Biomaterial Database

Synthesis of 4-methylthio analogues of FLT and AZT and their evaluation against HIV. 1995

A A Abel-Rahman, and H M Abdel-Bary, and E B Pedersen, and C Nielsen

Department of Chemistry, Odense University, Denmark.

Silylated 4-methylthiouracil and 4-methylthiothymine were condensed in the presence of TMS triflate with methyl 2,3-dideoxy-3-fluoro-5-O-(4- phenylbenzoyl)-D-erythro-pentofuranoside (3) and methyl 3-azido-5-O- (tert-butyldiphenylsilyl)-2,3-dideoxy-D-erythro-pentofuroside++ + (8), respectively, to give the corresponding nucleosides which were deprotected. The 3'-azido nucleoside was reduced with triphenylphosphine to the corresponding 3'-amino nucleoside. The 3'-amino nucleoside was also obtained by condensation of 4-methylthiothymidine with a 3-phthalimido sugar 14 followed by deprotection. The 4-methylthio analogue 11 of AZT showed moderate activity against HIV.

UI	MeSH Term	Description	Entries
D000998	Antiviral Agents	Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.	Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D015215	Zidovudine	A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.	AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D015224	Dideoxynucleosides	Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.	2',3'-Dideoxynucleosides,Dideoxyribonucleosides,ddNus,2',3' Dideoxynucleosides
D015497	HIV-1	The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.	Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human