2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaen-10-one

• ChemBase ID: 123
• Molecular Formular: C15H14N4O
• Molecular Mass: 266.29786
• Monoisotopic Mass: 266.11676109
• SMILES: O=c1[nH]c2c(n(C3CC3)c3ncccc13)nccc2C
• Canonical SMILES: Cc1ccnc2c1[nH]c(=O)c1c(n2C2CC2)nccc1
• InChI: InChI=1S/C15H14N4O/c1-9-6-8-17-14-12(9)18-15(20)11-3-2-7-16-13(11)19(14)10-4-5-10/h2-3,6-8,10H,4-5H2,1H3,(H,18,20)
• InChIKey: NQDJXKOVJZTUJA-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^3,^8]pentadeca-1(15),3(8),4,6,11,13-hexaen-10-one; 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one; 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-10-one; 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• IUPAC Traditional name: 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one; nevirapine; @nevirapine
• Brand Name: Viramune
• Synonyms: 11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2’,3’-e][1,4]diazepin-6-one; NSC 641530; Nevarapine; 11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one; Nevirapine; Viramune; BI-RG 587; 11-cyclopropyl-4-methyl-5H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6(11H)-one; NEV; NVP; Nevirapine; 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE; 2-cyclopropyl-7-methyl-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-10-one

Database IDs

• CAS Number: 129618-40-2
• MDL Number: MFCD00866928
• PubChem SID: 46506789; 160963586
• PubChem CID: 4463

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.371185
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 2.3533716
• LogD (pH = 7.4): 2.480226
• Log P: 2.4880428
• Molar Refractivity: 77.482 cm^3
• Polarizability: 28.112658 Å^3
• Polar Surface Area: 58.12 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.75
• LOG S: -3.41
• Solubility (Water): 1.05e-01 g/l

PROPERTIES

Physical Property

• Solubility: 0.7046 mg/L; Chloroform; DMSO: ≥22 mg/mL; Methanol
• Apperance: Off-white to Pale Yellow Solid; white to tan powder
• Melting Point: 247-249°C
• Hydrophobicity(logP): 2.5; 2.65

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• German water hazard class: 2
• Storage Temperature: room temp

Pharmacology Properties

• Mechanism of Action: Non-nucleoside reverse transcriptase inhibitor (NNRTI)

Product Information

• Purity: ≥98% (HPLC); 95%
• Salt Data: Free Base
• Application(s): Used to treat HIV-1 infection and AIDS; Virucide
• Empirical Formula (Hill Notation): C15H14N4O

DETAILS

DrugBank - DB00238

• Drug Groups: approved
• Description: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [PubChem]
• Indication: For use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.
• Pharmacology: Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time.
• Toxicity: Symptoms of overdose include edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonaryinfiltrates, rash, vertigo, vomiting, and weight decrease.
• Affected Organisms: Human Immunodeficiency Virus
• Biotransformation: Hepatic. In vivo studies in humans and in vitro studies with human liver microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 3A4 metabolism to several hydroxylated metabolites.
• Absorption: 90% (absolute bioavailability 93 ± 9%)
• Half Life: 45 hours
• Protein Binding: 60%
• Elimination: Thus cytochrome P450 metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent the primary route of nevirapine biotransformation and elimination in humans. Only a small fraction (<5%) of the radioactivity in urine (representing <3% of the total dose) was made up of parent compound; therefore, renal excretion plays a minor role in elimination of the parent compound.
• Distribution: * 1.21 ± 0.09 L/kg
• External Links: Wikipedia; RxList; Drugs.com

DrugBank - DB08311

Drug information: experimental

Selleck Chemicals - S1742

Research Area: Infection
Biological Activity:
Nevirapine(Viramune) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV-1 infection and AIDS.[1] Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class. [1]

Sigma Aldrich - SML0097

Biochem/physiol Actions
Nevirapine is an allosteric, non-nucleoside inhibitor of HIV reverse transcriptase (NNRTI). The Ki for inhibition of wild-type RT by Nevirapine is 200 nM.

Toronto Research Chemicals - N391275

A potent (IC50=84nM) and selective non-nucleoside inhibitor of HIV-1 reverse transcriptase. Antiviral.

REFERENCES

• http://en.wikipedia.org/wiki/Nevirapine
• Hargrave, K.D., et al.: J. Med. Chem., 34, 2231 (1991)
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• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 1393
• Grozinger, K.G. et al., J. Het. Chem., 1995, 32, 259, (synth)
• Pedersen, O.S. et al., Synthesis, 2000, 479-495, (rev)