title: Evaluation of secondary amide replacements in a series of CCR5 antagonists as a means to increase intrinsic membrane permeability. Part 1: Optimization of gem-disubstituted azacycles.
abstract: Replacement of a secondary amide with an N-acyl or N-sulfonyl gem-disubstituted azacyle in a series of CCR5 antagonists led to the identification of compounds with excellent in vitro HIV antiviral activity and increased intrinsic membrane permeability.
authors.affiliation: Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. remy.lemoine@roche.com
authors.forename: Rémy C
authors.initials: RC
authors.lastname: Lemoine
authors.forename: Ann C
authors.initials: AC
authors.lastname: Petersen
authors.forename: Lina
authors.initials: L
authors.lastname: Setti
authors.forename: Jutta
authors.initials: J
authors.lastname: Wanner
authors.forename: Andreas
authors.initials: A
authors.lastname: Jekle
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: André
authors.initials: A
authors.lastname: deRosier
authors.forename: Changhua
authors.initials: C
authors.lastname: Ji
authors.forename: Pamela
authors.initials: P
authors.lastname: Berry
authors.forename: David
authors.initials: D
authors.lastname: Rotstein
mesh_terms: D000577:Amides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D001372:Aza Compounds; D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5