Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase

Bin Ye; John Bauman; Ming Chen; David Davey; Seock-Kyu Khim; Beverly King; Thomas Kirkland; Monica Kochanny; Amy Liang; Dao Lentz; Karen May; Lisa Mendoza; Gary Phillips; Victor Selchau; Sabine Schlyer; Jih-Lie Tseng; Robert G Wei; Hong Ye; John Parkinson; William J Guilford

doi:10.1016/j.bmcl.2008.06.046

Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3891-4. doi: 10.1016/j.bmcl.2008.06.046. Epub 2008 Jun 18.

Affiliation

¹ Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.

PMID: 18586492
DOI: 10.1016/j.bmcl.2008.06.046

Abstract

The synthesis and biological evaluation of a series of N-alkyl glycine amide analogs as LTA(4)-h inhibitors and the importance of the introduction of a benzoic acid group to the potency and pharmacokinetic parameters of our analogs are described. The lead compound in the series, 4q, has excellent potency and oral bioavailability.

MeSH terms

Administration, Oral
Amides / chemistry*
Amines / chemistry
Anti-Inflammatory Agents / pharmacology
Benzoic Acid / chemistry
Biological Availability
Chemistry, Pharmaceutical
Drug Design
Enzyme Inhibitors / pharmacokinetics*
Epoxide Hydrolases / antagonists & inhibitors*
Ethers
Glycine / chemistry*
Inhibitory Concentration 50
Models, Chemical

Substances

Amides
Amines
Anti-Inflammatory Agents
Enzyme Inhibitors
Ethers
Benzoic Acid
Epoxide Hydrolases
Glycine
leukotriene A4 hydrolase