DE1289845B - 4- (4'-Hydroxy-4'-phenylpiperidino) -butyrophenones, their acid addition salts and processes for their preparation - Google Patents

4- (4'-Hydroxy-4'-phenylpiperidino) -butyrophenones, their acid addition salts and processes for their preparation

Info

Publication number
DE1289845B
DE1289845B DE1959J0016315 DEJ0016315A DE1289845B DE 1289845 B DE1289845 B DE 1289845B DE 1959J0016315 DE1959J0016315 DE 1959J0016315 DE J0016315 A DEJ0016315 A DE J0016315A DE 1289845 B DE1289845 B DE 1289845B
Authority
DE
Germany
Prior art keywords
butyrophenones
addition salts
acid addition
general formula
phenylpiperidino
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.)
Pending
Application number
DE1959J0016315
Other languages
German (de)
Inventor
Dr Med Paul Adriaan Jan
Janssen
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.)
Janssen Pharmaceutica NV
Original Assignee
Janssen Pharmaceutica NV
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 Janssen Pharmaceutica NV filed Critical Janssen Pharmaceutica NV
Publication of DE1289845B publication Critical patent/DE1289845B/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
    • C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
    • C07C1/325—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom
    • C07C1/326—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen the hetero-atom being a metal atom the hetero-atom being a magnesium atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/004—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with organometalhalides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/46—Friedel-Crafts reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
    • 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
    • C07D211/36—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 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
    • C07D211/38—Halogen atoms or nitro radicals
    • 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
    • C07D211/36—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 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
    • 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
    • C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hydrogenated Pyridines (AREA)

Description

Gegenstand der Erfindung sind 4-(4'-Hydroxy-4'-phenylpiperidino)-butyrophenone der allgemeinen Formel IThe invention relates to 4- (4'-hydroxy-4'-phenylpiperidino) -butyrophenones of the general formula I.

CO · CH, · CH, · CH,CO · CH, · CH, · CH,

/-\/OH N X
x /\Ar / - \ / OH NX
x / \ Ar

in der R entweder ein Wasserstoff- oder Halogenatom und Ar einen unsubstituierten Phenyl-, einen p-Halogenphenyl- oder einen p-Tolylrest bedeutet, deren pharmazeutisch · brauchbare Säureadditionssalze sowie Verfahren zu deren Herstellung. , ·in which R is either a hydrogen or halogen atom and Ar is an unsubstituted phenyl, a p-halophenyl or a p-tolyl radical, their pharmaceutically acceptable acid addition salts and processes for their preparation. , ·

Die neuen organischen Basen bilden mit einer Vielzahl von anorganischen und starken organischen Säuren für therapeutische Anwendung geeignete, nichttoxische Salze, z. B. mit Schwefelsäure, Phosphorsäure, Chlorwasserstoff, Bromwasserstoff, Jodwasserstoff, Sulfaminsäure, Zitronensäure, Milchsäure, Maleinsäure, Apfelsäure, Bernsteinsäure, Weinsäure, Zimtsäure, Essigsäure, Benzoesäure, Glukonsäure und Ascorbinsäure.The new organic bases form with a wide variety of inorganic and strong organic Acids suitable for therapeutic use, non-toxic salts, e.g. B. with sulfuric acid, phosphoric acid, Hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfamic acid, citric acid, lactic acid, Maleic acid, malic acid, succinic acid, tartaric acid, cinnamic acid, acetic acid, benzoic acid, gluconic acid and ascorbic acid.

Die erfindungsgemäßen Verbindungen können in an sich bekannter Weise durch Umsetzung eines Aroylalkylhalogenids der allgemeinen Formel IIThe compounds according to the invention can in a manner known per se by reacting a Aroylalkyl halide of the general formula II

-CO-CH2 · CH2 · CH2-Halogen (II)-CO-CH 2 CH 2 CH 2 -halogen (II)

in der Halogen ein Halogenatom bedeutet, -mit einem Äquivalent einer Verbindung der allgemeinen Formel IIIin which halogen means a halogen atom, -with one equivalent of a compound of the general Formula III

ΓΓ

hergestellt werden, wobei R und Ar die oben angegebene Bedeutung haben. are prepared, where R and Ar have the meaning given above.

Die Umsetzung erfolgt in einem inerten Lösungsmittel, z. B. in einem aromatischen Kohlenwasserstoff, wie Benzol, Toluol oder Xylol, in einem niederen Alkanol, wie Äthanol, Propanol oder Butanol, oder in einem niederen Alkanon, wie Aceton, Butanon oder Pentanon. In gewissen Fällen kann die Umsetzung durch erhöhte Temperatur wirksam beschleunigt werden.The reaction takes place in an inert solvent, z. B. in an aromatic hydrocarbon such as benzene, toluene or xylene, in a lower one Alkanol, such as ethanol, propanol or butanol, or in a lower alkanone, such as acetone or butanone or pentanone. In certain cases, the reaction can be effectively accelerated by increasing the temperature will.

Die Aroylalkyjhalogenide können in der von C. Van de Westeringh, B. Hermans, F. Raeymaekers und C. Van der Eycken in Ind. Chim. Beige 25, 1073 bis 1076 (1960), beschriebenen Weise hergestellt werden.The aroyl alkyl halides can be used in the from C. Van de Westeringh, B. Hermans, F. Raeymaekers and C. Van der Eycken in Ind. Chim. Beige 25, 1073-1076 (1960), described manner.

Diese Zwischenprodukte lassen sich auch durch katalytische Debenzylierung der entsprechenden l-Benzyl-4-arylpiperidin-4-ole herstellen. Diese Alkohole werden wiederum durch Behandlung der entsprechenden Arylmagnesiumhalogenide oder Aryllithiumverbindungen mit l-Benzyl-4-piperidon und anschließende Säurehydrolyse des Adduktes erhalten.These intermediates can also be obtained by catalytic debenzylation of the corresponding Prepare l-Benzyl-4-arylpiperidin-4-ols. These alcohols are in turn by treatment of the corresponding aryl magnesium halides or aryl lithium compounds obtained with l-benzyl-4-piperidone and subsequent acid hydrolysis of the adduct.

Die 4-Arylpiperidin-4-oIe können in der Weise hergestellt werden, daß man das entsprechende 4-Aryl-1,2,3,6-tetrahydropyridin mit Bromwasserstoff behandelt und das entstandene 4-Aryl-4-brompiperidin zu dem entsprechenden 4-Arylpiperidin-4-ol hydroly-■ siert.The 4-arylpiperidin-4-oils can be prepared in such a way that the corresponding 4-aryl-1,2,3,6-tetrahydropyridine Treated with hydrogen bromide and the resulting 4-aryl-4-bromopiperidine to hydrolyze the corresponding 4-arylpiperidin-4-ol sated.

Die neuen erfindungsgemäßen Verbindungen haben wertvolle pharmakologische Eigenschaften. Sie sind alle kräftige Beruhigungsmittel für das zentrale Nervensystem. Außerdem besitzen sie analgetische, antipyretische und spasmolytische Eigenschaften.The new compounds according to the invention have valuable pharmacological properties. she are all powerful central nervous system depressants. They also have analgesic, antipyretic and spasmolytic properties.

In den folgenden Beispielen sind die Mengen in Gewichtsteilen angegeben.In the following examples the amounts are given in parts by weight.

Beispiel 1example 1

Ein Gemisch von 8,7 Teilen y-Chlorbutyrophenon, 14,2 Teilen 4-PhenyIpiperidin-4-ol und 0,1 Teil Kaliumjodid in 150 Teilen Toluol wird in einem geschlossenen Gefäß auf 100 bis 110"C erhitzt. Der Inhalt des Gefäßes wird gekühlt und anschließend filtriert. Der feste Rückstand wird mit einem Gemisch von Wasser und Äther behandelt. Die Ätherschicht wird abgetrennt und dem Filtrat aus dem ursprünglichen Umsetzungsgemisch zugefügt. Die vereinigte Toluol- und Äther-Lösung wird über wasserfreiem Kaliumcarbonat getrocknet, filtriert und auf etwa ein Viertel ihres Volumens konzentriert. Das Konzentrat wird gekühlt, der entstandene Niederschlag abfiltriert und aus Diisopropyläther auskristallisiert. Man erhält so l-()<-Benzoyl-propyl)-4-phenylpiperidin-4-ol mit einem Schmelzpunkt von 129 bis 13011C.A mixture of 8.7 parts of γ-chlorobutyrophenone, 14.2 parts of 4-phenylpiperidin-4-ol and 0.1 part of potassium iodide in 150 parts of toluene is heated to 100 to 110 ° C. in a closed vessel The solid residue is treated with a mixture of water and ether. The ether layer is separated and added to the filtrate from the original reaction mixture. The combined toluene and ether solution is dried over anhydrous potassium carbonate, filtered and reduced to about one The concentrate is cooled, the resulting precipitate is filtered off and crystallized from diisopropyl ether. This gives l - () <- Benzoyl-propyl) -4-phenylpiperidin-4-ol with a melting point of 129 to 130 11 C.

Das Hydrochlorid davon wird so hergestellt, daß man.die Toluol-Äther-Lösung, nachdem diese getrocknet worden ist, mit wasserfreiem Chlorwasserstoffgas behandelt. Das so ausgefällte Salz wird abfiltriert und. aus 2-Propanol umkristallisiert. Auf diese Weise erhält man l-()'-Benzoyl-propyl)-4-phenylpiperidin-4-ol-hydrochlorid mit einem Schmelzpunkt von etwa 182 bis 184"C. Diese Verbindung hat die folgenden Formel :The hydrochloride thereof is prepared in such a way that one.die toluene-ether solution after it has been dried treated with anhydrous hydrogen chloride gas. The salt precipitated in this way is filtered off and. recrystallized from 2-propanol. In this way, 1- () '- Benzoyl-propyl) -4-phenylpiperidin-4-ol hydrochloride is obtained having a melting point of about 182 to 184 "C. This compound has the following formula:

OHOH

CO — CH, — CH, — CH, — NCO - CH, - CH, - CH, - N

HClHCl

B e i s ρ i e 1.2B e i s ρ i e 1.2

17 Teile 4-(p-Chlorphenyl)-piperidin-4-ol und 9,9 Teile y-Chlor-p-fluorbutyrophenon werden gemäß f>5 Beispiel! umgesetzt. Man erhält l-[y(p-Fluorbenzoyl) - propyl] - 4 - (p - chlorphenyl) - piperidin - 4 - öl (Schmelzpunkt 148 bis 149,4"C) und das entsprechende Hydrochlorid mit einem Schmelzpunkt von ungefähr 226 bis 227,5 "C.17 parts of 4- (p-chlorophenyl) -piperidin-4-ol and 9.9 parts of γ-chloro-p-fluorobutyrophenone are obtained according to f > 5 example! implemented. 1- [y (p-fluorobenzoyl) -propyl] -4- (p-chlorophenyl) -piperidine-4-oil (melting point 148 to 149.4 ° C.) and the corresponding hydrochloride with a melting point of approximately 226 to 227 are obtained , 5 "C.

Beispiel 3Example 3

Bei Verwendung von 15,3 Teilen 4-(p-Toluol)-piperidin-4-ol an Stelle der Piperidinverbindung des Beispiels 3 erhält man l-[)'-(p-Fluorbenzoyl)-propyl]-When using 15.3 parts of 4- (p-toluene) -piperidin-4-ol instead of the piperidine compound of Example 3, l - [) '- (p-fluorobenzoyl) propyl] -

4-(p-tolyl)-piperidin-4-ol-hydrochlorid mit einem Schmelzpunkt von ungefähr 216 bis 218ÜC.4- (p-tolyl) -piperidin-4-ol-hydrochloride with a melting point of about 216 to 218 ° C.

Beispiel 4Example 4

Bei Verwendung von 10,3 Teilen y-Chlor-m-chlorbutyrophenon an Stelle des v-Chlorbutyrophenons des Beispiels 1 erhält man l-|j<-(m-Chlorbenzoyl)-When using 10.3 parts of y-chloro-m-chlorobutyrophenone instead of the γ-chlorobutyrophenone of Example 1, l- | j <- (m-chlorobenzoyl) -

propyl] - 4 - phenylpiperidin - 4 - öl - hydrochlorid mit einem Schmelzpunkt von ungefähr 228,5 bis 229,80C.propyl] - 4 - phenylpiperidine - 4 - Oil - hydrochloride with a melting point of about 228.5 to 229.8 0 C.

Verwendet man äquivalente Mengen entsprechender Ausgangsstoffe und verfährt im übrigen auf die vorstehend beschriebene Weise, so erhält man ferner die nachstehend aufgeführten Verbindungen:If you use equivalent amounts of appropriate starting materials and proceed to the rest of the In the manner described above, the compounds listed below are also obtained:

Tabelle 1
Pharmakologische Daten (ED50-Werte in mpk se.)Table 1
Pharmacological data (ED 50 values in mpk se.)

OHOH

X^ ti?X ^ ti?

XX VergleichsComparison Heizplatten-
versuchHot plate
attempt Aufrichtungs
reflex-TestErecting
reflex test Maus1)Mouse 1 ) Rotarod-TestRotarod test Anti-
agressiveranti-
more aggressive IW-TestIW test Ratte2)Rat 2 ) Hund3)Dog 3 ) RR. produkt:product: Pento-
barbital-Pento-
barbital Testtest Anti-
Amphetamin-anti-
Amphetamine- Anti-
Apomorphin-anti-
Apomorphine ClCl 3-Chlor-N-[3'-3-chloro-N- [3'- 2,2 ·2.2 11,011.0 Potent-TestPotent test 0,350.35 Wirkungeffect Wirkungeffect HH FF. (l"-oxyäthyl-(l "-oxyethyl- 0,840.84 1,51.5 0,260.26 1,21.2 0,600.60 0,300.30 0,0430.043 0,060.06 FF. ClCl 4"-piper-azi-4 "-piper-azi- 0,460.46 4,44.4 0,130.13 0,400.40 0,720.72 0,270.27 0,0800.080 0,070.07 FF. CH:) CH :) nyl)-propyl]-nyl) -propyl] - 0,800.80 6,06.0 0,120.12 1,41.4 1,3 ·1.3 · 0,180.18 0,0380.038 0,0250.025 FF. phenothiazinphenothiazine 0,090.09 0,0230.023 0,0300.030 1,31.3 5,05.0 0,460.46 0,750.75 0,180.18 0,500.50 0,160.16 0,040.04

') Methoden: Journal of Medic, and Pharmacol. Chemistry, 1, 286 (1959). 2) Methoden: Arzneimittel-Forschung, 11, 819 und 932 (1961). Methoden: Arzneimittel-Forschung, 9, 765 (1959).Methods: Journal of Medic, and Pharmacol. Chemistry, 1, 286 (1959). 2 ) Methods: Drug Research, 11, 819 and 932 (1961). Methods: Drug Research, 9, 765 (1959).

TabelleTabel

pLJpLJ

OHOH

Sprungkasten-TestJump box test mit Hundenwith dogs Akute Toxizitätacute toxicity oralorally TherapeutischerMore therapeutic subkutansubcutaneous oralorally bei Versuchenwhen trying • ED50 oral• ED 50 orally bei Hundenin dogs >80*)> 80 *) Indexindex >1270> 1270 >808> 808 XX ED50 subkutanED 50 subcutaneous (mg/kg)(mg / kg) >80*)> 80 *) >1633> 1633 >258> 258 (mg/kg)(mg / kg) 0,099 ■0.099 ■ subkutansubcutaneous ClCl 0,0630.063 0,310.31 >80*)> 80 *) >40*)> 40 *) > 125> 125 > 45> 45 CH3 CH 3 0,0490.049 >80*)> 80 *) Vergleichsprodukt:Comparative product: 0,890.89 PerphenazinPerphenazine 0,160.16 >20*)> 20 *)

*) Höchste getestete Dosis: Kein Fall von Mortalität.*) Highest dose tested: No case of mortality.

Diese Tabelle veranschaulicht folgendes:This table illustrates the following:

1. Starke neuroleptische Wirksamkeit der erfindungsgemäßen Butyrophenonderivate bei beiden Verabreichungsarten, verglichen mit Perphenazin; 1. Strong neuroleptic effectiveness of the invention Butyrophenone derivatives in both modes of administration compared to perphenazine;

2. die relativ niedrige Toxizität dieser Verbindungen bei Hunden;2. the relatively low toxicity of these compounds in dogs;

3. die Überlegenheit der erfindungsgemäßen Verbindungen gegenüber der Vergleichssubstanz ih bezug auf den Sicherheitsspielraum (therapeutischer Index) bei denselben Tieren.3. the superiority of the compounds according to the invention over the comparison substance ih in terms of the margin of safety (therapeutic index) in the same animals.

Claims (2)

5 6 ■ ... ■ Patentansprüche:5 6 ■ ... ■ Claims: 1. 4-(4'-Hydrbxy^4'-phenyIpiperidino)-butyrophenone der allgemeinen Formel I1. 4- (4'-Hydrbxy ^ 4'-phenyIpiperidino) -butyrophenones of the general formula I. -CO-CH2-CH2-CH2-N-CO-CH 2 -CH 2 -CH 2 -N OHOH Ar'Ar ' in der R entweder ein Wasserstoff- oder ein Halogenatom und Ar einen unsubstituierten Phenyl-, einen p-Halogenphenyl- oder einen p-Tolylrest bedeutet, sowie deren pharmazeutisch brauchbare Säureadditionssalze.in which R is either a hydrogen or a halogen atom and Ar is an unsubstituted phenyl, a p-halophenyl or a p-tolyl radical means, as well as their pharmaceutically acceptable acid addition salts. 2. Verfahren zur Herstellung von 4-(4'-Hydroxy-4'-phenylpiperidino)-butyrophenonen der allgemeinen Formel I, dadurch gekennzeichnet, daß man in an sich bekannter Weise eine Verbindung der allgemeinen Formel II2. Process for the preparation of 4- (4'-Hydroxy-4'-phenylpiperidino) -butyrophenones of the general formula I, characterized in that a compound is formed in a manner known per se of the general formula II -CO-CH2-CH2-CH2 - Halogen-CO-CH 2 -CH 2 -CH 2 - halogen (II)(II) in der Halogen ein Halogenatorn bedeutet, mit wenigstens einem Äquivalent einer Verbindung der allgemeinen Formel IIIin which halogen means a halogenator, with at least one equivalent of a compound of the general formula III H-NH-N ArAr (III)(III) umsetzt, wobei R und Ar die oben angegebene Bedeutung haben, und die entstandenen Produkte gegebenenfalls in ihre pharmazeutisch brauchbaren Säureadditionssalze überführt.converts, where R and Ar have the meaning given above, and the resulting products optionally converted into their pharmaceutically acceptable acid addition salts.
DE1959J0016315 1958-04-22 1959-04-18 4- (4'-Hydroxy-4'-phenylpiperidino) -butyrophenones, their acid addition salts and processes for their preparation Pending DE1289845B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB1277958A GB881893A (en) 1958-04-22 1958-04-22 Arylpiperidine derivatives

Publications (1)

Publication Number Publication Date
DE1289845B true DE1289845B (en) 1969-02-27

Family

ID=10010962

Family Applications (1)

Application Number Title Priority Date Filing Date
DE1959J0016315 Pending DE1289845B (en) 1958-04-22 1959-04-18 4- (4'-Hydroxy-4'-phenylpiperidino) -butyrophenones, their acid addition salts and processes for their preparation

Country Status (5)

Country Link
BE (1) BE577977A (en)
CH (1) CH397677A (en)
DE (1) DE1289845B (en)
GB (1) GB881893A (en)
NL (1) NL110185C (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994000431A1 (en) * 1992-06-19 1994-01-06 Basf Aktiengesellschaft N-substitued 3-azabicyclo[3.2.0]heptane derivatives useful as neuroleptic agents etc.
WO1995015327A1 (en) * 1993-12-04 1995-06-08 Basf Aktiengesellschaft N-substituted azabicycloalkane derivatives as neuroleptika asf

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3408356A (en) * 1965-08-31 1968-10-29 Squibb & Sons Inc Long chain esters of 4'-fluoro-4-[4-hydroxy-4-(alpha, alpha, alpha-trifluorotolyl)piperi-dino]butyrophenone and the like
US3484446A (en) * 1967-01-16 1969-12-16 Aldrich Chem Co Inc 1-(3-(4-fluorobenzoyl)propyl) - and 1 - (1,1-ethylenedioxy - 1 - (4 - fluorophenyl)-4-butyl)-4-piperidyl carbamates
USH1209H (en) 1985-10-04 1993-07-06 The United States Of America As Represented By The United States Department Of Energy No-carrier-added (18F)-N-methylspiroperidol
KR20080016566A (en) * 2005-04-29 2008-02-21 클레라 아이엔씨. Substituted butyrophenone derivatives
EP2767275A1 (en) 2013-02-13 2014-08-20 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Nortriptyline, haloperidol or prochlorperazine edisylate for use in the treatment of tuberculosis as well as two screening methods

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994000431A1 (en) * 1992-06-19 1994-01-06 Basf Aktiengesellschaft N-substitued 3-azabicyclo[3.2.0]heptane derivatives useful as neuroleptic agents etc.
US5521209A (en) * 1992-06-19 1996-05-28 Basf Aktiengesellschaft N-substituted azabicyclo[3.2.0]heptane derivatives as neuroleptics, the preparation and use thereof
SG82540A1 (en) * 1992-06-19 2001-08-21 Basf Ag N-substituted azabicyclo [3.2.0] heptane derivatives as neuroleptics, the preparation and use thereof
WO1995015327A1 (en) * 1993-12-04 1995-06-08 Basf Aktiengesellschaft N-substituted azabicycloalkane derivatives as neuroleptika asf
AU680583B2 (en) * 1993-12-04 1997-07-31 Abbott Gmbh & Co. Kg N-substituted azabicycloalkane derivatives as neuroleptika ASF
US5703091A (en) * 1993-12-04 1997-12-30 Basf Aktiengesellschaft N-substituted azabicycloalkane derivatives, their preparation and use

Also Published As

Publication number Publication date
BE577977A (en) 1959-08-17
NL110185C (en)
CH397677A (en) 1965-08-31
GB881893A (en) 1961-11-08

Similar Documents

Publication Publication Date Title
DE3005948C2 (en)
DE1445080C3 (en) 1- (gamma-Benzoylpropyl&gt; 4-phenylpiperidine-4-carboxamides and process for their preparation
CH643542A5 (en) 4- (NAPHTHYLMETHYL) PIPERIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL PREPARATIONS CONTAINING THE SAME.
DE2628570C3 (en)
DE2166381B2 (en)
DE1695256A1 (en) Process for the preparation of new piperidine derivatives
DE1289845B (en) 4- (4&#39;-Hydroxy-4&#39;-phenylpiperidino) -butyrophenones, their acid addition salts and processes for their preparation
DE2241097A1 (en) NEW 3-SUBSTITUTED AMINOACETIDE DERIVATIVES AND PROCESS FOR THEIR PRODUCTION
AT200578B (en) Process for the preparation of new N-aminoalkyl derivatives of azepines
DE2167193C2 (en) 4- (4-Hydroxypiperidino) -N, N, 3-trimethyl-2,2-diphenylbutyramides and processes for their preparation
DE2313258A1 (en) PROCESS FOR THE PREPARATION OF BUTYROPHENONE DERIVATIVES AND THEIR SALTS NEW BUTYROPHENONE DERIVATIVES, THEIR SALTS AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
DE1518452B2 (en) 4-SUBSTITUTED 2-BENZHYDRYL-2BUTANOL DERIVATIVES AND PROCESS FOR THEIR PRODUCTION
DE2040231C3 (en) 4-Aryl-1- (4,4-diaryl-butyl) -4hydroxypiperidines, their preparation and use
DE2628464C2 (en) Xanthene-9-carboxylic acid esters, processes for their preparation and pharmaceutical compositions containing these compounds
DE2425767A1 (en) 3-ALKYL-9-AMINOALKYL-1,2,3,4-TETRAHYDROCARBAZOLES AND THEIR USE IN MEDICINAL PRODUCTS
DE1670007A1 (en) N- (tert-aminoalkyl) amide derivatives and processes for their preparation
CH493517A (en) Piperidyl piperidine derivs
CH644364A5 (en) 4- (NAPHTHALINYLOXY) PIPERIDINE DERIVATIVES.
AT208870B (en) Process for the production of new N-substituted azepines or dihydroazepines
AT276372B (en) Process for the preparation of new N- (tert-aminoalkyl) amide derivatives and their acid addition salts
DE1018868B (en) Process for the preparation of phenthiazine derivatives
DE2065426B2 (en)
AT257605B (en) Process for the preparation of new 4-substituted pyridine compounds
AT267075B (en) Process for the preparation of new 3- (dibenzo- [a, d] -1,4-cycloheptadien-5-yloxy) -nortropanes substituted on the nitrogen and of salts of these compounds
DE1470124C3 (en)