Oximino-piperidino-piperidine-based CCR5 antagonists. Part 2: synthesis, SAR and biological evaluation of symmetrical heteroaryl carboxamides.
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.
Palani
Anandan
A
Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. anandan.palani@spcorp.com
Shapiro
Sherry
S
Clader
John W
JW
Greenlee
William J
WJ
Vice
Susan
S
McCombie
Stuart
S
Cox
Kathleen
K
Strizki
Julie
J
Baroudy
Bahige M
BM
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
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