Broad-spectrum carbapenems

Patent metadata

Field	Value
Publication number	US-12084445-B2
Application number	US-201917057594-A
Country	US
Kind code	B2
Filing date	May 29, 2019
Priority date	May 30, 2018
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

The present disclosure provides broad-spectrum carbapenem derivatives and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such derivatives and/or compositions.

First claim

The invention claimed is:

1. A compound of Formula (IVa-1), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

wherein:
Ring A is cyclohexyl;
R 5 is hydrogen;
each R 6 is independently —NR 60 R 61 , —NR 60 (CR 62 R 63 ) w6 NR 60 R 61 , —NR 60 C(═NR 61 )NR 60 R 61 , —C(═NR 60 )NR 60 R 61 , —C(═NR 60 ) R 60 , —N(R 60 )C(═NR 61 ) R 60 , —(CR 62 R 63 ) NR 60 R 61 , —C(═O)NR 60 R 61 —C(═O)(CR 62 R 63 ) v6 NR 60 R 61 , —(CR 62 R 63 )\N(R 60 )C(═NR 61 )NR 60 R 61 , or
each R 60 and R 61 is independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
each R 62 and R 63 is independently selected from the group consisting of hydrogen, halogen, and C 1 -C 6 alkyl;
v6 is 1 or 2:
w6 is 2;
n is 0 or 1;
m is 0 or 1;
p is 1; and
q is 1 or 2.

2. The compound of claim 1 , wherein each R 6 is independently —NR 60 R 61 , —NR 60 (CR 62 R 63 ) w6 NR 60 R 61 , —NR 60 C(═NR 61 )NR 60 R 61 , —C(═NR 60 )NR 60 R 61 , —N(R 60 )C(═NR 61 )R 60 , or —(CR 62 R 63 ) v6 NR 60 R 61 .

3. The compound of claim 2 , wherein each R 6 is independently —NR 60 R 61 or —NR 60 C(═NR 61 )NR 60 R 61 .

4. The compound of claim 1 , wherein q is 1.

5. The compound of claim 1 , wherein n is 0 and m is 0 or 1.

6. The compound of claim 1 , wherein n is 0 and m is 0.

7. The compound of claim 1 , wherein n is 0 and m is 1.

8. The compound of claim 1 , wherein p is 1.

9. A compound of Formula (IIa-1), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

wherein:
Ring A is cyclohexyl;
L is —(CR 8 R 9 ) z —;
each R 8 and R 9 are independently hydrogen or C 1 -C 6 alkyl;
R 5 is hydrogen;
each R 6 is independently —NR 60 R 61 , —NR 60 (CR 62 R 63 ) w6 NR 60 R 61 , —NR 60 C(═NR 61 )NR 60 R 61 , —C(═NR 60 )NR 60 R 61 , —C(═NR 60 ) R 60 , —N(R 60 )C(═NR 61 )R 60 , —(CR 62 R 63 ) v6 NR 60 R 61 , —C(═O)NR 60 R 61 , —C(═O)(CR 62 R 63 ) v6 NR 60 R 61 , —(CR 62 R 63 ) v6 N(R 60 )C(═NR 61 )NR 60 R 61 , or —(CR 62 R 63 ) v6 C(═NR 61 )NR 6 ºR 61 ;
each R 60 and R 61 is independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
each R 62 and R 63 is independently selected from the group consisting of hydrogen, halogen, and C 1 -C 6 alkyl;
v6 is 1 or 2;
w6 is 2;
n is 1;
m is 0 or 1;
p is 1;
q is 1 or 2; and
z is 1 or 2.

10. A compound of Formula (IIIa-1), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

wherein:
Ring A is cyclohexyl;
L is —(CR 8 R 9 ) z —;
each R 8 and R 9 is independently hydrogen or C 1 -C 6 alkyl;
R 5 is hydrogen;
each R 6 is independently —NR 60 R 61 , —NR 60 (CR 62 R 63 )w 6 NR 60 R 61 , —NR 60 C(═NR 61 )NR 60 R 61 , —C(═NR 60 )NR 60 R 61 , —C(═NR 60 ) R 60 , —N(R 60 )C(═NR 61 ) R 60 , —(CR 62 R 63 ) v6 NR 60 R 61 , —C(═O)NR 60 R 61 , —C(═O)(CR 62 R 63 ) v6 NR 60 R 61 , —(CR 62 R 63 ) v6 N(R 60 )C(═NR 61 )NR 60 R 61 , or —(CR 62 R 63 )v6C(═NR 61 )NR 60 R 61 ;
each R 60 and R 61 is independently selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
each R 62 and R 63 is independently selected from the group consisting of hydrogen, halogen, and C 1 -C 6 alkyl;
v6 is 1 or 2:
w6 is 2;
n is 0 or 1;
m is 0 or 1;
p is 1;
q is 1 or 2; and
z is 1 or 2.

11. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof and a pharmaceutically acceptable excipient.

Assignees

• Venatorx Pharmaceuticals Inc

Inventors

• Burns Christopher J
• Chu Guo-Hua
• Hamrick Jodie
• Boyd Steven A
• Condon Stephen M

Classifications

• A61K31/403

  condensed with carbocyclic rings, e.g. carbazole · CPC title

• A61K45/06

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

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07D477/20 Primary

  Sulfur atoms · CPC title