Cyclic amides as MetAP-2 inhibitors

Patent metadata

Field	Value
Publication number	US-10093623-B2
Application number	US-201314390926-A
Country	US
Kind code	B2
Filing date	Mar 21, 2013
Priority date	Apr 4, 2012
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

Described are cyclic amide compounds of the formula (I):

in which R 1 , R 3 , R 5 , R 6 , R 7 , R, X and Y have the meanings as described. The compounds are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumors.

First claim

The invention claimed is:

1. A compound selected from the following compounds:

Com-

pound

No.
Name

“A56” 
(S)-3-(1,1-Dioxo-116-thiomorpholine-4-carbonyl)-3-hydroxy-1-

phenylpyrrolidin-2-one,

“A57” 
(S)-3-Hydroxy-3-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-1-

phenylpyrrolidin-2-one,

“A58” 
N-(3-Imidazol-1-ylpropyl)-(S)-3-hydroxy-2-oxo-1-phenyl-

pyrrolidine-3-carboxamide,

“A59” 
N-(2-Dimethylaminoethyl)-(S)-3-hydroxy-2-oxo-1-phenyl-

pyrrolidine-3-carboxamide,

“A60” 
N-[2-(4-Phenoxyphenyl)ethyl]-(S)-3-hydroxy-2-oxo-1-phenyl-

pyrrolidine-3-carboxamide,

“A61” 
N-(2-Dimethylaminoethyl)methyl)-(S)-3-hydroxy-2-oxo-1-

phenylpyrrolidine-3-carboxamide,

“A62” 
N-(2-Morpholin-4-yl-2-oxoethyl)-(S)-3-hydroxy-2-oxo-1-

phenylpyrrolidine-3-carboxamide,

“A63” 
N-[2-(1-Methylpyrrolidin-2-yl)ethyl]-(S)-3-hydroxy-2-oxo-1-

phenylpyrrolidine-3-carboxamide,

“A64” 
N-(3-Dimethylaminopropyl)-(S)-3-hydroxy-2-oxo-1-phenyl-

pyrrolidine-3-carboxamide,

“A68” 
N-(3-Chloro-5-fluorobenzyl)-3-hydroxy-1-(1H-indol-6-yl)-2-

oxopyrrolidine-3-carboxamide,

“A69” 
N-(3-Chloro-5-fluorobenzyl)-1-[3-(3-carbamoylphenyl-

carbamoyl)phenyl]-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A70” 
(S)-3-((E)-But-2-enoyl)-3-hydroxy-1-phenylpyrrolidin-2-one,

“A71” 
N-(3-Chloro-5-fluorobenzyl)-(S)-8-acetyl-4-hydroxy-3-oxo-2-

phenyl-2,8-diazaspiro[4.5]decane-4-carboxamide,

“A72” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-1-[3-(morpholine-4-

carbonyl)phenyl]-2-oxopyrrolidine-3-carboxamide,

“A73” 
N-(3-Chloro-5-fluorobenzyl)-3-hydroxy-1-[3-(methanesulfonyl-

methylamino)phenyl]-2-oxopyrrolidine-3-carboxamide,

“A74” 
N-(3-Chloro-5-fluorobenzyl)-(R)-3-hydroxy-1-[3-(morpholine-4-

carbonyl)phenyl]-2-oxopyrrolidine-3-carboxamide,

“A75” 
N-(3-Chloro-5-fluorobenzyl)-(S)-1-(3-

cyclopropylcarbamoylphenyl)-3-hydroxy-2-oxopyrrolidine-3-

carboxamide,

“A76” 
N-(3-Chloro-5-fluorobenzyl)-1-(3-cyclobutylcarbamoylphenyl)-

3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A77” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-2-oxo-1-[3-

(pyrrolidine-1-carbonyl)phenyl]pyrrolidine-3-carboxamide,

“A78” 
N-(3-Chloro-5-fluorobenzyl)-3-hydroxy-2-oxo-1-(6-

propionylaminopyridin-3-yl)pyrrolidine-3-carboxamide,

“A79” 
N-(3-Chloro-5-fluorobenzyl)-(S)-1-(3-ethanesulfonylamino-

phenyl)-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A80” 
N-(3-Chloro-5-fluorobenzyl)-(S)-1-(3-cyclopropanesulfonyl-

aminophenyl)-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A82” 
N-(3-Chloro-5-fluorobenzyl)-(R)-1-(3-cyclopropylcarbamoyl-

phenyl)-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A83” 
N-(3-Chloro-5-fluorobenzyl)-(R)-3-hydroxy-2-oxo-1-[3-

(pyrrolidine-1-carbonyl)phenyl]pyrrolidine-3-carboxamide,

“A84” 
N-(3-Chloro-5-fluorobenzyl)-(R)-1-(3-ethanesulfonylamino-

phenyl)-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A85” 
N-(3-Chloro-5-fluorobenzyl)-(R)-1-(3-cyclopropanesulfonyl-

aminophenyl)-3-hydroxy-2-oxopyrrolidine-3-carboxamide,

“A87” 
N-(3-Chloro-5-fluorobenzyl)-1-(3-cyano-1H-indol-5-yl)-3-

hydroxy-2-oxopyrrolidine-3-carboxamide,

“A88” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-1-[3-(2-hydroxy-

ethylcarbamoyl)phenyl]-2-oxopyrrolidine-3-carboxamide,

“A89” 
3-(2-Benzylacryloyl)-3-hydroxy-1-phenylpyrrolidin-2-one,

“A90” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-2-oxo-1-phenethyl-

pyrrolidine-3-carboxamide,

“A91” 
N-(3-Chloro-5-fluorobenzyl)-(R)-3-hydroxy-1-[3-(2-hydroxy-

ethylcarbamoyl)phenyl]-2-oxopyrrolidine-3-carboxamide

“A92” 
N-(3-Chloro-5-fluorobenzyl)-(R)-3-hydroxy-2-oxo-1-phenethyl-

pyrrolidine-3-carboxamide,

“A93” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-1-{3-[(2-hydroxy-

ethyl)methylcarbamoyl]phenyl}-2-oxopyrrolidine-3-

carboxamide,

“A94” 
N-(3-Chloro-5-fluorobenzyl)-(S)-3-hydroxy-1-[3-(3-hydroxy-

propy

Assignees

• Merck Patent Gmbh

Inventors

• Heinrich Timo
• Zenke Frank
• Krier Mireille
• Friese-Hamim Manja
• Seenisamy Jeyaprakashnarayanan

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P33/06

  Antimalarials · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title