Design, synthesis, and biological evaluation of novel coxsackievirus B3 inhibitors.
The synthesis and SAR study of a novel class of coxsackievirus B3 (CVB3) inhibitors are reported. These compounds could be considered as the 6-chloropurines substituted at position 9 with variously substituted bicyclic scaffolds (bicyclo[2.2.1]heptane/ene-norbornane or norbornene). The synthesis and biological evaluation of 31 target compounds are described. Several of the analogues inhibited CVB3 in the low micromolar range (0.66-2muM). Minimal or no cytotoxicity was observed.
Sála
Michal
M
Gilead Sciences & IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
De Palma
Armando M
AM
Hrebabecký
Hubert
H
Nencka
Radim
R
Dracínský
Martin
M
Leyssen
Pieter
P
Neyts
Johan
J
Holý
Antonín
A
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D015195:Drug Design; D029822:Enterovirus B, Human / Q000187:drug effects*; D006801:Humans; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000998:Antiviral Agents; D001643:Bridged Bicyclo Compounds; D011687:Purines; C116378:bicyclo(2.2.1)heptene; C079308:6-chloropurine