Discovery of novel and potent leukotriene B4 receptor antagonists. Part 1

…, N Fotouhi, J Tilley, N Cohen, S Choudhry…

Index: Goodnow, Robert A.; Hicks, Alexandra; Sidduri, Achyutharao; Kowalczyk, Agnieszka; Dominique, Romyr; Qiao, Qi; Lou, Jian Ping; Gillespie, Paul; Fotouhi, Nader; Tilley, Jefferson; Cohen, Noal; Choudhry, Satish; Cavallo, Gary; Tannu, Shahid A.; Ventre, Jessica D.; Lavelle, Danielle; Tare, Nadine S.; Oh, Hyesun; Lamb, Martin; Kurylko, Grazyna; Hamid, Rachid; Wright, Matthew B.; Pamidimukkala, Anjula; Egan, Thomas; Gubler, Ueli; Hoffman, Ann F.; Wei, Xin; Li, Ying L.; O'Neil, John; Marcano, Ruben; Pozzani, Karen; Molinaro, Tina; Santiago, Jennifer; Singer, Laura; Hargaden, Maureen; Moore, David; Catala, A. Robert; Chao, Lisa C. F.; Hermann, Gesine; Venkat, Radhika; Mancebo, Helena; Renzetti, Louis M. Journal of Medicinal Chemistry, 2010 , vol. 53, # 9 p. 3502 - 3516

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Citation Number: 7

Abstract

The inhibition of LTB4 binding to and activation of G-protein-coupled receptors BLT1 and BLT2 is the premise of a treatment for several inflammatory diseases. In a lead optimization effort starting with the leukotriene B4 (LTB4) receptor antagonist (2), members of a series of 3, 5-diarylphenyl ethers were found to be highly potent inhibitors of LTB4 binding to BLT1 and BLT2 receptors, with varying levels of selectivity depending on the substitution. In ...