[go: up one dir, main page]

WO1983000866A1 - Quinazolines de piperidinyl substitue - Google Patents

Quinazolines de piperidinyl substitue Download PDF

Info

Publication number
WO1983000866A1
WO1983000866A1 PCT/FI1982/000034 FI8200034W WO8300866A1 WO 1983000866 A1 WO1983000866 A1 WO 1983000866A1 FI 8200034 W FI8200034 W FI 8200034W WO 8300866 A1 WO8300866 A1 WO 8300866A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
compounds
hydroxy
reacted
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/FI1982/000034
Other languages
English (en)
Inventor
Oy Orion-Yhtymä
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.)
Orion Oyj
Original Assignee
Orion Yhtyma Oy
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 Orion Yhtyma Oy filed Critical Orion Yhtyma Oy
Priority to FI831585A priority Critical patent/FI831585A7/fi
Publication of WO1983000866A1 publication Critical patent/WO1983000866A1/fr
Priority to DK181083A priority patent/DK181083A/da
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention concerns 2-(4-substitutedpiperidino)- 4-amino-6,7-dimethoxyquinazolines. These new compounds have valuable pharmacological properties.
  • Patents FR 2 350 101 and PR 2 389621 refer to 2-(4-phenylpiperidino)-4-amino-6,7-dimethoxyquinazoline and corresponding compounds, in which the phenyl group is subs tituted with a fluoro or methoxy group.
  • Published patent application PI 80 0481 refers to 2-(4-alkylcarbonylpiperidino)- and 2-(4-cycloalkylcarbonyl- piperidino)-4-amino-6,7-dimethoxyquinazoline.
  • This invention deals with compounds of the formula
  • R is a cycloalkyl containing 3 to 7 carbon atoms, an alkenyl containing 2 to 6 carbon atoms, or a benzyl group.
  • This invention also deals with the methods for the preparation of the compounds with formula I, in which a) a compound with the formula
  • the invention also deals with the compounds of formula II, which are valuable intermediates for the prepara tion of the formula I compounds.
  • the formula I compounds can be used as pharmaceutical agents for the treatment of hypertension.
  • Pormula VI compounds can be pre pared from the corresponding ketones by reduction.
  • 4-(1-nydroxyethyl.)piperidi ⁇ e is l ⁇ fow ⁇ from J. Org. Chem.
  • the method;e -reduction is carried out with hydrogen under about 1 to 7 atm pressure and at about 20 to 100°C using common hydrogenation catalysts such as palladium, platinum or nickel.
  • common hydrogenation catalysts such as palladium, platinum or nickel.
  • Other reducing agents can also be used, e.g. sodium borohydride or aluminium isopropoxide.
  • Example 1 1.3 g of NaBH 4 in 15 ml of water is added at 0 °C toa-solution of 4.7 g (0.026 mol) of 4-cyclopentylcarbonyl- piperidine in 50 ml of methanol. This is stirred for 1 h at 0 °C and for 2 h at 20 °C. The methanol is evaporated off, water is added and the solution is extracted with chloroform and the extract evaporated to dryness. 3.4 g of 4-(1-hydroxy-1-cyclopentylmethyl)piperidine (VI) is obtained; mp. 123 - 5 °C, yield 72 %.
  • Method e 1.2 g of NaBH.in 10 ml of water is added in an ice bath to a solution of 4.35 g (0.01 mol) of 2-(4-cyclohexylcarbonylpiperidino)-4-amino-6,7-dimethoxy- quinazoline hydrochloride and 20 ml of 0.5 N NaOH solution in 80 ml of methanol. The solution is stirred for 1 h at 0 °C and for 18 h at 20 °C. Some of the methanol is removed under reduced pressure, the precipitate formed is filtered off, washed with water and dried. The product is dissolved in acetone and precipitated with gaseous HCl.
  • Method c A solution of 2.4 g (0.01 mol) of 2-chloro- 4-amlno-6,7-dimethoxyquinazoline and 2.0 g (0.01 mol) of 4-(1-hydroxy-1-cyclohexylmethyl)piperidine in 30 ml of iso amyl alcohol is refluxed for 18 h and cooled. The precipitated product is filtered, washed with ether and dried. De sired product is obtained.
  • Method d A solution of 2.5 g (0.01 mol) of S-methyl- N-cyano-N'-(3-,4 dimeth ⁇ xyphenyl)isothioufea and 3.0 g (0.01 mol) or 4-(1-hydroxy-1-cyclohexylmethyl)piperidine in 35 ml of diglycoldimethylether Is refluxed for 5 h and cooled.Water is added to the mixture, followed by extraction with chloroform. The solvent is evaporated off from the extract, and the residue is dissolved in acetone, into which HCl gas is led. Desired product is obtained.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

2-(4-(1-hydroxy-1-méthyle substitué)pipéridino)-4-amino-6,7-diméthoxyquinazolines de formule:$(10,)$dans laquelle R est un cycloalkyle contenant de 3 à 7 atomes de carbone, un alkényle contenant de 2 à 6 atomes de carbone, ou un groupe benzyle. Les composés sont préparés en faisant réagir du méthyl N-(2-cyano-4,5-diméthoxyphényle)(4-(1-hydroxy-1-méthyle substitué)pipéridino)thioformamidate avec du chlorure d'ammonium dans du formamide à environ 120oC. Les composés abaissent la pression artérielle.
PCT/FI1982/000034 1981-09-09 1982-09-03 Quinazolines de piperidinyl substitue Ceased WO1983000866A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
FI831585A FI831585A7 (fi) 1981-09-09 1982-09-03 Menetelmä ja välituote substituoitujen piperidinyyli- kinatsoliinien valmistamiseksi.
DK181083A DK181083A (da) 1981-09-09 1983-04-25 Substituerede piperidinylquinazoliner

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FI812796 1981-09-09
FI812796810909 1981-09-09

Publications (1)

Publication Number Publication Date
WO1983000866A1 true WO1983000866A1 (fr) 1983-03-17

Family

ID=8514689

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI1982/000034 Ceased WO1983000866A1 (fr) 1981-09-09 1982-09-03 Quinazolines de piperidinyl substitue

Country Status (11)

Country Link
EP (1) EP0087456A1 (fr)
JP (1) JPS58501513A (fr)
AU (1) AU8906682A (fr)
DK (1) DK181083A (fr)
ES (1) ES8405389A1 (fr)
FI (1) FI831585A7 (fr)
IT (1) IT1156319B (fr)
NO (1) NO831622L (fr)
PT (1) PT75525B (fr)
WO (1) WO1983000866A1 (fr)
ZA (1) ZA826596B (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3517005A (en) * 1967-10-26 1970-06-23 Pfizer & Co C Certain 2- and 4-substituted quinazolines
DE2720545A1 (de) * 1976-05-07 1977-11-10 Synthelabo Neue chinazolinderivate, ihre herstellung und pharmazeutische mittel
FR2389621A2 (en) * 1977-05-05 1978-12-01 Synthelabo Antihypertensive 4-amino 2-piperidino-quinazoline(s) - prepd. from a 2-halo-quinazoline and a piperidine
DE3003323A1 (de) * 1979-01-31 1980-08-14 Pfizer 4-amino-2-piperidinochinazolin-derivate, verfahren zu ihrer herstellung und solche derivate enthaltende arzneimittel
EP0028473A1 (fr) * 1979-11-01 1981-05-13 Pfizer Inc. Diamino-2,4 quinazolines substituées par un atome de chlore ou un groupe alkoxy et compositions pharmaceutiques les contenant
EP0034471A1 (fr) * 1980-02-19 1981-08-26 Orion-Yhtymä Oy Pipéridinoquinazolines et procédé pour leur préparation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3517005A (en) * 1967-10-26 1970-06-23 Pfizer & Co C Certain 2- and 4-substituted quinazolines
DE2720545A1 (de) * 1976-05-07 1977-11-10 Synthelabo Neue chinazolinderivate, ihre herstellung und pharmazeutische mittel
FR2389621A2 (en) * 1977-05-05 1978-12-01 Synthelabo Antihypertensive 4-amino 2-piperidino-quinazoline(s) - prepd. from a 2-halo-quinazoline and a piperidine
DE3003323A1 (de) * 1979-01-31 1980-08-14 Pfizer 4-amino-2-piperidinochinazolin-derivate, verfahren zu ihrer herstellung und solche derivate enthaltende arzneimittel
EP0028473A1 (fr) * 1979-11-01 1981-05-13 Pfizer Inc. Diamino-2,4 quinazolines substituées par un atome de chlore ou un groupe alkoxy et compositions pharmaceutiques les contenant
EP0034471A1 (fr) * 1980-02-19 1981-08-26 Orion-Yhtymä Oy Pipéridinoquinazolines et procédé pour leur préparation

Also Published As

Publication number Publication date
ES515338A0 (es) 1983-11-01
NO831622L (no) 1983-05-06
EP0087456A1 (fr) 1983-09-07
FI831585L (fi) 1983-05-09
ZA826596B (en) 1983-11-30
DK181083D0 (da) 1983-04-25
PT75525A (en) 1982-10-01
IT8223168A0 (it) 1982-09-08
ES8405389A1 (es) 1983-11-01
DK181083A (da) 1983-04-25
IT1156319B (it) 1987-02-04
PT75525B (en) 1984-12-12
FI831585A0 (fi) 1983-05-09
IT8223168A1 (it) 1984-03-08
FI831585A7 (fi) 1983-05-09
AU8906682A (en) 1983-03-28
JPS58501513A (ja) 1983-09-08

Similar Documents

Publication Publication Date Title
CH653021A5 (fr) Derives piperidino, piperazino et homopiperazino, n-substitues par un groupe heterocyclique aromatique, leur procede de preparation et composition therapeutique les contenant.
JPS6023114B2 (ja) アルキレンジアミンアミド誘導体
EP0187371A2 (fr) Composés de sulfonylisoquinoléine substitués
US5179108A (en) Derivatives of 4-(aminomethyl) piperidine, their preparation and their therapeutic application
DE2639718C2 (de) 1-[6,7-Dimethoxy-3,4-dihydro-2H-isochinolin-1-on-2-yl]-3-[N-methyl-N-(2-(3,4-dimethoxy-phenyl)-äthyl)-amino]-propan, dessen physiologisch verträgliche Säureadditionssalze und diese Verbindungen enthaltende Arzneimittel
EP0014951A2 (fr) Dérivés hétérocycliques d'oxypropanolamine, procédé pour leur préparation et médicaments contenant ces composés
RO118653B1 (ro) Derivati substituiti de benzamidina si procedeu pentru prepararea acestora
KR100234596B1 (ko) 3(2h)-피리다지논 유도체 및 그의 제조방법
EP0144991B1 (fr) Dérivés de polyméthoxybenzyl pipérazine, procédé pour leur préparation et compositions pharmaceutiques contenant ces dérivés
EP0306440A2 (fr) 1-Phényl-1H-imidazoles substitués en C-4 du groupe phényle comme agents cardiovasculaires
DE2830884C2 (fr)
US4673682A (en) Isoquinoline derivatives, pharmaceutical formulations based on these compounds and the use thereof
CA1075264A (fr) Procedes de preparation de derives de benzylalcool
US4147869A (en) 3,4-Dihydrocarbostyril derivatives and process for preparing the same
CS201544B2 (en) Process for preparing derivatives of piperazine
WO1983000866A1 (fr) Quinazolines de piperidinyl substitue
HUT61002A (en) Process for producing 2-aminopyrimdine-4-carboxamide derivatives and pharmaceutical compositions comprising such compounds
US5053409A (en) Aminobenzenesulfonic acid derivatives
US4218479A (en) Novel benzylalcohols and pharmaceutical compositions and use thereof
JPH069565A (ja) イソキノリンスルホン酸アミド化合物
JP3285421B2 (ja) ２−アミノ−ｎ−［［［４−（アミノカルボニル）ピリミジン−２−イル］アミノ］アルキル］ピリミジン−４−カルボキシアミド誘導体、その製造および医薬への応用
US5272157A (en) Derivatives of 4-(aminomethyl) piperidine, their preparation and their therapeutic application
EP0055145B1 (fr) Dérivés de l'acide (aminométhyl)-4 cyclohexane-carboxylique-1
US5162321A (en) 1-naphthyl piperazines useful as 5-HT1A receptor ligands
US4694020A (en) Derivatives of 2-(substituted sulfamyl)-6-nitrobenzoic acids and pharmaceutical compositions

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): AU DK FI HU JP NO SU US

AL Designated countries for regional patents

Designated state(s): AT BE CH DE FR GB LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1982902731

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 831585

Country of ref document: FI

WWP Wipo information: published in national office

Ref document number: 1982902731

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1982902731

Country of ref document: EP