4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzamide

• ChemBase编号: 486
• 分子式: C23H29ClFN3O4
• 平均质量: 465.9454632
• 单一同位素质量: 465.18306232
• SMILES: Clc1cc(C(=O)NC2C(OC)CN(CC2)CCCOc2ccc(F)cc2)c(OC)cc1N
• Canonical SMILES: COC1CN(CCCOc2ccc(cc2)F)CCC1NC(=O)c1cc(Cl)c(cc1OC)N
• InChI: InChI=1S/C23H29ClFN3O4/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29)
• InChIKey: DCSUBABJRXZOMT-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzamide
• IUPAC传统名: cisapride
• 商标名: Acenalin; Alimix; Cipril; Enteropride; Kinestase; Prepulsid; Pridesia; Propulsid; Propulsid Quicksolv; Propulsin; Risamal; Syspride; Prepulsid, Propulsid
• 别名: cisapride; Cisapride

登记号

• CAS号: 81098-60-4
• PubChem SID: 160963949
• PubChem CID: 2769
• ATC码: A03FA02
• CHEMBL: 1729
• Chemspider ID: 2667
• DrugBank ID: DB00604
• IUPHAR配体索引: 240
• KEGG ID: D00274
• 美国药典/FDA物质标识码: UVL329170W
• 维基百科标题: Cisapride
• Medline Plus: a694006

理论计算性质

JChem

• Acid pKa: 14.575678
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): -0.1796145
• LogD (pH = 7.4): 1.5941783
• Log P: 2.4913588
• 摩尔折射率: 122.9349 cm^3
• 极化性: 46.752495 Å^3
• 极化表面积: 86.05 Å^2
• 可自由旋转的化学键: 9
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.95
• LOG S: -4.59
• 溶解度: 1.20e-02 g/l

分子性质

理化性质

• 溶解度: 2.71 mg/L
• 疏水性(logP): 3.3

药理学性质

• 给药途径: oral (tablets), suspension
• 生物利用度: 30-40%
• 排泄: renal, biliary
• 半衰期: 10 hours
• 代谢: hepatic, intestinal
• 蛋白结合率: 97.5%
• 法定药品分级: POM (UK); Rx-only (US); Schedule 4 (Australia); Unscheduled (Australia)
• 妊娠期药物分类: B1 (Australia)

详细说明

DrugBank - DB00604

• Drug Groups: approved; withdrawn; investigational
• Description: In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients.
• Indication: For the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.
• Pharmacology: Cisapride is a parasympathomimetic which acts as a serotonin 5-HT₄ agonist. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Extensively metabolized via cytochrome P450 3A4 enzyme.
• Absorption: Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.
• Half Life: 6-12 hours
• Protein Binding: 97.5%
• References: Pearce RE, Gotschall RR, Kearns GL, Leeder JS: Cytochrome P450 Involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms. Drug Metab Dispos. 2001 Dec;29(12):1548-54. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Pearce RE, Gotschall RR, Kearns GL, Leeder JS: Cytochrome P450 Involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms. Drug Metab Dispos. 2001 Dec;29(12):1548-54. Pubmed