Atevirdine is a

non-nucleoside reverse transcriptase inhibitor Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replicatio ...

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 im ...

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 ...

. Reductive alkylation with acetaldehyde in the presence of

lithium cyanoborohydride Lithium (from , , ) is a chemical element; it has symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid element. Like all alkali metals, ...

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 man ...

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.

References

Abandoned drugs Carboxamides Indole ethers at the benzene ring Non-nucleoside reverse transcriptase inhibitors Piperazines Disubstituted pyridines {{Antiinfective-agent-stub

Synthesis

See also

References