2. Academic Validation
  3. Heterobiaryl human immunodeficiency virus entry inhibitors

Heterobiaryl human immunodeficiency virus entry inhibitors

  • J Med Chem. 2009 Jul 23;52(14):4481-7. doi: 10.1021/jm900330x.
Rong-Jian Lu 1,  John A Tucker,  Jason Pickens,  You-An Ma,  Tatiana Zinevitch,  Olga Kirichenko,  Vitalii Konoplev,  Svetlana Kuznetsova,  Sergey Sviridov,  Enugurthi Brahmachary,  Alisher Khasanov,  Charles Mikel,  Yang Yang,  Changhui Liu,  Jian Wang,  Stephanie Freel,  Shelly Fisher,  Alana Sullivan,  Jiying Zhou,  Sherry Stanfield-Oakley,  Brian Baker,  Jeff Sailstad,  Michael Greenberg,  Dani Bolognesi,  Brian Bray,  Barney Koszalka,  Peter Jeffs,  Cynthia Jeffries,  Alexander Chucholowski,  Connie Sexton
Affiliations

Affiliation

  • 1 Trimeris, Inc, Morrisville, North Carolina 27560, USA. rongjian.lu@sequoiapharma.com
PMID: 19534463 DOI: 10.1021/jm900330x
Abstract

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 IC(50) 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.

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