Design, synthesis and SAR study of bridged tricyclic pyrimidinone carboxamides as HIV-1 integrase inhibitors.

Autor: Patel M; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA. Electronic address: manoj.m.patel@viivhealthcare.com., Naidu BN; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Dicker I; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Higley H; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Lin Z; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Terry B; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Protack T; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Krystal M; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Jenkins S; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Parker D; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Panja C; Biocon-Bristol-Myers Squibb Research Center, Plot 2 & 3, Bommasandra Industrial Estate - Phase-IV, Bommasandra-Jigani Link Road, Bengaluru, Karnataka 560099, India., Rampulla R; Department of Discovery Chemistry Synthesis, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA., Mathur A; Department of Discovery Chemistry Synthesis, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA., Meanwell NA; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA., Walker MA; Departments of Discovery Chemistry and Molecular Technologies, 5 Research Parkway, Wallingford, CT 06492, USA; Assembly Biosciences, Inc. 331 Oyster Point Blvd, San Francisco, CA 94080, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2020 Jul 01; Vol. 28 (13), pp. 115541. Date of Electronic Publication: 2020 May 04.
DOI: 10.1016/j.bmc.2020.115541
Abstrakt: The design, synthesis and structure-activity relationships associated with a series of bridged tricyclic pyrimidinone carboxamides as potent inhibitors of HIV-1 integrase strand transfer are described. Structural modifications to these molecules were made in order to examine the effect on potency towards wild-type and clinically-relevant resistant viruses. The [3.2.2]-bridged tricyclic system was identified as an advantageous chemotype, with representatives exhibiting excellent antiviral activity against both wild-type viruses and the G140S/Q148H resistant virus that arises in response to therapy with raltegravir and elvitegravir.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: