Heterocyclic compounds and uses thereof as D-alanyl-D-alanine ligase inhibitors

US7345048B2 · kind B2 · utility

Assignee

• Pliva D.D. · HR

Inventors

• Paul Ala · Newark, US
• Janid Ali · Waltham, US
• Jacob Clement · Vancouver, CA
• Patrick R. Connelly · Harvard, US
• Carlos Faerman · Ithaca, US
• Christopher Faraday · San Francisco, US
• John Gazzaniga · Worcester, US
• Andrew Magee · Maynard, US
• Salvatore Marchese · Malden, US
• Scott Moe · Salt Lake City, US
• Manuel A. Navia · Lexington, US
• Emanuele Perola · Cambridge, US
• Paul Will · Stoneham, US

Key dates

• Filing date: Jun 28, 2002
• Grant date: Mar 18, 2008
• Expiry date: Jun 28, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The invention relates to D-Ala-D-Ala ligase inhibitors having the formula:wherein R1 is NH2; R2 is NH2; R3 is selected from hydrogen, alkyl, amino, hydroxy, alkoxy, and alkylamino; and R4 and R4′ are each independently hydrogen or a substituted or unsubstituted, linear, branched, or cyclic, alkyl, alkenyl, alkynyl, aryl, acyl, aralkyl, or alkaryl group wherein one or more carbon or hydrogen atoms may be substituted by a substituent selected from amino, alkylamino, hydroxyl, alkoxyl, thio, halogen, nitro, and carbonyl; wherein NR4R4′ incorporates a substituted or unsubstituted naphthyl group, wherein the substituents are selected from alkoxy, halogen, alkyl, and alkylene, and wherein said naphthyl group in NR4R4′ is bonded to N through a substituted or unsubstituted alkylene moiety. These compounds have antibacterial properties based on their ability to bind and inhibit D-Ala-D-Ala ligase, a critical pathway enzyme in bacterial cell-wall synthesis, and are suitable for various antibacterial uses.