Cyclopropaneamine compound

Patent metadata

Field	Value
Publication number	US-9682925-B2
Application number	US-201615005574-A
Country	US
Kind code	B2
Filing date	Jan 25, 2016
Priority date	Aug 9, 2011
Publication date	Jun 20, 2017
Grant date	Jun 20, 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 cancer, and central nervous system diseases, and the like. The present invention relates to a compound represented by the formula

wherein A is a hydrocarbon group or heterocyclic group optionally having substituent(s); R is H, a hydrocarbon group or heterocyclic group optionally having substituent(s); A and R are optionally bonded to each other to form a ring optionally having substituent(s); Q 1 , Q 2 , Q 3 and Q 4 are each a hydrogen atom or a substituent; Q 1 and Q 2 , and Q 3 and Q 4 , are each optionally bonded to each other to form a ring optionally having substituent(s); X is H, an acyclic hydrocarbon group or saturated cyclic group optionally having substituent(s); Y 1 , Y 2 and Y 3 are each H, a hydrocarbon group or heterocyclic group optionally having substituent(s); X and Y 1 , and Y 1 and Y 2 , are each optionally bonded to each other to form a ring optionally having substituent(s); and Z 1 , Z 2 and Z 3 are each H or a substituent, or a salt thereof.

First claim

The invention claimed is:

1. A compound represented by following formula (I):

wherein A is a hydrocarbon group optionally having substituent(s), or a heterocyclic group optionally having substituent(s);
R is a hydrogen atom, a hydrocarbon group optionally having substituent(s), or a heterocyclic group optionally having substituent(s); or
A and R are optionally bonded to each other to form a ring optionally having substituent(s);
Q 1 , Q 2 , Q 3 , and Q 4 are each independently a hydrogen atom or a substituent;
Q 1 and Q 2 , and Q 3 and Q 4 , are each optionally bonded to each other to form a ring optionally having substituent(s);
X is a hydrogen atom or a C 1-6 alkyl group optionally substituted by one C 3-6 cycloalkyl group;
Y 1 , Y 2 and Y 3 are each independently
(1) a hydrogen atom,
(2) a C 1-20 alkyl group optionally having from 1 to 3 substituents selected from the group consisting of an amino group, a C 1-6 alkoxy group, a phenyl group, a phenyloxy group, and a benzyloxy group,
(3) a C 3-8 cycloalkyl group,
(4) a phenyl group optionally having from 1 to 3 substituents selected from the group consisting of a halogen atom, a C 1-6 alkoxy group, a C 1-3 alkylenedioxy group, and a di-C 1-6 alkylamino group,
(5) a pyridyl group optionally having from 1 to 3 C 1-6 alkoxy groups,
(6) a naphthyl group,
(7) a biphenylyl group,
(8) a thienyl group,
(9) an imidazolyl group,
(10) a thiazolyl group,
(11) an imidazopyridyl group,
(12) an imidazothiazolyl group,
(13) a thienopyridyl group, or
(14) a 1,8-naphthyridinyl group;
Y 1 and Y 2 are optionally bonded to each other, together with an adjacent carbon atom that is bound to an adjacent nitrogen atom and Y 1 and Y 2 , to form
a C 3-8 cycloalkane ring,
a pyrrolidine ring,
a piperidine ring,
a tetrahydropyran ring,
a 2,3-dihydroindene ring,
a fluorene ring,
a 8-azabicyclo[3.2.1]octane ring, or
a tetrahydrothiopyran ring, each of which optionally has from 1 to 3 substituents selected from the group consisting of
(1) a halogen atom,
(2) a C 1-6 alkyl group optionally having from 1 to 3 substituents selected from the group consisting of a halogen atom and a phenyl group,
(3) a C 3-6 cycloalkyl group,
(4) an oxo group,
(5) a phenyl group,
(6) a C 2-6 alkenyloxy-carbonyl group, and
(7) a C 1-6 alkyl-carbonyl group; and
X and Y 1 are optionally bonded to each other to form a pyrrolidine ring, together with the adjacent nitrogen atom and the adjacent carbon atom; and
Z 1 , Z 2 , and Z 3 are each independently a hydrogen atom or a substituent,

or a salt thereof.

2. The compound according to claim 1 , wherein
A is
(1) a C 3-8 cycloalkyl group optionally having substituent(s),
(2) a C 6-14 aryl group optionally having substituent(s),
(3) a C 6-14 aryl C 1-6 alkyl group optionally having substituent(s),
(4) a C 6-14 aryl C 1-6 alkyl C 6-14 aryl group optionally having substituent(s),
(5) a from 4- to 11-membered heterocyclic group containing, as a ring-constituting atom besides carbon atom, from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom, and optionally having substituent(s), or
(6) a C 10-14 cyclic hydrocarbon group optionally having substituent(s);
R is a hydrogen atom or a C 1-6 alkyl group optionally having substituent(s); or
A and R are optionally bonded to each other to form a from 4- to 10-membered heterocycle optionally having substituent(s),

or a salt thereof.

3. The compound according to claim 1 , wherein
Q 1 is a hydrogen atom or a C 1-6 alkyl group, and
Q 2 , Q 3 and Q 4 are each a hydrogen atom,

or a salt thereof.

4. The compound according to claim 1 , wherein
Z 1 Z 2 and Z 3 are each a hydrogen atom,

or a salt thereof.

5. The compound according to claim 1 , wherein
A is
a phenyl-C 1-6 alkyl group,
a C 3-6 cycloalkyl group,
a tetrahydronaphthyl group,
a phenyl group,
a biphenylyl group,
a furyl group,
a thienyl group,
an oxazolyl group,
an isoxazolyl group,
a thiazolyl group,
a pyrazolyl group,
an indazolyl group,
a benzofuryl group,
a benzimidazolyl group,
a benzothiazolyl group,
an indolyl group, or
a tetrahydrobenzazepinyl group, each of which optionally has from 1 to 3 substituents selected from the group consisting of
(1) a halogen atom,
(2) a C 1-6 alkyl group optionally having from 1 to 3 substituents selected from the group consisting of a halogen atom, a phenyl group, an imidazolyl group, and a triazolyl group,
(3) a C 1-6 alkoxy group optionally having from 1 to 3 substituents selected from the group consisting of a halogen atom and a phenyl group,
(4) a C 1-6 alkyl-carbonyl group,
(5) a di-C 1-6 alkylamino group,
(6) a C 1-6 alkylsulfonyl group,
(7) a sulfamoyl group,
(8) a C 1-6 alkylsulfonylamino group,
(9) an oxo group,
(10) a C 3-6 cycloalkyl group,
(11) a phenyl group optionally having from 1 to 3 substituents selected from the group consisting of a halogen atom and a C 1-6 alkyl group,
(12) a phenoxy group,
(13) a phenylcarbonylamino group,
(14) a benzyloxycarbonylamino group,
(15) a benzoyl group,
(16) a benzylamino group,
(17) a pyrazolyl group,
(18) a dihydropyrazolyl group optionally having from 1 to 3 substituents selected from the group consisting of a C 1-6 alkyl group and an oxo group,
(19) an oxazolyl group,
(20) a thiazolyl group having 1 or 2 C 1-6 alkyl groups,
(21) a tetrazolyl group,
(22) a pyrrolyl group,
(23) a piperazinyl group having from 1 to 3 C 1-6 alkyl groups,
(24) an imidazolyl group,
(25) a pyridyl group,
(26) a pyrimidinyl group,
(27) a piperidyl group optionally having one oxo group,
(28) a thienyl group,
(29) a furyl group, and
(30) a thiadiazolyl group;
R is a hydrogen atom or a C 1-6 alkyl group; or
A and R are optionally bonded to each other to form a dihydroisoindole ring having 1 or 2 oxo groups;
Q 1 is a hydrogen atom or a C 1-6 alkyl group;
Q 2 , Q 3 , and Q 4 are each a hydrogen atom; and
Z 1 , Z 2 and Z 3 are each a hydrogen atom,

or a salt thereof.

6. The compound according to claim 1 , wherein
A is
a phenyl group optionally having from 1 to 3 C 1-6 alkyl groups substituted by from 1 to 3 halogen atoms,
a biphenylyl group, or
a pyrazolyl group;
R is a hydrogen atom; or
A and R are optionally bonded to each other to form a dihydroisoindole ring having 1 or 2 oxo groups;
Q 1 is a hydrogen atom or a C 1-6 alkyl group;
Q 2 , Q 3 , and Q 4 are each a hydrogen atom;
X is a hydrogen atom;
Y 1 , Y 2 ,and Y 3 are each independently a hydrogen atom or a C 3-8 cycloalkyl group;
Y 1 and Y 2 are optionally bonded to each other, together with the adjacent carbon atom, to form
a piperidine ring optionally having from 1 to 3 C 1-6 alkyl groups; and
Z 1 ,Z 2 , and Z 3 are each a hydrogen atom,

or a salt thereof.

7. A medicament comprising the compound according to claim 1 or a salt thereof.

8. The medicament according to claim 7 , which is a therapeutic agent for cancer.

9. The medicament according to claim 7 , which is an LSD1 inhibitor.

10. The medicament according to claim 7 , which is a therapeutic agent for schizophrenia, Alzheimer's diseas

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Tomita Naoki
• Kajii Shigeo
• Cary Douglas Robert
• Tomita Daisuke
• Imamura Shinichi
• Tsuchida Ken
• Matsuda Satoru
• Hara Ryujiro

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title