl)- 5-(2-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 449 (M + H)+964 embedded image

N-[1-ethyl-1-(4- methylphenyl)propyl]5-(2- methoxyphenyl)-7,7- dimethy-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 158-159° C. HCl salt965 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- methoxyphenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidtne-3-carboxamidemp 162-163° C. HCl salt966 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(3- methoxyphenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 146-146° C. HCl salt967 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(4- methoxyphenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 153-154° C. HCl salt968 embedded image

5-(2-chlorophenyl)-N-(1- ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 173-174° C. HCl salt969 embedded image

N-(1-(4- (dimethylamino)phenyl)-1- ethylpropyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 152-153° C. 2HCl salt970 embedded image

5-(2,4-dimethylphenyl)-N- (1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 150-151° C. HCl salt971 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(4- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 166-169° C. HCl salt972 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(3- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 152-155° C. HCl salt973 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-(4- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 152-154° C. HCl salt974 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-(3- methylphenyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 120-123° C. HCl salt975 embedded image

N-(1-ethyl-1-(4- methylphenyl)propyl)-2-(2- hydroxyethoxy)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 115-117° C.976 embedded image

N-(1-ethyl-1-(4- ((methoxy(methyl)amino) carbonyl)phenyl)propyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 518 (M + H)+977 embedded image

N-(1-(4-acetylphenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 200-202° C.978 embedded image

N-(1-ethyl-1-(4-(1- hydroxyethyl)phenyl)propyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 165-166° C.979 embedded image

4-(1-ethyl-1-(((2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)carbonyl)amino)propyl) benzoic acidmp 244-246° C.980 embedded image

7,7-dimethyl-N-phenyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 348 (M + H)+981 embedded image

N-2,3-dihydro-1H-inden-5- yl-7,7-dimethyl-5-(2- pyridinyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 388 (M + H)+982 embedded image

N-(3,5-dimethoxyphenyl)- 7,7-dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 408 (M + H)+983 embedded image

N-(4-benzylphenyl)-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 438 (M + H)+984 embedded image

N-1,1′-biphenyl-3-yl-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 424 (M + H)+985 embedded image

7,7-dimethyl-5-(2-pyridinyl)- N-6-quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 399 (M + H)+986 embedded image

N-1,3-benzothiazol-2-yl- 7,7-dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 405 (M + H)+987 embedded image

N-2,3-dihydro-1,4- benzodioxin-6-yl-7,7- dimethyl-5-(2-pyridinyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 406 (M + H)+988 embedded image

7,7-dimethyl-5-(2-pyridinyl)- N-3-quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 399 (M + H)+989 embedded image

5-cyclohexyl-7,7-dimethyl- N-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 353 (M + H)+990 embedded image

5-cyclohexyl-N-2,3-dihydro- 1H-inden-5-yl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 393 (M + H)+991 embedded image

5-cyclohexyl-N-(3,5- dimethoxyphenyl)-7,7- dimethyl-4,5,6,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 413 (M + H)+992 embedded image

N-(4-benzylphenyl)-5- cyclohexyl-7,7-dimethyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 443 (M + H)+993 embedded image

N-1,1′-biphenyl-3-yl-5- cyclohexyl-7,7-dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 429 (M + H)+994 embedded image

5-cyclohexyl-7,7-dimethyl- N-6-quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 404 (M + H)+995 embedded image

5-cyclohexyl-N-2,3-dihydro- 1,4-benzodioxin-6-yl-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 411 (M + H)+996 embedded image

5-cyclohexyl-7,7-dimethyl- N-(4- (trifluoromethoxy)phenyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 437 (M + H)+997 embedded image

5-cyclohexyl-7,7-dimethyl- N-3-pyridinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 354 (M + H)+998 embedded image

5-cyclohexyl-7,7-dimethyl- N-3-quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 404 (M + H)+999 embedded image

7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-N-phenyl- 4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 368 (M + H)+1000 embedded image

2,3-dihydro-1H-inden-5- yl-7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 408 (M + H)+1001 embedded image

N-(3,5-dimethoxyphenyl)- 7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 428 (M + H)+1002 embedded image

N-(4-benzylphenyl)-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 458 (M + H)+1003 embedded image

N-1,1′-biphenyl-3-yl-7,7- dimethyl-5-(5-methyl-1,3- thiazo-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 444 (M + H)+1004 embedded image

7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-N-6- quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 419 (M + H)+1005 embedded image

N-1,3-benzothiazol-2-yl- 7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 425 (M + H)+1006 embedded image

N-2,3-dihydro-1,4- benzodioxin-6-yl-7,7- dimethyl-5-(5-methyl-1,3- thiazol-2-yl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 426 (M + H)+1007 embedded image

7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-N-(4- (trifluoromethoxy)phenyl)- 4,5,6,7- tetrahydropyrazolo[1,5- a[pyrimidine-3-carboxamideMS(ESI, m/z) 452 (M + H)+1008 embedded image

7,7-dimethyl-5-(5-methyl- 1,3-thiazol-2-yl)-N-3- quinolinyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 419 (M + H)+

EXAMPLE 1009
Ethyl 7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate

Racemic compound obtained in Example 16 (80 g) was subjected to preparative high performance liquid chromatography (HPLC) to afford optically pure materials (38 g, 99.8% ee (shorter retention time) and 39 g, 99.4% ee (longer retention time)). [column: CHIRALCEL OD 50 mmφ×500 mm (manufactured by Daicel Kagaku Kogyo Kabushiki Kaisha), temperature: 30° C., mobile phase: hexane/Ethanol=95/5, flow rate: 60 ml/minute, detection wavelength: 254 nm, and 1 shot: about 800 mg].

Compounds of Examples 1010-1017 shown in the Table 8˜11, were prepared in a manner similar to that described in Example 1009.

TABLE 8ExampleStructureNamePhysiological Data1010 embedded image

ethyl 2,7,7-trimethyl- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 314 (M + H)+, shorter retention time1011 embedded image

ethyl 2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 314 (M + H)+, longer retention time

The determination of the optical purity was carried out by HPLC using a chiral column (column: CHIRALCEL OD 4.6 mmφ×250 mm (manufactured by Daicel Kagaku Kogyo Kabushiki Kaisha), temperature: about 30° C., mobile phase: hexane/ethanol=96/4, flow rate: 0.5 ml/minute, and detection wavelength: 254 nm).

TABLE 91012 embedded image

ethyl 5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 318 (M + H)+, shorter retention time1013 embedded image

ethyl 5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 318 (M + H)+, longer retention time

The determination of the optical purity was carried out by HPLC using a chiral column (column: CHIRALPAK AD 4.6 mmφ×250 mm (manufactured by Daicel Kagaku Kogyo Kabushiki Kaisha), temperature: about 30° C., mobile phase: hexane/IPA =95/5, flow rate: 0.5 ml/minute, and detection wavelength: 254 nm).

TABLE 101014 embedded image

ethyl 5-(2-fluorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 332 (M + H)+, shorter retention time1015 embedded image

ethyl 5-(2-fluorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 332 (M + H)+, longer retention time

The determination of the optical purity was carried out by HPLC using a chiral column (column: CHIRALPAK AD 4.6 mmφ×250 mm (manufactured by Daicel Kagaku Kogyo Kabushiki Kaisha), temperature: about 30° C., mobile phase: hexane/ethanol=995/5, flow rate: 0.5 ml/minute, and detection wavelength: 220 nm).

TABLE 111016 embedded image

ethyl 5-(2-chlorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 348 (M + H)+, shorter retention time1017 embedded image

ethyl 5-(2-chlorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 348 (M + H)+, longer retention time

The determination of the optical purity was carried out by HPLC using a chiral column (column: CHIRALCEL OD 4.6 mmφ×250 mm (manufactured by Daicel Kagaku Kogyo Kabushiki Kaisha), temperature: about 30° C., mobile phase: hexane/ethanol=95/5, flow rate: 0.5 ml/minute, and detection wavelength: 258 nm).

EXAMPLE 1018
(−)-7,7-Dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a)pyrimidine-3-carboxylic acid

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A mixture of 1(0.73 g) obtained in Example 1009, KOH (0.41 g), H₂O(20 ml) and EtOH (20 mL) was stirred at 90° C. for 12 h, acidified with 1N HCl, and extracted with AcOEt. The extract was washed with brine, dreid over MgSO₄, and concentrated in vacuo to give 0.55 g (83% yield) of the title compound as colorless prisms ([α]_D^{20° C.}=−85.33, in CHCl₃, C=0.46). mp 205-206° C., ¹H NMR (CDCl₃, 300 MHz): 1.59 (3H, s), 1.66 (3H, s), 2.05-2.15 (2H, m), 4.64 (1H, dd, J=9.6, 5.4 Hz), 6.04 (1H, s), 7.30-7.41 (5H, m), 7.73 (1H, s)

Compounds of Examples 1019-1027 shown in the Table 12, were prepared in a manner similar to that described in Example 1018.

TABLE 12ExampleStructureNamePhysiological Data1019 embedded image

(+)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 205-206° C. [α]_D^{20° C.}=86.01, in CHCl₃, C =0.48.1020 embedded image

(+)-2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 190-192° C. [α]_D^{21° C.}=103.65, in CHCl₃, C = 1.17.1021 embedded image

(−)-2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 190-192° C. [α]_D^{21° C.}=−109.21, in CHCl₃, C = 1.25.1022 embedded image

(+)-5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 169-170° C. [α]_D^{20° C.}=107.91, in CHCl₃, C = 0.48.1023 embedded image

(−)-5-(2-fluorophenyl)-7,7- dimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 165-166° C. [α]_D^{20° C.}=−108.59, in CHCl₃, C = 0.47.1024 embedded image

(+)-5-(2-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 150-151° C. [α]_D^{21° C.}=123.34, in CHCl₃, C = 0.33.1025 embedded image

(−)-5-(2-fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 150-151° C. [α]_D^{21° C.}=−122.39, in CHCl₃, C = 0.47.1026 embedded image

(+)-5-(2-chlorophenyl)- 2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 163-164° C. [α]_D^{21° C.}=177.21, in CHCl₃, C = 0.28.1027 embedded image

(−)-5-(2-chlorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylic acidmp 163-164° C. [α]_D^{21° C.}=−166.12, in CHCl₃, C = 0.25.

EXAMPLE 1028
(S)-N-(1-(4-Chlorophenyl)-1-ethylpropyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide hydrochloride

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Step A: To a solution of 1 (0.4 g, 1.47 mmol) and HATU (0.67 g, 1.77 mmol) in DMF (5 mL) was added DIPEA (0.57 g, 4.41 mmol) at room temperature. After 1 h, compound 2 (0.41 g, 1.77 mmol) was added thereto. The resulting mixture was stirred at 80° C. for 12 h, and concentrated in vacuo. The residue was diluted with AcOEt, washed with sat.NaHCO₃aq and brine, dried over MgSO₄, and concentrated in vacuo. The residue was chromatographed on silica gel with AcOEt/hexane (1/1) to give 0.41 g (62% yield) of compound 4 as colorless prisms. mp 105-106° C. [α]_D^{20° C.}=−17.68 in CHCl₃, C=0.30. Step B: To a stirred solution of compound 3 (90 mg, 0.2 mmol) in Et₂O (3 mL) was added 4M HCl-AcOEt (0.1 mL, 0.4 mmol) at room temperature. The precipitate was collected by filtration to give 60 mg (62% yield) of compound 4 as prisms. mp 130-132° C. [α]_D^{20° C.}=24.3 in CHCl₃C=0.48.

Compounds of Examples 1029-1122 shown in the Table 13, were prepared in a manner similar to that described in Example 1028.

TABLE 13ExampleStructureNamePhysiological Data1029 embedded image

(5S)-N-1-adamantyl-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 226-227° C. [α]_D^{20° C.}= −37.40 in CHCl₃, C = 0.24.1030 embedded image

(5R)-N-1-adamantyl-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 226-227° C. [α]_D^{20° C.}= 37.0 in CHCl₃, C = 0.24.1031 embedded image

(5S)-N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)prop yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro- pyrazolo]1,5- ]pyrimidine-3-carboxamidemp 165-166° C. [α]_D^{20° C.}= −15.10 in CHCl₃, C = 0.25.1032 embedded image

(5R)-N-(1-ethyl-1-(4- (trifluoromethyl)phenyl)prop yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro- pyrazolo[1,5- a]pyrimidine-3-carboxamidemp 185-166° C. [α]_D^{20° C.}= 14.4 in CHCl₃, C = 0.25.1033 embedded image

(5R)-N-(1-(4-chlorophenyl)- 1-ethylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 105-106° C. [α]_D^{20° C.}= 17.92 in CHCl₃, C = 0.28.1034 embedded image

(5S)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 139-140° C. [α]_D^{20° C.}= −19.67 in CHCl₃, C = 0.341035 embedded image

(5S)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 142-143° C., [α]_D^{21° C.}= 31.05 in CHCl₃, C = 0.65. HCl salt1036 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 139-140° C. [α]_D^{22° C.}= 16.33 in CHCl₃, C = 0.60.1037 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 150-151° C., [α]_D^{21° C.}= −27.99 in CHCl₃, C = 0.80. HCl salt1038 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 140-141° C. [α]_D^{22° C.}= −14.02 in CHCl₃, C = 0.30. PhSO₃H salt1039 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 151-152° C. [α]_D^{21° C.}= −14.42 in CHCl₃, C = 0.33. p-TsOH salt1040 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,8,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 140-141° C. [α]_D^{21° C.}= −9.10 in CHCl₃, C = 0.40. 0.5 H₂SO₄salt1041 embedded image

(5S)-N-(1-(4-chlorophenyl)- 1-ethylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 131-132° C. [α]_D^{20° C.}= −22.83 in CHCl₃, C = 0.22.1042 embedded image

(5R)-N-(1-(4-chlorophenyl)- 1-ethylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 128-129° C. [α]_D^{20° C.}= 22.44 in CHCl₃, C = 0.23.1043 embedded image

(5R)-N-(1-(4-chlorophenyl)- 1-ethylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 193-194° C. [α]_D^{21° C.}= −7.85 in CHCl₃, C = 0.30. HCl salt1044 embedded image

(5S)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7 tetrahydropyrazolo[1,5- pyrimidine-3-carboxamidemp 78-80° C. [α]_D^{20° C.}= −23.5 in CHCl₃, C = 0.51.1045 embedded image

(5S)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 194-195° C. [α]_D^{20° C.}= 9.3 in CHCl₃, C = 0.48. HCl salt1046 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 78-80° C. [α]_D^{20° C.}= 25.3 CHCl₃, C = 0.50.1047 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,8,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 206-207° C. [α]_D^{25° C.}= −8.1 in CHCl₃, C = 0.52. HCl salt1048 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 188-189° C. [α]_D^{20° C.}= −4.4 in CHCl₃, C = 0.44. CH₃SO₃H salt1049 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 161-162° C. [α]_D^{20° C.}= −9.5 in CHCl₃, C = 0.50. PhSO₃H salt1050 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 120-122° C. [α]_D^{20° C.}= −8.8 in CHCl₃, C = 0.51. p-TsOH salt1051 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 149-150° C. [α]_D^{21° C.}= −16.76 in CHCl₃, C = 0.39. HCl salt1052 embedded image

(5R)-N-(1-(4-tert- butylphenyl)-1-ethylpropyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro pyrazolo[1,5- a]pyrimidine-3-carboxamidemp 139-140° C., [α]_D^{21° C.}= −13.94 in CHCl₃, C = 0.36. HCl salt1053 embedded image

(5R)-N-(1-ethyl-1- phenylpropyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 129-130° C., [α]_D^{20° C.}= −24.66 in CHCl₃, C = 0.38. HCl salt1054 embedded image

(5R)-N-(1-ethyl-1- phenylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 185-186° C., [α]_D^{20° C.}= −10.56 in CHCl₃, C = 0.39 HCl salt1055 embedded image

(5R)-N-(1,1-diethylbutyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydro- pyrazolo[1,5- a]pyrimidine-3-carboxamidemp 176-177° C. [α]_D^{21° C.}= −1.98 in CHCl₃, C = 0.35. HCl salt1056 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 459 (M + H)+, [α]_D^{20° C.}= 25.0 in CHCl₃, C = 0.53.1057 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo]1,5- a]pyrimidine-3-carboxamidemp 163-164° C., [α]_D^{21° C.}= −7.96 CHCl₃, C = 0.46. HCl salt1058 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 160-161° C., [α]_D^{20° C.}= −2.9 in CHCl₃, C = 0.56. CH₃SO₃H salt1059 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 165-166° C., [α]_D^{21° C.}= −7.4 in CHCl₃, C = 0.49. PhSO₃H salt1060 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 160-161° C., [α]_D^{21° C.}= −8.1 in CHCl₃, C = 0.49. P-TsOH salt1061 embedded image

(5R)-N-(1-ethyl-1-(5-methyl- 1-phenyl-1H-pyrazol-3- yl)propyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 511 (M + H)+1062 embedded image

(5R)-N-(1-ethyl-1-(5-methyl- 1-phenyl-1H-pyrazol-3- yl)propyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 194-195° C. 2HCl salt1063 embedded image

(5R)-N-(1-ethyl-1-(2- fluorophenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 180-182° C., [α]_D^{21° C.}= −8.60 in CHCl₃, C = 0.62. HCl salt1064 embedded image

(5R)-N-(1-ethyl-1-(4- hydroxyphenyl)propyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydro- pyrazolo[1,5- a]pyrimidine-3-carboxamidemp 160-161° C., [α]_D^{21° C.}= 15.41 in CHCl₃, C = 0.36.1065 embedded image

(5S)-N-(1-ethyl-1- phenylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 182-183° C., [α]_D^{21° C.}= 11.36 in CHCl₃, C = 0.36. HCl salt1066 embedded image

(5R)-N-(1-(5-chloro-2- thienyl)-1-ethylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo]1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 471 (M + H)+1067 embedded image

(5R)-N-(1-ethyl-1-(4- (methylthio)phenyl)propyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro-pyrazolo]1,5- a]pyrimidine-3-carboxamidemp 151-152° C.,1068 embedded image

(5R)-N-(1-(4-chloro-3- methylphenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 150-151° C. HCl salt1069 embedded image

(5R)-N-(1-(3-chloro-4- methylphenyl)-1- ethylpropyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 129-130° C. HCl salt1070 embedded image

(5R)-N-(1-(1-benzothien-2- yl)-1-ethylpropyl)-2,7,7- trimethyl-5-phenyl-4,5,8,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 127-128° C. HCl salt1071 embedded image

(5R)-N-(1-(4-(dimethyl- amino)phenyl)-1-ethylpropyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydro-pyrazolo[1,5- a]pyrimidine-3-carboxamidemp 141-142° C. HCl salt1072 embedded image

(5R)-N-(1,1-diethylbutyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro-pyrazolo]1,5- a]pyrimidine-3-carboxamidemp 185-186° C., HCl salt1073 embedded image

(5R)-N-(1-ethyl-1-(4- iodophenyl)propyl)-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 179-180° C., HCl salt1074 embedded image

(5R)-ethyl 4-(1-ethyl-1- (((2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- amino)propyl)benzoatemp 125-126° C., HCl salt1075 embedded image

(5R)-N-(1-ethyl-1-(4- (hydroxymethyl)phenyl)- propyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 168-169° C. HCl salt1076 embedded image

(5R)-4-(1-ethyl-1-(((-2,7,7- trimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- amino)propyl)benzoic acidmp 234-236° C.1077 embedded image

(5R)-N-(1-ethyl-1-(4- (hydroxymethyl)phenyl)- propyl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 159-160° C., HCl salt1078 embedded image

(+)-N-[1-ethyl-1-(4- methylphenyl)propyl]-5-(2- fluorophenyl)-7,7-dimethyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 139-140° C., [α]_D^{20° C.}= +9.66 in CHCl₃, C = 0.47. HCl salt1079 embedded image

(+)-N-[1-ethyl-1-(4- methylphenyl)propyl]-5-(2- fluorophenyl)-7,7-dimethyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 161-163° C. [α]_D^{20° C.}= 39.5 in CHCl₃, C = 0.50.1080 embedded image

mp 135-136° C., [α]_D^{20° C.}= −11.19 in CHCl₃, C = 0.49. HCl salt of Example 10791081 embedded image

mp 144-146° C. [α]_D^{20° C.}= 5.1 in CHCl₃, C = 0.50. p-TsOH salt of Example 10791082 embedded image

mp 147-149° C. [α]_D^{20° C.}= −4.1 in CHCl₃, C = 0.49. PhSO₃H salt of Example 10791083 embedded image

(5S)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6.7- tetrahydropyrazolo]1,5- a]pyrimidine-3-carboxamidemp 203-204° C. [α]_D^{20° C.}= −1.29 in CHCl₃, C = 0.54. HCl salt1084 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 463 (M + H)+1085 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 156-158° C. [α]_D^{20° C.}= 1.29 in CHCl₃, C = 0.52. HCl salt1086 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 180-181° C. [α]_D^{20° C.}= 4.9 in CHCl₃, C = 0.52. CH₃SO₃H salt1087 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 172-174° C. [α]_D^{20° C.}= 0.4 in CHCl₃, C = 0.48. p-TsOH salt1088 embedded image

(5R)-N-(1-ethyl-1-(4- methylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 170-171° C. [α]_D^{20° C.}= −0.1 in CHCl₃, C = 0.49. PhSO₃H salt1089 embedded image

(5R)-N-(1-ethyl-1-(4- ethylphenyl)propyl)-5-(2- fluorophenyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 138-139° C. [α]_D^{20° C.}= 2.6 in CHCl₃, C = 0.57. HCl salt1090 embedded image

(5S)-5-(2-chlorophenyl)-N- (1-ethyl-1-(4-methyl- phenyl)propyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 173-174° C. [α]_D^{20° C.}= −48.2 in CHCl₃, C = 0.50. HCl salt1091 embedded image

(5R)-5-(2-chlorophenyl)-N- (1-ethyl-1-(4-methyl- phenyl)propyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 136-137° C. [α]_D^{20° C.}= 66.9 in CHCl₃, C = 0.50.1092 embedded image

(5R)-5-(2-chlorophenyl)-N- (1-ethyl-1-(4-methyl- phenyl)propyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 176-177° C. [α]_D^{20° C.}= 48.0 in CHCl₃, C = 0.57. HCl salt1093 embedded image

(5R)-5-(2-chlorophenyl)-N- (1-ethyl-1-(4-methyl- phenyl)propyl)-2,7,7- trimethyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 171-172° C. [α]_D^{20° C.}= 42.4 in CHCl₃, C = 0.62. CH₃SO₃H salt1094 embedded image

(5R)-5-(2-chlorophenyl)-N- (1-ethyl-methylphenyl)- propyl)-2,7,7-trimethyl-4,5,6,7- tetrahydropyrazolo]1,5- a]pyrimidine-3-carboxamidemp 150-151° C. [α]_D^{20° C.}= 37.8 in CHCl₃, C = 0.51. P-TsOH salt1095 embedded image

N-(1-ethyl-1-(4-isopropyl- phenyl)propyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamidemp 134-136° C. HCl salt1096 embedded image

(5R)-3-(((4R)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 501 (M + H)+HCl salt1097 embedded image

(3R)-5,5-diethyl-1-(((5R)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinolmp 162-164° C.1098 embedded image

(3R)-5,5-diethyl-1-(((5R)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 3-pyrrolidinolmp 140-142° C. HCl salt1099 embedded image

(5R)-3-(((4R)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-2,7,7-trimethyl-5- phenyl-4,5,6,7-tetrahydro- pyrazolo]1,5-a]pyrimidinemp 132-134° C.1100 embedded image

(5R)-3-(((4R)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7-tetrahydro- pyrazolo[1,5-a]pyrimidineHCl salt EA Calcd. For C₂₅H₃₇N₄O₂Cl.H₂O: C. 62.68; H. 8.21; N. 11.70. Found. C. 62.89; H. 8.43; N. 11.50.1101 embedded image

(5R)-3-((2,2-diethyl-4-fluoro- 1-pyrrolidinyl)carbonyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 413 (M + H)+1102 embedded image

(5R)-3-((2,2-diethyl-4-fluoro- 1-pyrrolidinyl)carbonyl)- 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- tetrahydropyrazolo[1,5- a]pyrimidineHCl salt EA Calcd. For C₂₄H₃₄N₄OCIF.0.9H₂O: C. 61.96; H. 7.76; N. 12.04. Found. C. 62.26; H. 8.01; N. 11.831103 embedded image

(5R)-3-(((4R)-4-(benzyloxy)- 2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 118-120° C.1104 embedded image

(5R)-3-(((4R)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineHCl salt EA Calcd. For C₃₀H₃₉N₄O₂Cl.H₂O: C. 66.59; H. 7.64; N. 10.35. Found. C. 66.83; H. 7.73; N. 10.051105 embedded image

(5S)-3-(((4R)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo]1,5- a]pyrimidinemp 172-174° C.1106 embedded image

(5S)-3-(((4R)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineHCl salt ¹H-NMR (CDCl₃) δ: 0.82 (6H, dt, J=36.3, 7.2 # Hz), 1.58-1.72 (1H, m), 1.93 (6H, d, J=54.3 Hz), 2.00-2.26 (7H, m), 3.67 (1H, dd, J=12.3, 2.7 Hz), 3.79 (1H, dd, J=9.9, 5.4 Hz), 4.15-4.24 (1H, m), 4.56 (2H, dd, J=39.3, 12.0 Hz), 4.64 (1H, dd, J=10.2, 4.8 Hz), 7.30-7.46 (10H, m), 7.88 (1H, bs).1107 embedded image

(5R)-3-(((4S)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 173-175° C.1108 embedded image

(5R)-3-(((4S)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineHCl salt ¹H-NMR (CDCl₃) δ: 0.83 (6H, dt, J=30.9, 7.5 # Hz), 1.60-1.78 (1H, m), 1.68 (6H, d, J=24.3 Hz), 1.96-2.24 (7H, m), 3.70-3.78 (1H, m), 3.88-4.00 (1H, m), 4.14-4.24 (1H, m), 4.54 (2H, dd, J=25.2, 11.7 Hz), 4.61 (1H, dd, J=9.6, 3.9 Hz), 7.28-7.44 (10H, m), 7.59 (1H, bs).1109 embedded image

(5S)-3-(((4S)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 116-118° C.1110 embedded image

(5S)-3-(((4S)-4-(benzyloxy)- 2,2-diethyl-1-pyrrolidinyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydro- pyrazolo[1,5-a]pyrimidineHCl salt ¹H-NMR (CDCl₃) δ: 0.84 (6H, dt, J=14.4, 9.2 # Hz), 1.68-2.24 (8H, m), 1.86 (6H, d, J=43.5 Hz), 3.50-3.60 (1H, m), 3.76-3.92 (1H, m), 4.14-4.27 (1H, m), 4.57 (2H, dd, J=33.9, 12.0 Hz), 4.58-4.68 (1H, m), 7.30-7.46 (10H, m), 7.79 (1H, bs).1111 embedded image

(5R)-3-(((4R)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 148-150° C.1112 embedded image

(5R)-3-(((4R)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 148-150° C. HCl salt1113 embedded image

(5R)-3-(((4S)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 122-124° C.1114 embedded image

(5R)-3-(((4S)-2,2-diethyl-4- methoxy-1-pyrrolidinyl)- carbonyl)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 122-124° C. HCl salt1115 embedded image

(3R)-1-(((5R)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo]1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3-pyrrolidinolmp 250-252° C.1116 embedded image

(3R)-1-(((5R)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3-pyrrolidinolmp 250-252° C. HCl salt1117 embedded image

(3S)-1-(((5R)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3-pyrrolidinolmp 249-251° C.1118 embedded image

(3S)-1-(((5R)-7,7-dimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)carbonyl)- 5,5-diethyl-3-pyrrolidinolmp 247-249° C. HCl salt1119 embedded image

(5R)-3-((2,2-diethyl-4-fluoro- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 210-212° C. more polar1120 embedded image

mp 209-211° C. HCl salt of Example 11191121 embedded image

(5R)-3-((2,2-diethyl-4-fluoro- 1-pyrrolidinyl)carbonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 216-218° C. less polar1122 embedded image

mp 216-218° C. HCl salt of Example 1121

EXAMPLE 435
N-(1-adamantyl)-7-ethyl-5-phenyl-7-(trifluoromethyl)-6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

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Step A: To a stirred solution of compound 1 (2.00 g, 6.00 mmol) in DCM (50 mL) was added triethylaluminium (2.0 M hexane solution, 18 mL, 36 mmol) at room temperature. After the mixture was stirred for 2 h, it was quenched with water, and extracted with AcOEt. The extract was successively washed with water and brine, dried over MgSO₄and then concentrated in vacuo to give compound 2 (2.20 g, 100% yield) as yellow syrup. MS(ESI,m/z) 366 (M+H)⁺.

Step B: A mixture of compound 2 (2.20 g, 6.00 mmol), LiOH (0.51 g, 12.15 mmol), EtOH (50 mL) and H₂O (30 mL) was stirred at 70° C. for 12 h, concentrated in vacuo, diluted with aq.citric acid solution and extracted with AcOEt. The extract was successively washed with water, saturated NaHCO₃solution and brine, dried over MgSO₄and then concentrated to give compound 3 (2.00 g, 100%) as colorless crystals. MS(ESI,m/z) 352 (M+H)⁺.

Step C: 1-Adamantylamine (0.72 g, 4.76 mmol) was added to a suspension of compound 3 (1.60 g, 4.74 mmol), WSC (0.91 g, 4.74 mmol), HOBt (0.64 g, 4.74 mmol) and DMAP (0.58 g, 4.75 mmol) in DMF (20 mL). The reaction mixture was stirred at 70° C. for 13 h and then concentrated in vacuo. The residue was chromatographed on silica gel with AcOEt/hexane (1/6) as an eluent to give compound 4 (0.71 g, 32%) as colorless crystals. MS(ESI,m/z) 472 (M+H)⁺.

Step D: To a solution of 4 (0.58 g, 1.23 mmol) in EtOH was added NaBH₄(0.2 g, 5.29 mmol) at room temperature. The whole was stirred at 60° C. for 3 h, concentrated in vacuo, diluted with water and extracted with AcOEt. The extract was successively washed with aq. NaHCO₃, water and brine, dried over MgSO₄and then concentrated to give 0.43 g (74%) of compound 5 as colorless crystals. MS(ESI,m/z) 474 (M+H)⁺.

Compounds of Examples 436, shown in the Table 5, were prepared in a manner similar to that described in Example 435.

TABLE 5ExampleStructureNamePhysical Data436 embedded image

N-(1-adamantyl)-7-methyl-5- phenyl-7-(trifluoromethyl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxamideMS(ESI, m/z) 462 (M + H)+

EXAMPLE 437
2-cyclohexyl-4-methyl-N-(1-methyl-1-phenylethyl)-1,2,3,4-tetrahydropyrazolo[5,1-c][1,2,4]triazine-8-carboxamide

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Step A: To a 250 mL round bottom flask equipped with magnetic stir bar and 2 addition funnels was added 1.0 g (6.44 mmol) of compound 1 by 3.5 ml of conc. hydrochloric acid and 7.0 ml of water. The solution was cooled to 0° C. and a solution containing 0.50 g (7.25 mmol) of sodium nitrite in 2 ml of water dropwise. After complete addition, the reaction was allowed to stir for 30 min. at 0° C., followed by the addition of 65 ml of dichloromethane and 35 ml of a saturated sodium bicarbonate solution while maintaining the reaction temperature below 10° C. A solution containing 2.05 g (6.44 mmol) of 1-triphenylphosphoroanylidene-2-propanone in 30 ml of dichloromethane was then added dropwise. After complete addition, the reaction was allowed to stir for 5 min., diluted with 50 ml of dichloromethane and washed with water. The organic phase was separate and the solvent removed under reduced pressure to afford 3.50 g (100%) of crude compound 2 which is taken on without further purification. MS Calcd.: 206; Found 207 (M+H).

Step B: To a solution containing the crude product from above in 30 ml of ethanol and 30 ml of THF under a nitrogen atmosphere was added 1.20 g (3.72 mmol) of sodium borohydride. The reaction was allowed to stir at room temperature for 30 min. The reaction was diluted with ethyl acetate and washed with water. The organic phase was dried over MgSO₄. Filtration, removal of solvent and purification of the residue via Biotage chromatography eluting with 70% AcOEt/hexanes gave 0.79 g (58.9%) of compound 3 as a pale yellow solid. MS Calcd.: 208; Found 209 (M+H)

Step C: A solution containing 0.54 g (2.59 mmol) of compound 3 and 0.18 g of LiOH (7.52 mmol) in 15 ml of ethanol and 10 ml of water was heated to 70° C. After 1.5 h, HPLC of reaction mixture indicated no starting material remaining. The ethanol was removed under reduced pressure and the residue acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate. Filtration and removal of solvent gave 0.48 g (92.2%) of compound 4. MS Calcd.: 180; Found 181 (M+H).

Step D: To a solution containing 2.80 g (15.54 mmol) of compound 4 in 150 ml of DMF under a nitrogen atmosphere was added 6.50 g (17.10 mmol) of HATU, 2.31 g (17.10 mmol) of cumyl amine and 2.98 ml (17.10 mmol) of diisopropylethylamine. The reaction was heated to 50° C. overnight, diluted with ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via Biotage chromatography eluting with 60% AcOEt/hexanes gave 3.09 g (66.9%) of compound 5. MS Calcd.: 297; Found 298 (M+H).

Step E: To a Parr flask was added 1.11 g (3.90 mmol) of compound 5 and 75 ml of EtOH. The flask was purged with nitrogen and 0.30 g of platinum oxide added. The flask was evacuated and pressurized to 20 psig hydrogen (3×) then pressurized to 50 psig hydrogen and shaken for 1 h. After completion as determined by HPLC, the reaction was filtered through GF/F filter paper and the filtrate concentrated under reduced pressure to afford 1.1 g (100%) of compound 6. MS Calcd.: 299; Found 300 (M+H)

Step F: To a solution containing 0.43 g (1.44 mmol) of compound 6 in 40 ml of DCE under a nitrogen atmosphere was added 0.30 ml (2.89 mmol) of cyclohexanone followed by 0.90 g (4.25 mmol) of sodium triacetoxy borohydride. The reaction was allowed to stir at room temperature overnight. The reaction was diluted with dichloromethane and washed with saturated sodium bicarbonate solution. The organic phase was dried over MgSO₄. Filtration, removal of solvent and purification of the residue via Biotage chromatography eluting with 75% AcOEt/hexanes gave 0.35 g (63.7%) of compound 7. MS Calcd.: 381; Found 382 (M+H)

EXAMPLE 438
4-Methyl-N-(1-methyl-1-phenylethyl)-2-phenyl-1,2,3,4-tetrahydropyrazolo[5,1-c][1,2,4]triazine-8-carboxamide

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To a solution containing 0.20 g (0.71 mmol) of compound 1 in 25 ml of DCM under a nitrogen atmosphere at −78° C. was added 0.36 g (0.64 mmol) of triphenylbismuth diacetate followed by 0.02 g (0.075 mmole) of copper (II) dipivalate. The reaction was allowed to warm to 0° C. over 1.5 h. The reaction was diluted with dichloromethane and washed with saturate sodium bicarbonate. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via Biotage chromatography eluting with 70% AcOEt/hexanes gave 0.025 g (9.4%) of compound 2. MS Calcd.: 375; Found 376 (M+H)

EXAMPLE 1123
1-(7,7-Dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-methyl-2-(4-methylphenyl)-1-propanone

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Step A

4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2)

To a 100 mL round bottom flask equipped with a magnetic stir bar was added 1.80 g (6.01 mmol) of 7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid ethyl ester, 30 mL of DMF and 0.786 mL (6.61 mmol) of benzyl bromide, followed by 0.265 g (6.6 mmol) of sodium hydride (60% dispersion in mineral oil) which was added in several portions. After 2 h, the reaction was quenched with water and the product was extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated to give the crude N-benzylated ester as a golden colored oil. The crude ester was dissolved in 15 mL of ethanol and 2.5 mL of 6 N potassium hydroxide was added. The solution was then heated to 70° C. for 18 h at which time no starting material could be detected by HPLC analysis. The crude reaction mixture was concentrated in vacuo and diluted with water. The aqueous solution was acidified with 6 N HCl and the resulting cream-colored precipitate was collected by filtration. The crude acid thus isolated was dissolved in AcOEt, dried over sodium sulfate, filtered and concentrated to a cream colored powder. The resulting acid was washed with several portions of hexanes and dried in vacuo to give 1.95 g (90%) of the title compound as an off white powder. ¹H NMR (DMSO-d₆) δ 1.10 (s, 3H), 1.40 (s, 3H), 1.98-2.16 (m, 2H), 3.71 (d, J=15.4 Hz, 1H), 4.36 (dd, J=4.5, 11.5 Hz, 1H), 5.81 (d, J=15.6 Hz), 6.97 (dd, J=1.4, 7.2 Hz, 2H), 7.26-7.45 (m, 7H), 7.67 (s, 1H), 11.81 (s, 1H). MS Calcd.: 361; Found: 344 (M-OH).

Step B

4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid methoxy-methyl-amide (3): To a 5 mL NMP solution containing 0.72 g (1.99 mmol) of 2 was added 0.91 g (2.39 mmol) of O-7-azabenzotriazolo-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU) and 0.416 mL (2.39 mmol) of diisopropylethylamine. After stirring for 30 min, 0.233 g (2.39 mmol) of O,N-dimethyl-hydroxylamine hydrochloride was added and the reaction heated to 50° C. After 1 h, the reaction mixture was poured into water and extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give a crude oil. Purification of this oil by flash chromatography eluting with a 60 to 50% hexanes/AcOEt gradient gave 0.65 g (81%) of the title compound as a light golden colored solid. ¹H NMR (CDCl₃) δ 1.37 (s, 3H), 1.56 (s, 3H), 2.06-2.16 (m, 2H), 3.25 (s, 3H), 3.49 (s, 3H), 3.90 (d, J=16.0 Hz, 1H), 4.45 (dd, J=5.1, 11.3 Hz, 1H), 5.06 (d, J=16.2 Hz, 1H), 6.98 (dd, J=1.8, 6.1 Hz, 2H), 7.20-7.24 (m, 3H), 7.30-7.34 (m, 1H), 7.37-7.41 (m, 4H), 7.74 (s, 1H). MS Calcd.: 404; Found: 405 (M+H).

Step C

1-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-(4-methylphenyl)ethanone (4): To 0.65 g (1.61 mmol) of 3 dissolved in 20 mL of THF was added 6.4 mL (3.2 mmol) of a 0.5 M solution of 4-methylbenzylmagnesium chloride in THF via syringe over 10 min. After stirring at room temperature for 1 h, the reaction was quenched by addition of approximately 2 mL of saturated aqueous ammonium chloride. The reaction was then diluted with AcOEt and dried over sodium sulfate. Filtering the solution through a short plug of silica gel and concentrating in vacuo provided the crude product as an oil. Purification of this oil by flash chromatography eluting with 75% hexanes/AcOEt gave 0.64 g (89%) of the title compound as a white foam. MS Calcd.: 449; Found: 450 (M+H).

Step D

1-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-(4-methylphenyl)-1-propanone (5): To 0.64 g (1.42 mmol) of 4 dissolved in 10 mL of THF was added 0.177 mL (2.85 mmol) of iodomethane followed by 0.11 g (2.8 mmol) of sodium hydride (60% dispersion in mineral oil). After stirring at room temperature for 2 h, the reaction was quenched by addition of approximately 2 mL of saturated aqueous ammonium chloride. The reaction was then diluted with AcOEt and dried over sodium sulfate. Filtering the solution through a short plug of silica gel and concentrating in vacuo provided the crude product. Purification by flash chromatography eluting with 90% hexanes/ethyl acetate gave 0.42 g (64%) of the title compound as a cream colored powder. MS Calcd.: 463; Found: 464 (M+H).

Step E

1-(4-Benzyl-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-methyl-2-(4-methylphenyl)-1-propanone (6): To 0.110 mL (0.785 mmol) of diisopropyl amine dissolved in 5 mL of THF at −78° C. was added 0.314 mL (0.785 mmol) of a 2.5 M solution of n-butyllithium in hexanes. After stirring for 30 min, 0.28 g (0.604 mmol) of 5 was added as a solution in 1 mL of THF. The reaction was stirred at room temperature for 1 h before 0.049 mL (0.79 mmol) of iodomethane was added as a solution in 1 mL of THF. After 1 h the reaction was quenched by addition of approximately 0.5 mL of saturated aqueous ammonium chloride, diluted with AcOEt and dried over sodium sulfate. Filtering the solution through a short plug of silica gel and concentrating in vacuo provided the crude product. Purification by flash chromatography eluting with 90% hexanes/AcOEt gave 0.067 g (23%) of the title compound as an off white solid. MS Calcd.: 477; Found: 478 (M+H).

Step F

1-(7,7-Dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-methyl-2-(4-methylphenyl)-1-propanone (7): To 0.060 g (0.126 mmol) of 6 dissolved in 4 mL of 1:1 THF:ethanol was added 0.080 g of 10% palladium on carbon. The reaction vessel was capped with a rubber septum and charged with hydrogen via a balloon. After 1 h, the catalyst was removed via filtration and the filtrate concentrated to a cream colored solid. Purification by flash chromatography eluting with 90% hexanes/ethyl acetate gave 0.041 g (84%) of the title compound as a white solid. ¹H NMR (CDCl₃) δ 1.49 (s, 3H), 1.54 (s, 9H), 2.04-2.11 (m, 2H), 2.32 (s, 3H), 4.63 (dd, J=4.1, 10.7 Hz, 1H), 6.66 (s, 1H), 7.12-7.26 (m, 5H), 7.31-7.44 (m, 5H). MS Calcd.: 387; Found: 388 (M+H).

Compounds of Examples 1124-1131 shown in the Table 14, were prepared in a manner similar to that described in Example 1123.

TABLE 141124 embedded image

2-(1,1′-biphenyl-4-yl)-1-(7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)ethanoneMS(ESI, m/z) 422 (M + H)+1125 embedded image

1-(4-benzyl-7,7-dimethy-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2- phenylethanoneMS(ESI, m/z) 436 (M + H)+1126 embedded image

1-(4-benzyl-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2-phenyl- 1-propanoneMS(ESI, m/z) 450 (M + H)+1127 embedded image

1-(7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2-phenyl- 1-propanoneMS(ESI, m/z) 360 (M + H)+1128 embedded image

(1-(7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2-methyl- 2-phenyl-1-propanoneMS(ESI, m/z) 374 (M + H)+1129 embedded image

2-(4-chlorophenyl)-1-(7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)- 1-propanoneMS(ESI, m/z) 395 (M + H)+1130 embedded image

2-(4-chlorophenyl)-1-(7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2-methyl- 1-propanoneMS(ESI, m/z) 409 (M + H)+1131 embedded image

1-(7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-2-(4- methylphenyl)-1-propanoneMS(ESI, m/z) 374 (M + H)+

EXAMPLE 1132
7,7-Dimethyl-3-((1-methyl-1-(4-methylphenyl)ethyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine

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p-Tolylmethanesulfonylacetonitrile (2): To a 10 mL ethanol solution containing 4.1 g (30 mmol) of p-tolylmethanethiol at 0° C. was added 4.1 mL (30 mmol) of triethylamine and 4.4 g (30 mmol) of sodium iodide. After allowing the reaction to stir at room temperature for approximately 30 min, the reaction cooled to 0° C. and 1.9 mL (30 mmol) of chloroacetonitrile was added dropwise as a solution in 10 mL of ethanol. The reaction was allowed to reach room temperature overnight and was subsequently filtered and concentrated. The concentrate was partitioned between water and ether and separated. The ether layer was washed successively with 2 N sodium carbonate and brine and was then concentrated to an oil that solidified. The crude solid was then dissolved in 90 mL of glacial acetic acid, treated with 12.1 mL (107 mmol) of 30% hydrogen peroxide and heated to 100° C. The reaction was cooled to room temperature after 3 h at which time a white solid precipitated. The precipitate was collected via filtration, washed with glacial acetic acid and dried in vacuo to give 6.4 g (69%) of the title compound as a white solid. ¹H NMR (CDCl₃) δ 2.39 (s, 3H), 3.70 (s, 2H), 4.48 (s, 2H), 7.32 (dd, J=7.3, 40.2 Hz, 4H).

Step B

3-Ethoxy-2-p-tolylmethanesulfonylacrylonitrile (3): To a solution of 4.4 g (21 mmol) of 2 in 17.5 mL (105 mmol) of triethylorthoformate was added 9.9 mL (105 mmol) of acetic anhydride. The resulting solution was heated to reflux for 18 h before being concentrated to a solid. Recrystallization from AcOEt-hexanes gave 5.0 g (90%) of the title compound as a white solid.

¹H NMR (CDCl₃) δ 1.29 (t, J=7.0 Hz, 3H), 2.36 (s, 3H), 4.19 (q, J=7.0 Hz, 2H), 4.35 (s, 2H), 7.23 (dd, J=8.0, 19.9 Hz) 7.37 (s, 1H).

Step C

7,7-Dimethyl-3-(4-methylbenzyl)sulfonyl)-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine (4): A slurry of 1.9 g (7.2 mmol) of 3 in 25 mL of ethanol was treated with 0.38 mL (7.9 mmol) of hydrazine monohydrate and heated to reflux for 3 h. The reaction was concentrated in vacuo to give crude 4-p-tolylmethanesulfonyl-2H-pyrazol-3-ylamine as a tan solid. The crude pyrazole, 1.3 g (7.9 mmol) of 3-methyl-1-phenyl-but-2-en-1-one and 2.8 mL (36 mmol) of trifluoroacetic acid was dissolved in 25 mL of 2-methoxyethanol and heated to reflux for 3 days. The reaction was then cooled to room temperature, concentrated in vacuo and dissolved in AcOEt. This solution was washed successively with saturated sodium bicarbonate, water and brine before being dried over sodium sulfate. The solution was filtered, concentrated in vacuo and the resulting crude material was purified by flash chromatography eluting with a 75 to 33% hexanes/AcOEt gradient to give 1.25 g (44%) of the title compound as a powder. ¹H NMR (CDCl₃) δ 1.67 (s, 6H), 2.13 (s, 3H), 4.26 (s, 2H), 4.81 (d, J=2.0 Hz, 1H), 6.39 (s, 1H), 7.05 (dd, J=8.0, 18.5 Hz, 4H), 7.20 (dd, J=3.7, 7.4 Hz, 2H), 7.36-7.39 (m, 3H), 7.52 (s, 1H). MS Calcd.: 393; Found: 394 (M+H).

Step D

7,7-Dimethyl-3-((4-methylbenzyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (5): To 0.500 g (1.27 mmol) of 4 dissolved in 8 mL of 1:1 THF:ethanol was added 0.50 g of 10% palladium on carbon. The reaction vessel was capped with a rubber septum and charged with hydrogen via a balloon. After 2 days at room temperature, the catalyst was removed via filtration and the filtrate concentrated to a solid. Purification by flash chromatography eluting with a 75 to 33% hexanes/AcOEt gradient gave 0.385 g (77%) of the title compound as a white solid. ¹H NMR (CDCl₃) δ 1.49 (s, 3H), 1.59 (s, 3H), 1.83-1.97 (m, 2H), 2.37 (s, 3H), 4.09-4.24 (m, 3H), 5.03 (s, 1H), 7.06-7.13 (m, 6H), 7.30-7.39 (m, 3H), 7.45 (s, 1H). MS Calcd.: 395; Found: 396 (M+H).

Step E

4-Benzyl-7,7-dimethyl-3-((4-methylbenzyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (6): To a solution of 0.34 g (0.86 mmol) of 5 in 10 mL of THF at 0° C. was added 0.128 mL (1.07 mmol) of benzyl bromide followed by 0.034 g (0.86 mmol) of sodium hydride (60% dispersion in mineral oil). The reaction was allowed to warm to room temperature after 30 min and stirred for an additional 30 min before being quenched with water. The quenched reaction was diluted with five volumes of water and extracted with AcOEt. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography eluting with 70% hexanes/AcOEt to give 0.39 g (93%) of the title compound as a white solid. ¹H NMR (CDCl₃) δ 1.27 (s, 3H), 1.52 (s, 3H), 1.93-2.05 (m, 2H), 2.27 (s, 3H), 3.83 (d, J=15.8 Hz, 1H), 4.18-4.30 (m, 3H), 5.51 (d, J=15.8 Hz, 1H), 6.98-7.00 (m, 2H), 7.09 (dd, J=8.2, 12.1 Hz, 4H), 7.17 (d, J=6.8 Hz, 2H), 7.26-7.30 (m, 3H), 7.32-7.40 (m, 3H), 7.47 (s, 1H)

Step F

4-Benzyl-7,7-dimethyl-3-((1-(4-methylphenyl)ethyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (7): A solution of 0.23 g (0.47 mmol) of 6 in 4 mL of THF was cooled to 0° C. and treated with 0.24 mL (0.59 mmol) of n-butyllithium (2.5 M solution in hexanes) and allowed to reach room temperature for 20 min. After cooling the reaction to 0° C., 0.103 mL (1.66 mmol) of iodomethane was added as a solution in 2 mL of THF. The reaction was allowed to warm to room temperature for 30 min at which time the reaction was quenched with a few drops of saturated ammonium chloride. The reaction was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 80% hexanes/AcOEt to give 0.14 g (60%) of the title compound as a white solid. MS Calcd.: 499; Found: 500 (M+H).

Step G

4-Benzyl-7,7-dimethyl-3-((1-methyl-1-(4-methylphenyl)ethyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (8): Using the method described for the synthesis of 7, the title compound was prepared in 51% isolated yield. MS Calcd.: 513; Found: 514 (M+H).

Step H

7,7-Dimethyl-3-((1-methyl-1-(4-methylphenyl)ethyl)sulfonyl)-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (9): To 0.075 g (0.146 mmol) of 8 dissolved in 6 mL of 1:1 THF:ethanol was added 0.10 g of 10% palladium on carbon. The reaction vessel was capped with a rubber septum and charged with hydrogen via a balloon. After 2 h at room temperature, the catalyst was removed via filtration and the filtrate concentrated to give 0.056 g (91%) of the title compound as a white solid. MS Calcd.: 423; Found: 424 (M+H).

Compounds of Examples 1133-1134, shown in the Table 15, were prepared in a manner similar to that described in Example 1132.

TABLE 151133 embedded image

3-((1-(4- chlorophenyl)ethyl)sulfonyl)- 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 431 (M + H)+1134 embedded image

3-((1-(4-chlorophenyl)-1- methylethyl)sulfonyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 445 (M + H)+

EXAMPLE 1135
3-(3-Benzylpyrrolidine-1-sulfonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine

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(3-Benzylpyrrolidine-1-sulfonyl)acetonitrile (2): To a 20 mL ether solution containing 1.34 g (8.31 mmol) of 3-benzylpyrrolidine cooled to −45° C. was added 0.61 g (4.4 mmol) of 2-cyanoethanesulfonyl chloride as a solution in 10 mL of ether. The reaction was allowed to warm to room temperature and was stirred for 24 h over which time an oil formed on the flask wall. The ether solution was poured away from the oil and filtered through a short plug of silica gel. The filtrate thus obtained was concentrated in vacuo to give a solid that was purified by flash chromatography eluting with 75% hexanes/AcOEt to give 1.25 g (44%) of the title compound as a wax.

¹H NMR (CDCl₃) δ 1.73-1.83 (m, 1H), 2.08-2.15 (m, 1H), 2.57-2.67 (m, 1H), 2.71-2.79 (m, 2H), 3.21 (dd, J=8.2, 9.7, Hz, 1H), 3.49-3.55 (m, 1H), 3.63 (dd, J=7.0, 9.4 Hz, 1H), 3.69-3.74 (m, 1H), 3.95 (s, 2H), 7.16 (d, J=7.4 Hz, 2H), 7.21-7.33 (m, 3H).

Step B

2-(3-Benzylpyrrolidine-1-sulfonyl)-3-ethoxyacrylonitrile (3): To a solution of 0.14 g (0.53 mmol) of 2 in 0.43 mL (2.6 mmol) of triethylorthoformate was added 0.25 mL (2.6 mmol) of acetic anhydride. The resulting solution was heated to reflux for 4 h before being concentrated to an oil. The crude oil thus obtained was purified by flash chromatography eluting with 75% hexanes/AcOEt to give 0.079 g (46%) of the title compound as a yellow oil. ¹H NMR (CDCl₃) δ 1.42 (t, J=7.2 Hz, 3H), 1.67-1.77 (m, 1H), 2.01-2.09 (m, 1H), 2.53-2.62 (m, 1H), 2.71 (d, J=7.4 Hz, 2H), 3.05 (dd, J=8.4, 9.8 Hz, 1H), 3.35-3.41 (m, 1H), 3.48 (dd, J=7.0, 9.5 Hz, 1H), 3.53-3.59 (m, 1H), 4.31 (q, J=7.2 Hz, 2H), 7.15-7.17 (m, 2H), 7.19-7.23 (m, 1H), 7.26-7.31 (m, 2H), 7.76 (s, 1H).

Step C

3-(3-Benzylpyrrolidine-1-sulfonyl)-7,7-dimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine (4): A 2 mL ethanol solution containing 0.079 g (0.247 mmol) of 3 was treated with 0.013 mL (0.27 mmol) of hydrazine monohydrate and heated to reflux for 5 h. The reaction was concentrated in vacuo to give crude 4-(3-benzylpyrrolidine-1-sulfonyl)-2H-pyrazol-3-ylamine. The crude pyrazole thus obtained was dissolved in 2 mL of 2-methoxyethanol containing 0.044 g (0.27 mmol) of 3-methyl-1-phenyl-but-2-en-1-one and 0.038 mL (0.49 mmol) of trifluoroacetic acid was added. The mixture was refluxed for three days then concentrated and purified by flash chromatography eluting with 60% hexanes/AcOEt to give 3-(3-benzylpyrrolidine-1-sulfonyl)-7,7-dimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine that was found to be only 90% pure by HPLC analysis. This material was then dissolved in 1 mL of 1:1 THF:ethanol and 0.010 g of 10% palladium on carbon. The reaction vessel was capped with a rubber septum and charged with hydrogen via a balloon. After 90 min at room temperature, the catalyst was removed via filtration and the filtrate concentrated to an oil. Purification by flash chromatography eluting with 75% hexanes/AcOEt gave 0.024 g (20% from 3) of the title compound as a light yellow oil. ¹H NMR (CDCl₃) δ 1.55-1.66 (m, 7H), 1.94-2.03 (m, 1H), 2.08-2.16 (m, 2H), 2.37-2.50 (m, 1H), 2.58-2.70 (m, 2H), 2.90-2.97 (m, 1H), 3.18-3.27 (m, 1H), 3.31-3.42 (m, 2H), 4.53-4.60 (m, 1H), 5.71 (s, 1H), 7.11-7.14 (m, 2H), 7.19-7.23 (m, 1H), 7.26-7.40 (m, 7H), 7.53 (s, 1H). MS Calcd.: 450; Found: 451 (M+H).

EXAMPLE 1136
4,4-Dimethyl-8-[5-(1-methyl-1-phenyl-ethyl)-[1,3,4]oxadiazol-2-yl]-2-phenyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine

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2-Amino-1H-pyrrole-3-carboxylic acid ethyl ester (1): Carbamimidoyl-acetic acid ethyl ester (3.357 g, 25.8 mmol) was dissolved in AcOEt (20 mL). Chloroacetaldehyde (50% solution in water, 1.8 mL, 28.7 mmol) was added rapidly at room temperature. The solution stirred for 2 minutes until a precipitant formed. The solution was then brought to 65° C. for 0.5 h. The reaction mixture was then cooled and flash chromatographed with AcOEt. Product containing fractions were concentrated to give the desired material as a green solid. 0.68 g obtained, 31% yield. ¹H NMR (400 MHz, CDCl₃) δ 1.32 (t, J=7.2 Hz, 3H), 4.24 (q, J=7.0 Hz, 2H), 5.08 (brs, 2H), 6.10-6.13 (m, 1H), 6.25 (t, J=3.12, 1 Hz), 8.60 (brs, 1H); MS Calcd.: 154; Found 155 (M+H).

Step B

4,4-Dimethyl-2-phenyl-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrimidine-8-carboxylic acid ethyl ester (2): Compound 1 (0.68 g, 4.41 mmol) was dissolved in DMF (5 mL). NaH (60% in mineral oil, 0.19 g, 4.7 mmol) was added at room temperature affording rapid gas evolution. The reaction stirred for 0.5 h upon which 3-methyl-1-phenyl-but-2-en-1-one (0.50 g, 3.15 mmol) was added. The reaction stirred for 0.5 h upon which EtOH (5 mL) and NaBH₄(1.19 g) were added. The solution was brought to 60° C. for 0.5 h. and then cooled to room temperature. The solution was quenched with water, extracted with Et₂O (3 times), dried (Na₂SO₄) and concentrated. Flash chromatography (10% AcOEt) to give the desired product as a tan solid (0.60 g, 63% yield). MS Calcd.: 298; Found 299 (M+H).

Step C

4,4-Dimethyl-2-phenyl-1,2,3,4-tetrahydro-pyrrolo[1,2,-a]pyrimidine-8-carboxylic acid hydrazide (3): Compound 2 (0.210 g, was diluted with anhydrous hydrazine (5 mL) and heated to 100° C. for 3 days. The reaction was then cooled and diluted with water. The solution was extracted with AcOEt (3 times), dried (Na₂SO₄) and concentrated. The residue was flash chromatographed (10% MeOH/AcOEt) to give the desired material. 0.12 g, 60% yield). ¹H NMR (400 MHz, CDCl₃) δ 1.54 (s, 6H), 1.99-2.13 (m, 2H), 3.89 (brs, 2H), 4.64 (dd, J=3.5, 11.7 Hz, 1H), 6.02 (d, J=3.9 Hz), 6.22 (d, J=3.9 Hz, 1H), 6.55 (brs, 1H), 6.74 (brs, 1H), 7.31-7.46 (m, 5H). MS Calcd.: 284; Found 285 (M+H).

Step D

4,4-Dimethyl-2-phenyl-1,2,3,4-tetrahydro-pyrrolo[1,2,-a]pyrimidine-8-carboxylic acid N-(2-methyl-2-phenyl-propionyl)-hydrazide (4)

Compound 3 (0.085 g, 0.30 mmol) was dissolved in THF (2 mL). HBTU (0.136 g, 0.36 mmol), α,α-dimethyl-phenylacetic acid (0.059 g, 0.36 mmol), and DIEA (0.10 mL, 0.60 mmol) were added. The reaction stirred for 2 h. and was concentrated. Flash chromatography (50% AcOEt/hexanes) gave the desired product. 0.123 g obtained (96% yield). ¹H NMR (400 MHz, CDCl₃) & 1.49 (s, 3H), 1.50 (s, 3H), 1.60 (s, 3H), 1.61 (s, 3H), 1.95-2.10 (m, 2H), 4.56 (dd, J=3.1, 11.3 Hz, 1H), 6.13 (d, J=3.5 Hz, 1H), 6.17 (d, 3.5 Hz, 1H), 6.65 (brs, 1H), 7.22-7.43 (m, 1H), 7.81 (brs, 1H), 7.92 (brs, 1H). MS Calcd.: 430; Found 431 (M+H).

Step E

4,4-Dimethyl-8-[5-(1-methyl-1-phenyl-ethyl)-[1,3,4]oxadiazol-2-yl]-2-phenyl-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine (5): Compound 4 (0.060 g, 0.14 mmol) was diluted in POCl₃(3 mL). The solution was heated to 75° C. for 3 h. The solution was cooled and carefully quenched with water. The solution was diluted with AcOEt and the mixture carefully neutralized with sat. NaHCO₃. The organic layer was separated and the aqueous layer was extracted twice more with AcOEt portions. The combined organic layers were dried (Na₂SO₄), concentrated, and flash chromatographed to give the desired product as a white solid. 0.016 g obtained (28% yield). ¹H NMR (400 MHz, CDCl₃) δ 1.55 (s, 6H), 1.80 (s, 6H), 2.02-2.16 (m, 2H), 4.68 (dd, J=3.2, 11.6 Hz, 1H), 6.23 (d, J=3.2 Hz, 1H), 6.30 (d, J=3.2 Hz, 1H), 7.20-7.46 (m, 10H). MS Calcd.; 412; Found 413 (M+H).

EXAMPLE 1137
3-Methyl-2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-7-carboxylic acid [1-ethyl-1-(4-trifluoromethyl-phenyl)-propyl]-amide

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5-Amino-1-(1-methyl-2-oxo-2-phenyl-ethyl)-1H-pyrazole-4-carboxylic acid ethyl ester (1): 5-Amino-1H-pyrazole-4-carboxylic acid ethyl ester (7.35 g, 47.3 mmol) was dissolved in 160 mL of DMF. Na₂CO₃(5.02 g, 47.3 mmol) was added followed by 2-bromopropiophenone (7.2 mL, 47.3 mmol). The reaction stirred at room temperature for 2 days. The solution was diluted with AcOEt and the organic layer was washed with sat. NaHCO₃, brine, dried (MgSO₄), and concentrated. Flash chromatography (20-45% AcOEt/hexane) gave the desired product (1.58 g, 12% yield). ¹H NMR (400 MHz, CDCl₃) δ 1.3 (t, J=7.0 Hz, 3H), 1.7 (d, J=7.4 Hz, 3H), 4.2 (q, J=7.0 Hz, 2H), 5.4 (bs, 2H), 5.9 (q, J=7.0 Hz, 1H), 7.41-7.59 (m, 3H), 7.60 (s, 1H), 8.0 (d, J=8.0 Hz, 2H).

Step B

5-Amino-1-(2-hydroxy-1-methyl-2-phenyl-ethyl)-1H-pyrazole-4-carboxylic acid ethyl ester (2): Compound 1 (0.7 g, 2.43 mmol) was dissolved in 34 mL EtOH. NaBH₄(0.18 g, 4.87 mmol) was added in one shot. The reaction stirred at room temperature for 0.5 h. The solution was quenched with sat. NH₄Cl and extracted with CH₂Cl₂(3 times). The organic layer was washed with brine, dried (MgSO₄), concentrated to give a fluffy white solid 2 (0.69 g, 98% yield). MS: Calcd.: 289; Found: 290 (M+H).

Step C

3-Methyl-2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-7-carobxylic acid ethyl ester (3): Compound 2 (0.80 g, 2.8 mmol) was dissolved in CH₂Cl₂. SOCl₂(0.61 mL, 8.3 mmol) was added dropwise. After 90 minutes, the solution was concentrated to give a yellow solid. After pumping on high vacuum for 5 minutes, the solid was dissolved in CHCl₃. Et₃N (2.7 mL, 19.5 mmol) was added dropwise and the reaction mixture stirred for 1 hour. The reaction was quenched with water and diluted with AcOEt. The solution was washed with sat. NH₄Cl, sat. NaHCO₃, brine, and then dried (MgSO₄). Flash chromatography (20% AcOEt/hexane) gave both the syn (0.10 g, 14%) and anti (0.62 g, 82%) isomers 3. Anti isomer ¹H NMR (400 MHz, CDCl₃) δ 1.23 (t, J=7.0 Hz, 3H), 1.80 (d, J=6.6 Hz, 3H), 4.10-4.20 (m, 2H), 4.25-4.35 (m, 1H), 4.38 (brs, 1H), 5.10 (d, J=9.8 Hz, 1H), 7.17-7.25 (m, 5H), 7.59 (s, 1H). Syn isomer ¹H NMR (400 MHz, CDCl₃) δ 1.28 (d, J=7.0 Hz, 3H), 7.38 (t, J=7.4 Hz, 3H), 4.25-4.35 (m, 2H), 7.43-7.52 (m, 1H), 5.17 (brs, 1H), 5.23 (d, J=9.8 Hz, 1H), 7.37-7.45 (m, 5H).

Step D and E

3-Methyl-2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-7-carboxylic acid [1-ethyl-1-(4-trifluoromethyl-phenyl)-propyl]-amide (5)

Compound 3 (0.085 g, 0.3 mmol) was dissolved in EtOH (3 mL). KOH (6M in water, 0.9 mL, 1.78 mmol) was added. The reaction stirred at 60° C. for 3 h. The solution was cooled, diluted with AcOEt (10 mL) and water (10 mL) and shaken vigorously. The Aqueous layer was separated and acidified to pH=3. This acidic layer was then extracted with AcOEt (3 times). The combined AcOEt layers were washed with brine, dried (Na₂SO₄) and concentrated. The residue was then dissolved in NMP (1 mL) and 1-ethyl-1-(4-trifluoromethyl-phenyl)-propylamine (0.087 g, 0.37 mmol), HATU (0.14 g, 0.37 mmol), and DIEA (0.14 mL, 0.78 mmol) were added. The reaction was heated to 80° C. for 2 days. The solution was then cooled, washed with water, dried (MgSO₄), and concentrated. Flash chromatography (20% AcOEt/hexanes) gave 0.017 g (12% yield) of amide 5.

¹H NMR (400 MHz, CDCl₃) δ 0.79-0.83 (m, 6H), 1.26 (d, J=7.0 Hz, 3H), 1.99-2.05 (m, 2H), 2.23-2.31 (m, 2H), 4.44-4.48 (m, 1H), 5.19 (brs, 1H), 5.24 (d, J=10 Hz, 1H), 5.66 (brs, 1H), 7.37-7.63 (m, 9H). MS Calcd.: 456; Found: 457 (M+H).

EXAMPLE 1138
8-Methyl-5-phenyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5,a][1,3]diazepine-3-carboxylic acid (1-methyl-1-phenyl-ethyl)-amide

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5-Amino-1-[4-tert-butyl-dimethyl-silanyloxy]-1-methyl-4-phenyl-butyl]-1H-pyrazole-4-carboxylic acid ethyl ester (1)

5-Amino-1H-pyrazole-4-carboxylic acid ethyl ester (1.60 g, 10.3 mmol) was dissolved in 10 mL of DMF. The solution was cooled to 0° C. and NaH (60% in mineral oil, 0.82 g, 20.6 mmol) was added in one portion. The reaction warmed to room temperature after H₂evolution ceased. The reaction stirred for 0.5 h till a bright orange color persisted. The reaction was again brought to 0° C. and methanesulfonic acid 4-(tert-butyl-dimethyl-silanyloxy)-1-methyl-4-phenyl-butyl ester (3.49 g, 9.38 mmol) was then added as a solution in 6 mL DMF. The reaction warmed to room temperature and stirred for 2.5 days. The solution was quenched with water and diluted with AcOEt. The organic layer was separated and the aqueous layer was extracted twice more with AcOEt. The combined organic layers were dried (MgSO₄), concentrated and flash chromatographed (15% AcOEt/hexanes) to give 0.530 g (13% yield) of the desired product as an oil. ¹H NMR (400 MHz, CDCl₃) δ 0.16 (s, 3H), 0.17 (s, 3H), 1.04 (d, J=10 Hz, 9H), 1.48-1.52 (m, 3H), 1.55 (d, J=6.4 Hz, 3H), 1.60 (d, J=6.8 Hz, 3H—other diastereomer), 1.62-1.75 (m, 2H), 1.97-2.07 (m, 2H), 2.10-2.20 (m, 2H—other diastereomer), 4.02-4.07 (m, 1H), 4.21-4.29 (m, 1H—other diastereomer), 4.40-4.43 (m, 2H), 4.79-4.86 (m, 1H), 5.04 (brs, 1H), 5.25 (brs, 1H—other diastereomer), 7.36-7.47 (m, 5H), 7.79 (s, 1H); MS Calcd.: 431; Found 432 (M+H).

Step B and C

8-Methyl-5-phenyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5,a][1,3]diazepine-3-carboxylic acid ethyl ester (3): Compound 1 (2.0 g, 4.6 mmol) was dissolved in 9 mL THF. TBAF (1M in THF, 13.9 mL, 13.9 mmol) was added at room temperature. The reaction stirred for 0.5 h. The reaction was diluted with ether and washed with brine and water. The ether layer was dried (MgSO₄) and concentrated to give the crude alcohol product 2. MS Cald.: 317; Found 318 (M+H).

Alcohol 2 was taken up in CH₂Cl₂(80 mL). SOCl₂(1.7 mL, 23.4 mmol) was added. After 1 h, the solution was concentrated and re-dissolved in 80 mL DMF. CsCO₃(12.6 g, 39 mmol) was added. After 3 h, additional CsCO₃(12.6 g, 39 mmol) was added. The reaction ran 1.5 days. The reaction was quenched with water and diluted with AcOEt. After separation of the organic layer, the aqueous layer was washed twice with AcOEt. The combined organic layers were dried (MgSO₄), concentrated, and flash chromatographed to give 0.35 g (26% yield) of a mixture of cis and trans isomers which were readily separated.

Anti isomer—¹H NMR (400 MHz, CDCl₃) δ 1.24 (t, J=7.0 Hz, 3H), 1.40 (d, J=7.0 Hz, 3H), 1.93-2.34 (m, 4H), 4.05 (d, 1H), 4.09-4.23 (m, 2H), 4.79-4.85 (m, 1H), 6.40 (bs, 1H), 7.27-7.44 (m, 5H), 7.64 (s, 1H). MS Calcd.: 299; Found 300 (M+H). Syn isomer—¹H NMR (400 MHz, CDCl₃) δ 1.24 (t, J=7.0 Hz, 3H), 1.68 (d, J=7.0 Hz, 3H), 1.70-1.80 (m, 1H), 2.00-2.23 (m, 3H), 4.17-4.30 (m, 4H), 6.43 (brs, 1H), 7.22-7.40 (m, 5H), 7.63 (s, 1H). MS Calcd.: 299; Found 300 (M+H).

Step D

8-Methyl-5-phenyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5,a][1,3]diazepine-3-carboxylic acid (1-methyl-1-phenyl-ethyl)-amide (4): Compound 3 (0.074 g, 0.25 mmol) was diluted with EtOH (0.8 mL). KOH (6M in water, 0.23 mL) was added and the reaction stirred at 60° C. for 3.5 h. The solution was cooled and diluted with AcOEt and water. After vigorous shaking, the aqueous layer was removed and acidified to pH=3. The aqueous layer was then extracted with AcOEt(3 times). The organic layers were combined, dried (MgSO₄), and concentrated to give 0.070 g of desired carboxylic acid. MS Calcd.: 271; Found 272 (M+H).

This acid residue (0.070 g, 0.26 mmol) was dissolved in NMP (2 mL). HATU (0.12 g, 0.31 mmol) and cumylamine (0.042 g, 0.31 mmol) were added followed by DIEA (0.090 mL, 0.52 mmol). The reaction stirred at 90° C. for 2 h. The solution was cooled to room temperature and diluted with water. The solution was extracted from AcOEt (3 times), dried (MgSO₄), and concentrated. Flash chromatography (30% AcOEt/hexanes) gave the desired product. 0.065 g obtained (65% yield). ¹H NMR (400 MHz, CDCl₃) δ 1.65 (d, J=6.6 Hz, 3H), 1.71 (s, 3H), 1.75 (s, 3H), 2.00-2.21 (m, 4H), 4.21-4.29 (m, 2H), 5.80 (brs, 1H), 7.02 (brs, 1H), 7.18-7.47 (m, 10H), 7.49 (s, 1H); MS Calcd.: 388; Found 389 (M+H).

EXAMPLE 1142
(1R,4S)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl-5-(2-fluorophenyl)-2,7,7-trimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxylate

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1) To a solution of 1 (0.4 g, 1.32 mmol) and DMF (1 drop) in toluene (4 mL) was added SOCl₂(0.31, 2.64 mmol) at room temperature. After stirring at 60° C. 1 h, the solvent was concentrated in vacuo. The residue was diluted with toluene, and borneol (0.3 g, 1.98 mmol) and Et₃N (0.3 g, 2.90 mmol) was added there to. After stirring at 60° C. 1 h, the reaction mixture was washed with 1N HCl and brine, dried over MgSO₄, and concentrated in vacuo. Flash chromatography to give the desired product as oil. To a stirred solution of the oil obtained (90 mg, 0.2 mmol) in AcOEt (2 mL) was added 4M HCl-AcOEt (0.5 mL, 2.0 mmol) at room temperature. The precipitate was collected by filtration to give 2 as HCl salt. MS Calcd.: 440; Found 441 (M+H).

Compounds of Examples 1139-1141 shown in the Table 16, were prepared in a manner similar to that described in Example 1142.

TABLE 161139 embedded image

1-propyl-1-(4- (trifluoromethyl)phenyl)butyl 7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylateMS(ESI, m/z) 514 (M + H)+1140 embedded image

(2R,5S)-2-isopropyl-5- methylcyclohexyl 7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 123-124° C.1141 embedded image

(1R,4S)-1,3,3- trimethylbicyclo[2.2.1]hept-2- yl 2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidine-3-carboxylatemp 149-150° C. HCl salt

Compounds of Examples 868-923 and 1143-1146 shown in the table 6, were prepared from compound of Examples 35 in a manner similar to that described in followed reference 1˜6.

1) Poulan R F., Tartar A L., Deprez B p., Tetrahedron Lett. 2001, 42, 1495.
2) Rigo B., Cauliesz P., Fasseur D., Couturier D., Synthetic Communications 1986, 16, 1665.
3) Carlsen H J., Jorgensen K B., J. Heterocyclic Chem., 1994, 31, 805.
4) Kiryanov A A., Sampson P., Seed J., J. Org. Chem., 2001, 66, 7925.
5) Kelly T R., Lang F R., Tetrahedron Lett., 1995, 36, 5319.

6) Walia J S., Walia A S., Lankin D C., Petterson R C., Singh J., J. Heterocyclic Chem., 1985, 22, 1117.

TABLE 6ExampleStructureNamePhysiological Data868 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- phenylethyl)-1,3,4-oxadiazol- 2-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 414 (M + H)+869 embedded image

7,7-dimethyl-3-(3-(1-methyl-1- phenylethyl)-1,2,4-oxadiazol- 5-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 414 (M + H)+870 embedded image

3-(5-(1-(4-chlorophenyl)-1- methylethyl)-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 449 (M + H)+871 embedded image

3-(5-tert-butyl-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 352 (M + H)+872 embedded image

7,7-dimethyl-5-phenyl-3-(5- phenyl-1,3,4-oxadiazol-2-yl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 372 (M + H)+873 embedded image

7,7-dimethyl-3-(5-methyl- 1,3,4-oxadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 310 (M + H)+874 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- phenylethyl)-1,3,4-thiadiazol- 2-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 430 (M + H)+875 embedded image

7,7-dimethyl-5-phenyl-3-(5- phenyl-1,3-oxazol-2-yl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 371 (M + H)+876 embedded image

7,7-dimethyl-5-phenyl-3-(4- phenyl-1,3-oxazol-2-yl)- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 371 (M + H)+877 embedded image

7,7-dimethyl-3-(4-(1-methyl-1- phenylethyl)-1,3-oxazol-2-yl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 413 (M + H)+888 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- phenylethyl)-1,2,4-oxadiazol- 3-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 414 (M + H)+889 embedded image

3-(5-(1-(4-methoxyphenyl)-1- methylethyl)-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 444 (M + H)+890 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- (2-pyridinyl)ethyl)-1,3,4- oxadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 415 (M + H)+891 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- (4-pyridinyl)ethyl)-1,3,4- oxadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 415 (M + H)+892 embedded image

3-(5-(1-(4-iodophenyl)-1- methylethyl)-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 540 (M + H)+893 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- (3-pyridinyl)ethyl)-1,3,4- oxadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 415 (M + H)+894 embedded image

3-(5-isopropyl-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 338 (M + H)+895 embedded image

3-(5-(4-chlorobenzyl)-1,3,4- oxadiazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo(1,5- a]pyrimidineMS(ESI, m/z) 421 (M + H)+896 embedded image

ethyl 4-(1-(5-(7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-1,3,4- oxadiazol-2-yl)-1- methylethyl)benzoateMS(ESI, m/z) 486 (M + H)+897 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- phenylethyl)-1,3-oxazol-2-yl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 413 (M + H)+898 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- (4-methylphenyl)ethyl)-1,3,4- oxadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 414 (M + H)+899 embedded image

3-(5-(1-(4-methoxyphenyl)-1- methylethyl)-1,3,4-oxadiazol- 2-yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 444 (M + H)+900 embedded image

2-(4-(1-(5-(7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-1,3,4- oxadiazol-2-yl)-1- methylethyl)phenyl)-2-propanolMS(ESI, m/z) 472 (M + H)+901 embedded image

N-((7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)(imino)methyl)-2-methyl-2- phenylpropanamideMS(ESI, m/z) 416 (M + H)+902 embedded image

3-(4,4-dimethyl-6-phenyl-1,4- dihydro-2-pyrimidinyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 412 (M + H)+903 embedded image

7,7-dimethyl-3-(5-(1-methyl-1- (4-methylphenyl)ethyl)-1,3,4- thiadiazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 444 (M + H)+904 embedded image

7,7-dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3- carboximidamideMS(ESI, m/z) 270 (M + H)+905 embedded image

3-(4-(4-fluorophenyl)-1H- imidazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 388 (M + H)+906 embedded image

N-((7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidin-3- yl)(imino)methyl)-2-ethyl-2-(4- methylphenyl)butanamideMS(ESI, m/z) 458 (M + H)+907 embedded image

3-(4,4-dimethyl-6-(4- methylphenyl)-1,4-dihydro-2- pyrimidinyl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 426 (M + H)+908 embedded image

7,7-dimethyl-N-(((1-methyl-1- phenylethyl)amino)carbonyl)- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboximidamideMS(ESI, m/z) 431 (M + H)+909 embedded image

7,7-dimethyl-5-phenyl-N- ((((lS)-1-phenylethyl)- amino)carbonyl)-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidine-3-carboximidamideMS(ESI, m/z) 417 (M + H)+910 embedded image

7,7-dimethyl-3-(1-methyl-5-(1- methyl-1-phenylethyl)-1H- imidazol-2-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 427 (M + H)+911 embedded image

3-(5-(1-ethyl-1-(4- methylphenyl)propyl)-1,3,4- oxadiazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 457 (M + H)+912 embedded image

7,7-dimethyl-3-(3-(1-methyl-1- phenylethyl)-1H-1,2,4-triazol- 5-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 414 (M + H)+913 embedded image

3-(4,4-dimethyl-6-(4- methylphenyl)-1,4,5,6- tetrahydro-2-pyrimidinyl)-7,7- dimethyl-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 428 (M + H)+914 embedded image

7,7-dimethyl-3-(3-(1-methyl-1- (4-methylphenyl)ethyl)-1H- pyrazol-5-yl)-5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 426 (M + H)+915 embedded image

3-(5-(1-ethyl-1-(4- iodophenyl)propyl)-1,3,4- oxadiazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 568 (M + H)+916 embedded image

3-(5-(1-(4-chlorophenyl)-1- ethylpropyl)-1,3,4-oxadiazol-2- yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 476 (M + H)+917 embedded image

ethyl 4-(1-(5-(7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidin-3-yl)-1,3,4- oxadiazol-2-yl)-1- ethylpropyl)benzoateMS(ESI, m/z) 514 (M + H)+918 embedded image

7,7-dimethyl-3-(4-methyl-5-(1- methyl-1-phenylethyl)-4H- 1,2,4-triazol-3-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo]1,5- a]pyrimidineMS(ESI, m/z) 427 (M + H)+919 embedded image

7,7-dimethyl-3-(1-methyl-3-(1- methyl-1-phenylethyl)-1H- 1,2,4-triazol-5-yl)-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 427 (M + H)+920 embedded image

3-(5-(1-ethyl-1-(4- methoxyphenyl)propyl)-1,3,4- oxadiazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 472 (M + H)+921 embedded image

7,7-dimethyl-3-(1-methyl-3-(1- methyl-1-(4-methylphenyl)- ethyl)-1H-pyrazol-5-yl)-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 440 (M + H)+922 embedded image

3-(5-(1-ethyl-1-(4- methylphenyl)propyl)-1,3,4- thiadiazol-2-yl)-7,7-dimethyl-5- phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 472 (M + H)+923 embedded image

3-(5-(1-(4-chlorophenyl)-1- ethylpropyl)-1,3,4-thiadiazol-2- yl)-7,7-dimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 492 (M + H)+1143 embedded image

(5R)-3-(5-(1-ethyl-1-(4- methylphenyl)propyl)-1,3,4- thiadiazol-2-yl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidinemp 132-134° C.1144 embedded image

(5R)-3-(5-(1-ethyl-1-(4- methylphenyl)propyl)-1,3,4- oxadiazol-2-yl)-2,7,7-trimethyl- 5-phenyl-4,5,6,7- tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) 470 (M + H)+1145 embedded image

(5R)-3-(5-(1-ethyl-1- phenylpropyl)-1,3,4-thiadiazol- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidinemp 174-175° C.1146 embedded image

(5R)-3-(5-(1-ethyl-1- phenylpropyl)-1,3,4-oxadiazol- 2-yl)-2,7,7-trimethyl-5-phenyl- 4,5,6,7-tetrahydropyrazolo[1,5- a]pyrimidineMS(ESI, m/z) (M + H)+

Experiment 1

Strategy for cloning of the cDNAs encoding the human CaR

Strategy for cloning of the cDNAs encoding the human CaR is shown below. To amplify the cDNA encoding the N-terminal moiety of the human CaR, the synthetic DNA primers, Cal-U: 5′-AGAGTCGACGCCACCATGGCATTTTATAGCTGCTGCTGG-3′ and Cal-L: 5′-AAATGAGCTCTCGGTTGGTGGCCTTGAC-3′, were constructed. In this case, SalI site was added at the 5′ end of amplified cDNA. To amplify the cDNA encoding the C-terminal moiety of the human CaR, the synthetic DNA primers, Ca2-U: 5′-AAACGAGCTCTCCTACCTCCTCCTCTTC-3′ and Ca2-L: 5′-TCTGCGGCCGCTCCCTAGCCCAGTCTTCTCCTTCC-3′, were constructed. In this case, NotI site was added at the 3′ end of amplified cDNA. PCR was carried out by Hot Start method. The reaction solution of the upper phase was added of 1 pg of the human kidney-derived cDNA (TOYOBO), 0.3 mM dNTPs and 2.5 unit LA Taq DNA polymerase (Takara shuzo co.) and filled up to 30 μl with water and buffer attached to the enzyme. To the reaction solution of the lower phase was added 12.5 μM each of the synthetic primers and 0.5 mM dNTPs and filled up to 20 μl with water and buffer attached to the enzyme. The reaction solution of the upper phase was added on the lower phase covered with an AmpliWax PCR Gem100 (Takara Shuzo Co.). The samples were subject to PCR amplification using a Thermal Cycler (Perkin-Elmer Co.). The amplified cDNAs were confirmed by agarose gel electrophoresis.

Experiment 2

Preparation of CaR-Expression CHO Cells

The PCR products obtained in Experiment 1 were separated by agarose gel electrophoresis. The PCR products were excised and purified from the gel and subcloned into pT7Blue-T vector (Takara Shuzo Co.). The cDNA fragment encoding the N-terminal moiety of the human CaR was released from the subcloned pT7Blue-T vector treated with SalI and SacI. The cDNA fragment encoding the C-terminal moiety of the human CaR was released from the subcloned pT7Blue-T vector treated with SacI and NotI. Using DNA Ligation kit (Takara Shuzo Co.), these fragments were inserted between the site of SalI- and NotI- in the digested pMSRαneo vector. Thus, the pMSRαneo-CaR for animal cell expression was constructed.

Ten μg of the pMSRαneo-CaR was added to the solution containing 8×10⁶CHO-K1 cells, and transfection was carried out using Gene Pulser (0.4 cm cuvette, 0.25 kV, 960 mF) (Bio-Rad Laboratories). The cells were cultured in HamF12 containing 10% fetal calf serum for one day. After passage, the cells were cultured in HamF12 containing 10% fetal and 500 μg/ml Genetisine. The cells were seeded on 96-well plate in 1×10 ³cells/well and transformants, CaR-expressing CHO cells, were selected in the selection medium.

Experiment 3

Selection of the CaR-Expressing CHO Cell Line by Calcium Mobilization Assay

A method for calcium mobilization assay is shown below. The CaR-expressing CHO cells were seeded on a 96-well white plate in 2×10⁴cells/well, followed by cultivation for 48 hours. After washing the cells with Phosphate-Buffered Saline, 100 μl of buffer solution (120 mM NaCl, 22 mM NaHCO₃, 6 mM KCl, 0.2 mM CaCl₂, 1 mM MgCl₂, 5 mM glucose, 5 mM HEPES (pH 7.4)) containing 5 μM FuraPE3AM (Texas Fluorescence Laboratories) was added to the wells and kept at 37° C. for 1 hour. The cells were washed twice with Phosphate-Buffered Saline. After adding 180 μl of the reaction buffer solution (130 mM NaCl, 5.4 mM KCl, 0.2 mM CaCl₂, 0.9 mM MgCl₂, 10 mM glucose, 20 mM HEPES (pH 7.4)) to the wells, 20 μl of 60 mM CaCl₂was added and intracellular calcium concentration were measured with a fluorometric imaging plate reader (FDSS 2000, Hamamatsu photonics). One clone increasing intracellular calcium concentration was selected and used for the following experiment.

Experiment 4

GTPγS Binding Assay

Preparation of membrane fraction is described bellow. The human CaR-expressing CHO cells were inoculated to a F500 flask in 1.8×10⁵cells/flask followed by cultivation for 2 days. The cells were scraped with 10 ml of Phosphate-Buffered Saline containing 0.02% EDTA. After centrifugation (2000 rpm, 10 min) of the cells, the cell pellet was resuspended into 12 ml of homogenate buffer solution (10 mM NaHCO₃, 1 mM EDTA, 1× Protease inhibitor cocktail (pH 7.4)) and homogenized by Polytron™ (20000 rpm, 1 min). The cell debris was removed by centrifugation (2000 rpm, 10 min), and then the CaR-expressing cell membrane fraction was collected by ultracentrifugation (Beckman 70 Ti type rotor, 30000 rpm, 1 hour).

The GTPγS binding activity was measured as follows. Twenty μg of the CaR-expressing cell membrane was incubated with test compounds for 10 min. The assays were carried out at room temperature for an hour in a reaction solution mixture containing 20 mM HEPES (pH.7.4), 100 mM NaCl, 1 mM MgCl₂, 167 μg/ml DTT, 5 μM guanosine 5′-diphosphate, 0.4 nM [³⁵S]-guanosine 5′-(γ-thio) triphosphate ([³⁵S]-GTPγS) and 6 mM CaCl₂. The mixture was filtered through a GF/C filter. After washing fourth with 300 μl of Phosphate-Buffered Saline, the amount of [³⁵S]-GTPγS bound to the filter was measured using a Top-count scintillation counter.

Effects of test compounds on [³⁵S]-GTPγS binding were expressed in percentage terms. This was calculated from the equation [100×(t′-b)]/(t-b) where t′, t and b are values of [³⁵S]-GTPγS binding (dpm), t′ in the presence of 6 mM calcium and the test compound, t in the presence of 6 mM calcium only and b in the absence of both 6 mM calcium and the test compound.

The antagonist dose-dependently decreased [³⁵S]-GTPγS binding in membrane preparation. The agonist dose-dependently increased [³⁵S]-GTPγS binding in membrane preparation.

The results are shown in Table 7.

TABLE 7Ex. No.[³⁵S]-GTP γ S binding (%)318*34 (1 μM)335* 0 (1 μM)310* 0 (1 μM)312*10 (1 μM)436*12 (1 μM)423* 0 (1 μM)111**256 (10 μM)
*antagonist

**agonist

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Calcium receptor modulating compound and use thereof

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