Heterocyclic amides useful as protein modulators

Patent metadata

Field	Value
Publication number	US-10189820-B2
Application number	US-201815730664-A
Country	US
Kind code	B2
Filing date	Jan 3, 2018
Priority date	Apr 7, 2016
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

Disclosed are compounds having the formula:

wherein q, r, s, A, B, C, R A1 , R A2 , R B1 , R B2 , R C1 , R C2 , R 3 , R 4 , R 5 , R 6 , R 14 , R 15 , R 16 , and R 17 , are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.

First claim

The invention claimed is:

1. A compound which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide having the structure of

or a tautomer thereof,
or a pharmaceutically acceptable salt thereof,
or a hydrate thereof.

2. The compound according to claim 1 , which is a hydrate of (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide,
or a tautomer thereof,
or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , which is a pharmaceutically acceptable salt of (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol -1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide, or a tautomer thereof.

4. The compound according to claim 1 , which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide, or a tautomer thereof.

5. The compound according to claim 1 , which is represented by (E)-1-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-(3-morpholinopropoxy)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro-1H-benzo[d]imidazole-5-carboxamide having the structure of

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , which is (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide tris hydrochloride, or a tautomer thereof.

7. A pharmaceutical composition comprising a compound of (E)-1-(4-(5-carbamoyl-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-(3-morpholinopropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-(1-ethyl-3-methyl-1H-pyrazole-5-carboxamido)-7-methoxy-1H-benzo[d]imidazole-5-carboxamide having the structure of

or a tautomer thereof,
or a pharmaceutically acceptable salt thereof,
or a hydrate thereof, and
a pharmaceutically acceptable excipient.

8. The pharmaceutical composition according to claim 7 , wherein the compound is represented by
(E)-1-((E)-4-((E)-5-carbamoyl-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-(3-morpholinopropoxy)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-2-((1-ethyl-3-methyl-1H-pyrazole-5-carbonyl)imino)-7-methoxy-2,3-dihydro -1H-benzo[d]imidazole-5-carboxamide having the structure of

or a pharmaceutically acceptable salt thereof.

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Mehlmann John F
• Romano Joseph J

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P31/20

  for DNA viruses · CPC title