5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide

• ChemBase ID: 4419
• Molecular Formular: C22H21Cl3N4O
• Molecular Mass: 463.78734
• Monoisotopic Mass: 462.07809435
• SMILES: Clc1c(n2nc(C(=O)NN3CCCCC3)c(c2c2ccc(Cl)cc2)C)ccc(Cl)c1
• Canonical SMILES: Clc1ccc(cc1)c1c(C)c(nn1c1ccc(cc1Cl)Cl)C(=O)NN1CCCCC1
• InChI: InChI=1S/C22H21Cl3N4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)
• InChIKey: JZCPYUJPEARBJL-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
• IUPAC Traditional name: rimonabant
• Brand Name: Acomplia; Riobant; Slimona; Rimoslim; Zimulti
• Synonyms: 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; SR141716; SR 141716; SR 141716A; SR141716A; rimonabant; Rimonabant; Rimonabant (SR141716)

Database IDs

• CAS Number: 158681-13-1; 168273-06-1
• MDL Number: MFCD04034714
• PubChem SID: 99443236; 160967851
• PubChem CID: 104850

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.421862
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 5.9079313
• LogD (pH = 7.4): 5.907993
• Log P: 5.9079976
• Molar Refractivity: 122.8308 cm^3
• Polarizability: 48.45934 Å^3
• Polar Surface Area: 50.16 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.47
• LOG S: -5.36
• Solubility (Water): 2.00e-03 g/l

PROPERTIES

Safety Information

• Storage Warning: IRRITANT
• TSCA Listed: false

Pharmacology Properties

• Target: Cannabinoid Receptor

Product Information

• Purity: 95+%; 97%
• Salt Data: Free Base

DETAILS

DrugBank - DB06155

• Drug Groups: approved; investigational
• Description: Rimonabant is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States. This decision was made after a U.S. advisory panel recommended the medicine not be approved because it may increase suicidal thinking and depression.
• Indication: For use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m^2, or patients wih a BMI greater than 27 kg/m^2 with associated risk factors, such as type 2 diabetes or dyslipidaemia.
• Pharmacology: In the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day). Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo.
• Toxicity: Almost twice as many people discontinued rimonabant compared with placebo because of adverse events (13.8% vs. 7.2%). These consistently involved psychiatric disorders (8.5% vs. 3.2%), including depression and anxiety. Other common side effects included insomnia, nausea, vomiting, diarrhoea and fatigue.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, CYP3A4 involved.
• Absorption: Undetermined
• Half Life: 6 to 9 days with normal BMI and 16 days if BMI is greater than 30
• Protein Binding: Almost 100%
• References: Gelfand EV, Cannon CP: Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs. 2006 Mar;15(3):307-15. [Pubmed] ; Xie S, Furjanic MA, Ferrara JJ, McAndrew NR, Ardino EL, Ngondara A, Bernstein Y, Thomas KJ, Kim E, Walker JM, Nagar S, Ward SJ, Raffa RB: The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism--or inverse agonism--as potential obesity treatment and other therapeutic use. J Clin Pharm Ther. 2007 Jun;32(3):209-31. [Pubmed] ; Cahill K, Ussher M: Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005353. [Pubmed] ; Maldonado R, Valverde O, Berrendero F: Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 2006 Apr;29(4):225-32. Epub 2006 Feb 17. [Pubmed] ; Deadwyler SA, Goonawardena AV, Hampson RE: Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol. 2007 Sep;18(5-6):571-80. [Pubmed] ; Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA: Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. [Pubmed]
• External Links: Wikipedia; Drugs.com

REFERENCES

• Gelfand EV, Cannon CP: Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs. 2006 Mar;15(3):307-15. Pubmed
• Xie S, Furjanic MA, Ferrara JJ, McAndrew NR, Ardino EL, Ngondara A, Bernstein Y, Thomas KJ, Kim E, Walker JM, Nagar S, Ward SJ, Raffa RB: The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism--or inverse agonism--as potential obesity treatment and other therapeutic use. J Clin Pharm Ther. 2007 Jun;32(3):209-31. Pubmed
• Cahill K, Ussher M: Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005353. Pubmed
• Maldonado R, Valverde O, Berrendero F: Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 2006 Apr;29(4):225-32. Epub 2006 Feb 17. Pubmed
• Deadwyler SA, Goonawardena AV, Hampson RE: Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol. 2007 Sep;18(5-6):571-80. Pubmed
• Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA: Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. Pubmed