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

Design, synthesis and SAR study of bridged tricyclic pyrimidinone carboxamides as HIV-1 integrase inhibitors.
Bioorg Med Chem. 2020 May 04;:115541
Authors: Patel M, Naidu BN, Dicker I, Higley H, Lin Z, Terry B, Protack T, Krystal M, Jenkins S, Parker D, Panja C, Rampulla R, Mathur A, Meanwell NA, Walker MA
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.
PMID: 32389483 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - May 3, 2020 Category: Chemistry Authors: Patel M, Naidu BN, Dicker I, Higley H, Lin Z, Terry B, Protack T, Krystal M, Jenkins S, Parker D, Panja C, Rampulla R, Mathur A, Meanwell NA, Walker MA Tags: Bioorg Med Chem Source Type: research