EP0353821A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Antipsychotic 3-piperazinyl-benzazole derivatives
Assignee: Janssen Pharmaceutica NV
•
Filing: 1989-07-28
•
Granted: —
•
Expires: 2009-07-28
Abstract
Abstract Novel 3-piperazinyl-1,2-benzazoles of formula wherein Q is a radical of formula R is hydrogen or C₁₋₆alkyl; R¹ and R² are hydrogen, halo, hydroxy, C₁₋₆alkyloxy or C₁₋₆alkyl; X is O, S or NR³; the pharmaceutically acceptable acid addition salts and possible stereochemically isomeric forms thereof, which compounds are antipsychotic agents; pharmaceutical compositions containing such compounds as an active ingredient and methods of preparing said compounds and pharmaceutical compositions.
Inventors
- 👤 Ludo Edmond Josephine Kennis
- 👤 Jan Vandenberk
- 👤 Josephus Carolus Mertens
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-06 00:59
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/14; C07D231/00; C07D231/54; C07D231/56; A; A61; A61P; A61P25/00; A61P25/02; A61P43/00; C07D403/00; C07D403/02; C07D403/12; C07D413/00; C07D413/02; C07D413/12; C07D417/00; C07D417/02; C07D417/12; C07D471/00; C07D471/02; C07D471/04; C07D513/00; C07D513/02; C07D513/04
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
232 words
A chemical compound having the formula a pharmaceutically acceptable acid addition salt form thereof or a stereochemically isomeric form thereof, wherein R is hydrogen or C₁₋₆alkyl; R¹ and R² each independently are hydrogen, halo, hydroxy, C₁₋₆alkyloxy or C₁₋₆alkyl; X is O, S or NR³; said R³ being hydrogen, C₁₋₆alkyl, aryl or arylC₁₋₆alkyl; Alk is C₁₋₄alkanediyl; and Q is a radical of formula wherein Y¹ and Y² each independently are O or S; R⁴ is hydrogen, halo, C₁₋₆alkyl, C₁₋₆alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C₁₋₁₀alkylcarbonyl)oxy, amino, mono- and di(C₁₋₆alkyl)amino, (C₁₋₁₀alkylcarbonyl)amino, phenylmethoxy or azido; R⁵ is hydrogen or halo; or Q is a radical of formula wherein R⁶ is hydrogen or C₁₋₆alkyl; Z is -S- or -CR⁷=CR⁸-; said R⁷ and R⁸ each independently being hydrogen or C₁₋₆alkyl; or Z is -CH₂- wherein one hydrogen atom may be replaced by hydroxy or C₁₋₆alkyl; A is a bivalent radical -CH₂-CH₂- or -CH₂-CH₂-CH₂- wherein in the latter two radicals one or two hydrogen atoms may be replaced by C₁₋₆alkyl; or A is a bivalent radical -CR⁹=CR¹⁰, wherein R⁹ and R¹⁰ each independently are hydrogen, halo, amino or C₁₋₆alkyl; or when Z is -S-, then A may also be -CR¹¹=N-, R¹¹ being hydrogen or C₁₋₆alkyl; or when Z is -CR⁷=CR⁸-, then A also may be -O-; and each aryl is phenyl optionally substituted with up to three substituents independently selected from C₁₋₆alkyl, C₁₋₆alkyloxy, hydroxy, halo, amino, nitro and trifluoromethyl.
Claim 2
Dependent Claim
232 words
A chemical compound having the formula a pharmaceutically acceptable acid addition salt form thereof or a stereochemically isomeric form thereof, wherein R is hydrogen or C₁₋₆alkyl; R¹ and R² each independently are hydrogen, halo, hydroxy, C₁₋₆alkyloxy or C₁₋₆alkyl; X is O, S or NR³; said R³ being hydrogen, C₁₋₆alkyl, aryl or arylC₁₋₆alkyl; Alk is C₁₋₄alkanediyl; and Q is a radical of formula wherein Y¹ and Y² each independently are O or S; R⁴ is hydrogen, halo, C₁₋₆alkyl, C₁₋₆alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C₁₋₁₀alkylcarbonyl)oxy, amino, mono- and di(C₁₋₆alkyl)amino, (C₁₋₁₀alkylcarbonyl)amino, phenylmethoxy or azido; R⁵ is hydrogen or halo; or Q is a radical of formula wherein R⁶ is hydrogen or C₁₋₆alkyl; Z is -S- or -CR⁷=CR⁸-; said R⁷ and R⁸ each independently being hydrogen or C₁₋₆alkyl; or Z is -CH₂- wherein one hydrogen atom may be replaced by hydroxy or C₁₋₆alkyl; A is a bivalent radical -CH₂-CH₂- or -CH₂-CH₂-CH₂- wherein in the latter two radicals one or two hydrogen atoms may be replaced by C₁₋₆alkyl; or A is a bivalent radical -CR⁹=CR¹⁰, wherein R⁹ and R¹⁰ each independently are hydrogen, halo, amino or C₁₋₆alkyl; or when Z is -S-, then A may also be -CR¹¹=N-, R¹¹ being hydrogen or C₁₋₆alkyl; or when Z is -CR⁷=CR⁸-, then A also may be -O-; and each aryl is phenyl optionally substituted with up to three substituents independently selected from C₁₋₆alkyl, C₁₋₆alkyloxy, hydroxy, halo, amino, nitro and trifluoromethyl.
Claim 3
Dependent Claim
52 words
A chemical compound according to claim 1 wherein R is hydrogen; R¹ and R² each independently are hydrogen, halo or C₁₋₆alkyl; Q is a radical of formula (a) wherein Y¹ and Y² are oxygen, and R⁴ and R⁵ are hydrogen, or Q is a radical of formula (b) wherein R⁶ is C₁₋₆alkyl.
Claim 4
Dependent Claim
88 words
A chemical compound according to claim 2 wherein R² is hydrogen or halo; X is O, S or NH; Q is a radical of formula (b), Z is -S- or -CR⁷=CH-, said R⁷ being hydrogen or C₁₋₆alkyl, or Z is CH₂ wherein one hydrogen atom may be replaced by C₁₋₆alkyl; and A is -CH₂-CH₂- or -CH₂-CH₂-CH₂-, wherein in each of the latter two radicals one or two hydrogen atoms may be replaced by C₁₋₆alkyl, or A is -CR⁹=CR¹⁰-, said R⁹ and R¹⁰ each independently being hydrogen or C₁₋₆alkyl.
Claim 5
Dependent Claim
32 words
A chemical compound according to claim 3 wherein R¹ is hydrogen, fluoro or methyl; R² is hydrogen; -Z-A- is -S-CH₂-CH₂-, -S-CH₂-CH₂-CH₂-, -S-CH=CR¹⁰-, -CH₂-CH₂-CH₂-CH₂-, -CH(CH₃)-CH₂-CH₂-CH₂-, -C(CH₃)=CH-CH=CH- or -CH=CH-CH=CR¹⁰-, R¹⁰ being hydrogen or methyl.
Claim 6
Dependent Claim
19 words
A chemical compound according to claim 4 wherein X is O or NH; and R¹ is hydrogen or 6-fluoro.
Claim 7
Dependent Claim
28 words
An antipsychotic composition comprising an inert carrier and as active ingredient an antipsychotic effective amount of a chemical compound as claimed in any of claims 1 to 5.
Claim 8
Dependent Claim
37 words
A method of preparing a pharmaceutical composition according to claim 6 characterized in that a therapeutically effective amount of a compound as defined in any of claims 1 to 5 is intimately mixed with a pharmaceutical carrier.
Claim 9
Dependent Claim
17 words
A compound as claimed in any one of claims 1 to 5 for use as a medicine.
Claim 10
Dependent Claim
18 words
A compound as claimed in any one of claims 1 to 5 for use as an antipsychotic medicine.
Claim 11
Dependent Claim
92 words
A process for preparing a chemical compound as claimed in any one of claims 1 to 5, characterized by a) N -alkylating a reagent of formula wherein R, R¹, R² and X are as defined under formula (I) with an alkylating reagent of formula Q-Alk-W (II) wherein Q and Alk are as defined under formula (I) and wherein W is a leaving group, in a reaction-inert organic solvent, optionally in the presence of a base and optionally in the presence of an alkali metal iodide, by stirring at an elevated temperature; or
Claim 12
Dependent Claim
205 words
b) N -alkylating a piperazine derivative of formula wherein Q, Alk and R are as defined under formula (I) with a benzazole of formula wherein R¹, R² and X are as defined under formula (I) and wherein W¹ is a leaving group, in a reaction-inert organic solvent, optionally in the presence of a base and optionally in the presence of an alkali metal iodide, by stirring at an elevated temperature; or c) cyclizing an intermediate of formula wherein X¹ is oxygen or NR³ and W is a leaving group and wherein Q, Alk, R, R¹, R² and R³ are as defined under formula (I) by treatment with a base in a reaction-inert solvent, optionally at an elevated temperature, thus yielding a compound of formula wherein X¹ is oxygen or NR³ and Q, Alk, R, R¹, R² and R³ are as defined under formula (I); or d) cyclizing an intermediate of formula wherein Q, Alk, R, R¹, R² and R¹² are as defined under formula (I), at an elevated temperature, optionally in the presence of a reaction-inert solvent and optionally in the presence of a base, thus yielding a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I); or
Claim 13
Dependent Claim
205 words
b) N -alkylating a piperazine derivative of formula wherein Q, Alk and R are as defined under formula (I) with a benzazole of formula wherein R¹, R² and X are as defined under formula (I) and wherein W¹ is a leaving group, in a reaction-inert organic solvent, optionally in the presence of a base and optionally in the presence of an alkali metal iodide, by stirring at an elevated temperature; or c) cyclizing an intermediate of formula wherein X¹ is oxygen or NR³ and W is a leaving group and wherein Q, Alk, R, R¹, R² and R³ are as defined under formula (I) by treatment with a base in a reaction-inert solvent, optionally at an elevated temperature, thus yielding a compound of formula wherein X¹ is oxygen or NR³ and Q, Alk, R, R¹, R² and R³ are as defined under formula (I); or d) cyclizing an intermediate of formula wherein Q, Alk, R, R¹, R² and R¹² are as defined under formula (I), at an elevated temperature, optionally in the presence of a reaction-inert solvent and optionally in the presence of a base, thus yielding a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I); or
Claim 14
Dependent Claim
126 words
e) N -alkylating a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I), with an alkylating reagent of formula R 3-a -W (VIII) wherein W is a leaving group and R 3-a is C₁₋₆alkyl, aryl or arylC₁₋₆alkyl, by treatment with a base in a reaction-inert solvent, optionally at an elevated temperature, thus yielding a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I) and R 3-a is C₁₋₆alkyl, aryl or arylC₁₋₆alkyl; and if desired, converting the compounds of formula (I) into a therapeutically active non-toxic acid addition salt form by treatment with an acid; or conversely, converting the acid salt into the free base with alkali, and/or preparing stereochemically isomeric forms thereof.
Claim 15
Dependent Claim
126 words
e) N -alkylating a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I), with an alkylating reagent of formula R 3-a -W (VIII) wherein W is a leaving group and R 3-a is C₁₋₆alkyl, aryl or arylC₁₋₆alkyl, by treatment with a base in a reaction-inert solvent, optionally at an elevated temperature, thus yielding a compound of formula wherein Q, Alk, R, R¹ and R² are as defined under formula (I) and R 3-a is C₁₋₆alkyl, aryl or arylC₁₋₆alkyl; and if desired, converting the compounds of formula (I) into a therapeutically active non-toxic acid addition salt form by treatment with an acid; or conversely, converting the acid salt into the free base with alkali, and/or preparing stereochemically isomeric forms thereof.
Claim 16
Dependent Claim
45 words
A chemical compound having the formula a pharmaceutically acceptable acid addition salt form thereof or a stereochemically isomeric form thereof, wherein R is hydrogen or C₁₋₆alkyl; R¹ and R² each independently are hydrogen, halo, hydroxy, C₁₋₆alkyloxy or C₁₋₆alkyl; R 3-b is hydrogen, C₁₋₆alkyl or arylC₁₋₆alkyl.
Claim 17
Dependent Claim
45 words
A chemical compound having the formula a pharmaceutically acceptable acid addition salt form thereof or a stereochemically isomeric form thereof, wherein R is hydrogen or C₁₋₆alkyl; R¹ and R² each independently are hydrogen, halo, hydroxy, C₁₋₆alkyloxy or C₁₋₆alkyl; R 3-b is hydrogen, C₁₋₆alkyl or arylC₁₋₆alkyl.
References Cited (Backward Citations)
US4452799A
Cited
EP0135781A1
Cited
US4524206A
Cited
US4590196A
Cited
EP0196132A2
Cited
US4804663A
Cited
EP0302423A2
Cited
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.