Palmer, Michael J. published the artcilePotent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series, Synthetic Route of 328-90-5, the publication is Journal of Medicinal Chemistry (2021), 64(9), 6085-6136, database is CAplus and MEDLINE.
Dihydroorotate dehydrogenase (DHODH) has been clin. validated as a target for the development of new antimalarials. Experience with clin. candidate triazolopyrimidine DSM265 (1) suggested that DHODH inhibitors have great potential for use in prophylaxis, which represents an unmet need in the malaria drug discovery portfolio for endemic countries, particularly in areas of high transmission in Africa. We describe a structure-based computationally driven lead optimization program of a pyrrole-based series of DHODH inhibitors, leading to the discovery of two candidates for potential advancement to preclin. development. These compounds have improved physicochem. properties over prior series frontrunners and they show no time-dependent CYP inhibition, characteristic of earlier compounds Frontrunners have potent antimalarial activity in vitro against blood and liver schizont stages and show good efficacy in Plasmodium falciparum SCID mouse models. They are equally active against P. falciparum and Plasmodium vivax field isolates and are selective for Plasmodium DHODHs vs. mammalian enzymes.
Journal of Medicinal Chemistry published new progress about 328-90-5. 328-90-5 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Carboxylic acid,Benzene,Phenol, name is 2-Hydroxy-4-(trifluoromethyl)benzoic acid, and the molecular formula is C8H5F3O3, Synthetic Route of 328-90-5.
Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts