WO1982000824A1 - 1h and 2h indazol derivatives and medicaments containing them - Google Patents

1h and 2h indazol derivatives and medicaments containing them Download PDF

Info

Publication number
WO1982000824A1
WO1982000824A1 PCT/EP1980/000094 EP8000094W WO8200824A1 WO 1982000824 A1 WO1982000824 A1 WO 1982000824A1 EP 8000094 W EP8000094 W EP 8000094W WO 8200824 A1 WO8200824 A1 WO 8200824A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
indazole
amino
formula
imidazolin
Prior art date
Application number
PCT/EP1980/000094
Other languages
German (de)
English (en)
French (fr)
Inventor
Ag Siegfried
Original Assignee
Geissmann F
Molnar I
Jahn U
Thiele K
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 Geissmann F, Molnar I, Jahn U, Thiele K filed Critical Geissmann F
Priority to PCT/EP1980/000094 priority Critical patent/WO1982000824A1/en
Priority to JP55502109A priority patent/JPS57501378A/ja
Priority to EP80105327A priority patent/EP0047328B1/de
Priority to US06/375,116 priority patent/US4436913A/en
Publication of WO1982000824A1 publication Critical patent/WO1982000824A1/en
Priority to US06/530,145 priority patent/US4526898A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the invention relates to 1H and 2H indazole derivatives of the formula
  • R1 is hydrogen, a lower alkyl, a lower aralkyl or an aryl group and is bonded to one of the two nitrogen atoms in the 1- or 2-position, the aryl group and the aryl part of the aralkyl group being identical or different, identical or different, to a radical R4 can be substituted R2 and
  • R3 are identical or different from each other and are hydrogen, halogen, the hydroxyl group, a lower alkyl group, a lower alkoxy group or a lower alkylthio group, and
  • R the same or different from each other is a halogen atom or one of the secondary or tertiary amino groups
  • radicals R or R4 are one of the aforementioned secondary or tertiary amino groups and R for the 1H-indazole derivatives only in the 4- or 7-position also mean one of the secondary or tertiary amino groups mentioned can if the radical R1 is simultaneously an aryl or aralkyl group, and where R5 is hydrogen, the hydroxyl group or a lower alkyl or alkoxy group.
  • the invention further relates to the use of the substances mentioned above as blood pressure-lowering active ingredients for the manufacture of medicaments for veterinary and human medicine.
  • lower in connection with alkyl groups or alkyl parts in other groups, especially in the alkoxy and aralkyl groups, denotes alkyl groups or alkyl parts with up to 6 carbon atoms, whereby these alkyls can also be cycloalkyls. In this context, however, the term “lower” preferably denotes saturated, branched or unbranched acyclic hydrocarbon residues with a total of up to 4 carbon atoms.
  • radical R tautomerism is observed for the 2-imidazolin-2-yl derivatives and the imidazolidine derivatives as well as for the 3,4,5,6-tetrahydropyrimidine derivatives and the hexahydropyrimidine derivatives.
  • the radical R is preferably a 2-imidazolin-2-yl-amino group (or its tautomer) or a chlorine atom, the radical R4 in the latter case being a 2-imidazolin-2-yl-phenyl or is benzyl group.
  • the radical R1 is preferably the methyl group or an optionally substituted benzyl group, while the radicals R2 and R3 preferably each represent a hydrogen atom.
  • the indazoles of the formula I can be prepared by a wide variety of processes.
  • a process for the preparation of the indazoles of the formula I is that when R is not halogen, a correspondingly substituted indazole which has an amino group in the position of the benzene ring in which the radical R is to be introduced carries, with a compound of formula
  • X is a group which can be split off with hydrogen under condensation conditions, preferably a halogen, in particular chlorine
  • Ac is an acyl group, preferably a lower alkyl acyl group or a substituted or unsubstituted phenylacyl group.
  • Q means the ethylene or propylene group.
  • a compound of the formula Ha is used as the starting substance for this condensation, it is preferably used in the form of the free base in the presence of a polar or non-polar solvent. Alcohols, ethers or chlorinated hydrocarbons are used as solvents. The condensation is carried out in the temperature range between room temperature and approx. 150 ° C. The product which precipitates as such or in the form of its salt is separated off and worked up.
  • the substance of the formula IIa is preferably used as a salt and the condensation is carried out in methanol or ethanol at elevated temperature. If the condensation is carried out with a substance of the formula IIb, it is possible in particular to work in a solution or suspension of the amine, preferably in POCl 3 . The condensation is carried out at elevated temperature, specifically when using POCl 3 at temperatures up to the boiling point of POCl 3 . The acetyl compound of the end product is obtained, which is then converted into the compound of the formula I in acetic acid or methanol.
  • a second process for the preparation of the substances of the formula I has the characteristic feature of the formation of the imidazoline, imidazolidine or pyrimidine ring in situ.
  • a diamine of the formula H 2 NQ-NH 2 in which Q is the ethylene or propylene group, is reacted as a free base or in the form of a monoacid addition salt with an appropriately substituted indazole which, in the position in which the radical R to be introduced, either a cyanamino group, a group
  • the indazole ring system preferably carries an isothiuronium amino group of the formula where the substituent R is to be introduced
  • the halide is preferably iodide.
  • the ring closure condensation is carried out in an inert solvent in the temperature range from about 40 to 210 ° C., for example in methanol or dioxane.
  • the substituent on the indazole ring system is the cyanamino group, the reaction in aliphatic alcohols, ether or aliphatic hydrocarbons takes place at elevated temperatures in the range from about 60 to 220 ° C.
  • reaction product obtained by one of these process variants can be separated off in a conventional manner and purified by recrystallization.
  • the radical R if this represents one of the secondary or tertiary amino groups, can finally be introduced in such a way that the grouping at the point on the indazole ring intended for the radical R is first the grouping is introduced, in which group the sulfur can also be replaced by an oxygen atom and Q in turn means the ethylene or propylene group, and the ring-closing condensation is then carried out on this group.
  • the reaction is preferably carried out in a polar solvent, for example dimethylformamide, methanol, ethanol or water at moderately elevated temperatures in the range from about 30 to 160 ° C. in the presence of basic substances such as, for example, alkali metal hydroxides.
  • the product hydrochloride After standing for three days at 20 ° C, the product hydrochloride has completely failed. The product is filtered off and recrystallized from isopropanol. The recrystallized hydrochloride has a melting point of 270 to 271 ° C and is obtained with a yield of 60%.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/EP1980/000094 1980-09-05 1980-09-05 1h and 2h indazol derivatives and medicaments containing them WO1982000824A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
PCT/EP1980/000094 WO1982000824A1 (en) 1980-09-05 1980-09-05 1h and 2h indazol derivatives and medicaments containing them
JP55502109A JPS57501378A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1980-09-05 1980-09-05
EP80105327A EP0047328B1 (de) 1980-09-05 1980-09-05 1H- und 2H-Indazolderivate und diese enthaltendes Arzneimittel
US06/375,116 US4436913A (en) 1980-09-05 1980-09-05 1H- and 2H- indazole derivatives
US06/530,145 US4526898A (en) 1980-09-05 1983-09-07 Antihypertensive 4-(2-imidazolin-2-yl-amino)-2-methyl-indazole

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
WOEP80/00094800905 1980-09-05
PCT/EP1980/000094 WO1982000824A1 (en) 1980-09-05 1980-09-05 1h and 2h indazol derivatives and medicaments containing them
EP80105327A EP0047328B1 (de) 1980-09-05 1980-09-05 1H- und 2H-Indazolderivate und diese enthaltendes Arzneimittel

Publications (1)

Publication Number Publication Date
WO1982000824A1 true WO1982000824A1 (en) 1982-03-18

Family

ID=26069259

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1980/000094 WO1982000824A1 (en) 1980-09-05 1980-09-05 1h and 2h indazol derivatives and medicaments containing them

Country Status (4)

Country Link
US (1) US4436913A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
EP (1) EP0047328B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
JP (1) JPS57501378A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
WO (1) WO1982000824A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4526898A (en) * 1980-09-05 1985-07-02 Siegfried Aktiengesselschaft Antihypertensive 4-(2-imidazolin-2-yl-amino)-2-methyl-indazole
US5478858A (en) * 1993-12-17 1995-12-26 The Procter & Gamble Company 5-(2-imidazolinylamino) benzimidazole compounds useful as alpha-2 adrenoceptor agonists
ES2150546T3 (es) * 1993-12-17 2000-12-01 Procter & Gamble Compuestos de 6-(2-imidazolinilamino)quinoxalina utiles como agonistas de alfa-2-adrenoceptores.
US5578607A (en) * 1993-12-17 1996-11-26 The Procter & Gamble Company 6-(2-imidazolinylamino)quinoline compounds useful as alpha-2 adrenoceptor agonists
US5576437A (en) * 1993-12-17 1996-11-19 The Procter & Gamble Company 7-(2-imidazolnylamino) quinoline compounds useful as alpha-2 adrenoceptor agonists
EP0736020B1 (en) * 1993-12-17 2000-04-26 The Procter & Gamble Company 6-(2-imidazolinylamino)quinoline compounds useful as alpha-2 adrenoceptor agonists
US5916900A (en) 1995-06-29 1999-06-29 The Procter & Gamble Company 7-(2-imidazolinylamino)quinoline compounds useful as alpha-2 adrenoceptor agonists
US6486190B1 (en) 1997-11-24 2002-11-26 The Procter & Gamble Company 5-(2-imidazolinylamino)-benzimidazole derivatives, their preparation and their use as .alpha.-adrenoceptor agonists with improved metabolic stability
TW200302722A (en) * 2002-02-13 2003-08-16 Astrazeneca Ab Therapeutic agents
ITMI20062230A1 (it) * 2006-11-22 2008-05-23 Acraf Composto 2-alchil-indazolico procedimento per preparalo e composizione farmaceutica che lo comprende
PL212581B1 (pl) * 2007-12-05 2012-10-31 Akademia Medyczna W Gdansku Nowe pochodne 1-[(imidazolidyn-2-ylo)imino)]indazolu, sposób ich otrzymywania, zastosowanie i zwiazki posrednie
DK3027605T3 (en) 2013-07-31 2018-01-22 Council Scient Ind Res Hitherto UNKNOWN INDAZOL RELATIONS AND PROCEDURES FOR PREPARING IT

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3847934A (en) * 1971-12-01 1974-11-12 Wander Ag Dr A 7-(imidazolinyl-(2)-amino)-indazoles
CH579076A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * 1973-04-05 1976-08-31 Wander Ag Dr A
US4036976A (en) * 1973-04-05 1977-07-19 Sandoz, Inc. Substituted imidazolinylamino-indazoles

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2653005A1 (de) * 1975-12-03 1977-06-08 Sandoz Ag Neue organische verbindungen, ihre verwendung und herstellung

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3847934A (en) * 1971-12-01 1974-11-12 Wander Ag Dr A 7-(imidazolinyl-(2)-amino)-indazoles
CH579076A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * 1973-04-05 1976-08-31 Wander Ag Dr A
US4036976A (en) * 1973-04-05 1977-07-19 Sandoz, Inc. Substituted imidazolinylamino-indazoles

Also Published As

Publication number Publication date
US4436913A (en) 1984-03-13
JPS57501378A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1982-08-05
EP0047328A1 (de) 1982-03-17
EP0047328B1 (de) 1984-05-09

Similar Documents

Publication Publication Date Title
DE69110320T2 (de) Stickstoff enthaltende heterozyklische Verbindungen, ihre Herstellung und Verwendung.
EP0129128B1 (de) 2-Pyrimidinyl-l-piperazin-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
EP0384370B1 (de) Substituierte Pyrimidin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Tool
DE1445151A1 (de) Verfahren zur Herstellung chemischer Verbindungen
DD150609A5 (de) Verfahren zur herstellung von pyrimidin-verbindungen
DE2139526A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
DE69024778T2 (de) 2-Aminopyrimidin-4-carboxamid-Derivate, deren Herstellung und deren therapeutische Anwendung
EP0047328B1 (de) 1H- und 2H-Indazolderivate und diese enthaltendes Arzneimittel
EP0000220B1 (de) Dihydrouracile, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel
DE2849537A1 (de) Substituierte 5-(2-imidazolin-2-yl)- aminopyrimidine und verfahren zu deren herstellung
DE2165056C3 (de) Verfahren zur Herstellung von CMnazollnonen
DE2205745A1 (de) Neue durch den n-cyaniminorest substituierten heterocyclen und verfahren zu ihrer herstellung
EP0093252B1 (de) Thiomethylpyridin-Derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE3011809A1 (de) Pyrimidyl-chinazoline, verfahren zu ihrer herstellung, sie enthaltende pharmazeutische praeparate und ihre verwendung
DE69400692T2 (de) Substituierte Piperazine, ihre Verfahrensherstellung und die enthaltenen pharmazeutischen Zusammenfassungen
DE1927759A1 (de) Neue basische Derivate des Benzoxazolin-2-ons und Verfahren zur Herstellung derselben
DE3133302A1 (de) Isoindolin-2-yl-amino-imidazoline und isoindolin-2-yl-guanidine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
CH641782A5 (en) 1H- and 2H-indazole derivatives
DE69104797T2 (de) 2-Substituierte-1-Hydroxyindole.
DE2030314A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
DE2051013A1 (de) 1,2-Dihydropyrido eckige Klammer auf 2,3-d eckige Klammer zu pyrimidin-2-one und Verfahren zu deren Herstellung
DE2511599B2 (de) 3,7-Dihydro-5-phenyl-6-methyl- pyrrole [3,4-e] [1,4] gleich diazepin-2 (lH)-one, Verfahren zu ihrer Herstellung und Arzneimittel
EP0144892B1 (de) Bisamidindiphenylderivate, ein Verfahren zu ihrer Herstellung und ihre Verwendung als chemotherapeutika
EP0113911B1 (de) Pyrido-triazolochinazoline, ihre Herstellung und Verwendung
CH651036A5 (de) 1-benzyl-4-(4-(2-pyrimidinylamino)-benzyl)-2,3-dioxopiperazin-derivate, salze derselben, verfahren zur herstellung derselben und carcinostatische mittel mit einem gehalt derselben.

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): JP US