title: II. Discovery of a novel series of CXCR3 antagonists with a beta amino acid core.
abstract: A new series of beta amino acids, which act as CXCR3 antagonists, has been identified. The formerly optimized N,N-disubstituted benzylamine derivatives with carboxylic acid function on the N-atom was used as starting point and compounds with carboxyl function not attached to the N-atom were investigated. Affinity, metabolic stability in human and mouse liver microsomes and Caco-2 permeability were optimized. Compounds with double-digit nanomolar CXCR3 affinity, favourable microsomal stability and Caco-2 permeability have been identified.
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary. Electronic address: batai@richter.hu.
authors: Imre
authors: I
authors: Bata
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: Zsuzsanna
authors: Z
authors: Tömösközi
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: Péter
authors: P
authors: Buzder-Lantos
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: Attila
authors: A
authors: Vasas
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: Gábor
authors: G
authors: Szeleczky
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: László
authors: L
authors: Balázs
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary.
authors: Veronika
authors: V
authors: Barta-Bodor
authors: Sanofi Co. Ltd, H-1045 Budapest, Tó u. 1-5, Hungary. Electronic address: ferenczy.gyorgy@med.semmelweis-univ.hu.
authors: György G
authors: GG
authors: Ferenczy
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D018938:Caco-2 Cells; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001596:Benzylamines; C515187:CXCR3 protein, human; D054367:Receptors, CXCR3
keywords: CXCR3 antagonist; Caco-2 permeability; Chemokine receptor; Inflammatory disease; Microsomal stability