Design, synthesis and SAR study of novel C2-pyrazolopyrimidine amides and amide isosteres as allosteric integrase inhibitors.

Autor: Patel M; Departments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA. Electronic address: manoj.m.patel@viivhealthcare.com., Cianci C; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Allard CW; Departments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Parker DD; Departments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Simmermacher J; Departments of Discovery Chemistry and Molecular Technologies, 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, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Mcauliffe B; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA., Minassian B; Virology, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Discotto L; 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., Meanwell NA; Departments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA., Naidu BN; Departments of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA; ViiV Healthcare, 36 East Industrial Parkway, Branford, CT 06405, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Nov 01; Vol. 30 (21), pp. 127516. Date of Electronic Publication: 2020 Aug 27.
DOI: 10.1016/j.bmcl.2020.127516
Abstrakt: The design, synthesis and structure-activity relationships associated with a series of C2-substituted pyrazolopyrimidines as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) are described. Structural modifications to these molecules were made in order to examine the effect on potency and, for select compounds, pharmacokinetic properties. We examined a variety of C2-substituted pyrazolopyrimidines and found that the C2-amide derivatives demonstrated the most potent antiviral activity of this class against HIV-1 infection in cell culture.
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
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