Work

Diaryl Ureas as an Antiprotozoal Chemotype

Year: 2021

Type: article

Abstract: We now describe the physicochemical profiling, in vitro ADME, and antiparasitic activity of eight N, N′ -diarylureas to assess their potential as a broad-spectrum antiprotozoal chemotype. Chromatographic LogD 7.4 values ranged from 2.5 to 4.5; kinetic aq. solubilities were ≤6.3 μg/mL, and plasma protein binding ranged from 95 to 99%. All of the compounds had low intrinsic clearance values in human, but not mouse, liver microsomes. Although no N, N′ -diarylurea had submicromolar potency against Trypanosoma cruzi, two had submicromolar potencies against Toxoplasma gondii and Trypanosoma brucei rhodesiense, and five had submicromolar potencies against Leishmania donovani . Plasmodium falciparum appeared to be the most susceptible to growth inhibition by this compound series. Most of the N, N′ -diarylureas had antiprotozoal selectivities ≥10. One N, N′ -diarylurea had demonstrable activity in mouse models of malaria and toxoplasmosis.

Source: ACS Infectious Diseases

DOI: 10.1021/acsinfecdis.1c00135