3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid as a highly potent and selective retinoic acid metabolic blocking agent

Mark J Mulvihill; Julie L C Kan; Andrew Cooke; Shripad Bhagwat; Patricia Beck; Mark Bittner; Cara Cesario; David Keane; Viorica Lazarescu; Anthony Nigro; Christy Nillson; Bijoy Panicker; Vanessa Smith; Mary Srebernak; Feng-Lei Sun; Matthew O'Connor; Suzanne Russo; Gia Fischetti; Michael Vrkljan; Shannon Winski; Arlindo L Castelhano; David Emerson; Neil W Gibson

doi:10.1016/j.bmcl.2006.02.020

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid as a highly potent and selective retinoic acid metabolic blocking agent

Bioorg Med Chem Lett. 2006 May 15;16(10):2729-33. doi: 10.1016/j.bmcl.2006.02.020. Epub 2006 Feb 28.

Affiliation

¹ OSI Pharmaceuticals, Inc., 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. mmulvihill@osip.com

PMID: 16504501
DOI: 10.1016/j.bmcl.2006.02.020

Abstract

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid and analogs were designed and synthesized as highly potent and selective CYP26 inhibitors, serving as retinoic acid metabolic blocking agents (RAMBAs), with demonstrated in vivo efficacy to increase the half-life of exogenous atRA.

MeSH terms

Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology*
Half-Life
Mass Spectrometry
Naphthalenes / pharmacokinetics
Naphthalenes / pharmacology*
Propionates / pharmacokinetics
Propionates / pharmacology*
Retinoic Acid 4-Hydroxylase
Tretinoin / antagonists & inhibitors
Tretinoin / metabolism*

Substances

3-(6-(2-dimethylamino-1-imidazol-1-yl-butyl)naphthalen-2-yloxy)-2,2-dimethyl-propionic acid
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Naphthalenes
Propionates
Tretinoin
Cytochrome P-450 Enzyme System
Retinoic Acid 4-Hydroxylase