Arylacetate Derivatives Having Isoxazole Skeleton

• US 20090062531A1
• Filed: 05/23/2006
• Published: 03/05/2009
• Est. Priority Date: 05/27/2005
• Status: Active Grant

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Kanda, Yasuhiko
• Granted Patent: US 7,781,469 B2
• Time in Patent Office: Days
• US Class Current: 544/60
• 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 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• 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 19/10 for osteoporosis
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• 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: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 261/08 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links

Abstract

A compound of the formula (I):

• pharmaceutically acceptable salt or solvate thereof,
• wherein
• Y is a group of the formula:

• wherein Ring A is optionally substituted aryl or optionally substituted heteroaryl, X³ is COOR¹⁷ or the like
• Y is not optionally substituted phenyl which is substituted with the formula: —CR⁹R¹⁰X³ at the para position,
• R¹ to R¹⁰ are each independently halogen, hydroxy, optionally substituted lower alkyl, optionally substituted aryl or the like,
• X¹ is —O—, —S— or the like.

Claims

1. A compound of the formula (I):

2. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein Y is a group of the formula:

3. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein R¹ is optionally substituted aryl or heterocycle.

4. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein R² is optionally substituted lower alkyl.

5. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein R³ and R⁴ are hydrogen.

6. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 2, wherein R⁵, R⁶, R⁷ and R⁸ are each independently hydrogen, halogen, optionally substituted lower alkyl or optionally substituted lower alkoxy.

7. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein R⁹ and R¹⁰ are each independently hydrogen or halogen.

8. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein X¹ is O, S or —

ON═

CR¹⁴—

wherein R¹⁴ is hydrogen.

9. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 1, wherein X³ is COOR¹⁷ wherein R¹⁷ is hydrogen or optionally substituted lower alkyl.

10. The compound, pharmaceutically acceptable salt or solvate thereof according to claim 2, wherein R¹ is optionally substituted aryl or heterocycle, the substituent(s) of said aryl of R¹ is/are selected from a group consisting of halogen, optionally substituted lower alkyl and optionally substituted lower alkoxy,

R² is optionally substituted lower alkyl,

the substituent(s) of said lower alkyl of R² is/are selected from a group consisting of optionally substituted lower alkoxy, lower alkylamino, optionally substituted imino, optionally substituted iminooxy, lower alkylsulfonyl, cycloalkyloxy, optionally substituted aryl and optionally substituted heterocycle,

R³ and R⁴ are hydrogen,

R⁵, R⁶, R⁷ and R⁸ are each independently, hydrogen, halogen, lower alkyl or lower alkoxy,

R⁹ and R¹⁰ are each independently hydrogen or halogen,

X¹ is O, S or —

ON═

CR¹⁴—

wherein R¹⁴ is hydrogen, and

X³ is COOR¹⁷ wherein R¹⁷ is hydrogen or lower alkyl.

11. A pharmaceutical composition comprising the compound, pharmaceutically acceptable salt or solvate thereof according to any one of claims 1 to 10 as an active ingredient.

12. A pharmaceutical composition for prevention and/or treatment for a disease concerning peroxisome proliferator-activated receptor(s), which comprises the compound, pharmaceutically acceptable salt or solvate thereof according to any one of claims 1 to 10 as active ingredient.