Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives

Bioorganic & Medicinal Chemistry Letters
Volume 19, Issue 16, 15 August 2009, Pages 4538-4541

Chaewoon Lee, Jin Moo Lee, Na- Ra Lee, Dong-Eun Kim, Yong-Joo Jeong, You hoon Chong.


Abstract

Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.

Keywords

SARS (Severe Acute Respiratory Syndrome), NTPase/helicase, Dihydroxychromone, Pharmacophore