Amide compound and pharmaceutical comprising same

Patent metadata

Field	Value
Publication number	US-2016297764-A1
Application number	US-201415100866-A
Country	US
Kind code	A1
Filing date	Dec 9, 2014
Priority date	Dec 10, 2013
Publication date	Oct 13, 2016
Grant date	—

Abstract

Provided is a novel compound which has an excellent Aβ aggregation inhibitory effect and is useful as a pharmaceutical. An amide compound represented by the formula (1) or a salt thereof, wherein Z represents CH or N; A and B are the same or different and each represents —CH 2 —, —O—, —S—, or —NH—; R 1 and R 2 are the same or different and each represents a branched alkyl group, a branched alkenyl group, an optionally substituted aromatic hydrocarbon group, an optionally substituted aralkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aromatic heterocyclic group; and R 3 represents a branched alkyl group, a branched alkenyl group, an optionally substituted cycloalkyl group, or an optionally substituted aralkyl group.

First claim

1 : An amide compound represented by the formula (1) or a salt thereof:

wherein
Z represents CH or N;
A and B are the same or different and each represents —CH 2 —, —O—, —S—, or —NH—;
R 1 and R 2 are the same or different and each represents a branched alkyl group, a branched alkenyl group, an optionally substituted aromatic hydrocarbon group, an optionally substituted aralkyl group, an optionally substituted cycloalkyl group, or an optionally substituted aromatic heterocyclic group; and
R 3 represents a branched alkyl group, a branched alkenyl group, an optionally substituted cycloalkyl group, or an optionally substituted aralkyl group.

2 : The amide compound according to claim 1 or a salt thereof,
wherein A and B are the same or different and each is —CH 2 — or —O—.

3 : The amide compound according to claim 1 or a salt thereof, wherein A is —CH 2 — or —O—, and B is —CH 2 —.

4 : The amide compound according to claim 1 or a salt thereof, wherein A is —O—, and B is —CH 2 —.

5 : The amide compound according to claim 1 or a salt thereof, wherein R 1 and R 2 are the same or different and each is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted aromatic hydrocarbon group having 6 to 14 carbon atoms, an optionally substituted aralkyl group having 7 to 18 carbon atoms, or an optionally substituted cycloalkyl group having 3 to 12 carbon atoms; and R 3 is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 12 carbon atoms, or an optionally substituted aralkyl group having 6 to 18 carbon atoms.

6 : The amide compound according to claim 1 or a salt thereof, wherein R 1 and R 2 are the same or different and each is an optionally substituted aromatic hydrocarbon group having 6 to 14 carbon atoms, an optionally substituted aralkyl group having 7 to 18 carbon atoms, or an optionally substituted cycloalkyl group having 3 to 12 carbon atoms; and R 3 is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 12 carbon atoms, or an optionally substituted aralkyl group having 6 to 18 carbon atoms.

7 : The amide compound according to claim 1 or a salt thereof, wherein R 1 and R 2 are the same or different and each is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted aromatic hydrocarbon group having 6 to 14 carbon atoms, an optionally substituted aralkyl group having 7 to 18 carbon atoms, or an optionally substituted cycloalkyl group having 3 to 12 carbon atoms; and R 3 is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 12 carbon atoms, or an optionally substituted aralkyl group having 6 to 18 carbon atoms, wherein the group(s) capable of substituting the aromatic hydrocarbon group, the aralkyl group, or the cycloalkyl group is 1 to 5 groups selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxy group, a halogen atom, a nitro group, an amino group, a mono-C 1-4 alkylamino group, a di-C 1-4 alkylamino group, and a halogeno-C 1-4 alkyl group.

8 : The amide compound according to claim 1 or a salt thereof, wherein R 1 and R 2 are the same or different and each is an optionally substituted aromatic hydrocarbon group having 6 to 14 carbon atoms, an optionally substituted aralkyl group having 7 to 18 carbon atoms, or an optionally substituted cycloalkyl group having 3 to 12 carbon atoms; and R 3 is a branched alkyl group having 3 to 12 carbon atoms, a branched alkenyl group having 3 to 12 carbon atoms, an optionally substituted cycloalkyl group having 3 to 12 carbon atoms, or an optionally substituted aralkyl group having 6 to 18 carbon atoms, wherein the group(s) capable of substituting the aromatic hydrocarbon group, the aralkyl group, or the cycloalkyl group is 1 to 5 groups selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a hydroxy group, a halogen atom, a nitro group, an amino group, a mono-C 1-4 alkylamino group, a di-C 1-4 alkylamino group, and a halogeno-C 1-4 alkyl group.

9 : An amyloid β peptide aggregation inhibitor comprising an amide compound according to claim 1 or a salt thereof as an active ingredient.

10 : A pharmaceutical comprising an amide compound according to claim 1 or a salt thereof.

11 : The pharmaceutical according to claim 10 , which exhibits a prophylactic or therapeutic effect on Alzheimer's disease.

12 : A pharmaceutical composition comprising an amide compound according to claim 1 or a salt thereof and a pharmaceutically acceptable carrier.

13 : The pharmaceutical composition according to claim 12 , which comprises an amount of said amide compound or salt thereof sufficient to prevent or treat Alzheimer's disease.

14 : An amyloid β peptide aggregation inhibitor comprising the amide compound of claim 1 or a salt thereof.

15 : A prophylactic or therapeutic agent for Alzheimer's disease comprising the amide compound of claim 1 or a salt thereof.

16 : The amide compound according to claim 1 or a salt thereof, that inhibits amyloid β peptide aggregation.

17 : The amide compound according to claim 1 or a salt thereof, that prevents or treats Alzheimer's disease.

18 : A method for inhibiting amyloid β peptide aggregation, comprising administering an amide compound according to claim 1 or a salt thereof a subject in need thereof.

19 : A method for preventing or treating Alzheimer's disease, comprising administering an amide compound according to claim 1 or a salt thereof to a subject in need thereof.

Assignees

• Japan Science & Tech Agency

Inventors

• Kanai Motomu
• Soma Yohei
• Arai Tadamasa
• Araya Takushi

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D213/81 Primary

  Amides; Imides · CPC title

• A61P25/28

  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 title

• C07D239/30

  Halogen atoms or nitro radicals · CPC title