5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1H,2H,3H,4H,5H-pyrido[4,3-b]indol-1-one

• ChemBase编号: 844
• 分子式: C17H18N4O
• 平均质量: 294.35102
• 单一同位素质量: 294.14806122
• SMILES: O=C1N(CCc2n(c3c(c12)cccc3)C)Cc1nc[nH]c1C
• Canonical SMILES: O=C1N(CCc2c1c1ccccc1n2C)Cc1nc[nH]c1C
• InChI: InChI=1S/C17H18N4O/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19)
• InChIKey: JSWZEAMFRNKZNL-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1H,2H,3H,4H,5H-pyrido[4,3-b]indol-1-one
• IUPAC传统名: lotronex
• 商标名: Lotronex
• 别名: Alosetron HCl; Alosetron

登记号

• CAS号: 122852-42-0
• PubChem SID: 46506274; 160964307
• PubChem CID: 2099

理论计算性质

JChem

• Acid pKa: 13.315839
• 质子受体: 2
• 质子供体: 1
• LogD (pH = 5.5): 0.3275648
• LogD (pH = 7.4): 1.1223476
• Log P: 1.2119008
• 摩尔折射率: 86.4054 cm^3
• 极化性: 33.097813 Å^3
• 极化表面积: 53.92 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.85
• LOG S: -2.83
• 溶解度: 4.38e-01 g/l

分子性质

理化性质

• 疏水性(logP): 2

详细说明

DrugBank - DB00969

• Drug Groups: approved; withdrawn
• Description: Alosetron is a 5-HT3 antagonist used only for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) in women. Alosetron has an antagonist action on the 5-HT3 receptors and thus may modulate serotonin-sensitive gastrointestinal (GI) processes. Alosetron was voluntarily withdrawn from the US market in November 2000 by the manufacturer due to numerous reports of severe adverse effects including ischemic colitis, severely obstructed or ruptured bowel, and death. In June 2002, the FDA approved a supplemental new drug application allowing the remarketing of the drug under restricted conditions of use.
• Indication: Only for the treatment of symptoms of severe diarrhea-predominant irritable bowel syndrome (IBS) in women with chronic symptoms (generally lasting greater than 6 months) who does not present with anatomic or biochemical GI abnormalities and have not responded to conventional therapy.
• Pharmacology: Alosetron is a potent and selective antagonist of the serotonin 5-HT₃ receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, via microsomal cytochrome P450 (CYP)
• Absorption: 50-60 %
• Half Life: 1.5 hours
• Protein Binding: 82%
• Elimination: Renal elimination of unchanged alosetron accounts for only 6% of the dose. Alosetron is extensively metabolized in humans.
• Distribution: * 65 to 95 L
• Clearance: * 600 mL/min
• References: Andresen V, Hollerbach S: Reassessing the benefits and risks of alosetron: what is its place in the treatment of irritable bowel syndrome? Drug Saf. 2004;27(5):283-92. [Pubmed] ; Camilleri M: Pharmacology and clinical experience with alosetron. Expert Opin Investig Drugs. 2000 Jan;9(1):147-59. [Pubmed] ; Mayer EA, Bradesi S: Alosetron and irritable bowel syndrome. Expert Opin Pharmacother. 2003 Nov;4(11):2089-98. [Pubmed] ; Rahimi R, Nikfar S, Abdollahi M: Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther. 2008 May;30(5):884-901. [Pubmed] ; Lewis JH: Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and efficacy in perspective. Expert Rev Gastroenterol Hepatol. 2010 Feb;4(1):13-29. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Andresen V, Hollerbach S: Reassessing the benefits and risks of alosetron: what is its place in the treatment of irritable bowel syndrome? Drug Saf. 2004;27(5):283-92. Pubmed
• Camilleri M: Pharmacology and clinical experience with alosetron. Expert Opin Investig Drugs. 2000 Jan;9(1):147-59. Pubmed
• Mayer EA, Bradesi S: Alosetron and irritable bowel syndrome. Expert Opin Pharmacother. 2003 Nov;4(11):2089-98. Pubmed
• Rahimi R, Nikfar S, Abdollahi M: Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther. 2008 May;30(5):884-901. Pubmed
• Lewis JH: Alosetron for severe diarrhea-predominant irritable bowel syndrome: safety and efficacy in perspective. Expert Rev Gastroenterol Hepatol. 2010 Feb;4(1):13-29. Pubmed