title: Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment 13. Synthesis and profiling of a novel amminium prodrug of the HIV-1 attachment inhibitor BMS-585248.
abstract: In vitro studies suggested that the ammonium salt 2 could be a viable prodrug of the HIV-1 attachment inhibitor 1. Increased systemic exposure of the parent drug 1 following oral administration of the amminium salt 2 when compared to similar studies using solution dosing of the parent compound was observed in the in vivo studies in both rats and dogs. At high doses, the improvement in oral exposure of the parent drug was even more evident, indicating that the increased solubility of the amminium salt 2 can overcome dissolution-limited absorption and demonstrating the potential utility of this compound as a prodrug of 1.
authors: Department of Medicinal Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States. alicia.regueiroren@bms.com
authors: Alicia
authors: A
authors: Regueiro-Ren
authors: Jean
authors: J
authors: Simmermacher-Mayer
authors: Michael
authors: M
authors: Sinz
authors: Kim A
authors: KA
authors: Johnson
authors: Xiaohua Stella
authors: XS
authors: Huang
authors: Susan
authors: S
authors: Jenkins
authors: Dawn
authors: D
authors: Parker
authors: Sandhya
authors: S
authors: Rahematpura
authors: Ming
authors: M
authors: Zheng
authors: Nicholas A
authors: NA
authors: Meanwell
authors: John F
authors: JF
authors: Kadow
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D004285:Dogs; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D057166:High-Throughput Screening Assays; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D053585:Virus Attachment / Q000187:drug effects
chemical_list: C582545:1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-(1,2,3)triazol-1-yl-1H-pyrrolo(2,3-c)pyridin-3-yl)-ethane-1,2-dione; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D010879:Piperazines; D011355:Prodrugs; D011725:Pyridines; D011758:Pyrroles; D014227:Triazines; D014230:Triazoles