Synthesis of 5'-triphosphate mimics (P3Ms) of 3'-azido-3',5'-dideoxythymidine and 3',5'-dideoxy-5'-difluoromethylenethymidine as HIV-1 reverse transcriptase inhibitors.
3'-Azido-3',5-dideoxythymidine 5'-phosphonate and 3',5'-dideoxy-5'-difluoromethylenethymidine 5'-phosphonate were prepared by multistep syntheses. The nucleoside 5'-phosphonates were converted to their triphosphates and triphosphate mimics (P3Ms) containing beta,gamma-difluoromethylene, beta,gamma-dichloromethylene, or beta,gamma-imodo by condensation with pyrophosphate or pyrophosphate mimics, respectively. Inhibition of HIV-1 reverse transcriptase by the nucleoside P3Ms is briefly discussed.
Rajwanshi
Vivek K
VK
Research Laboratories, Biota, Inc., 2232 Rutherford Road, Carlsbad, CA 92008, USA.
Prhavc
Marija
M
Fagan
Patrick
P
Brooks
Jennifer L
JL
Hurd
Tiffany
T
Cook
P Dan
PD
Wang
Guangyi
G
D054306:Dideoxynucleotides; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C513639:3',5'-dideoxy-5'-difluoromethylenethymidine; D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D054303:HIV Reverse Transcriptase; D013936:Thymidine