# US 9,751,885 B2 · Cyclopropanamine compound and use thereof

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- Number: US 9,751,885 B2
- Document ID: US9751885B2
- Status: Granted
- Kind: B2
- Application number: 14/435,085
- Filed: 2013-10-11
- Published: 2015-09-24
- Granted: 2017-09-05
- Earliest claimed: 2012-10-12
- Assignees: Takeda Pharmaceutical Company Limited
- Applicants: Takeda Pharmaceutical Company Limited
- Inventors: Naoki Tomita; Daisuke Tomita; Yusuke Tominari; Shinichi Imamura; Shinji Morimoto; Takuto Kojima; Masashi Toyofuku; Yasushi Hattori; Tomohiro Kaku; Mitsuhiro Ito
- Web page: https://patentgrep.com/patent/US9751885B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 237/30: having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
- C07C 237/38: having the nitrogen atom of the carboxamide group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C 237/40: having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
- C07C 255/29: containing cyano groups and acylated amino groups bound to the carbon skeleton
- C07C 255/58: containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
- C07C 255/60: at least one of the singly-bound nitrogen atoms being acylated
- C07C 317/40: Y being a hydrogen or a carbon atom
- C07D 207/12: Oxygen or sulfur atoms
- C07D 207/46: with hetero atoms directly attached to the ring nitrogen atom
- C07D 211/58: attached in position 4
- C07D 213/36: Radicals substituted by singly-bound nitrogen atoms (nitro radicals C07D213/26)
- C07D 213/40: Acylated substituent nitrogen atom
- C07D 223/12: Nitrogen atoms not forming part of a nitro radical
- C07D 231/38: Nitrogen atoms (nitro radicals C07D231/16)
- C07D 231/40: Acylated on said nitrogen atom
- C07D 241/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 241/18: Oxygen or sulfur atoms
- C07D 261/14: Nitrogen atoms
- C07D 265/36: condensed with one six-membered ring
- C07D 277/38: Nitrogen atoms
- C07D 285/135: Nitrogen atoms
- C07D 295/135: with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D 309/14: Nitrogen atoms not forming part of a nitro radical
- C07D 319/18: Ethylenedioxybenzenes, not substituted on the hetero ring
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 513/04: Ortho-condensed systems
- C07C 2601/02: with a three-membered ring
- C07C 2601/04: with a four-membered ring
- C07C 2601/08: the ring being saturated
- C07C 2601/14: The ring being saturated
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## 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); R1, R2 and R3 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent(s), or a heterocyclic group optionally having substituent(s); A and R1 are optionally bonded to each other to form, together with the adjacent nitrogen atom, a cyclic group optionally having substituent(s); and R2 and R3 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.

## Claims

### Claim 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 C1-6 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 C1-6 alkyl group, and
(3) a C1-6 alkoxy group;
R1 is a hydrogen atom;
R2 is a hydrogen atom; and
R3 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 C1-6 alkyl group having one tetrahydropyranyl group, or
(4) a piperidinyl group or a tetrahydropyranyl group, each optionally having one substituent selected from
(a) a C1-6 alkyl group optionally having 1 to 3 fluorine atoms, and
(b) a cyclopropyl group,
or a salt thereof.

### Claim 2 (depends on 1)

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 C1-6 alkyl group optionally having 1 to 3 fluorine atoms;
B is a benzene ring;
R1 is a hydrogen atom;
R2 is a hydrogen atom; and
R3 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.

### Claim 3

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

### Claim 4

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

### Claim 5

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1, 6)

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

### Claim 8 (depends on 1, 6)

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.

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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.