Ateviridine is a
non-nucleoside reverse transcriptase inhibitor that has been studied for the treatment of
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
.
Synthesis
Preparation of the pyridylpiperazine moiety starts by aromatic displacement of chlorine from 2-chloro-3-nitropyridine by piperazine to give 3. The secondary amine is then protected as its BOC derivative by reaction with
di-tert-butyl dicarbonate
Di-''tert''-butyl dicarbonate is a reagent widely used in organic synthesis. Since this compound can be regarded formally as the acid anhydride derived from a ''tert''-butoxycarbonyl (Boc) group, it is commonly referred to as Boc anhydride. This ...
(
Boc anhydride
Di-''tert''-butyl dicarbonate is a reagent widely used in organic synthesis. Since this compound can be regarded formally as the acid anhydride derived from a ''tert''-butoxycarbonyl (Boc) group, it is commonly referred to as Boc anhydride. This ...
) to give 4. The nitro group is then reduced by
catalytic hydrogenation
Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic co ...
. Reductive alkylation with acetaldehyde in the presence of
lithium cyanoborohydride gives the corresponding N-ethyl derivative. The
protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In many ...
is then removed by reaction with
TFA. Reaction of the resulting amine with the imidazolide derivative of 5-methoxy-3-indoleacetic acid produces the amide reverse transcriptase inhibitor, atevirdine.
See also
*
Delavirdine
Delavirdine (DLV) (brand name Rescriptor) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency vir ...
References
Abandoned drugs
Carboxamides
Indole ethers at the benzene ring
Non-nucleoside reverse transcriptase inhibitors
Piperazines
Aminopyridines
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