title: Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action.
abstract: A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.
authors.affiliation: Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
authors.forename: M
authors.initials: M
authors.lastname: Evers
authors.forename: C
authors.initials: C
authors.lastname: Poujade
authors.forename: F
authors.initials: F
authors.lastname: Soler
authors.forename: Y
authors.initials: Y
authors.lastname: Ribeill
authors.forename: C
authors.initials: C
authors.lastname: James
authors.forename: Y
authors.initials: Y
authors.lastname: Lelièvre
authors.forename: J C
authors.initials: JC
authors.lastname: Gueguen
authors.forename: D
authors.initials: D
authors.lastname: Reisdorf
authors.forename: I
authors.initials: I
authors.lastname: Morize
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: Y
authors.initials: Y
authors.lastname: Hénin
authors.forename: A
authors.initials: A
authors.lastname: Bousseau
authors.forename: J F
authors.initials: JF
authors.lastname: Mayaux
authors.forename: J B
authors.initials: JB
authors.lastname: Le Pecq
authors.forename: N
authors.initials: N
authors.lastname: Dereu
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C098648:N-(3,30-dihydroxylup-20(29)-en-28-oyl)-11-aminoundecanoic acid; C098647:N-(3-hydroxy-30-((2'-hydroxyethyl)thio)lup-20(29)-en-28-oyl)-11-aminoundecanoic acid; D053978:Pentacyclic Triterpenes; D018894:Reverse Transcriptase Inhibitors; D014315:Triterpenes; C098645:betulinylaminoundecanoic acid; D000094062:Betulinic Acid