Cyclopropanamine compound and use thereof

Patent metadata

Field	Value
Publication number	US-9751885-B2
Application number	US-201314435085-A
Country	US
Kind code	B2
Filing date	Oct 11, 2013
Priority date	Oct 12, 2012
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

The present invention provides a compound having a lysine specific demethylase 1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, Alzheimer's disease, Parkinson's disease or Huntington's disease, and the like. The present invention relates to a compound represented by the formula

wherein A is a hydrocarbon group optionally having substituent(s), or a heterocyclic group optionally having substituent(s);
B is a benzene ring optionally having further substituent(s); R 1 , R 2 and R 3 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent(s), or a heterocyclic group optionally having substituent(s); A and R 1 are optionally bonded to each other to form, together with the adjacent nitrogen atom, a cyclic group optionally having substituent(s); and R 2 and R 3 are optionally bonded to each other to form, together with the adjacent nitrogen atom, a cyclic group optionally having substituent(s), or a salt thereof.

First claim

The invention claimed is:

1. A compound represented by the formula

wherein A is
(1) a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, each optionally having 1 or 2 fluorine atoms,
(2) a phenyl group optionally having one pyrimidinyl group, or
(3) a piperidinyl group, a pyrazolyl group, an isoxazolyl group, a thiazolyl group, a thiadiazolyl group, or a tetrahydropyranyl group, each optionally having 1 or 2 substituents selected from C 1-6 alkyl groups optionally having 1 to 3 substituents selected from a fluorine atom and a cyclopropyl group;
B is a benzene ring optionally further having one substituent selected from
(1) a halogen atom,
(2) a C 1-6 alkyl group, and
(3) a C 1-6 alkoxy group;
R 1 is a hydrogen atom;
R 2 is a hydrogen atom; and
R 3 is
(1) a cyclohexyl group, a cyclopentyl group, or a cyclobutyl group, each optionally having 1 or 2 fluorine atoms,
(2) a cyclopropylmethyl group,
(3) a C 1-6 alkyl group having one tetrahydropyranyl group, or
(4) a piperidinyl group or a tetrahydropyranyl group, each optionally having one substituent selected from
(a) a C 1-6 alkyl group optionally having 1 to 3 fluorine atoms, and
(b) a cyclopropyl group,

or a salt thereof.

2. The compound according to claim 1 , wherein A is
(1) a cyclopentyl group or a cyclohexyl group, each optionally having 1 or 2 fluorine atoms, or
(2) a piperidinyl group, an isoxazolyl group, a thiadiazolyl group, or a tetrahydropyranyl group, each optionally having one C 1-6 alkyl group optionally having 1 to 3 fluorine atoms;
B is a benzene ring;
R 1 is a hydrogen atom;
R 2 is a hydrogen atom; and
R 3 is
(1) a cyclohexyl group or a cyclobutyl group, each optionally having 1 or 2 fluorine atoms,
(2) a cyclopropylmethyl group, or
(3) a piperidinyl group or a tetrahydropyranyl group, each optionally having one cyclopropyl group,
or a salt thereof.

3. 3-(trans-2-((Cyclopropylmethyl)amino)cyclopropyl)-N-(5-methyl-1,2-oxazol-3-yl)benzamide or a salt thereof.

4. 3-(trans-2((1-Cyclopropylpiperidin-4-yl)amino)cyclopropyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide or a salt thereof.

5. 3-(trans-2-(Cyclobutylamino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)benzamide or a salt thereof.

6. A pharmaceutical composition comprising an effective amount of the compound according to claim 1 or a salt thereof, and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition according to claim 6 , wherein the compound according to claim 1 or a salt thereof is an LSD1 inhibitor.

8. The pharmaceutical composition according to claim 6 , wherein the compound according to claim 1 or a salt thereof is a therapeutic agent for at least one selected from the group consisting of schizophrenia, Alzheimer's disease, Parkinson's disease and Huntington's disease.

9. A method of inhibiting LSD1 in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.

10. A method for the treatment of schizophrenia, Alzheimer's disease, Parkinson's disease or Huntington's disease in a mammal, comprising administering an effective amount of the compound according to claim 1 or a salt thereof to the mammal.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Tomita Naoki
• Tomita Daisuke
• Tominari Yusuke
• Imamura Shinichi
• Morimoto Shinji
• Kojima Takuto
• Toyofuku Masashi
• Hattori Yasushi
• Kaku Tomohiro
• Ito Mitsuhiro

Classifications

• A61P43/00

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

• C07C2601/04

  with a four-membered ring · CPC title

• C07D207/12

  Oxygen or sulfur atoms · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · 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