Heterocyclic compound

Patent metadata

Field	Value
Publication number	US-10519110-B2
Application number	US-201816175144-A
Country	US
Kind code	B2
Filing date	Oct 30, 2018
Priority date	Apr 20, 2015
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

The present invention relates to a compound which can be useful for the treatment or prevention of SPT-related diseases including cancer and congenital diseases associated with sphingolipid accumulation (including Niemann-Pick disease).

First claim

The invention claimed is:

1. A method for treating Niemann-Pick disease in a mammal, comprising administering an effective amount of a compound or a salt thereof to the mammal, wherein the compound is represented by a formula:

wherein
ring Ar represents an optionally further substituted aromatic heterocycle or an optionally further substituted C 6-14 aromatic hydrocarbon ring;
ring A represents an optionally further substituted C 6-14 aromatic hydrocarbon ring or an optionally further substituted heterocycle;
R 1 represents an optionally substituted C 6-14 aryl group, an optionally substituted C 3-10 cycloalkyl group or an optionally substituted heterocyclic group

except that when R 1 is an optionally substituted heterocyclic group, R 1 is represented by a formula:

wherein ring B represents an optionally further substituted heterocycle, and

represents a single bond or a double bond, or a formula:

wherein ring D represents an optionally further substituted nitrogen-containing heterocycle,
R 2 represents a hydrogen atom, or
R 1 and R 2 are bonded to each other to form an optionally substituted 5- or 6-membered aromatic heterocycle or an optionally substituted benzene ring.

2. The method according to claim 1 , wherein
ring Ar is

(I) an aromatic heterocycle optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) a cyano group,
(3) a hydroxy group,
(4) an optionally halogenated C 1-6 alkyl group,
(5) a C 3-10 cycloalkyl group,
(6) an optionally halogenated C 1-6 alkoxy group,
(7) a hydroxy-C 1-6 alkoxy group,
(8) a C 3-10 cycloalkyloxy group,
(9) a C 1-6 alkyl-carbonyl group,
(10) a C 1-6 alkoxy-carbonyl group,
(11) an amino group,
(12) a mono- or di-C 1-6 alkylamino group,
(13) a mono- or di-C 1-6 alkyl-carbonylamino group,
(14) a mono- or di-C 3-10 cycloalkyl-carbonylamino group,
(15) a 5- to 14-membered aromatic heterocyclic group, and
(16) a C 1-6 alkylsulfonyl group,

or
(II) a C 6-14 aromatic hydrocarbon ring optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) a cyano group,
(3) an optionally halogenated C 1-6 alkyl group,
(4) a C 3-10 cycloalkyl group,
(5) an optionally halogenated C 1-6 alkoxy group,
(6) a mono- or di-C 1-6 alkylamino group,
(7) a C 1-6 alkyl-5- to 14-membered aromatic heterocyclic group, and
(8) a C 1-6 alkylsulfonyl group;
ring A is

(I) a C 6-14 aromatic hydrocarbon ring optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) a cyano group,
(3) an optionally halogenated C 1-6 alkyl group,
(4) an optionally halogenated C 1-6 alkoxy group, and
(5) a C 1-6 alkylsulfonyl group,

or
(II) a heterocycle optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) an optionally halogenated C 1-6 alkyl group,
(3) a C 3-10 cycloalkyl group,
(4) an optionally halogenated C 1-6 alkoxy group,
(5) a hydroxy-C 1-6 alkoxy group,
(6) a C 1-6 alkoxy-C 1-6 alkoxy group,
(7) a 3- to 14-membered non-aromatic heterocycle-C 1-6 alkoxy group,
(8) a 3- to 14-membered non-aromatic heterocyclyloxy-C 1-6 alkoxy group,
(9) a mono- or di-C 1-6 alkylamino-C 1-6 alkoxy group,
(10) a mono- or di-C 7-16 aralkyl phosphate-C 1-6 alkoxy group,
(11) a 5- to 14-membered aromatic heterocyclic group,
(12) a 5- to 14-membered aromatic heterocyclyloxy group,
(13) a C 1-6 alkylsulfonyl group, and
(14) a C 1-6 alkylsulfanyl group;
R 1 is

(I) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) an optionally halogenated C 1-6 alkyl group, and
(3) a C 1-6 alkoxy group,

(II) a C 3-10 cycloalkyl group, or
(III) an optionally substituted heterocyclic group represented by any of
(1) a heterocyclic group represented by a formula:

which is selected from pyrazolyl, thienyl and pyridyl and optionally substituted by 1 to 3 C 1-6 alkyl groups, and
(2) a nitrogen-containing heterocyclic group represented by a formula:

which is selected from pyrazol-1-yl, 1,2,3-triazol-1-yl and piperidinyl;
R 2 is a hydrogen atom; or
R 1 and R 2 are bonded to each other to form

(I) a 5- or 6-membered aromatic heterocycle optionally substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) an optionally halogenated C 1-6 alkyl group,
(3) a C 7-20 alkyl group,
(4) a hydroxy-C 1-6 alkyl group,
(5) a C 1-6 alkoxy-C 1-6 alkyl group,
(6) an optionally halogenated C 3-10 cycloalkyl-C 1-6 alkyl group,
(7) a C 3-10 cycloalkyl group,
(8) a C 1-6 alkoxy-C 7-16 aralkyl group,
(9) a 3- to 14-membered non-aromatic heterocyclic group,
(10) an optionally halogenated C 1-6 alkyl-3- to 14-membered non-aromatic heterocyclic group,
(11) a C 1-6 alkyl-3- to 14-membered non-aromatic heterocycle-C 1-6 alkyl group,
(12) a carbamoyl-C 1-6 alkyl group,
(13) an amino-C 1-6 alkyl group,
(14) a C 1-6 alkoxy-carbonylamino-C 1-6 alkyl group,
(15) a fluorenyl-C 1-6 alkoxy-carbonylamino-C 1-6 alkyl group, and
(16) a mono- or di-C 1-6 alkyl nitrogen-containing heterocycle-C 1-6 alkyl-nitrogen-containing heterocycle-κ 2 N (boron halide)-C 1-6 alkyl-carbonylamino-C 1-6 alkyl group,

or
(II) a benzene ring optionally substituted by one halogen atom.

3. The method according to claim 2 , wherein
R 1 represents a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from (1) a halogen atom, (2) an optionally halogenated C 1-6 alkyl group and (3) a C 1-6 alkoxy group,
R 2 is a hydrogen atom, or
R 1 and R 2 are bonded to each other to form a 5- or 6-membered aromatic heterocycle optionally substituted by 1 to 3 substituents selected from (1) a halogen atom, (2) an optionally halogenated C 1-6 alkyl group, (3) a C 7-20 alkyl group, (4) a hydroxy-C 1-6 alkyl group, (5) a C 1-6 alkoxy-C 1-6 alkyl group, (6) an optionally halogenated C 3-10 cycloalkyl-C 1-6 alkyl group, (7) a C 3-10 cycloalkyl group, (8) a C 1-6 alkoxy-C 7-16 aralkyl group, (9) a 3- to 14-membered non-aromatic heterocyclic group, (10) an optionally halogenated C 1-6 alkyl-3- to 14-membered non-aromatic heterocyclic group, (11) a C 1-6 alkyl-3- to 14-membered non-aromatic heterocycle-C 1-6 alkyl group, (12) a carbamoyl-C 1-6 alkyl group, (13) an amino-C 1-6 alkyl group, (14) a C 1-6 alkoxy-carbonylamino-C 1-6 alkyl group, (15) a fluorenyl-C 1-6 alkoxy-carbonylamino-C 1-6 alkyl group, and (16) a mono- or di-C 1-6 alkyl nitrogen-containing heterocycle-C 1-6 alkyl-nitrogen-containing heterocycle-κ 2 N (boron halide)-C 1-6 alkyl-carbonylamino-C 1-6 alkyl group.

4. The method according to claim 2 , wherein
ring Ar represents an aromatic heterocycle optionally substituted by 1 to 3 substituents selected from (1) a halogen atom, (2) a cyano group, (3) a hydroxy group, (4) an optionally halogenated C 1-6 alkyl group, (5) a C 3-10 cycloalkyl group, (6) an optionally halogenated C 1-6 alkoxy group, (7) a hydroxy-C 1-6 alkoxy group, (8) a C 3-10 cycloalkyloxy group, (9) a C 1-6

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Asano Yasutomi
• Kojima Takuto
• Kurasawa Osamu
• Wong Tzu-Tshin
• Hirata Yasuhiro
• Iwamura Naoki
• Saito Bunnai
• Tanaka Yuta
• Arai Ryosuke
• Imamura Shinichi
• Yonemori Kazuko
• Miyamoto Yasufumi
• Kitamura Shuji
• Sano Osamu

Classifications

• C07D211/58 Primary

  attached in position 4 · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D413/06

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

• A61K31/443

  containing a five-membered ring with oxygen as a ring hetero atom · CPC title

• A61K31/4433

  containing a six-membered ring with oxygen as a ring hetero atom · CPC title