Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-2016376244-A1
Application number	US-201615190642-A
Country	US
Kind code	A1
Filing date	Jun 23, 2016
Priority date	Jun 26, 2015
Publication date	Dec 29, 2016
Grant date	—

Abstract

The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, which may be useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies and the like. The present invention relates to a compound represented by the formula (I) or a salt thereof:

wherein each symbol is as defined in the attached DESCRIPTION.

First claim

1 . A compound represented by the formula

wherein
R 1 and R 2 are each independently a hydrogen atom or a substituent, or
a partial structure:

is optionally

(wherein X 1 and X 2 are each independently CH or N),
R 3 is a hydrogen atom, an optionally substituted C 1-6 alkyl group or an optionally substituted cyclic group, and
ring A is a ring which is optionally further substituted, excluding 6-[(2,4-dioxothiazolidin-5-yl)methyl]-3-[((4-trifluoromethyl)phenyl)methyl]-1,3-benzoxazin-4-one, or a salt thereof.

2 . The compound according to claim 1 , wherein R 3 is (1) a hydrogen atom, (2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group, (3) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups, (4) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms or (5) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups, or a salt thereof.

3 . The compound according to claim 1 , wherein the ring A is an optionally further substituted 6-membered aromatic ring, or a salt thereof.

4 . The compound according to claim 1 , wherein the ring A is a 6-membered aromatic ring optionally further substituted by 1 to 5 substituents selected from
(i) a halogen atom, (ii) a cyano group, (iii) a C 1-6 alkyl group, (iv) a C 2-6 alkenyl group, (v) a C 2-6 alkynyl group optionally substituted by a tri-C 1-6 alkylsilyl group, (vi) a C 1-6 alkoxy group and (vii) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 1-6 alkyl group, or a salt thereof.

5 . The compound according to claim 1 , wherein at least one of R 1 and R 2 is a substituent, or a salt thereof.

6 . The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group; or the partial structure:

is

(wherein X 1 and X 2 are each CH);
R 3 is a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-10 cycloalkyl group, an optionally substituted C 6-14 aryl group or an optionally substituted 3- to 14-membered non-aromatic heterocyclic group; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted, or a salt thereof.

7 . The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group; or the partial structure:

is

(wherein X 1 and X 2 are each CH);
R 3 is

(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group,
(3) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups,
(4) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms or
(5) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from

(i) a halogen atom,
(ii) a cyano group,
(iii) an oxo group,
(iv) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(v) a C 2-6 alkenyl group,
(vi) a C 2-6 alkynyl group optionally substituted by a tri-C 1-6 alkylsilyl group,
(vii) a C 1-6 alkoxy group,
(viii) a C 1-6 alkoxy-carbonyl group and
(ix) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 1-6 alkyl group,
or a salt thereof.

8 . The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-5 alkyl group;
R 2 is a hydrogen atom, a halogen atom, a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group; or the partial structure:

is

(wherein X 1 and X 2 are each CH);
R 3 is

(1) a hydrogen atom,
(2) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group,
(3) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups,
(4) a C 6-14 aryl group optionally substituted by 1 to 3 halogen atoms or
(5) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a 6-membered aromatic ring optionally further substituted by 1 to 5 substituents selected from

(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group,
(iv) a C 2-6 alkenyl group,
(v) a C 2-6 alkynyl group optionally substituted by a tri-C 1-6 alkylsilyl group,
(vi) a C 1-6 alkoxy group and
(vii) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a halogen atom and a C 1-6 alkyl group,
or a salt thereof.

9 . The compound according to claim 1 , wherein R 1 is a hydrogen atom, a halogen atom or a C 1-6 alkyl group;
R 2 is a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 1-6 alkoxy group; or the partial structure:

is

(wherein X 1 and X 2 are each CH);
R 3 is

(1) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 hydroxy groups or
(2) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by 1 to 3 hydroxy groups; and
ring A is a C 6-14 aromatic hydrocarbon ring, a 3- to 14-membered non-aromatic heterocycle or a 5- to 14-membered aromatic heterocycle, each of which is optionally further substituted by 1 to 5 substituents selected from

(i) a halogen atom,
(ii) a cyano group,
(iii) a C 1-6 alkyl group,
(iv) a C 1-6 alkoxy group and
(v) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 C 1-5 alkyl groups,
or a salt thereof.

10 . The compound according to cla

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Sugimoto Takahiro
• Suzuki Shinkichi
• Sakamoto Hiroki
• Yamada Masami
• Nakamura Minoru
• Kamata Makoto
• Shimokawa Kenichiro
• Ogino Masaki
• Kimura Eiji
• Murakami Masataka
• Yonemori Jinichi
• Kojima Takuto

Classifications

• C07D413/10

  linked by a carbon chain containing aromatic rings · 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

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D417/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07F7/02

  Silicon compounds · CPC title