Benzodiazepine derivatives as RSV inhibitors

Patent metadata

Field	Value
Publication number	US-10865215-B2
Application number	US-202016739312-A
Country	US
Kind code	B2
Filing date	Jan 10, 2020
Priority date	Jul 22, 2015
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:

which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

First claim

What is claimed:

1. A compound represented by Formula (Ib):

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or methyl;
R 2 and R 5 are each independently hydrogen or methyl;
A is selected from the groups below:

R 3 is phenyl optionally substituted with one to three substituents selected from the group consisting of hydrogen, halo, —CF 3 , —OCF 3 , —CH 3 , —SO 2 Me, and cyano;
R 4 is selected from aryl and heteroaryl; wherein R 4 is optionally substituted with 1 to 3 substituents independently selected from halo, —CH 3 , —CF 3 , —OCF 3 , —CN, —NH 2 , —OH, —CH 2 N(CH 3 ) 2 , —C(O)CH 3 , —NH—(C 1 -C 6 )alkyl, —NH—(C 1 -C 6 )alkyl-(C 1 -C 6 )alkoxy, —SO 2 —(C 1 -C 6 )alkyl, —SO 2 —NH—(C 1 -C 6 )alkyl, —NH—SO 2 —(C 1 -C 6 )alkyl, 3- to 12-membered heterocyclyl, aryl, heteroaryl, C 1 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkenyl, C 1 -C 8 -alkoxy, CH 3 OCH 2 —, CH 3 OCH 2 CH 2 O—,

each R 6 is independently selected from halogen, methyl, CF 3 and cyano;
and n is 0 to 2.

2. The compound of claim 1 , wherein R 4 is selected from the following by removal of one hydrogen atom:

wherein each of the above shown is optionally substituted.

3. The compound of claim 1 , wherein R 4 is optionally substituted by one, two or three substituents independently selected from the group consisting of: halo, —CH 3 , —CF 3 , —OCF 3 , —CN, —NH 2 , —OH, —CH 2 N(CH 3 ) 2 , —C(O)CH 3 , optionally substituted —NH—(C 1 -C 6 )alkyl, optionally substituted —NH—(C 1 -C 6 )alkyl-(C 1 -C 6 )alkoxy, optionally substituted —SO 2 —(C 1 -C 6 )alkyl, optionally substituted —SO 2 —NH—(C 1 -C 6 )alkyl, optionally substituted —NH—SO 2 —(C 1 -C 6 )alkyl, optionally substituted 3- to 12-membered heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —C 1 -C 8 -alkyl, optionally substituted —C 1 -C 8 -alkenyl, optionally substituted —C 3 -C 8 -cycloalkyl, optionally substituted —C 3 -C 8 -cycloalkenyl, and optionally substituted —C 1 -C 8 -alkoxy.

4. The compound of claim 1 , wherein R 4 is optionally substituted by one, two or three of the following substituents:
CH 3 , CN, fluoro, chloro, CH 3 O—, CH 3 C(O)—, CH 3 OCH 2 —, CH 3 OCH 2 CH 2 O—, —CF 3 , CF 3 O—,

5. The compound of claim 1 , represented by Formula (IVb-1), (IVb-2), (IVb-3), or (IVb-4), or a pharmaceutically acceptable salt thereof,

wherein R 1 , R 2 , and R 5 are hydrogen, R 3 is phenyl, R 6 is fluorine or chlorine, and n is 0 or 1.

6. A pharmaceutical composition, comprising the compound according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

7. A method of treating an RSV infection in an subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound claim 1 .

8. The compound of claim 1 , wherein A is

9. The compound of claim 1 , wherein n is 0.

10. The compound of claim 1 , wherein R 1 , R 2 and R 5 are hydrogen.

11. The compound of claim 1 , wherein R 3 is unsubstituted phenyl.

12. The compound of claim 1 , wherein R 4 is selected from the groups below

each of which is optionally substituted.

13. The compound of claim 5 , wherein R 4 is selected from the groups below

Assignees

• Enanta Pharm Inc

Inventors

• Shook Brian C
• Kim In Jong
• Blaisdell Thomas P
• Yu Jianming
• Panarese Joseph
• Or Yat Sun

Classifications

• C07D513/04 Primary

  Ortho-condensed systems · CPC title

• C07D498/08

  Bridged systems · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title