{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}dimethylamine

• ChemBase ID: 976
• Molecular Formular: C17H26ClN
• Molecular Mass: 279.84804
• Monoisotopic Mass: 279.17537752
• SMILES: Clc1ccc(C2(CCC2)C(N(C)C)CC(C)C)cc1
• Canonical SMILES: CC(CC(C1(CCC1)c1ccc(cc1)Cl)N(C)C)C
• InChI: InChI=1S/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3
• InChIKey: UNAANXDKBXWMLN-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: {1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}dimethylamine
• IUPAC Traditional name: sibutramine
• Brand Name: Medaria; Meridia; Reductil; Butramin
• Synonyms: Sibutramina [Spanish]; Sibutraminum [Latin]; Sibutramine

Database IDs

• CAS Number: 106650-56-0
• PubChem SID: 160964439; 46507740
• PubChem CID: 5210

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 0
• LogD (pH = 5.5): 1.7681136
• LogD (pH = 7.4): 2.8568501
• Log P: 5.20185
• Molar Refractivity: 83.9214 cm^3
• Polarizability: 33.18467 Å^3
• Polar Surface Area: 3.24 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.05
• LOG S: -5.47
• Solubility (Water): 9.40e-04 g/l

PROPERTIES

Physical Property

• Solubility: 2.9 mg/mL (in pH 5.2 water)
• Hydrophobicity(logP): 5.2

DETAILS

DrugBank - DB01105

• Drug Groups: illicit; approved; withdrawn; investigational
• Description: Sibutramine (trade name Meridia in the USA, Reductil in Europe and other countries), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. It is a centrally acting stimulant chemically related to amphetamines. Sibutramine is classified as a Schedule IV controlled substance in the United States. In October 2010, Sibutramine was withdrawn from Canadian and U.S. markets due to concerns that the drug increases the risk of heart attack and stroke in patients with a history of heart disease.
• Indication: For the treatment of obesity.
• Pharmacology: Sibutramine is an orally administered agent for the treatment of obesity. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin and norepinephrine reuptake in vivo, but not in vitro. However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vitro and in vivo. In human brain tissue, M1 and M2 also inhibit dopamine reuptake in vitro, but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine. Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT₁, 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2C), norepinephrine (b, b1, b3, a1 and a2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activity in vitro and in vivo.
• Toxicity: Side effects include dry mouth, anorexia, insomnia, constipation and headache.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: Rapid absorption following oral administration. Absolute bioavailability is not known, but at least 77% of a single oral dose of sibutramine is absorbed.
• Half Life: 1.1 hours
• Protein Binding: 97% (to human plasma proteins)
• Elimination: Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme, to desmethyl metabolites, M1 and M2. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M5 and M6. Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. The primary route of excretion for M1 and M2 is hepatic metabolism and for M5 and M6 is renal excretion.
• Clearance: * Oral cl=1750 L/h [oral administration]
• References: Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. [Pubmed] ; Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. [Pubmed] ; Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetham SC: Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine. Int J Obes Relat Metab Disord. 1998 Aug;22 Suppl 1:S18-28; discussion S29. [Pubmed] ; Stock MJ: Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord. 1997 Mar;21 Suppl 1:S25-9. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. Pubmed
• Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. Pubmed
• Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetham SC: Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine. Int J Obes Relat Metab Disord. 1998 Aug;22 Suppl 1:S18-28; discussion S29. Pubmed
• Stock MJ: Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord. 1997 Mar;21 Suppl 1:S25-9. Pubmed