IP Library Granted Patent US 11,084,796
Granted Patent B2
US 11,084,796 · App. 16/099,957 · Granted Aug 10, 2021

Heterocyclic derivatives for the treatment of RSV

Inventors: Richard K. Plemper (Decatur, GA); Eddy Lee (Alpharetta, GA); John Vernachio (Alpharetta, GA); Elyse Bourque (L'etang-du Nord, CA)
Assignee: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.
C07D279/16A61K31/542A61K31/5415A61P31/14C07D417/06C07D417/12C12N2760/18511
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Quick Facts
Patent No.
US 11,084,796
App. No.
16/099,957
Granted
Aug 10, 2021
Kind
B2
Abstract

Disclosed herein are compounds and compositions for treating or inhibiting RSV and related members of the pneumovirus and paramyxovirus families such as human metapneumovirus, mumps virus, human parainfluenzaviruses, and Nipah and hendra virus, and methods of treatment or prevention thereof.

Claims (30)

1. A compound of Formula 1b-1:

or a pharmaceutically acceptable salt, diastereomer, or enantiomer thereof, wherein

z is 0;

y is 1;

R 1 and R 2 are independently selected from the group consisting of R a , OR a ′, N(R a ) 2 , SR a , C(═O)R a , C(═O)OR a ′, C(═O)N(R a ) 2 , and C(═O)SR a ;

wherein two or more R 1 , R 2 , or R a groups may independently form a ring;

wherein R a is selected from the group consisting of hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, C 3-12 heteroaryl, C 1-8 alkyl-C 3-8 cycloalkyl, C 1-8 alkyl-C 2-8 heterocyclyl, C 1-8 alkyl-C 6-12 aryl, and C 1-8 alkyl-C 3-12 heteroaryl;

wherein a is 1, 2, 3 or 4; and R 8 is selected from the group consisting of —OR a ′, —N(R a ) 2 , —SR a , —SO 2 R a , —SO 2 N(R a ) 2 ; —C(O)R a , OC(O)R a , —COOR a , —C(O)N(R a ) 2 , —OC(O)N(R a ) 2 , —N(R a )C(O), —N(R a )C(O)N(R a ) 2 , —F, —Cl, —Br, —I, —CN, and —NO 2 ; and

wherein R 1 is not NH—CH2-CH2-phenyl.

2. The compound according to claim 1 wherein the compound is selected from the group consisting of:

3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, vehicle, or excipient.

4. The pharmaceutical composition according to claim 3 wherein the compound is selected from the group consisting of:

5. The pharmaceutical composition according to claim 4 wherein the compound is selected from the group consisting of:

6. The compound according to claim 1 , wherein R 1 is selected from the group consisting of:

b is 0, 1, 2, 3, or 4,

R 9 is selected from the group consisting of —R a , —OR a ′, —N(R a ) 2 , —SR a , —SO 2 R a , —SO 2 N(R a ) 2 ; —C(O)R a , OC(O)R a , —COOR a , —C(O)N(R a ) 2 , —OC(O)N(R a ) 2 , —N(R a )C(O), —N(R a )C(O)N(R a ) 2 , —F, —Cl, —Br, —I, —CN, and —NO 2 , wherein any two or more R 9 groups may together form a ring;

wherein R 10 is selected from the group consisting of R a , C(O)R a , SO 2 R a , COOR a , and C(O)N(R a ) 2 , and wherein R 10 may form a ring with any R 1 , R 2 , R 8 , or R a groups.

7. A method of inhibiting RSV comprising administering to a patient in need thereof an effective amount of the compound of claim 1 .

8. The method according to claim 7 , wherein R 1 is selected from the group consisting of:

b is 0, 1, 2, 3, or 4,

R 9 is selected from the group consisting of —R a , —OR a ′, —N(R a ) 2 , —SR a , —SO 2 R a , —SO 2 N(R a ) 2 ; —C(O)R a , OC(O)R a , —COOR a , —C(O)N(R a ) 2 , —OC(O)N(R a ) 2 , —N(R a )C(O), —N(R a )C(O)N(R a ) 2 , —F, —Cl, —Br, —I, —CN, and —NO 2 , wherein any two or more R 9 groups may together form a ring;

wherein R 10 is selected from the group consisting of R a , C(O)R a , SO 2 R a , COOR a , and C(O)N(R a ) 2 , and wherein R 10 may form a ring with any R 1 , R 2 , R 8 , or R a groups.

9. The method according to claim 7 , wherein R 1 is a group of the formula:

10. The method according to claim 7 , wherein R 2 is C(═O)NHR a1 , wherein said R a1 is selected from the group consisting of C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 3-12 heteroaryl.

11. The method according to claim 7 , wherein R 2 is C(═O)NH—C 3-8 cycloalkyl.

12. The method according to claim 7 , wherein R 2 is C(═O)NHcyclohexyl.

13. The method according to claim 7 wherein the compound is selected from the group consisting of:

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

15. The method of treating an RSV infection according to claim 14 wherein the compound is administered via a route of administration selected from the group consisting of buccal, oral, intravenous, inhalation, intradermal, intramuscular, topical, subcutaneous, rectal, vaginal, parenteral, pulmonary, intranasal, and ophthalmic.

16. The method of treating an RSV infection according to claim 14 wherein the compound is selected from the group consisting of:

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2021
From: LEE, EDDY; VERNACHIO, JOHN; BOURQUE, ELYSE
To: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.
Reel/Frame 056416/0629 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2021
From: PLEMPER, RICHARD K.
To: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.
Reel/Frame 056416/0771 →
CONFIRMATORY LICENSE Recorded Apr 23, 2019
From: GEORGIA STATE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 048973/0720 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 5, 2019
From: VAXART, INC.
To: GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.
Reel/Frame 048499/0399 →
Continuity (2)
Provisional Application 62333996 · May 10, 2016
Related Publication 20190135770A1 · May 9, 2019