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

• ChemBase ID: 486
• Molecular Formular: C23H29ClFN3O4
• Molecular Mass: 465.9454632
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzamide
• IUPAC Traditional name: cisapride
• Brand Name: Acenalin; Alimix; Cipril; Enteropride; Kinestase; Prepulsid; Pridesia; Propulsid; Propulsid Quicksolv; Propulsin; Risamal; Syspride; Prepulsid, Propulsid
• Synonyms: cisapride; Cisapride

Database IDs

• CAS Number: 81098-60-4
• PubChem SID: 160963949
• PubChem CID: 2769
• ATC CODE: A03FA02
• CHEMBL: 1729
• Chemspider ID: 2667
• DrugBank ID: DB00604
• IUPHAR ligand ID: 240
• KEGG ID: D00274
• Unique Ingredient Identifier: UVL329170W
• Wikipedia Title: Cisapride
• Medline Plus: a694006

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.575678
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): -0.1796145
• LogD (pH = 7.4): 1.5941783
• Log P: 2.4913588
• Molar Refractivity: 122.9349 cm^3
• Polarizability: 46.752495 Å^3
• Polar Surface Area: 86.05 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.95
• LOG S: -4.59
• Solubility (Water): 1.20e-02 g/l

PROPERTIES

Physical Property

• Solubility: 2.71 mg/L
• Hydrophobicity(logP): 3.3

Pharmacology Properties

• Admin Routes: oral (tablets), suspension
• Bioavailability: 30-40%
• Excretion: renal, biliary
• Half Life: 10 hours
• Metabolism: hepatic, intestinal
• Protein Bound: 97.5%
• Legal Status: POM (UK); Rx-only (US); Schedule 4 (Australia); Unscheduled (Australia)
• Pregnancy Category: B1 (Australia)

DETAILS

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• Drug Groups: approved; withdrawn; investigational
• Description: In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias.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

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