Heterocyclic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2016222016-A1
Application number	US-201415026947-A
Country	US
Kind code	A1
Filing date	Oct 3, 2014
Priority date	Oct 4, 2013
Publication date	Aug 4, 2016
Grant date	—

Abstract

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

First claim

What is claimed is:

1 . A compound of Formula (I′):

or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
B is —(C 1 -C 4 )alkylene-R 18 ;
R 3 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro;
each R 5 is independently hydrogen, alkyl or halogen;
R 8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro;
R 9 is hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
W d is heterocyclyl, aryl, cycloalkyl, or heteroaryl, each of which is substituted with one or more R 10 , R 11 , R 12 , or R 13 ;
R 10 , R 11 , R 12 , and R 13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR′R″ wherein R′ and R″ together with the nitrogen to which they are attached form a cyclic moiety;
R 18 is aryl, heteroaryl, alkynyl, —OR 19 , —NHS(O) 2 R 20 , —NR 20 C(O)OR 21 , —NR 20 C(O)R 21 , —NR 20 C(O)NR 21 R 22 , —NR 20 R 21 , —S(O) 2 R 20 , or —S(O) 2 NR 20 R 21 ;
R 19 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
R 20 is hydrogen, amino, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
R 21 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; and
R 22 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; or when R 21 and R 22 are attached to one nitrogen, the R 21 and R 22 together with the nitrogen to which they are attached form a 3- to 7-membered heterocyclyl ring;
wherein the compound is not one of the following compounds:

2 . A compound of Formula (I):

or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
B is —(C 1 -C 4 )alkylene-R 18 ;
R 3 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro;
R 8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro;
R 9 is hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl;
W d is heterocyclyl, aryl, cycloalkyl, or heteroaryl, each of which is substituted with one or more R 10 , R 11 , R 12 , or R 13 ;
R 10 , R 11 , R 12 , and R 13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR′R″ wherein R′ and R″ together with the nitrogen to which they are attached form a cyclic moiety;
R 18 is aryl, heteroaryl, alkynyl, —OR 19 , —NHS(O) 2 R 20 , —NR 20 C(O)OR 21 , —NR 20 C(O)R 21 , —NR 20 C(O)NR 21 R 22 , —NR 20 R 21 , —S(O) 2 R 20 , or —S(O) 2 NR 20 R 21 ;
R 19 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
R 20 is hydrogen, amino, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;
R 21 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; and
R 22 is hydrogen, alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl;

or when R 21 and R 22 are attached to one nitrogen, the R 21 and R 22 together with the nitrogen to which they are attached form a 3- to 7-membered heterocyclyl ring;
wherein the compound is not one of the following compounds:

3 . The compound of claim 1 or 2 , wherein R 3 is halogen.

4 . The compound of any one of claims 1 - 3 , wherein R 8 is hydrogen.

5 . The compound of any one of claims 1 - 4 , wherein R 9 is methyl or ethyl.

6 . The compound of any one of claims 1 - 5 , wherein W d is heteroaryl.

7 . The compound of claim 6 , wherein W d is a 9-membered bicyclic heteroaryl, optionally substituted by at least one amino.

8 . The compound of claim 7 , wherein W d is

9 . The compound of any one of claims 1 - 8 , wherein B is —CH 2 —R 18 or —CH 2 —CH 2 —R 18 .

10 . The compound of any one of claims 1 - 9 , wherein R 18 is optionally substituted phenyl.

11 . The compound of any one of claims 1 - 9 , wherein R 18 is optionally substituted tetrazolyl, optionally substituted triazolyl, optionally substituted 1,2,4-triazolyl, or optionally substituted oxadiazolyl. In specific embodiments, R 18 is optionally substituted 1,2,4-oxadiazolyl.

12 . The compound of any one of claims 1 - 9 , wherein R 18 is (C 2 -C 6 ) alkynyl.

13 . The compound of any one of claims 1 - 9 , wherein R 18 is —OR 19 , and R 19 is (C 1 -C 3 )alkyl.

14 . The compound of any one of claims 1 - 9 , wherein R 18 is —NHS(O) 2 R 20 , —NR 20 C(O)OR 21 , —NR 20 R 21 or —NR 20 C(O)R 21 .

15 . The compound of any one of claims 1 - 9 , wherein R 18 is —S(O) 2 NR 20 R 21 or —S(O) 2 R 20 .

16 . The compound of claim 9 , wherein B is —CH 2 —CH 2 —R 18 , and R 18 is heteroaryl or —NHS(O) 2 R 20 .

17 . The compound of claim 2 , wherein the compound is:

18 . A compound of Formula (I):

or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein
B is hydrogen, alkyl, amino, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R 2 ;
each R 2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, am

Assignees

• Infinity Pharmaceuticals Inc

Inventors

• Castro Alfredo C
• Evans Catherine A
• Janardanannair Somarajannair
• Lescarbeau Andre
• Liu Tao
• Tremblay Martin R

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D403/12

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

• C07D401/12

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

• A61P35/00

  Antineoplastic agents · CPC title

• C07D405/12

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