Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A(4) hydrolase

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Leukotriene B-4 (LTB4) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB4 and possibly identify novel treatments, inhibitors of the LTB4 biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.

Detaljer

Författare
  • Thomas A. Kirkland
  • Marc Adler
  • John G. Bauman
  • Ming Chen
  • Jesper Z. Haeggstrom
  • Beverly King
  • Monica J. Kochanny
  • Amy M. Liang
  • Lisa Mendoza
  • Gary B. Phillips
  • Marjolein Thunnissen
  • Lan Trinh
  • Marc Whitlow
  • Bin Ye
  • Hong Ye
  • John Parkinson
  • William J. Guilford
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biologiska vetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)4963-4983
TidskriftBioorganic & Medicinal Chemistry
Volym16
Utgåva nummer9
StatusPublished - 2008
PublikationskategoriForskning
Peer review utfördJa