Heterocycle amines and uses thereof

Patent metadata

Field	Value
Publication number	US-2016347767-A1
Application number	US-201615006940-A
Country	US
Kind code	A1
Filing date	Jan 26, 2016
Priority date	Nov 19, 2010
Publication date	Dec 1, 2016
Grant date	—

Abstract

Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using heterocycle amines. Some of the disclosed embodiments include heterocycle amines useful to treat inflammatory disorders.

First claim

What is claimed is:

1 . A compound of Formula (I):

or a salt, ester, amide, or prodrug thereof,
wherein
is a single or double bond;
W is selected from CH, CH—CH, O, S, NR 6 , and CO;
Y is N or CR 9 ;
Z is N or C, and Z is N if W is CH and Y is CR 9 ;
R 4 is selected from hydrogen, halogen, OR 6 , CN, NR 7 R 8 , CH 2 OR 6 , an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted carbocycle, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, CO 2 R 6 , SO 3 R 6 , SO 2 R 6 and SO 2 NR 7 R 8 ;
R 5 is selected from hydrogen, halogen, OR 6 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 haloheteroalkyl, an optionally substituted C 1 -C 6 alkenyl, and an optionally substituted C 1 -C 6 alkynyl;
or R 4 and R 5 are linked to form an optionally substituted non-aromatic ring;
each R 6 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, and an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C 1 -C 10 alkyl, an optionally substituted C 1 -C 10 haloalkyl, and an optionally substituted C 1 -C 10 heteroalkyl;
each R 7 and R 8 is independently selected from an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, each optionally fused with a substituted aryl or a substituted heteroaryl, hydrogen, an optionally substituted C 1 -C 10 alkyl, an optionally substituted C 1 -C 10 haloalkyl, an optionally substituted C 1 -C 10 alkenyl, an optionally substituted C 1 -C 10 alkynyl, and an optionally substituted C 1 -C 10 heteroalkyl, or R 7 and R 8 are linked to form an optionally substituted non-aromatic ring;
R 9 is selected from hydrogen, halogen, OR 6 , CN, NR 7 R 8 , CH 2 OR 6 , an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, CO 2 R 6 , SO 3 R 6 , and SO 2 NR 7 R 8 ;
A is an optionally substituted aryl or an optionally substituted heteroaryl group;
each optionally substituted group is either unsubstituted or substituted with one or more groups independently selected from alkyl, heteroalkyl, alkenyl, alkynyl, haloalkyl, heterohaloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic ring, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, trihalomethanesulfonyl, ═O, ═S, amino, and protected derivatives of amino groups.

2 . The compound of claim 1 , wherein R 4 is selected from hydrogen, halogen, OR 6 , CN, NR 7 R 8 , CH 2 OR 6 , an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted non-aromatic ring, an optionally substituted carbocycle, an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, CO 2 R 6 , SO 3 R 6 , SO 2 R 6 and SO 2 NR 7 R 8

3 . The compound of claim 1 , wherein if R 4 is pyrazolyl, the pyrazolyl is not substituted with aryl or heteroaryl groups.

4 . The compound of claim 1 , wherein if R 4 is oxazolyl, isoxazolyl, or imidazoyl, the oxazolyl, isoxazolyl, or imidazoyl radical is not substituted with aryl or heteroaryl groups.

5 . The compound of claim 1 , represented by Formula (I-A):

or a salt, ester, amide, or prodrug thereof,
wherein
X is N or CR 5 ′, wherein R 5 ′ is selected from hydrogen, halogen, OR 6 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 haloheteroalkyl, an optionally substituted C 1 -C 6 alkenyl, and an optionally substituted C 1 -C 6 alkynyl;
R 1 is selected from hydrogen, halogen, OR 6 , CN, NR 7 R 8 , CH 2 OR 6 , CH 2 NR 7 R 8 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, an optionally substituted C 1 -C 6 heteroalkyl, CO 2 R 6 , CONR 7 R 8 , SO 3 R 6 , and SO 2 NR 7 R 8 ;
R 2 and R 3 are independently selected from hydrogen, halogen, OR 6 , NR 7 R 8 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, and an optionally substituted C 1 -C 6 heteroalkyl.

6 . The compound of claim 1 , represented by Formula (II):

or a salt, ester, amide, or prodrug thereof.

7 . The compound of claim 1 , represented by Formula (III):

or a salt, ester, amide, or prodrug thereof,
wherein
X is N or CR 5 ′, wherein R 5 ′ is selected from hydrogen, halogen, OR 6 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 heteroalkyl, an optionally substituted C 1 -C 6 haloheteroalkyl, an optionally substituted C 1 -C 6 alkenyl, and an optionally substituted C 1 -C 6 alkynyl;
R 1 is selected from hydrogen, halogen, OR 6 , CN, NR 7 R 8 , CH 2 OR 6 , CH 2 NR 7 R 8 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, an optionally substituted C 1 -C 6 heteroalkyl, CO 2 R 6 , CONR 7 R 8 , SO 3 R 6 , and SO 2 NR 7 R 8 ;
R 2 and R 3 are independently selected from hydrogen, halogen, OR 6 , NR 7 R 8 , an optionally substituted C 1 -C 6 alkyl, an optionally substituted C 1 -C 6 haloalkyl, an optionally substituted C 1 -C 6 alkenyl, an optionally substituted C 1 -C 6 alkynyl, and an optionally substituted C 1 -C 6 heteroalkyl.

8 . The compound of claim 1 , wherein W is S.

9 . The compound of claim 7 , wherein X is N.

10 . The compound of claim 1 , wherein Y is CR 9 .

11 . The compound of claim 1 , wherein R 4 is selected from the group consisting of pyridyl, pyrazolyl, cyano, triazolyl, and oxazolyl.

12 . The compound of claim 1 , wherein Y is N.

13 . The compound of claim 1 , wherein R 4 is selected from the group consisting of pyridyl, pyrazolyl, pyrimidinyl, pyridazinyl, and C 1 -C 6 al

Assignees

• Ligand Pharm Inc

Inventors

• Ho Koc-Kan
• Diller David
• Letourneau Jeffrey J
• Mcguinness Brian F
• Cole Andrew G
• Rosen David
• Van Oeveren Cornelis A
• Pickens Jason C
• Zhi Lin
• Shen Yixing
• Pedram Bijan

Classifications

• A61K31/4168

  having a nitrogen attached in position 2, e.g. clonidine · CPC title

• C07D277/60

  condensed with carbocyclic rings or ring systems · CPC title

• C07D417/14 Primary

  containing three or more hetero rings · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title