Sulfamoylheleroaryl pyrazole compounds as anti-inflammatory/analgesic agents

• US 6,603,008 B1
• Filed: 11/28/2000
• Issued: 08/05/2003
• Est. Priority Date: 12/03/1999
• Status: Expired due to Fees

• Current Assignee: Pfizer Inc.
• Original Assignee: Pfizer Inc.
• Inventors: Ando, Kazuo, Kawamura, Kiyoshi
• Primary Examiner(s): FAN, JANE T
• Application Number:
  US09/723,661
• Time in Patent Office: 980 Days
• Field of Search: 546/269.7, 546/271.4, 546/275.4, 514/340, 514/341, 514/342
• US Class Current: 546/269.7
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings

Abstract

This invention relates to a compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein A and R¹ are each an optionally substituted 5 to 6-membered heteroaryl, wherein the heteroaryl is optionally fused to a carbocyclic ring or 5 to 6-heteroaryl; R² is NH₂; R³ and R⁴ are each hydrogen, halo, (C₁-C₄)alkyl optionally substituted with halo and the like; and X¹ to X⁴ are each hydrogen, halo, hydroxy, (C₁-C₄)alkyl optionally substituted with halo and the like. These compounds have COX-2 inhibiting activity and thus useful for treating or preventing inflammation or other COX-2 related diseases.

Claims

1. A compound having the formula

R¹ is furyl, thiazolyl or oxazolyl;

R² is NH₂;

R³ is trifluoroomethyl;

R⁴ is hydrogen, fluoro or ethyl;

X¹ and X² are independently hydrogen or chloro; and

X³ and X⁴ are hydrogen.

2. A compound according to claim 1 selected from the group consisting of

5-(5-(4-(2-furyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-chloro-4-(1,3-oxazol-2-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-chloro-5-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesul formamide;

5-(5-ethyl-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-ethyl-5-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-fluoro-5-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-fluoro-5-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-chloro-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-chloro-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-chloro-5-(3-chloro-4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-methyl-4-(1,3-thiazol-4-yl)phenyl)-3(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-ethyl-5-(3-fluoro-4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-chloro-4-(2-furyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide; and

salts thereof.

3. A compound according to claim 1 selected from the group consisting of

5-(5-(4-(2-furyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-chloro-4-(1,3-oxazol-2-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-ethyl-5-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-fluoro-5-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-chloro-(4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-chloro-4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-methyl-4-(1,3-thiazol-4-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(4-ethyl-5-(3-fluoro-4-(1,3-thiazol-5-yl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide;

5-(5-(3-chloro-4-(2-furyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-2-pyridinesulfonamide; and

salts thereof.