Development of Pyrazolopyrimidine Anti-Wolbachia Agents for the Treatment of Filariasis.

ABSTRACT: Anti-Wolbachia therapy has been identified as a viable treatment for combating filarial diseases. Phenotypic screening revealed a series of pyrazolopyrimidine hits with potent anti-Wolbachia activity. This paper focuses on the exploration of the SAR for this chemotype, with improvement of metabolic stability and solubility profiles using medicinal chemistry approaches. Organic synthesis has enabled functionalization of the pyrazolopyrimidine core at multiple positions, generating a library of compounds of which many analogues possess nanomolar activity against Wolbachia in vitro with improved DMPK parameters. A lead compound, 15f, was selected for in vivo pharmacokinetics (PK) profiling in mice. The combination of potent anti-Wolbachia activity in

SUBMITTER: McGillan P 

PROVIDER: S-EPMC8436242 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature