GB1570371A - Creación de Inventos y Patentes con Inteligencia Artificial

GB1570371A – 1-(diarylmethyl) aminoalkyl piperidines
– Google Patents

GB1570371A – 1-(diarylmethyl) aminoalkyl piperidines
– Google Patents
1-(diarylmethyl) aminoalkyl piperidines

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Publication number
GB1570371A

GB1570371A
GB4132/78A
GB413278A
GB1570371A
GB 1570371 A
GB1570371 A
GB 1570371A
GB 4132/78 A
GB4132/78 A
GB 4132/78A
GB 413278 A
GB413278 A
GB 413278A
GB 1570371 A
GB1570371 A
GB 1570371A
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United Kingdom
Prior art keywords
compound
formula
radical
fluorophenyl
group
Prior art date
1977-02-14
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GB4132/78A
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Janssen Pharmaceutica NV

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Janssen Pharmaceutica NV
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1977-02-14
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1978-02-01
Publication date
1980-07-02

1978-02-01
Application filed by Janssen Pharmaceutica NV
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Janssen Pharmaceutica NV

1980-07-02
Publication of GB1570371A
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patent/GB1570371A/en

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legal-status
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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

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

C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 – C07D463/00

C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 – C07D463/00 in which the condensed system contains two hetero rings

C07D471/10—Spiro-condensed systems

Description

PATENT SPECIFICATION
( 21) Application No 4132/78 ( 22) Filed 1 Feb 1978 ( 31) Convention Application No 768 527 ( 32) Filed 14 Feb 1977 in ( 33) United States of America (US) Ul ( 44) Complete Specification published 2 July 1980 ( 51) INT CL 3 C 07 D 211/36; A 61 K 31/445; C 07 D 211/52, 401/04; (C 07 D 401/04, 211/58, 211/66, 233/32, 235/26) ( 52) Index at acceptance C 2 C 1414 1416 1532 211 213 215 220 226 227 22 Y 246 250 251 252 25 Y 28 X 29 X 29 Y 30 Y 311 313 31 Y 322 32 Y 337 338 339 351 352 360 363 36 Y 43 X 440 618 620 623 625 650 672 682 694 697 699 761 762 766 776 778 802 80 Y AA LF LK NN ( 11) 1 570 371 ( 54) 1 l(DIARYLMETHYL)AMINOALKYLl PIPERIDINES ( 71) We, JANSSEN PHARMACEUTICA N V, a Belgian Body Corporate, of Turnhoutsebaan 30, Beers e, Belgium, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following
statement:-
This invention relates to novel chemical compounds and more particularly to a’ novel series of I l(diarylmethyl)aminoalkyllpiperidines having the formula:
Ar 1 .{-_NH-(CH 2) n-N f»\A Ar ( 1) and the pharmaceutically acceptable acid addition salts thereof, wherein Ar’ and Ar 2 are each independently a phenyl group optionally substituted with I or 2 halo, lower alkyl, lower alkoxy or trifluoromethyl substituents which may be the same or different; N is 2 or 3; and the radical -M 6 A is a) a radical of the formula wherein R’ and R 2 are each independently a hydrogen or halogen atom or a lower alkyl or lower alkoxy group, b) a radical of the formula ( 19) 1.570,371 wherein R 3 and R 4 are each independently a hydrogen or halogen atom or a lower alkyl, lower alkoxy or trifluoromethyl group; a c) a radical of the formula OH -N 5 R 5 R 6 wherein R 5 is a hydrogen atom or a methyl group and R 8 is a hydrogen or halogen atom or a lower alkyl or trifluoromethyl group As used in the foregoing and in the following definitions, the term «lower alkyl» is meant to include straight and branched chain hydrocarbon radicals having from I to 5 carbon atoms such as, for example, methyl, ethyl, 1methylethyl, 1,1 10 dimethylethyl, propyl, 1-methylpropyl, butyl and pentyl, and the term «halogen» is generic to halogens of atomic weight less than 127, i e, fluorine, chlorine, bromine and iodine The term «lower alkoxy» is meant to include straight and branched chain alkoxy groups having from 1 to 5 carbon atoms.
The compounds of formula (I) can generally be prepared by the reaction of an 15 appropriate reactive ester of formula (II) with an appropriate piperidine derivative of formula (III) following standard N-alkylating procedures.
Ar 1 CH-NH-(CH 2)n-X + HN A Ar (II) (III) Ar’, Ar 2 and N as they appear in formula (II) have the same meaning as assigned to them previously, while X represents an appropriate reactive ester residue such as, 20 for example, halo, preferably chloro or bromo; or a sulfonyloxy group, e g, methylsulfonyloxy or 4-methyl-phenylsulfonyloxy The radical in formula (III) has the previously indicated meaning.
The foregoing N-alkylation reaction is preferably conducted in an appropriate 25 reaction-inert organic solvent, such as, for example, a lower C,_ 6 alkanol, e g, methanol, ethanol, propanol, or butanol; a ketone, e g, 4-methyl-2pentanone; an ether, e g, 1 M 4-dioxane or l,l’-oxybisethane; N,N-dimethylformamide; nitrobenzene; or a mixture of such solvents.
In order to pick up the acid which is liberated during the course of the reaction it is appropriate to add to the reaction mixture an appropriate base such as, for example, an alkali metal carbonate or hydrogen carbonate In some instances it may be advantageous to add a small amount of an appropriate iodide salt, preferably an alkali metal iodide, as a reaction promoter Somewhat elevated 5 temperatures are appropriate to enhance the reaction rate and most preferably the reaction is carried out at the reflux temperature of the reaction mixture.
In this and following preparations the reaction products are separated from the mixture, and, if necessary, further purified by the application of methodologies which are generally known in the art 10 Compounds of formula (I) wherefn N is-2, (I-a), may also be obtained by the reaction of ( 11 I) with an aziridine of formula (IV) wherein Ar’ and Ar 2 are as previously defined.
1 Arl U +, (III) > Ar 2 (Iv) Ar 1 CH-NH-CH 2-CH 2-N A Ar 2 (I-a) Said reaction may conveniently be carried out by stirring the reactants together, preferably while heating and most preferably under reflux, in an appropriate 15 reaction-inert organic solvent In general the same solvents as described hereabove in connection with the synthesis of compounds (I) starting from (II) and (III) may be employed.
The starting materials of formula (II), a number of which are known compounds, may all be prepared following methodologies known in the art For 20 example, such compounds are easily obtained by the reaction of an appropriate reactive ester of formula (V) wherein Ar 1, Ar 2 and X are as previously defined, with an appropriate aminoalkanol of formula (VI) wherein N has the same meaning as indicated hereinabove, followed by the conversion of the hydroxyl group of the thus obtained intermediate (VII) into a reactive ester group 25 Ar’ CH-X H 2 N-(CH 2)n-OH > Ar 2 (V) (VI) Ar’ «N reac’tive ester / CH-NH-(CH 2)n-O Hrati (II) Ar 2 formation (VII) The reaction of (V) with (VI) may be carried out in an analogous manner as described above for the preparation of compounds (I) starting from (II) and (III).
The conversion of (VII) into a reactive ester (II) may be accomplished by the application of art-known methods of preparing reactive esters from alcohols In the 30 preparation of halides there may be used common halogenating agents such as hydrohalic acid, e g, hydrochloric or hydrobromic acid; or other halogenating agents, e g, sulfinyl chloride Methanesulfonates and 4methylbenzenesulfonates are conveniently prepared by the reaction of (VII) with respectively methanesulfonyl chloride or 4-methylbenzenesulfonyl chloride 35 1,570,371 The precursor reactive esters of formula (V) herein are generally known and may be prepared following art-known procedures, for example, by converting the corresponding diarylmethanol into a reactive ester according to procedures previously described herein.
Aziridines of formula (IV) can be derived from the corresponding reactive 5 esters of formula (II) wherein N is 2 by treating the latter with alkali.
The piperidine derivatives of formula (III) are generally known compounds.
Such compounds and methods of preparing the same are described, for example, in U.S Pat Nos 3,910,930, 3,989,707, 3,155,670, 3,438,991, 3,518,276, 3,575, 990 and 3,714,151 10 The compounds of this invention may be converted to their therapeutically useful acid addition salts by treatment with an appropriate acid, such as, for example, an inorganic acid, such as hydrohalic acid, e g, hydrochloric, or hydrobromic acid, and sulfuric acid, nitric acid or phosphoric acid; or an organic acid, such as, for example, acetic, propanoic, 2-hydroxyacetic, 2 15 hydroxypropanoic, 2-oxopropanoic, propanedioic, butanedioic, (Z)-2butenedioic, (E)-2-butenedioic, 2-hydroxybutanedioic, 2,3-dihydroxybutanedioic, 2hydroxy1,2,3-propanetricarboxylic, benzoic, 3-phenyl-2-propenoic, a-hydroxybenzeneacetic, methanesulfonic, ethanesulfonic, benzenesulfonic, 4-methylbenzenesulfonic, cyclohexanesulfamic, 2-hydroxybenzoic or 4-amino-2 20 hydroxybenzoic acid.
Conversely the salt form can be converted by treatment with alkali into the free base form.
The compounds of formula (I) and the pharmaceutically acceptable acid addition salts thereof were found to be potent neuroleptics and as such they can be 25 used as tranquilizing agents, for example, in the treatment of various forms of mental illness.
They may be formulated, for ease of administration, with inert carriers or diluents, to form pharmaceutical compositions.
The useful neuroleptic properties of the compounds (I) are clearly evidenced 30 by the experimental data given hereafter.
Neuroleptic drugs are known to inhibit emesis induced by apomorphine in dogs The compounds listed in tables I and II were administered either subcutaneously or orally to a minimum of a group of 3 beagle dogs The animals were challenged 1, 4 or 16 hours after subcutaneous administration or 4 hours after 35 oral administration with a standard dose of 0 31 mg/kg of apomorphine hydrochloride (subcutaneously) This high dose of apomorphine induces emesis in all untreated dogs.
Tables I and II give the PD 1 o-values (in mg/kg subcutaneously or orally) , i e, the dose of the compound protecting at the stated time half of the animals from 40 emesis The compounds listed therein are not given for the purpose of limiting the invention thereto but only to exemplify the useful properties of all the compounds within the scope of formula I.
1.570 371 1,570,371 5 TABLE I: Compounds of the formula:
Ar 1 r Anti-apomorphine-activity in dogs:
PD 5,d-value in mg/kg 1 hour 4 hours 16 hours 4 hours Ar’ Ar’ R’ SC s C S C oral C^H 4-CH,-CAH H 0 06 0 25 0 5 1 5 C,1 H, 3-CF 3-CH, H 2 5 4-C 1-C^H 4-CI-CH 4 H 2 0 C^H 3-CI-CH 4 cl 2 5 C 6,H 5 4-C Hr C 2-C 14cl 0 50 0 10 0 5 0 63 4-F-CH 4 4-F-C 6 H 4 cl 0 16 0 035 0 06 0 07 4-Cl-C 6 H 44-CI-CH, cl 2 5 1,570,371 TABI E II Compounds of the fi)rmula:
-‘ CH-M-NH-CH Ar 29 R 3 Anti-apomorphine-activity in dogs.
P Ds,0 in mg ‘kg I hour 4 hours 16 hours 4 hours Ar’ Ar 2 R 3 s c s c s c oral C Hs C 6 Hs H O 06 0 10 0 25 C 6 Hs 4-CH 3-C 6 H 4 H 0 015 0 015 0 07 C 6 Hs 3-CF 3-C 6 H 4 H 1 0 0 20 2 O 4-F-C 6 H 4 4-F-C 6 H 4 H 0 015 0 008 0 03 C Hs 3-C 1-C 6 H 4 H 0 10 0 015 0 06 1 0 C 6 Hs 2,3-(CH 3)2-CH 3 F 0 50 4-F-C 6 H 4 4-F-C 6 H 4 F O 015 0 008 O 010 0 25 4-CI-C 6 H 44-CI-C 6 H 4 F 1 25 The following examples are intended to illustrate but not to limit the scope of the present invention Unless otherwise stated all parts therein are by weight.
Examples I to III relate to the preparation of starting materials.
EXAMPLE I 5
To a stirred mixture of 40 parts of sulfinyl chloride in 150 parts of trichloromethane is added dropwise a solution of 64 parts of a phenyl 3 (trifluoromethyl)benzenemethanol in 375 parts of trichloromethane Upon completion, stirring is continued for one hour at room temperature The whole is heated to reflux and stirring is continued for 3 hours at reflux temperature After 10 stirring overnight at room temperature, the solvent is evaporated The residue is taken up in methylbenzene and the latter is evaporated again, yielding 70 parts ( 100) of I -(chlorophenylmethyl) 3 (trifluoromethyl)benzene as an oily residue.
A mixture of 70 parts of I (chlorophenylmethyl) 3 (trifluoro 15 methyl)benzene and 250 parts of 2-aminoethanol is stirred for 3 hours at 140 C.
The reaction mixture is cooled and poured onto water The product is extracted with 4-methyl-2-pentanone The extract is dried, filtered and evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol ( 95:5 by volume) as eluent The pure fractions are 20 collected and the eluent is evaporated, yielding 60 parts ( 82,’) of 2 lIphenyll 3 (trifluoromethyl)phenylllmethyllaminollethanol as a residue.
To a stirred and cooled ( 5-10 C) mixture of 60 parts of 2 l{phenyll 3 (trifluoromethyl)phenyllmethylfaminolethanol and 540 parts of methylbenzene are added dropwise 40 parts of sulfinyl chloride Upon completion, stirring is 25 continued first till room temperature is reached and further overnight at reflux temperature The reaction mixture is concentrated to one third its volume After cooling to 10 C, the solid product is filtered off, washed with 2,2 ‘oxybispropane and dried in vacuo at 75 C, yielding 28 5 parts ( 40 %/) of N ( 2 chloroethyl) a phenyl3 (trifluoromethyl)benzenemethanamine hydrochloride, mp 187 C.
EXAMPLE II.
Following the procedure of Example I and using equivalent amounts of the appropriate starting materials the following N ( 2 chloroethyl) 5 diarylmethanamine hydrochloride salts are obtained.
Ar 1 CH-NH-CH 2-CH 2 Cl HCI Ar 2 Arl Ar 2 Melting Point C 6 Hs 3-CI-C 6 H 4 228 5 C 4-F-C 6 H 4 4-F-C 6 H 4 C 611 S 4-CH 3-C 6 H 4 4-CI-C 6 H 4 4-CI-C 6 H 4 C 6 Hs 2 5-(CH 3)2-C 6 H 3 220 C C 6 HS 2,3-(CH 3)2-C 6 H 3 220 C EXAMPLE III.
Following the procedure of Example I and using an equivalent amount of 3aminopropanol in place of the 2-aminoethanol used therein, the following N ( 3 10 chloropropyl) diarylamines are obtained:
N ( 3 chloropropyl) a phenyl 3 (trifluoromethyl)benzenemethan amine; 3 chloro N ( 3 chloropropyl) a phenylbenzenemethanamine; N ( 3 chloropropyl) 4 methyl a phenylbenzenemethanamine; 15 4 chloro N ( 3 chloropropyl) a ( 4 chlorophenyl)benzenemethanamine; and N ( 3 chloropropyl) 2,5 dimethyl a phenylbenzenemethanamine.
EXAMPLE IV.
A mixture of 10 parts of N ( 2 chloroethyl) 4 fluoro ca ( 4 20 fluorophenyl)benzenemethanamine hydrochloride, 7 3 parts of 5 chloro 1,3 dihydro I ( 4 piperidinyl) 2 H benzimidazol 2 one, 10 6 parts of sodium carbonate, 0 1 parts of potassium iodide and 80 parts of 4 methyl 2 pentanone is stirred and refluxed overnight Water is added to the reaction mixture The precipitated product is filtered off and set aside From the filtrate, the organic 25 phase is separated, washed with water, dried, filtered and evaporated The residue is stirred in 4 methyl 2 pentanone The solid product is filtered off, combined with the precipitated product, obtained above, and crystallized from 4 methyl 2 pentanone The product is filtered off and dried in vacuo at 95 C, yielding 5 parts of 1 11 l 2 llbis( 4 -fluorophenyl)methyllaminolethyll 4 piperidinyl} 30 chloro 1,3 dihydro 2 H benzimidazol 2 one; mp 198 6 C.
EXAMPLE V.
Following the procedure of Example IV and using equivalent amounts of the appropriate starting materials, the following compounds are obtained in free base form or in the form of an acid addition salt after treatment of the free base with the 35 appropriate acid:
1,570,371 s-R o CH-NHCH -CH 29 ( N Ar 2 / R 1 Base or Melting Point Ar’ Ar 2 Rt Salt form in C C 6 Hs C 6 Hs Cl base 155 9 C 6 Hs 4-CH 3-C 6 H 4 Cl base 169 4 4-Cl-C 6 H 44-CI-C 6 H 4 H base 224 6 4-CI-C 6 H 44-Cl-C 6 H 4 Cl base 192 6 C 6 Hs 3-C 1-C 6 H 4 Cl base 139 3 C 6 Hs 3-CI-C 6 H 4 H base 178 6 C 6 Hs 4-CH 3-C 6 H 4 H base 189 3 C 6 Hs 2,3-(CH 3)2-C 6 H 3 Cl base 155 9 C 6 Hs 2,5-(CH 3)2-C 6 H 3 H base 141 8 C 6 Hs 3-CF 3-C 6 H 4 H base 152 C 6 Hs 3-CF 3-C 6 H 4 Cl (E)-2-butene 227 5 dioate ( 1:1) EXAMPLE VI.
A mixture of 8 parts of N ( 2 chloroethyl) 4 fluoro ( 4fluorophenyl)benzenemethanamine hydrochloride, 5 7 parts of 1 ( 4 fluorophenyl) 1,3,8 triazaspirol 4,5 ldecan 4 one, 10 parts of sodium carbonate, O 1 parts of potassium iodide and 80 parts of 4 methyl 2 pentanone is stirred and refluxed overnight The reaction mixture is taken up in water and after stirring for a while, the precipitated product is filtered off The product is washed with 4 methyl 2 pentanone, dried and crystallized from 4 methyl 2 pentanone (activated charcoal) It is filtered off and dried, yielding 4 parts of 8 l 2 {lbis( 4 fluorophenyl)methyllaminolethyll 1 ( 4 fluorophenyl)1,3,8 triazaspirol 4,5 ldecan 4 one; mp 193 C.
EXAMPLE VII.
Following the procedure of Example VI and using equivalent amounts of the appropriate starting materials the following compounds are prepared:
1 570371 R 1,570,371 Melting Point Ar’ Ar’ R 3 in C C 6 Hs C 6 Hs H 183 6 4-F-C 6 H 4 4-F-C 6 H 4 H 192 5 C 6 Hs 4-CH 3-C 6 H 4 H 176 4-CI-C 6 H 44-Cl-C 614 F 217 8 C 6 Hs 3-CI-C 6 H 4 H 169 9 C 6 Hs 3-Cl-C 6 H 4 F 180 5 C 6 Hs 2,5-(CH 3)2-C 6 H 3 H 163 8 C 6 Hs 2 3-(CH 3)2-C 6 H, F 147 1 C 6 Hs 2,5-(CH 3)2-C 6 H 3 F 177 9 C 6 Hs 2,3-(CH 3)2-C 6 H 3 H 159 3 4-Cl-C 6 H 44-CI-C 6 H 4 H 182 6 (hemihydrate) C 6 Hs 3-CF 3-C 6 H 4 H 154 3 EXAMPLE VIII.
A mixture of 10 parts of N ( 2 chloroethyl) a phenylbenzenemethanamine hydrochloride 7 parts of 4 ( 4 chlorophenyl) 4 piperidinol, 10 6 parts of sodium carbonate, 0 1 parts of potassium iodide and 80 parts of 4 methyl 2 pentanone is stirred and refluxed overnight The reaction mixture is taken up in water and the layers are separated The aqueous phase is extracted with 4 methyl 2 pentanone The combined organic phases are washed with water, dried, filtered and evaporated The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol ( 96:4 by volume) as eluent The pure fractions are collected and the eluent is evaporated The residue is crystallized from a mixture of methylbenzene and 2,2 ‘-oxybispropane The product is filtered off and dried, yielding 4 5 parts of 4 ( 4 chlorophenyl) I 12 l(diphenylmethyl)aminolethyl} 4 piperidinol; mp 113 9 C.
EXAMPLE IX.
Following the procedure of Example VIII there is prepared 1 l 2 {lbis( 4 fluorophenyl)methyllamino}ethyll 4 ( 4 chlorophenyl) 4 piperidinol dihydrochloride; mp 208 3 C by the reaction of N ( 2 chloroethyl) 4 fluoro a ( 4 fluorophenyl)benzenemethanamine hydrochloride with 4 ( 4 chlorophenyl) 4 piperidinol.
EXAMPLE X.
In a similar manner as described in Examples IV, VI and VIII the following compounds are obtained by the reaction of an appropriate N ( 3 chloropropyl) diarylmethanamine with an appropriate piperidine derivative of formula (III):
1 11 l 3 {lbis( 4fluorophenyl)methyllamino}propyll 4 piperidinyl} 5 5 chloro 1,3 dihydro 2 H benzimidazol 2 one; chloro 1 l 1 l 3 l(diphenylmethyl)aminolpropyll 4 piperidinyll 1,3 dihydro 2 H benzimidazol 2 one; chloro 1 { 1 l 3 {l( 3chlorophenyl)phenylmethyllamino} propyll 4 piperidinyl} 1,3 dihydro 2 H benzimidazol 2 one; 10 1,3 dihydro 1 11 l 3 1 l( 4 methylphenyl)phenylmethyllamino} propyll 4 piperidinyll 2 H benzimidazol 2 one; 1 11 3 {lbis( 4 chlorophenyl)methyllamino}propyll 4 piperidinyl} 1,3 dihydro 2 H benzimidazol 2 one; 8 { 3 l(diphenylmethyl)aminolpropyll 1 phenyl 1,3,8 15 triazaspirol 4,5 ldecan 4 one; 8 l 3 {lbis( 4 fluorophenyl)methyllamino}propyll 1 ( 4 fluorophenyl) 1,3,8 triazaspirol 4,5 ldecan 4 one; 8 l 3 {lbis( 4 chlorophenyl)methyllamino}propyll 1 ( 4 fluorophenyl) 1,3,8 triazaspirol 4,5 ldecan4 one; 20 8 l 3 {l( 2,5 dimethylphenyl)phenylmethyllamino}propyll 1 phenyl 1,3,8 triazaspirol 4,5 ldecan 4 one; 4 ( 4 chlorophenyl) 1 { 3 l(diphenylmethyl)aminolpropyl}l 4piperidinol; and 1 l 3 {lbis( 4 fluorophenyl)methyllamino}propyll 4 ( 4 25 chlorophenyl) 4 piperidinol.

Claims (1)

WHAT WE CLAIM IS:-
1 A compound of the formula Ar 1 ACH-NH-(CH 2)n-N A Ar wherein Ar’ and Ar 2 are each independently a phenyl group optionally substituted 30 with I or 2 halo, lower alkyl, lower alkoxy or trifluoromethyl substituents, which may be the same or different, N is 2 or 3; and the radical _A is a) a radical of the formula 35 \Ho RR wherein R’ and R 2 are each independently a hydrogen or halogen atom or a lower alkyl or lower alkoxy group; b) a radical of the formula 2;b&.i i 2 ll:
1,570,371 1,570,371 wherein R 3 and R 4 are each independently a hydrogen or halogen atom or a lower alkyl, lower alkoxy or trifluoromethyl group, or c) a radical of the formula OH / 5 R 5 >(-XNR 6 wherein R 5 is a hydrogen atom or a methyl group and R 6 is a hydrogen or halogen atom or a lower alkyl or trifluoromethyl group.
2 A compound as claimed in claim 1 and substantially as described in Table 1 or Table 2.
3 A compound as claimed in claim 1 and substantially as hereinbefore described 10 in any one of the specific Examples.
4 1 11 l 2 llbis( 4fluorophenyl)methyllaminol ethyll 4 piperidinyll chloro 1,3 dihydro 2 H benzimidazol 2 one.
8 l 2 {l( 4 methylphenyl)phenylmethyllaminolethyll 1 phenyl 1,3,8 triazaspirol 4,5 ldecan4 one 15 6 8 l 2 {lbis( 4 fluorophenyl)methyllamino}ethyll I phenyl 1,3,8 triazaspirol 4,5 ldecan 4 one.
7 8 l 2 llbis( 4 fluorophenyl)methyllaminolethyll I ( 4 fluorophenyl) 1,3,8 triazaspirol 4,5 ldecan 4 one.
8 A process for preparing a compound as claimed in claim 1, which comprises 20 reacting a compound of formula Ar 1 > CH-NH-(CH 2)6-X Ar 2 with a compound of formula HN A, wherein X is a reactive ester residue or a sulfonyloxy group, and Ar 1, Ar 2 and 25 -N A are as defined in claim 1.
9 A process for preparing a compound as claimed in claim I wherein N is 2, which comprises reacting a compound of formula with a compound of the formula Ar 1 \CH-N = Ar wherein Ar 1, Ar 2, and -IA are each as defined in claim 1 5 A compound as claimed in claim I when prepared by a process as claimed in claim 8 or claim 9.
11 A pharmaceutically acceptable acid addition salt of a compound as claimed in any one of claims I to 7, or in claim 10.
12 A pharmaceutical composition which comprises a compound as claimed in 10 any one of claims 1 to 7 or claim 10, or a salt as claimed in claim 11, together with an inert carrier of diluent.
13 A method of inducing neuroleptic activity in a non-human animal, which.
comprises administering to the animal a compound as claimed in any one of claims 1 to 7 or claim 10, a salt as claimed in claim 11, or a composition as claimed in claim 15 12.
BOULT, WADE & TENNANT, Chartered Patent Agents, 34 Cursitor Street, London EC 4 A IPQ.
Printed for Her Majesty’s Stationery Office by the Courier Press, Leamington Spa, 1980.
Published by the Patent Office, 25 Southampton Buildings, London, WC 2 A l AY, from which copies may be obtained.
1,570,371

GB4132/78A
1977-02-14
1978-02-01
1-(diarylmethyl) aminoalkyl piperidines

Expired

GB1570371A
(en)

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US05/768,527

US4082755A
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1977-02-14
1977-02-14
1-[(Diarylmethyl)aminoalkyl]piperidimes

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1977-02-14
1978-02-01
1-(diarylmethyl) aminoalkyl piperidines

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DE2806233A1
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FR2380278A1
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US4292321A
(en)

1979-05-24
1981-09-29
Warner-Lambert Company
1,3,8-Triazaspirodecane-4-ones, pharmaceutical compositions thereof and method of use thereof

US4364954A
(en)

1980-01-10
1982-12-21
Warner-Lambert Company
Diphenylpropanamines, compositions thereof and use thereof

DE3723797A1
(en)

1987-07-18
1989-01-26
Merck Patent Gmbh

OXAZOLIDINONE

AT388731B
(en)

1987-12-15
1989-08-25
Gerot Pharmazeutika

NEW DERIVATIVES OF BENZIMIDAZOLE, THEIR PRODUCTION AND USE

DE4005371A1
(en)

1990-02-21
1991-08-22
Merck Patent Gmbh
New N-(hetero)aryl-substd. 2-piperidino:ethyl oxazolidinone derivs.

ATE192149T1
(en)

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2000-04-21
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1977

1977-02-14
US
US05/768,527
patent/US4082755A/en
not_active
Expired – Lifetime

1978

1978-02-01
GB
GB4132/78A
patent/GB1570371A/en
not_active
Expired

1978-02-10
BE
BE185052A
patent/BE863835A/en
unknown

1978-02-13
FR
FR7804012A
patent/FR2380278A1/en
active
Granted

1978-02-14
DE
DE19782806233
patent/DE2806233A1/en
not_active
Withdrawn

1978-02-14
NL
NL7801650A
patent/NL7801650A/en
not_active
Application Discontinuation

Also Published As

Publication number
Publication date

FR2380278B1
(en)

1981-07-24

DE2806233A1
(en)

1978-08-17

US4082755A
(en)

1978-04-04

NL7801650A
(en)

1978-08-16

BE863835A
(en)

1978-08-10

FR2380278A1
(en)

1978-09-08

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