Inhibiting agents for bruton's tyrosine kinase

Patent metadata

Field	Value
Publication number	US-2020239459-A1
Application number	US-201916534540-A
Country	US
Kind code	A1
Filing date	Aug 7, 2019
Priority date	Apr 14, 2017
Publication date	Jul 30, 2020
Grant date	—

Abstract

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and methods for their use and production.

First claim

What is claimed is:

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
Ring A is 5-membered monocyclic heteroaryl containing 3 heteroatoms independently selected from N, O and S, wherein said 5-membered monocyclic heteroaryl is optionally substituted with one or more R 1 ;
Q 1 , Q 2 , and Q 3 are each, independently, selected from O, N(R 2 ), and CH—R 3 , wherein at least two of Q 1 , Q 2 , and Q 3 are C—R 3 ;
W is selected from CH and N;
Y is selected from CH and N;
R 1 in each occurrence is independently selected from C 1-6 alkyl and 3- to 5-membered carbocyclyl, wherein said C 1-6 alkyl and 3- to 5-membered carbocyclyl are optionally substituted with one or more R 10 ;
R 10 in each occurrence is independently selected from halo, —CN, C 1-6 alkyl, and 3- to 5-membered carbocyclyl;
R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, 4- to 6-membered monocyclic heterocyclyl, —CN, —C(O)R 2a , —C(O) 2 R 2a , —C(O)N(R 2a ) 2 , —S(O) 2 R 2a , and —S(O) 2 N(R 2a ) 2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl are optionally substituted with one or more R 20 ;
R 2a in each occurrence is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl in each occurrence are optionally and independently substituted with one or more R 20 ;
R 20 in each occurrence is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, 4- to 6-membered monocyclic heterocyclyl, halo, —CN, —C(O)R 20a , —C(O) 2 R 20a , —C(O)N(R 20a ) 2 , —N(R 20a ) 2 , —N(R 20a )C(O)R 20a , —N(R 20a )C(O) 2 R 20a , —N(R 20a )C(O)N(R 20a ) 2 , —N(R 20a )S(O) 2 R 20a , —OR 20a , —OC(O)R 20a , —OC(O)N(R 20a ) 2 , —SR 20a , —S(O)R 20a , —S(O) 2 R 20a , —S(O)N(R 20a ) 2 , and —S(O) 2 N(R 20a ) 2 ;
R 20a in each occurrence is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl;
R 3 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, 4- to 6-membered monocyclic heterocyclyl, halo, —CN, —C(O)R 3a , —C(O) 2 R 3a , —C(O)N(R 3a ) 2 , —N(R 3a ) 2 , —N(R 3a )C(O)R 3a , —N(R 3a )C(O) 2 R 3a , —N(R 3a )C(O)N(R 3a ) 2 , —N(R 3a )S(O) 2 R 3a , —OR 3a , —OC(O)R 3a , —OC(O)N(R 3a ) 2 , —SR 3a , —S(O)R 3a , —S(O) 2 R 3a , —S(O)N(R 3a ) 2 , and —S(O) 2 N(R 3a ) 2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl are optionally substituted with one or more R 30 ;
R 3a in each occurrence is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl in each occurrence are optionally and independently substituted with one or more R 30 ;
R 30 in each occurrence is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, 4- to 6-membered monocyclic heterocyclyl, halo, —CN, —C(O)R 30a , —C(O) 2 R 30a , —C(O)N(R 30a ) 2 , —N(R 30a ) 2 , —N(R 30a )C(O)R 30a , —N(R 30a )C(O) 2 R 30a , —N(R 30a )C(O)N(R 30a ) 2 , —N(R 30a )S(O) 2 R 30a , —OR 30a , —OC(O)R 30a , —OC(O)N(R 30a ) 2 , —SR 30a , —S(O)R 30a , —S(O) 2 R 30a , —S(O)N(R 30a ) 2 , and —S(O) 2 N(R 30a ) 2 ;
R 30a in each occurrence is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 4- to 6-membered monocyclic carbocyclyl, and 4- to 6-membered monocyclic heterocyclyl;
R 4 is selected from H and C 1-6 alkyl, wherein said C 1-6 alkyl is optionally substituted with one or more halo;
R 5 is selected from H and C 1-6 alkyl wherein said C 1-6 alkyl is optionally substituted with one or more halo;
R 6 is selected from H and C 1-6 alkyl, wherein said C 1-6 alkyl is optionally substituted with one or more halo;
or R 5 and R 6 , together with the atoms to which they are attached, form a ring containing one or two heteroatoms selected from O, N, and S, wherein the ring is optionally substituted with one or more R 50 ; and
R 50 is a C 1-6 alkyl.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q 1 , Q 2 and Q 3 are each independently CH—R 3 .

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q 2 is N(R 2 ) and Q 1 and Q 3 are each independently CH—R 3 .

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q 3 is N(R 2 ) and Q 1 and Q 2 are each independently CH—R 3 .

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Q 1 is O and Q 2 and Q 3 are each independently CH—R 3 .

6 . The compound of any one of claims 1 - 5 , or a pharmaceutically acceptable salt thereof, wherein W is CH.

7 . The compound of any one of claims 1 - 6 , or a pharmaceutically acceptable salt thereof, wherein Y is N.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by one of following formulas:

or a pharmaceutically acceptable salt thereof.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is represented by one of following formulas:

or a pharmaceutically acceptable salt thereof.

10 . The compound of any one of claims 1 - 9 , or a pharmaceutically acceptable salt thereof, wherein ring A is selected from 1,2,3-oxadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,2,3-thiadiazole, 1,3,4-thiadiazole, 1,2,4-thiadiazole, 1,2,3-triazole, and 1,2,4-triazole, each of which is optionally substituted with one or two R 1 .

11 . The compound of any one of claims 1 - 9 , or a pharmaceutically acceptable salt thereof, wherein ring A is represented by one of the following formula:

12 . The compound of any one of claims 1 - 11 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 in each occurrence is independently C 1-6 alkyl or C 3-5 cycloalkyl; wherein said C 1-6 alkyl and C 3-5 cycloalkyl are optionally substituted with one to three R 10 ; and R 10 in each occurrence is independently selected from halo, —CN and C 1-6 alkyl.

13 . The compound of any one of claims 1 - 11 , wherein:
R 1 in each occurrence is independently C 1-4 alkyl, cyclopropyl, or cyclobutyl; wherein said C 1-4 alkyl, cyclopropyl and cyclobutyl are optionally substituted with one to three R 10 ; and R 10 in each occurrence is independently selected from halo, —CN and C 1-3 alkyl.

14 . The comp

Assignees

• Biogen Ma Inc

Inventors

• Hopkins Brian T
• Ma Bin
• Prince Robin
• Marx Isaac
• Lyssikatos Joseph P
• Zheng Fengmei
• Peterson Matthew
• Patience Daniel B

Classifications

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D403/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title