5-heteroaryl-1H-pyrazol-3-amine derivative

Patent metadata

Field	Value
Publication number	US-12410154-B2
Application number	US-202117772093-A
Country	US
Kind code	B2
Filing date	Nov 29, 2021
Priority date	Nov 30, 2020
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

The present disclosure provides a compound that exerts an anticancer action based on CHK1 inhibition. The present disclosure was completed by finding that a compound represented by formula (1) or a pharmaceutically acceptable salt thereof exhibits an excellent antitumor action by having a potent inhibitory action against CHK1:

wherein R 1 , R 2 , L, V, W, and Q are as defined herein, X, Y, and Z each independently represent CR 8 or a nitrogen atom, wherein X, Y, and Z are not simultaneously CR 8 , and R 8 is as defined herein.

First claim

The invention claimed is:

1. A compound represented by

or a pharmaceutically acceptable salt thereof, wherein
R 1 represents a hydrogen atom, optionally substituted C 1-6 alkyl, optionally substituted C 3-10 cycloalkyl, an optionally substituted 3- to 10-membered saturated heterocyclic group, optionally substituted C 6-10 aryl, or optionally substituted 5- to 12-membered heteroaryl,
R 2 represents a hydrogen atom, a halogen atom, cyano, nitro, carboxyl, sulfonic acid, phosphoric acid, —OR 3 , —SR 3 , —COR 4 , —CO 2 R 4 , —CONR 5 R 6 , —SO 2 R 4 , —SO 2 NR 5 R 6 , —OCOR 4 , —OCO 2 R 4 , —OCONR 5 R 6 , —NR 5 R 6 , —NR 7 COR 4 , —NR 7 CO 2 R 4 , —NR 7 CONR 5 R 6 , —NR 7 SO 2 R 4 , —NR 7 SO 2 NR 5 R 6 , optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 3-10 cycloalkyl, an optionally substituted 3- to 10-membered saturated heterocyclic group, optionally substituted C 6-10 aryl, or optionally substituted 5- to 12-membered heteroaryl,
R 3 represents a hydrogen atom or C 1-6 alkyl,
R 4 represents C 1-6 alkyl,
R 5 , R 6 , and R 7 each independently represent a hydrogen atom or C 1-6 alkyl, wherein R 5 and R 6 that attach to the same nitrogen atom, when both are C 1-6 alkyl, together with the nitrogen atom to which each is attached, may form a 3- to 8-membered nitrogen-containing saturated heterocycle,
X, Y, and Z each independently represent CR 8 or a nitrogen atom, wherein X, Y, and Z are not simultaneously CR 8 ,
R 8 , if there are multiple instances, each independently represent a hydrogen atom, a halogen atom, cyano, nitro, carboxyl, sulfonic acid, phosphoric acid, —OR 9 , —SR 9 , —COR 10 , —CO 2 R 10 , —CONR 11 R 12 , —SO 2 R 10 , —SO 2 NR 11 R 12 , —OCOR 10 , —OCO 2 R 10 , —OCONR 11 R 12 , —NR 11 R 12 , —NR 13 COR 10 , —NR 13 CO 2 R 10 , —NR 13 CONR 11 R 12 , —NR 13 SO 2 R 10 , —NR 13 SO 2 NR 11 R 12 , optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 3-10 cycloalkyl, an optionally substituted 3- to 10-membered saturated heterocyclic group, optionally substituted C 6-10 aryl, or optionally substituted 5- to 12-membered heteroaryl,
R 9 represents a hydrogen atom or C 1-6 alkyl,
R 10 represents C 1-6 alkyl,
R 11 , R 12 , and R 13 each independently represent a hydrogen atom or C 1-6 alkyl, wherein R 11 and R 12 that attach to the same nitrogen atom, when both are C 1-6 alkyl, together with the nitrogen atom to which each is attached, may form a 3- to 8-membered nitrogen-containing saturated heterocycle,
L represents a single bond or optionally substituted C 1-6 alkylene,
V represents a single bond, optionally substituted C 3-10 cycloalkylene, or an optionally substituted 3- to 10-membered divalent saturated heterocyclic group,
W represents a single bond or optionally substituted C 1-6 alkylene,
Q represents a hydrogen atom or NHR 14 , and
R 14 represents a hydrogen atom, optionally substituted C 1-6 alkyl, optionally substituted C 3-10 cycloalkyl, or an optionally substituted 3- to 10-membered saturated heterocyclic group.

2. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein
optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted C 2-6 alkynyl, optionally substituted C 3-10 cycloalkyl, an optionally substituted 3- to 10-membered saturated heterocyclic group, optionally substituted C 6-10 aryl, optionally substituted 5- to 12-membered heteroaryl, optionally substituted C 1-6 alkylene, optionally substituted C 3-10 cycloalkylene, or an optionally substituted 3- to 10-membered divalent saturated heterocyclic group in R 1 , R 2 , R 8 , R 14 , L, V, and W is, each independently, optionally substituted with 1 to 5 of the same or different substituents selected from the group consisting of
(1) a halogen atom,
(2) a hydroxyl group,
(3) C 6-10 aryl,
(4) 5- to 12-membered heteroaryl,
(5) C 1-6 alkyl,
(6) C 2-6 alkenyl,
(7) C 2-6 alkynyl,
(8) C 1-6 alkoxy,
(9) C 1-6 alkylthio
(10) C 3-10 cycloalkyl,
(11) a 3- to 10-membered saturated heterocyclic group,
(12) carboxyl,
(13) —COR 15 ,
(14) —CO 2 R 15 ,
(15) —CONR 16 R 17 ,
(16) —NR 16 R 17 ,
(17) —NR 18 COR 15 ,
(18) —NR 18 CO 2 R 15 ,
(19) —NR 18 SO 2 R 15 ,
(20) —NR 18 CONR 16 R 17 ,
(21) —NR 18 SO 2 NR 16 R 17 ,
(22) —SO 2 R 15 ,
(23) —SO 2 NR 16 R 17 ,
(24) —OCOR 15 ,
(25) —OCO 2 R 15 ,
(26) —OCONR 16 R 17 ,
(27) sulfonic acid,
(28) phosphoric acid,
(29) cyano, and
(30) nitro,
wherein the groups represented by (3) C 6-10 aryl, (4) 5- to 12-membered heteroaryl, (5) C 1-6 alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl, (8) C 1-6 alkoxy, (9) C 1-6 alkylthio, (10) C 3-10 cycloalkyl, and (11) a 3- to 10-membered saturated heterocyclic group are optionally substituted with 1 to 5 of the same or different substituents selected from the group consisting of
(a) a halogen atom,
(b) a hydroxyl group,
(c) C 6-10 aryl,
(d) 5- to 12-membered heteroaryl,
(e) C 1-6 alkyl,
(f) C 2-6 alkenyl,
(g) C 2-6 alkynyl,
(h) C 1-6 alkoxy,
(i) C 3-10 cycloalkyl,
(j) a 3- to 10-membered saturated heterocyclic group,
(k) carboxyl,
(l) —COR 15 ,
(m) —CO 2 R 15 ,
(n) —CONR 16 R 17 ,
(o) —NR 16 R 17 ,
(p) —NR 18 COR 15 ,
(q) —NR 18 SO 2 R 15 ,
(r) —SO 2 R 15 ,
(s) —SO 2 NR 16 R 17 ,
(t) sulfonic acid,
(u) phosphoric acid,
(v) cyano, and
(w) nitro,
R 15 , if there are multiple instances, are each independently C 1-6 alkyl,
R 16 and R 17 are each independently a hydrogen atom or C 1-6 alkyl, and if there are multiple instances of R 16 or R 17 , each of R 16 or R 17 may be the same or different, wherein R 16 and R 17 that attach to the same nitrogen atom, when both are C 1-6 alkyl, together with the nitrogen atom to which each is attached, may form a 3- to 8-membered nitrogen-containing saturated heterocycle, and
R 18 is a hydrogen atom or C 1-6 alkyl.

3. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is a hydrogen atom or C 1-6 alkyl optionally substituted with 1 to 3 fluorine atoms.

4. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 1 is a methyl group.

5. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 2 is a hydrogen atom, a halogen atom, cyano, —OR 3 , C 1-6 alkyl, C 3-10 cycloalkyl, or a 3- to 10-membered saturated heterocyclic group.

6. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 2 is cyano.

7. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R 8 , if there are multiple instances, are each independently a hydrogen atom, a halogen atom, cyano, —OR 9 , —CO 2 R 10 , —CONR 11 R 12 , —NR 11 R 12 , —NR 13 COR 10 , C 1-6 alkyl (wherein the alkyl is optionally substituted with 1 to 3 of the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, phenyl, 5- to 6-membered heteroaryl, C 1-6 alkoxy, C 3-7 cycloalkyl, a 3- to 7-membered saturated heterocyclic group, —CONR 16 R 17 , —NR 16 R 17 , and cyano), C 3-10 cycloalkyl (wherein the cycloalkyl is optionally substituted with 1 to 3 of the same or different substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, phenyl, 5- to 6-membered heteroaryl, C 1-6 alkyl, C 1-6 alkoxy, C 3-7 cycloalkyl, a 3- to 7-membered saturated heterocyclic group, —CONR 16 R 17 , —NR 16 R 17 , and cyan

Assignees

• Sumitomo Pharma Co Ltd

Inventors

• Kamioka Seiji
• Ban Hitoshi
• Matsuoka Makoto
• Hirose Wataru
• Shimada Naoaki
• Hayashi Kento
• Umehara Hiroki

Classifications

• C07D403/14

  containing three or more hetero rings · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title