Novel hexahydropyrrolo[3,4- c]pyrrole CCR5 antagonists

Utilizing a high-throughput screening lead as a starting point, an information-based approach led to the discovery of a novel series of CCR5 antagonists, exemplified by compound 4. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synth...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-05, Vol.20 (10), p.3116-3119
Hauptverfasser:	Rotstein, David M., Melville, Chris R., Padilla, Fernando, Cournoyer, Dick, Lee, Eun K., Lemoine, Remy, Petersen, Ann C., Setti, Lina Q., Wanner, Jutta, Chen, Lijing, Filonova, Lubov, Loughhead, David G., Manka, Jason, Lin, Xiao-Fa, Gleason, Shelley, Sankuratri, Surya, Ji, Changhua, deRosier, Andre, Dioszegi, Marianna, Heilek, Gabrielle, Jekle, Andreas, Berry, Pamela, Mau, Cheng-I, Weller, Paul
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-HIV Agents - chemical synthesis Anti-HIV Agents - chemistry Anti-HIV Agents - pharmacokinetics Anti-HIV-1 Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral Antiviral agents Benzamides - chemical synthesis Benzamides - chemistry Benzamides - pharmacology Biological and medical sciences CCR5 antagonist CCR5 Receptor Antagonists Chemokine HIV Fusion Inhibitors - chemical synthesis HIV Fusion Inhibitors - chemistry HIV Fusion Inhibitors - pharmacokinetics Humans Medical sciences Microsomes, Liver - metabolism Pharmacology. Drug treatments Pyrroles - chemical synthesis Pyrroles - chemistry Pyrroles - pharmacokinetics Rats Receptors, CCR5 - metabolism Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	Utilizing a high-throughput screening lead as a starting point, an information-based approach led to the discovery of a novel series of CCR5 antagonists, exemplified by compound 4. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described. Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.03.095