← Back to Patent Explorer
US4689330A Expired / Lapsed US ⏱️ 0.0 years remaining

Antidepressive substituted N-[(4-piperidinyl)alkyl] bicyclic condensed oxazol- and thiazolamines

Assignee: Janssen Pharmaceutica NV
•
Filing: 1986-02-27
•
Granted: 1987-08-25
•
Expires: 2006-02-27
📄 Original PDF 🌐 Google Patents 🔄 Sync Now

Abstract

Abstract Novel substituted N-[(4-piperidinyl)alkyl] bicyclic condensed oxazol- and thiazolamines useful as anti-depressives, in the treatment of Parkinson's disease and in the treatment of diseases related with disturbed enterokinesia.

Inventors

  • 👤 Frans E. Janssens
  • 👤 Theophilus T. J. M. Van Offenwert
  • 👤 Raymond A. Stokbroekx
  • 👤 Bernard R. Boar

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-07 19:36
CPC Classifications
C; C07; C07D; C07D413/00; C07D413/02; C07D413/12; C07D413/14; C07D417/00; C07D417/02; C07D417/12; C07D417/14; C07D513/00; C07D513/02; C07D513/04

Claims Analysis

Total Claims: 26
Claim 1
Independent Claim 296 words
A chemical compound having the formula ##STR24## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a), may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atoms in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 --O-- or --OCH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR25## and a radical of formula ##STR26## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 2
Dependent Claim 296 words
A chemical compound having the formula ##STR24## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a), may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atoms in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 --O-- or --OCH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR25## and a radical of formula ##STR26## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 3
Dependent Claim 59 words
A chemical compound according to claim 1, wherein L is a radical of formula (h) wherein R 3 and R 4 are both hydrogen; or L is a radical of formula (i) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy or phenyl C 1-6 alkyloxy and R 4 is hydrogen, halo or C 1-6 alkyloxy.
Claim 4
Dependent Claim 68 words
A chemical compound according to claim 2, wherein R is hydrogen; L is a radical of formula (h) wherein R 2 is hydrogen, or L is a radical of formula (i) wherein R 3 is hydrogen or halo and R 4 is hydrogen; and R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl and arylcarbonyl.
Claim 5
Dependent Claim 88 words
A chemical compound according to claim 3, wherein Q is C 1-3 alkanediyl; L is a radical of formula (h) wherein Alk is methylene; and R 1 is a member selected from the group consisting of hydrogen, C 1-4 alkyl, aryl C 1-2 alkyl and arylcarbonyl, wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, furanyl and thiazolyl; said substituted phenyl being phenyl substituted with up to 2 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, methyl and methoxy.
Claim 6
Dependent Claim 25 words
A chemical compound according to claim 4 wherein said bivalent radical of formula (a) is optionally substituted with up to three C 1-6 alkyloxy radicals.
Claim 7
Dependent Claim 11 words
A chemical according to claim 1 wherein the compound is N-[[1-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.
Claim 8
Dependent Claim 12 words
A chemical compound according to claim 1 wherein the compound is (S)-(-)-N-[[1-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.
Claim 9
Dependent Claim 87 words
A chemical compound according to claim 1, wherein Z is --O-- or --S--; R 1 is hydrogen or C 1-6 alkyl; Q is CH 2 ; R is hydrogen; and L is a radical of formula (h) wherein Alk is --CH 2 --, X is --O--, R 2 is hydrogen and R 3 and R 4 are hydrogen; and wherein one or two hydrogen atoms in said radical (a) may each independently from each other be replaced by halo, C 1-6 alkyl, hydroxy or C 1-6 alkyloxy.
Claim 10
Dependent Claim 11 words
A chemical compound according to claim 1, wherein Z is --S--.
Claim 11
Dependent Claim 312 words
A pharmaceutical composition comprising an inert carrier and a anti-depressive or anti-Parkinson or enterokinetically effective amount of a compound having the formula ##STR27## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a) may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atom in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 --O-- or --O--CH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR28## and a radical of formula ##STR29## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 12
Dependent Claim 312 words
A pharmaceutical composition comprising an inert carrier and a anti-depressive or anti-Parkinson or enterokinetically effective amount of a compound having the formula ##STR27## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a) may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atom in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 --O-- or --O--CH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR28## and a radical of formula ##STR29## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 13
Dependent Claim 59 words
A pharmaceutical composition according to claim 10, wherein L is a radical of formula (h) wherein R 3 and R 4 are both hydrogen; or L is a radical of formula (i) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy or phenyl C 1-6 alkyloxy and R 4 is hydrogen, halo or C 1-6 alkyloxy.
Claim 14
Dependent Claim 68 words
A pharmaceutical composition according to claim 9, wherein R is hydrogen; L is a radical of formula (h) wherein R 2 is hydrogen, or L is a radical of formula (i) wherein R 3 is hydrogen or halo and R 4 is hydrogen; and R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl and arylcarbonyl.
Claim 15
Dependent Claim 88 words
A pharmaceutical composition according to claim 12, wherein Q is C 1-3 alkanediyl; L is a radical of formula (h) wherein Alk is methylene; and R 1 is a member selected from the group consisting of hydrogen, C 1-4 alkyl, aryl C 1-2 alkyl and arylcarbonyl, wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, furanyl and thiazolyl; said substituted phenyl being phenyl substituted with up to 2 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, methyl and methoxy.
Claim 16
Dependent Claim 25 words
A pharmaceutical composition according to claim 11 wherein said bivalent radical of formula (a) is optionally substituted with up to three C 1-6 alkyloxy radicals.
Claim 17
Dependent Claim 12 words
A pharmaceutical composition according to claim 8 wherein the compound is N-[[1-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.
Claim 18
Dependent Claim 12 words
A pharmaceutical composition according to claim 10 wherein the compound is (S)-(-)-N-[[1-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.
Claim 19
Independent Claim 338 words
A method of treating depressive conditions, Parkinson's disease or diseases related with disturbed enterokinesia in warm blooded animals suffering from the same, which method comprises the systemic administration to warm blooded animals of an effective anti-depressive or anti-Parkinson or enterokinesia effective amount of a compound having the formula ##STR30## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a) may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atoms in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 -- or --O--CH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR31## and a radical of formula ##STR32## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 20
Independent Claim 338 words
A method of treating depressive conditions, Parkinson's disease or diseases related with disturbed enterokinesia in warm blooded animals suffering from the same, which method comprises the systemic administration to warm blooded animals of an effective anti-depressive or anti-Parkinson or enterokinesia effective amount of a compound having the formula ##STR30## or a pharmaceutically acceptable acid addition salt or a possible stereochemically isomeric form thereof, wherein ═A 1 --A 2 ═A 3 --A 4 ═ is a bivalent radical having the formula ═CH--CH═CH--CH═ (a) wherein up to three hydrogen atoms in said radical (a) may each independently from each other be replaced by halo, hydroxy, amino, trifluoromethyl, C 1-6 alkyl or C 1-6 alkyloxy, or two hydrogen atoms in said radical (a) substituted on adjacent carbon atoms may be replaced by a bivalent radical of formula --O--CH 2 -- or --O--CH 2 --CH 2 --O--; Z is --O-- or --S--; R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl, arylcarbonyl and C 1-6 alkyloxycarbonyl; Q is C 1-4 alkanediyl; R is a member selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy and C 1-6 alkyloxy; L is a member selected from the group consisting of a radical of formula ##STR31## and a radical of formula ##STR32## Alk is C 1-4 alkanediyl; X is --O-- or --CH 2 --; R 2 is hydrogen or C 1-6 alkyl; R 3 and R 4 are each independently selected from the group consisting of hydrogen, halo, trifluoromethyl, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy and phenyl C 1-6 alkyloxy; wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, pyridinyl, mono- and di(C 1-6 alkyloxy)-pyridinyl, thienyl, halothienyl, C 1-6 alkylthienyl, pyrrolyl, C 1-6 alkylpyrrolyl, furanyl, furanyl substituted with C 1-6 alkyl, pyrazinyl, thiazolyl and imidazolyl; said substituted phenyl being phenyl substituted with up to 3 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, C 1-6 alkyl and C 1-6 alkyloxy.
Claim 21
Dependent Claim 58 words
A method according to claim 17, wherein L is a radical of formula (h) wherein R 3 and R 4 are both hydrogen; or L is a radical of formula (i) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy or phenyl C 1-6 alkyloxy and R 4 is hydrogen, halo or C 1-6 alkyloxy.
Claim 22
Dependent Claim 67 words
A method according to claim 18, wherein R is hydrogen; L is a radical of formula (h) wherein R 2 is hydrogen, or L is a radical of formula (i) wherein R 3 is hydrogen or halo and R 4 is hydrogen; and R 1 is a member selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, aryl C 1-6 alkyl and arylcarbonyl.
Claim 23
Dependent Claim 87 words
A method according to claim 19, wherein Q is C 1-3 alkanediyl; L is a radical of formula (h) wherein Alk is methylene; and R 1 is a member selected from the group consisting of hydrogen, C 1-4 alkyl, aryl C 1-2 alkyl and arylcarbonyl, wherein aryl is a member selected from the group consisting of phenyl, substituted phenyl, furanyl and thiazolyl; said substituted phenyl being phenyl substituted with up to 2 substituents each independently selected from the group consisting of halo, hydroxy, trifluoromethyl, methyl and methoxy.
Claim 24
Dependent Claim 24 words
A method according to claim 20 wherein said bivalent radical of formula (a) is optionally substituted with up to three C 1-6 alkyloxy radicals.
Claim 25
Dependent Claim 11 words
A method according to claim 17 wherein the compound is N-[[1-(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.
Claim 26
Dependent Claim 11 words
A method according to claim 17 wherein the compound is (S)-(-)-N-[[1-[(2,3-dihydro-1,4-benzodioxin-2-yl)methyl]-4-piperidinyl]methyl]-2-benzothiazolamine.

References Cited (Backward Citations)

US3953461A Cited
US4224333A Cited
US4342761A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1990-08-24 1991-02-23 1991-08-25 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1994-08-24 1995-02-23 1995-08-25 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1998-08-24 1999-02-23 1999-08-25 $7700.00 Window Closed / Lapsed

Assigned Categories & Tags

No categories assigned to this patent yet.

Assign Category Tag