Antiviral compounds and methods using same

Patent metadata

Field	Value
Publication number	US-10160756-B2
Application number	US-201515128471-A
Country	US
Kind code	B2
Filing date	Mar 31, 2015
Priority date	Mar 31, 2014
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present invention includes compounds that are useful in preventing or treating viral infections, such as viral infections caused by a filovirus, arenavirus, rhabdovirus, paramyxovirus, and/or retrovirus. The present invention further includes compositions comprising such compounds, and methods of treating a viral infection in a subject using such compounds.

First claim

What is claimed:

1. A compound of formula (II):

wherein:
ring a is fused with ring b to form bicyclic core ab, wherein ring a is selected from the group consisting of benzene and, pyridine
wherein a is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 4 alkyl optionally substituted with one or more fluoro atoms, C 3 -C 6 cycloalkyl optionally substituted with one or more fluoro atoms, nitro, cyano, halogen, hydroxy, C 1 -C 4 alkoxy optionally substituted with one or more fluoro atoms, C 1 -C 4 thioalkoxy optionally substituted with one or more fluoro atoms, —SO 2 (C 1 -C 4 alkyl), —C(═O)OR, —NRR, and —C(═O)NRR;

Q is S, S(═O), S(═O) 2 , O or NR;
each occurrence of R is independently H or C 1 -C 4 alkyl;
R 1 is selected from the group consisting of H, C 1 -C 4 alkyl optionally substituted with one or more fluoro atoms, C 3 -C 6 cycloalkyl optionally substituted with one or more fluoro atoms, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyl, substituted heteroalkyl, —C(═O)OR, and —C(═O)NRR;
R 2 is selected from the group consisting of —C(═O)N(R)C(═O)NR 3 R 4 and —C(═O)N(R)C(═O)OR 3 ;
R 3 is selected from the group consisting of H, C 1 -C 4 alkyl optionally substituted with one or more fluoro atoms, C 3 -C 6 cycloalkyl optionally substituted with one or more fluoro atoms, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyl, substituted heteroalkyl, —C(═O)OR and —C(═O)NRR;
R 4 is H or C 1 -C 4 alkyl, or R 3 and R 4 are taken together with the N atom to which both groups are bound to form a four- to seven-membered optionally substituted heterocyclic or heteroaromatic ring;
R 5 is selected from the group consisting of H and C 1 -C 4 alkyl optionally substituted with at least one substituent selected from the group consisting of halo, hydroxy, C 1 -C 4 alkoxy, C 1 -C 4 thioalkoxy, —SO 2 (C 1 -C 4 alkyl), —C(═O)OR, —NRR and —C(═O)NRR;
wherein the compound is not selected from the group consisting of 2-((3-methylquinoxalin-2-yl)thio)-N-((2,2,2-trifluoroethyl)carbamoyl) acetamide (3); 2-((3-methylquinoxalin-2-yl)thio)-N-(phenylcarbamoyl)acetamide (5); 2-((3-methylquinoxalin-2-yl)thio)-N-((thiophen-2-ylmethyl)carbamoyl)acetamide (3i); N-[(cyclopentylamino)carbonyl]-2-[(3-methyl-2-quinoxalinyl)thio]-acetamide; N-[(ethylamino)carbonyl]-2-[(3-methyl-2-quinoxalinyl)thio]-propanamide; N-[(methylamino)carbonyl]-2-[(3-methyl-2-quinoxalinyl) thio]-propanamide; N-[aminocarbonyl]-2-[(3-methyl-2-quinoxalinyl)thio]-3-methyl-butanamide; N-[(methylamino)carbonyl]-2-(2-quinoxalinylthio)-propanamide; N-[(ethylamino)carbonyl]-2-(2-quinoxalinylthio)-propanamide; N-[[(1-methylethyl)amino]carbonyl]-2-(2-quinoxalinylthio)-propanamide; N-[[(phenylmethyl)amino]carbonyl]-2-(2-quinoxalinyloxy)-acetamide; N-[[(1-methylethyl)amino]carbonyl]-2-(2-quinoxalinyloxy)-acetamide; and ethyl (2-((3-methylquinoxalin-2-yl)thio)acetyl)carbamate (3y).

2. The compound of claim 1 , which is at least one selected from the group consisting of:
N-(ethylcarbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3f)

N-(cyclopropylcarbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3g)

N-(benzylcarbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3o)

2-((3-methylquinoxalin-2-yl)thio)-N-(pyridin-2-ylcarbamoyl)acetamide (3p)

2-((3-methylquinoxalin-2-yl)thio)-N-(pyridin-3-ylcarbamoyl)acetamide (3q)

N-((1H-pyrazol-3-yl)carbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3r)

N-(3,5-dimethyl-1H-pyrazol-4-yl)carbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3s)

2-((3-methylquinoxalin-2-yl)thio)-N-((1,3,5-trimethyl-1H-pyrazol-4-yl)carbamoyl)acetamide (3t)

N-((2-fluorophenyl)carbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3u)

N-((3-fluorophenyl)carbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3v)

N-((4-fluorophenyl)carbamoyl)-2-((3-methylquinoxalin-2-yl)thio)acetamide (3w)

1-[2-(3-methyl-quinoxalin-2-yloxy)-acetyl]-3-phenyl-urea (3x)

1-Methyl-3-[2-(3-methyl-quinoxalin-2-ylsulfanyl)-acetyl]-1-phenyl-urea (3aa)

1-[2-(3-Benzyl-quinoxalin-2-ylsulfanyl)-acetyl]-3-(3,5-dimethyl-1H-pyrazol-4-yl)-urea (3ab)

2-((3-benzylquinoxalin-2-yl)thio)-N41,3,5-trimethyl-1H-pyrazol-4-yl)carbamoyl)acetamide (3ac)

and,
2-((3-benzylquinoxalin-2-yl)thio)-N-((4-fluorophenyl)carbamoyl)acetamide (3ad)

3. A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier and
a compound of formula (II):

wherein
ring a is fused with ring b to form bicyclic core ab, wherein ring a is selected from the group consisting of benzene and pyridine,
wherein a is optionally substituted with one or more substituents independently selected from the group consisting of C 1 -C 4 alkyl optionally substituted with one or more fluoro atoms, C 3 -C 6 cycloalkyl optionally substituted with one or more fluoro atoms, nitro, cyano, halogen, hydroxy, C 1 -C 4 alkoxy optionally substituted with one or more fluoro atoms, C 1 -C 4 thioalkoxy optionally substituted with one or more fluoro atoms, —SO 2 (C 1 -C 4 alkyl), —C(═O)OR, —NRR, and —C(═O)NRR;

Q is S, S(═O), S(═ 0 ) 2 , O or NR;
each occurrence of R is independently H or C 1 -C 4 alkyl;
R 1 is selected from the group consisting of H, C 1 -C 4 alkyl optionally substituted with one or more fluoro atoms, C 3 -C 6 cycloalkyl optionally substituted with one or more fluoro atoms, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroalkyl, substituted heteroalkyl, —C(═O)OR, and —C(═O)NRR;
R 2 is selected from the group consisting of —C(═O)N(R)C(═O)NR 3 R 4 and —C(═O)N(R)C(═O)OR 3 ;
R 3 is sele

Assignees

• Univ Pennsylvania

Inventors

• Harty Ronald N
• Freedman Bruce D
• Wrobel Jay E
• Reitz Allen B
• Loughran H Marie

Classifications

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• A61K31/428

  condensed with carbocyclic rings · CPC title

• A61K45/06

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

• A61P31/14

  for RNA viruses · CPC title