Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones.

ABSTRACT:

Background

The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.

Methods

The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived f

SUBMITTER: Chen Y 

PROVIDER: S-EPMC7893776 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature