Boron-containing small molecules as anti-inflammatory agents

Patent metadata

Field	Value
Publication number	US-9682092-B2
Application number	US-201514688581-A
Country	US
Kind code	B2
Filing date	Apr 16, 2015
Priority date	Feb 16, 2006
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

Abstract

Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.

First claim

What is claimed is:

1. A method of treating an inflammatory-related disease in a human or an animal, said method comprising administering to the human or the animal a therapeutically effective amount of a compound having a structure according to Formula I:

wherein B is boron;
R 1a is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
M is a member selected from oxygen, sulfur and NR 2a ;
R 2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

J is a member selected from (CR 3a R 4a ) n1 and CR 5a ;
R 3a , R 4a , and R 5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
n1 is an integer selected from 0 to 2;
W is a member selected from C═O (carbonyl), (CR 6a R 7a ) m1 and CR 8a ;
R 6a , R 7a , and R 8a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;

m1 is an integer selected from 0 and 1;
A is a member selected from CR 9a and N;
D is a member selected from CR 10a and N;
E is a member selected from CR 11a and N;
G is a member selected from CR 12a and N;
R 9a , R 10a , R 11a and R 12a are members independently selected from H, OR*, NR*R**, SR*, —S(O)R*, —S(O) 2 R*, —S(O) 2 NR*R**, —C(O)R*, —C(O)OR*, —C(O)NR*R**, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
wherein each R* and R** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
the combination of nitrogens (A+D+E+G) is an integer selected from 0 to 3;
a member selected from R 3a , R 4a and R 5a and a member selected from R 6a , R 7a and R 8a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring;
R 3a and R 4a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring;
R 6a and R 7a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring;
R 9a and R 10a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring;
R 10a and R 11a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring;
R 11a and R 12a , together with the atoms to which they are attached, are optionally joined to form a 4 to 7 membered ring.

2. The method of claim 1 , further comprising administering said compound as part of a pharmaceutical formulation, said formulation further comprising a pharmaceutically acceptable excipient.

3. The method of claim 1 , wherein said compound has a structure according to:

4. The method of claim 3 , wherein said compound has a structure according to:

wherein
R 4a is a member selected from H, methyl, ethyl and substituted or unsubstituted aryl and substituted or unsubstituted arylalkyl;
R 10a is a member selected from H, halogen, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkoxy, substituted or unsubstituted arylthio and substituted or unsubstituted arylalkylthio; and
R 11a is a member selected from H, OH, methyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkoxy, substituted or unsubstituted arylthio and substituted or unsubstituted arylalkylthio.

5. The method of claim 4 , wherein said compound has a structure according to the following formula:

6. The method of claim 5 , wherein R 10a is a member selected from

wherein
R 15 is a member selected from CN, COOH and

R 16 and R 17 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
p is an integer selected from 1 to 5;
z is an integer selected from 1 to 8; and
X is a member selected from S and 0.

7. The method of claim 3 , wherein said compound has a structure according to:

wherein
R 4a is a member selected from substituted or unsubstituted aryl and substituted or unsubstituted arylalkyl;
R 10a is a member selected from H, halogen, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkoxy, substituted or unsubstituted arylthio and substituted or unsubstituted arylalkylthio.

8. The method of claim 6 , wherein said compound is a member selected from:

9. The method of claim 3 , wherein said compound is

10. The method of claim 3 , wherein said compound is a member selected from:

11. The method of claim 1 , wherein said compound is a member selected from:

12. The method of claim 3 , wherein R 1a is H.

13. The method of claim 3 , wherein R 10a and R 11a are H.

14. The method of claim 3 , wherein one member selected from R 10a and R 11a is H and the other member selected from R 10a and R 11a is a member selected from halogen, methyl, cyano, methoxy, hydroxymethyl and p-cyanophenyloxy.

15. The method of claim 3 , wherein R 10a and R 11a a

Assignees

• Anacor Pharmaceuticals Inc

Inventors

• Baker Stephen J
• Sanders Virginia
• Akama Tsutomu
• Bellinger-Kawahara Carolyn
• Freund Yvonne
• Maples Kirk R
• Plattner Jacob J
• Zhang Yong-Kang
• Zhou Huchen
• Hernandez Vincent S

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · 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

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/12

  Antihypertensives · CPC title