title: Piperazine-based CCR5 antagonists as HIV-1 inhibitors. III: synthesis, antiviral and pharmacokinetic profiles of symmetrical heteroaryl carboxamides.
abstract: The unsymmetrical nicotinamide-N-oxide moiety in compound 1 was replaced with symmetrical isonicotinamides as well as 4,6-dimethyl pyrimidine-5-carboxamides. Compound 16 from the latter set reduced the number of rotamers, improved potency of inhibiting UIV entry, slightly diminished the affinity for the muscarine receptors and showed very good oral absorption.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-2B-2800, Kenilworth, NJ 07033, USA.
authors.forename: Stuart W
authors.initials: SW
authors.lastname: McCombie
authors.forename: Jayaram R
authors.initials: JR
authors.lastname: Tagat
authors.forename: Susan F
authors.initials: SF
authors.lastname: Vice
authors.forename: Sue-Ing
authors.initials: SI
authors.lastname: Lin
authors.forename: Ruo
authors.initials: R
authors.lastname: Steensma
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Neustadt
authors.forename: Bahige M
authors.initials: BM
authors.lastname: Baroudy
authors.forename: Julie M
authors.initials: JM
authors.lastname: Strizki
authors.forename: Michael
authors.initials: M
authors.lastname: Endres
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cox
authors.forename: Niya
authors.initials: N
authors.lastname: Dan
authors.forename: Chuan-Chu
authors.initials: CC
authors.lastname: Chou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D065100:CCR5 Receptor Antagonists; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015497:HIV-1 / Q000187:drug effects*; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D006571:Heterocyclic Compounds; D010879:Piperazines; D011976:Receptors, Muscarinic