US4804663A
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US
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3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles
Assignee: Janssen Pharmaceutica NV
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Filing: 1986-02-05
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Granted: 1989-02-14
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Expires: 2006-02-05
Abstract
Abstract 3-Piperdinyl-1,2-benzisothiazoles and 3-piperidinyl-1,2-benzisoxazoles and their pharmaceutically acceptable acid addition salts having useful antipsychotic properties and being useful in the treatment of a variety of complaints in which serotonin release is of predominant importance.
Inventors
- 👤 Ludo E. J. Kennis
- 👤 Jan Vandenberk
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 04:09
CPC Classifications
C; C07; C07D; C07D413/00; C07D413/14; A; A61; A61P; A61P1/00; A61P1/12; A61P25/00; A61P25/18; A61P25/20; A61P43/00; A61P7/00; A61P7/02; C07D417/00; C07D417/14; C07D471/00; C07D471/02; C07D471/04; C07D487/00; C07D487/02; C07D487/04; C07D497/00; C07D497/02; C07D497/04; C07D513/00; C07D513/02; C07D513/04
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
203 words
A chemical compound having the formula ##STR17## or a pharmaceutically acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR18## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR19## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --, said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 2
Dependent Claim
203 words
A chemical compound having the formula ##STR17## or a pharmaceutically acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR18## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR19## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --, said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 3
Dependent Claim
90 words
A chemical compound according to claim 1, wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, hydroxy, amino or azido and R 4 is hydrogen; or Q is a radical of formula (b) wherein R 5 is C 1-6 alkyl and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or C 1-6 alkyl.
Claim 4
Dependent Claim
28 words
A chemical compound according to claim 2, wherein R is hydrogen, R 1 is hydrogen or halo and R 2 is hydrogen, halo, hydroxy or C 1-6 alkyloxy.
Claim 5
Dependent Claim
93 words
A chemical compound according to claim 3, wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo or methyl and Y 1 is O; or Q is a radical of formula (b) wherein --Z--A-- is --S--CH 2 --CH 2 --, --S--(CH 2 ) 3 --, --S--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, --CH═CH--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, or --CH 2 --CH 2 --CH 2 --CH 2 --.
Claim 6
Dependent Claim
21 words
A chemical compound according to claim 4, wherein R 1 is hydrogen, and R 2 is hydrogen, halo, hydroxy or methoxy.
Claim 7
Dependent Claim
14 words
A chemical compound according to claim 1 wherein the compound is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one or 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
Claim 8
Dependent Claim
224 words
A pharmaceutical composition for treating psychotic diseases, comprising an inert carrier and as an active ingredient a pharmaceutically effective amount of a chemical compound having the formula ##STR20## or a pharmaceutically acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR21## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR22## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --, said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 9
Dependent Claim
224 words
A pharmaceutical composition for treating psychotic diseases, comprising an inert carrier and as an active ingredient a pharmaceutically effective amount of a chemical compound having the formula ##STR20## or a pharmaceutically acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR21## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR22## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --, said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 10
Dependent Claim
90 words
A pharmaceutical composition according to claim 7 wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, hydroxy, amino or azido and R 4 is hydrogen; or Q is a radical of formula (b) wherein R 5 is C 1-6 alkyl and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or C 1-6 alkyl.
Claim 11
Dependent Claim
28 words
A pharmaceutical composition according to claim 8 wherein R is hydrogen, R 1 is hydrogen or halo and R 2 is hydrogen, halo, hydroxy or C 1-6 alkyloxy.
Claim 12
Dependent Claim
93 words
A pharmaceutical composition according to claim 9 wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo or methyl and Y 1 is O; or Q is a radical of formula (b) wherein --Z--A-- is --S--CH 2 --CH 2 --, --S--(CH 2 ) 3 --, --S--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, --CH═CH--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, or --CH 2 --CH 2 --CH 2 --CH 2 --.
Claim 13
Dependent Claim
21 words
A pharmaceutical composition according to claim 10 wherein R 1 is hydrogen, and R 2 is hydrogen, halo, hydroxy or methoxy.
Claim 14
Dependent Claim
14 words
A pharmaceutical composition according to claim 7 wherein the compound is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one or 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
Claim 15
Independent Claim
224 words
A method of treating warm-blooded animals suffering from psychotic diseases which comprises the administration thereto of a pharmaceutically effective amount of a chemical compound having the formula ##STR23## or a pharmaceutical acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR24## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR25## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --; said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 16
Independent Claim
224 words
A method of treating warm-blooded animals suffering from psychotic diseases which comprises the administration thereto of a pharmaceutically effective amount of a chemical compound having the formula ##STR23## or a pharmaceutical acceptable acid addition salt thereof, wherein R is hydrogen or C 1-6 alkyl; R 1 and R 2 are each independently members selected from the group consisting of hydrogen, halo, hydroxy, C 1-6 alkyloxy and C 1-6 alkyl; X is O or S; Alk is C 1-4 alkanediyl; and Q is a radical of formula ##STR24## wherein Y 1 and Y 2 are each independently O or S; R 3 is a member selected from the group consisting of hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, nitro, cyano, hydroxy, (C 1-10 alkylcarbonyl)oxy, amino, mono- and di(C 1-6 alkyl)amino, (C 1-10 alkylcarbonyl)amino, phenylmethoxy and azido; R 4 is hydrogen or halo; or a radical of formula ##STR25## wherein R 5 is hydrogen or C 1-6 alkyl; Z is --S--, --CH 2 -- or --CR 6 ═CR 7 --; said R 6 and R 7 being each independently hydrogen or C 1-6 alkyl; and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 --; said R 8 and R 9 being each independently hydrogen, halo, amino or C 1-6 alkyl.
Claim 17
Dependent Claim
89 words
A method according to claim 13 wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, hydroxy, amino or azido and R 4 is hydrogen; or Q is a radical of formula (b) wherein R 5 is C 1-6 alkyl and A is a bivalent radical --CH 2 --CH 2 --, --CH 2 --CH 2 --CH 2 -- or --CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or C 1-6 alkyl.
Claim 18
Dependent Claim
27 words
A method according to claim 14 wherein R is hydrogen, R 1 is hydrogen or halo and R 2 is hydrogen, halo, hydroxy or C 1-6 alkyloxy.
Claim 19
Dependent Claim
92 words
A method according to claim 15 wherein Q is a radical of formula (a) wherein R 3 is hydrogen, halo or methyl and Y 1 is O; or Q is a radical of formula (b) wherein --Z--A-- is --S--CH 2 --CH 2 --, --S--(CH 2 ) 3 --, --S--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, --CH═CH--CR 8 ═CR 9 -- wherein R 8 and R 9 are each independently hydrogen or methyl, or --CH 2 --CH 2 --CH 2 --CH 2 --.
Claim 20
Dependent Claim
20 words
A method according to claim 16 wherein R 1 is hydrogen, and R 2 is hydrogen, halo, hydroxy or methoxy.
Claim 21
Dependent Claim
13 words
A method according to claim 13 wherein the compound is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one or 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-02-14 | 1992-08-15 | 1993-02-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-02-14 | 1996-08-15 | 1997-02-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-02-14 | 2000-08-15 | 2001-02-14 | $7700.00 | Window Closed / Lapsed |