- 6-methyl 7-position-denitrified purine nucleoside compounds and application thereof
-
The invention discloses6-methyl 7-position-denitrified purine nucleoside compounds and an application thereof and belongs to the field of medicinal chemistry. The 6-methyl 7-position-denitrified purine nucleoside compounds or pharmaceutically acceptable salts of the compounds having characteristics of a structure shown as formula I are a kind of novel-structured compounds designed and synthesized according to protein structure characteristics of RNA virus polymerase, and the compounds can inhibit RNA viruses, thereby being capable of serving as potential drugs for preventing and treating infection of RNA viruses such as HCV (hepatitis c virus), influenza virus, HRV (rhinovirus), RSV, Ebola virus, DENV (Dengue virus), enterovirus and the like.
- -
-
-
- Synthesis and Cytostatic and Antiviral Activities of 2′-Deoxy-2′,2′-difluororibo- and 2′-Deoxy-2′-fluororibonucleosides Derived from 7-(Het)aryl-7-deazaadenines
-
A series of sugar-modified derivatives of cytostatic 7-heteroaryl-7-deazaadenosines (2′-deoxy-2′-fluororibo- and 2′-deoxy-2′,2′-difluororibonucleosides) bearing an aryl or heteroaryl group at position7 was prepared and screened for biological activity. The difluororibonucleosides were prepared by non- stereoselective glycosidation of 6-chloro-7-deazapurine with benzoyl-protected 2-deoxy-2,2-difluoro-D-erythro-pentofuranosyl-1-mesylate, followed by amination and aqueous Suzuki cross-couplings with (het)arylboronic acids. The fluororibo derivatives were prepared by aqueous palladium-catalyzed cross-coupling reactions of the corresponding 7-iodo-7-deazaadenine 2′-deoxy-2′-fluororibonucleoside 20 with (het)arylboronic acids. The key intermediate 20 was prepared by a six-step sequence from the corresponding arabinonucleoside by selective protection of 3′- and 5′-hydroxy groups with acid-labile groups, followed by stereoselective SN2 fluorination and deprotection. Some of the title nucleosides and 7-iodo-7-deazaadenine intermediates showed micromolar cytostatic or anti-HCV activity. The most active were 7-iodo and 7-ethynyl derivatives. The corresponding 2′-deoxy-2′,2′-difluororibonucleoside 5′-O-triphosphates were found to be good substrates for bacterial DNA polymerases, but are inhibitors of human polymeraseα. Sugar modified: Fluorinated analogues of 7-(het)aryl-7-deazaadenines were synthesized, and these nucleosides showed micromolar cytostatic activity against cancer cell lines and moderate anti-HCV activity. The corresponding nucleoside 5′-O-triphosphates were found to be good substrates for bacterial DNA polymerases, but are inhibitors of human polymeraseα.
- Perlikova, Pavla,Eberlin, Ludovic,Menova, Petra,Raindlova, Veronika,Slavetinska, Lenka,Tloustova, Eva,Bahador, Gina,Lee, Yu-Jen,Hocek, Michal
-
p. 832 - 846
(2013/08/25)
-