Substituted bicyclic dihydropyrimidinones and their use as inhibitors of neutrophil elastase activity

Patent metadata

Field	Value
Publication number	US-9440930-B2
Application number	US-201514809311-A
Country	US
Kind code	B2
Filing date	Jul 27, 2015
Priority date	Jul 31, 2014
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

Substituted bicyclic dihydropyrimidinones of formula 1

and their use as inhibitors of neutrophil elastase activity. An exemplary compound is

First claim

What we claim:

1. A compound of formula 1

wherein
R 1 is phenyl,
substituted with CN and
substituted with a second substituent R 1.1 ,
R 1.1 is selected from the group consisting of
—SO 2 —CH 3 , —SO—CH 3 , —CH 2 —OH, —SO 2 —CH 2 CH 2 —OH, —SO 2 —CH 2 CH 2 —OCH 3 and —SO 2 —CH 2 CH 2 CH 2 —OH,

R 2 is phenyl substituted with CF 3 ,
R 3 is selected from the group consisting of H, CH 3 , —CO—NH—CH 3 , —CH 2 CH 2 —OH and —CH 2 -oxetane,
or a pharmaceutically acceptable salt thereof,
provided that a compound of formula 1 is not a compound selected from the group consisting of

2. A compound of formula 1 according to claim 1 , wherein
R 1 is phenyl,
substituted with CN and
substituted with a second substituent R 1.1 ,
R 1.1 is selected from the group consisting of
—SO 2 —CH 3 , —SO—CH 3 and —SO 2 —CH 2 CH 2 —OH,

R 2 is phenyl substituted with CF 3 ,
R 3 is selected from the group consisting of
H, CH 3 and —CH 2 CH 2 —OH

or a pharmaceutically acceptable salt thereof.

3. A compound of formula 1 according to claim 1 , wherein
R 1.1 is —SO 2 —CH 3 .

4. A compound of formula 1 according to claim 1 , wherein
R 1.1 is —SO—CH 3 .

5. A compound of formula 1 according to claim 1 , selected from the group consisting of compounds 1.a to 1.d.

6. A compound according to claim 1 , wherein the configuration of formula 1 is formula 1′

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising a compound of according to claim 1 , and a pharmaceutically acceptable carrier.

8. A method of treating COPD which comprises administering to a host suffering from COPD a therapeutically effective amount of a compound according to claim 1 .

Assignees

• Boehringer Ingelheim Int

Inventors

• Oost Thorsten
• Anderskewitz Ralf
• Gnamm Christian
• Morschhaeuser Gerd
• Peters Stefan
• Ries Uwe Joerg

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P37/08

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

• A61P43/00

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