Asthma and allergic inflammation modulators

• US 7,541,383 B2
• Filed: 11/26/2007
• Issued: 06/02/2009
• Est. Priority Date: 12/20/2002
• Status: Expired due to Term

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Fu, Zice, Tang, H. Lucy, Huang, Xi Alan, Xu, Qingge, Medina, Julio C., Liu, Jiwen, Schmitt, Michael J., Wang, Yingcai
• Primary Examiner(s): Shiao; Rei-Tsang
• Assistant Examiner(s): Coppins; Janet L
• Application Number:
  US11/986,863
• Publication Number:
  US 20080085891A1
• Time in Patent Office: 554 Days
• Field of Search: 514/562, 514/602, 514/604, 514/605, 562/430, 564/83, 564/92, 564/97, 564/99
• US Class Current: 514/602
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 205/37 : the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 205/56 : having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
• CPC Class Codes: C07C 233/75 : with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 2601/04 : with a four-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 271/28 : to a carbon atom of a non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 275/42 : being further substituted by carboxyl groups
• CPC Class Codes: C07C 311/08 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/21 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/29 : having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 317/44 : having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07D 209/22 : with an aralkyl radical attached to the ring nitrogen atom
• CPC Class Codes: C07D 209/26 : with an acyl radical attached to the ring nitrogen atom
• CPC Class Codes: C07D 213/71 : to which a second hetero atom is attached
• CPC Class Codes: C07D 215/36 : Sulfur atoms C07D215/24 takes precedence
• CPC Class Codes: C07D 233/84 : Sulfur atoms
• CPC Class Codes: C07D 243/12 : 1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
• CPC Class Codes: C07D 243/24 : Oxygen atoms
• CPC Class Codes: C07D 257/04 : Five-membered rings
• CPC Class Codes: C07D 295/192 : from aromatic carboxylic acids
• CPC Class Codes: C07D 307/91 : Dibenzofurans; Hydrogenated dibenzofurans
• CPC Class Codes: C07D 333/34 : Sulfur atoms
• CPC Class Codes: C07D 333/62 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring

Abstract

Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of inflammatory and immune-related diseases and conditions. In particular, the invention provides compounds which modulate the function and/or expression of proteins involved in atopic diseases, inflammatory conditions and cancer. The subject compounds are carboxylic acid derivatives.

Claims

1. A method for treating a respiratory allergic disease or a disease or condition selected from group consisting of asthma, allergic rhinitis, eczema, psoriasis, atopic dermatitis, rheumatoid arthritis, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, chronic obstructive pulmonary disease, conjunctivitis, nasal congestion and urticaria, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (XVI):

2. The method of claim 1, wherein the subject has allergic rhinitis.

3. The method of claim 2, wherein the subject has asthma.

4. The method of claim 1, wherein R⁴ is —

NHC(O)-cyclo(C₅-C₇)alkyl.

5. The method of claim 1, wherein R² is a substituted benzene ring and at least one substituent on the benzene ring is selected from the group consisting of halogen, —

OCF₃, —

OCH₃, —

(C₁-C₅)alkyl, —

CN, and —

NO₂.

6. The method of claim 1, wherein R¹⁰ is hydrogen.

7. The method of claim 6, wherein R⁴ is —

C(O)NH—

(C₁-C₄)alkyl, and R⁶ is hydrogen.

8. The method of claim 7, wherein R² is a benzene ring substituted with 1, 2, or 3 chlorine atoms.

9. The method of claim 1, wherein -L-Z taken together are —

CH₂COOH.

10. The method of claim 9, wherein the subscript n is 1 or 2.

11. The method of claim 10, wherein R¹⁴ is —

OCH₂CH₃ or —

OCH₃.

12. The method of claim 1, wherein R³, R⁵ and R⁶ are each hydrogen.

13. The method of claim 1, wherein the compound has the formula (XVIII):

14. The method of claim 1, wherein the compound is selected from the group consisting of

15. The method of claim 1, wherein the compound is

16. The method of claim 1, wherein R⁶ in the formula (XVI) is hydrogen.

17. The method of claim 1, wherein the subject has eczema, psoriasis or urticaria.

18. The method of claim 1, wherein the subject has atopic dermatitis.

19. The method of claim 1, wherein the subject has rheumatoid arthritis.

20. The method of claim 1, wherein the subject has inflammatory bowel disease, Crohn'"'"'s disease or ulcerative colitis.

21. The method of claim 1, wherein the subject has chronic obstructive pulmonary disease.

22. The method of claim 1, wherein the subject has conjunctivitis.

23. The method of claim 1, wherein the subject has nasal congestion.

24. A method as in any one of claims 2, 3, 21 and 23, wherein said compound is administered orally, parenterally or topically.