Nevirapine

Base Information

• Chemical Name: Nevirapine
• CAS No.: 129618-40-2
• Molecular Formula: C15H14N4O
• Molecular Weight: 266.302
• Hs Code.: 29339900
• NSC Number: 759902,641530
• UNII: 99DK7FVK1H
• DSSTox Substance ID: DTXSID7031797
• Nikkaji Number: J420.601K
• Wikipedia: Nevirapine
• Wikidata: Q263713
• NCI Thesaurus Code: C29277
• RXCUI: 53654
• Metabolomics Workbench ID: 42640
• ChEMBL ID: CHEMBL57
• Mol file: 129618-40-2.mol

Synonyms:11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido(3,2-b:2,3-e)(1,4)diazepin-6-one;Viramune;BIRG 0587;BI-RG-587;BI-RG-587;6H-Dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one,11-cyclopropyl-5,11-dihydro-4-methyl-;99% Nevirapine;Nevirapine [USAN:INN];BI-RG 587;BIRG 587;BIRG 0587;Viramune (TN);NVP;Nevirapine (JP14/USAN);11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido;Viramune (Nevirapine);

Chemical Property of Nevirapine

Chemical Property:

• Appearance/Colour: white or off-white crystalline powder
• Vapor Pressure: 4.13E-07mmHg at 25°C
• Melting Point: 247 °C
• Refractive Index: 1.671
• Boiling Point: 415.4 °C at 760 mmHg
• PKA: 2.8(at 25℃)
• Flash Point: 205 °C
• PSA: 63.57000
• Density: 1.351 g/cm³
• LogP: 2.47830
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: ≥22mg/mL
• Water Solubility.: 0.1g/L(temperature not stated)
• XLogP3: 2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 1
• Exact Mass: 266.11676108
• Heavy Atom Count: 20
• Complexity: 397

Purity/Quality:

99% ^*data from raw suppliers

Nevirapine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: CC1=C2C(=NC=C1)N(C3=C(C=CC=N3)C(=O)N2)C4CC4
• Recent ClinicalTrials: Population Pharmacokinetics of Antiretroviral in Children
• Recent EU Clinical Trials: A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
• Description: Nevirapine and its analogues exhibit antiretroviral effect against azothymidine-resistant HIV strains. Nevirapine in combination with ZDV and ddI produced approximately 18% higher CD4 cell counts and a decrease in viral load compared with patients who took ZDV and ddI. Nevirapine is recommended with nucleosides for patients infected with HIV-1 who have experienced clinical or immunologic deterioration. The significant side effects of nevirapine are liver dysfunction and skin rashes.
• Uses: amyloidosis therapy Labelled Nevirapine , a potent (IC50=84nM) and selective non-nucleoside inhibitor of HIV-1 reverse transcriptase. Antiviral.;Labeled Nevirapine, intended for use as an internal standard for the quantification of Nevirapine by GC- or LC-mass spectrometry. A potent (IC50=84nM) and selective non-nucleoside inhibitorf HIV-1 reverse transcriptase
• Indications: Nevirapine (Viramune) is approved for the treatment of HIV infection in adults and children as part of a combination therapy. During the first 12 weeks of treatment, patients must be closely monitored for the development of potentially fatal hepatic toxicity (i.e., hepatitis, hepatic necrosis, and hepatic failure) and skin reactions (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions). Although these toxicities are rare, common side effects include mild to moderate rash, fever, nausea, fatigue, headache, and elevated liver enzymes.
• Therapeutic Function: Antiviral
• Clinical Use: Treatment of HIV-1 infection in adults and children over 2 months old (in combination with other antiretroviral therapies) Reduction of maternal transmission of HIV to the fetus (recommended only for use in HIV-infected treatment-naive women in labor who have had no prior HIV therapy)
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: reduces concentration of clarithromycin, but concentration of active metabolite increased, also concentration of nevirapine increased; concentration decreased by rifampicin - avoid; possibly increased rifabutin concentration. Anticoagulants: may increase or reduce effect of warfarin. Antidepressants: concentration reduced by St John’s wort - avoid. Antifungals: concentration of ketoconazole reduced - avoid; concentration increased by fluconazole; possibly reduced caspofungin and itraconazole concentration - may need to increase caspofungin and itraconazole dose. Antipsychotics: possibly reduced aripiprazole concentration - increase aripiprazole dose. Antivirals: concentration of dolutegravir, indinavir and efavirenz reduced and possibly etravirine, fosamprenavir, lopinavir, simeprevir and atazanavir - avoid with atazanavir, etravirine and simeprevir consider increasing lopinavir dose; increased risk of granulocytopenia with zidovudine. Cytotoxics: avoid with olaparib. Guanfacine: concentration possibly reduced - increase guanfacine dose. Oestrogens and progestogens: accelerated metabolism (reduced contraceptive effect). Orlistat: absorption possibly reduced by orlistat. Ulipristal: possibly reduces contraceptive effect.

Technology Process of Nevirapine

There total 25 articles about Nevirapine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (133627-47-1) → Nevirapine (129618-40-2)

Guidance literature:

With diethylene glycol dimethyl ether; sodium hydride; at 100 - 125 ℃; for 2.5h; Inert atmosphere;

Reference yield: 96.0%

methyl 2-(cyclopropylamino)nicotinate + 3-Amino-2-chloro-4-methylpyridine (133627-45-9) → Nevirapine (129618-40-2)

Guidance literature:

With sodium hydride; In diethylene glycol dimethyl ether; at 65 - 165 ℃; Flow reactor; Green chemistry;

DOI:10.1039/c7gc00937b

Reference yield: 91.0%

2-(Cyclopropylamino)-N-(2-methoxy-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (162709-30-0) → Nevirapine (129618-40-2)

Guidance literature:

With pyridine; sodium hexamethyldisilazane; at 90 ℃; for 6h;

DOI:10.1021/jo00111a056

upstream raw materials:

N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide

2-chloro-11-cyclopropyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one

2-(Cyclopropylamino)-N-(2-methoxy-4-methyl-3-pyridinyl)-3-pyridinecarboxamide

2-Chloronicotinoyl chloride

Downstream raw materials:

11-cyclopropyl-5,11-dihydro-4-(hydroxymethyl)-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one

11-cyclopropyl-5,11-dihydro-4-<(dimethylphenylsilyl)methyl>-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one

11-cyclopropyl-5,11-dihydro-7-(dimethylphenylsilyl)-4-methyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one

11-cyclopropyl-5,11-dihydro-4-methyl-3-nitro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

Refernces

• 1、 Norman,Minick,Martin. "Structural elucidation of an oxazolo[5,4-b]pyridine: An alternative cyclization product related to nevirapine". . p. 771 - 779. Retrieved 1993.
• 2、 -. "LOWCOST, HIGH YIELD SYNTHESIS OF NEVIRAPINE". Page/Page column 16; 17. . Retrieved 2016/12/22.