title: Effect of substitution on novel tricyclic HIV-1 integrase inhibitors.
abstract: A series of novel tricyclic inhibitors of HIV-1 integrase enzyme was prepared. The effect of substitution at C-6 of the 9-hydroxy-6,7-dihydropyrrolo[3,4-g]quinolin-8-one compounds was studied in vitro. Inhibitors with small side chains at C-6 were generally well tolerated by the enzyme, and the physicochemical properties of the inhibitors were improved by substitution of a small alkyl group at this position. A second series of analogs bearing a sulfamate at the C-5 position with various C-6 substituents were prepared to explore the interplay between the two groups. The SAR of the two classes are not parallel; modification at C-5 impacts the effect of substitutions at C-6.
authors.affiliation: Department of Medicinal Chemistry, Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA. mfardis@gilead.com
authors.forename: Maria
authors.initials: M
authors.lastname: Fardis
authors.forename: Haolun
authors.initials: H
authors.lastname: Jin
authors.forename: Salman
authors.initials: S
authors.lastname: Jabri
authors.forename: Ruby Z
authors.initials: RZ
authors.lastname: Cai
authors.forename: Michael
authors.initials: M
authors.lastname: Mish
authors.forename: Manuel
authors.initials: M
authors.lastname: Tsiang
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase