Compounds and methods for the treatment of inflammatory and immune disorders

• US 6,294,574 B1
• Filed: 06/06/1995
• Issued: 09/25/2001
• Est. Priority Date: 07/13/1992
• Status: Expired due to Fees

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: CytoMed, Inc. (Takeda Pharmaceutical Company Limited)
• Inventors: Cai, Xiong, Killian, David, Hussoin, Sajjat, Hwang, San-Bao, Shen, T. Y.
• Primary Examiner(s): Kight, John
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US08/469,073
• Time in Patent Office: 2,303 Days
• Field of Search: 544/174, 544/176, 544/180, 546/256, 546/283, 546/284, 549/67, 549/70, 549/71, 549/72, 549/73, 549/74, 549/75, 549/78, 549/79, 549/80, 549/473, 549/478, 549/476, 549/477, 549/480, 549/483, 549/484, 549/487, 549/488, 549/491, 549/492, 549/494, 549/495, 549/496, 549/497, 549/498, 549/499, 549/500, 549/501, 549/502, 514/231.5, 514/237.2, 514/333, 514/337, 514/438, 514/445, 514/448, 514/471, 514/472, 514/473, 514/340, 514/913
• US Class Current: 514/473
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/09 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 307/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 307/14 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/16 by oxygen atoms
• CPC Class Codes: C07D 333/18 by sulfur atoms
• CPC Class Codes: C07D 333/20 by nitrogen atoms nitro, nitroso radicals C07D333/12
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 2,4-diaryl tetrahydrofurans, 2,4-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes, 2,4-diaryl pyrrolidines, and 2,5-diaryl pyrrolidines are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.

A method to treat disorders mediated by PAF or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

Claims

1. A method for the treatment of disorder mediated by platelet activating factor or products of 5-lipoxygenase in an animal, comprising adminstering an effective amount of trans-2-[5-N′

-methyl-N′

-hydroxyureidylmethyl)-3-methoxy-4-p-chlorophenylthioethoxphenyl]-5-(3,4,5-trimethoxphenyl)tetrahydrofuran or its pharmaceutically acceptable salt.

2. The method of claim 1, wherein the animal is a mammal.

3. The method of claim 1, wherein the animal is a human.

4. The method of claim 1, wherein the mammal is equine.

5. The method of claim 1, wherein the mammal is canine.

6. The method of claim 1, wherein the mammal is bovine.

7. The method of claim 1, wherein the disorder is psoriasis.

8. The method of claim 1, wherein the disorder is inflammatory bowel disease.

9. The method of claim 1, wherein the disorders are respiratory including, but not limited to, asthma, adult respiratory distress disorder (ARDS), and rhinitis.

10. The method of claim 1, wherein the disorder is ophthalmic inflammatory disorder.