Kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9505766-B2
Application number	US-201414462158-A
Country	US
Kind code	B2
Filing date	Aug 18, 2014
Priority date	Nov 16, 2009
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.

First claim

What is claimed is:

1. A compound having the formula:

wherein
W is —C(O)— or S(O) 2 —;
z is 0 or 1;
X is O or N, wherein if X is O, then z is 0;
R 1 is R 7 -substituted 7H-pyrrolo[2,3-d]pyrimidin-6-yl, R 7 -substituted 7H-pyrrolo[2,3-d]pyrimidin-7-yl or R 7 -substituted pyrazolopyrimidin-1-yl;
R 7 is independently halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 8 -substituted or unsubstituted alkyl, R 8 -substituted or unsubstituted heteroalkyl, R 8 -substituted or unsubstituted cycloalkyl, R 8 -substituted or unsubstituted heterocycloalkyl, R 8 -substituted or unsubstituted aryl, R 8 -substituted or unsubstituted heteroaryl, or -L 6 -R 7A ;
L 6 is —O—, —C(O)—, —C(O)NH—, —S(O) m —, or —S(O) m NH—;
m is 0, 1, or 2;
R 7A is hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 8 -substituted or unsubstituted alkyl, R 8 -substituted or unsubstituted heteroalkyl, R 8 -substituted or unsubstituted cycloalkyl, R 8 -substituted or unsubstituted heterocycloalkyl, R 8 -substituted or unsubstituted aryl, or R 8 -substituted or unsubstituted heteroaryl;
R 8 is independently hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 9 -substituted or unsubstituted alkyl, R 9 -substituted or unsubstituted heteroalkyl, R 9 -substituted or unsubstituted cycloalkyl, R 9 -substituted or unsubstituted heterocycloalkyl, R 9 -substituted or unsubstituted aryl, or R 9 -substituted or unsubstituted heteroaryl;
R 9 is independently hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 10 -substituted or unsubstituted alkyl, R 10 -substituted or unsubstituted heteroalkyl, R 10 -substituted or unsubstituted cycloalkyl, R 10 -substituted or unsubstituted heterocycloalkyl, R 10 -substituted or unsubstituted aryl, or R 10 -substituted or unsubstituted heteroaryl;
R 10 is independently halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;
R 3 and R 4 are independently hydrogen, unsubstituted alkyl, alkyl substituted with one or two hydroxy or di(unsubstituted alkyl)amino, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted aryl, wherein R 3 and R 4 are optionally joined together with X to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
L 1 is a bond or unsubstituted phenylene;
L 4 and L 5 are independently a bond, unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene; and
wherein if L 1 is a bond and R 1 is (3-(4-amino-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propan-1-ol)-6-yl, then at least one of R 3 and R 4 are not hydrogen.

2. The compound of claim 1 , wherein X is N.

3. The compound according to claim 1 , having the structure

4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

5. A compound having the formula:

wherein
W is —C(O)— or —S(O) 2 —;
z is 1;
R 1 is R 7 -substituted 7H-pyrrolo[2,3-d]pyrimidin-6-yl, R 7 -substituted 7H-pyrrolo[2,3-d]pyrimidin-7-yl or R 7 -substituted pyrazolopyrimidin-1-yl;
R 7 is halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 8 -substituted or unsubstituted alkyl, R 8 -substituted or unsubstituted heteroalkyl, R 8 -substituted or unsubstituted cycloalkyl, R 8 -substituted or unsubstituted heterocycloalkyl, R 8 -substituted or unsubstituted aryl, R 8 -substituted or unsubstituted heteroaryl, or -L 6 -R 7A ;
L 6 is —O—, —C(O)—, —C(O)NH—, —S(O) m —, or —S(O) m NH—;
m is 0, 1, or 2;
R 7A is hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 8 -substituted or unsubstituted alkyl, R 8 -substituted or unsubstituted heteroalkyl, R 8 -substituted or unsubstituted cycloalkyl, R 8 -substituted or unsubstituted heterocycloalkyl, R 8 -substituted or unsubstituted aryl, or R 8 -substituted or unsubstituted heteroaryl;
R 8 is independently hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 9 -substituted or unsubstituted alkyl, R 9 -substituted or unsubstituted heteroalkyl, R 9 -substituted or unsubstituted cycloalkyl, R 9 -substituted or unsubstituted heterocycloalkyl, R 9 -substituted or unsubstituted aryl, or R 9 -substituted or unsubstituted heteroaryl;
R 9 is independently hydrogen, halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , R 10 -substituted or unsubstituted alkyl, R 10 -substituted or unsubstituted heteroalkyl, R 10 -substituted or unsubstituted cycloalkyl, R 10 -substituted or unsubstituted heterocycloalkyl, R 10 -substituted or unsubstituted aryl, or R 10 -substituted or unsubstituted heteroaryl;
R 10 is independently halogen, —CN, —OH, —NH 2 , —COOH, —CF 3 , unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl;
R 3 and R 4 are independently hydrogen, unsubstituted alkyl, alkyl substituted with one or two hydroxy or di-(unsubstituted alkyl)amino, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted aryl wherein R 3 and R 4 are optionally joined together with X to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
L 1 is a bond or unsubstituted phenylene;
L 4 and L 5 are independently a bond, unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene; and
wherein if L 1 is a bond and R 1 is (3-(4-amino-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)propan-1-ol)-6-yl, then at least one of R 3 and R 4 are not hydrogen.

6. The compound according to claim 5 , wherein R 1 is R 7 -substituted 7H-pyrrolo[2,3-d]pyrimidinyl.

7. The compound according to claim 6 , wherein R 3 and R 4 are hydrogen.

8. The compound according to claim 6 ,
wherein
R 3 is unsubstituted alkyl; and
R 4 is hydrogen.

9. The compound according to claim 6 , wherein R 3 and R 4 join with N to form R 23 -substituted or unsubstituted pyrrolidinyl.

10. The compound according to claim 5 ,
wherein
R 1 is R 7 -substituted 7H-pyrrol

Assignees

• Univ California

Inventors

• Taunton Jr John William
• Maglathlin Rebecca
• Serafimova Iana
• Cohen Michael S
• Miller Rand
• Paavilainen Ville
• Mcfarland Jesse
• Krishnan Shyam

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title