948990-76-9Relevant articles and documents
Heterobiaryl human immunodeficiency virus entry inhibitors
Lu, Rong-Jian,Tucker, John A.,Pickens, Jason,Ma, You-An,Zinevitch, Tatiana,Kirichenko, Olga,Konoplev, Vitalii,Kuznetsova, Svetlana,Sviridov, Sergey,Brahmachary, Enugurthi,Khasanov, Alisher,Mikel, Charles,Yang, Yang,Liu, Changhui,Wang, Jian,Freel, Stephanie,Fisher, Shelly,Sullivan, Alana,Zhou, Jiying,Stanfield-Oakley, Sherry,Baker, Brian,Sailstad, Jeff,Greenberg, Michael,Bolognesi, Dani,Bray, Brian,Koszalka, Barney,Jeffs, Peter,Jeffries, Cynthia,Chucholowski, Alexander,Sexton, Connie
supporting information; experimental part, p. 4481 - 4487 (2010/03/01)
Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC50 values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates. Moreover, current structure-activity relationship studies of these novel biaryl gp120 inhibitors revealed that around the biaryl, a fine crevice might exist in the gp120 binding site. Taken in sum, these data reveal a hitherto unsuspected flexibility in the structure-activity relationships for these inhibitors and suggest new avenues for exploration and gp120 inhibitor design. 2009 American Chemical Society.
