Cyclic amino benzoic acid derivative

• US 7,902,367 B2
• Filed: 08/11/2005
• Issued: 03/08/2011
• Est. Priority Date: 08/11/2004
• Status: Expired due to Fees

• Current Assignee: Kyorin Pharmaceutical Company Limited (Kyorin Holdings Incorporated)
• Original Assignee: Kyorin Pharmaceutical Company Limited (Kyorin Holdings Incorporated)
• Inventors: Takano, Yasuo, Murakami, Koji, Isogai, Shigeki, Yumoto, Kazuhiro, Nomura, Masahiro, Shinozaki, Takehiro
• Primary Examiner(s): Desai; Rita J
• Assistant Examiner(s): Mabry; John
• Application Number:
  US11/659,854
• Publication Number:
  US 20070249580A1
• Time in Patent Office: 2,035 Days
• Field of Search: 546/209, 514/326
• US Class Current: 546/209
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07D 211/22 by oxygen atoms
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/42 attached in position 3 or 5
• CPC Class Codes: C07D 211/56 Nitrogen atoms nitro radicals C07D211/38
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to cyclic amino benzoic acid derivatives which are effective in therapy of lipid metabolism abnormality, diabetes and the like as a human peroxisome proliferators-activated receptor (PPAR) agonist, in particular, as an agonist against human PPARα isoform, and addition salts thereof, and pharmaceutical compositions containing these compounds.

A cyclic amino benzoic acid derivative represented by the general formula (1)

[wherein a ring Ar represents an aryl group which may have substituent, or the like; Y represents a C₁-C₄ alkylene, C₂-C₄ alkenylene, C₂-C₄ alkynylene, or the like; Z represents an oxygen atom, sulfur atom or —(CH₂)_n— (n represents 0, 1 or 2); X represents a hydrogen atom, halogen atom, lower alkyl group which may be substituted with a halogen atom, or the like; R represents a hydrogen atom or lower alkyl group, and —COOR substitutes for an ortho position or metha position of binding position of ring W] or a pharmaceutically acceptable salt thereof.

Claims

1. A cyclic amino benzoic acid derivative represented by general formula (1)

2. A cyclic amino benzoic acid derivative according to claim 1, wherein in the general formula (1), Y

represents a C₁-C₄ alkylene, C₂-C₄ alkenylene, C(O)NH, NHC(O)NH, C(O)NH—

C₁-C₄ alkylene, C(O)—

C₁-C₄ alkylene, C₁-C₄ alkylene-NHC(O), C₁-C₄ alkylene-C(O)NH, C₂-C₄ alkenylene-C(O)NH, C₁-C₄ alkylene-O, C₁-C₄ alkylene-O—

C₁-C₄ alkylene or C₁-C₄ alkylene-NH,

or a pharmaceutically acceptable salt thereof.

3. A cyclic amino benzoic acid derivative according to claim 1, wherein the compound represented by the general formula (1) is

2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxy]piperidin-1-yl] benzoic acid,

2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid,

2-[3-[N-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methyl] carbamoyl]piperidin-1-yl] benzoic acid,

(S)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

(R)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

(R)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxy]piperidin-1-yl] benzoic acid,

(S)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

(R)-2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

(S)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid, or

(R)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid,

or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.

5. A cyclic amino benzoic acid derivative according to claim 1, wherein the general formula (1) represents general formula (1a)

6. A cyclic amino benzoic acid derivative according to claim 5, wherein in the general formula (1a), Y^a represents a C(O)NH, C(O)NH—

C₁-C₄ alkylene, C₁-C₄ alkylene-NHC(O), C₁-C₄ alkylene-C(O)NH, C₁-C₄ alkylene-O or C₁-C₄ alkylene-O—

C₁-C₄ alkylene, or a pharmaceutically acceptable salt thereof.

7. A cyclic amino benzoic acid derivative according to claim 1, wherein the compound represented by the general formula (1) is

2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxymethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methoxy]piperidin-1-yl] benzoic acid,

2-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylaminomethyl]piperidin-1-yl] benzoic acid,

3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid,

2-[3-[N-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]methyl]carbamoyl]piperidin-1-yl] benzoic acid,

(S)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid or

(R)-3-[3-[[2-(4-chlorophenyl)-4-methylthiazol-5-yl]carbonylamino]piperidin-1-yl] benzoic acid,

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 2 as an active ingredient.

9. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 3 as an active ingredient.

10. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 5 as an active ingredient.

11. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 6 as an active ingredient.

12. A pharmaceutical composition comprising at least one cyclic amino benzoic acid derivative or a pharmaceutically acceptable salt thereof according to claim 7 as an active ingredient.