Atevirdine: Difference between revisions

{{Short description|Reverse-transcriptase inhibitor}}

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| ImageFile = Atevirdine structure.svg

| ImageSize = 220px

| PIN = {4-[3-(Ethylamino)pyridin-2-yl]piperazin-1-yl}(5-methoxy-1''H''-indol-2-yl)methanone

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| Section1 = {{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 54835

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| CASNo = 136816-75-6

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| StdInChI = 1S/C21H25N5O2/c1-3-22-18-5-4-8-23-20(18)25-9-11-26(12-10-25)21(27)19-14-15-13-16(28-2)6-7-17(15)24-19/h4-8,13-14,22,24H,3,9-12H2,1-2H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| PubChem = 60848

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| SMILES = O=C(N2CCN(c1ncccc1NCC)CC2)c4cc3cc(OC)ccc3[nH]4

| Section2 = {{Chembox Properties

| Formula = C₂₁H₂₅N₅O₂

| MolarMass = 379.46 g/mol

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|Section3 = {{Chembox Hazards

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'''Atevirdine''' is a [[non-nucleoside reverse transcriptase inhibitor]] that has been studied for the treatment of [[HIV]].<ref name="pmid10774589">{{cite journal |vauthors=Morse GD, Reichman RC, Fischl MA |title=Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams |journal=Antiviral Res. |volume=45 |issue=1 |pages=47–58 |date=January 2000 |pmid=10774589 |doi= 10.1016/S0166-3542(99)00073-X|display-authors=etal}}</ref>

==Synthesis==

[[File:Atevirdine synthesis.png|thumb|center|500px|Atevirdine synthesis:<ref>D. L. Romero, Drugs Future 19, 9 (1995).</ref><ref>{{Cite patent|country=WO|number=9109849

|title=Diaromatic substituted anti-AIDS compounds|pubdate=1991-07-11|assign=[[Upjohn]]|inventor1-last=Romero|inventor1-first=Donna Lee |inventor2-last=Mitchell |inventor2-first=Mark Allen|inventor3-last=Thomas|inventor3-first=Richard Charles |inventor4=John Raymond Palmer;William Gary Tarpley;Paul Adrian Aristoff;Herman W. Smith}}</ref> [[Structure-activity relationship|SAR]]:<ref>{{Cite journal | doi = 10.1021/jm00033a018| pmid = 7512142| title = Discovery, Synthesis, and Bioactivity of Bis(heteroaryl)piperazines. 1. A Novel Class of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors| journal = Journal of Medicinal Chemistry| volume = 37| issue = 7| pages = 999–1014| year = 1994| last1 = Romero | first1 = D. L. | last2 = Morge | first2 = R. A. | last3 = Biles | first3 = C. | last4 = Berrios-Pena | first4 = N. | last5 = May | first5 = P. D. | last6 = Palmer | first6 = J. R. | last7 = Johnson | first7 = P. D. | last8 = Smith | first8 = H. W. | last9 = Busso | first9 = M. |display-authors=etal }}</ref>]]

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]] ([[Boc anhydride]]) to give '''4'''. The nitro group is then reduced by [[catalytic hydrogenation]]. Reductive alkylation with acetaldehyde in the presence of [[lithium cyanoborohydride]] gives the corresponding N-ethyl derivative. The [[protecting group]] is then removed by reaction with [[Trifluoroacetic acid|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]]

[[Category:Abandoned drugs]]

[[Category:Carboxamides]]

[[Category:Indole ethers at the benzene ring]]

[[Category:3-Aminopyridines]]