Tricyclic HIV integrase inhibitors: VI. SAR studies of 'benzyl flipped' C3-substituted pyrroloquinolines.
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.
Metobo
Sammy
S
Gilead Sciences, Medicinal Chemistry, Inc. 333 Lakeside Drive, Foster City, CA 94404, USA.
Mish
Michael
M
Jin
Haolun
H
Jabri
Salman
S
Lansdown
Rachael
R
Chen
Xiaowu
X
Tsiang
Manuel
M
Wright
Matthew
M
Kim
Choung U
CU
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
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D011758:Pyrroles; D011804:Quinolines; C410406:pyrroloquinoline