Preparation of (R,R)-fenoterol and (R,R)- or (R,S)-fenoterol analogues and their use in treating congestive heart failure

Patent metadata

Field	Value
Publication number	US-9908841-B2
Application number	US-201615347354-A
Country	US
Kind code	B2
Filing date	Nov 9, 2016
Priority date	Aug 10, 2006
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

This disclosure concerns the discovery of (R,R)- and (R,S)-fenoterol analogs which are highly effective at binding β2-adrenergic receptors. Exemplary chemical structures for these analogs are provided. Also provided are pharmaceutical compositions including the disclosed (R,R)-fenoterol and fenoterol analogs, and methods of using such compounds and compositions for the treatment of cardiac disorders such as congestive heart failure and pulmonary disorders such as asthma or chronic obstructive pulmonary disease.

First claim

We claim:

1. A compound having the formula:

wherein R 1 -R 3 independently are hydrogen, acyl, alkoxy carbonyl or a combination thereof;
R 4 is hydrogen or lower alkyl; and
R 5 is

and wherein the compound is optically active.

2. The compound of claim 1 , wherein R 5 is

3. The compound of claim 2 , wherein R 4 is lower alkyl.

4. The compound of claim 3 , wherein the compound is a (R,R)- or (R,S)-compound.

5. The compound of claim 4 , wherein R 5 is

6. The compound of claim 5 , wherein R 4 is methyl, ethyl, n-propyl, or isopropyl.

7. The compound of claim 5 , wherein R 4 is methyl or ethyl.

8. The compound of claim 5 , wherein R 1 -R 3 are hydrogen.

9. The compound of claim 8 , wherein R 4 is methyl or ethyl.

10. The compound of claim 1 , wherein the compound is

11. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11 , wherein R 5 is

13. The pharmaceutical composition of claim 12 , wherein R 4 is lower alkyl.

14. The pharmaceutical composition of claim 13 , wherein the compound is a (R,R)- or (R,S)-compound.

15. The pharmaceutical composition of claim 14 , wherein R 5 is

16. The pharmaceutical composition of claim 15 , wherein R 4 is methyl, ethyl, n-propyl, or isopropyl.

17. The pharmaceutical composition of claim 15 , wherein R 4 is methyl or ethyl.

18. The pharmaceutical composition of claim 15 , wherein R 1 -R 3 are hydrogen.

19. The pharmaceutical composition of claim 18 , wherein R 4 is methyl or ethyl.

20. The pharmaceutical composition of claim 11 , wherein the compound is

Assignees

• Us Health

Inventors

• Wainer Irving William
• Zhu Weizhong
• Chakir Khalid
• Xiao Rui Ping
• Abernethy Darrell R
• Beigi Abhari Farideh M

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · 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

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title