Heterocyclic compounds as anti-viral agents

Patent metadata

Field	Value
Publication number	US-11420976-B2
Application number	US-202117155159-A
Country	US
Kind code	B2
Filing date	Jan 22, 2021
Priority date	Jan 24, 2020
Publication date	Aug 23, 2022
Grant date	Aug 23, 2022

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:which inhibit Respiratory Syncytial Virus (RSV) or HMPV. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV or HMPV infection. The invention also relates to methods of treating an RSV or HMPV 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 (I):

or a pharmaceutically acceptable salt thereof, wherein:
A is an optionally substituted aryl or optionally substituted heteroaryl;
B is O or S;
R 1 and R 2 are each independently hydrogen or an optionally substituted C 1 -C 4 alkyl;
alternatively, R 1 and R 2 are taken together with carbon atom to which they attached to form an optionally substituted 3-6-membered cyclic ring;
R 3 is selected from the group consisting of hydrogen, hydroxy, and optionally substituted C 1 -C 6 alkoxy;
R 4 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 1 -C 6 alkynyl, optionally substituted C 3 -C 6 cycloalkyl, and optionally substituted 3-6 membered heterocyclic;
Z is selected from the group consisting of hydrogen, halogen, cyano, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, and optionally substituted C 1 -C 6 alkoxy;
E is an optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclic;
G is NR 5 R 6 ;
R 5 and R 6 are each independently selected from:
1) hydrogen,
2) optionally substituted C 1 -C 6 alkyl,
3) optionally substituted C 3 -C 6 cycloalkyl,
4) optionally substituted 3-6 membered heterocyclic,
5) optionally substituted aryl,
6) optionally substituted heteroaryl,
7) —C(═O)R 7 ,
8) —C(═O)OR 7 ,
9) —C(═O)NHR 7 ,
10) —C(═NH)R 7 ,
11) —C(═NH)NHR 7 ,
12) —C(═NH)NHCN,
13) —C(═NH)NHC(═O)R 7 ,
14) —SO 2 R 7 , and
15) —SO 2 NHR 7 ,
alternatively, R 5 and R 6 are taken together with the nitrogen they are attached to form an optionally substituted 3-8-membered heterocyclic ring;
wherein, R 7 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted 3-6 membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; and

n is 1, 2 or 3.

2. The compound of claim 1 , wherein E is selected from the groups set forth below,

3. The compound of claim 1 , wherein G is selected from the groups below:

4. The compound of claim 1 , represented by Formula (IIIa) or a pharmaceutically acceptable salt thereof:

wherein A, G, n, E, R 3 , and R 4 are as defined in claim 1 .

5. The compound of claim 1 , represented by one of Formulas (Va′) to (Vd′), or a pharmaceutically acceptable salt thereof:

wherein A, R 4 , E and G are as defined in claim 1 .

6. The compound of claim 1 , represented by one of Formulas (VIIa) and (VIIb), or a pharmaceutically acceptable salt thereof:

wherein each R 11 is independently optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; m is 0, 1, 2, 3, 4 or 5; R 8 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted 3-6 membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; and A, G, R 3 , R 4 , and R 7 are as defined in claim 1 .

7. The compound of claim 1 , represented by one of Formulas (VIIIa) to (VIIIf), or a pharmaceutically acceptable salt thereof:

wherein each R 11 is independently optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; R 8 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted 3-6 membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; each p is independently 0, 1, 2 or 3; each p′ is 0, 1 or 2; each m′ is independently 1, 2 or 3; and G, R 3 , R 4 , and R 7 are as defined in claim 1 .

8. The compound of claim 1 , represented by one of Formulas (Xa), (Xb), (Xc-1), (Xd)˜(Xh), (Xi-1), (Xj), (Xk-1), and (Xm-1), or a pharmaceutically acceptable salt thereof:

wherein each R 11 is independently optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; R 8 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted 3-6 membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; each R 12 is independently hydrogen, optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; each R 13 is hydrogen, halo, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 3 -C 6 cycloalkyl, or optionally substituted 3-6-membered heterocyclic; each p is independently 0, 1, 2 or 3; each m′ is independently 1, 2 or 3; and G, R 3 , R 4 , and R 7 are as defined in claim 1 .

9. The compound of claim 1 , represented by one of Formulas (XIVa) to (XIVb), or a pharmaceutically acceptable salt thereof:

wherein each R 11 is independently optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; each R 12 is independently hydrogen, optionally substituted —C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxyl, optionally substituted —C 3 -C 6 cycloalkyl, halo, —CN, or —NR 7 R 8 ; each R 13 is hydrogen, halo, optionally substituted —C 1 -C 6 alkyl, optionally substituted —C 3 -C 6 cycloalkyl, or optionally substituted 3-6-membered heterocyclic; R 8 is selected from the group consisting of hydrogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted 3-6 membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl; R 7 , G and R 4 are as defined in claim 1 .

10. The compound of claim 1 , selected from the compounds set forth below, or a pharmaceutically acceptable salt thereof:

Compound
Structure

 1

Assignees

• Enanta Pharm Inc

Inventors

• He Yong
• Xing Xuechao
• Wang Guoqiang
• Shen Ruichao
• Granger Brett
• Long Jiang
• Or Yat Sun

Classifications

• C07D491/048 Primary

  the oxygen-containing ring being five-membered · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title