US 5,672,598 AGranted

Lactam-containing hydroxamic acids

AssigneeThe Procter & Gamble Company

InventorsBiswanath De, Christopher Thomas Wahl, Michael George Natchus, Menyan Cheng

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Abstract

The present invention relates to compounds that exhibit inhibitory activity against matrix metalloproteases ("MMPs"). Because MMPs are known to play a role in tissue degradation, the compounds of the present invention may be useful in preventing or treating diseases associated with excess MMP activity. In particular, the compounds have a structure according to Formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are various substituents as described in the specification; and Q is an alkyl chain, an alkenyl chain, a heteroalkyl chain, or a heteroalkenyl chain, wherein said chain has 2, 3, or 4 chain atoms and is unsubstituted or substituted with one or more alkyl moieties; or a pharmaceutically-acceptable salt, or biohydrolyzable alkoxyamide, acyloxyamide, or imide thereof. Preferred are those compounds where Q is an alkyl chain having 2, 3 or 4 chain atoms. The invention also relates to pharmaceutical compositions comprising these compounds, and methods for preventing or treating diseases associated with unwanted MMP activity using the compounds and compositions.

A compound selected from:

(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propanoic acid amide of 1N-(carbomethoxy-methyl)-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propionic acid amide of 1N-(methyl-carboxamidomethyl)-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propionic acid amide of 1N-(carbo-tert-butoxy-methyl)-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propionic acid amide of 1N-Benzyl-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-N-hydroxycarboxamidopropionic acid amide of 1N-(carbo-benzyloxy-methyl)-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propionic acid amide of 1N-(N-benzylcarboxamidomethyl)-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-N-hydroxycarboxamidopropionic acid amide of 1N-(n-butyl-carboxamidomethyl)-caprolactam-(3S)-amine;
(2R)-N-Hydroxycarboxamidomethyl heptanoic acid amide of N-(carbomethoxymethyl)-caprolactam-(3S )-amine;
(2R)-N-hydroxycarboxamidemethyldecanoic acid amide of 1N-(carbomethoxymethyl)-caprolactam-(3S)-amine;
(2R)-N-Hydroxycarboxamidomethyl decanoic acid amide of N-toluenesulfonyl-caprolactam-(3S)-amine;
(2R)-N-Hydroxycarboxamidomethyl decanoic acid amide of N-(2-methoxy)ethyl!-caprolactam-(3S)-amine;
(2R)-N-Hydroxycarboxamidomethyl decanoic acid amide of 1N-n-butyl-caprolactam-(3S)-amine;
(2R)-Isobutyl-(3S)-N-hydroxycarboxamido!-butanoic acid amide of (1N)-carbomethoxymethyl-caprolactam-(3S)-amine;
(2R)-Isobutyl-(3R)-N-hydroxycarboxamido!-butanoic acid amide of (1N)-carbomethoxymethyl-caprolactam-(3S)-amine;
(2R)-Isobutyl-(3S)-N-hydroxycarboxamido!-hexanoic acid amide of (1N)-carbomethoxymethyl-caprolactam-(3S)-amine;
(2R)-Isobutyl-(3S)-N-hydroxycarboxamido!-6-hydroxyhexanoic acid amide of (1N)-carbomethoxymethyl-caprolactam-(3S )-amine;
(2R)-(1S)-N-hydroxycarboxamido!-ethyldecanoic acid amide of 1N-(carbomethoxy-methyl)-caprolactam-(3S)-amine;
(2R)-(1R)-N-hydroxycarboxamido!-ethyldecanoic acid amide of 1N-(carbomethoxy-methyl)-caprolactam-(3S )-amine;
(2R)-(1S)-N-Hydroxycarboxamido!-ethyldecanoic acid amide of N-(2-methoxy)ethyl!-caprolactam-(3S)-amine;
(2R)-(1R)-N-Hydroxycarboxamido!-ethyldecanoic acid amide of N-(2-methoxy)ethyl!-caprolactam-(3S)-amine;
(2R)-Isobutyl-3-(N-hydroxycarboxamido)-propanoic acid amide of N-(carbomethoxymethyl)-valerolactam-(3S)-amine;
and
(2R)-Isobutyl-3-(N-hydroxylcarboxamido)!-propanoic acid amide of 2-oxo-3-amino-N-(carbomethoxymethyl)-pyridinone.

20 more elements

Abstract

Claims2