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allied
academies
IMMUNOLOGY AND CELL BIOLOGY
BACTERIOLOGY AND INFECTIOUS DISEASES
&
Global Summit on
Global Congress on
J u n e 2 5 - 2 6 , 2 0 1 8 | A m s t e r d a m , N e t h e r l a n d s
Virology Research Journal
|
Volume 2
Page 19
Note:
Joint Event on
4’-C-Ethynyl-2-fluoro-2’-deoxyadenosine (EFdA) has attracted much attention
due to its extremely excellent anti-HIV activity, for example, EFdA prevents the
emergence of resistant HIV mutants, and is over 400 times more active than
AZTand several orders ofmagnitudemore active than the other clinical reverse-
transcriptase inhibitory 2’, 3’-dideoxy-nucleoside drugs, very low toxic, very
long acting, very useful for the prevention of HIV-infection. EFdA is now under
clinical investigation by Merck & Co. as MK-8591. In the beginning, a general
idea for the development of anti-viral modified nucleosides will be presented,
and then the development of EFdA will be discussed and the clinical results
by Merck will be also presented. For the design of the modified nucleoside
which could solve the problems that the clinical drugs have (emergence of
drug-resistant HIV mutants, adverse effect by drugs, necessity to take quite
a few amount of drugs), the following working hypotheses were proposed.
They are: The way to prevent the emergence of drug-resistant HIV mutants,
the way to decrease the toxicity of modified nucleosides, the way to provide
the modified nucleoside with stability to both enzymatic and acidic glycolysis
for long acting. 4’-C-substituted-2’-deoxynucleoside (4’SdN) was designed to
meet the hypotheses (1), (3), and the additional modification of 4’SdN was
performed to meet the hypothesis. The details of the hypotheses and the
reasons for the design of 4’SdN will be discussed. To prevent the deamination
of adenine base by adenosine deaminase, a fluorine atom was introduced at
the 2-position of adenine. Finally, EFdA, modified at the two position (2 and
4’) of the physiologic 2’-deoxyadenosine and has extremely excellent anti-HIV
activity, was successfully developed.
Biography
Hiroshi Ohrui received PhD degree (1971) from
The University of Tokyo. He joined Riken (1966)
and moved to Tohoku University (1981). He
moved to Yokohama University of Pharmacy
(2006). He worked for Dr. J J Fox at Sloan-Ket-
tering Institute for Cancer Research (1972-1973)
and for Dr. J GMoffatt at Syntex Research (1973-
1974). He received several awards including Ja-
pan Academy Prize (2001). His research interests
cover organic synthesis, chemical biology, and
chiral discrimination.
h.ohrui@hamayaku.ac.jpEFDA: AN EXTREMELY EXCELLENT
ANTI-HIV MODIFIED NUCLEOSIDE,
-FROM DESIGN TO THE CURRENT
CLINICAL TRIAL RESULTS
Hiroshi Ohrui
Yokohama University of Pharmacy, Japan
Hiroshi Ohrui, Virol Res J 2018, Volume 2