Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir.

ABSTRACT: The discovery and development of fostemsavir (2), the tromethamine salt of the phosphonooxymethyl prodrug of temsavir (1), encountered significant challenges at many points in the preclinical and clinical development program that, in many cases, stimulated the implementation of innovative solutions in order to enable further progression. In the preclinical program, a range of novel chemistry methodologies were developed during the course of the discovery effort that enabled a thorough examination and definition of the HIV-1 attachment inhibitor (AI) pharmacophore. These discoveries helped to address the challenges associated with realizing a molecule with all of the properties necessary to successfully advance through development and this aspect of the program is the major fo

SUBMITTER: Wang T 

PROVIDER: S-EPMC8476988 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature