Heterocyclic amide compound

Patent metadata

Field	Value
Publication number	US-10774083-B2
Application number	US-201716333296-A
Country	US
Kind code	B2
Filing date	Sep 14, 2017
Priority date	Sep 15, 2016
Publication date	Sep 15, 2020
Grant date	Sep 15, 2020

Abstract

Provided is a heterocyclic amide compound that may have a PRS inhibitory action and is expected to be useful as a prophylactic or therapeutic agent for PRS associated diseases and the like including cancer. A compound represented by the following formula (I):

wherein a group represented by

is a group represented by the following formula (II) or the following formula (III):

and other symbols are as described in the DESCRIPTION, or a salt thereof.

First claim

The invention claimed is:

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

wherein a group represented by

is an optionally substituted aromatic ring group; and
a group represented by

is a group represented by the following formula (III):

wherein
R 5 is a hydrogen atom, a halogen atom, a cyano group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted amino group, or an optionally substituted hydroxy group;
X 2 is CR 6 ;
X 3 is CR 7 ;
R 6 and R 7 are each independently a hydrogen atom, a halogen atom, or an optionally substituted alkyl group;
X 4 is CR 8 R 9 or NR 10 , X 5 is CR 11 R 12 or carbonyl, X 6 is CR 13 R 14 or an oxygen atom;
R 8 and R 9 are each independently a hydrogen atom, a cyano group, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
R 8 and R 9 are optionally bonded to each other to form, together with the adjacent carbon atom, an optionally further substituted ring;
R 10 , R 13 , and R 14 are each independently a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group;
R 11 and R 12 are each independently a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted hydroxy group;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein the group represented by

is a C 6-14 aryl group, a 5- or 6-membered monocyclic aromatic heterocyclic group or a 8 to 14-membered fused polycyclic aromatic heterocyclic group, each of which is optionally substituted by 1 to 5 substituents selected from the group consisting of:
(1) a halogen atom,
(2) a cyano group,
(3) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms,
(4) a C 6-14 aryl group,
(5) a C 1-6 alkoxy group,
(6) a carboxy group,
(7) a C 1-6 alkoxy-carbonyl group,
(8) a carbamoyl group optionally mono- or di-substituted by a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6 alkyl groups, and
(9) a 5- to 14-membered aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from the group consisting of:
(i) a cyano group,
(ii) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, a hydroxy group and a 3- to 14-membered non-aromatic heterocyclic group,
(iii) a C 3-10 cycloalkyl group,
(iv) a C 1-6 alkoxy group,
(v) an oxo group,
(vi) a C 1-6 alkoxy-carbonyl group, and
(vii) a 3- to 14-membered non-aromatic heterocyclic group;

the group represented by

is
a group represented by the following formula (III):

R 5 is a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, a cycloalkyl group, or a hydroxy group optionally substituted by a C 1-6 alkyl group;
X 2 is CR 6 (R 6 is a hydrogen atom);
X 3 is CR 7 (R 7 is a hydrogen atom);
X 4 is CR 8 R 9 or NR 10 ;
R 8 and R 9 are each independently selected from the group consisting of:

(1) a hydrogen atom,
(2) a cyano group,
(3) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from the group consisting of a hydroxy group and a C 3-10 cycloalkyl group, and
(4) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 C 1-6 alkyl groups, or
R 8 and R 9 are bonded to each other to form C 3-10 cycloalkane together with the adjacent carbon atom;
R 10 is a C 1-6 alkyl group;
X 5 is CR 11 R 12 (R 11 and R 12 are each independently a hydrogen atom or a hydroxy group) or a carbonyl; and
X 6 is CR 13 R 14 (R 13 and R 14 are each independently a hydrogen atom or a C 1-6 alkyl group) or an oxygen atom;
or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmacologically acceptable carrier.

4. A method for inhibiting PRS in a mammal, comprising administering an effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof to the mammal.

5. A method for treating ovarian or skin cancer in a mammal, comprising administering an effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof to the mammal.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Hirayama Takaharu
• Hirata Yasuhiro
• Tominari Yusuke
• Iwamura Naoki
• Sasaki Yusuke
• Asano Moriteru
• Takagi Terufumi
• Okaniwa Masanori
• Imamura Shinichi

Classifications

• C12N9/99

  Enzyme inactivation by chemical treatment · CPC title

• C07D473/00

  Heterocyclic compounds containing purine ring systems · CPC title

• C07D473/32

  Nitrogen atom · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title

• A61K31/501

  not condensed and containing further heterocyclic rings · CPC title