915-30-0

Basic information

• Product Name: Diphenoxylate
• Synonyms: DIPHENOXYLATE;1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylicacidethylester;1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylicaciethyl;1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecoticacidethylester;1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecoticacidethylester;1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecoticaciethylester;2,2-diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile;ethyl1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate
• CAS NO: 915-30-0
• Molecular Formula: C₃₀H₃₂N₂O₂
• Molecular Weight: 452.59
• EINECS: 213-020-1
• Mol File: 915-30-0.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 602.3 °C at 760 mmHg
• Flash Point: 318 °C
• Appearance: /
• Density: 1.123 g/cm³
• PKA: pKa 7.1 (Uncertain)
• CAS DataBase Reference: Diphenoxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Diphenoxylate(915-30-0)
• EPA Substance Registry System: Diphenoxylate(915-30-0)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28-42/43
• Safety Statements: 22-26-45
• Hazardous Substances Data: 915-30-0(Hazardous Substances Data)

Usage

Uses

This drug is a structural analog of meperidine and loperamide; however, it practically duplicates all of the pharmacological properties of loperamide. Being analogous to loperamide, it is mainly used for treating diarrhea. Synonyms for this drug are fentanest, leprofen, and others.

Indications

Diphenoxylate (marketed in combination with atropine as Lomotil in the United States) is chemically related to both analgesic and anticholinergic compounds. It is as effective in the treatment of diarrhea as the opium derivatives, and at the doses usually employed, it has a low incidence of central opioid actions. Diphenoxylate is rapidly metabolized by ester hydrolysis to the biologically active metabolite difenoxylic acid.

Definition

ChEBI: A piperidinecarboxylate ester that is the ethyl ester of difenoxin.

Brand name

Diarphem;Diarsed-neomycin;Diatro;Eldox;Logen;Lomanate;Lomax;Lomotil liquid;Lonox;Protector;Reasec;Saleton;Sedistal.

World Health Organization (WHO)

Diphenoxylate, a derivative of pethidine without analgesic activity, is used in the symptomatic treatment of acute and chronic diarrhoea to reduce intestinal motility. There is no clear evidence that it has any beneficial effect in diminishing fluid losses and it has been associated with central nervous system toxicity, particularly in children, which results in anorexia, nausea and vomiting, headache, drowsiness, confusion, insomnia, dizziness, restlessness, euphoria and depression. The World Health Organization recommends that diphenoxylate should not be used for the management of diarrhoea in children and many countries have since withdrawn products containing this compound indicated for paediatric use. (Reference: (WHORUD) The Rational Use of Drugs, , , 1990)

General Description

Diphenoxylate is a weak opioid agonist and isavailable combined with atropine (Lomotil) for use as an antidiarrhealagent. At low doses, the opioid effect is minimal,and the atropine is added to dissuade abuse. One studyfound both codeine and loperamide to be superior to diphenoxylatefor treating chronic diarrhea.83 The manufacturerhas strict dosing guidelines for pediatric use because opioidintoxication and deaths from diphenoxylate have beenreported.

Clinical Use

Lomotil is recommended as adjunctive therapy in the management of diarrhea. It is contraindicated in children under 2 years old and in patients with obstructive jaundice.

Side effects

Adverse reactions often caused by the atropine in the preparation include anorexia, nausea, pruritus, dizziness, and numbness of the extremities.

Synthesis

Diphenoxylate, ethyl ester of 1-(3-cyano-3,3-diphenylpropyl)- 4-phenylpiperidine-4-carboxylic acid (3.1.58), is also a drug of 4-phenylpiperidine series. In practice there are two ways of making it. The first way is by the alkylation of the ethyl ester of 4-phenylpiperidine-4-carboxylic acid (3.1.56) with 2,2-diphenyl-4-bromobutyronitrile, which in turn is synthesized from 1-benzyl-4-phenyl-4-cyanopiperidine. The product undergoes ethanolysis in the presence of acid, followed by benzylation. The second way is a synthesis accomplished by alkylation of diphenylacetonitrile using ethyl ester of 1-(2-chloroethyl)-4-phenylpiperidine-4-carboxylic acid (3.1.57), which is synthesized by reaction of ethyl ester of 4-phenylpiperidine-4-carboxylic acid with β-chloroethanol or ethylenoxide with the subsequent substitution of hydroxyl group, which results from the opening of the epoxide ring, by chlorine via action of thionyl chloride [37,38].

InChI:InChI=1/C30H32N2O2/c1-2-34-28(33)29(25-12-6-3-7-13-25)18-21-32(22-19-29)23-20-30(24-31,26-14-8-4-9-15-26)27-16-10-5-11-17-27/h3-17H,2,18-23H2,1H3

Relevant articles and documents

Combination of selected opioids with muscarine antagonists for treating urinary incontinence

Active compound combinations of compounds of group A, particularly opioids, and compounds of group B, particularly anti-muscarine agents and other substances suitable for treatment of an increased urge to urinate or urinary incontinence. Related pharmaceutical formulations and methods of treatment of an increased urge to urinate or urinary incontinence are also provided.