Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives.
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.
Lee
Chaewoon
C
Department of Bioscience & Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
Lee
Jin Moo
JM
Lee
Na-Ra
NR
Kim
Dong-Eun
DE
Jeong
Yong-Joo
YJ
Chong
Youhoon
Y
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002396:Catechols / Q000737:chemistry; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D002396:Catechols; D002867:Chromones; D004791:Enzyme Inhibitors; D004265:DNA Helicases; C034221:catechol