Quest for a potent antimalarial drug lead: Synthesis and evaluation of 6,7-dimethoxyquinazoline-2,4-diamines.

Abstract

Quinazolines have long been known to exert varied pharmacologic activities that make them suitable for use in treating hypertension, viral infections, tumors, and malaria. Since 2014, we have synthesized approximately 150 different 6,7-dimethoxyquinazoline-2,4-diamines and evaluated their antimalarial activity via structure-activity relationship studies. Here, we summarize the results and report the discovery of 6,7-dimethoxy-N4-(1-phenylethyl)-2-(pyrrolidin-1-yl)quinazolin-4-amine (20, SSJ-717), which exhibits high antimalarial activity as a promising antimalarial drug lead.

• Authors: Yuki Mizukawa, Mayumi Ikegami-Kawai, Masako Horiuchi, Marcel Kaiser, Masayoshi Kojima, Seiki Sakanoue, Seiya Miyagi, Christian Nanga Chick, Hiroyuki Togashi, Masayoshi Tsubuki, Masataka Ihara, Toyonobu Usuki, Isamu Itoh
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 33 Pg. 116018 (03 01 2021) ISSN: 1464-3391 [Electronic] England
• PMID: 33524940 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antimalarials

Topics

• Animals
• Antimalarials (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Discovery
• Female
• Malaria, Falciparum (drug therapy)
• Mice
• Mice, Inbred ICR
• Molecular Structure
• Parasitic Sensitivity Tests
• Plasmodium falciparum (drug effects)
• Structure-Activity Relationship