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Atevirdine

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Reverse-transcriptase inhibitor

Pharmaceutical compound

Atevirdine
Identifiers

IUPAC name [4-[3-(ethylamino)pyridin-2-yl]piperazin-1-yl]-(5-methoxy-1H-indol-2-yl)methanone
CAS Number	136816-75-6
PubChemCID	60848
DrugBank	DB12264
ChemSpider	54835
UNII	N24015WC6D
ChEMBL	ChEMBL280527
CompTox Dashboard(EPA)	DTXSID40159940
Chemical and physical data
Formula	C₂₁H₂₅N₅O₂
Molar mass	379.464 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCNC1=C(N=CC=C1)N2CCN(CC2)C(=O)C3=CC4=C(N3)C=CC(=C4)OC
InChI InChI=InChI=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 Key:UCPOMLWZWRTIAA-UHFFFAOYSA-N

Atevirdine is anon-nucleoside reverse transcriptase inhibitor that has been studied for the treatment ofHIV.^[1]

Synthesis

[edit]

Preparation of the pyridylpiperazine moiety starts by aromatic displacement of chlorine from 2-chloro-3-nitropyridine by piperazine to give3. The secondary amine is then protected as its BOC derivative by reaction withdi-tert-butyl dicarbonate (Boc anhydride) to give4. The nitro group is then reduced bycatalytic hydrogenation. Reductive alkylation with acetaldehyde in the presence oflithium cyanoborohydride gives the corresponding N-ethyl derivative. Theprotecting group is then removed by reaction withTFA. Reaction of the resulting amine with the imidazolide derivative of 5-methoxy-3-indoleacetic acid produces the amide reverse transcriptase inhibitor, atevirdine.

References

[edit]

^Morse GD, Reichman RC, Fischl MA, Para M, Leedom J, Powderly W, et al. (January 2000). "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".Antiviral Research.45 (1):47–58.doi:10.1016/S0166-3542(99)00073-X.PMID 10774589.
^Romero M (1994). "Atevirdine Mesylate".Drugs of the Future.19 (1): 9.doi:10.1358/dof.1994.019.01.235297.
^WO 9109849, Romero DL, Mitchell MA, Thomas RC, Palmer JR, Tarpley WG, Aristoff PA, Smith HW, "Diaromatic substituted anti-AIDS compounds", published 1991-07-11, assigned toUpjohn
^Romero DL, Morge RA, Biles C, Berrios-Pena N, May PD, Palmer JR, et al. (Apr 1994). "Discovery, Synthesis, and Bioactivity of Bis(heteroaryl)piperazines. 1. A Novel Class of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors".Journal of Medicinal Chemistry.37 (7):999–1014.doi:10.1021/jm00033a018.PMID 7512142.

Antiviral drugs:antiretroviral drugs used againstHIV (primarilyJ05)

Capsid inhibitors

Lenacapavir (LEN)

Entry/fusion inhibitors
(Discovery and development)

gp41 (Enfuvirtide (ENF, T-20))^◊
CCR5 (Maraviroc (MVC)
Vicriviroc^†,Cenicriviroc^†,Leronlimab^†)
CD4 (Ibalizumab (IBA),Semzuvolimab^§)
gp120 (Fostemsavir (FTR))

Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))

Maturation inhibitors

Protease Inhibitors (PI)
(Discovery and development)

1^st generation	Amprenavir (APV)^‡ Fosamprenavir (FPV) Indinavir (IDV)^◊ Lopinavir (LPV) Nelfinavir (NFV)^◊ Ritonavir (RTV)^# Saquinavir (SQV)^◊
2^nd generation	Atazanavir (ATV)°^# Darunavir (DRV)°^# Tipranavir (TPV)^◊ TMC-310911^§

Reverse-transcriptase
inhibitors (RTIs)

Nucleoside and
nucleotide (NRTI)

Nucleoside analogues/NRTIs:Abacavir (ABC)^#
Didanosine (ddI)^◊
Emtricitabine (FTC)
Lamivudine (3TC)^#
Stavudine (d4T)^◊
Zalcitabine (ddC)^‡
Zidovudine (AZT, ZDV)^#
Amdoxovir^†
Apricitabine^†
Censavudine^†
Elvucitabine^†
Islatravir (EFdA, ISL)^§
Racivir^†
Stampidine^†

Non-nucleoside (NNRTI)
(Discovery and development)

1^st generation	Efavirenz (EFV)^# Nevirapine (NVP)^# Delavirdine (DLV)^‡
2^nd generation	diarylpyrimidines Dapivirine (DPV) Etravirine (ETR) Rilpivirine (RPV) Doravirine (DOR) Elsulfavirine (ESV)

Combined formulations

Pharmacokinetic boosters

Experimental agents

Uncoating inhibitors	TRIM5alpha (gene)
Transcription inhibitors	Tat antagonists
Translation inhibitors	Trichosanthin
BNAbs	Elipovimab
Other	Abzyme BIT225^† Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) Foscarnet Fosdevirine^† Griffithsin Hydroxycarbamide KP-1461^† Miltefosine North-methanocarbathymidine Portmanteau inhibitors Scytovirin Seliciclib^† Synergistic enhancers Tre recombinase Zinc finger protein transcription factor
Failed agents	Aplaviroc Atevirdine Brecanavir Capravirine Dexelvucitabine Droxinavir Lasinavir Emivirine Lersivirine Lodenosine Loviride Mozenavir Palinavir Telinavir

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

°DHHSrecommendedinitial regimen options.^◊Formerly or rarely used agent.

v t e Arylpiperazines
Phenylpiperazines	1-Phenylpiperazine (1-PP; PP) 3,4-CFP 2C-B-PP Acaprazine Antrafenine Aripiprazole Batoprazine Bifeprunox BRL-15,572 Ciprofloxacin Dapiprazole DCPP DMPP Diphenylpiperazine Dropropizine EGIS-7625 EGIS-12,233 Elopiprazole Eltoprazine Enpiprazole Ensaculin Etoperidone Flesinoxan Fluanisone Flibanserin Fluprazine Itraconazole Ketoconazole Levodropropizine Lorpiprazole mCPP Mefway MeOPP Mepiprazole Naftopidil Naluzotan Nefazodone Niaprazine Oxypertine Pardoprunox pCPP pFPP Posaconazole S-14,506 S-14,671 S-15,535 SB-258,585 SB-271,046 SB-357,134 SB-399,885 Sonepiprazole TFMPP Tolpiprazole Trazodone Urapidil Vesnarinone Vilazodone Vortioxetine WAY-100,135 WAY-100,635
Benzylpiperazines	2C-B-BZP 3-Methylbenzylpiperazine Befuraline Bifeprunox Buclizine BZP Chlorbenzoxamine DBZP EGIS-7625 Fipexide Imatinib MBZP MDBZP Meclozine Methoxypiperamide NSI-189 Piberaline Piribedil RN-1747 Sunifiram Trimetazidine Vesnarinone
Naphthylpiperazines	1-Naphthylpiperazine (1-NP) 2-Naphthylpiperazine (2-NP) CSP-2503 F-11,461 S-14,506 S-14671
Quinolinylpiperazines	FPPQ 6-Nitroquipazine Isoquipazine Quipazine
Diphenylalkylpiperazines	AD-1211 Almitrine Amperozide BRL-15,572 Buclizine BW373U86 Cetirizine Chlorbenzoxamine Chlorcyclizine Cinnarizine Clocinizine Cyclizine DBL-583 Diphenpipenol Diphenylmethylpiperazine Dotarizine DPI-221 DPI-287 DPI-3290 GBR-12,783 GBR-12,935 GBR-13,069 GBR-13,098 GBR-13,119 Hydroxyzine JJC8-088 Lidoflazine Manidipine Meclozine MT-45 Oxatomide SNC-80 Vanoxerine
Pyrimidinylpiperazines	Buspirone Dasatinib Eptapirone Gepirone Ipsapirone Piribedil Pyrimidinylpiperazine Revospirone Tandospirone Tirilazad Trimazosin Umespirone Zalospirone
Pyridinylpiperazines	Atevirdine Azaperone Delavirdine Mirtazapine ORG-12962 Pyridinylpiperazine
Benzo(iso)thiazolyl piperazines	Lurasidone Perospirone Revospirone Tiospirone Ziprasidone
Tricyclic-linked piperazines	Amoxapine Clopenthixol Clorotepine Clozapine Cyanothepin Doclothepin Docloxythepin Flupentixol Fluphenazine Isofloxythepin Loxapine Meperathiepin Metitepine Octomethothepin Olanzapine Opipramol Oxyclothepin Oxyprothepin Peradithiepin Perathiepin Perazine Perphenazine Pirenzepine Prochlorperazine Thiethylperazine Thiothixene Trifluoperazine Trifluthepin Zuclopenthixol
Others/uncategorized	AP-238 Azimilide Bucinnazine Cinepazet Cinepazic acid Cinepazide CPD-1 Cyclohexylpiperazine Hexocyclium Indinavir JNJ-7777120 Lodenafil MK-212 Mirodenafil PB-28 Ranolazine SA-4503 Sildenafil Tadalafil Vardenafil VUF-6002 WY-46824 Zipeprol

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