title: Tricyclic HIV integrase inhibitors: VI. SAR studies of 'benzyl flipped' C3-substituted pyrroloquinolines.
abstract: A series of C3 halobenzyl-substituted tricyclic HIV integrase inhibitors was prepared. Improvement in cell-based inhibitor potency was observed in comparison to previously disclosed tricyclic pyrroloquinolines carrying the 'halobenzyl tail' at the lactam nitrogen. Animal PK for several of the C3-substituted inhibitors was examined, with a dihaloaryl analog achieving good balance in protein-shifted EC(50) and t(1/2) in animal PK studies.
authors.affiliation: Gilead Sciences, Medicinal Chemistry, Inc. 333 Lakeside Drive, Foster City, CA 94404, USA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Metobo
authors.forename: Michael
authors.initials: M
authors.lastname: Mish
authors.forename: Haolun
authors.initials: H
authors.lastname: Jin
authors.forename: Salman
authors.initials: S
authors.lastname: Jabri
authors.forename: Rachael
authors.initials: R
authors.lastname: Lansdown
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Chen
authors.forename: Manuel
authors.initials: M
authors.lastname: Tsiang
authors.forename: Matthew
authors.initials: M
authors.lastname: Wright
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D011758:Pyrroles; D011804:Quinolines; C410406:pyrroloquinoline