WO2007026215A1

WO2007026215A1 - Pyrazole derivatives as cannabinoid receptor ligands, pharmaceutical compositions containing? them, and processes for their preparation

Info

Publication number: WO2007026215A1
Application number: PCT/IB2006/002355
Authority: WO
Inventors: Mrinalkanti Kundu; Suhas M. Nadkarni; Srinivas Gullapalli; Neelima Khairatkar Joshi; Pallavi V. Karnik
Original assignee: Glenmark Pharmaceuticals S.A.
Priority date: 2005-08-29
Filing date: 2006-08-29
Publication date: 2007-03-08

Abstract

The present invention relates to cannabinoid receptor modulators of general formulas (I) and (II) prodrugs thereof, pharmaceutically acceptable salts thereof, and hydrates and solvates thereof, wherein the meaning of the substituents is as recited in the claims.

Description

PYRAZOLE DERIVATIVES AS CANNABINOID RECEPTOR LIGANDS , PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESSES FOR THEIR PREPARATION

This application claims the benefit of Indian Patent Application No. 1020/MUM/2005, filed on August 29, 2005, and U.S. Provisional Application No. 60/717,546 filed September 14, 2005, both of which are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CBl) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and/or disorders modulated by a cannabinoid receptor (such as pain, neurodegenerative disorders, eating disorders, weight loss or control, and obesity).

BACKGROUND

The endogenous cannabinoid system comprises two main receptors, CBl and CB2, and a number of ligands including anandamide and virodhamine which demonstrate the greatest activity at the cannabinoid receptor (Jonathan A W & Louis J A, Obes Man., 5-19, 2005). Anandamide, which is produced postsynaptically, is the main fatty acid involved in the system. It gains access to the extra cellular space and activates CBl cannabinoid receptors located on presynaptic nerve terminals. This activation causes presynaptic inhibition of γ-aminobutyric acid or glutamate through inhibition of calcium channels, while simultaneously interfering with vesicle release and activating potassium channels.

However, anandamide is prone to rapid enzymatic hydrolysis. This represents a serious drawback in its use as a drug because, inter alia, substances which are susceptible to hydrolytic cleavage may undergo changes in the gastrointestinal tract.

CBl receptors are predominantly located in the brain and other neurons, while CB2 receptors are predominantly located in immune cells. Stimulation of these receptors is known to affect the central and peripheral action on lipid and glucose metabolism in adipose tissue and most notably, helps to regulate food intake, energy balance and nicotine dependence as well as regulate fear and anxiety.

There is evidence suggesting that CBl agonists or antagonists, respectively, increase or decrease the motivation to work for palatable ingesta (Gallate J E and McGregor I S, Psychopharmacology, 142, 302-308, 1999 and Gallate J E, Saharov T, Mallet P E and McGregor I S, 1999, Eur. J. Pharmacol., 370, 233-240, 1999). Cannabinoids appear to directly stimulate eating by actions on appetitive processes, making food stimuli more salient and rapidly inducing eating even in satiated animals (Williams C M and Kirkham TC, Physiol. Behav., 76, 241-250, 2002).

Current data reveals that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of CB2 receptors (Ehrhart J, et. al., J. Neuroinfiammation, 2, 29, 2005). The inflammatory mediators such as nitric oxide, cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease, multiple sclerosis, HIV and dementia.

Compounds capable of modulating the cannabinoid (CB) receptor activity can be used in the treatment of CB receptor mediated syndromes, diseases or disorders which include appetite, metabolism, diabetes, obesity, glaucoma associated intra-ocular pressure, mood disorders, seizures, substance abuse, learning disorders, cognition disorders, memory disorders, organ contraction, muscle spasm, respiratory disorders, locomotor activity disorders, movement disorders, immune disorders, inflammation, cell growth disorders, eye-diseases, allergies and allergic reactions, pain, anxiety, psychotic afflictions, pathological states of brain, gastrointestinal disorders, nausea, vomiting, giddiness, urinary and fertility problems, cardiovascular diseases, neuroinflammatory pathologies, diseases of the central nervous system, neurodegenerative syndromes, diseases and disorders, sleep disorders, dermatological disorders, leukocyte activation- associated disorder, autoimmune diseases, nephrological pathologies, delayed or immediate hypersensitivity, infectious parasitic, and viral and bacterial diseases.

At present, various CB modulators have been characterized as agonists, inverse agonists or antagonists to CBl and/or CB2 receptors. These modulators include naphthaIen-lyl-(4-pentyloxy-naphthalen-l-yl) methanone (SAB-378), 4-(2,4- dichlorophenylamino)-N-(terahydro-pyran-4ylmethyl)-2-trifluoromethyl-benzamide (GW-842166X), N-(l-piρeridinyl)-5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4- methyIpyrazole-3-carboxamide (SRl 41716A), 3-(4-chlorophenyl-N'-(4- chlorophenyl)sulfonyl-N-methyl-4-phenyl-4,5-dihydro-lH-pyrazole-l-carboxamide (SLV-319), and (R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[l,2,3- de]-l,4-benzoxazin-6-yI](l-naphthyl) methanone (WIN 55212-2).

SAB-378 (CBl Agonist) GW-842166X (CB2 Agonist)

SR-141716A SLV-319 (WIN 55212-2) (CBl inverse agonist) (CBl Antagonist)

These modulators have reached advanced stages of clinical trials for the treatment of pain, neurodegenerative disorders, psychotic disorders, neurological syndromes, diseases or disorders, eating disorders, Alzheimer's disease, alcohol dependency, diabetes, obesity and/or smoking cessation.

U.S. Patent Nos. 5,624,941, 6,028,084, and 6,509,367; PCT Publication Nos. WO 98/31227, WO 98/41519, WO 98/43636 and WO 98/43635; and European Publication No. EP 0 658 546 disclose certain substituted pyrazoles having activity against the cannabinoid receptors. U.S. Patent Nos. 6,355,631 and 6,479,479 and PCT Publication Nos. WO 01/64632, WO 01/64633, and WO 01/64634 disclose certain azetidine derivatives, which are cannabinoid antagonists.

Other cannabinoid receptor modulating compounds are disclosed in U.S. Patent Nos. 4,973,587, 5,013,837, 5,081,122, 5,1 12,820, 5,292,736, and 5,532,237, and PCT Publication Nos. WO 97/29079, WO 98/37061, WO 99/02499, WO 00/10967, WO 00/10968, WO 01/58869, WO 01/70700, WO 02/076949, WO 03/026647, WO 03/026648, WO 03/027069, WO 03/027076, WO 03/027114, WO 03/077847, WO 03/088968, WO 04/13120, WO 04 /69837, WO 04/058145, WO 04/2630I₅ WO 04/058744, WO 04/096763 and WO06/030124.

There exists an unmet need for treatment of alcohol abuse. Health risks associated with alcoholism include impaired motor control and decision making, cancer, liver disease, birth defects, heart disease, drug/drug interactions, pancreatitis and interpersonal problems. Studies have suggested that endogenous cannabinoid tone plays a critical role in the control of ethanol intake. The endogenous CBl receptor antagonist SR-141716 A has been shown to block voluntary ethanol intake in rats and mice. (See, Arnone, M., et al., "Selective Inhibition of Sucrose and Ethanol Intake by SR141716, an Antagonist of Central Cannabinoid (CBl) Receptors," Psychopharmacol, 132,104-106 (1997)). For a review, see, Hungund, B. L and B. S. Basavarajappa, "Are Anadamide and Cannabinoid Receptors involved in Ethanol Tolerance? A Review of the Evidence," Alcohol & Alcoholism, 35(2) 126-133, 2000.

Current treatments for alcohol abuse or dependence generally suffer from non- compliance or potential hepatotoxicity. There is an unmet need for more effective treatments of alcohol abuse/dependence.

There also still exists a need for safer and more effective therapeutic treatments for diseases, conditions and/or disorders modulated by cannabinoid receptors(such as pain_?obesity), including those modulated by CBl or CB2 receptors.

U.S. Patent No. 4,134,987 discloses fungicidal compositions containing pyrazole derivatives as active ingredients and methods of combating plant fungal disease with them. In particular the patent discloses pyrazole derivatives of the formula:

(A) where R¹ or R² is -C(=X)NHR^S and X is O or S. When R² or R⁴ is a hydroxy or mercapto, the compound may exist in a tautomeric form of the formula B or C shown below

R₃ R₃

(B) . (C)

U.S. Patent Publication No. 2003/0207874 discloses gastrin and cholecystokinin receptor ligands of formulae D, E, and F shown below

Summary of Invention

The present invention relates to cannabinoid receptor modulators of general formulas (I) and (II)

(I) (H) prodrugs thereof, pharmaceutically acceptable salts thereof, and hydrates and solvates thereof, wherein

A and B are independently substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted cycloalkyl; Z is -(C=O)-, -CH₂-, or CH; D is -O- or -NR¹; the dotted line in the 5 membered ring represents an optional bond; R¹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl or a protecting group;

R² and R³ are independently hydrogen or R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O);

R⁴ and R⁵ may be the same or different and are independently hydrogen, -0R^a, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -NR^aR^b, -C(=L)-R^a, -C(O)O-R⁸, -C(0)NR^aR^b, -S(O)_m-R^a, -S(O)_n,- NR^aR^b, or a protecting group or R⁴ and R⁵ may be joined together along with the nitrogen atom to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^aor S; each occurrence of R^a and R^b may be the same or different and are independently hydrogen, -OR^C, -SR^C, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -C(=L)-R^C, -C(O)O-R⁰, -C(0)NR^cR^d, - S(O)_m-R^c, -S(0)_m-NR^cR^d, -NR^cR^d, or a protecting group, or R^a and R^b may be joined together along with the nitrogen atom to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR⁰ or S; each occurrence of R^c and R^d may be the same or different and are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, or a substituted or unsubstituted heteroarylalkyl or a protecting group, or R^c and R^d may be joined together to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^eor S; each occurrence of R^e is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, or a protecting group; p is 0, 1 or 2; q is 0, 1 or 2; each occurrence of m is independently 0, 1 or 2; and each occurrence of L is independently O, S, or NR⁰ , where R^c is the same as defined above.

Preferred compounds include those of formula (II)

(H) prodrugs thereof, pharmaceutically acceptable salts thereof, and hydrates and solvates thereof, wherein A, B, Z, R²-R⁵, p and q are as defined above.

Further preferred is a compound of formula (II) where Z is -CH₂.

Further preferred is a compound of formula (II) where Z is -CH- and the dotted line in the 5-membered ring represents a bond.

Further preferred is a compound of formula (II) where R² is hydrogen.

Further preferred is a compound of formula (II) where R³ is hydrogen.

Further preferred is a compound of formula (II) where R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O).

Further preferred is a compound of formula (II) where R⁴ is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group.

Further preferred is a compound of formula (II) where R⁴ is n-butyl.

Further preferred is a compound of formula (II) where R⁴ is n-pentyl.

Further preferred is a compound of formula (II) where R⁴ is cyclohexyl.

Further preferred is a compound of formula (II) where R⁴ is 4-hydroxy cyclohexyl.

Further preferred is a compound of formula (II) where R⁴ is 4-methyl sulphanyl phenyl.

Further preferred is a compound of formula (II) where R⁴ is methyl sulfonyl phenyl or 4-methylsulfonylphen-l-yl.

Further preferred is a compound of formula (II) where R⁴ is 4-methylphenyl.

Further preferred is a compound of formula (II) where R⁴ is 4-methoxyphenyI.

Further preferred is a compound of formula (II) where R⁴ is 4-chlorophenyl.

Further preferred is a compound of formula (II) where R⁴ is 4-bromophenyl.

Further preferred is a compound of formula (II) where R⁴ is 3 -fluorophenyl.

Further preferred is a compound of formula (II) where R⁴ is 4-fluorophenyl.

Further preferred is a compound of formula (II) where R⁴ is 3,4-difluorophenyl.

Further preferred is a compound of formula (II) where R is 3,5-difluorophenyl.

Further preferred is a compound of formula (II) where R⁴ is 4- trifluoromethylphenyl .

Further preferred is a compound of formula (II) where R⁴ is 4-chlorobenzyl.

Further preferred is a compound of formula (II) where R⁴ is 1-adamantyl. Further preferred is a compound of formula (II) where R⁴ is 3-hydroxyadaman

-1-yl.

Further preferred is a compound of formula (II) where R⁴ is (2R)-(6,6- dimethyl-bicyclo[3.1.1]hept-3-yl-methyl).

Further preferred is a compound of formula (II) where R⁴ is (5S,lR,2R,3R)-2,6,6- trimethylbicyclo[3.1. l]hept-3-yl.

Further preferred is a compound of formula (II) where R⁴ is piperidin-1-yl.

Further preferred is a compound of formula (II) where R⁴ is morpholinyl.

Further preferred is a compound of formula (II) where R⁴ is 6-chloro-pyridyl-3-yl.

Further preferred is a compound of formula (II) where R⁴ is 4-cyanophenyl.

Further preferred is a compound of formula (II) where R⁴ is 4-hydroxyphenyl.

Further preferred is a compound of formula (II) where R⁴ is 1,1-dimethylethyl.

Further preferred is a compound of formula (II) where R⁴ is -NR^aR^b wherein R^a is phenyl and R^b is hydrogen.

Further preferred is a compound of formula (II) where R⁴ is -NR^aR^b wherein R^a is

4-chlorophenyl and R^b is hydrogen.

2-fluorophenyl and R^b is hydrogen.

Further preferred is a compound of formula (II) where R⁵ is hydrogen.

Further preferred is a compound of formula (II) where R⁴ and R⁵ are joined together along with the nitrogen atom to which they are attached to form an optionally substituted 3 to 7 membered saturated cyclic ring, and which optionally includes at least two heteroatoms selected from O, NR^cand S.

Further preferred is a compound of formula (II) where -NR⁴R⁵ is [4-(4- chlorophenyl) piperizin-1-yl].

Further preferred is a compound of formula (II) where p=l.

Further preferred is a compound of formula (II) where q=0.

Further preferred is a compound of formula (II) where A and B are independently selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted alkyl.

Further preferred is a compound of formula (II) where A is hexyl.

Further preferred is a compound of formula (II) where A is cyclohexyl.

Further preferred is a compound of formula (H) where A is phenyl. Further preferred is a compound of formula (II) where A is 2-chlorophenyI.

Further preferred is a compound of formula (II) where A is 3-chlorophenyl.

Further preferred is a compound of formula (II) where A is 4-chlorophenyl.

Further preferred is a compound of formula (II) where A is 2,4-dichlorophenyI.

Further preferred is a compound of formula (II) where A is 2,6-dichlorophenyl.

Further preferred is a compound of formula (II) where A is 2-bromophenyl.

Further preferred is a compound of formula (II) where A is 4-bromophenyl.

Further preferred is a compound of formula (II) where A is 3 -fluorophenyl.

Further preferred is a compound of formula (II) where A is 4-fluorophenyl.

Further preferred is a compound of formula (II) where A is 2,6-difluorophenyl.

Further preferred is a compound of formula (II) where A is 2-trifluoromethyl phenyl.

Further preferred is a compound of formula (II) where A is 3-trifluoromethyl phenyl.

Further preferred is a compound of formula (II) where A is 4-trifluoromethyl phenyl.

Further preferred is a compound of formula (II) where A is 6-chloropyridin-3-yl.

Further preferred is a compound of formula (II) where B is 2,4-dichlorophenyl.

Further preferred is a compound of formula (II) where B is 4-chlorophenyl.

Further preferred is a compound of formula (II) where B is 4-bromophenyl.

Further preferred is a compound of formula (II) where B is 2,4-difluorophenyl.

Further preferred is a compound of formula (II) where B is 3-trifluoromethyl phenyl.

Further preferred is a compound of formula (II) where B is 4-trifluoromethyl phenyl.

Further preferred is a compound of formula (II) where B 2,5-dichlorophenyl.

Representative compounds of the present invention include those specified below and pharmaceutically acceptable salts thereof. The present invention should not be construed to be limited to them.

1. l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantyl-1-ylamide;

2. l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid piperidine-1-ylamide; 3. l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -(4-methylsulfanylphenyl)amide;

4. l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4carboxylic acid morpholin-4-yI-amide;

5. l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methanesulfonylphenyl)-amide;

6. l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid cyclohexyl amide;

7. l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-4-chlorobenzylamide;

8. l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4-hydroxycyclohexyl)-amide;

9. N4-[(2R)-(6,6-diemthyl-bicyclo[3.1. l]hept-3-ylmethyl)- 1 -Benzyl-2-(2,4- dichlorophenyl)-3 -oxo-2, 3 -dihydro- 1 H-4-pyrazole carboxam ide;

10. 1 -Benzyl-4-[4-(4-chlorophenyl)-piperazine- 1 -carbonyl]-2-(2,4-dichlorophenyl)- 1 ,2-dihydro-pyrazole-3 -one;

1 Oa.1 -Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid N'-(4-chloro-phenyl)-hydrazide;

11. l-(3-Chlorbenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2.3-dihydro-lH-pyrazole-4- carboxylic acid-(4-methylsulfonyl-phenyl)-amide;

12. l-(3-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carbaxolic acid-(4-raethylsulfanylphenyI)-amide;

13. 1 -(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid-(4-chlorophenyl)-amide;

14. 1 -(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid-(3,4-difluorophenyl)-araide;

15. 1 -(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid-(4-methanesulfonylphenyl)-amide;

16. l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-trifluoromethylphenyl)-amide;

17. N4-(4-methylsulfanylphenyl)-l-(4-chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo- 2,3-dihydro-lH-4-pyrazolecarboxamide;

18. l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid adamantan-1-yl amide; 19. 2-(2,4-Dichlorophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-fluorophenyl)-amide;

19a.1 -(4-Chlorophenyl)-2-(2,4-Dichlorophenyl)-3 -oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid (4-cyanophenyl)-amide;

19b.1 -(4-Chlorobenzyl)-2-(2,4-Dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid (4-hydroxyphenyl)-amide;

20. l-(2-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid (4-methanesulfanylphenyl)-amide;

21. l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid (4-fluoro-phenyl)-amide;

22. l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid(adamantan-l-yl)-amide;

23. l-(2-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid cyclohexyl amide;

24. 2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (3-hydroxy-adamantan-l-yl)-amide;

25. 2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid N'-phenyl-hydrazide;

26. N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(2,4- dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH~4- pyrazolecarboxamide;

27. 2-(2,4-DichlorophenyI)- 1 -(3-fluorobenzyl)-3~oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid -(4-trifluoromethyl phenyl)-amide;

28. 2-(2,4-Dichlorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsuIphonyl phenyl)-amide;

29. 2-(2,4-Dichlorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

30. 2-(2,4-Dichlorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide;

31. 2-(2,4-Dichlorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

32. 2-(2₅4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid - (4-chlorophenyl)-amide; 33. 2-(2,4-DichIorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid adamantan-1-ylamide;

34. 2-(2,4-DichIorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-4-methylsulfanylphenyl amide;

35. N4-[(2R)-2-(2,4-Dichlorophenyl)- 1 -(3 -fluorobenzyl)-3 -oxo-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid-(6,6-dimethylbicyclo[3.1. l]hept-3-ylmethyl)-amide;

36. l-CyclohexylmethyI-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-methylsulfanylphenyl)-amide;

37. l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-niethoxyphenyl)-amide;

38. 1 -(6-Chloro-pyridin-3ylmethyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid-{(lR,2R,3R,5S)-2,6,6-trimethyl-bicyclo-[3.1.1] -hept- 3-ylamide};

39. 2-(2,4-Dichloroρhenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid N'-(2-fluoro-phenyl)-hydrazide;

40. 2-(2,4-Dichlorophenyl)- 1 -cyclohexylmethyl-3 -oxo-2,3 -dihydro- 1 H-4-ρyrazole carboxylic acid cyclohexyl amide;

40a.2-(2,4-Dichlorophenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid (3-hydroxy-adamantan-l-yl)-amide;

41. N4-(l-adamantyl)-l-(2-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

42. N4-(l-adamantyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

43. N4-(4-fluorophenyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

44. N4-(3 -hydroxy- 1 -adamantyl)- 1 -(3 -chlorobenzyl)-2-(2, 5 -dichlorophenyl)-4- pyrazolidine carboxamide;

45. N4-(p-tolyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4- pyrazolidinecarboxamide;

46. N4-(4-methoxyphenyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

47. N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-l-benzyl-2-(4- chlorophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxamide; 48. l-Benzyl-2-(4-chloroρhenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid morpholin-4-yl-amide;

49. l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4-carboxylic acid adamantyl- 1 -yl-amide;

50. l-BenzyI-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - 4-chlorobenzyl amide;

51. l-Benzyl^^-chloropheny^-S-oxo^^-dihydro-lH-pyrazole^-carboxylic acid cyclohexyl amide;

52. 1 -Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -(4-methylsulfanylphenyl)amide;

53. l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxyIic acid - N' -(4-chlorophenyl)hydrazide;

54. N4-[(2R)-(6,6-diemthyl-bicyclo[3.1. l]hept-3-ylmethyl)-l -Benzyl-2-(4- chloropheny l)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide ;

55. 1 -Benzyl-4-[4-(4-chlorophenyl)-piperazine- 1 -carbonyl]-2-(4-chlorophenyl)- 1 ,2- dihydro-pyrazole-3-one;

56. N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chIorophenyl)-l- (3~chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

57. N4-(4-methoxyphenyl) -l-(3-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3- dihydro-lH-4-pyrazolecarboxamide;

58. 2-(4-Chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid -p-tolylamide;

59. N-4-2-di-(4-chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxamide;

60. N4-(l -adamantyl) -l-(3-chlorobenzyl)-2-(4-chlorophenyl) -3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide;

61.2-(4-Chlorophenyl)-l-(2,4-Dichlorobenzyl)-3-oxo-2,3-dihydro-l-H-pyrazole-4- carboxylic acid -(4-chlorophenyl)amide;

61 a.2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-l H-4-pyrazole carboxylic acid (4-hydroxyphenyl) amide;

61b.2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid pentyl amide;

61 c.2-(4-Chlorophenyl)- 1 ~(2,4-dichlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid t-butyl amide; 62. 2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4- carbaxolic acid adamantan-1-ylamide;

63. 2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid-(4-fluorophenyl)-amide;

64. 2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid cyclohexyl-amide;

65. 2-(4-Chlorophenyl)-l-(2,4-dichlobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-methoxyphenyl)~amide;

66. 2-(4-Chlorophenyl)-l-(2,4-dichIorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(3-hydroxyadamantan)-l-yl-amide;

67. N4-(4-methoxyphenyl) -l-(4-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide;

68. N-4,2-di-(4-chlorophenyl)- 1 -(4-chlorobenzy l)-3 -oxo-2, 3 -dihydro- 1 H-4-pyrazole carboxamide;

69. N4-(l-adamantyl) -l-(4-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

70. 2-(4-Chlorophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-bromophenyl)-amide;

71. N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chlorophenyl)-l- (4-chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

72. 2-(4-chlorophenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)-2,6,6- trimethylbicyclo[3.1.1]hept-3-ylamino]yl}-2,3-dihydro-lH-3-pyrazolone;

73. 2-(4-Chlorophenyl)- 1 -(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4- pyrazolecarboxylic acid (3,5-difluorophenyl)-amide;

74.2-(4-ChlorophenyI)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazoIe carboxylic acid (4-chlorophenyl)-amide;

75.2-(4-ChIorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2₃3-dihydro-lH-4-pyrazole carboxylic acid adamantan-1-ylamide;

76. N4-(3-hydroxy-l-adamantyl)-2-(4-chIorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide;

77. N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chIorophenyl)-l- (3-fluorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

78. N4-[(2R)-6,6-dimethylbicyclo[3.1.1]hept-3-ylmethyI]-2-(4-chlorophenyl)-l-(3- flυorobenzyl) -3-oxo-2,3-dihydro-l H-4-pyrazolecarboxamide; 79. N4-(4-methylsulfanylphenyl)-2-(4-chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide;

80. l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid piperidin-1- ylamide;

81. l~Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid adamantan-1- ylamide;

82. l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid morpholin-4- ylamide;

83. 1 ~Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid-4-chlorobenzyl amide;

84. l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid cyclohexyl amide;

85. l-Benzyl-2-(2,4-dichlorophenyl)-pyrazoIidine-4-carboxylic acid-(4- methylsulfanyl phenyl)amide;

86. N4-[(5S, IR, 2R, 3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3~yI]-l-(2,4- dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidinecarboxamide;

87. N4-[(2R)-6-6-dimethylbicyclo[3.1.1]hept-3-yl methyl]-l-(2,4-dichlorophenyl)-2- (3-fluoro benzyl)-4-pyrazolidine carboxamide;

88. N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidine carboxamide;

89. N4-(4-trifluoromethylphenyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4- pyrazolidine carboxamide;

90. N4-(4-methylsulphanylphenyl)- 1 -(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4- pyrazolidine carboxamide;

91. N4-(4-chlorophenyl)- 1 -(2,4-dichlorophenyl)-2-(3 -fluorobenzy I)-4-pyrazolidine carboxamide;

92. N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide;

93. N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-l-(2,4-dichloro phenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide;

93a.N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4- dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide;

93b.N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4- dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide; 94. N4-(4-methylsulphanylphenyl)- 1 -(2,4-dichIorophenyl)-2-(4-fluorobenzyl)-4- pyrazolidine carboxamide;

95. N4-(4-chloroρhenyl)- 1 -(2,4-dichloroρhenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide;

96. 2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4- carboxylic acid adamantan-1-yl amide;

97. 2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid - (4-chlorophenyl)-amide;

98. 2-(4-Bromoρhenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid adamantan-1-yl amide;

99. 2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-methylsulfanyl phenyl)-amide;

100. 2-(4-Bromophenyl)-l-(2,6-Difluorobenzyl)-4-{(lR,2R,3R,5S)-2,6,6- trimethylbicyclo-tS.ljlJ -hept-S-ylaminoJ-ylj^jS-dihydro-lH-S-pyrazolone;

101. 2-(4-Bromophenyl)-l -(2,6-difluorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid adamantan-1-yl amide;

102. 2-(4-bromophenyl)- 1 -(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid-(3-fluorophenyl)-amide;

103. 2-(4-bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(4-fluorophenyl)-amide;

104. 2-(4-Bromophenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)~2,6,6- trimethylbicyclo[3.1. l]hept-3-ylamino]yl}-2,3-dihydro-lH-3-pyrazolone;

105. 2-(4-Bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid adamantan-1-yl amide;

106. 2-(4-Bromophenyl)- 1 -(3-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxyl i c acid-(4-methoxyphenyl)-am ide;

107. 2-(4-Bromophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid adamantan-1-yl amide;

108. N4-cyclohexyl-2-(4-bromophenyl)-l-(2,4-dichlorobeπzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

109. N4-(4-chlorophenyl)-l-(4-bromobenzyl)-2-(4-bromophenyl)-3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide;

110. N4-(l-adamantyI) -l-(4-bromobenzyl)-2-(4-bromophenyl) -3-oxo-2,3-dihydro- lH-4-pyrazolecarboxamide; 111. N4-(4-fluorophenyl) -2-(4-bromophenyl) -l-(4-chlorobenzyl) -3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide;

112. N4-(4-methylsulfanylphenyl)-2-(4-bromophenyl)-l-(4-chlorobenzyl)-3-oxo- 2,3-dihydro-lH-4-pyrazolecarboxamide;

113. N4-(l-adamantyl) -2-(4-bromophenyl) -l-(4-chlorobenzyl) ~3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

1 14. 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-l H-4-pyrazole carboxylic acid (4-chlorophenyl)-amide;

115. 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (3,5-difluorophenyl)-amide;

116. 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (4-fluorophenyl)-amide;

117. 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (6-chloropyridin-3-yl)-amide;

118. N4-[(5S, lR,2R,3R)-2,6,6-trimethylbicyclo[3.1. l]hept-3-yl]-2-(4-bromophenyl)- l-(2-chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazoIecarboxamide;

119. 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide;

120. 2-(4-Bromophenyl)- 1 -(2-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4- pyrazolecarboxylic acid adamantan-1-ylamide;

121. 2-(4-Bromoρhenyl)- 1 -(2-chlorobenzyl)-3-oxo-2,3 -dihydro-1 H-4- pyrazolecarboxylic acid cyclohexyl amide;

122. 2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid adamantan-1-yl amide;

123. N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]- l-(2-bromobenzyl) -2-(4-bromophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

124. 2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4- pyrazolecarboxylic acid cyclohexyl amide;

125. 2-(4-Bromoρhenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid butyl amide;

126. 2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid piperidin-1-yl amide;

127. 2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide; 128. 2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxylic acid (4-fluorophenyl)-amide;

129. 2-(4-bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylicacid adamantan-1-yl amide;

130. 2-(4-Bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylicacid piperidin-1-yl amide;

131. 2-(4-Bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4-fluorophenyl)-amide;

132. 2-(4-Bromophenyl)-l-hexyl-3-oxo-2, 3-dihydro-lH-4-pyrazolecarboxylic acid (4-methylsulphanyl phenyl)-amide;

133. 2-(2,4-Difluorophenyl)- 1 -(4-trifluoromethylbenzyl)-3 -oxo-2,3-dihydro- 1 H-4- pyrazole carboxylic acid --(4-methylsulphonyl phenyl)-amide;

134. 2-(2,4-Difluorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH~4- pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

135. 2-(2,4-Difluorophenyl)-l-(3-trifluoromethylbenzyI)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide;

136. 2-(2,4-Difluorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

137. N4-(3-hydroxy-l-adamantyl)-l-(3-chlorobenzyl)-2-(3-triflouromethylphenyl)- 4-ρyrazolidinecarboxamide;

138. N4-(4-methoxyphenyl)- 1 -(3-chloro-benzyl)-2-(3-trifluoromethyl-phenyl)-4- pyrazolidinecarboxamide;

139. 2-(4-Trifluoromethylρhenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid adamantan-1-yl amide;

140. 2-(4-Trifluoromethylphenyl)- 1 -(2-trifluoromethylbenzyl)-3-oxo-2,3-dihydro- lH-4-pyrazole carboxylic acid adamantan-1-yl amide;

141. 2-(4-Trifluoromethylphenyl)-l-(2,4-dichloromethylbenzyl)-3-oxo-2,3-dihydro- lH-4-pyrazole carboxylic acid adamantan-1-yl amide;

142. 2-(4-Trifluoromethylphenyl)-l-(2-chloromethylbenzyl)-3-oxo-2,3-dihydro-lH- 4-pyrazole carboxylic acid adamantan-1-yl amide;

143. N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2(4trifluoromethyl- phenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide; and pharmaceutically acceptable salts thereof. The present invention also provides a pharmaceutical composition comprising at least one compound of the present invention and a pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the pharmaceutical composition comprises a therapeutically effective amount of the compound(s) of the present invention. The compound of the present invention may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container.

The compounds and pharmaceutical compositions of the present invention are useful in the treatment of diseases, conditions and/or disorders modulated by cannabinoid CBl receptor antagonists or inverse agonists.

The present invention further provides a method of treating a disease, condition and/or disorder modulated by cannabinoid CB 1 receptor antagonists or inverse agonists in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound or a pharmaceutical composition of the present invention.

Detailed Description of the Invention Definitions

The term "aryl" refers to aromatic radicals having 6 to 14 carbon atoms such as phenyl, naphthyl, tetrahydronapthyl, indanyl, and biphenyl.

The term "arylalkyl" refers to an aryl group as defined above directly bonded to an alkyl group as defined above, e.g., -CH₂CeH₅ and -C₂HsCeHs.

The term "heterocyclic ring" refers to a stable 3- to 15-membered ring radical which consists of carbon atoms and from one to five heteroatoms selected from nitrogen, phosphorus, oxygen and sulfur. For purposes of this invention, the heterocyclic ring radical may be a monocyclic, bicyclic or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quaternized; and the ring radical may be partially or fully saturated (i.e., heterocyclic or heteroaryl). Examples of such heterocyclic ring radicals include, but are not limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofurnyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl, naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl, tetrahydroisoυinolyl, piperidinyl, piperazinyl, 2- oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4- piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl, oxasolidinyl, triazolyl, indanyl, isoxazolyl, isoxasolidinyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl, isoquinolyl, decahydroisoquinolyl, benziraidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzooxazolyl, ftiryl, tetrahydrofurtyl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, dioxaphospholanyl, oxadiazolyl, chromanyl, and isochromanyl. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

The term "heteroaryl" refers to an aromatic heterocyclic ring radical. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

The term "heteroarylalkyl" refers to a heteroaryl ring radical directly bonded to an alkyl group. The heteroarylalkyl radical may be attached to the main structure at any carbon atom from the alkyl group that results in the creation of a stable structure.

The term "heterocyclyl" refers to a heterocyclic ring radical as defined above. The heterocyclyl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure.

The term "heterocyclylalkyl" refers to a heterocyclic ring radical directly bonded to an alkyl group. The heterocyclylalkyl radical may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure.

The term "alkyl" refers to a saturated straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms having from one to eight carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, and 1,1-dimethylethyl (t- butyl).

The term "alkenyl" refers to an aliphatic hydrocarbon group containing a carbon- carbon double bond and which may be a straight or branched chain having 2 to about 10 carbon atoms, e.g., ethenyl, 1-propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl-l- propenyl, 1-butenyl, and 2-butenyl. The term "alkynyl" refers to a straight or branched chain hydrocarbyl radical having at least one carbon-carbon triple bond, and having 2 to about 12 carbon atoms (with radicals having 2 to about 10 carbon atoms being preferred), e.g., ethynyl, propynyl, and butynyl.

The term "alkoxy" denotes an alkyl group attached via an oxygen linkage to the rest of the molecule. Representative examples of such groups are -OCH₃ and -OC₂H₅.

The term "cycloalkyl" denotes a non-aromatic mono or multicyclic ring system of 3 to about 12 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of multicyclic cycloalkyl groups include, but are not limited to, perhydronapththyl, adamantyl and norbornyl groups, bridged cyclic groups or sprirobicyclic groups, e.g., sprio (4,4) non-2 -yl.

The term "cycloalkylalkyl" refers to a cyclic ring-containing radical, having 3 to about 8 carbon atoms, directly attached to an alkyl group. The cycloalkylalkyl group may be attached to the main structure at any carbon atom in the alkyl group that results in the creation of a stable structure. Non-limiting examples of such groups include cyclopropylmethyl, cyclobutylethyl, and cyclopentylethyl.

The term "cycloalkylaryl" refers to a cyclic ring-containing radical, having 3 to about 8 carbon atoms, directly attached to an aryl group Non-limiting examples of such groups include phenylcyclopropyl, phenylcylobutyl and phenylcyclopentyl.

The term "cycloalkenyl" refers to a cyclic ring-containing radical having 3 to about 8 carbon atoms with at least one carbon- carbon double bond, such as cyclopropenyl, cyclobutenyl, and cyclopentenyl.

Unless otherwise specified, the term "substituted" as used herein refers to substitution with any one or any combination of the following substituents: hydroxy, halogen, carboxyl, cyano, nitro, oxo (=0), thio (=S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstiuted guanidine, -COOR_x, -C(O)R_x, -C(S)R_x, -C(O)NR_xRy, - C(O)ONR_xRy, -NR_xCONRyR₂, -N(R_x)SORy, -N(R_x)SO₂Ry, -(=N-N(R_x)R_y), - NR_xC(O)OR_y, -NR_xRy, -NR_xC(0)R_y, -NR_xC(S)Ry₅ -NR_xC(S)NR_yR_z, -SONR_xR_y, - SO₂NR_xRy, -OR_x, -OR_xC(O)NRyR₂, -OR_xC(O)ORy, -OC(O)R_x, -OC(O)NR_xRy₅ - R_xNRyC(O)R₂, -R_x0R_y, -R_xC(O)ORy, -R_xC(O)NR_yR₂, -R_xC(O)Ry, -R_xOC(O)R_y, -SR_x, - SOR_x, -SO₂R_x, and -ONO₂, wherein R_x, R_y and R₂ are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted aϊkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted heterocyclylalkyl ring, substituted or unsubstituted heteroarylalkyl, or substituted or unsubstituted heterocyclic ring. According to one embodiment, the substituents in the aforementioned "substituted" groups cannot be further substituted. For example, when the substituent on "substituted alkyl" is "substituted aryl" the substituent on "substituted aryl" cannot be "substituted alkenyl".

The term "protecting group" or "PG" refers to a substituent that is employed to block or protect a particular functionality. Other functional groups on the compound may remain reactive. For example, an "amino-protecting group" is a substituent attached to an amino group that blocks or protects the amino functionality in the compound. Suitable amino-protecting groups include, but are not limited to, acetyl, trifluoroacetyl, t- butoxycarbonyl (BOC), benzyloxycarbonyl (CBz) and 9-fluorenylmethylenoxycarbonyl (Fmoc). Similarly, a "hydroxy-protecting group" refers to a substituent of a hydroxy group that blocks or protects the hydroxy functionality. Suitable hydroxy-protecting groups include, but are not limited to, acetyl and silyl. A "carboxy-protecting group" refers to a substituent of the carboxy group that blocks or protects the carboxy functionality. Suitable carboxy-protecting groups include, but are not limited to, - CH₂CH₂SO₂Ph, cyanoethyl, 2-(trimethylsilyl)ethyl, 2-(trimethylsilyl)ethoxymethyl, 2-(p- toluenesulfonyl)ethyl, 2-(p-nitrophenylsulfenyl)ethyl, 2-(diphenylphosphino)-ethyl, and nitroethyl. For a general description of protecting groups and their use, see T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, New York, 1991.

The term "cannabinoid receptor" refers to any one of the known or heretofore unknown subtypes of the class of cannabinoid receptors, including CBl and/or CB2 receptors, that may be bound by a cannabinoid modulator compound of the present invention.

The term "modulator" further refers to the use of a compound of the invention as a CB (e.g., CBl and/or CB2) receptor agonist, partial agonist, antagonist or inverse-agonist. The term "treating" or "treatment" of a state, disorder or condition includes:

(1) Preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition;

(2) Inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof; or

(3) Relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.

The benefit to a subject to be treated is either statistically significant or at least perceptible to the subject or to the physician.

The term "subject" includes mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife).

A "therapeutically effective amount" means the amount of a compound that, when administered to a subject for treating a state, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the subject to be treated.

Pharmaceutically acceptable salts forming part of this invention include salts derived from inorganic bases (such as Li, Na, K, Ca, Mg, Fe, Cu, Zn, and Mn), salts of organic bases (such as N,N'-diacetylethylenediamine, glucamine, triethylamine, choline, hydroxide, dicyclohexylamine, metformin, benzylamine, trialkylamine, and thiamine), salts of chiral bases (such as alkylphenylamine, glycinol, and phenyl glycinol), salts of natural amino acids (such as glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, proline, hydroxy proline, histidine, ornithine, lysine, arginine, and serine), salts of non-natural amino acids (such as D-isomers or substituted amino acids), salts of guanidine, salts of substituted guanidine (wherein the substituents are selected from nitro, amino, alkyl, alkenyl, or alkynyl), ammonium salts, substituted ammonium salts, and aluminum salts. Other pharmaceutically acceptable salts include acid addition salts (where appropriate) such as sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates (such as trifluoroacetate), tartrates, maleates, citrates, fumarates, succinates, palmoates, methanesulphonates, benzoates, salicylates, benzenesulfonates, ascorbates, glycerophosphates, and ketoglutarates. Yet other pharmaceutically acceptable salts include, but are not limited to, quaternary ammonium salts of the compounds of invention with alkyl halides or alkyl sulphates (such as MeI or (Me)₂SO₄).

Pharmaceutically acceptable solvates includes hydrates and other solvents of crystallization (such as alcohols). The compounds of the present invention may form solvates with standard low molecular weight solvents by methods known in the art.

Pharmaceutical Compositions

The pharmaceutical composition of the present invention comprises at least one compound of the present invention and a pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Preferably, the pharmaceutical composition comprises a therapeutically effective amount of the compound(s) of the present invention. The compound of the present invention may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container.

Examples of suitable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethyl cellulose and polyvinylpyrrolidone.

The carrier or diluent may include a sustained release material, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax.

The pharmaceutical composition may also include one or more pharmaceutically acceptable auxiliary agents, wetting agents, emulsifying agents, suspending agents, preserving agents, salts for influencing oxmetic pressure, buffers, sweetening agents, flavoring agents, colorants, or any combination of the foregoing. The pharmaceutical composition of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the subject by employing methods known in the art.

The pharmaceutical compositions of the present invention may be prepared by conventional techniques, e.g., as described in Remington: The Science and Practice of Pharmacy. 20^th Ed., 2003 (Lippincott Williams & Wilkins). For example, the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of an ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container, for example, in a sachet.

The pharmaceutical compositions may be in conventional forms, for example, capsules, tablets, aerosols, solutions, suspensions or products for topical application.

The route of administration may be any route which effectively transports the active compound of the invention to the appropriate or desired site of action. Suitable routes of administration include, but are not limited to, oral, nasal, pulmonary, buccal, subdermal, intradermal, transdermal, parenteral, rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic (such as with an ophthalmic solution) or topical (such as with a topical ointment). The oral route is preferred.

Solid oral formulations include, but are not limited to, tablets, capsules (soft or hard gelatin), dragees (containing the active ingredient in powder or pellet form), troches and lozenges. Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, cornstarch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.

A typical tablet that may be prepared by conventional tabletting techniques may contain: (1) Core: Active compound (as free compound or salt thereof), 250 mg colloidal silicon dioxide (Aerosil®), 1.5 mg macrocrystalline cellulose (Avicel®), 70 mg modified cellulose gum (Ac-Di-Sol®), and 7.5 mg magnesium stearate; (2) Coating: HPMC, approx. 9 mg Mywacett 9-40 T and approx. 0.9 mg acylated monoglyceride

Liquid formulations include, but are not limited to, syrups, emulsions, soft gelatin and sterile injectable liquids, such as aqueous or non-aqueous liquid suspensions or solutions.

For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. Methods of Treatment

The present invention provides compounds and pharmaceutical formulations thereof that are useful in the treatment, amelioration, and/or prevention of diseases, conditions and/or disorders modulated by a cannabinoid (CB) receptor, especially those modulated by the CBl or CB2 receptor including those discussed below.

The present invention further provides a method of treating a disease, condition and/or disorder modulated by a cannabinoid receptor (CB), and in particular the CBl or CB2 receptor, in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound or a pharmaceutical composition of the present invention.

Diseases, conditions, and/or disorders that are modulated by a CB receptor, include, but are not limited to, appetite disorders, metabolism disorders, catabolism disorders, ophthalmic diseases, diabetes, obesity, social related disorders, mood disorders, seizures, substance abuse, learning disorders, cognition disorders, memory disorders, organ contraction, muscle spasm, respiratory disorders, locomotor activity disorders, movement disorders, kidney dysfunction, immune disorders (such as autoimmune disorders), inflammation, cell growth, pain (such as neuropathic pain) and neurodegenerative related syndromes, disorders and diseases.

Appetite related syndromes, disorders or diseases include, but are not limited to, obesity, overweight conditions, anorexia, bulimia, cachexia, dysregulated appetite and the like. Obesity related syndromes, disorders or diseases include, but are not limited to, obesity as a result of genetics, diet, food intake volume, metabolic syndrome, disorder or disease, hypothalmic disorder or disease, age, abnormal adipose mass distribution, abnormal adipose compartment distribution, compulsive eating disorders, motivational disorders which include the desire to consume sugars, carbohydrates, alcohols or drugs or any ingredient with hedonic value and the like. Symptoms associated with obesity related syndromes, disorders, and diseases include, but are not limited to, reduced activity.

Metabolism related syndromes, disorders or diseases include, but are not limited to, metabolic syndrome, dyslipidemia, elevated blood pressure, insulin sensitivity or resistance, hyperinsulinemia, hypercholesterolemia, hyperlipidemias, atherosclerosis, hypertriglyceridemias, arteriosclerosis, other cardiovascular diseases, osteoarthritis, dermato logical diseases, sleep disorders (disturbances of circadian rhythm, dyssomnia, insomnia, sleep apnea and narcolepsy), cholelithiasis, hepatomegaly, steatosis, abnormal alanine aminotransferase levels, polycystic ovarian disease, inflammation, and the like. Diabetes related syndromes, disorders or diseases include, but are not limited to, glucose dysregulation, insulin resistance, glucose intolerance, hyperinsulinemia, dyslipidemia, hypertension, obesity, hyperglycemia and the like.

Catabolism related syndromes, disorders or diseases include, but are not limited to, catabolism in connection with pulmonary dysfunction and ventilator dependency; cardiac dysfunction, e.g., associated with valvular disease, myocardial infarction, cardiac hypertrophy or congestive heart failure.

Ophthalmic diseases include, but are not limited to, glaucoma, glaucoma- associated intraocular pressure retinitis, retinopathies, uveitis, acute injury to the eye tissue (e.g. conjunctivitis).

Social or mood related syndromes, disorders or diseases include, but are not limited to, depression (including, but not limited to, bipolar depression, unipolar depression, single or recurrent major depressive episodes with or without psychotic features, catatonic features, melancholic features, atypical features or postpartum onset, seasonal affective disorder, dysthymic disorders with early or late onset and with or without atypical features, neurotic depression and social phobia, depression accompanying dementia, anxiety, psychosis, social affective disorders, cognitive disorders and the like).

Substance abuse related syndromes, disorders or diseases include, but are not limited to, drug abuse and drug withdrawal. Abused substances include, but are not limited to, alcohol, amphetamines (or amphetamine like substances), caffeine, cannabis, cocaine, hallucinogens, inhalants, opioids, nicotine (and/or tobacco products), heroin abuse, barbiturates, phencyclidine (or phencyclidine-like compounds), sedative- hypnotics, benzodiazepines, or combinations of any of the foregoing. The compounds and pharmaceutical compositions can also be used to treat withdrawal symptoms and substance-induced anxiety or mood disorder.

The present invention further provides a method of treating nicotine dependency, addiction or withdrawal or aiding in the cessation or lessening of tobacco use in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound or a pharmaceutical composition of the present invention.

Learning, cognition or memory related syndromes, disorders or diseases which can be treated with the compounds of the present invention include, but are not limited to, memory loss or impairment as a result of age, disease, side effects of medications (adverse events) or the like. Memory impairment is a primary symptom of dementia and can also be a symptom associated with such diseases as Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeld-Jakob disease, HIV, cardiovascular disease, and head trauma, as well as age-related cognitive decline. Generally, dementias are diseases that include memory loss and additional intellectual impairment separate from memory. The compounds and pharmaceutical compositions of the present invention are also useful in treating cognitive impairments related to attentional deficits, such as attention deficit disorder.

Muscle spasm syndromes, disorders or diseases include, but are not limited to, multiple sclerosis, cerebral palsy and the like.

Locomotor activity and movement syndromes, disorders or diseases include, but are not limited to, stroke, Parkinson's disease, multiple sclerosis, epilepsy and the like.

Respiratory related syndromes, disorders or diseases include, but are not limited to, diseases of the respiratory tract, chronic obstructive pulmonary disorder, emphysema, asthma, bronchitis and the like.

Kidney dysfunction which can be treated with the modulators of the present invention include, but is not limited to, mesangial proliferative glomerulonephritis, nephritic syndrome, and liver dysfunction (hepatitis, cirrhosis).

Immune or inflammation related syndromes, disorders or diseases include, but are not limited to, psoriasis, lupus erythematosus, diseases of the connective tissue, Sjogren's syndrome, ankylosing spondylarthritis, rheumatoid arthritis, reactional arthritis, undifferentiated spondylarthritis, Behcet's disease, autoimmune hemolytic anaemias, multiple sclerosis, amyotrophic lateral sclerosis, amyloses, graft rejection or diseases affecting the plasma cell line; allergic diseases: delayed or immediate hypersensitivity, allergic rhinitis, contact dermatitis or allergic conjunctivitis infectious parasitic, viral or bacterial diseases (such as ADDS and meningitis), inflammatory diseases (such as diseases of the joints including, but not limited to, arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS)) and osteoporosis.

Cell growth related syndromes, disorders or diseases include, but are not limited to, dysregulated mammalian cell proliferation, breast cancer cell proliferation, prostrate cancer cell proliferation and the like.

Pain related syndromes, disorders or diseases include, but are not limited to, central and peripheral pathway mediated pain, bone and joint pain, migraine headache associated pain, cancer pain, dental pain, menstrual cramps, labor pain, chronic pain of the inflammatory type, allergies, rheumatoid arthritis, dermatitis, immunodeficiency, chronic neuropathic pain, (e.g. pain associated with diabetic neuropathy, sciatica, non specific lower back pain, fibromyalgia; HIV-related neuropathy; post herpetic neuralgia, trigeminal neuralgia, and pain resulting from physical trauma, amputation, cancer, toxins or chronic inflammatory conditions), Hodgkin's disease, myasthenia gravis, nephrotic syndrome, scleroderma, thyroiditis and the like.

Neurodegenerative related syndromes, disorders or diseases include, but are not limited to, Parkinson's disease, multiple sclerosis, epilepsy, ischemia or secondary biochemical injury collateral to traumatic head or brain injury, brain inflammation, eye injury or stroke and the like.

The compounds of this invention may also be used in conjunction with other pharmaceutical agents for the treatment of the diseases, conditions and/or disorders described herein. Therefore, methods of treatment that include administering compounds of the present invention in combination with other pharmaceutical agents are also provided. Suitable pharmaceutical agents that may be used in combination with the compounds of the present invention include, but are not limited to, anti-obesity agents such as apolipoprotein-B secretion/microsomal triglyceride transfer protein (apo-B/MTP) inhibitors, l lβ-hydroxy steroid dehydrogenase-1 (l lβ-HSD type 1) inhibitors, peptide YY₃..₃6 or analogs thereof, MCR-4 agonists, cholecystokinin-A (CCK-A) agonists, monoamine reuptake inhibitors (such as sibutramine), sympathomimetic agents, β₃ adrenergic receptor agonists, dopamine receptor agonists (such as bromocriptine), melanocyte-stimulating hormone receptor analogs, 5HT_2c receptor agonists, melanin concentrating hormone antagonists, leptin (the OB protein), leptin analogs, leptin receptor agonists, galanin antagonists, lipase inhibitors (such as tetrahydrolipstatin, i.e. orlistat), anorectic agents (such as a bombesin agonist), neuropeptide-Y receptor antagonists, thyromimetic agents, dehydroepiandrosterone or an analog thereof, glucocorticoid receptor agonists or antagonists, orexin receptor antagonists, glucagon-like peptide- 1 (GLP-I) receptor agonists, Protein Tyrosine Phosphatase (PTP-IB) inhibitors, dipeptidyl peptidase IV (DPP-IV) inhibitors, ciliary neurotrophic factors (such as Axokine™ available from Regeneron Pharmaceuticals, Inc., Tarrytown, N.Y. and Procter & Gamble Company, Cincinnati, Ohio), human agouti-related protein (AGRP) inhibitors, ghrelin receptor antagonists, histamine 3 receptor antagonists or inverse agonists, and neuromedin U receptor agonists. Other anti-obesity agents, including the preferred agents set forth herein below, are well known, or will be readily apparent in light of the instant disclosure, to one of ordinary skill in the art.

Especially preferred are anti-obesity agents such as orlistat, sibutramine, bromocriptine, ephedrine, leptin, peptide YY₃-36 or an analog thereof (including the complete peptide YY), and pseudoephedrine. Preferably, compounds of the present invention and combination therapies are administered in conjunction with exercise and a sensible diet.

Anti-obesity agents for use in the combinations, pharmaceutical compositions, and methods of the invention can be prepared using methods known to one of ordinary skill in the art, for example, sibutramine can be prepared as described in U.S. Pat. No. 4,929,629; bromocriptine can be prepared as described in U.S. Pat. Nos. 3,752,814 and 3,752,888; orlistat can be prepared as described in U.S. Pat. Nos. 5,274,143, 5,420,305, 5,540,917, and 5,643,874; and PYY_3-36 (including analogs) can be prepared as described in U.S. Patent Publication No. 2002/0141985 and International Publication No. WO 03/027637. All of the above recited references are incorporated herein by reference.

Other suitable pharmaceutical agents that may be administered in combination with the compounds of the present invention include agents designed to treat tobacco abuse (e.g., nicotine receptor partial agonists, bupropion hypochloride (also known under the tradename Zyban™) and nicotine replacement therapies), agents to treat erectile dysfunction (e.g., dopaminergic agents, such as apomorphine), ADD/ADHD agents (e.g., Ritalin™ (methylphenidate hydrochloride), Strattera™ (atomoxetine hydrochloride), Concerta™ (methylphenidate hydrochloride) and Adderall™ (amphetamine aspartate; amphetamine sulfate; dextroamphetamine saccharate; and dextroamphetamine sulfate)), and agents to treat alcoholism, such as opioid antagonists (e.g., naltrexone (also known under the tradename ReVia™) and nalmefene), disulfiram (also known under the tradename Antabuse™), and acamprosate (also known under the tradename Campral™)). In addition, agents for reducing alcohol withdrawal symptoms may also be coadministered, such as benzodiazepines, beta-blockers, clonidine, carbamazepine, pregabalin, and gabapentin (Neurontin™). Treatment for alcoholism is preferably administered in combination with behavioral therapy including such components as motivational enhancement therapy, cognitive behavioral therapy, and referral to self-help groups, including Alcohol Anonymous (AA).

Other pharmaceutical agents that may be useful include antihypertensive agents; antidepressants (e.g., fluoxetine hydrochloride (Prozac™)); cognitive improvement agents (e.g., donepezil hydrochloride (Aircept™.) and other acetylcholinesterase inhibitors); neuroprotective agents (e.g., memantine); antipsychotic medications (e.g., ziprasidone (Geodon™), risperidone (Risperdal™), and olanzapine (Zyprexa™)); insulin and insulin analogs (e.g., LysPro insulin); GLP-I (7-37) (insulinotropin) and GLP-I (7- 36)-NH₂; sulfonylureas and analogs thereof: chlorpropamide, glibenclamide, tolbutamide, tolazamide, acetohexamide, Glypizide^®, glimepiride, repaglinide, meglitinide; biguanides: metformin, phenfoπnin, buformin; α2-antagonists and imidazolines: midaglizole, isaglidole, deriglidole, idazoxan, efaroxan, fluparoxan; other insulin secretagogues: linogliride, A-4166; glitazones: ciglitazone, Actos^® (pioglitazone), englitazone, troglitazone, darglitazone, Avandia^® (BRL49653); fatty acid oxidation inhibitors: clomoxir, etomoxir; α-glucosidase inhibitors: acarbose, miglitol, emiglitate, voglibose, MDL-25,637, camiglibose, MDL-73,945; β-agonists: BRL 35135, BRL 37344, RO 16-8714, ICI D7114, CL 316,243; phosphodiesterase inhibitors: L-386,398; lipid-lowering agents: benfluorex: fenfluramine; vanadate and vanadium complexes (e.g., Naglivan^®) and peroxovanadium complexes; amylin antagonists; glucagon antagonists; gluconeogenesis inhibitors; somatostatin analogs; antilipolytic agents: nicotinic acid, acipimox, WAG 994, pramlintide (Symlin™), AC 2993, nateglinide, aldose reductase inhibitors (e.g., zopolrestat), glycogen phosphorylase inhibitors, sorbitol dehydrogenase inhibitors, sodium-hydrogen exchanger type 1 (NHE-I) inhibitors and/or cholesterol biosynthesis inhibitors or cholesterol absorption inhibitors, especially a HMG-CoA reductase inhibitor, or a HMG-CoA synthase inhibitor, or a HMG-COA reductase or synthase gene expression inhibitor, a CETP inhibitor, a bile acid sequesterant, a fibrate, an ACAT inhibitor, a squalene synthetase inhibitor, an anti-oxidant or niacin. The compounds of the present invention may also be administered in combination with a naturally occurring compound that acts to lower plasma cholesterol levels. Such naturally occurring compounds are commonly called nutraceuticals and include, for example, garlic extract, Hoodia plant extracts, and niacin.

The compounds of the present invention (including the pharmaceutical compositions and processes used therein) may be used alone or in combination with other pharmaceutical agents in the manufacture of a medicament for the therapeutic applications described herein. General method of preparation

The compounds according to the present invention may be prepared by the following processes. The symbols A, B, D, Z, R², R³, R⁴ and R⁵ when used in the formulae below are to be understood to present those groups described above in relation to formula (I) and formula ( II ) unless otherwise indicated.

( I ) and ( II )

The compounds of formula (I) wherein D is NR¹, Z is -CH₂ or -CH-, R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O) and A, B, R⁴ and R⁵ are as defined above can be synthesized by using the general process described in synthetic scheme I.

Scheme - 1

The compound of formula 4 (where Pgi is a protecting group) can be prepared by mixing the compound of formula (1) with a compound of formula (2), preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediate (3) (which can also be isolated). The compounds of formula (4) can then be derivatised, in the presence of a base (such as sodium hydride or sodium carbonate or potassium carbonate or cesium carbonate), to produce the compound of formula (5) (where A and B are as defined above). The compound of formula (5) can be deprotected, such as by methods known in the art, to give the compound of formula (6). The compound of formula (6) can then be converted to a corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (I). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of organic base (such as triethyl amine or pyridine) to give compound of formula (I). Alternately the compound of formula (6) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula

(I).

In another embodiment, the compounds of general formula (I) wherein D is NR¹ or O, Z is -CH₂ or -CH-, R² and R³ both are hydrogen and A, B, R⁴ and R⁵ are as defined above can be synthesized by the general process described in synthetic scheme II

Scheme II

The compound of formula (8) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (7) with a compound of formula (2), for example, under accelerated temperature conditions (such as heating at 120 - 130° C). The compound of formula (8) is then converted to the compound of formula (9) (where L is a leaving group such as O-mesyl, O-tosyl, or halogen except F), e.g., by any method known in the art. The compound of formula (9) thus obtained can be converted to a compound of formula (10) with a suitable base (such as triethylamine (TEA)). Alternately the compound of formula (8) can directly be converted to a compound of formula (10) in the presence of a trialkyl or triaryl phosphine (such as triphenyl phosphine or tributyl phosphine), a di alkylazadicarboxylate (such as diethyl azadicarboxylate or diisopropylazadicarboxylate) in a suitable solvent (such as tetrahydrofuran, dioxane or a mixture thereof) at 0° C to ambient temperature. The compounds of formula (10) can then be derivatised in the presence of a base (such as sodium hydride, sodium carbonate, potassium carbonate or cesium carbonate), to produce the compound of formula (11) (where A and B are as described above). The compound of formula (11) can be deprotected, such as by methods known in the art, to give the compound of formula (12). The compound of formula (12) can then be converted to the corresponding acid chloride, (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵, preferably in the presence of organic base (such as triethyl amine or pyridine), to give the compound of formula (I). Alternately, the compound of formula (12) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R^S to produce the compound of formula (I).

In yet another embodiment, the compound of formula (II) wherein Z is -CH₂ or - CH-, R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O), and p, q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme III. Scheme III

In the above scheme, the compound of formula (15) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (1) with a compound of formula (13), preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediate (14) (which can also be isolated). The compound of formula (15) can then be derivatised in the presence of a base (such as sodium hydride, sodium carbonate, potassium carbonate, or cesium carbonate), to produce the compound of formula (16) (where A and B are as defined above). The compound of formula (16) can be deprotected, such as by any method known in the art, to give a compound of formula (17). The compound of formula (17) can then be converted to the corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (IF). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (17) can be treated with (benzotriazol-l-yl- oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula (II).

In yet another embodiment, the compounds of general formula (II) wherein Z is -CH₂ or -CH-, R² and R³ both are hydrogen, and p, q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme IV.

Scheme IV

The compound of formula (18) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (7) with a compound of formula (13), preferably under accelerated temperature conditions (such as heating at 120 - 130° C). The compound of formula (18) is then converted to the compound of formula (19) (where L is a leaving group such as O-mesyl, O-tosyl, or halogen except F), such as by any method known in the art. The compound of formula (19) thus obtained can be converted to a compound of formula (20) in the presence of a suitable base (such as triethylamine (TEA)). Alternately the compound of formula (18) can directly be converted to a compound of formula (20) in the presence of a trialkyl or triaryl phosphine (such as triphenyl phosphine or tributyl phosphine), a di alkylazadicarboxylate (such as diethyl azadicarboxylate or diisopropylazadicarboxylate) in a suitable solvent (such as tetrahydrofuran, dioxane or mixture thereof) at 0° C to ambient temperature. The compound of formula (20) can then be derivatised in the presence of a base (such as sodium hydride, sodium carbonate, potassium carbonate, or cesium carbonate), to produce the compound of formula (21) (where A and B are as defined above). The compound of formula (21) may be deprotected, such as by methods known in the art, to give the compound of formula (22). The compound of formula (22) can then be converted to the corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula PINR⁴R⁵ to yield the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvents(such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (22) can be treated with (benzotriazol-1-yl- oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of formula (II).

In yet another embodiment, the compounds of formula (I) wherein D is NR¹, Z is -C(=0), R² and R³ are hydrogen and A, B, R⁴ and R⁵ are as defined above can be synthesized by using the general process described in synthetic scheme V.

Scheme - V

The compound of formula (26) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (23) with a compound of formula (24), preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediate (25) (which can also be isolated). The compounds of formula (26) can then be derivatised, with a compound of formula R¹ -L (wherein L is leaving group) in the presence of a base (such as sodium carbonate or potassium carbonate or cesium carbonate), to produce the compound of formula (27).The compound of formula (27) can then be further derivatised, in the presence of a base (such as sodium hydride) followed by deprotection (such as by methods known in the art) to give the compound of formula (28)(where A , B and D are as defined above). The compound of formula (28) can then be converted to a corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (I). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of organic base (such as triethyl amine or pyridine) to give compound of formula (I). Alternately the compound of formula (28) can be treated with (benzotriazol-l-yl-oxy)tris(dirnethylamino)phosphoniurn hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula

CO- In yet another embodiment, the compound of formula (II) wherein Z is -C(=O) ,

R² and R³ are hydrogen and p, q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme VI.

Scheme VI

In the above scheme, the compound of formula (26) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (23) with a compound of formula (24) preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediate (25) (which can also be isolated). The compound of formula (26) can then be derivatised in the presence of a base (such as sodium carbonate, potassium carbonate, or cesium carbonate) to produce the compound of formula (29) (where B is as defined above). The compound of formula (29) can then be further derivatised in the presence of a base (such as sodium hydride) followed by deprotection (such as methods known in the art) to produce the compound of formula (30) (where A is as defined above). The compound of formula (30) can then be converted to the corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (30) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula (II).

In yet another embodiment, the compound of formula (II) wherein Z is -CH₂ or - CH-, R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O), p = 0 and q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme VII.

Scheme VII

In the above scheme, the compound of formula (15) (where Pg₁ is a protecting group) can be prepared by mixing the compound of formula (1) with a compound of formula (13), preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediate (14) (which can also be isolated). The compound of formula (15) can then be derivatised in the presence of catalytic amount of an metal (such as copper), metal oxide (such as copper oxide) or metal halide (such as copper iodide or copper bromide), a bi-, tri-, or tetradentate ligand (such as salidehydeoxime or dimethylglyoxime or 2-pyridine aldoxime or 1,10-phenanthroline or trans- 1,2-diamino cyclohexane) and a base (such as sodium carbonate or potassium carbonate or cesium carbonate) in a suitable solvent (such as pyridine, acetonitrile, ethyl cyanide, toluene or tetarahydrofuran) either at ambient temperature or preferably at the accelerated temperature to furnish compound of the formula (31) (where A and B are as defined above and p = O). The compound of formula (31) can be deprotected, such as by any method known in the art, to give a compound of foπnula (32). The compound of formula (32) can then be converted to the corresponding acid chloride, (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (32) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylarnino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula (II).

In yet another embodiment, the compounds of general formula (II) wherein Z is -CH₂ or -CH-, R² and R³ both are hydrogen, p = 0 and q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme VIII.

Scheme VIII

The compound of formula (18) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (7) with a compound of formula (13), preferably under accelerated temperature conditions (such as heating at 120 - 130° C). The compound of formula (18) is then converted to the compound of formula (19) (where L is a leaving group such as O-mesyl, O-tosyl, or halogen except F), such as by any method known in the art. The compound of formula (19) thus obtained can be converted to a compound of formula (20) in the presence of a suitable base (such as triethylamine (TEA)). Alternately the compound of formula (18) can directly be converted to a compound of formula (20) in the presence of a trialkyl or triaryl phosphine (such as triphenyl phosphine or tributyl phosphine), a dialkylazadicarboxylate (such as diethyl azadicarboxylate or diisopropylazadicarboxylate) in a suitable solvent (such as tetrahydrofuran, dioxane or mixture thereof ) at 0° C to ambient temperature.The compound of formula (20) can then be derivatised in the presence of catalytic amount of an metal (such as copper), metal oxide (such as copper oxide) or metal halide (such as copper iodide or copper bromide), a bi or tri or tetradentate ligand (such as salidehydeoxime or dimethylglyoxime or 2- pyridine aldoxime or 1,10-phenanthroline or trans- 1,2-diamino cyclohexane) and a base (such as sodium carbonate or potassium carbonate or cesium carbonate) in a suitable solvent (such as pyridine, acetonitrile, ethyl cyanide, toluene or tetarahydrofuran) either at ambient temperature or preferably at the accelerated temperature to furnish compound of the formula (33) (where A and B are as defined above and p = 0). The compound of formula (33) may be deprotected, such as by methods known in the art, to give the compound of formula (34). The compound of formula (34) can then be converted to the corresponding acid chloride, (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to yield the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvents (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (34) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino)phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of formula (II). In yet another embodiment, the compound of formula (II) wherein Z is -CH₂ or - CH-, R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O) and p, q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme IX.

Scheme IX

(38B)

In the above scheme, the compounds of formulas (37A) and (37B) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (1) with a compound of formula (35), preferably under accelerated temperature conditions (such as heating at 120 - 130° C), via the intermediates [(36A) and (36B)] (which can also be isolated). The compounds of formulas (37A) and (37B) can then be separated using column chromatography. The compounds of formulas (37A) and (37B) can then be independently deprotected, e.g., by any method known in the art, to give compounds of formulas (38A) and (38B) respectively. The compound of formula (38A) or (38B) can then be independently converted to the corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to form the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvent (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (38A) or (38B) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino) phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethyl amine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of general formula (II).

In yet another embodiment, the compound of formula (II) wherein Z is -CH₂ or - CH-, R² and R³ are hydrogen and p, q, A, B, R⁴ and R⁵ are as defined above, can be synthesized by using the general process described in synthetic scheme X.

Scheme X

(42 B)

The compounds of formulas (39A) and (39B) (where Pgi is a protecting group) can be prepared by mixing the compound of formula (7) with a compound of formula (35), preferably under accelerated temperature conditions (such as heating at 120 - 130° C). The compounds of formulas (39A) and (39B) are then converted to the compounds of formulas (40A) and (40B) (where L is a leaving group such as O-mesyl, O-tosyl, or halogen except F), such as by any method known in the art. The compounds of formulas

(40A) and (40B) thus obtained can be converted to compounds of formulas (41A) and (41B), such as with a suitable base (such as triethylamine (TEA)). Alternately the compounds of formulas (39A) and (39B) can directly be converted to compounds of formulas (41A) and (41B), respectively, in the presence of a trialkyl or triaryl phosphine (such as triphenyl phosphine or tributyl phosphine), a dialkylazadicarboxylate (such as diethyl azadicarboxylate or diisopropylazadicarboxylate) in a suitable solvent (such as tetrahydrofuran, dioxane or mixture thereof ) at 0° C to ambient temperature.The compounds of formulas (41A) and (41B) can then be separated using column chromatography. The compounds of formula (41A) and (41B) may be independently deprotected, e.g., by any known in the art, to give compounds of formulas (42A) and (42B) respectively. The compound of formula (42A) or (42B) can then be independently converted to the corresponding acid chloride (such as by treatment with thionyl chloride or oxalyl chloride) in a suitable solvent (such as benzene, toluene, dichloromethane, or chloroform). The acid chloride thus produced (with or without purification) can be reacted with an amine of the formula HNR⁴R⁵ to yield the compound of formula (II). For example, the acid chloride can be dissolved in a chlorinated solvents (such as dichloromethane, chloroform, or dichloroethane) followed by the addition of an amine of the formula HNR⁴R⁵ in the presence of an organic base (such as triethylamine or pyridine) to give the compound of formula (II). Alternately, the compound of formula (42A) or (42B) can be treated with (benzotriazol-l-yl-oxy)tris(dimethylamino) phosphonium hexafluoro phosphate (BOP) in the presence of a suitable solvent system (such as dimethyl formamide) and an organic base (such as triethylamine or pyridine) followed by the addition of an amine of the formula HNR⁴R⁵ to produce the compound of formula (II).

Experimental section:

Intermediate 1 l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid:

Step - 1: 2-(2,4-Dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester: A mixture of ethyl ethoxymethelene malonate (17.2 gm, 0.079 mole), prepared according to literature (see, Fuson et al., J. Org. Chem., 1946, 11, 194) and 2,4- dichlorophenyl hydrazine (14.1 gm, 0.079 mole) was heated at 130 ⁰C for 30 hours with constant removal of ethanol. After completion of reaction, the mixture was diluted with chloroform and washed with water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give spectroscopically homogenous title compound (23.1 gm).

¹H NMR (CDCl₃)S: 7.81 (s, IH), 7.56 (s, IH), 7.38 (s, 2H), 4.40-4.33 (q, J=7.5 Hz, 2H), 1.41-1.36 (t, J=7.2 Hz, 3H).

Step - 2: l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester: : 3.90 gm (0.013 mole) of the pyrazole compound as prepared in Step - 1 was dissolved in dimethyl formamide (25 mL) followed by the addition of potassium carbonate (5.33 gm, 0.038 mole). The mixture was stirred at room temperature for -30 minutes followed by the drop wise addition of benzyl bromide (2.86 gm) and the resultant mixture was stirred overnight at the ambient temperature. The usual work up followed by dilution of the reaction mixture with water and the extraction of the organic compounds with ethyl acetate successively. The combined organic phase was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude residue was subjected to column chromatography over silica gel using ethyl acetate and petroleum ether mixture to furnish the title compound (2.70 gm).

¹H NMR (DMSOd₆)O: 8.00 (s, IH), 7.87 (d, J=2.1 Hz, IH), 7.56-7.52 (dd, J=8.1 and 1.8

Hz, IH), 7.34-7.26 (m, 4H), 7.13-7.1 1 (dd, J=7.8 andl.5 Hz, 2H), 5.38 (s, 2H), 4.33-4.26

(q, J=6.9 Hz, 2H), 1.34-1.29 (t, J=7.2 Hz, 3H).

Step - 3: l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-ρyrazole-4-carboxylic acid: :The ester (2.69 gm, 0.0068 mole) obtained in Step - 2 was hydrolyzed under basic condition using lithium hydroxide (461.8 mg, 0.011 mole) in a mixture of solvent (25 mL,

THF : MeOH : Water = 3:1:1) and stirred for 20 hours at room temperature. The volatile matters were removed in vacuum and the residue was dissolved in water. The apolar impurities were washed with ether followed by acidification of the aqueous layer to pH =

4.0-5.0 with IN HCl. Then the acid was extracted with chloroform and was dried over sodium sulfate. Chloroform was removed to afford spectroscopically pure compound

(2.10 gm) that was used directly in the next step.

¹H NMR (DMSO-dβjδ: 7.96 (s, IH), 7.86 (d, J=2.4 Hz, IH), 7.55-7.51 (dd, J=8.4 and 2.1

Hz, IH), 7.32-7.25 (m, 4H), 7.11 (d, J=9.0 Hz, 2H), 5.41 (s, 2H).

Step 1 of Intermedites 2-8 was prepared according to the process as described in step 1 of

Intermediate 1

Intermediate 2

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(4-trifluoromethylbenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid

This compound was synthesized in 3 steps according to the process as described for

Intermediate 1 with the exception being use of 4-trifluorobenzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(2₅4-dichlorophenyl)-3-oxo-l-(4-trifluoromethylbenzyl)-2,3-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 61%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.03 (s, IH); 7.84 (d, J= 2.1 Hz, IH);

7.64 (d, J= 8.1 Hz, 2H); 7.52 (dd, J= 2.7 Hz and 8.4 Hz, IH); 7.44 (d, J= 8.7 Hz, IH);

7.36 (d, J= 8.1 Hz, 2H); 5.47 (s, 2H); 4.32-4.25 (q, J= 6.6 Hz₅ 2H); 1.32-1.26 (t, J= 6.6

Hz, 3H).

Step3 :2-(2,4-dichlorophenyl)-3 -oxo- 1 -(4-trifluoromethylbenzyl)-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid

Yield: 94.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.77 (b s, IH); 7.98 (s, IH); 7.84 (d,

J= 2.1 Hz, IH); 7.64 (d, J= 8.1 Hz, 2H); 7.52 (dd, J= 2.1 Hz and 8.4 Hz, IH); 7.42 (d, J=

8.4 Hz, IH); 7.36 (d, J= 8.4 Hz, 2H); 5.51 (s, 2H).

Intermediate 3

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(3 -trifluoromethyl benzy l)-2, 3 -dihydro- 1 H-pyrazole-4- carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 3-trifJourobenzyl bromide in place of benzyl bromide in Step 2.

StepZ^^^-dichlorophenyO-S-oxo-l-CS-trifluoromethyl benzyO^^-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 66.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.03 (s, IH); 7.85 (d, J= 2.4 Hz, IH); 7.68 (d, J= 7.5 Hz, IH); 7.56-7.40 (m, 5H); 5.47 (s, 2H); 4.33-4.26 (q, J= 6.9 Hz, 2H); 1.33-1.29 (t, J= 6.9 Hz, 3H).

Step3:2-(2,4-dichlorophenyl)-3-oxo-l-(3-trifluoromethylbenzyl)-2,3-dihydro-lH- pyrazole-4-carboxylic acid Yield: 97.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.6 (b s, IH); 7.99 (s, IH); 7.85 (d, J= 2.4 Hz, IH); 7.68 (d, J= 7.2 Hz, IH); 7.56-7.39 (m, 5H); 5.50 (s, 2H).

Intermediate 4

2-(2,4-dichlorophenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 3-chloro benzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(2,4-dichlorophenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

Yield: 49.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.04 (s, IH); 7.89 (d, J= 2.1 Hz, IH); 7.58 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.43-7.30 (m, 3H); 7.13-7.08 (m, 2H); 5.38 (s, 2H); 4.35-4.28 (q, J= 6.9 Hz, 2H); 1.35-1.30 (t, J= 6.9 Hz₅ 3H).

Step3: 2-(2,4-dichlorophenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 80%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.98 (s, IH); 7.87 (d. J= 2.1 Hz, IH); 7.57-7.54 (dd, J= 1.2 Hz and 7.2 Hz, IH); 7.37 (d, J= 8.4 Hz, 2H); 7.33-7.28 (t, J= 7.2 Hz, IH); 7.10 (d, J= 7.5 Hz, IH); 7.07 (s, IH); 5.40 (s, 2H).

Intermediate 5

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of 4-chloro benzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(2,4-dichlorophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

Yield: 47.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.01 (s, IH); 7.86 (d, J= 2.1 Hz, IH);

7.55 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.41 (d, J= 8.4 Hz, IH); 7.35 (d, J= 8.4 Hz, 2H);

7.16 (d, J= 8.4 Hz, 2H); 5.36 (s, 2H); 4.32-4.25 (q, J= 7.2 Hz, 2H); 1.33-1.28 (t, J= 7.2

Hz, 3H).

Step3 :2-(2,4-dichlorophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3 -dihydro-1 H-pyrazole-4- carboxylic acid

Yield: 67.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.75 (b s, IH); 7.96 (s, IH); 7.86 (d,

J= 2.1 Hz, IH); 7.56-7.53 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.39-7.33 (m, 3H); 7.16 (d, J=

8.4 Hz, 2H); 5.41 (s, 2H).

Intermediate 6

2-(2,4-dichlorophenyl)-3-oxo-l-(2-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 2-chloro benzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(2,4-dichlorophenyl)-3 -oxo- 1 -(2-chloro benzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester

Yield: 50%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.02 (s, IH); 7.85 (s, IH); 7.51 (s, IH);

7.38-7.25 (m, 5H); 5.45 (s, 2H); 4.34-4.26 (q, J= 7.2 Hz, 2H); 1.34-1.28 (t, J= 7.2 Hz,

3H).

Step3:2-(2,4-dichlorophenyl)-3-oxo-l-(2-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid Yield: 66%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.76 (b s, IH); 7.97 (s, IH); 7.84 (d, J= 2.4 Hz, IH); 7.51 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.39-7.21 (m, 5H); 5.49 (s, 2H).

Intermediate 7

2-(2,4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of 3-fluorobenzyl bromide in place of benzyl bromide in Step 2.

Step-2:2-(2,4-diChlorophenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester

¹U NMR (CDCl₃)δ:. 7.98 (s, IH), 7.51 (d, J=2.1 Hz, IH), 7.31-7.19 (m, 3H), 7.07 (d,

J=9.0 Hz, IH), 6.99 (t, IH), 6.91 (d, J=7.5 Hz, IH), 6.82 (d, J=9.6 Hz, IH), 5.44 (s, 2H),

4.39-4.32 (q, 2H), 1.39 (t, J=7.5 Hz, 3H).

Step-3:2-(2,4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid

¹H NMR (DMSO-d^δ: 7.97 (s, IH), 7.87 (d, J=2.1 Hz, IH), 7.57-7.54 (dd, J=9.0 and 2.4

Hz, IH), 7.38 (d, J=8.7 Hz, IH), 7.36-7.29 (m, IH), 7.17-7.11 (dt, J=2.4 and 8.1 Hz, IH),

6.97 (d, J=7.8 Hz, IH), 6.88 (d, J=9.9 Hz, IH), 5.41 (s, 2H).

Intermediate 8 l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of cyclohexyl methyl bromide in place of benzyl bromide in Step2.

Step2:l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

¹H NMR (CDCl₃)δ: 7.97 (s, IH)₅ 7.56 (d, J=2.1 Hz, IH), 7.40-7.32 (m, 2H)₅ 4.35-4.27 (q,

2H), 4.18 (d, J=5.7 Hz, 2H), 1.62-1.50 (m, 5H), 1.39-1.34 (t, 3H), 1.16-1.04 (m, 3H),

0.87-0.79 (m, 2H).

Step3 : 1 -Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid-

¹H NMR (DMSO-de)δ: 12.54 (s, IH), 7.96 (s, IH), 7.93 (s, IH), 7.65 (s, 2H)₅ 4.14 (d,

J=6.3 Hz, 2H), 1.55-1.36 (m, 6H)₅ 1.05-1.02 (m, 3H), 0.76-0.72 (m, 2H).

Intermediate 9

1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid

Step-l:3-[N'-(2,4-Dichlorophenyl)-hydrazino]-2-hydroxymethyl-propionic acid ethyl ester: A mixture of 2-hydroxymethyl acrylic acid ethyl ester (6.0 gm, 46.15 mmol, prepared following literature procedure) and 2,4-dichlorophenyl hydrazine (8.20 gm, 46.15 mmol) was heated at 120 ⁰C for 6 hours followed by purification over silica gel column using a mixture of petroleum ether and ethyl acetate to afford target compound (3.10 gm). ¹H NMR (CDCIa) δ: 7.23(s, IH), 7.13 (s₅ 2H), 5.64 (bs, IH), 4.25-4.17 (q, 2H)₅ 4.00-3.88 (m, 2H)₅ 3.29-3.17 (m, 2H)₅ 2.84-2.77 (m₅ IH)₅ 1.29 (t₅ J=7.5 Hz, 3H). Step-2: l-(2,4-dichlorophenyl)-ρyrazolidine-4-carboxylic acid ethyl ester To a cold (10 ⁰C) solution of the compound as prepared in Step-1 (3.0 gm, 9.77 mmol) in tetrahydrofuran (3.0 mL), was charged triphenylphosphine (5.12 gm, 19.54 mmol) followed by the drop wise addition of diethylazadicarboxylate (3.4 gm, 19.54 mmol) and the resultant mixture was stirred at ambient condition for 3 hours The volatile matters were removed under reduced pressure and the crude residue was subjected to column chromatography. The compound was eluted with a mixture of petroleum ether and ethyl acetate (2.0 gm). ¹H NMR (CDCla)δ:7.43(d, J=9.0 Hz, IH), 7.31 (d, J=2.4 Hz₅ IH), 7.13 and 7.10 (dd, 3=8.7 and 2.1 Hz, IH), 4.19-4.12 (q, 2H), 3.77-3.64 (m₅ 2H), 3.38-3.35 (m,

IH), 3.29-3.18 (m, 2H), 1.25 (t, J=7.2 Hz, 3H).

Step-3:l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid ethyl ester :Was synthesized according to the procedure as described in Step-2 for Intermediate -1.

¹H NMR (CDCl₃) δ: 7.55(d, J=9.0 Hz, IH), 7.38-7.24 (m, 6H), 7.12 and 7.10 (dd, J=8.7 and 2.1 Hz, IH), 4.15-4.07 (q, J=6.9 Hz, 2H), 3.88 (bs, 3H), 3.66 (bs, IH), 3.31-3.20 (m,

3H), 1.21 (U=7.2 Hz, 3H).

Step-4: l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid :

This compound was synthesized according to the procedure as described in Step-3 for

Intermediate -1.

¹HNMR (CDCl₃)B: 7.53 (d, J=8.7 Hz, IH), 7.38-7.22 (m, 6H), 7.13 and 7.10 (dd, J-8.7 and 2.1 Hz, IH), 3.88 (bs, 3H), 3.66 (bs, IH), 3.35-3.22 (m, 3H).

Step 1 and 2 for IntermediteslO&l 1 is same as described in Intermediate 9

Intermediate 10 l-(2,4-dichlorophenyl)-2-(3-fiuorobenzyl)-4-pyrazolidinecarboxylicacid

This compound was synthesized in 4 steps, according to process as described for Intermediate 9 with the exception being use of 3-fluorobenzyl bromide in place of benzyl bromide in Step3.

Step3: l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidinecarboxylicacid ethyl ester Yield: 55%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.51 (d, J= 8.7 Hz, IH); 7.29-7.21 (m, 2H); 7.13-7.06 (m, 3H); 6.96-6.90 (dt, J= 1.2 Hz₃ 1.8 Hz and 7.8 Hz, IH); 4.15-4.08 (q, J= 6.9 Hz, 2H); 3.88 (b s, 3H); 3.67 (b s, IH); 3.31-3.23 (m, 3H); 1.24-1.19 (t, J= 6.9 Hz and 7.2 Hz, 3H). Step4:l-(2,4-dichlorophenyl)-2-(3-fluorobe.nzyl)-4-pyrazolidinecarboxylicacid Yield: 98%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.60 (d, J= 8.7 Hz, IH); 7.23-7.17 (m, 2H); 7.10-6.99 (m, 3H); 6.94-6.88 (t, J= 8.4 Hz, IH); 3.78 (b s, 2H); 3.42 (b s, 3H); 3.21 (b s, IH); 3.06 (b s, IH).

Intermediate 11 l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidinecarboxylicacid

This compound was synthesized in 4 steps, according to process as described for Intermediate 9 with the exception being use of 4-fluorobenzyI bromide in place of benzyl bromide in Step3.

Step3: l-(2,4-dichlorophenyl)-2-(4-fluorobenzyI)-4-pyrazoHdinecarboxyHcacid ethyl ester

Yield: 36%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.48 (d, J- 9.0 Hz₅ IH); 7.36-7.26 (m, 3H); 7.11-7.08 (dd, J= 2.4 Hz and 8.7 Hz, IH); 6.99-6.93 (t, J= 8.7 Hz, 2H); 4.15-4.08 (q, J= 6.9 Hz, 2H); 3.84 (s, 3H); 3.65 (b s, IH); 3.29-3.21 (m, 3H); 1.23-1.18 (t, J= 6.9 Hz, 3H).

Step4 : 1 -(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidinecarboxylicacid Yield: 93%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.48 (d, J= 8.7 Hz, IH); 7.32-7.27 (m, 3H); 7.12-7.08 (dd, J= 2.1 Hz and 8.7 Hz, IH); 6.99-6.94 (t, J= 8.7 Hz and 9.0 Hz, 2H); 4.00- 3.60 (m, IH); 3.83 (s, 3H); 3.35-3.23 (m, 3H).

Intermediate 11a l-(6-Chloro-pyridin-3ylmethyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole- 4-carboxylic acid

Step2:l-(6-Chloro-pyridin-3ylmethyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 45%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.20 (d, J= 2.4 Hz, IH); 8.04 (s, IH);

7.86 (d, J= 2.4 Hz, IH); 7.66-7.62 (dd, J= 2.4 Hz and 8.1 Hz, IH); 7.58-7.55 (dd, J= 2.1

Hz and 8.7 Hz, IH); 7.47 (d, J= 6.0 Hz, IH); 7.45 (d, J= 5.4 Hz, IH); 5.43 (s, 2H); 4.33-

4.26 (q, J= 7.5 Hz, 2H); 1.33-1.28 (t, J= 7.2 Hz, 3H).

StepSα-Cδ-Chloro-pyridin-SylmethyO^^^-dichlorophenyO-S-oxo^^-dihydro-lH- pyrazole-4-carboxylic acid

Yield: 72%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.66 (b s, IH); 8.19 (s, IH); 7.98 (s,

IH); 7.86 (d, J= 1.8 Hz, IH); 7.65-7.62 (dd, J= 2.4 Hz and 8.1 Hz, IH); 7.58-7.54 (dd, J=

2.4 Hz and 8.7 Hz, IH); 7.45 (d, J= 9.3 Hz, 2H); 5.46 (s, 2H).

Intermediate 12 l-(2₅5-dichlorophenyl)-2-(3-chlorobenzyl)-4-pyrazolidinecarboxylicacid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 3-chloro benzyl bromide in place of benzyl bromide in Step2.

Stepl : 1 -(2,5-dichlorophenyl)-pyrazolidine-4-carboxylicacid ethyl ester

Yield: 60.4%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.52 (d, J= 2.4 Hz, IH); 7.21 (d, J= 8.4 Hz,

IH); 6.88-6.84 (dd, J= 2.4 Hz and 8.7 Hz, IH); 4.20-4.13 (q, J= 6.9 Hz, 2H); 4.25 (b s,

IH); 3.81-3.67 (m, 2H); 3.40-3.36 (dd, J= 2.7 Hz, 3.6 Hz and 9.6 Hz₅ IH); 3.31-3.19 (m,

2H); 1.29-1.24 (t, J= 6.6 Hz and 7.5 Hz, 3H).

Step2: 1 -(2,5-dichlorophenyl)-2-(3-chlorobenzyl)-4-pyrazolidinecarboxylicacidethyl ester

Yield: 33%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.55 (d, J- 2.4 Hz, IH); 7.35 (s, IH); 7.24-

7.17 (m, 4H); 6.86-6.83 (dd, J= 2.7 Hz and 8.1 Hz, IH); 4.16-4.08 (q, J= 6.9 Hz₅ 2H);

3.85 (b s, 4H); 3.31-3.21 (m, 3H); 1.24-1.20 (t, J= 6.3 Hz and 7.5 Hz, 3H). Step3:l-(2,5-dichlorophenyl)-2-(3-chlorobenzyl)-4-pyrazolidinecarboxylicacid Yield: 99%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.54 (d, J= 2.4 Hz, IH); 7.34 (s, IH); 7.25- 7.18 (m, 4H); 6.87-6.84 (dd, J= 2.7 Hz and 8.4 Hz, IH); 3.86 (b s, 4H); 3.37-3.26 (m, 3H).

Step 1 of Intermediate 13 was prepared according to the process as described in step 1 of Intermediate 12

Intermediate 13 l-(2,5-dichlorophenyl)-2-(2-chlorobenzyl)-4-pyrazolidinecarboxylicacid

Intermediate 1 with the exception being use of 2,5dichloro phenyl hydrazine in place of

2,4-dichlorophenyl hydrazine in Step 1 and 2-chloro benzyl bromide in place of benzyl bromide in Step2.

Step2: 1 -(2,5-dichlorophenyl)-2-(2-chlorobenzyl)-4-pyrazolidinecarboxyIicacid ethyl ester

Yield: 10.7%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.59 (d, J= 2.7 Hz, IH); 7.46-7.43 (m, IH);

7.33-7.28 (m, IH); 7.20-7.14 (m, 3H); 6.82-6.79 (dd, J= 2.4 Hz and 8.4 Hz, IH); 4.14-

4.12 (m, 3H); 4.01 (s, 2H); 3.38-3.27 (m, 4H); 1.25-1.20 (t, J= 6.6 Hz and 7.2 Hz, 3H).

Step3:l-(2,5-dichlorophenyl)-2-(2-chlorobenzyl)-4-pyrazolidinecarboxylicacid

Yield: 99%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.58 (d, J= 2.4 Hz, IH); 1 Al-I Al (m, IH);

7.36-7.29 (m, IH); 7.22-7.15 (m, 3H); 6.83-6.80 (dd, J= 2.1 Hz and 8.4 Hz, IH); 4.01 (b s, 3H); 3.50-3.24 (m, 4H).

Intermediate 14 l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid:

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1.

Stepl: 2-(4-chlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester: ¹H NMR (DMSO-d^δ: 7.84 (s, IH), 7.74 (d. J=9.0 Hz, 2H), 7.57 (d, J=9.0 Hz, 2H), 4.26-4.19 (q, 2H), 1.28 (t, 3H).

Step2:l-Benzyl-2-(4-chlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4-carboxylic acid ethyl ester:

¹H NMR (DMSO-d₆)δ:7.99 (s, IH), 7.54 (s, 4H), 7.33-7.22 (m, 5H), 5.41 (s, 2H), 4.33- 4.26 (q, J=6.9 Hz, 2H), 1.31 (t, J=6.9 Hz, 3H).

Step3:l-Benzyl-2-(4-chloro-phenyl)-3-oxo~2,3-dihydro-lH-pyrazole-4-carboxylic acid: ¹H NMR (DMSOd₆)) δ:7.95 (s, IH), 7.52 (s, 4H), 7.31-7.22 (m, 5H), 5.45 (s, 2H). Stepl of Intermediates 15-19 was prepared according to the process as described in step 1 of Intermediate 14

Intermediate 15

2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1 and 3-fluoro benzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester ¹H NMR (DMSO-d6)δ: 8.00 (s, IH), 7.55 (s, 4H), 7.38-7.31 (m, IH), 7.18-7.03 (m, 3H),

5.41 (s, 3H), 4.29 (q, 2H), 1.30 (t, 3=6.9 Hz, 3H).

Step3:2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid

¹H NMR (DMSO-d6)δ:. 12.72 (bs, IH), 7.96 (s, IH), 7.54 (s, 4H), 7.37-7.30 (m, IH),

7.17-7.02 (m, 3H), 5.45 (s, 2H).

Intermediate 16

2-(4-chloro phenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1 and 2,4dichloro benzyl bromide in place of benzyl bromide in Step 2.

Step2 :2-(4-chloro phenyl)-3-oxo- 1 ~(2,4-dichlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester

Yield: 61.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.02 (s, IH); 7.52-7.45 (m, 6H); 7.37 (d, J= 1.5 Hz, 2H); 5.46 (s, 2H); 4.31-4.24 (q, J= 6.9 Hz, 2H); 1.32-1.27 (t, J= 7.2 Hz, 3H).

Step3:2-(4-chloro phenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 75.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.85 (s, IH); 7.52-7.44 (m, 6H); 7.36 (dd, J= 2.1 Hz and 8.1 Hz, IH); 5.62 (s, 2H).

Intermediate 17

2-(4-chloro phenyl)-3-oxo-l-(2, δ-dichlorobenzyl^S-dihydro-lH-pyrazole^-carboxylic acid

. This compound was synthesized in 3 steps according to the process as described for

Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1 and 2,6dichloro benzyl bromide in place of benzyl bromide in Step 2.

Step2 :2-(4-chloro phenyl)-3-oxo- 1 -(2, 6-dichlorobenzyl)-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester

Yield: 57%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.96 (s, IH); 7.36 (d, J= 8.1 Hz, 2H);

7.23-7.20 (m, 2H); 7.17-7.11 (m, 3H); 5.69 (s, 2H); 4.40-4.33 (q, J= 7.2 Hz, 2H); 1.43-

1.38 (t, J= 7.2 Hz, 3H).

Step3: 2-(4-chloro phenyl)-3-oxo-l-(2, 6-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 63%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.74 (s, IH); 7.95 (s, IH); 7.41-7.30

(m, 3H); 7.29 (s, 4H)); 5.61 (s, 2H).

Intermediate 18

2-(4-chlorophenyl)-3-oxo-l-(4-chlorobenzyl)-2, 3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1 and 4-chlorobenzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(4-chloro phenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester Yield: 48%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH); 7.54 (s, 4H); 7.36 (dd, J=

1.8 Hz and 6.9 Hz, 2H); 7.27 (d, J= 8.4 Hz, 2H); 5.40 (s, 2H); 4.32-4.25 (q, J=7.2 Hz,

2H); 1.33-1.28 (t, J= 7.2 Hz, 3H).

Step3 :2-(4-chlorophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxy.lic acid

Yield: 84%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.70 (b s, IH); 7.96 (s, IH); 7.53 (s,

4H); 7.35 (d, J= 8.1 Hz, 2H); 7.26 (d, J= 8.1 Hz, 2H); 5.43 (s, 2H).

Intermediate 19

2-(4-chloro phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of p-chloro phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1 and 3-chlorobenzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(4-chloro phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

Yield: 46%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH); 7.53 (s, 4H); 7.36-7.29 (m,

2H); 7.24-7.17 (m, 2H); 5.39 (s, 2H); 4.32-4.22 (q, J=6.9 Hz, 2H); 1.35-1.28 (t, J= 6.9 Hz,

3H).

Step3: Yield: 92%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.76 (s, IH); 7.96 (s, IH); 7.53

(s, 4H); 7.36 (d, J= 8.1 Hz, IH); 7.33-7.28 (t, J= 7.2 Hz, IH); 7.24 (s, IH); 7.18 (d, J= 7.5

Hz, IH); 5.43 (s, 2H).

Intermediate 20

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 3-chloro benzyl bromide in place of benzyl bromide in Step 2.

Stepl: 2-(4-Bromophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester

¹H NMR (CDCyδ: 7.65 (s, IH), 7.72 (d. J=8.7 Hz, 2H), 7.59 (d, J=8.7 Hz, 2H), 4.41-

4.34 (q, 2H), 1.39 (t, 3H).

Step2:2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

¹H NMR (DMSO-d₆)δ: 8.01 (s, IH), 7.68_. (d, J=9.0, 2H), 7.47 (d, J=9.0 Hz, 2H), 7.36-

7.18 (m, 4H), 5.40 (s, 2H), 4.32-4.25 (q, 2H), 1.33-1.28 (t, 3H).

Step3 :2-(4-Bromophenyl)- 1 -(3 -chlorobenzyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid

¹H NMR (DMSO-d_<0δ: 12.7 (bs, IH), 7.96 (s, IH), 7.66 (d, J=9.0 Hz, 2H), 7.45 (d, J=9.0

Hz, 2H), 7.38-7.28 (m, 2H), 7.24 (s, IH), 7.19-7.17 (d, J=6 Hz, IH), 5.42 (s, 2H).

Stepl of Intermedites 21-29 was prepared according to the process as described in step 1 of Intermediate 20

Intermediate 21

2-(4-bromo phenyl)-3 -oxo- 1 -(2,6-dichlorobenzyl)-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 4-bromo benzyl bromide in place of benzyl bromide in Step 2.

Step2:2-(4-bromophenyl)-3-oxo-l-(2,6-dichlorobenzyi)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

Yield: 50%. ¹H NMR (δ, DMSO-dό, 300 MHz): 8.01 (s, IH); 7.55 (d, J= 8.1 Hz, 2H);

7.34-7.29 (m, 5H); 5.58 (s, 2H); 4.32-4.25 (q, J= 6.9 Hz₅ 2H); 1.35-1.30 (t, J= 6.9 Hz,

3H).

Step3:2-(4-bromo phenyl)-3-oxo-l-(2,6-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 78.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.7 (b s, IH); 7.95 (s, IH); 7.52 (d, J=

9.0 Hz, 2H); 7.30-7.25 (m, 5H); 5.61 (s, 2H).

Intermediate 22

2-(4-bromo phenyl)-3-όxo-l-(2,6-difluorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 2,6-difluoro benzyl bromide in place of benzyl bromide in Step 2

Step2 :2-(4-bromo phenyl)-3 -oxo- 1 -(2,6-difluorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester

Yield: 21.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.95 (s, IH); 7.44 (d, J= 9.0 Hz, 2H);

7.34 (d, J= 8.7 Hz, 2H); 7.33-7.24 (m, IH); 6.77-6.71 (t, J= 7.5 Hz, 2H); 5.50 (s, 2H);

4.40-4.33 (q, J= 7.2 Hz, 2H); 1.42-1.38 (t, J= 7.2 Hz, 3H).

Step3:2-(4-bromo phenyl)-3-oxo-l-(2,6-difluorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 79.0%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.78 (b s, IH); 7.95 (s, IH); 7.59 (d,

J= 8.4 Hz, 2H); 7.42-7.37 (t, J= 8.4 Hz, IH); 7.31 (d, J= 8.7 Hz, 2H); 6.96-6.91 (t, J= 8.1

Hz, 2H); 5.50 (s, 2H). Intermediate 23

2-(4-bromo phenyl)-3 -oxo- 1 -(2-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 2-chloro benzyl bromide in place of benzyl bromide in Step 2

Step2:2-(4-bromo phenyl)-3-oxo-l-(2-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester: Yield: 4O⁰Zo- ¹H NMR (δ, DMSO-d6, 300 MHz): 8.01 (s, IH); 7.63 (d, J= 8.4 Hz, 2H); 7.42 (d, J= 8.7 Hz, 2H); 7.39-7.27 (m, 4H); 5.51 (s, 2H); 4.32- 4.25 (q, J= 7.2 Hz, 2H); 1.32-1.27 (t, J= 7.2 Hz, 3H).

Step3 :2-(4-bromo phenyl)-3 -oxo-1 -(2-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid :Yield: 74%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.75 (b s, IH); 7.80 (s, IH); 7.60 (d, J= 8.4 Hz, 2H); 7.45 (d, J= 8.7 Hz, 2H); 7.39-7.26 (m, 4H); 5.70 (s, 2H).

Intermediate 24

2-(4-bromophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxyIic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 4-chloro benzyl bromide in place of benzyl bromide in Step 2 Step2:2-(4-bromophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester: Yield: 73%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH); 7.67 (dd, J= 1.8 Hz and 7.2 Hz, 2H); 7.47 (dd, J= 1.8 Hz and 6.6 Hz, 2H); 7.36 (d, J= 8.4 Hz, 2H); 7.27 (d, J= 8.4 Hz, 2H); 5.40 (s, 2H); 4.32-4.25 (q, J= 7.2 Hz₃ 2H); 1.32-1.28 (t, J= 7.2 Hz, 3H).

Step3 :2-(4-bromophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid: Yield: 60%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.75 (b s, IH); 7.96 (s, IH); 7.66 (d, J= 9.0 Hz, 2H); 7.46 (d, J= 8.7 Hz, 2H); 7.35 (d, J= 8.4 Hz, 2H); 7.26 (d, J= 8.4 Hz, 2H); 5.43 (s, 2H).

Intermediate 25

2-(4-bromo phenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 2,4-dichloro benzyl bromide in place of benzyl bromide in Step 2

Step2:2-(4-bromophenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester: Yield: 38%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.02 (s, IH); 7.64 (d, J= 8.4 Hz, 2H); 7.52 (d, J= 1.5 Hz, IH); 7.44-7.37 (m, 4H); 5.47 (s, 2H); 4.32- 4.25 (q, J=7.2 Hz, 2H); 1.32-1.27 (t, J= 7.2 Hz₅ 3H).

Step3 :2-(4~bromo phenyl)-3 -oxo- 1 -(2,4-dichlorobenzyl)-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid:Yield: 52%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.87 (s, IH); 7.62 (d, J= 9.0 Hz, 2H); 7.52 (d, J= 2.1 Hz, IH); 7.45-7.34 (m, 4H); 5.60 (s, 2H).

Intermediate 26 2-(4-bromo phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 3-chloro benzyl bromide in place of benzyl bromide in Step 2

Step2:2-(4-bromo phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester

Yield: 44%. ¹H NMR (δ, DMSO-dό, 300 MHz): 8.0 l(s, IH); 7.67 (d, J= 9.3 Hz, 2H);

7.47 (d, J= 9.0 Hz, 2H); 7.36-7.18 (m, 4H); 5.40 (s, 2H); 4.32-4.25 (q, J=7.2 Hz, 2H);

1.33-1.28 (t, J= 7.2 Hz, 3H).

Step3:2-(4-bromo phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Yield: 84%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.75 (b s, IH); 7.96(s, IH); 7.67 (d, J=

8.4 Hz, 2H); 7.45 (d, J= 9.0 Hz, 2H); 7.38-7.28 (m, 2H); 7.24 (s, IH); 7.18 (d, J= 7.5 Hz,

IH); 5.42 (s, 2H).

Intermediate 27 2-(4-bromophenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 2-bromo benzyl bromide in place of benzyl bromide in Step 2

Step2 : 2-(4-bromo pheny l)-3 -oxo- 1 -(2-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester: Yield: 65%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.0 l(s, IH); 7.63 (d, J= 8.7 Hz, 2H); 7.55 (d, J= 8.7 Hz, IH); 7.43 (d, J= 8.7 Hz, 2H); 7.40-7.26 (m, 3H); 5.50 (s, 2H); 4.31-4.24 (q, J= 7.5 Hz, 2H); 1.31-1.26 (t, J= 7.5 Hz, 3H). Step3:2-(4-bromophenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole-4~ carboxylic acid :Yield: 74%. ¹H NMR (δ, DMSO-d6, 400 MHz): 7.96 (s, IH); 7.62 (d, J= 6.8 Hz, 2H); 7.58 (dd, J= 1.17 and 7.8 Hz, IH); 7.41 (d, J= 6.8 Hz, 2H); 7.40-7.31 (m, 3H); 5.53 (s, 2H).

Intermediate 28

2-(4-bromophenyl)-3-oxo-l-(4-bromobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid

Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and 4-bromo benzyl bromide in place of benzyl bromide in Step 2

Step2 :2-(4-bromophenyl)-3-oxo- 1 -(4-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester: Yield: 47%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH);

7.67 (d, J= 8.7 Hz, 2H); 7.51-7.46 (m, 4H); 7.21 (d, J= 8.7 Hz, 2H); 5.38 (s, 2H); 4.32-

4.25 (q, J= 7.2 Hz, 2H); 1.32-1.27 (t, J= 6.6 Hz, 3H).

Step3 :2-(4-bromophenyl)-3-oxo- 1 -(4-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid: Yield: 96%. ¹H NMR (δ, DMSO-d6, 400 MHz): 7.90 (s, IH); 7.66 (d, J=

8.7 Hz, 2H); 7.50-7.45 (m, 4H); 7.21 (d, J= 8.4 Hz, 2H); 5.46 (s, 2H).

Intermediate 29

2-(4-bromo phenyl)-3-oxo-l-hexyl-2,3-dihydro-lH-pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of p-bromo phenyl hydrazine in place of 2,4- dichlorophenyl hydrazine in Step 1, and hexyl bromide in place of benzyl bromide in Step 2

Step2:2-(4-bromophenyl)-3-oxo-l-hexyl-2,3-dihydro-lH-pyrazole-4-carboxylicacid ethyl esteriYield: 71%. ¹H NMR (δ, DMSO-d6, 400 MHz): 7.93 (s, IH); 7.58 (b s, 4H); 4.39- 4.28 (m, 4H); 1.66-1.64 (m, 2H); 1.40-1.35 (t, J= 6.9 Hz, 3H); 1.31-1.23 (m, 6H); 0.87- 0.83 (t, J= 6.6 Hz₅ 3H).

Step3:2-(4-bromo phenyl)-3~oxo-l-hexyl-2,3-dihydro-lH-pyrazoIe-4-carboxylic acid Yield: 76%. ¹H NMR (δ, DMSO-d6, 400 MHz): 12.57 (s, IH); 7.93 (s, IH); 7.74 (d, J= 8.7 Hz, 2H); 7.59 (d, J= 9.0 Hz, 2H); 4.40-4.36 (t, J= 6.3 Hz, 2H); 1.58-1.51 (m, 2H); 1.18-1.14 (m, 6H); 0.81-0.77 (t, J- 5.7Hz, 3H).

Intermediate 30

2-(2,4-difluorophenyl)-3-oxo-l-(4-trifluoromethylbenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 2,4 difluoro phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 4-trifluoromethyl benzyl bromide in place of benzyl bromide in Step 2 Stepl:2-(2,4-difluorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester :Yield: 32%. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.83 (s, IH); 7.64-7.51 (m, 2H);

7.30-7.23 (m, IH); 4.25-4.18 (q, J= 6.9 Hz, 2H); 1.29-1.24 (t, J= 6.9 Hz, 3H).

Step2:2-(2,4-difluorophenyl)-3 -oxo- 1 -(4-trifluoromethylbenzyl)-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid ethyl ester

Yield: 43%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.04 (s, IH); 7.65 (d, J= 8.1 Hz, 2H);

7.52-7.44 (m, 2H); 7.37 (d, J= 7.5 Hz, 2H); 7.23-7.16 (m, IH); 5.47 (s, 2H); 4.33-4.26 (q,

J= 6.9 Hz, 2H); 1.33-1.27 (t, J= 7.2 Hz, 3H).

Step3 :2-(2,4-difluorophenyl)-3-oxo- 1 -(4-trifluoromethylbenzyl)-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid

Yield: 80%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.82 (b s, IH); 7.99 (s, IH); 7.64 (d, J=

8.1 Hz, 2H); 7.53-7.40 (m, 2H); 7.36 (d, J= 8.1 Hz, 2H); 7.21-7.16 (t, J= 6.6 Hz and 9.0

Hz, IH); 5.51 (s, 2H).

Step 1 for Intermedites 31 is same as described in Intermediate 30

Intermediate 31

2-(2,4-difluorophenyl)-3-oxo- 1 -(3-trifluoromethylbenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 2,4 difluoro phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 3-trifluoromethyl benzyl bromide in place of benzyl bromide in Step 2

Step2:2-(2,4-difluorophenyl)-3-oxo-l-(3-trifluoromethylbenzyl)-2,3-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 63%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.03 (s, IH); 7.67-7.65 (m, IH); 7.32- 7.40 (m, 6H); 7.18 (m, IH); 5.45 (s, 2H); 4.33-4.25 (q, J= 7.2 Hz, 2H); 1.33-1.28 (t, J= 7.2 Hz, 3H). StepS^-Cl^-difluorophenyO-S-oxo-l-CS-trifluoromethylbenzyO-l^-dihydro-lH- pyrazole-4-carboxylic acid

Yield: 95%. ¹H NMR (δ, DMSO-d6, 300 MHz): 11.00 (b s, IH); 8.09 (s, IH); 7.57 (d, J=

6.9 Hz, 2H); 7.43-7.47 (m, 3H); 7.29-7.22 (m, IH); 6.97-6.91 (t, J= 8.4 Hz, 2H); 5.55 (s,

2H).

Intermediate 32 l-(3-chloro-benzyl)-2-(3-trifluoromethyl- phenyl)-4-pyrazolidinecarboxylicacid

Intermediatel with the exception being use of 3-trifluoromethyl phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 3-chloro benzyl bromide in place of benzyl bromide in Step 2

Stepl : l-(3-TrifluoromethyI-phenyl)-pyrazolidine-4-carboxylicacid ethyl ester

Yield: 30.6%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.34-7.27 (m, 2H); 7.12 (d, J= 7.2 Hz, IH);

7.04 (d, J= 7.8 Hz, IH); 4.23-4.16 (q, J= 7.2 Hz, 2H); 3.68-3.62 (m, 2H); 3.36-3.30 (m,

2H); 3.15-3.08 (m, IH); 1.31-1.26 (t, J= 7.5 Hz, 3H).

Step2:l-(3-chloro-benzyl)-2-(3-trifluoromethyl- phenyl)-4-pyrazolidinecarboxylicacid ethyl ester

Yield: 53.8%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.39 (s, IH); 7.33-7.25 (m, 5H); 7.16 (b s,

IH); 7.03 (d, J= 7.5 Hz, IH); 4.17 (b s, 2H); 3.84 (b s, 5H); 3.26-3.21 (m, 2H); 1.25 (b s,

3H).

Step3 : 1 -(3 -chloro-benzyl)-2-(3 -trifluoromethyl- ρhenyI)-4-pyrazo lidinecarboxy licacid

Yield: 98.8%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.38 (s, IH); 7.34-7.24 (m₅ 5H); 7.14 (bd,

J= 7.2 Hz, IH); 7.04 (d, J= 7.5 Hz, IH); 4.00-3.60 (m, 5H); 3.31-3.10 (m, 2H).

Intermediate33

2-(4-Trifluoromethylphenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid

Intermediate 1 with the exception being use of 3-trifluoromethyl phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 2-chloro benzyl bromide in place of benzyl bromide in Step 2

Stepl:2-(4-Trifluoromethyl phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester :Yield: 47.0%. ¹H NMR (δ, DMSO-d₆, 300 MHz): 8.00 (d, J=8.7 Hz, 2H), 7.90

(s, IH), 7.87 (d, J=7.8 Hz, 2H), 4.26-4.19 (q, J= 6.9 Hz, 2H); 1.30-1.25 (t, J= 6.9 Hz, 3H).

Step2:2-(4-Trifluoromethyl phenyl)- 1 -(2-chlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-pyrazole-

4-carboxylic acid ethyl ester

Yield: 45.0%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.07 (s, IH), 7.79 (d, J=8.4 Hz, 2H),

7.70 (d, J=8.7 Hz, 2H), 7.37 (d, J=6.9 Hz, IH), 132-121 (m, 3H), 5.52 (s, 2H), 4.33-4.26

(q, J= 7.2 Hz, 2H); 1.33-1.26 (t, J= 6.9 Hz, 3H).

Step3:2-(4-Trifluoromethylphenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-

4-carboxylic acid

Yield: 44.6%. ¹H NMR (δ, DMSO-d₆, 300 MHz): 12.9 (bs, IH). 8.02 (s, IH), 7.79 (d,

J=8.7 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 7.37-7.21 (m, 4H), 5.56 (s, 2H).

Steplof Intermedites 34-36 was prepared according to the process as described in step 1 of Intermediate 33

Intermediate 34

2-(4-Trifluoromethyl phenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4- carboxylic acid

Intermediate 1 with the exception being use of 4-trifluoromethyl phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 2,4-dichloro benzyl bromide in place of benzyl bromide in Step 2

Step2:2-(4-Trifluoromethyl phenyl)-l-(2, 4-dichlorobenzyl)-3-oxo-2, 3-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 64.4%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.07 (s, IH), 7.79 (d, J=8.7 Hz, 2H),

7.68 (d, J=8.4 Hz₅ 2H), 7.42 (d, J=1.8 Hz, IH), 7.39-7.29 (m, 2H), 5.47 (s, 2H), 4.32-4.25

(q, J= 6.9 Hz, 2H); 1.33-1.28 (t, J= 7.2 Hz, 3H).

Step3:2-(4-Trifluoromethylphenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH- pyrazole-4-carboxylic acid

Yield: 54.2%. ¹H NMR (δ, DMSOd₆, 300 MHz): 12.9 (bs, IH), 8.02 (s, IH), 7.79 (d,

J=8.7 Hz, 2H), 7.67 (d, J=8.4 Hz,-2H), 7.43 (d, J=I.5 Hz, IH), 7.38-7.30 (m, 2H), 5.51 (s,

2H).

Intermediate 35

2-(4-Trifluoromethyl phenyl)- 1 -(2-trifluoromethylbenzyl)-3 -oxo-2,3 -dihydro- 1 H- pyrazole-4-carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 4-trifluoromethyl phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 4-trifluoromethyl benzyl bromide in place of benzyl bromide in Step 2

Step2: 2-(4-Trifluoromethylphenyl)-l-(2-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH- pyrazole-4-carboxylic acid ethyl ester

Yield: 43.2%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.09 (s, IH), 7.79 (d, J=8.1 Hz, 2H),

7.69 (d, J=8.4 Hz, 2H), 7.65-7.53 (m, 4H), 5.61 (s, 2H), 4.32-4.25 (q, J= 6.9 Hz, 2H);

1.31-1.26 (t, J= 6.9 Hz, 3H).

Step3 :2-(4~Trifluoromethyl phenyl)- 1 -(2-trifluoromethylbenzyl)-3 -oxo-2,3-dihydro- 1 H- pyrazole-4-carboxylic acid

Yield: 66.7%. ¹H NMR (δ, DMSO-d₆, 300 MHz): 12.9 (bs, IH), 8.03 (s, IH), 7.78 (d,

J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H), 7.64-7.50 (m, 4H), 5.65 (s, 2H).

Intermediate 36

2-(4-trifluoromethyl phenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid

This compound was synthesized in 3 steps according to the process as described for Intermediate 1 with the exception being use of 4-trifluoromethyl phenyl hydrazine in place of 2,4-dichlorophenyl hydrazine in Step 1, and 2-bromo benzyl bromide in place of benzyl bromide in Step 2

Step2: 2-(4-trifluoromethyl phenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole- 4-carboxylic acid ethyl esteπYield: 43%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.06 (s, IH); 7.80-7.69 (AB q, J= 8.4 Hz and 8.1 Hz, 4H); 7.50-7.20 (m, 4H); 5.51 (s, 2H); 4.32- 4.26 (q, J= 7.2 Hz and 6.6 Hz, 2H); 1.32-1.27 (t, J= 6.6 Hz, 3H).

Step3 :2-(4-trifiuoromethyl phenyl)-3-oxo- 1 -(2-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole- 4-carboxyIic acid:Yield: 70%. ¹H NMR (δ, DMSO-d6, 300 MHz): 12.80 (b s, IH); 8.02 (s, IH); 7.80-7.69 (AB q, J= 8.4 Hz and 9.0 Hz, 2H); 7.49 (d, J= 7.5 Hz, 2H); 7.39-7.36 (dd, J= 7.8 Hz and 2.1 Hz, IH); 7.30 (d, J= 7.2 Hz, IH); 7.27-7.19 (m, 2H); 5.55 (s, 2H). Example - 1

1 -Benzyl-2-(2,4-dichIorophenyI)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylicacid adamantyl- 1 -ylamide:

The amide was prepared following two protocols:

(A) To a solution of intermediate -1 (190 mg, 0.52 mmol) in benzene (10 mL) in the presence of catalytic amount of dimethyl formamide was slowly charged oxalyl chloride (132 μL, 1.57 mmol) in an ice bath and under inert atmosphere. The mixture was allowed to come to room temperature and stirred for 3 hours after which the volatile matters were removed. The resultant residue was dissolved in dichloromethane (DCM) (15 mL) followed by the addition of triethylamine (219 μL, 1.57 mmol) and adamantane-1 -amine (95 mg, 0.63 mmol) and the mixture was stirred for 3 hours. The reaction mixture was diluted with DCM and the organic layer was washed with water, and saturated sodium bicarbonate solution followed by brine; dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified over silica gel column chromatography using mixture of methanol and chloroform as mobile phase to give amide (yield = 90 mg). (B) To a solution of intermediate -1 (500 mg, 1.37 mmol) in dimethyl formamide (10 mL) was charged BOP (610 mg, 1.37 mmol) and triethylamine (211 mL, 1.51 mmol). The mixture was stirred for 10 minutes at room temperature under inert atmosphere. Adamantane-1 -amine (208.3 mg, 1.37 mmol) was added to the mixture at once and the mixture was stirred for another 1 hour at the same condition. The reaction mixture was diluted with water and the organic layer was extracted with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate and concentrated and the residue was subjected to column chromatography to give the title amide (415 mg). ¹H NMR (DMSOd₆)S: 8.00(s, IH), 7.87 (d, J=2.1 Hz, IH), 7.56-7.53 (dd, J=8.4 and 2.1 Hz, IH), 7.31-7.28 (m, 3H), 7.21 (s, IH), 7.13-7.10 (m, 2H), 5.30 (s, 2H), 2.05 (s, 9H), 1.66 (s, 6H). MS: m/z = 496. Examples 2-10 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using suitable amines.

Example - 2 l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid piperidine- 1 -ylamide.

¹H NMR (DMSO-d^δ: 9.11 (s, IH), 7.99 (s, IH)₅ 7.86 (d, J=2.4 Hz, IH), 7.56-7.52 (dd, J=8.1 and 1.8 Hz, IH), 7.30-7.28 (m, 4H), 7.12 (m, 2H), 5.37 (s, 2H), 2.80 (bt, 4H), 1.6 (bt, 4H), 1.40 (m, 2H). MS: m/z = 445.

Example - 3 l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -(4- methylsulfanylphenyl)amide.

H NMR (CDCl₃) δ: 8.08 (s, IH), 7.91 (bs, IH), 7.59 (d, J=2.1 Hz, IH), 7.93-7.15 (m, 1 IH), 5.00 (s, 2H), 2.47 (s, 3H).

Example - 4 l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4carboxylicacid morpholin-4-yl-amide.

¹H NMR (DMSO-dejδ: . 9.24(s, IH), 7.99 (s, IH), 7.87 (d, J=2.4 Hz, IH), 7.55 and 7.53 (dd, J=8.4 and 2.4 Hz, IH), 7.30-7.28 (bm, 4H), 7.13-7.11 (bm, 2H), 5.37 (s, 2H), 3.67 (bs, 4H), 2.89 (bs, 4H). MS: m/z = 447.

Example - 5 l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4- methanesulfonylphenyl)-amide.

¹H NMR (DMSO-d_δ)δ: . 10.38(s, IH), 8.30 (s, IH), 8.02 (d, J=8.4 Hz, 2H), 7.92 (d, J=9.0 Hz, 2H), 7.90 (s, IH), 7.58 and 7.55 (dd, J=8.4 and 2.4 Hz, IH), 7.36-7.25 (m, 4H), 7.15- 7.13 (m, 2H), 5.42 (s, 2H), 3.20 (s, 3H). Purity (HPLC): 94.5%.

Example - 6 l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylicacid cyclohexyl amide.

¹H NMR (DMSOd₆) δ: . 8.06(s, IH), 7.89 (s, IH), 7.86 (d, J=2.4 Hz, IH), 7.55 and 7.52 (dd, J=8.4 and 3.0 Hz, IH), 7.30-7.24 (m, 4H), 7.12 (d, J=7.5 Hz, 2H), 5.37 (s, 2H), 3.74 (m, IH), 1.85-1.59 (m, 5H), 1.34-1.11 (m, 5H). MS: m/z = 444. Purity (HPLC): 98.9%. Example - 7 l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylicacid-4- chlorobenzylzmide

¹H NMR (DMSO-d^δ: . 8.76(t, 1=6 Hz, IH), 8.10 (s, IH), 7.86 (d, J=2.4 Hz, IH), 7.55 and 7.52 (dd, J=8.4 and 2.1 Hz, IH), 7.44-7.36 (q, 2H), 7.31-7.23 (m, 4H), 7.07 (d, J=6.3 Hz, 2H), 5.39 (s, 2H), 4.45 (d, J=6.3 Hz, 2H). MS: m/z=486. Purity (HPLC): 98.0%.

Example - 8 l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4- hydroxycyclohexyl)-amide.

H NMR (DMSO-d₆)) δ:. 8.04(s, IH), 7.86 (d, J=2.4 Hz, IH), 7.84 (s, IH), 7.56 and 7.52 (dd, J=8.4 and 2.4 Hz, IH), 7.30-7.25 (4H), 7.11 (d, J=8.4 Hz, 2H), 5.37 (s, 2H), 4.58 (bs, IH), 3.72-3.70 (bm, IH), 3.40 (bm, IH), 1.86-1.83 (m, 4H), 1.39-1.19 (m, 4H). Purity (HPLC): 99.1%.

Example - 9

N4-[(2R)-(6,6-diemthyl-bicyclo[3.1. l]hept-3-ylmethyl)-l-Benzyl-2-(2,4-dichlorophenyl)- 3-oxo-2,3-dihydro-lH-4-pyrazole carboxamide

¹H NMR (CDCl_a)δ: . 7.96 (s, IH), 7.54 (d, J=1.8 Hz, IH), 7.35-7.28 (m, 4H), 7.17-7.09 (m, 3H), 6.13 (bt, IH), 5.04 (s, 2H), 3.34 (t, J= 7.2 and 6.3 Hz, 2H), 2.36-2.30 (m, IH), 2.18-2.11 (m, IH), 1.95-1.82 (m, 5H), 1.57 (bs, 2H), 1.52-1.44 (m, IH), 1.18 (s, 3H), 1.04 (s, 3H), 0.87 (d, J=9.9 Hz, IH). Purity (HPLC): 96.5%.

Example - 10

1 -Benzyl-4-[4-(4-chlorophenyl)-piperazine- 1 -carbonyl]-2-(2,4-dichlorophenyl)- 1 ,2- dihydro-pyrazole-3-one

¹H NMR (DMSO-d6)δ:. 7.90 (d, J=I.8 Hz, IH), 7.77 (s, IH), 7.60-7.57 (dd, J=9.0 and 2.4 Hz, IH), 7.46 (d, J=8.4 Hz, IH), 7.30-7.25 (m, 5H), 7.16-7.12 (m, 2H), 6.97 (d, J=8.7 Hz, 2H), 5.21 (s, 2H), 3.64 (bs, 4H), 3.16 (bs, 4H). Purity (HPLC): 97.6%.

Example - 10a l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid N'- (4-chloro-phenyl)-hydrazide]

Yield: 22.34%. M. Pt.: 149-153 ⁰C. ¹H NMR (DMSO-d₆, 300 MHz) δ: 10.15 (s, IH); 8.21 (s, IH); 8.13 (s, IH); 7.88 (d, J=2.7 Hz, IH), 7.57-7.54 (dd, J=8.4 & 2.1 Hz, IH); 7.35- 7.20 (m, 6H), 7.10 (d, J=6.6 Hz, 2H), 6.81 (d, J= 8.7 Hz, 2H); 5.38 (s, 2H). Purity: 99.20%. EIMS (m/z): 487.4, 489.1.

Examples 11-12 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 with exception being use of intermediate 4 instead of intermediatel and reacting with suitable amines.

Example - 11 l-(3-Chlorbenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2.3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methylsulfonyl-phenyl)-amide

Yield: 47%. M. Pt: 141-142⁰C. ¹H NMR (DMSO-d6, 300 MHz)δ: 10.40 (s, IH); 8.32 (s, IH); 8.01 (d, J= 8.1 Hz, 2H); 7.93-7.90 (m, 3H); 7.59 (dd, J= 2.1 Hz and 8.4 Hz, IH); 7.43-7.28 (m, 3H); 7.13-7.08 (m, 2H); 5.41 (s, 2H); 3.20 (s, 3H). Purity: 99.07%.

Example - 12

1 -(3 -Chlorobenzyl)-2-(2,4-dichlorophenyl)-3 -oxo-2,3 -dihydro- 1 H-pyrazole-4-carbaxolic acid-(4-methylsulfanylphenyl)-amide

Yield: 38%. M. Pt: 121-122⁰C. ¹H NMR (DMSO-d6, 300 MHz)δ: 10.00 (s, IH); 8.27 (s, IH); 7.89 (d, J= 2.4 Hz, IH); 7.70 (d, J= 8.7 Hz, 2H); 7.58 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.42-7.27 (m, 5H); 7.13-7.08 (m, 2H); 5.40 (s, 2H); 2.48 (s, 3H). Purity: 97.52%.

Examples 13- 19b were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediates in place of intermediate 1 and suitable amines

Example - 13 l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-chlorophenyl)-amide

Yield: 40%. M. Pt: 147-148⁰C. ¹H NMR (DMSO-d6, 300 MHz)δ: 10.11 (s, IH); 8.26 (s, IH); 7.88 (d, J= 2.1 Hz, IH); 7.77 (d, J= 8.7 Hz, 2H); 7.57 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.42 (d, J= 8.4 Hz₅ 2H); 7.34 (d, J= 8.4 Hz, 2H); 7.18 (d, J=8.4 Hz, 2H); 5.40 (s, 2H). Purity: 98.82%.

Example - 14 l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(3,4-difluorophenyl)-amide

Yield: 20%. M. Pt: 133-134⁰C. ¹H NMR (DMSO-d6, 300 MHz) δ: 10.18 (s, IH); 8.24 (s, IH); 7.93-7.87 (m, 2H); 7.57 (dd, J= 2.7 Hz and 8.4 Hz, IH); 7.48-7.41 (m, 3H); 7.34 (d, J= 8.4 Hz, 2H); 7.18 (d, J=8.4 Hz, 2H); 5.39 (s, 2H). Purity: 97.6%.

Example - 15 l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methanesulfonylphenyl) amide

Yield: 51%. M. Pt.: 87-89⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.37 (s, IH); 8.28 (s, IH); 7.99 (d, J= 8.7 Hz, 2H); 7.91-7.87 (m, 3H); 7.56 (dd, J= 2.1 Hz and 8.4 Hz, IH); 7.41 (d, J= 8.7 Hz, IH); 7.32 (d, J= 7.5 Hz, 2H); 7.16 (d, J= 8.4 Hz, 2H); 5.39 (s, 2H); 3.17 (s, 3H). Purity: 98.6%.

Example - 16 l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-trifluoromethylphenyl)-amide

Yield: 13%. M. Pt.: 154-155°C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.31 (s, IH); 8.29 (s, IH); 7.97 (d, J= 8.4 Hz, IH); 7.89 (d, J= 2.4 Hz, IH); 7.73 (d, J= 8.4 Hz, 2H); 7.58 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.43 (d, J= 8.4 Hz, IH); 7.34 (d, J= 8.4 Hz, 2H); 7.18 (d, J= 8.4 Hz, 2H); 5.40 (s, 2H). Purity: 96.53%.

Example - 17

N4-(4-methylsulfanylphenyl)-l-(4-chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide

Yield: 43%. M. Pt: 129-130⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.99 (s, IH); 8.25 (s, IH); 7.88 (d, J= 2.4 Hz, IH); 7.69 (d, J= 8.4 Hz, 2H); 7.57 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.42 (d, J= 8.4 Hz, IH); 7.34 (d, J= 8.4 Hz, 2H); 7.28 (d, J= 8.4 Hz, 2H); 7.18 (d, J= 8.4 Hz, 2H); 5.40 (s, 2H); 2.47 (s, 3H). Purity: 97.94%.

Example - 18 l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide

Yield: 34%. M. Pt.: 158-159°C. ¹H NMR (δ, DMS0-d6, 300 MHz): 8.01 (s, IH); 7.86 (d, J= 2.4 Hz, IH); 7.55 (dd, J= 2.7 Hz and 8.4 Hz, IH); 7.39-722 (m, 4H); 7.15 (d, J= 8.1 Hz, 2H); 5.31 (s, 2H); 2.04 (b s, 9H); 1.65 (b s, 6H). Purity: 97.55%.

Example - 19

2-(2,4-Dichlorophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-flυorophenyl)-amide

Yield: 53%. M. Pt.: 133-135 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.05 (s, IH); 8.25 (s, IH); 7.88 (d, J= 2.1 Hz, IH); 7.76-7.71 (m, 2H); 7.59-7.56 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.42 (d, J= 8.4 Hz, IH); 7.34 (d, J= 8.4 Hz, 2H); 7.24-7.16 (m, 4H); 5.40 (s, 2H). Purity: 99.1%.

Example - 19a

1 -(4-Chlorophenyl)-2-(2,4-Dichlorophenyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid (4-cyanophenyl) amide

Yield: 19%. M. Pt: 162-166 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 10.37 (bs, IH); 8.28 (s, IH); 7.94- 7.84 (m, 5H), 7.56-7.18 (m, 6H), 5.39 (s, 2H). Purity: 97.25%.

Example - 19b l-(4-Chlorobenzyl)-2-(2,4-Dichlorophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-hydroxyphenyl) amide

Yield: 9.5%. M. Pt: 158-163 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.76 (s, IH); 9.26 (s, IH), 8.22 (s, IH); 7.87 (d, J=2.1 Hz, IH), 7.58-7.55 (dd, J=8.4 & 2.4 Hz, IH), 7.47 (d, J=8.7 Hz, 2H), 7.41 (d, J=8.4 Hz, IH), 7.34 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 6.75 (d, J=8.4 Hz, 2H), 5.40 (s, 2H). Purity: 94.3%.

Examples 20-23 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediateόin place of intermediate 1 and suitable amines

Example -20

1 -(2-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid (4-methanesulfanylphenyl)-amide

Yield: 29%. M. Pt.: 136-137⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.00 (s, IH); 8.28 (s, IH); 7.86 (d, J= 2.1 Hz, IH); 7.70 (d, J= 8.7 Hz, 2H); 7.53 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.36-7.27 (m, 7H); 5.49 (s, 2H); 2.48 (s, 3H). Purity: 96.16%.

Example - 21 l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid (4-fluoro-phenyl)-amide

Yield: 25%. M. Pt: 140-141⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.06 (s, IH); 8.27 (s, IH); 7.86 (d, J= 1.5 Hz, IH); 7.77-7.72 (m, 2H); 7.54 (d, J= 7.5Hz, IH); 7.36-7.18 (m, 7H); 5.49 (s, 2H). Purity: 97.68%.

Example - 22 l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid(adamantan-l-yl)-amide

Yield: 60%. M. Pt.: 171-172⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.04 (s, IH); 7.84 (d, J= 2.1 Hz, IH); 7.51 (d, J= 9.3 Hz, IH); 7.37-7.24 (m, 6H); 5.40 (s, 2H); 2.05 (b s, 9H); 1.66 (b s, 6H). Purity: 98.04%.

Example - 23 l-(2-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxyIic acid cyclohexyl amide

Yield: 70%. M. Pt: 125-126⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 7.91 (d, J= 8.1 Hz, IH); 7.84 (d, J= 2.1 Hz, IH); 7.52 (dd, J= 2.4 Hz and 8.4 Hz, IH); 7.39-7.23 (m, 5H); 5.46 (s, 2H); 3.75 (s, IH); 1.85-1.60 (m, 5H); 1.29-1.15 (m, 5H). Purity:

98.19%.

Examples 24-27 were prepared according to either procedure (A) or (B) as mentioned in

Example - 1 above using intermediate7in place of intermediate 1 and suitable amines

Example - 24

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (3-hydroxy-adamantan- 1 -yl)amide

Yield: 18%. M. Pt.: 177-179⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.04 (s, IH); 7.87 (d, J= 2.1 Hz, IH); 7.58-7.54 (dd, J= 2.4 Hz and 9.0 Hz, IH); 7.38-7.30 (m, 2H); 7.17-7.12 (m, IH); 6.97 (d, J= 7.2 Hz, IH); 6.88 (d, J= 8.7 Hz, IH); 5.34 (s, 2H); 2.17 (b s, 2H); 1.95 (b s, 6H); 1.60-1.50 (m, 6H). Purity: 93.49%.

Example - 25

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid N'-phenyl-hydrazide

Yield: 28%. M. Pt: 127-13O⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.13 (d, J= 2.4 Hz, IH); 8.23 (s, IH); 7.93-7.89 (dd, J= 2.1 Hz and 9.3 Hz, 2H); 7.60-7.56 (dd, J= 2.1 Hz and 8.7 Hz, IH); 7.43 (d, J= 8.4 Hz, IH); 7.34-7.29 (m, IH); 7.21-7.14 (m, 3H); 6.95 (d, J= 7.5 Hz₅ IH); 6.87 (d, J= 9.9 Hz, IH); 6.81 (d, J= 7.8 Hz, 2H); 6.76-6.71 (t, J= 7.5 Hz, IH); 5.40 (s, 2H). Purity: 97.7%. Example - 26

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(2,4-dichlorophenyl)-l-(3- fluorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 55%. M. Pt.: 145-148 ⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.11 (s, IH); 7.88 (d, J= 2.1 Hz, 2H); 7.59-7.55 (dd, J= 2.1 Hz and 8.4 Hz, IH); 7.39 (d, J= 8.4 Hz, IH); 7.34- 7.29 (m, IH); 7.17-7.10 (t, J= 8.4 Hz, IH); 6.97 (d, J= 7.2 Hz, IH); 6.87 (d, J= 9.3 Hz, IH); 5.42 (s, 2H); 4.39-4.34 (m, IH); 2.44-2.35 (m, 2H); 2.06-2.01 (t, J= 7.5 Hz, IH); 1.94 (b s, IH); 1.82-1.80 (m, IH); 1.69-1.63 (m, IH); 1.23 (s, 3H); 1.18-1.15 (m, IH); 1.07 (s, 6H). Purity: 99.09%.

Example - 27

2-(2,4-Dichlorophenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxylic acid -(4-trifluoromethyl phenyl)-amide

Yield: 07%. M. Pt: 103-105 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.32 (s, IH); 8.31 (s, IH); 7.97 (d, J= 8.4 Hz, 2H); 7.90 (d, J= 2.1 Hz, IH); 7.74 (d, J= 8.4 Hz, 2H); 7.61-7.57 (dd, J= 2.4 Hz and 8.7 Hz, IH); 7.43 (d, J= 8.7 Hz, IH); 7.33-7.29 (m, IH); 7.17-7.11 (m, IH); 6.98 (d, J= 7.2 Hz, IH); 6.91 (d, J= 10.2 Hz, IH); 5.42 (s, 2H). Purity: 94.5%. Examples 28-29 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediates in place of intermediate 1 and suitable amines

Example - 28 2-(2,4-Dichlorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide

Yield: 38%. M. Pt.: 157-16O⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 10.40 (s, IH); 8.33 (s, IH); 8.01 (d, J= 8.7 Hz, 2H); 7.92 (d, J= 9.0 Hz, 2H); 7.87 (d, J= 2.1 Hz, IH); 7.67 (d, J= 6.9 Hz, IH); 7.58-7.41 (m, 5H); 5.51 (s, 2H); 3.20 (s, 3H). Purity: 99.4%.

Example - 29

2-(2,4-Dichlorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide

Yield: 43%. ¹H NMR (δ, DMSO-d₆, 300 MHz): 10.01 (s, IH); 8.28 (s, IH); 7.86 (d, J= 1.8 Hz, IH); 7.71-7.65 (m, 3H); 7.57-7.41 (m, 5H); 7.28 (d, J= 9.0 Hz, 2H); 5.51 (s, 2H); 2.47 (s, 3H).

Examples 30-31 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate2 in place of intermediate 1 and suitable amines

Example -30

2-(2,4-Dichlorophenyl)- 1 -(4-trifluoromethylbenzyl)-3-oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide

Yield: 34%. M. Pt.: 175-177 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.40 (s, IH); 8.33 (s, IH); 8.00 (d, J= 8.7 Hz, 2H); 7.91 (d, J= 9.3 Hz, 2H); 7.87 (d, J= 2.4 Hz, IH); 7.65 (d, J= 8.4 Hz, 2H); 7.57-7.54 (dd, J= 6.3 Hz and 2.7 Hz, IH); 7.47 (d, J= 8.1 Hz, 2H); 7.38 (d, J= 7.8 Hz, 2H); 5.51 (s, 2H); 3.19 (s, 3H). Purity: 99.6%.

Example -31

2-(2,4-Dichlorophenyl)- 1 -(4-trifluoromethylbenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide

Yield: 74%. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.00 (s, IH); 8.27 (s, IH); 7.95 (s, IH); 7.86 (d, J= 2.1 Hz, IH); 7.69 (d, J= 8.4 Hz, 2H); 7.64 (d, J= 8.1 Hz, 2H); 7.57-7.53 (dd, J= 2.1 Hz and 8.7 Hz, IH); 7.46 (d, J= 8.7 Hz, 2H); 7.38 (d, J= 8.1 Hz, 2H); 7.28 (d, J= 8.4 Hz, 2H); 5.51 (s, 2H); 2.47 (s, 3H).

Examples 32-31 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 7 in place of intermediate 1 and suitable amines

Example 32

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4-chlorophenyl)-amide:

¹H NMR (DMSOdQS:. 10.12 (s, IH), 8.27 (s, IH), 7.90 (d, J=2.4 Hz, IH), 7.77 (d, J=8.7 Hz, 2H), 7.60-7.56 (dd, J=8.4 and 2.1 Hz, IH), 7.42 (d, J=8.7 Hz, 3H), 7.36-7.28 (q, IH), 7.13 (t, J=8.4 Hz, IH), 6.99 (d, J=7.5 Hz, IH), 6.90 (d, J=9.6 Hz, IH), 5.41 (s, 2H). Purity (HPLC): 99.4%.

Example - 33

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-ylamide:

¹H NMR (DMSO-d6jδ: 8.02 (s, IH), 7.87 (d, J=2.1 Hz, IH), 7.58-7.55 (dd, J=8.4 and 2.1 Hz, IH), 7.38 (d, J=8.7 Hz, IH), 7.37-7.30 (m, IH), 7.26 (s, IH), 7.17-7.11 (dt, J=8.4 and 2.7 Hz, IH), 6.97 (d, J=7.8 Hz, IH), 6.89 (d, J=9.9 Hz, IH), 5.34 (s, 2H), 2.05 (s, 9H), 1.66 (s, 6H). Purity (HPLC): 97.2%.

Example - 34

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-4-methylsulfanylphenyl amide:

¹H NMR (DMSO-d6)δ:. 9.99 (s, IH), 8.26 (s, IH), 7.89 (d, J=2.1 Hz, IH), 7.69 (d, J=9.0 Hz, 2H), 7.60-7.56 (dd, J=8.7 and 2.4 Hz, IH), 7.42 (d, J=8.7 Hz, IH), 7.36-7.27 (m, 4H), 7.17-7.10 (dt, J=8.7 and 2.7 Hz, IH), 6.99 (d, J=7.2 Hz, IH), 6.90 (d, J=9.6 Hz, IH), 5.41 (s, 2H), 2.47 (s, 3H). MS: m/z = 502 (M⁺+!). Purity (HPLC): 98.8%.

Example - 35

N4-[(2R)-(6,6-dimethylbicyclo[3.1.1]hept-3-yl-methyl)-2-(2,4-Dichlorophenyl)-l-(3- fluorobenzyO-S-oxo^S-dihydro-lH-pyrazole^-carboxylic acid amide

¹H NMR (CDCyδ: 7.91 (s, IH), 7.54 (d, J=2.4 Hz, IH), 7.35-7.17 (m, 3H), 7.05-6.99 (bt, IH), 6.90 (d, J=7.5 Hz, IH), 6.82 (d, J=9.3 Hz, IH), 6.06 (bt, IH), 5.12 (s, 2H), 2.40- 2.13 (m, 3H), 1.96-1.84 (m, 5H), 1.55-1.46 (m, IH), 1.18 (s, 3H), 1.05 (s, 3H), 0.87 (bd, IH). MS: m/z = 516 (M⁺+l). Purity (HPLC): 96.7%.

Examples 36-40 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 8 in place of intermediate 1 and suitable amines.

Example - 36

1 -Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid-(4-methylsulfanylphenyl)-amide

¹H NMR (DMSO-d_tOδ: 9.92 (s, IH), 8.21 (s, IH), 7.96 (s, IH), 7.68-7.65 (m, 4H), 7.27 (d, J=8.7 Hz, 2H), 4.12 (d, J=4.2 Hz, 2H), 2.46 (s, 3H), 1.55-1.38 (m, 6H), 1.10-1.02 (m, 3H), 0.81-0.73 (m, 2H). Purity (HPLC): 94.9%.

Example -37 l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide

¹H NMR (DMSOd₆)S: 9.78 (s, IH), 8.18 (s, IH), 7.95 (s, IH), 7.65 (s, 2H), 7.59 (d, J=9.3 Hz, 2H), 6.91 (d, J=9.3 Hz, 2H), 4.11 (d, J=6.9 Hz, 2H), 3.74 (s, 3H), 1.55-1.37 (m, 6H), 1.11-1.01 (m, 3H), 0.81-0.73 (m, 2H). Purity (HPLC): 98.5%.

Example - 38

2-(2,4-Dichlorophenyl)-l-cyclohexyImethyl-3-oxo-2,3-dihydro-lH-4-ρyrazole carboxylic acid N ' -(2-fluoro-phenyl)-hydrazide

Yield: 58%. M. Pt: 53-55 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.08 (s, IH); 8.18 (s, IH); 7.95 (s, IH); 7.64 (s, 2H); 7.13-7.07 (m, IH), 7.034-6.98 (t, J=7.8 & 8.4 Hz, IH), 6.86-6.80 (t, J= 8.4 Hz, IH); 6.77-6.71 (m, IH); 4.10 (d, J= 6.3 Hz, 2H); 1.54-1.35 (m, 6H); 1.09-0.96 (m, 3H); 0.78-0.70 (m, 2H). Purity: 97.76%.

Example - 39

2-(2,4-Dichlorophenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid cyclohexyl amide

Yield: 68%^' M. Pt.: 123-125⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.02 (s, IH), 7.93 (d, J=2.1 Hz, IH), 7.76 (d, J=7.8 Hz, IH), 7.65-7.61 (dd, J=2.1 & 8.4 Hz, IH), 7.58 (d, J=8.4 Hz, IH), 4.07 (d, J= 6.0 Hz, 2H); 3.69 (b s, IH); 1.82-1.71 (m, 4H); 1.62-1.23 (m, HH); 1.13-1.02 (m, 4H); 0.79-0.72 (m, 2H). Purity: 99.46%.

Example - 40

2-(2,4-Dichlorophenyl)- 1 -cyclohexyl methyl-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (3-hydroxy-adamantan-l-yl)-amide

Yield: 53%. M. Pt.: 122-124 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 7.97 (s, IH); 7.93 (d, J= 1.8 Hz, IH); 7.63 (dd, J=8.7 & 1.8 Hz, IH), 7.58 (d, J=8.4 Hz, IH); 7.23 (s, IH), 4.53 (bs, IH); 4.01 (d, J= 5.7 Hz, 2H); 2.16 (bs, 2H); 1.95-1.86 (m, 6H); 1.55-1.37 (m, 12H); 1.10-1.02 (m, 3H); 0.76-0.72 (m, 2H). Purity: 99.48%.

Examples 40a was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 1 Ia in place of intermediate 1 and suitable amines.

ExampIe-40a

^(o-Chloro-pyridin-SylmethyO^^^-dichlorophenyO-S-oxo^^-dihydro-lH-pyrazole- 4-carboxylic acid-{(lR,2R,3R,5S)-2,6,6- trimethyl-bicyclo-[3.1.1] -hept-3-ylamide}

Yield: 26%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.18 (s, IH); 8.13 (s, IH); 8.07 (d, J= 8.4 Hz, IH); 7.86 (s, IH); 7.64 (d, J= 6.0 Hz, IH); 7.57 (d, J= 8.7 Hz, IH); 7.45 (b s, 2H); 5.47 (s, 2H); 4.37 (b t, IH); 2.45-2.32 (m, 2H); 2.04 (b t, IH); 1.94 (b s, IH); 1.81 (b s, IH); 1.72-1.60 (m, IH); 1.30-1.15 (m, 4H); 1.06 (b s, 6H). Purity [HPLC]: 97.78%. Examples 41 was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 13 in place of intermediate 1 and suitable amines.

Example - 41

N4-(l-adamantyl)-l-(2-chlorobenzyl)-2-(2, 5-dichloro phenyl)-4- pyrazolidinecarboxamide

Yield: 52%. M. Pt.: 182-185 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.63 (s, IH); 7.45-7.42 (m, IH); 7.35-7.32 (m, IH); 7.26 (s, 2H); 7.2-7.15 (m, IH); 6.84-6.80 (dd, J= 2.4 Hz and 8.1 Hz, IH); 5.46 (b s, IH); 4.04 (s, 2H); 3.65-3.05 (m, 5H); 2.06 (s, 3H), 1.94 (s, 6H); 1.66 (s, 6H). Purity [HPLC]: 98.56%

Examples 42-46 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 12 in place of intermediate 1 and suitable amines.

Example - 42

N4-(l-adamantyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidinecarboxamide

Yield: 49.5%. M. Pt.: 72-75 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.56 (d, J= 2.4 Hz, IH); 7.35 (s, IH); 7.26-7.18 (m, 4H); 6.87-6.80 (dd, J= 2.7 Hz and 8.7 Hz, IH); 5.36 (b s, IH); 3.94-3.80 (bs, 3H); 3.62 (b s, 2H); 3.29 (m, IH); 3.17-3.11 (t, J= 6.9 Hz, IH); 2.98-2.96 (m, IH); 2.06 (s, 3H); 1.94 (s, 6H); 1.66 (s, 6H). Purity [HPLC]: 97.76%

Example - 43 N4-(4-fluorophenyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4- pyrazolidinecarboxamide

Yield: 53.7%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.61 (d, J= 2.7 Hz, 2H); 7.46-7.42 (m, 2H); 7.35 (s, IH); 7.26-7.21 (m, 3H); 7.04-6.98 (t, J= 8.4 Hz, 2H); 6.92-6.89 (dd, J= 2.7 Hz and 8.4 Hz, IH); 5.30 (s, IH); 3.93 (bs, 3H); 3.76 (m, IH); 3.44-3.41 (m, IH); 3.31-3.17 (m, 2H). Purity [HPLC]: 96.05%

Example - 44

N4-(3-hydroxy-l-adamantyl)-l-(3-chlorobenzyl)-2-(2,5-dichloro phenyl)-4-pyrazolidine carboxamide

Yield: 57.7%. M. Pt.: 148-150 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.56 (d, J= 2.7 Hz, IH); 7.34 (s, IH); 7.30-7.18 (m, 4H); 6.88-6.85 (dd, J= 2.4 Hz and 8.4 Hz, IH); 5.50 (s, IH); 3.94-3.85 (bs, 3H); 3.65-3.55 (m, IH); 3.35-3.23 (m, IH), 3.17—3.12 (m, IH), 3.00- 2.95 (m, 2H); 2.26 (b s, 2H); 1.93 (s, 2H); 1.86 (s, 3H); 1.67 (s, 6H), 1.59-1.54 (bs, 3H). Purity [HPLC]: 94.83%

Example - 45

N4-(p-tolyl)-l-(3-chlorobenzyl)-2-(2₅5-dichloro phenyl)-4-pyrazolidinecarboxamide

Yield: 27%. M. Pt.: 47-50 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.62 (d, J= 2.7 Hz, IH); 7.49 (s, IH); 7.37-7.35 (m, 3H); 7.26-7.21 (m, 4H); 7.12 (d, J= 8.4 Hz, 2H); 6.91-6.87 (dd, J= 2.7 Hz and 8.4 Hz, IH); 3.94-3.60 (m, 4H); 3.44-3.17 (m, 3H); 2.31 (s, 3H). Purity [HPLC]: 96:52%

Example - 46

N4-(4-methoxyphenyl)-l-(3-chlorobenzyl)-2-(2,5-dichIorophenyl)-4- pyrazolidinecarboxamide

Yield: 42%. M. Pt: 133-134 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.62 (d, J= 2.4 Hz, IH); 7.45 (s, IH); 7.39-7.36 (d, J= 8.7 Hz, 4H); 7.26-7.21 (m, 3H); 6.91-6.87 (dd, J= 2.7 Hz and 8.4 Hz, IH); 6.85 (d, J= 8.7 Hz, 2H); 3.94 (s, 2H); 3.86-3.72 (m, IH); 3.78 (s, 3H); 3.45-3.16 (m, 3H). Purity [HPLC]: 98.07%

Examples 47-55 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 14 in place of intermediate 1 and suitable amines.

Example - 47

N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-l-benzyl-2-(4-chlorophenyl)- 3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxamide

¹H NMR (DMSO-d<0δ: 8.07 (s, IH), 7.99 (d, J=9 Hz, IH), 7.54 (s, 4H), 7.31-7.23 (m, 5H), 5.44 (s, 2H), 4.39-4.34 (m, IH), 2.44-2.35 (m, 2H), 2.04-1.99 (t, IH), 1.82-1.80 (bt, IH), 1.68-1.62 (m, IH), 1.23 (s, 3H), 1.16 (d, J=9 Hz, IH), 1.07-1.05 (m, 6H). Purity (HPLC): 98.0%. Example -48

Step - 3: l-Benzyl-2-(4-chlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid morpholin-4-yl-amide.

¹H NMR (DMSO-deOδ: . 9.21(s, IH), 7.97 (s, IH), 7.54 (s, 4H), 7.31-7.24 (m, 5H), 5.40 (s, 2H), 3.67 (bs, 4H)₃ 2.88 (bs, 4H). MS: m/z=413 (M⁺+2). Purity (HPLC): 96.8%.

Example - 49

1 -Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylicacid adamantyl- 1 -y lam ide :

¹H NMR (DMSO-d^δ: . 7.97 (s, IH), 7.55 (s, 4H), 7.32-7.21 (m, 5H), 7.19 (s, IH), 5.33 (s, 2H), 2.03 (s, 9H), 1.65 (s, 6H). MS: m/z = 462 (M⁺+l). Purity (HPLC): 96.2%.

Example - 50 l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -4- chlorobenzyl amide:

¹H NMR (DMSOd₆)S: 8.75-8.71 (t, J=5.4 and 6.0 Hz, IH), 8.09 (s, IH), 7.54 (s, 4H), 7.43-7.35 (q, 4H), 7.30-7.17 (m, 5H), 5.42 (s, 2H), 4.45 (d, J=6 Hz, 2H). MS: m/z=452.9. Purity (HPLC): 96.6%. Example -51 l-Benzyl-2-(4-chlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylicacid cyclohexyl amide.

¹H NMR (DMSOd₆) δ: . 8.04(s, IH), 7.84 (d, J=7.8 Hz, IH), 7.54 (s, 4H), 7.31-7.24 (m, 5H), 5.40 (s, 2H), 3.74 (bm, IH), 1.85-1.59 (m, 5H), 1.29-1.14 (m, 5H). Purity (HPLC): 96%.

Example - 52

1 -Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro- lH-pyrazole-4-carboxylic acid -(4- methylsulfanylphenyl)amide.

¹H NMR (DMSOd₆) δ: . 9.95(s, IH), 8.23 (s, IH), 7.70 (d, J=6.0 Hz, 2H), 7.56 (s, 4H), 7.30-7.27 (m, 7H), 5.44 (s, 2H), 2.47 (s, 3H). Purity (HPLC): 90.8%.

Example - 53 l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - N'-(4- chlorophenyl)hydrazide.

H NMR (DMSO-dβ)δ: 10.13(s, IH), 8.19 (s, IH), 8.13 (bs, IH)₅ 7.55 (s, 4H), 7.31-7.20 (m, 7H), 6.82 (d, J=9 Hz, 2H), 5.42 (s, 2H). Purity (HPLC): 93.8%. Example -54

N4-[(2R)-(6,6-diemthyl-bicyclo[3.1. l]hept-3-ylmethyl)-l-Benzyl-2-(4-chlorophenyl)-3- oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide

¹H NMR (DMSO-d6J δ: 8.09 (bt, IH), 8.00 (s, IH), 7.53 (s, 4H)₅ 7.29-7.23 (m, 5H), 5.42 (s, 2H), 3.40-3.20 (m, 2H), 2.40-2.20 (m, 2H), 2.00-1.80 (m, 5H), 1.60-1.40 (m, IH), 1.17 (s, 3H), 1.08 (s, 3H), 0.86 (bd, IH). Purity (HPLC): 92.0%.

Example - 55

1 -Benzyl-4-[4-(4-chlorophenyl)-piperazine- 1 -carbonyl]-2-(4-chlorophenyl)- 1 ,2-dihydro- pyrazole-3-one

¹H NMR (DMSO-d6)δ:. 7.76 (s, IH), 7.66-7.54 (q, 4H), 7.30-7.25 (m, 7H), 6.96 (d, J=9.0 Hz, 2H), 5.28 (s, 2H), 3.64 (m, 4H), 3.15 (bs, 4H). Purity (HPLC): 90.8%.

Examples 56-60 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 19 in place of intermediate 1 and suitable amines.

Example - 56

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chlorophenyl)-l-(3- chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 49%. M. Pt.: 93-95 ⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 8.01 (d, J= 8.4 Hz, IH); 7.54 (b s, 4H); 7.37-7.28 (m, 2H); 7.23-7.16 (m, 2H); 5.43 (s, 2H); 4.38- 4.33 (m, IH); 2.44-2.35 (m, 2H); 2.04-1.94 (m, 2H); 1.82-1.80 (m, IH); 1.68-1.62 (m, IH); 1.23-1.14 (m, 4H); 1.07-1.05 (m, 6H). Purity: 99.4%.

Example -57

N4-(4-methoxyphenyl) - 1 -(3-chlorobenzyl)-2-(4-chlorophenyl) -3 -oxo-2,3-dihydro- 1 H-4- pyrazolecarboxamide

M. PL: 142-144°C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.85 (s, IH); 8.23 (s, IH); 7.63- 7.56 (m, 6H); 7.37-7.19 (m, 4H); 6.93 (d, J= 9.3 Hz, 2H); 5.43 (s, 2H); 3.75 (s, 3H). Purity: 97.2%.

Example - 58

2-(4-Chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid -p-tolylamide

Yield: 44%. M. Pt.: 135-137 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.88 (s, IH); 8.25 (s, IH); 7.61 (d, J= 8.4 Hz, 2H); 7.56 (s, 4H); 7.37-7.15 (m, 6H); 5.43 (s, 2H); 2.28 (s, 3H). Purity: 98.5%.

Example - 59

N-4-2-di-(4-chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxamide

Yield: 38%. M. Pt.: 143-148⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.08 (s, IH); 8.26 (s, IH); 7.77 (d, J= 8.7 Hz, 2H); 7.56 (s, 4H); 7.42 (d, J= 8.7 Hz, 2H); 7.37-7.19 (m, 4H); 5.42 (s, 2H). Purity: 96.2%.

Example - 60

N4-(l-adamantyl) -l-(3-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3-dihydro-lH-4- pyrazole carboxamide

Yield: 41%. M. Pt.: 128-133⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.99 (s, IH); 7.55 (s, 4H); 7.38-7.30 (m, 2H); 7.22 (d, J= 9.0 Hz, 2H); 7.16 (d, J= 6.9 Hz, IH); 5.34 (s, 2H); 2.04 (b s, 9H); 1.65 (b s, 6H). Purity: 99.05%.

Examples 61-66 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 16 in place of intermediate 1 and suitable amines.

Example -61 2-(4-Chlorophenyl)-l-(2,4-Dichlorobenzyl)-3-oxo-2,3-dihydro-l-H- pyrazole-4- carboxylic acid -(4-chlorophenyl)amide

Yield: 33%. M. Pt.: 143-144⁰C. ¹H NMR (δ, DMSO-dό, 300 MHz): 10.09 (s, IH); 8.27 (s, IH); 7.76 (d, J= 8.7 Hz, 2H); 7.52 (b s, 5H); 7.43-7.34 (m, 4H); 5.49 (s, 2H). Purity: 98.1%.

Example -61a

2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-hydroxyphenyl) amide

Yield: 14.2%. M. Pt.: 162-166 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.75 (s, IH); 9.26 (s, IH), 8.23 (s, IH); 7.52-7.34 (m, 9H), 6.74 (d, J=8.7 Hz, 2H), 5.50 (s, 2H). Purity: 94.7%.

Example -61b

2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3-oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid pentyl amide

Yield: 23.18%. M. Pt.: 100-101 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.13 (bs, IH); 8.05 (s, IH), 7.49 (bs, 4H), 7.38 (bs, 2H), 5.48 (s, 2H), 3.30-3.20 (m, 2H), 1.51 (bs, 2H), 1.35-1.23 (m, 4H), 0.88 (bs, 3H). Purity: 99.1%.

Example -61c

2-(4-ChlorophenyI)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid t-butyl amide

Yield: 37.8%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.02 (s, IH); 7.53 (s, IH), 7.50 (s, 3H), 7.38 (bs, 3H), 5.42 (s, 2H), 1.36 (s, 9H). Purity: 98.28%.

Example - 62

2-(4-Chlorophenyl)-l-(2,4-dichloro benzyl)-3-oxo-2,3-dihydro-lH-ρyrazole-4- carbaxyolic acid adamantan-1-ylamide

Yield: 37%. M. Pt: 157-158⁰C. ¹H NMR (δ, DMSO-dό, 300 MHz): 8.01 (s, IH); 7.54 (s, IH); 7.50 (b s, 4H); 7.37 (s, 2H); 7.22 (s, IH); 5.41 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 99.1%.

Example -63

2-(4-ChIorophenyl)- 1 -(2,4-dichlorobenzyl)-3-oxo-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid-(4-fluorophenyl)-amide

Yield: 29%. M. Pt.: 139-14O⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.02 (s, IH); 8.26 (s, IH); 7.76-7.73 (m, 2H); 7.52 (s, 5H); 7.42-7.34 (m, 2H); 7.23-7.17 (t, J= 9.3 Hz, 2H); 5.49 (s, 2H). Purity: 99.41%.

Example - 64

2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid cyclohexyl-amide]

Yield: 40%. M. Pt.: 154-155°C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.08 (s, IH); 7.89 (d, J= 7.8 Hz, IH); 7.53-7.47 (m, 5H); 7.38 (d, J= 1.8 Hz, 2H); 5.47 (s, 2H); 3.73 (s, IH); 1.84-1.59 (m, 5H); 1.33-1.10 (m, 5H). Purity: 98.87%.

Example - 65

2-(4-Chlorophenyl)-l-(2,4-dichlobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide

Yield: 28%. M. Pt.: 151-152⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.85 (s, IH); 8.25 (s, IH); 7.61 (d, J= 9.0 Hz, 2H); 7.52 (s, 4H); 7.42-7.34 (m, 2H); 6.93 (d, J= 9.0 Hz, 2H); 5.50 (s, 2H); 3.75 (s, 3H). Purity: 99.67%.

Example - 66

2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(3-hydroxyadamantan)-l-yl-amide

Yield: 16%. M. Pt: 134-135⁰C. I ¹ ₁H NMR (δ, DMSO-d6, 300 MHz): 8.02 (s, IH); 7.53- 7.49 (m, 5H); 7.37-7.33 (m, 3H); 5.41 (s, 2H); 2.16 (s, 2H); 1.92 (b d, J= 7.8 Hz, 6H); 1.56-1.49 (m, 6H). Purity: 94.64%.

Examples 67-71 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 18 in place of intermediate 1 and suitable amines.

Example - 67

N4-(4-methoxyphenyl) - 1 -(4-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3-dihydro- 1 H-4- pyrazolecarboxam ide

I₁

Yield: 54%. M. Pt: 149-151⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.84 (s, IH); 8.23 (s, IH); 7.63-7.53 (m, 6H); 7.37-7.27 (AB q, J= 9.3 Hz, 4H); 6.93 (d, J= 9.3 Hz, 2H); 5.43 (s, 2H); 3.75 (s, 3H). Purity: 97.2%.

Example-68 N-4,2-di-(4-chlorophenyl)- 1 -(4-chlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide

Yield: 42%. M. Pt.: 157-159⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.07 (s, IH); 8.25 (s, IH); 7.77 (d, J= 8.7 Hz, 2H); 7.57 (s, 4H); 7.42 (d, J= 8.7 Hz, 2H); 7.37-7.27 (AB q, J= 8.1 Hz, 4H); 5.42 (s, 2H). Purity: 95.98%.

Example - 69

N4-( 1 -adamantyl) - 1 -(4-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide

Yield: 40%. M. Pt.: 142-146⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.99 (s, IH); 7.55 (s, 4H); 7.37 (d, J= 8.1 Hz, 2H); 7.25 (d, J= 8.4 Hz, 2H); 7.18 (s, IH); 5.33 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 98.4%.

Example - 70

2-(4-Chlorophenyl)- 1 -(4-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid (4-bromophenyl)-amide

Yield: 12%. M. Pt.: 155-157 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.08 (s, IH); 8.26 (s, IH); 7.73 (d, J= 8.7 Hz, 2H); 7.59-7.55 (m, 6H); 7.38-7.28 (AB q, J= 9.0 Hz, 4H); 5.44 (s, 2H). Purity: 97.4%.

Example - 71

N4-[(5S, lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1 ]hept-3-yl]-2-(4-chlorophenyl)-l -(4- chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 58%. M. Pt: 122-125 ⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 8.00 (d, J= 8.7 Hz, IH); 7.55 (b s, 4H); 7.35 (d, J= 8.7 Hz, 2H); 7. 27 (d, J= 8.4 Hz, 2H); 5.42 (s, 2H); 4.37-4.33 (m, IH); 2.43-2.35 (m, 2H); 2.04-1.93 (m, 2H); 1.82-1.72 (m, IH); 1.67- 1.61 (m, IH); 1.23 (s, 3H); 1.17-1.14 (m, IH); 1.06-1.04 (m, 6H). Purity: 98.79%.

Examples 72-75 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediated in place of intermediate 1 and suitable amines.

Example - 72

2-(4-chlorophenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)-2,6,6- trimethylbicyclo[3.1.1]hept-3-ylamino]yl}-2,3-dihydro-lH-3-pyrazolone

Yield: 23%. M. Pt.: 144-145⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 7.96 (d, J= 8.4 Hz, IH); 7.40-7.29 (m, 7H); 5.65-5.56 (AB q, J= 12.0 Hz, 2H); 4.40-4.34 (m, IH); 2.43-2.35 (m, 2H); 2.05-1.94 (m, 2H); 1.83-1.81 (m, IH); 1.69-1.62 (m, IH); 1.23 (b s, 5H); 1.07 (b s, 6H). Purity: 99.75%. Example - 73

2-(4-Chlorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (3,5-difluorophenyl)-amide

Yield: 35%. M. Pt.: 137-140 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 8.06 (s, IH); 7.41 (d, J= 9.0 Hz, 2H); 7.28-7.25 (m, 4H); 7.21-7.13 (m, 4H); 5.82 (s, 2H). Purity: 95.9%.

Example - 74

2-(4-Chlorophenyl)- 1 -(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid (4-chlorophenyl)-amide

Yield: 37%. M. Pt: 152-155 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.05 (s, IH); 8.24 (s, IH); 7.63 (d, J= 9.3 Hz, 2H); 7.43-7.38 (m, 7H); 7.30 (s, 2H); 5.59 (s, 2H). Purity: 98.5%.

Example - 75

2-(4-Chlorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-l H-4-pyrazole carboxylic acid adamantan-1-ylamide

Yield: 37%. M. Pt.: 172-175 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 8.00 (s, IH); 7.40- 7.33 (m, 7H); 7.09 (s, IH); 5.50 (s, 2H); 2.03 (bs, 9H); 1.65 (b s, 6H). Purity: 96.7%.

Examples 76-79 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 15 in place of intermediate 1 and suitable amines.

Example - 76

N4-(3 -hydroxy- 1 -adamantyl)-2-(4-chlorophenyl)- 1 -(3 -fluorobenzyl)-3 -oxo-2, 3 -dihydro- 1 H-4-pyrazolecarboxamide

Yield: 49%. M. Pt.: 165-17O⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH); 7.55 (s, 4H); 7.38-7.31 (m, 2H); 7.17-7.01 (m, 3H); 5.36 (s, 2H); 4.75 (s, IH); 2.16 (b s, 2H); 1.93 (b s, 6H); 1.56-1.49 (m, 6H). Purity: 97.7%.

Example - 77

N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chlorophenyl)-l-(3- fluorobenzyl) -3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxam ide

Yield: 50%. M. Pt.: 100-105⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 8.02 (d, J= 8.1 Hz₅ IH); 7.55 (s, 4H); 7.35-7.30 (m, IH); 7.16-7.03 (m, 3H); 5.45 (s, 2H); 4.39- 4.34 (m, IH); 2.44-2.37 (m, 2H); 2.04-2.00 (t, J= 6.3 Hz, IH); 1.94 (b s, IH); 1.80 (s, IH); 1.66-1.62 (m, IH); 1.23 (s, 3H); 1.16 (d, J= 9.0 Hz, IH); 1.07 (s, 6H). Purity: 98.5%.

Example - 78 N4-[(2R)-6,6-dimethylbicyclo[3.1. l]hept-3-ylmethyl]-2-(4-chlorophenyl)- 1-(3- fluorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 61%. ¹HNMR (δ, DMSO-d6₅ 300 MHz): 8.13 (b s, IH); 8.03 (s, IH); 7.55 (s, 4H); 7.35-7.30 (m, IH); 7.16-7.02 (m, 3H); 5.43 (s, 2H); 3.38-3.21 (m, 2H); 2.35-2.24 (m, 2H); 1.94-1.82 (m, 5H); 1.53-1.49 (m, IH); 1.17 (s, 3H); 1.08 (s, 3H); 0.86 (d₅ J= 9.6 Hz, IH). Purity. 95.7%.

Example - 79

N4-(4-methylsulfanylphenyl)-2-(4-chlorophenyl)-l-(3-fluorobenzyl) -3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxam ide

Yield: 33%. M. Pt: 133-138⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.97 (s, IH); 8.25 (s, IH); 7.69 (d, J= 8.7 Hz, 2H); 7.57 (s, 4H); 7.35-7.27 (m, 3H); 7.17-7.04 (m, 3H); 5.44 (s, 2H); 2.47 (s, 3H). Purity: 97.05%.

Examples 80-85 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 9 in place of intermediate 1 and suitable amines.

Example 80

Step - 5: l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid piperidin-1- ylamide:

¹H NMR (DMSO-d<0δ:. 7.55 and 7.52 (dd, J=8.7 and 3.0 Hz, IH), 7.37-7.19 (m, 7H), 3.89-3.76 (m, 3H), 3.48-3.40 (m, IH), 3.32-3.10 (m, 2H), 3.01-2.95 (m, IH), 2.71-2.42 (m, 4H), 1.55-1.26 (m, 6H). Purity (HPLC): 98.1%.

Example - 81 l-Benzyl-2-(2,4-dichloroρhenyl)-pyrazolidine-4-carboxylic acid adamantan-1 -ylamide:

¹H NMR (CDCla)δ: 7.56 (d, J=8.7 Hz, IH), 7.36-7.21 (m, 6H), 7.14 and 7.1 1 (dd, J=8.7 and 2.1 Hz, IH), 5.38 (s, IH), 3.95-3.80 (m, 3H), 3.58 (bm, IH), 3.29-3.23 (m, IH), 3.16- 3.10 (m, IH), 3.00-2.90 (m, IH), 2.05 (s, 3H), 1.93 (bs, 6H), 1.65 (s, 6H). Purity (HPLC): 98.8%.

Example - 82

1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid morpholin-4-ylamide:

¹H NMR (CDCIa) δ: 7.58 (d, J=9.0 Hz, IH), 7.39-7.23 (m, 6H), 7.14 (t, J=9.0 Hz, IH), 3.98-3.59 (m, 9H), 3.32-3.12 (m, 2H), 3.00-2.59 (m, 4H). Purity (HPLC): 98.9%.

Example - 83 l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid -4-chlorobenzyl amide:

¹H NMR (CDCl_a)δ: . 7.52 (d, J=8.7 Hz, IH), 7.33-7.23 (m, 8H), 7.14 (d, J=8.4 Hz, 2H), 7.09 (d, J=2.1 Hz, IH), 6.10 (bs, IH), 4.35 (d, J=5.4 Hz, 2H), 3.94-3.83 (m, 3H), 3.63 (bm, IH), 3.33-3.06 (m, 3H). Purity (HPLC): 98.2%

Example - 84 l-Benzyl-2-(2,4-dichloroρhenyl)-pyrazolidine-4-carboxylic acid cyclohexyl amide:

¹H NMR (CDCla)δ: . 7.58 (d, J=8.7 Hz, IH), 7.36-7.24 (m, 6H), 7.15 and 7.12 (dd, J=8.7 and 2.4 Hz, IH), 5.62 (d, J=7.5 Hz, IH), 3.96-3.61 (m, 5H), 3.31-2.98 (m, 3H), 1.90-1.60 (m, 5H), 1.40-1.03 (m, 5H). Purity (HPLC): 99.6%.

Example -85 l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylicacid-(4-methylsulfany lphenyl)amide:

¹H NMR (CDCl₅)S: . 7.79 (s, IH), 7.63 (d, J=8.4 Hz, IH), 7.43-7.16 (m, HH), 3.93 (bs, 2H), 3.90-3.70 (m, 2H), 3.43-3.37 (m, IH), 3.29-3.16 (m, 2H), 2.46 (s, 3H). Purity (HPLC): 97.5%.

- I l l - Examples 86-91 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 10 in place of intermediate 1 and suitable amines.

Example - 86

N4-[(5S, IR, 2R, 3R)-2,6,6-trimethyl bicycloβ.1.1] hept-3-yl]-l-(2,4-dichlorophenyl)-2- (3-fluorobenzyl)-4-pyrazolidinecarboxamide

Yield: 64%. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.03 (d, J= 8.4 Hz, IH); 7.54 (d, J= 9.0 Hz, IH); 7.43 (s, IH); 7.35-7.25 (m, IH); 7.25 (d, J= 2.7 Hz, IH); 7.16 (d, J= 7.5 Hz, 2H); 7.11-7.00 (m, IH); 4.03 (b s, 2H); 3.88 (s, 2H); 3.04-2.95 (m, IH); 2.31-2.20 (m, 2H); 1.86-1.73 (m, 3H); 1.46-1.43 (m, IH); 1.24 (s, 2H); 1.18 (s, 3H); 0.96-0.83 (m, 8H). Purity [HPLC]: 94.36%

Example - 87

N4-[(2R)-6-6-dimethyl bicyclo[3.1.1] hept-3-yl methyl]- l-(2,4-dichlorophenyl)-2-(3- fluoro benzyl)-4-pyrazolidinecarboxamide

Yield: 87.6%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.54 (d, J= 8.7 Hz, IH); 7.30-7.19 (m, 2H), 7.16-7.12 (dd, J=8.7 & 2.1 Hz, IH), 7.09-7.06 (d, J=9.9 Hz, 2H); 6.96-6.90 (dt, J=9.0 & 1.8 Hz, IH); 5.67 (b s, IH); 3.92 (s, 3H); 3.81-3.62 (m, IH); 3.32-3.02 (m, 4H); 2.38-2.32 (m, IH); 2.15-2.09 (m, IH); 1.92-1.82 (m, 4H); 1.51 (s, 3H); 1.48-1.42 (m, IH); 1.17 (s, 3H); 1.00 (s, 2H); 0.87 (d, J= 8.7 Hz, 2H). Purity [HPLC]: 96.6%

Example - 88

N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidinecarboxamide

Yield: 63.7%. M. Pt.: 154-156 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.53 (d, J= 8.4 Hz, IH); 7.29-7.20 (m, 2H), 7.15-7.11 (dd, J=9.0 & 2.4 Hz, IH), 7.10-7.06 (d, J=I 1.4 Hz, 2H); 6.95-6.89 (dt, J=9.0 & 1.8 Hz, IH); 5.32 (s, IH); 3.92 (s, 2H); 3.79 (b s, IH); 3.60 (b s, IH); 3.31-3.28 (m, IH); 3.18-3.12 (m, IH); 2.99-2.97 (m, IH); 2.06 (s, 3H); 1.94 (s, 6H); 1.66 (s, 6H). Purity [HPLC]: 99.58 %

Example -89

N4-(4-triflυoromethylphenyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4- pyrazolidinecarboxamide

Yield: 51%. M. Pt.: 53-56 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.96 (b s, IH); 7.64-7.56 (m, 4H); 7.35 (d, J= 2.4 Hz, IH); 7.30-7.19 (m, 3H); 7.12-7.06 (m, 2H); 6.98-6.91 (t, J= 11.1 Hz and 9.0 Hz, IH); 3.94 (s, 2H); 3.78 (b s, 2H); 3.49 (b s, IH); 3.26 (b t, 2H). Purity [HPLC]: 96.99%

Example -90

N4-(4-methylsulphanylphenyl)- 1 ~(2,4-dichlorophenyl)-2-(3 -fluorobenzyl)-4- pyrazolidinecarboxamide

Yield: 50%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.63-7.58 (m, 2H); 7.42 (d, J= 8.7 Hz, 2H); 7.33 (d, J= 2.4 Hz, IH); 7.24-7.16 (m, 4H); 7.12-7.06 (m, 2H); 6.97-6.91 (t, J= 8.4 Hz, IH); 3.94 (s, 2H); 3.90-3.60 (m, 2H); 3.48-3.42 (m, IH); 3.30-3.18 (m, 2H); 2.46 (s, 3H). Purity [HPLC]: 91.88%

Example -91

N4-(4-chlorophenyl)- 1 -(2,4-dichlorophenyl)-2-(3 -fluorobenzy l)-4- pyrazolidinecarboxamide

Yield: 56%. M. Pt.: 51-53 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.72 (b s, IH); 7.61 (m, IH); 7.45 (d, J= 8.7 Hz, 2H); 7.34 (d, J= 2.7 Hz, IH); 7.30-7.18 (m, 4H); 7.12-7.06 (m, 2H); 6.97-6.91 (t, J= 10.2 Hz and 7.8 Hz, IH); 3.94 (s, 2H); 3.90-3.60 (b s, 2H); 3.49-3.44 (m, IH); 3.28-3.22 (m, 2H). Purity [HPLC]: 97.78%

Examples 92-95 were prepared according to either procedure (A) or (B) as mentioned in Example - 1 above using intermediate 11 in place of intermediate 1 and suitable amines.

Example - 92

N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidinecarboxamide

Yield: 54%. M. Pt.: 163-165 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.50 (d, J= 8.7 Hz, IH); 7.33-7.27 (m, 3H); 7.13-7.09 (dd, J= 2.4 Hz and 9.0 Hz, IH); 6.99-6.93 (t, J= 8.4 Hz, 2H); 5.32 (b s, IH); 3.87 (s, 3H); 3.79 (b s, IH); 3.58 (b s, IH); 3.28-3.25 (m, IH); 3.17- 3.11 (m, IH); 2.97-2.95 (m, IH); 2.06 (s, 3H); 1.94 (s, 6H); 1.66 (s, 6H). Purity [HPLC]: 98.65%

Example - 93

N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4-dichlorophenyl)-2- (4-fluorobenzyl)-4-pyrazolidinecarboxamide

Yield: 47.5%. M. Pt: 50-52 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.53 (d, J= 9.0 Hz, IH); 7.33-7.28 (m, 3H); 7.14-7.10 (dd, J= 2.4 Hz and 9.0 Hz, IH); 6.99-6.94 (t, J= 8.7 Hz, 2H); 5.67-5.60 (b t, IH); 4.26-4.21 (m, IH); 3.88 (s, 2H); 3.90-3.60 (m, 2H); 3.35-3.28 (m, IH); 3.21-3.15 (m, IH); 3.06-3.01 (m, IH); 2.61-2.50 (m, IH); 2.44-2.37 (m, IH); 2.00-1.90 (m, IH); 1.85-1.79 (m, IH); 1.73-1.66 (m, IH); 1.47-1.38 (m, IH); 1.21 (s, 3H); 1.09-1.04 (t, J= 7.5 Hz, 3H); 1.02 (s, 3H); 0.78 (d, J= 9.6 Hz, IH). Purity [HPLC]: 97.3%

Example - 93a

Yield: 4.4%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.53 (d, J= 8.4 Hz₃ IH); 7.33-7.28 (m, 3H); 7.14-7.11 (dd, J= 2.4 & 8.7 Hz, IH); 6.99-6.94 (t, J= 8.1 Hz, 2H); 5.62-5.59 (bd, IH); 4.26-4.20 (m, IH); 3.89 (s, 2H); 3.90-3.63 (m, 2H); 3.35-3.15 (m, 2H); 3.10-3.00 (m, IH); 2.64-2.52 (m, IH); 2.44-2.35 (m, IH); 1.98-1.90 (m, IH); 1.85-1.66 (m, 2H); 1.47- 1.38 (m, IH); 1.21 (s, 3H); 1.05 (d, J= 7.2 Hz, 3H); 1.02 (s, 3H); 0.78 (d, J= 9.6 Hz, IH). Purity [HPLC]: 96.27%

Example - 93b

Yield: 4.4%. ¹H NMR (δ, CDCl₃, 300 MHz): 7.53 (d, J= 8.4 Hz, IH); 7.33-7.29 (m, 3H); 7.13 (d, J= 8.7 Hz, IH); 7.00-6.94 (t, J= 8.7 Hz, 2H); 5.65 (m, IH); 4.26-4.18 (m, IH); 3.89 (s, 2H); 3.90-3.65 (m, 2H); 3.36-3.25 (m, IH); 3.24-3.15 (m, IH); 3.10-2.95 (m, IH); 2.65-2.38 (m, 2H); 1.94 (bs, IH); 1.82 (bs, IH); 1.75-1.62 (m, IH); 1.50-1.38 (m, IH); 1.21 (s, 3H); 1.09-1.04 (t, J= 7.5 Hz, 3H); 1.02 (s, 3H); 0.78 (d, J= 9.6 Hz, IH). Purity [HPLC]: 97.24%

Example - 94

N4-(4-methylsulphanylphenyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4- pyrazolidinecarboxamide

Yield: 55%. M. Pt: 51-53 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.63 (b s, IH); 7.57 (d, J= 8.7 Hz, IH); 7.41 (d, J= 8.7 Hz, 2H); 7.33-7.29 (m, 3H); 7.23 (d, J= 8.1 Hz, 2H); 7.19- 7.15 (dd, J= 2.7 Hz and 9.0 Hz, IH); 7.01-6.95 (t, J= 8.7 Hz, 2H); 3.90 (s, 2H); 3.90-3.80 (m, IH); 3.80-3.70 (m, IH); 3.45-3.39 (m, IH); 3.30-3.16 (ra, 2H); 2.46 (s, 3H). Purity [HPLC]: 97.72%

Example - 95

N4-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4- pyrazolidinecarboxamide

Yield: 51%. M. Pt.: 51-53 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.72 (s, IH); 7.58 (d, J= 9.0 Hz, IH); 7.44 (d, J= 8.7 Hz, 2H); 7.33-7.26 (m, 6H); 7.19-7.16 (dd, J= 2.1 Hz and 8.4 Hz, IH); 7.01-6.95 (t, J= 8.4 Hz and 9.0 Hz, IH); 3.90 (s, 2H); 3.80-3.65 (m, 2H); 3.45- 3.41 (m, IH); 3.28-3.20 (m, 2H). Purity [HPLC]: 93.14%

Examples 96-97 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 15 in place of intermediate 1 and suitable amines.

Example - 96

2-(4-Chlorophenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid adamantan- 1 -ylamide:

¹H NMR (DMSO-d6Jδ: . 7.99 (s, IH), 7.55 (s, 4H), 7.36-7.31 (m, IH), 7.22 (s, IH), 7.14 (t, J=9.0 Hz, IH), 7.07-7.02 (m, 3H), 5.35 (s, 2H), 2.03 (s, 9H), 1.65 (s, 6H). MS: m/z = 480 (M⁺+l). Purity (HPLC): 99.0%.

Example - 97

2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4-chlorophenyl)-amide:

¹H NMR (DMSO-d6)δ: 10.08 (s, IH), 8.25 (s, IH), 7.77 (d, J=8.7 Hz, 2H), 7.60-7.54 (q, 4H), 7.42 (d, J=9.0 Hz, 2H), 7.37-7.30 (m, IH), 7.16-7.04 (m, 3H), 5.44 (s, 2H). Purity (HPLC): 98.2%. Examples 98-99 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 20 in place of intermediate 1 and suitable amines.

Example - 98

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide

¹H NMR (DMSO-d<0δ: 7.99 (s, IHT), 7.67 (d, J=9.0 Hz, 2H), 7.48 (d, J=9.0 Hz, 2H), 7.39-7.30 (m, 2H), 7.24-7.15 (m, 3H), 5.34 (s, 2H), 2.03 (s, 9H), 1.65 (s, 6H). Purity (HPLC): 97.8%.

Example -99

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methylsulfanyl phenyl)-amide

¹H NMR (DMSO-dβ)δ: 9.97 (s, IH), 8.25 (s, IH), 7.69 (d, J=9.0 Hz, 4H), 7.50 (d, J=9.0 Hz, 2H), 7.38-7.20 (m, 6H), 5.43 (s, 2H), 2.47 (s, 3H). Purity (HPLC): 96.7%.

Examples 100-101 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 22 in place of intermediate 1 and suitable amines. Example -100

2-(4-Bromophenyl)-l-(2,6-Difluorobenzyl)-4-{(lR,2R,3R,5S )-2,6,6- trimethylbicyclo- [3,1,1] -hept-3-ylamino}-yl]-2,3-dihydro-lH-3-pyrazolone

Yield: 53%. M. Pt: 119-12O⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.10 (s, IH); 7.97 (d, J= 8.4 Hz, IH); 7.57 (d, J= 8.7 Hz, 2H); 7.40-7.35 (m, IH); 7.30 (d, J= 8.7 Hz, 2H); 6.92 (t, J= 8.1 Hz, 2H); 5.53-5.44 (AB q, J= 11.7 Hz, 2H); 4.39-4.34 (m, IH); 2.43-2.35 (m, 2H); 2;06-2.01 (m, IH); 1.94 (b s, IH); 1.83-1.81 (m, IH); 1.69-1.63 (m, IH); 1.23 (b s, 4H); 1.07-1.05 (b d, J= 5.7 Hz, 6H). Purity: 95.2%.

Example -101

2-(4-Bromophenyl)-l-(2,6-difluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide

Yield: 23%. M. Pt.: 141-142⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.01 (s, IH); 7.60 (d, J= 8.7 Hz, 2H); 7.45-7.33 (m, 3H); 7.11 (s, IH); 6.98-6.93 (t, J= 8.1 Hz, 2H); 5.37 (s, 2H); 2.04 (b s, 9H); 1.66 (b s, 6H). Purity: 98.43%.

Examples 102-105 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 21 in place of intermediate 1 and suitable amines

Example -102

2-(4-bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid- (3-fluorophenyl)amide

Yield: 24%. M. Pt: 128-130⁰C. ¹H NMR (δ, DMSO-dό, 300 MHz): 10.11 (s, IH); 8.26 (s, IH); 7.71 (d, J= 12.9 Hz, IH); 7.57 (dd, J= 2.1 Hz and 6.9 Hz, 2H); 7.52-7.31 (m, 7H); 6.97-6.91 (t, J= 8.4 Hz, IH); 5.60 (s, 2H). Purity: 98.6%.

Example -103

2-(4-bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid- (4-fluorophenyl)amide

Yield: 54%. M. Pt.: 176-177⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.98 (s, IH); 8.23 (s, IH); 7.76-7.71 (m, 2H); 7.55 (d, J= 7.8 Hz, 2H); 7.35-7.29 (m, 5H); 7.23-7.17 (t, J= 9.0 Hz, 2H); 5.59 (s, 2H). Purity: 98.28%.

Example -104

2-(4-Bromoρhenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo [3.1.1]hept-3-ylamino]yl}-2,3-dihydro-lH-3-pyrazolone

Yield: 46%. M. Pt.: 151-152⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.09 (s, IH); 7.96 (d, J= 8.4 Hz, IH); 7.52 (d, J= 8.7 Hz, 2H); 7.30-7.26 (m, 5H); 5.65-5.56 (AB q, J= 12.0 Hz, 2H); 4.40-4.34 (m, IH); 2.43-2.35 (m, 2H); 2.03-1.99 (m, IH); 1.94 (b s, IH); 1.83-1.81 (m, IH); 1.70-1.65 (m, IH); 1.23-1.16 (m, 5H); 1.07-1.05 (b d, J= 6.9 Hz, 6H). Purity: 98.66%.

Example -105

2-(4-Bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide

Yield: 42%. M. Pt.: 169-17O⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.00 (s, IH); 7.55 (d, J= 8.7 Hz, 2H); 7.35-7.3 (m, 4H); 7.10 (s, IH); 5.51 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 98.83%.

Examples 106 was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using inteπnediate 26 in place of intermediate 1 and suitable amines

Example -106

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide

Yield: 42%. M. Pt.: 147-148⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.85 (s, IH); 8.23 (s, IH); 7.69 (d, J= 8.1 Hz, 2H); 7.62 (d, J= 9.3 Hz, 2H); 7.50 (d, J= 8.7 Hz, 2H); 7.38-7.20 (m, 4H); 6.94 (d, J= 8.4 Hz, 2H); 5.43 (s, 2H); 3.75 (s, 3H). Purity: 98.04%.

Examples 107-108 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 25 in place of intermediate 1 and suitable amines

Example -107 2-(4-Bromophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide

Yield: 29%. M. Pt: 162-163⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.02 (s, IH); 7.64 (d, J= 8.7 Hz, 2H); 7.54 (s, IH); 7.43 (d, J= 9.0 Hz, 2H); 7.38 (s, 2H); 7.22 (s, IH); 5.41 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 98.41%.

Example -108

N4-cyclohexyl-2-(4-bromophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide

Yield: 51%. M. Pt: 163-164°C. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.08 (s, IH); 7.89 (d, J= 7.5 Hz, IH); 7.63 (d, J= 9.0 Hz, 2H); 7.53 (s, IH); 7.45-7.36 (m, 3H); 5.47 (s, 2H); 3.73 (s, IH); 1.84-1.59 (m, 5H); 1.33-1.14 (m, 5H). Purity: 98.9%.

Examples 109-110 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 28 in place of intermediate 1 and suitable amines

Example -109

N4-(4-chlorophenyl)-l-(4-bromobenzyl)-2-(4-bromophenyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide

Yield: 22%. M. Pt.: 125-126⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.08 (s, IH); 8.25 (s, IH); 7.77 (d, J= 9.0 Hz, 2H); 7.69 (d, J= 9.0 Hz, 2H); 7.53-7.47 (m, 4H); 7.42 (d, J= 9.0 Hz, 2H); 7.22 (d, J= 8.4 Hz, 2H); 5.41 (s, 2H). Purity: 97.73%.

Example -110

N4-(l-adamantyl) -l-(4-bromobenzyl)-2-(4-bromophenyl) -3-oxo-2,3-dihydro-lH-4~ pyrazolecarboxamide

Yield: 47%. M. Pt.: 143-144⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.99 (s, IH); 7.67 (d, J= 8.7 Hz, 2H); 7.52-7.48 (m, 4H); 7.19 (d, J= 8.1 Hz, 3H); 5.31 (s, 2H); 2.02 (b s, 9H); 1.65 (b s, 6H). Purity: 99.28%.

Examples 111-113 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 24 in place of intermediate 1 and suitable amines

Example -111

N4-(4-fluorophenyl) -2-(4-bromophenyl) -l-(4-chlorobenzyl) -3-oxo-2,3-dihydro-lH-4- pyrazolecagboxam ide

Yield: 38%. M. Pt.: 155-157⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 10.01 (s, IH); 8.24 (s, IH); 7.76-7.68 (m, 4H); 7.52 (d, J= 8.7 Hz, 2H); 7.37-7.28 (AB q, J= 8.7 Hz, 4H); 7.23-7.17 (t, J= 9.0 Hz, 2H); 5.42 (s, 2H). Purity: 94.8%.

Example -112

N4-(4-methylsulfanylpheny l)-2-(4-bromophenyl)- 1 -(4-chlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxam ide

Yield: 13%. M. Pt: 144-146⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 9.96 (s, IH); 8.24 (s, IH); 7.69 (d, J= 8.4 Hz, 4H); 7.52 (d, J= 8.4 Hz, 2H); 7.37-7.27 (m, 6H); 5.42 (s, 2H); 2.47 (s, 3H). Purity: 89%.

Example -113

N4-(l-adamantyl) -2-(4-bromophenyl) -l-(4-chlorobenzyl) -3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide

Yield: 65%. M. Pt.: 156-158⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.99 (s, IH); 7.67 (d, J= 8.7 Hz, 2H); 7.49 (d, J= 9.0 Hz, 2H); 7.37 (d, J= 8.4 Hz, 2H); 7.26 (d, J= 8.4 Hz₅ 2H); 5.33 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 97.8%.

Examples 114-121 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 23 in place of intermediate 1 and suitable amines

Example -114 2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-chlorophenyl)-amide

Yield: 55%. M. Pt.: 160 ⁰C [Dec]. ¹H NMR (δ, CDCl₃, 300 MHz): 8.06 (s, IH); 7.95 (b s, IH); 7.64-7.56 (AB q, J= 9.0 Hz, 4H); 7.38 (d, J= 8.7 Hz, 2H); 7.30-7.25 (m, 4H); 7.19- 7.16 (m, IH); 5.14 (s, 2H). Purity: 93.9%.

Example -115

2-(4-Bromophenyl)- 1 -(2-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxylic acid (3,5-difluorophenyl)-amide

Yield: 26%. M. Pt: 112-115 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 8.07 (s, IH); 8.00 (bs, IH); 7.66-7.57 (m, 4H); 7.34-7.16 (m, 4H); 7.00-6.97 (dd, J=1.8 Hz and 9.0 Hz; 2H); 6.57-6.51 (t, J= 9.0 Hz, IH); 5.13 (s, 2H).

Example -116

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazoIecarboxylic acid (4-fluorophenyl)-amide

Yield: 53%. M. Pt.: 148-150 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.02 (s, IH); 8.25 (s, IH); 7.76-7.71 (m, 2H); 7.64 (d, J= 8.7 Hz, 2H); 7.47 (d, J= 8.7 Hz, 2H); 7.41-7.17 (m, 6H); 5.53 (s, 2H). Purity: 98.14%.

Example -117

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (6-chloropyridin-3-yl)-amide

Yield: 10%. M. Pt: 165-167 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.30 (s, IH); 8.74 (s, IH); 8.27-8.22 (m, 2H); 7.65 (d, J= 8.7 Hz, 2H); 7.55-7.27 (m, 7H); 5.52 (s, 2H). Purity: 98.66%.

Example -118

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-bromophenyl)-l-(2- chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 50%. M. Pt.: 92-94 ⁰C. ¹H NMR (δ, DMSOd6, 300 MHz): 8.09 (s, IH); 8.03 (d, J= 8.7 Hz, IH); 7.63 (d, J= 8.7 Hz, 2H); 7.44 (d, J= 8.7 Hz, 2H); 7.39-7.24 (m, 4H); 5.53 (s, 2H); 4.40-4.35 (m, IH); 2.44-2.34 (m, 2H); 2.04-1.91 (m, 2H); 1.82-1.80 (m, IH); 1.69-1.63 (m, IH); 1.23-1.14 (m, 4H); 1.07-1.05 (m, 6H). Purity: 98.1%.

Example -119

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide

Yield: 51%. M. Pt.: 167-170 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.97 (s, IH); 8.25 (s, IH); 7.70 (d, J= 9.0 Hz, 2H); 7.65 (d, J= 9.3 Hz, 2H); 7.47 (d, J= 8.7 Hz, 2H); 7.41-7.25 (m, 6H); 5.53 (s, 2H); 2.89 (s, 3H). Purity: 98.81%.

Example -120

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid adamantan- 1 -ylamide

Yield: 70%. M. Pt: 140-143 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.00 (s, IH); 7.64 (d, J= 9.0 Hz, 2H); 7.45 (d, J= 9.0 Hz, 2H); 7.40-7.23 (m, 4H); 5.43 (s, 2H); 2.03 (b s, 9H); 1.65 (b s, 6H). Purity: 97.9%.

Example -121

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid cyclohexyl amide

Yield: 58%. M. Pt.: 133-135 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.07 (s, IH); 7.88 (d, J= 8.1 Hz, 1H);7.63 (d, J= 8.7 Hz, 2H); 7.44 (d, J= 9.0 Hz, 2H); 7.40-7.26 (m, 4H); 5.50 (s, 2H); 3.73 (b s, IH); 1.85-1.59 (m, 5H); 1.33-1.24 (m, 5H). Purity: 96.35%. Examples 122-128 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 27 in place of intermediate 1 and suitable amines

Example -122

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid adamantan- 1 -ylam ide

Yield: 77%. M. Pt.: 173-175 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 7.99 (s, IH); 7.64 (d, J= 8.7 Hz, 2H); 7.56 (d, J= 7.5 Hz, IH); 7.46 (d, J= 8.7 Hz, 2H); 7.37-7.24 (m, 4H); 5.40 (s, 2H); 2.02 (bs, 9H); 1.64 (bs, 6H). Purity: 96.8%.

Example -123

N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]- l-(2-bromobenzyl) -2-(4- bromophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

¹H NMR (δ, DMSOd₆, 300 MHz): 8.10 (s, IH), 8.03 (d, J=9.0 Hz, IH), 7.63 (d, J=8.7 Hz, 2H), 7.55 (d, J=7.8 Hz, IH), 7.46 (d, J=8.7 Hz, 2H), 7.41-7.30 (m, 3H), 5.51 (s, 2H), 4.39-4.33 (m, IH), 2.43-2.35 (m, 2H), 2.04-1.99 (m, IH), 1.94 (bs, IH), 1.82-1.78 (bt, IH), 1.69-1.63 (m, IH), 1.23-1.14 (m, 4H), 1.06 (bs, 6H).

Example -124

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid cyclohexyl amide

Yield: 59%. M. Pt.: 141-146 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 8.07 (s, IH); 7.89 (d, J= 8.1 Hz, 1H);7.63 (d, J= 8.7 Hz, 2H); 7.57-7.54 (dd, J=I.2 Hz and 7.8 Hz, IH); 7.45 (d, J= 8.7 Hz, 2H); 7.42-7.23 (m, 3H); 5.48 (s, 2H); 3.73 (b s, IH); 1.85-1.59 (m, 5H); 1.33- 1.13 (m, 5H). Purity: 99.3%.

Example -125

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid butyl amide

Yield: 59%. M. Pt.: 100-103 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.14-8.11 (t, J= 2.7 Hz, IH); 8.05 (s, IH); 7.63 (d, J= 8.4 Hz, 2H); 7.55 (d, J= 7.5 Hz, IH); 7.45 (d, J= 8.4 Hz, 2H); 7.40-7.25 (m, 3H); 5.49 (s, 2H); 3.26-3.20 (q, J= 6.0 Hz, 2H); 1.52-1.45 (m, 2H); 1.37-1.29 (m, 2H); 0.93-0.88 (t, J= 7.5 Hz, 3H). Purity: 99.31%.

Example -126

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid piperidin- 1 -ylamide

Yield: 51%. M. Pt: 184-187⁰C. ¹HNMR (δ, DMSOd₆, 300 MHz): 9.24 (s, IH); 8.00 (s, IH); 7.63 (d, J= 9.0 Hz, 2H); 7.55 (d, J= 7.5 Hz, IH); 7.44 (d, J= 8.7 Hz, 2H); 7.39-7.23 (m, 3H); 5.47 (s, 2H); 3.66 (b s, 4H); 3.41 (b s, 2H); 2.88 (b s, 4H). Purity: 96.4%.

Example -127

2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2,3-dihydro- 1 H-4-pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide

Yield: 10%. M. Pt.: 177-179 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.98 (s,lH); 8.26 (s, IH); 7.69 (d, J= 8.4 Hz, 2H); 7.65 (d, J= 9.0 Hz, 2H); 7.54 (d, J= 6.0 Hz, IH); 7.47 (d, J= 8.7 Hz, IH); 7.41 (d, J= 7.2 Hz, IH); 7.32-7.26 (m, 4H); 5.51 (s, 2H); 2.47 (s, 3H). Purity: 98.0%.

Example -128

2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxylic acid (4-fluorophenyl)-am ide

Yield: 58%. M. Pt.: 168-170 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.04 (s, IH); 8.25 (s, IH); 7.76-7.71 (m, 2H); 7.65 (d, J= 8.7 Hz, 2H); 7.55 (d, J= 7.5 Hz, IH); 7.48 (d, J= 8.7 Hz, 2H); 7.41 (d, J= 7.2 Hz, IH); 135-1 Al (m, 4H); 5.51 (s, 2H). Purity: 99.4%.

Examples 129-132 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 29 in place of intermediate 1 and suitable amines Example -129

2-(4-bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1 -ylamide

Yield: 34%. M. Pt.: 60-61⁰C. ¹H NMR (δ, DMSO-d6, 300 MHz): 7.93 (s, IH); 7.72 (d, J= 8.7 Hz, 2H); 7.58 (d, J= 9.0 Hz, 2H); 7.17 (s, IH); 4.23-4.19 (t, J= 6.0 Hz, 2H); 2.03 (b s, 9H); 1.64 (b s, 6H); 1.58-1.54 (t, J= 6.9 Hz, 2H); 1.16 (b s, 6H); 0.82-0.78 (t, J= 7.5 Hz, 3H). Purity: 96.09%.

Example -130

2-(4-Bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid piperidin- 1 -ylamide

Yield: 41%. M. Pt.: 118-120 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 8.99 (s, IH); 7.93 (s, IH); 7.72 (d, J= 9.0 Hz, 2H); 7.57 (d, J= 8.7 Hz, 2H); 4.31 (t, J= 6.3 Hz, 2H); 2.79 (b s, 4H); 1.57 (b d, J -5.4 Hz, 6H); 1.36 (b s, 2H); 1.15 (b s, 6H); 0.82-0.77 (t, J= 5.7 Hz, 3H). Purity: 97.3%.

Example -131

2-(4-Bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4- fluorophenyl)-amide

Yield: 53%. M. Pt.: 105-107⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.97 (s, IH); 8.19 (s, IH); 7.76-7.69 (m, 4H); 7.62 (d, J= 8.7 Hz, 2H); 7.22-7.16 (t, J= 9.0 Hz, 2H); 4.36-4.32 (t, J= 6.0 Hz, 2H); 1.60-1.55 (m, 2H); 1.22-1.12 (m, 6H); 0.80-0.76 (t, J= 6.6 Hz, 3H). Purity: 97.7%.

Example -132

2-(4-Bromophenyl)-l-hexyl-3-oxo-2, 3-dihydro-lH-4-pyrazolecarboxylic acid (4- methylsulphanyl phenyl)-amide

Yield: 60%. M. Pt.: 89-91 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 9.91 (s, IH); 8.19 (s, IH); 7.74 (d, J= 9.0 Hz, 2H); 7.68-7.60 (m, 4H); 7.26 (d, J= 8.4 Hz, 2H); 4.35-4.31 (t, J= 6.0 Hz, 2H); 2.46 (s, 3H); 1.59-1.55 (m, 2H); 1.22-1.14 (m, 6H); 0.79-0.75 (t, J= 6.0 Hz, 3H). Purity: 96.3%.

Examples 133-134 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 30 in place of intermediate 1 and suitable amines

Example -133

2-(2,4-Difluorophenyl)- 1 -(4-trifluoromethylbenzyl)-3-oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide

Yield: 28%. M. Pt: 191-194 ⁰C. ¹H NMR (δ, DMSO-d₆, 300 MHz): 8.09-8.07 (m, 2H); 7.88 (d, J= 8.7 Hz, 2H); 7.65 (d, J= 8.7 Hz, 2H); 7.54 (d, J= 8.1 Hz, 2H); 7.39-7.29 (m, 3H); 7.03-6.97 (m,.2H); 5.25 (s, 2H); 3.05 (s, 3H). Purity: 98.47%.

Example -134

2-(2,4-Difluorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide

Yield: 55%. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.00 (s, IH); 8.28 (s, IH); 7.71-7.63 (2d, J= 8.7 Hz and 8.1 Hz, 4H); 7.55-7.46 (m, 2H); 7.38 (d, J= 8.1 Hz, 2H); 7.28 (d, J= 8.4 Hz, 2H); 7.26-7.19 (m, 3H); 5.51 (s, 2H); 2.47 (s, 3H). Purity: 98.7%

Examples 135-136 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 31 in place of intermediate 1 and suitable amines

Example -135

2-(2,4-Difluorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide

Yield: 38%. M. Pt.: 172.8 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.39 (s, IH); 8.34 (s, IH); 8.02 (d, J= 9.0 Hz, 2H); 7.93 (d, J= 8.7 Hz₅ 2H); 7.67 (d, J= 7.5 Hz, IH); 7.55-7.42 (m, 5H); 7.25-7.20 (t, J= 9.3 Hz and 6.6 Hz, IH); 5.51 (s, 2H); 3.20 (s, 3H). Purity: 99.3%,

Example -136

2-(2,4-Diflυorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide

Yield: 74%. M. Pt.: 139-141 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 10.00 (s, IH); 8.28 (s, IH); 7.72-7.65 (m, 3H); 7.52-7.41 (m, 5H); 7.28 (d, J= 9.0 Hz, 2H); 7.24-7.19 (t, J= 6.3 Hz, IH); 5.49 (s, 2H); 2.47 (s, 3H). Purity: 99.4%.

Examples 137-138 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 32 in place of intermediate 1 and suitable amines

Example -137

N4-(3-hydroxy-l-adamantyl)-l-(3-chlorobenzyl)-2-(3-triflouromethylphenyl)-4- pyrazolidinecarboxamide

Yield: 45%. M. Pt.: 59-61 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.40 (s, IH); 7.33-7.17 (m, 6H); 7.04 (d, J= 7.5 Hz, IH); 5.31 (s, IH); 3.97-3.84 (m, 3H); 3.73 (bs, IH); 3.17-3.03 (m, 3H); 2.26 (s, 2H); 1.93 (bs, 2H), 1.86 (bs, 3H); 1.67 (bs, 6H); 1.59-1.54 (s, 3H). Purity [HPLC]: 99.79%

Example -138

N4-(4-methoxyphenyl)-l-(3-chloro-benzyl)-2-(3-trifluoromethyl-phenyl)-4- pyrazolidinecarboxamide

Yield: 56%. M. Pt.: 145-146 ⁰C. ¹H NMR (δ, CDCl₃, 300 MHz): 7.42-7.21 (m, 9H); 7.06 (d, J= 7.2 Hz, IH); 6.85 (d, J= 8.7 Hz, 2H); 4.02-3.85 (m, 4H); 3.78 (s, 3H); 3.30-3.19 (m, 3H). Purity [HPLC]: 99.52%

Examples 139 was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 36 in place of intermediate 1 and suitable amines

Example -139

2-(4-Trifluoromethylphenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid adamantan-1-ylamide

M. Pt.: 156-158 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.05 (s, IH); 7.82-7.73 (AB q, J= 8.7 Hz and 9.6 Hz, 4H); 7.53-7.50 (dd, J= 6.6 Hz and 1.2 Hz, IH); 7.40-7.24 (m, 4H); 5.45 (s, 2H); 2.04 (s, 9H); 1.65 (b s, 6H). Purity: 98.7%.

Examples 140 was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 35 in place of intermediate 1 and suitable amines

Example -140

2-(4-Trifluoromethylphenyl)- 1 -(2-trifluoromethyl benzyl)-3 -oxo-2,3-dihydro- 1 H-4- pyrazole carboxylic acid adamantan-1-ylamide

Yield: 23.08%. M. Pt.: 131-134 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.08 (s, IH); 7.79 (d, J=8.4 Hz, 2H)₅ 7.71 (d, J=8.4 Hz, 2H), 7.68-7.53 (m, 4H), 7.35 (s, IH), 5.54 (s, 2H); 2.04 (s, 9H); 1.65 (b s, 6H). Purity: 99.1%.

Examples 141 was prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 34 in place of intermediate 1 and suitable amines

Example -141 2-(4-Trifluoromethylphenyl)-l-(2,4-dichloromethyl benzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid adamantan-1-ylamide

Yield: 6.11%. M. Pt: 150-153 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.07 (s, IH); 7.80 (d, J=8.7 Hz, 2H), 7.70 (d, J=8.4 Hz, 2H), 7.47 (s, IH), 7.35 (d, J=I .5 Hz, IH), 7.29 (s, 2H), 5.43 (s, 2H); 2.04 (s, 9H); 1.65 (bs, 6H). Purity: 95.53%.

Examples 142-143 were prepared according to procedure either (A) or (B) as mentioned in Example - 1 above using intermediate 33 in place of intermediate 1 and suitable amines

Example -142

2-(4-Trifluoromethylphenyl)-l-(2-chloromethyl benzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid adamantan-1-ylamide

Yield: 25.5%. M. Pt.: 148-150 ⁰C. ¹H NMR (δ, DMSOd₆, 300 MHz): 8.06 (s, IH); 7.80 (d, J=8.7 Hz, 2H), 7.73 (d, J=9.0 Hz, 2H), 7.38-7.28 (m, 5H), 5.47 (s, 2H); 2.05 (s, 9H); 1.66 (bs, 6H). Purity: 99.02%.

Example -143

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-trifluoromethylphenyl)- l-(2-chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide

Yield: 34.5%. ¹H NMR (δ, DMSO-d6, 300 MHz): 8.14 (s, IH); 8.07 (s, IH), 7.79 (d, J= 9.0 Hz, 2H); 7.72 (d, J=8.7 Hz, 2H), 7.39-7.18 (m, 4H); 5.55 (s, 2H); 4.39-4.34 (m, IH); 2.44-2.21 (m, 2H); 2.05-2.03 (m, IH); 1.93 (bs, IH); 1.82-1.78 (m, IH); 1.70-1.64 (m, IH); 1.23 (s, 3H); 1.16 (m, IH); 1.06 (s, 6H). Purity: 97.3%.

Protocols

I. In vitro Protocol for rat CBl receptor binding using brain membrane

In this assay, [³H]SR141716A (5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4- methyl-N-(l-piperidyl)pyrazole-3-carboxaniide) was used to bind the CBl receptor present in a rat brain membrane preparation which can be displaced by unlabeled ligands having affinity to the CBl receptor.

The assay was performed according to the modified method of Thomas et al., 1998 (JPET 285: 285-292). The total reaction mixture (250 ml) contained Tris-BSA buffer (50 mM Tris, pH 7.4 with 1.5 % BSA) or unlabeled SR141716A (1 mM) or test samples (1 mM), [³H] SR141716A (2 nM) and 100 mg of rat brain membrane. The nonspecific binding was defined by 1 mM of SR141716A. The assay mixture was incubated at 37⁰C for 1 hour. The reaction was then stopped by rapid filtration under vaccum using Whatman GF/B-96 micro filter plate. A scintillation cocktail was added and radioactive counts were measured using a Topcount beta scintillation counter.

The standard and test sample dilutions were made in an assay buffer containing either ethanol or DMSO at a final concentration of 1%.

The percent (%) displacement by a test ligand was calculated by comparing the specific bound values. The results of the assay are shown in Table below.

II. Protocol for in vitro assay using hCBl-CHO membranes

In this assay, [³H]-CP-55,940 ((-)-3-[2-hydroxyl-4-(l,l-dimethylheptyl)-phenyl]- 4-[3-hydroxypropyl]cyclohexan-l-ol) was used as the radioligand to bind human CBl receptors expressed on the membranes from CHO cells (the hCBl-CHO cell line was generated in-house) which can be displaced by unlabeled ligands having affinity to the CBl receptor.

The assay was performed according to the modified method of Ross et al.,1999 (Br. J. Pharmacol. 128, 735-743). The reaction was set up in a total volume of 200 μL in PEI (Poly(ethyleneimine)) (0.2 %) precoated Millipore GFB (Glass Fibre-B) filter plates.

ImM stocks of test compounds were prepared in DMSO and tested at a final concentration of 300 nM. The non-specific binding was determined by 0.5 μM CP-55,

940. The total reaction mixture contained Tris-BSA buffer (5OmM Tris, 5 mM MgCl₂, 1 mM EDTA, pH 7.4 with 0.1 % BSA), unlabelled CP-55, 940 (0.5 μM) or test samples,

[³H]-CP-55, 940 (0.75 nM) and 50 μg of human CBl receptor preparation. The assay mixture (with or without the test compound) was incubated at 37 ⁰C for 1 hour. The reaction was stopped by rapid filtration under vacuum and the radioactivity on the filters was measured by liquid scintillation counting. The results of the assay are shown in Table below.

III. Protocol for in vitro assay using hCB2-CHO membranes:

In this assay, [³H]-CP-55,940 was used as the radioligand to bind human CB2 receptor expressed on the membranes from CHO cells (hCB2-CHO cell line was generated in-house) which can be displaced by unlabeled ligands having affinity to the CB2 receptor.

The assay was performed according to the modified method of Ross et al., \999 (Br. J. Pharmacol. 128, 735-743). The reaction was set up in a total volume of 200 μl in PEI (0.2 %) precoated Millipore GFB filter plates. ImM stocks of test compounds were prepared in DMSO and tested at a final concentration of 300 nM. The non-specific binding was determined by 0.5 μM CP-55, 940. The total reaction mixture contained Tris-BSA buffer(50mM Tris, 5 mM MgCl₂, 1 mM EDTA, pH 7.4 with 0.1 % BSA), unlabelled CP-55, 940 (0.5 μM) or test samples, [³H]-CP-55, 940 (0.75 nM ) and 25-50 μg of human CB2 receptor preparation. The assay mixture (with or without the test compound) was incubated at 30 ⁰C for 1 hour. The reaction was stopped by rapid filtration under vacuum and the radioactivity on the filters was measured by liquid scintillation counting. The percent (%) displacement by a test ligand was calculated by comparing the specific bound values. The results of the assay are shown in Table 1 below.

Table 1

Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above.

All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.

Claims

We Claim

1. A compound of general formula (I)

(I) prodrugs thereof, pharmaceutically acceptable salts thereof, and hydrates and solvates thereof, wherein

A and B are independently substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted cycloalkyl; Z is -(C=O)-, -CH₂-, or CH; D is -O- or -NR¹; the dotted line in the 5 membered ring represents an optional bond;

R¹ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl or a protecting group; R² and R³ independently are hydrogen or alkyl,

R² and R³ together with the carbon atom to which they are attached represent carbonyl (C=O);

R⁴ and R⁵ are independently hydrogen, -0R^a, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -NR^aR^b, -C(=L)-R^a, -C(O)O-R³, -C(O)NR^aR^b, -S(O)_m-R^a, -S(O)_m-NR^aR^b, or a protecting group or R⁴ and R⁵ may be joined together along with the nitrogen to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^aor S; each occurrence of R^a and R^b may be the same or different and are independently hydrogen, -OR^C, -SR⁰, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -C(=L)-R^C, -C(O)O-R⁰, -C(0)NR°R^d, - S(O)_m-R°, -S(0)_m-NR°R^d, -NR^cR^d, or a protecting group, or R^a and R^b may be joined together along with the nitrogen to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR⁰ or S; each occurrence of R^c and R^d are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, cycloalkenylalkyl substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, or a substituted or unsubstituted heteroarylalkyl or a protecting group, or R° and R^d may be joined together to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatom selected from O, NR^e or S; each occurrence of R^e is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, or a protecting group; each occurrence of m is independently 0,1 or 2; and each occurrence of L is independently O, S, or NR⁰ , where R^c is the same as defined above.

2. A compound of general formula (II)

(II) prodrugs thereof, pharmaceutically acceptable salts thereof, and hydrates and solvates thereof, wherein

A and B are independently substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or^" substituted or unsubstituted cycloalkyl; Z is -(C=O)-, -CH₂-, or CH; the dotted line in the 5 membered ring represents an optional bond; R² and R³ are independently alkyl or hydrogen,

R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O);

R⁴ and R⁵ are independently hydrogen, -0R^a, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -NR^aR^b, -C(=L)-R^a, - C(O)O-R^a, -C(O)NR^aR^b, -S(O)_m-R^a, -S(0)_m-NR^aR^b, or a protecting .group or R⁴ and R⁵ may be joined together along with the nitrogen to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^a or S; each occurrence of R^a and R^b may be the same or different and are independently hydrogen, -OR^C, -SR^C, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, -C(=L)-R^C, -C(O)O-R⁰, -C(0)NR°R^d, - S(O)_m-R^c, -S(O)_m-NR^cR^d, -NR°R^d, or a protecting group, or R^a and R^b may be joined together along with the nitrogen to which they are attached to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^C or S; each occurrence of R^c and R^d may be the same or different and are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, or a substituted or unsubstituted heteroarylalkyl or a protecting group, or R^c and R^d may be joined together to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring, which may optionally include at least two heteroatoms selected from O, NR^e or S; each occurrence of R^e is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl, or a protecting group; p is 0, 1 or 2; q is 0, 1 or 2; . each occurrence of m is independently 0,1 or 2; and each occurrence of L is independently O, S, or NR^C , where R° is the same as defined above.

3. A compound according to claim 1 or 2, wherein A and B are independently selected from substituted or unsubstituted aryl, cycloalkyl, and alkyl.

4. A compound according to claim 3, wherein A is selected from phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 3 -fluorophenyl, 4-fluorophenyl, 2,6-diflurophenyl, 2-bromophenyl, 4-bromophenyl, cyclohexyl, hexyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 6-chloropyridin-3-yl.

5. A compound according to claim 3, wherein B is selected from 4-chlorophenyl, 2,4- dichlorophenyl, 2,5-dichlorophenyl, 4-bromophenyl, 2,4-difluorophenyl, 3- trifluoromethylphenyl and 4-trifluoromethylphenyl.

6. A compound according to claim 1 or 2, wherein R⁴ is selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted heteroaryl.

7. A compound according to claim 6, wherein R⁴ is selected from n-butyl, n-pentyl, 1,1- dimethylethyl, cyclohexyl, 1-adamantyl, 3-hydroxyadaman-l-yl, 4-hydroxycyclohexyl, sulphanylphenyl, methylsulfonylphenyl, 4-cyanophenyl, 4-hydroxyphenyl, 4- methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-bromophenyl, 3-fluoroρhenyl, 4- fluorophenyl, 3,4-difluorophenyl, 3,5-difiuorophenyl, 4-trifluoromethylphenyl, 4- chlorobenzyl, (2R)-(6,6-dimethyl-bicyclo[3.1. l]hept-3-yl-methyl), (5S, lR,2R,3R)-2,6,6- trimethylbicyclo[3.1.1] hept-3-yl, piperidin-1-yl, morpholinyl, 6-chloro-pyridyl-3-yl, -NR^aR^b wherein R^a and R^b are selected from hydrogen and substituted or unsubstituted phenyl.

8. A compound according to claim 1 or 2, wherein R⁴ and R⁵ are joined together to form an optionally substituted 3 to 7 membered saturated, which optionally includes at least two heteroatoms selected from O, NR^a and S.

9. A compound according to claim 8, wherein the compound is 4-(4-chlorophenyl)- piperazine-lyl.

10. A compound according to claim 1 or 2, wherein R^s is hydrogen.

11. A compound according to claim 1 or 2, wherein Z is -CH₂-.

12. A compound according to claim 1 or 2, wherein Z -CH- and the dotted line represents a bond.

13. A compound according to claim 1 or 2 wherein R² and R³ are hydrogen or R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O).

14. A compound according to claim 2, wherein the compound is selected from

1 -Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-l H-pyrazole-4-carboxylic acid adamantyl- 1 -ylamide; l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid piperidine-1 -ylamide; l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -(4- methylsulfanylphenyl)atnide;

l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4carboxylic acid morpholin-4-yl~amide; l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4- methanesulfonylphenyl)-amide; l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid cyclohexyl amide; l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-4- chlorobenzylzmide; l-Benzyl-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4- hydroxycyclohexyl)-amide;

N4-[(2R)-(6,6-diemthyl-bicyclo[3.1.1 ]hept-3-ylmethyl)- 1 -Benzyl-2-(2,4-dichlorophenyl)- 3-oxo-2,3-dihydro-lH~4-pyrazole carboxamide; l-Benzyl-4-[4-(4-chloroρhenyl)-piperazine-l-carbonyl]-2-(2,4-dichlorophenyl)-l,2- dihydro-pyrazole-3-one; l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid N'- (4-chloro-phenyl)-hydrazide; l-(3-Chlorbenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2.3-dihydro-lH-pyrazole-4-carboxylic acid~(4-methylsulfonyl-phenyl)-amide; l-(3-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carbaxolic acid-(4-methyIsulfanylphenyl)-amide; l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-chlorophenyl)-amide; l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxyIlc acid-(3 ,4-difluorophenyl)-amide; l-(4-Chlorobenzyl)-2-(2,4-dichIorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methanesuIfonylphenyl) amide;

I-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-trifluoromethylphenyl)-amide;

N4-(4-methyIsulfanylphenyl)-l-(4-chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3- dihydro- 1 H-4-pyrazolecarboxamide; l-(4-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide;

2-(2,4-Dichlorophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-fluorophenyl)-amide; l-(4-Chlorophenyl)-2-(2,4-DichIorophenyI)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-cyanophenyI) amide; l-(4-Chlorobenzyl)-2-(2,4-Dichlorophenyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid (4-hydroxyphenyl) amide; l-(2-Chlorobenzyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid (4-methanesulfanylphenyl)-amide; l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid (4-fluoro-phenyl)-amide; l-(2-Chloro-benzyl)-2-(2,4-dichloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazoIe-4- carboxylic acid(adamantan- 1 -yl)-amide; l-(2-Chlorobenzyl)-2-(2,4-dichlorophenyI)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid cyclohexyl amide;

2-(2,4-Dichloroρhenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxylic acid (3-hydroxy-adamantan- 1 -yl)amide;

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid N'-phenyl-hydrazide;

N4-[(5S_JlR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(2,4-dichlorophenyl)-l-(3- fluorobenzyl)~3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxyIic acid -(4-trifluoromethyl phenyl)-amide;

2-(2,4-Dichloroρhenyl)-l -(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid -(4-methylsuIphonyl phenyl)-amide; 2-(2,4-Dichlorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

2-(2,4-Dichlorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide;

2-(2,4-Dichlorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

2-(2,4-Dichloroρhenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4-chlorophenyl)-amide;

2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-ylamide;

2-(2,4-Dichlorophenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid-4-methylsulfanylphenyl amide;

N4-[(2R)-2-(2,4-Dichlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid-(6,6-dimethylbicyclo[3.1. l]hept-3-ylmethyl)-amide; l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro÷-lH-pyrazole-4-carboxylic acid-(4-methylsulfanylphenyl)-amide; l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide; l-(6-Chloro-pyridin-3ylmethyl)-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole- 4-carboxylic acid-{(lR,2R,3R,5S)-2,6,6-trimethyl-bicyclo-[3.1.1] -hept-3-ylamide} ;

2-(2,4-Dichlorophenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid N'-(2-fluoro-phenyl)-hydrazide;

2-(2,4-Dichlorophenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid cyclohexyl amide;

2-(2,4-Dichlorophenyl)-l-cyclohexylmethyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (3-hydroxy-adamantan-l-yl)-amide;

N4-(l-adamantyl)-l-(2-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

N4-(l-adamantyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

N4-(4-fluorophenyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

N4-(3-hydroxy-l-adamantyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide; N4-(p-tolyl)-l-(3-chlorobenzyl)-2-(2,5-dichloro phenyl)-4-pyrazolidinecarboxamide;

N4-(4-methoxyphenyl)-l-(3-chlorobenzyl)-2-(2,5-dichlorophenyl)-4-pyrazolidine carboxamide;

N4-[(lR,2R,3R,5S)-2,6,6-triraethylbicyclo[3.1.1]hept-3-yl]-l-benzyl-2-(4-chlorophenyl)- 3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide;

1 -Benzyl-2-(4-chlorophenyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid morpholin-4-yl-amide;

1 -Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid adamantyl- 1 -ylamide; l-BenzyI-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -4- chlorobenzyl amide; l~Benzyl-2-(4-chlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylicacid cyclohexyl amide; l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid -(4- methylsulfanylphenyl)amide; l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - N'-(4- chlorophenyl)hydrazide;

N4-[(2R)-(6,6-diemthyl-bicyclo[3.1. l]hept-3-ylmethyl)-l -Benzyl-2-(4-chlorophenyl)-3- oxo-2,3-dihydro-lH-4-pyrazole carboxamide;

1 -Benzyl-4-[4-(4-chlorophenyl)-piperazine- 1 -carbonyl]-2-(4-chlorophenyl)- 1 ,2-dihydro- pyrazole-3-one;

N4-[(5S, lR,2R,3R)-2,6,6-trimethylbicyclo[3.1. l]hept-3-yl]-2-(4-chlorophenyl)-l -(3- chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

N4-(4-methoxyphenyl) -l-(3-chlorobenzyl)-2-(4-chlorophenyl) -3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide;

2-(4-Chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid -p-tolylamide;

N-4-2-di-(4-chlorophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxamide;

N4-( 1 -adamantyl)- 1 -(3-chlorobenzyl)-2-(4-chlorophenyl)-3-oxo-2,3 -dihydro- 1 H-4- pyrazole carboxamide;

2-(4-Chlorophenyl)-l-(2,4-Dichlorobenzyl)-3-oxo-2,3-dihydro-l-H-pyrazole-4- carboxylic acid -(4-chlorophenyl)amide; 2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid (4-hydroxyphenyl) amide;

2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid pentyl amide;

2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid t-butyl amide;

2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3-dihydro- 1 H-pyrazole-4-carbaxolic acid adamantan-1-ylamide;

2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3 -oxo-2,3 -dihydro- 1 H-pyrazole-4-carboxy 1 ic acid-(4-fluorophenyl)-amide;

2-(4-Chlorophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid cyclohexyl-amide;

2-(4-Chlorophenyl)- 1 -(2,4-dichIobenzyl)-3 -oxo-2,3-dihydro-l H-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide;

2-(4-Chlorophenyl)- 1 -(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro- lH-pyrazole-4-carboxylic acid-(3-hydroxyadamantan)- 1 -yl-amide;

N4-(4-methoxyphenyl) - 1 -(4-chlorobenzyl)-2-(4-chlorophenyl) -3 -oxo-2, 3 -dihydro- 1 H-4- pyrazolecarboxamide;

N-4,2-di-(4-chlorophenyl)- 1 -(4-chlorobenzyl)-3-oxo-2,3 -dihydro- 1 H-4-pyrazole carboxamide;

N4-( 1 -adamantyl)- 1 -(4-chlorobenzyl)-2-(4-chlorophenyl)-3-oxo-2,3-dihydro- 1 H-4- pyrazolecarboxamide;

2-(4-Chlorophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-bromophenyl)-amide;

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chlorophenyl)-l-(4- chlorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

2-(4-chlorophenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)-2,6,6- trimethylbicyclo [3.1.1 ]hept-3 -ylamino]yl } -2,3 -dihydro- 1 H-3 -pyrazolone;

2-(4-Chlorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (3,5-difluorophenyl)-amide;

2-(4-Chlorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid (4-chlorophenyl)-amide;

2-(4-Chlorophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid adamantan-1-ylamide; N4-(3-hydroxy-l-adamantyl)-2-(4-chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxam ide;

N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-chlorophenyl)-l-(3- fluorobenzyl) -3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

N4-[(2R)-6,6-dimethylbicyclo[3.1.1]hept-3-ylmethyl]-2-(4-chlorophenyl)-l-(3- fluorobenzyl) -3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxamide;

N4-(4-methylsulfanylphenyl)-2-(4-chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid piperidin- 1 -ylamide; 1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid adamantan- 1 -ylamide; 1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid morpholin-4-ylamide; l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid -4-chlorobenzyl amide; l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid cyclohexyl amide; l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid-(4-methylsulfanyl phenyl)amide;

N4-[(5S, IR, 2R, SRJ^^^-trimethylbicyclotS.l.ηhept-S-yll-l^^-dichlorophenyl)^- (3-fluorobenzyl)-4-pyrazolidinecarboxamide;

N4-[(2R)-6-6-dimethylbicyclo[3.1. l]hept-3-yl methyl]- 1 -(2,4-dichlorophenyl)-2-(3- fluoro benzyl)-4-pyrazolidinecarboxamide;

N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidine carboxamide;

N4-(4-trifluoromethylphenyl)-l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4- pyrazolidinecarboxamide;

N4-(4-methylsulphanylphenyl)- 1 -(2,4-dichlorophenyl)-2-(3 -fluorobenzyl)-4- pyrazolidinecarboxamide;

N4-(4-chlorophenyl)- 1 -(2,4-dichlorophenyl)-2-(3 -fluorobenzyl)-4-pyrazolidine carboxamide;

N4-(l-adamantyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidine carboxamide;

N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4-dichlorophenyl)-2- (4-fluorobenzyl)-4-pyrazolidinecarboxamide; N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4-dichlorophenyl)-2- (4-fluorobenzyl)-4-pyrazolidinecarboxamide;

N4- [(5S,lR,2R,3R)-2,6,6-trimethyl bicyclo[3.1.1] hept-3-yl]-l-(2,4-dichlorophenyl)-2- (4-fluorobenzyl)-4-pyrazolidinecarboxamide;

N4-(4-methylsulphanylphenyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4- pyrazolidinecarboxamide;

N4-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4- pyrazolidinecarboxamide;

2-(4-Chloropheny I)- 1 -(3 -fluorobenzyl)-3 -oxo-2, 3 -dihydro- 1 H-pyrazole-4-carboxylic acid adamantan-1 -ylamide;

2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid - (4-chlorophenyl)-amide;

2-(4-Bromophenyl)-l-(3-chIorobenzyl)-3-oxo-2,3-^'dihydro-lH-pyrazole-4-carboxylic acid adamantan-1 -yl amide;

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methylsulfanyl phenyl)-amide;

2-(4-Bromophenyl)-l-(2,6-Difluorobenzyl)-4-{(lR,2R,3R,5S)-2,6,6-trimethylbicyclo- [3,1,1] -hept-3-ylamino} -yl]-2,3-dihydro- 1 H-3-pyrazolone;

2-(4-Bromophenyl)-l-(2,6-difluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1 -yl amide;

2-(4-bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid- (3-fluorophenyl)amide;

2-(4-bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid- (4-fluorophenyl)amide;

2-(4-Bromophenyl)-l-(2,6-dichlorobenzyl)-4-{l-[(lR,2R,3R,5S)-2,6,6- trimethylbicyclo[3.1. l]hept-3-ylamino]yl} -2,3-dihydro-lH-3-pyrazolone;

2-(4-Bromophenyl)-l-(2,6-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1 -yl amide;

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid-(4-methoxyphenyl)-amide;

2-(4-Bromophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1 -yl amide;

N4-cyclohexyl-2-(4-bromophenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide; N4-(4-chlorophenyl)-l-(4-bromobenzyl)-2-(4-bromophenyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide;

N4-( 1 -adaraantyl)- 1 -(4-bromobenzyl)-2-(4-bromophenyl)-3 -oxo-2,3 -dihydro- 1 H-4- pyrazolecarboxamide;

N4-(4-fluorophenyl)-2-(4-bromoρhenyl)- 1 -(4-chlorobenzyl)-3 -oxo-2,3-dihydro- 1 H-4- pyrazolecarboxamide;

N4-(4-methylsulfanylphenyl)-2-(4-bromophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazolecarboxamide;

N4-(l-adamantyl)-2-(4-bromophenyl)-l-(4-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazolecarboxamide;

2-(4-Bromophenyl)- 1 -(2-chlorobenzyl)-3-oxo-2,3-dihydro- 1 H-4-pyrazole carboxylic acid (4-chlorophenyl)-amide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (3 , 5 -difluorophenyl)-amide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4-fluorophenyl)-amide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (6-chloropyridin-3-yl)-amide;

N4-[(5S,lR,2R,3R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-2-(4-bromophenyl)-l-(2- chlorobenzyl) -3 -oxo-2,3-dihydro- 1 H-4-pyrazolecarboxam ide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid adamantan- 1 -ylamide;

2-(4-Bromophenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid cyclohexyl amide;

2-(4-Bromophenyl)-l~(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid adamantan- 1 -ylamide;

N4-[(lR,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]-l-(2-bromobenzyl)-2-(4- bromophenyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide;

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid cyclohexyl amide; 2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxylic acid butyl amide;

2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2, 3 -dihydro- 1 H-4-pyrazolecarboxylic acid piperidin- 1 -ylamide;

2-(4-Bromophenyl)- 1 -(2-bromobenzyl)-3 -oxo-2,3-dihydro- 1 H-4-pyrazolecarboxylic acid (4-methylsulphanyl-phenyl)-amide;

2-(4-Bromophenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylic acid (4-fluorophenyl)-amide;

2-(4-bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid adamantan-1-yl amide;

2-(4-Bromophenyl)-l-hexyl-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxylicacid piperidin-1- ylamide;

2-(4-Bromophenyl)- 1 -hexyl-3 -oxo-2,3 -dihydro- 1 H-4-pyrazolecarboxylic acid (4- fluorophenyl)-amide;

2-(4-Bromophenyl)-l -hexyl-3 -oxo-2, 3-dihydro-lH-4-pyrazolecarboxylic acid (4- methylsulphanyl phenyl)-amide;

2-(2,4-Difluorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide;

2-(2,4-Difluorophenyl)-l-(4-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -{4-methylsulphanyl phenyl)-amide;

2-(2,4-Difluorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphonyl phenyl)-amide;

2-(2,4-Difluorophenyl)-l-(3-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid -(4-methylsulphanyl phenyl)-amide;

N4-(3 -hydroxy- 1 -adamantyl)- 1 -(3-chIorobenzyl)-2-(3-triflouromethylphenyl)-4- pyrazolidinecarboxamide;

N4-(4-methoxyphenyl)-l-(3-chloro-benzyl)-2-(3-trifluoromethyl-phenyl)-4- pyrazolidinecarboxamide;

2-(4-Trifluoromethylphenyl)-l-(2-bromobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazole carboxylic acid adamantan-1-ylamide;

2-(4-Trifluoromethylphenyl)-l-(2-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH-4- pyrazole carboxylic acid adamantan-1-ylamide;

2-(4-Trifluoromethylphenyl)- 1 -(2,4-dichloromethylbenzyl)-3 -oxo-2,3 -dihydro- 1 H-4- pyrazole carboxylic acid adamantan-1-ylamide; 2-(4-Trifluoromethylphenyl)- 1 -(2-chloromethylbenzyl)-3-oxo-2,3 -dihydro- 1 H-4-pyrazole carboxylic acid adamantan-1-ylamide;

N4-[(5S, 1 R,2R,3R)-2,6,6-trimethylbicyclo[3.1. l]hept-3-yl]-2(4trifluoromethyl- phenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-4-pyrazolecarboxamide and pharmaceutically acceptable salts thereof.

15. A compound according to claim 2, wherein the compound is selected from

l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(2,4-dichlorophenyl)-3-oxo-l-(4-trifluoromethylbenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid;

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(3 -trifluoromethylbenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid;

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(3 -chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(2,4-dichlorophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-l H-pyrazole-4-carboxylic acid;

2-(2,4-dichlorophenyl)-3-oxo-l-(2-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(2,4-Chlorophenyl)- 1 -(3-fluorobenzyl)-3-oxo-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid; l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

1 -Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid; l-(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidinecarboxylic acid; l-(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidinecarboxylic acid;

1 -(2,5 -dichlorophenyl)-2-(3-chlorobenzyl)-4-pyrazolidinecarboxylic acid; l-(2,5-dichlorophenyl)-2-(2-chlorobenzyl)-4-pyrazolidinecarboxylic acid; l-Benzyl-2-(4-chloro-phenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-chloro phenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid; 2-(4-chloro phenyl)-3 -oxo- 1 -(2, 6-dichlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxyllc acid;

2-(4-chlorophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(4-chlorophenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2₃3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3-oxo-l-(2,6-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3-oxo-l-(2,6-difluorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3-oxo-l-(2-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3-oxo- 1 -(2,4-dichlorobenzyl)-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid;

2-(4-bromophenyl)-3-oxo- 1 -(2-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(4-bromophenyl)-3-oxo- 1 -(4-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(4-bromo phenyl)-3 -oxo- 1 -hexyl-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid;

2-(2,4-difluorophenyl)-3-oxo-l-(4-trifluoromethylbenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid;

2-(2,4-difluorophenyl)-3 -oxo- 1 -(3 -trifluoromethylbenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid; l-(3-chloro-benzyl)-2-(3-trifluoromethyl- phenyl)-4-pyrazolidine carboxylic acid;

2-(4-Trifluoromethylphenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid;

2-(4-Trifluoromethylphenyl)-l-(2,4-dichlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid; 2-(4-Trifluoromethylphenyl)-l-(2-trifluoromethylbenzyl)-3-oxo-2,3-dihydro-lH- pyrazole-4-carboxylic acid;

2-(4-tr ifluoromethylphenyl)-3 -oxo- 1 -(2-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid and pharmaceutically acceptable salts thereof.

16. A compound according to claim 2, wherein the compound is selected from l-Benzyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(2,4-dichlorophenyl)-3-oxo- 1 -(4-trifluoromethylbenzyl)-2,3-dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester;

2-(2,4-dichlorophenyl)-3-oxo-l-(3-trifluoromethyl benzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester;

2-(2,4-dichlorophenyl)-3-oxo-l-(3-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(2,4-dichlorophenyl)-3 -oxo- 1 -(4-chlorobenzyl)-2,3-dihydro- 1 H-pyrazole-4-carboxylic acid ethyl ester;

2-(2,4-dichIorophenyl)-3-oxo-l-(2-chloro benzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(2,4-diChlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester; l-Cyclohexylmethyl-2-(2,4-dichlorophenyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester; l-Benzyl-2-(2,4-dichlorophenyl)-pyrazolidine-4-carboxylic acid ethyl ester; 1 -(2,4-dichlorophenyl)-2-(3-fluorobenzyl)-4-pyrazolidinecarboxylicacid ethyl ester; 1 -(2,4-dichlorophenyl)-2-(4-fluorobenzyl)-4-pyrazolidinecarboxylicacid ethyl ester; 1 -(2,5-dichlorophenyl)-2-(3-chlorobenzyl)-4-pyrazolidinecarboxylicacid ethyl ester; 1 -(2,5-dichlorophenyl)-2-(2-chlorobenzyl)-4-pyrazolidinecarboxylicacid ethyl ester;

1 -Benzyl-2-(4-chlorophenyl)-3-oxo-2,3-dihydro-l H-pyrazole-4-carboxylic acid ethyl ester;

2-(4-Chlorophenyl)-l-(3-fluorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-chloro phenyl)-3-oxo-l-(2,4-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester; 2-(4-chloro phenyl)-3-oxo-l-(2, δ-dichlorobenzyO^^-dihydro-lH-pyrazole^-carboxylic acid ethyl ester;

2-(4-chloro phenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-chloro phenyl)-3 -oxo- 1 -(3 -chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid ethyl ester;

2-(4-Bromophenyl)-l-(3-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromophenyl)-3-oxo-l-(2,6-dichlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromo phenyl)-3-oxo-l-(2,6-difluorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromo phenyl)-3 -oxo- 1 ~(2-chlorobenzyl)~2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromophenyl)-3-oxo-l-(4-chlorobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromophenyl)-3 -oxo- 1 -(2,4-dichlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxyl ic acid ethyl ester;

2-(4-bromo phenyl)-3 -oxo- 1 -(3-chlorobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromo phenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromophenyl)-3-oxo- 1 -(4-bromobenzyl)-2,3 -dihydro- 1 H-pyrazole-4-carboxylic acid ethyl ester;

2-(4-bromophenyl)-3-oxo- 1 -hexyl-2,3-dihydro- 1 H-pyrazole-4-carboxylicacid ethyl ester;

2-(2,4-difluorophenyl)-3 -oxo- 1 -(4-trifluoromethylbenzyl)-2,3 -dihydro- 1 H-pyrazole-4- carboxylic acid ethyl ester;

2-(2,4-difluorophenyl)-3-oxo-l-(3-trifluoromethylbenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester; l-(3-chloro-benzyl)-2-(3-trifluoromethyl- phenyl)-4-pyrazolidine carboxylic acid ethyl ester;

2-(4-Trifluoromethylphenyl)-l-(2-chlorobenzyl)-3-oxo-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester; 2-(4-Trifluoromethyl phenyl)-l-(2, 4-dichlorobenzyl)-3-oxo-2, 3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester;

2-(4-Trifluoromethylphenyl)- 1 -(2-trifluoromethylbenzyl)-3-oxo-2, 3 -dihydro- 1 H- pyrazole-4-carboxylic acid ethyl ester;

2-(4-trifluoromethylphenyl)-3-oxo-l-(2-bromobenzyl)-2,3-dihydro-lH-pyrazole-4- carboxylic acid ethyl ester and pharmaceutically acceptable salts thereof.

17. A process for preparing a compound of formula II,

(II) wherein Z is -CH₂ or -CH-, R² and R³ both are hydrogen and p, q, A, B, R⁴ and R⁵ are the same as defined in claim 2, comprising the steps of:

(a) reacting a compound of formula (7) with a compound of formula (13),

(7) (13) to form a compound of formula (18)

(b) deprotecting a compound of formula (18) and reacting it with LX wherein L is leaving group and X is halogen to form a compound of formula (19)

(19) .

(c) cyclizing a compound of formula (19) to form a compound of formula (20)

(20)

(d) reacting a compound of formula 20 with a compound of formula 20(a)

to form a compound of formula (

(e) deprotecting the compound of formula (21) to form a compound of formula

(22)

(22) ; and

(f) reacting a compound of formula (22) with a halogenating agent to form a corresponding acid chloride, which is further reacted with HNR⁴R⁵ to form compound offormula(II).

18. A process for preparing a compound of formula II

(H) wherein Z is -CH₂ or -CH-, R² and R³ both are hydrogen, and p, q, A, B, R⁴ and R⁵ are the same as defined in claim 2, comprising the steps of:

(a) reacting a compound of formula (7) with a compound of formula (13),

(7) (13) to form a compound of formula (18)

(b) reacting a compound of formula (18) in the presence of trialkyl or triaryl phosphine and a dialkylazadicarboxylate in a suitable solvent to form a compound of formula (20)

(c) reacting a compound of formula 20 with a compound of formula 20(a)

S^¹ o form a compound of formula (21)

( (2211)

(d) deprotecting a compound of formula (21) to form a compound of formula(22)

⁽²²⁾ ; and

(e) reacting a compound of formula (22) with a halogenating agent to form a corresponding acid chloride, which is further reacted with HNR⁴R⁵ to form compound of formula(II).

19. A process for preparing a compound of formula II,

(II) wherein Z is -CH₂ or -CH-, R² and R³ along with the carbon atom to which they are attached represent carbonyl (C=O), and p, q, A, B, R⁴ and R⁵ are the same as defined in claim 2, comprising the steps of

(a) reacting a compound of formula (1) with a compound of formula (13),

(D (13) to form a compound of formula (14)

heating a compound of formula (14) to form a compound of formula (15)

(b) reacting compound of formula (15) a compound of formula 20(a)

S<" to form a compound of formula (16)

(d) deprotecting the compound of formula (16) to form a compound of formula

(17)

(e) reacting a compound of formula (17) with a halogenating agent to form a corresponding acid chloride, which is further reacted with HNR⁴R⁵ to form compound of formula(II).

20. A pharmaceutical composition comprising a compound according to any of claims 1-16 either as a free base or in pharmaceutically acceptable salt form and a pharmaceutically acceptable excipient.

21. The pharmaceutical composition according to claim 20, wherein the pharmaceutically acceptable excipient is a carrier or diluent.

22. A method for the manufacture of a pharmaceutical composition comprising admixing a compound according to any of claims 1-16 either as a free base or in pharmaceutically acceptable salt form and a pharmaceutically acceptable excipient.

23. A method for preventing, ameliorating or treating a cannabinoid receptor mediated disease, disorder or syndrome in a subject in need thereof comprising administering to the subject an effective amount of a compound according to any of claims 1-16.

24. A method for preventing, ameliorating or treating a cannabinoid receptor mediated disease, disorder or syndrome in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition of claim 20.

25. The method of claims 23-24 wherein the cannabinoid receptor mediated disease, disorder or syndrome is selected from appetite disorders, metabolism disorders, catabolism disorders, diabetes, obesity, ophthalmic diseases, social related disorders, mood disorders, seizures, substance abuse, learning disorders, cognition disorders, memory disorders, organ contraction, muscle spasm, respiratory disorders, disorders and diseases, locomotor activity disorders, movement disorders, immune disorders (such as autoimmune disorders), inflammation, cell growth , pain or neurodegenerative related syndromes.

26. The method of claim 25, wherein the wherein the cannabinoid receptor mediated disease, disorder or syndrome is selected from appetite disorders, social related disorders, autoimmune or inflammation, pain and neurodegenerative related syndromes, disorders and diseases and substance abuse.

27. The method of claim 26, wherein the appetite related disease, disorder or syndrome, includes obesity, overweight conditions, anorexia, bulimia, cachexia, dysregulated appetite, obesity related syndromes, disorders, diseases or symptoms include; obesity as a result of genetics; diet; food intake volume; metabolic syndrome; disorder or disease; hypothalmic disorder or disease; age; abnormal adipose mass distribution; abnormal adipose compartment distribution; compulsive eating disorders; motivational disorders which include the desire to consume sugars; carbohydrates; alcohols or drugs or any ingredient with hedonic value, reduced activity.

28. The method of claim 26, wherein the social related disease, disorder or syndrome, is depression, includes bipolar depression, unipolar depression, single or recurrent major depressive episodes with or without psychotic features, catatonic features, melancholic features, atypical features or postpartum onset, seasonal affective disorder, dysthymic disorders with early or late onset and with or without atypical features, neurotic depression and social phobia, depression accompanying dementia, anxiety, psychosis, social affective disorders, cognitive disorders.

29. The method of claim 26, wherein the autoimmune or inflammation related disease, disorder or syndrome, includes psoriasis, lupus erythematosus, diseases of the connective tissue, Sjogren's syndrome, ankylosing spondylarthritis, rheumatoid arthritis, reactional arthritis, undifferentiated spondylarthritis, Behcet's disease, autoimmune hemolytic anaemias, multiple sclerosis, amyotrophic lateral sclerosis, amyloses, graft rejection or diseases affecting the plasma cell line; allergic diseases: delayed or immediate hypersensitivity, allergic rhinitis, contact dermatitis or allergic conjunctivitis infectious parasitic, viral or bacterial diseases (such as AIDS and meningitis), inflammatory diseases (such as diseases of the joints including, but not limited to, arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS)) and osteoporosis.

30. The method of claim 26, wherein the pain and neurodegenerative related syndromes, disorders and diseases includes central and peripheral pathway mediated pain, bone and joint pain, migraine headache associated pain, cancer pain, menstrual cramps, labor pain, chronic pain of the inflammatory type, allergies, rheumatoid arthritis, dermatitis, immunodeficiency, chronic neuropathic pain, includes, pain associated with diabetic neuropathy; sciatica; non specific lower back pain; fibromyalgia; HIV-related neuropathy; post herpetic neuralgia; trigeminal neuralgia; pain resulting from physical trauma, dental pain, amputation, cancer, toxins or chronic inflammatory conditions), hodgkin's disease, myasthenia gravis, nephrotic syndrome, scleroderma and thyroiditis.

31. The method of claim 26, wherein the substance abuse related syndromes, disorders or diseases include, drug abuse and drug withdrawal in which substance of abuse or dependence include alcohol, amphetamines, amphetamine like substances, caffeine, cannabis, cocaine, hallucinogens, inhalants, opioids, nicotine, heroin abuse, barbiturates, phencyclidine or its derivatives, sedative- hypnotics, benzodiazepines, combinations of substances of abuse.

32. The method of claim 26, wherein the ophthalmic diseases include, glaucoma, glaucoma-associated intraocular pressure, retinitis, retinopathies, uveitis, acute injury to the eye tissue.

33. A method for treating an ophthalmic disease, respiratory disorder, immune disorder, inflammation, pain or a neurodegenerative related syndrome, in a subject in need thereof comprising administering to the subject an effective amount of a compound according to any of claims 1-16.

34. A method for treating pain in a subject in need thereof comprising administering to the subject an effective amount of a compound according to any of claims 1-16.

35. The method of claim 34, wherein the pain is neuropathic pain.