(1R,12S)-5,8,14-triazatetracyclo[10.3.1.0^{2,11}.0^{4,9}]hexadeca-2(11),3,5,7,9-pentaene

• ChemBase ID: 1136
• Molecular Formular: C13H13N3
• Molecular Mass: 211.26242
• Monoisotopic Mass: 211.11094743
• SMILES: N1C[C@H]2C[C@H](c3c2cc2nccnc2c3)C1
• Canonical SMILES: N1C[C@@H]2C[C@H](C1)c1c2cc2c(c1)nccn2
• InChI: InChI=1S/C13H13N3/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1/h1-2,4-5,8-9,14H,3,6-7H2/t8-,9+
• InChIKey: JQSHBVHOMNKWFT-DTORHVGOSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1R,12S)-5,8,14-triazatetracyclo[10.3.1.0^{2,11}.0^{4,9}]hexadeca-2(11),3,5,7,9-pentaene; (1R,12S)-5,8,14-triazatetracyclo[10.3.1.0^2,^1^1.0^4,^9]hexadeca-2(11),3,5,7,9-pentaene
• IUPAC Traditional name: varenicline; chantix
• Brand Name: Chantix; Champix
• Synonyms: Varenicline tartrate; varenicline; CP-526,555; Varenicline; varenicline 7,8,9,10-tetrahydro- 6,10-methano- 6H-pyrazino (2,3-h)(3) benzazepine

Database IDs

• CAS Number: 249296-44-4
• PubChem SID: 46505502; 160964599
• PubChem CID: 5310966

CALCULATED PROPERTIES

JChem

• LogD (pH = 7.4): -1.2709792
• Log P: 1.007628
• Molar Refractivity: 61.303 cm^3
• Polarizability: 25.210518 Å^3
• Polar Surface Area: 37.81 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): -2.1916635

ALOGPS 2.1

• Log P: 1.39
• LOG S: -3.38
• Solubility (Water): 8.77e-02 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 0.9

Product Information

• Purity: 98%

DETAILS

DrugBank - DB01273

• Drug Groups: approved; investigational
• Description: Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors.
• Indication: For use as an aid in smoking cessation.
• Pharmacology: Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.
• Affected Organisms: Humans and other mammals
• Biotransformation: Metabolism is limited (<10%). Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose.
• Half Life: The elimination half-life of varenicline is approximately 24 hours
• Protein Binding: Less than 20%.
• Elimination: Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2.
• References: Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. [Pubmed] ; Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. [Pubmed] ; Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW: Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121-30. Epub 2005 Oct 12. [Pubmed] ; Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. [Pubmed] ; Kuehn BM: FDA speeds smoking cessation drug review. JAMA. 2006 Feb 8;295(6):614. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Mihalak KB, Carroll FI, Luetje CW: Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. Epub 2006 Jun 9. Pubmed
• Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW: Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121-30. Epub 2005 Oct 12. Pubmed
• Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT: Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005 May 19;48(10):3474-7. Pubmed
• Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR: Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. Pubmed
• Kuehn BM: FDA speeds smoking cessation drug review. JAMA. 2006 Feb 8;295(6):614. Pubmed