WO1992017462A1 - Compose heterocyclique n-cyanoimino - Google Patents

Compose heterocyclique n-cyanoimino Download PDF

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Publication number
WO1992017462A1
WO1992017462A1 PCT/JP1992/000412 JP9200412W WO9217462A1 WO 1992017462 A1 WO1992017462 A1 WO 1992017462A1 JP 9200412 W JP9200412 W JP 9200412W WO 9217462 A1 WO9217462 A1 WO 9217462A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
group
heterocyclic compound
formula
cyanoimino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP1992/000412
Other languages
English (en)
Japanese (ja)
Inventor
Toshihisa Ogawa
Tomomi Ota
Minoru Taguchi
Misa Yoshimura
Katsuo Hatayama
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taisho Pharmaceutical Co Ltd
Original Assignee
Taisho Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Priority to JP04507512A priority Critical patent/JP3136609B2/ja
Publication of WO1992017462A1 publication Critical patent/WO1992017462A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/18—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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/28—Nitrogen atoms not forming part of a nitro radical

Definitions

  • the present invention relates to an N-cyanino heterocyclic compound having a vasodilatory effect.
  • vasodilators such as nitroglycerin, isosorbide dinitrate, diltiazem, verapamil, diphedivine, and nicorandil are known, but none of the compounds of the present invention have a similar structure.
  • the present invention uses the formula — A— ON 0 2 ⁇ ,
  • X represents an oxygen atom or a sulfur atom
  • ⁇ represents an alkylene group having 1 to 5 carbon atoms substituted with an alkylene group having 1 to 5 carbon atoms or a nitroxy group.
  • an alkylene group having 1 to 5 carbon atoms refers to a direct group such as a methylene group, an ethylene group, a trimethylene group, a 1-methylethylene group, a 2-methylethylene group, a tetramethylene group, a benthamethylene group, and the like. It refers to a chain or branched chain.
  • the alkylene group having 1 to 5 carbon atoms substituted by a nitroxy group means that an alkylene group having 1 to 5 carbon atoms is replaced with a 1 ⁇ dinitrooxy group at any position. What is
  • the compound of formula (I) has two types of geometric isomers, anti-type and syn-type, and the present invention includes both anti-type, syn-type, and mixtures thereof.
  • the compound of (I> has the formula
  • X is as defined above, and a compound represented by the formula: . ) Can be produced by reacting the compound represented by the formula (1) in an organic solvent in the presence of a base.
  • the halogen atom means a chlorine atom, a bromine atom or an iodine atom.
  • bases include sodium hydroxide, hydroxide hydroxide, potassium carbonate and other salts, dimethylamine, getylamine, disopropylamine, pyrrolidine, piperidine, piperazine, N-methylpiperazine, Amines such as morpholine, organic metals such as n-butyllithium and lithium diisopropylamide, alcohols such as sodium methoxide and sodium ethoxide, and sodium hydride can be used.
  • reaction temperature is 5 to: L 0 C, and the reaction time is 2 to 5 hours.
  • the compound of formula (I) thus obtained can be converted into a hydrochloride, a nitrate, a P-toluenesulfonate or the like by a conventional method, if necessary.
  • the compounds of the present invention can be administered orally or parenterally in conventional dosage forms.
  • Dosage forms include tablets, capsules, injections, ointments, tablets and the like, all of which can be manufactured by conventional methods.
  • the dosage When used as an antianginal agent or an antihypertensive agent for humans, for example, the dosage varies depending on the condition, administration route and the like, but is usually 20 to Lmg per day.
  • Example 1 2-(: N-cyanomino) -1-3-nitroxetylthiazolidy'C compound 1)
  • Example 1 The following compounds were obtained in substantially the same manner as in Example 1 except that the corresponding compound of the formula (1) was used in place of 2-nitrooxhetylpromide in Example 1 described above.
  • N-dimethylformamide was added 1.32 g (0.055 mol) of sodium hydride at room temperature under a nitrogen stream, and the mixture was stirred for 30 minutes.
  • N-Cyanoyminoxazolidine (5.56 g C, 0.05 mol) dissolved in 10 ml of N-dimethylformamide was added dropwise, and the mixture was further stirred for 1 hour.
  • trooxoshethyl bromide (8.50 g C, 0.05 mol)
  • the mixture was further stirred at the same temperature for 5 hours. Water was added to the reaction solution, and extracted with dichloromethane. The extract was washed with water, dried and concentrated under reduced pressure.
  • Example 2 the following compound was obtained in substantially the same manner as in Example 2, except that the corresponding compound of the formula (BI) was used in place of 2-2-troxoxetyl bromide.
  • the compound of the present invention exhibits a strong vasodilatory effect, has a long lasting property, and has a good absorbability, and is therefore useful as an antianginal agent or an antihypertensive agent.
  • Test Example 1 Vasodilator Fiber:]

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

L'invention concerne un nouveau type de composé présentant une action vasodilatatrice, c'est-à-dire un composé hétérocyclique N-cyanoimino représenté par la formule générale (I) et un sel dudit dérivé. Dans la formule (I) X représente oxygène ou soufre; et A représente alkylène C1 à C5 qui peut être substitué par nitroxy.
PCT/JP1992/000412 1991-04-04 1992-04-03 Compose heterocyclique n-cyanoimino Ceased WO1992017462A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP04507512A JP3136609B2 (ja) 1991-04-04 1992-04-03 Ｎ−シアノイミノ複素環式化合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP3/154214 1991-04-04
JP15421491 1991-04-04

Publications (1)

Publication Number Publication Date
WO1992017462A1 true WO1992017462A1 (fr) 1992-10-15

Family

ID=15579339

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1992/000412 Ceased WO1992017462A1 (fr) 1991-04-04 1992-04-03 Compose heterocyclique n-cyanoimino

Country Status (2)

Country Link
JP (1) JP3136609B2 (fr)
WO (1) WO1992017462A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4427539A1 (de) * 1994-08-04 1996-02-08 Sueddeutsche Kalkstickstoff Verfahren zur Herstellung von 2-Cyaniminothiazolidin
JP3168747B2 (ja) 1993-01-20 2001-05-21 大正製薬株式会社 Ｎ−シアノイミノ複素環式化合物
US6858737B2 (en) 2001-12-28 2005-02-22 Nippon Carbide Kogyo Kabushiki Kaisha Process for producing 2-cyanoimino-1,3-thiazolidine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4832657B1 (fr) * 1969-12-17 1973-10-08
JPS50103326A (fr) * 1974-01-14 1975-08-15

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4832657B1 (fr) * 1969-12-17 1973-10-08
JPS50103326A (fr) * 1974-01-14 1975-08-15

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3168747B2 (ja) 1993-01-20 2001-05-21 大正製薬株式会社 Ｎ−シアノイミノ複素環式化合物
DE4427539A1 (de) * 1994-08-04 1996-02-08 Sueddeutsche Kalkstickstoff Verfahren zur Herstellung von 2-Cyaniminothiazolidin
US6858737B2 (en) 2001-12-28 2005-02-22 Nippon Carbide Kogyo Kabushiki Kaisha Process for producing 2-cyanoimino-1,3-thiazolidine

Also Published As

Publication number Publication date
JP3136609B2 (ja) 2001-02-19

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