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. 2020 Jul 1;28(13):115541.
doi: 10.1016/j.bmc.2020.115541. Epub 2020 May 4.

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

Manoj Patel  1 , B Narasimhulu Naidu  2 , Ira Dicker  3 , Helen Higley  4 , Zeyu Lin  4 , Brian Terry  4 , Tricia Protack  4 , Mark Krystal  3 , Susan Jenkins  2 , Dawn Parker  2 , Chiradeep Panja  5 , Richard Rampulla  6 , Arvind Mathur  6 , Nicholas A Meanwell  7 , Michael A Walker  8
Affiliations

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

Manoj Patel et al. Bioorg Med Chem. .

Abstract

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.

Keywords: Bridged tricyclic pyrimidinone; HIV; HIV Integrase; Integrase inhibitor; Strand transfer inhibitor.

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Conflict of interest statement

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.

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