title: Oximino-piperidino-piperidine-based CCR5 antagonists. Part 2: synthesis, SAR and biological evaluation of symmetrical heteroaryl carboxamides.
abstract: The synthesis, SAR and biological evaluation of symmetrical amide analogues of our clinical candidate SCH 351125 are described. A series of potent and orally bioavailable CCR5 antagonists containing symmetrical 2,6-dimethyl isonicotinamides and 2, 6-dimethyl pyrimidines amides were generated with enhanced affinity for the CCR5 receptor.
authors.affiliation: Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. anandan.palani@spcorp.com
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: Sherry
authors.initials: S
authors.lastname: Shapiro
authors.forename: John W
authors.initials: JW
authors.lastname: Clader
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Susan
authors.initials: S
authors.lastname: Vice
authors.forename: Stuart
authors.initials: S
authors.lastname: McCombie
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cox
authors.forename: Julie
authors.initials: J
authors.lastname: Strizki
authors.forename: Bahige M
authors.initials: BM
authors.lastname: Baroudy
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D003497:Cyclic N-Oxides; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010091:Oximes; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011725:Pyridines; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D018946:Chemokine CCL5; D003497:Cyclic N-Oxides; D006575:Heterocyclic Compounds, 3-Ring; D010091:Oximes; D010880:Piperidines; D011725:Pyridines; C438583:Ancriviroc