Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
  • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
  • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
  • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
  • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/06—Antiarrhythmics

Definitions

• 2-[2-[(4-Methoxybenzoyl)amino]phenyl]ethyl]-1-methyl-1- alkylpiperidinium halides and 2-[2-[(4-methoxybenzoyl)amino]- phenyl]ethyl]-1-methyl-1-benzylpiperidinium halides are heterocyclic carbon compounds of the quaternary piperidinium series having an additional ring and having nitrogen attached indirectly to the piperidine ring by non-ionic bonding (Class 546, Subclass 229).
• encainide is an antiarrhythmic compound which is also referred to in the literature as MJ 9057 (USAN And The USP Dictionary of Drug Names 1980, page 122, United States Pharmacopeial Convention, Inc., 12501 Twinbrook Parkway, Rockville, MD 20852, Library of Congress Catalog Card No. 72-88571).
• Encainide has structural formula I
• N-oxide derivative of encainide as an anti arrhythmic agent is the subject of a co-pending application Serial No. 160,900 filed June 19, 1980.
• the present invention is concerned with quaternary piperidinium halides which have structural formula II , where R is lower alkyl of 1 -4 carbon atoms inclusive or benzyl and X is halide such as chlorine, bromine, iodine.
• the process used for preparation of compounds of formula II in the present invention involves heating approximately stoichiometric quantities of encainide (I) and R-X, (where R is lower alky! of 1-4 carbon atoms inclusive or benzyl; and X is halide such as chlorine, bromine, iodine) in a suitable organic solvent at reflux for a period of time ranging from 6 to 24 hours.
• Acetone is a preferred solvent for carrying out the process although other solvents employed in forming quaternary ammonium salts such as acetonitrile, benzene, chloroform, methanol, dichloroethane, and others are generally operable.
• the solvent is evaporated and the reaction residue distributed between HpO and benzene.
• Toxicity ALD 50 50-100 mg/kg >2000 mg/kg >1000 mg/kg
• ATD 50 (1) 5-10 mg/kg 250 mg/kg 125-250 mg/kg
• ALD 50 is the approximate lethal dose for half the animals
• ATD 50 is the approximate lowest dose where signs of physiologic or neurologic deficit appear.
• the nuclear magnetic resonance (NMR) values refer to chemical shifts (6) expressed as parts per million (ppm) versus tetramethylsilane as reference standard.
• the relative area reported for the various shifts corresponds to the number of hydrogen atoms in the individual substituent and the nature of the shift as to multiplicity is reported as broad singlet (bs), singlet (s), or multiplet (m).
• the format is NMR (solvent): ⁇ (relative area, multiplicity).
• the infrared (IR) was measured on a disperson of the solid material in crystalline potassium bromide. The wave numbers of significant absorption maxima are listed.
• IR 768, 1175, 1255, 1310, 1490, 1500, 1608, 1650, 2940,
• IR 770, 1170, 1255, 1312, 1500, 1610, 1655, 2950, 3220 cm -1 .

Landscapes

• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Cardiology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Medicinal Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Heart & Thoracic Surgery (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Hydrogenated Pyridines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (1)

Family

ID=22860396

Family Applications (1)

Country Status (19)

Cited By (5)

Citations (3)

• 1981
  • 1981-01-28 US US06/229,244 patent/US4321386A/en not_active Expired - Lifetime
• 1982
  • 1982-01-27 GB GB08220076A patent/GB2100736B/en not_active Expired
  • 1982-01-27 WO PCT/US1982/000108 patent/WO1982002551A1/en not_active Ceased
  • 1982-01-27 AT AT0900782A patent/AT378183B/de active
  • 1982-01-27 AU AU81485/82A patent/AU551523B2/en not_active Ceased
  • 1982-01-27 JP JP57500784A patent/JPH0348904B2/ja not_active Expired - Lifetime
  • 1982-01-27 CH CH5828/82A patent/CH651021A5/de not_active IP Right Cessation
  • 1982-01-27 DE DE823223499T patent/DE3223499T1/de active Granted
  • 1982-01-28 BE BE0/207171A patent/BE891938A/fr not_active IP Right Cessation
  • 1982-01-28 NL NL8220049A patent/NL8220049A/nl unknown
  • 1982-01-28 CA CA000395068A patent/CA1184917A/en not_active Expired
  • 1982-01-28 YU YU197/82A patent/YU43063B/xx unknown
  • 1982-01-28 IE IE191/82A patent/IE52420B1/en unknown
  • 1982-01-28 AR AR288281A patent/AR230266A1/es active
  • 1982-01-28 GR GR67146A patent/GR74720B/el unknown
  • 1982-01-28 IT IT47667/82A patent/IT1147809B/it active
  • 1982-07-08 FI FI822443A patent/FI65239C/fi not_active IP Right Cessation
  • 1982-09-27 DK DK429382A patent/DK156649C/da not_active IP Right Cessation
  • 1982-09-28 SE SE8205535A patent/SE435057B/sv not_active IP Right Cessation

Patent Citations (3)

Non-Patent Citations (2)

Also Published As

Similar Documents

Legal Events