title: Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.
abstract: A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.
authors.affiliation: Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
authors.forename: F
authors.initials: F
authors.lastname: Soler
authors.forename: C
authors.initials: C
authors.lastname: Poujade
authors.forename: M
authors.initials: M
authors.lastname: Evers
authors.forename: J C
authors.initials: JC
authors.lastname: Carry
authors.forename: Y
authors.initials: Y
authors.lastname: Hénin
authors.forename: A
authors.initials: A
authors.lastname: Bousseau
authors.forename: T
authors.initials: T
authors.lastname: Huet
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
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; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D019426:Integrases; 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; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; D053978:Pentacyclic Triterpenes; D018894:Reverse Transcriptase Inhibitors; D014315:Triterpenes; C098649:RPR 103611; D004254:DNA Nucleotidyltransferases; D019426:Integrases; D000094062:Betulinic Acid