US4758559A
Expired / Lapsed
US
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Pyrrolo[1,2-a] [4,1]benzoxazepine derivatives useful as calmodulin and histamine inhibitors
Assignee: Novartis Consumer Health Inc
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Filing: 1986-01-21
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Granted: 1988-07-19
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Expires: 2006-01-21
Abstract
Abstract Disclosed are the compounds of the formula ##STR1## wherein n represents the integer 1,2,3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; R 4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl piperazino, pyrrolidino, piperidino or substituted piperidino selected from ##STR2## in which R 5 represents hydrogen, halogen or lower alkyl; and pharmaceutically acceptable salts thereof; which are useful in mammals as calmodulin antagonists for the treatments of gastrointestinal disorders.
Inventors
- 👤 Jan W. F. Wasley
- 👤 Jon Norman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 04:25
CPC Classifications
C; C07; C07D; C07D498/00; C07D498/02; C07D498/04; A; A61; A61P; A61P1/00; A61P1/12; C07D519/00
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
93 words
A compound of the formula ##STR12## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; R 4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl-piperazino in which aryl represents phenyl or phenyl monosubstituted by lower alkyl or halogen, pyrrolidino, piperidino or substituted piperidino selected from ##STR13## in which R 5 represents hydrogen, halogen or lower alkyl; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
93 words
A compound of the formula ##STR12## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; R 4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl-piperazino in which aryl represents phenyl or phenyl monosubstituted by lower alkyl or halogen, pyrrolidino, piperidino or substituted piperidino selected from ##STR13## in which R 5 represents hydrogen, halogen or lower alkyl; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
31 words
A compound according to claim 1 of formula I wherein n represents 1 or 2; R 4 represents substituted piperidino as defined in claim 1; or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
53 words
A compound according to claim 1 of the formula ##STR14## wherein R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; n represents an integer from 1 to 4; and R 5 represents hydrogen, halogen or lower alkyl; or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
45 words
A compound according to claim 3 of formula II wherein n represents the integer 1 or 2; R 2 represents straight chain lower alkyl of 1 to 4 carbon atoms; R 1 and R 5 represent hydrogen or halogen; or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
33 words
A compound according to claim 3 of formula II wherein R 1 and R 5 represent hydrogen; R 2 represents methyl; and n represents the integer 1; or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
31 words
A gastrointestinal antisecretory pharmaceutical composition suitable for administration to a mammal comprising an effective antisecretory amount of a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.
Claim 8
Dependent Claim
30 words
An antidiarrheal pharmaceutical composition suitable for administration to a mammal comprising an effective antidiarrheal amount of a compound of claim 5 in combination with one or more pharmaceutically acceptable carriers.
Claim 9
Dependent Claim
53 words
A method of treating calmodulin mediated diarrhea in a mammal which comprises administering to a mammal in need thereof an effective antidiarrheal amount of a compound of claim 3 or an effective antidiarrheal amount of a pharmaceutical composition comprising a compound of claim 3 in combination with one or more pharmaceutically acceptable carriers.
Claim 10
Dependent Claim
53 words
A method of treating calmodulin mediated diarrhea in a mammal which comprises administering to a mammal in need thereof an effective antidiarrheal amount of a compound of claim 4 or an effective antidiarrheal amount of a pharmaceutical composition comprising a compound of claim 4 in combination with one or more pharmaceutically acceptable carriers.
Claim 11
Dependent Claim
53 words
A method of treating calmodulin mediated diarrhea in a mammal which comprises administering to a mammal in need thereof an effective antidiarrheal amount of a compound of claim 5 or an effective antidiarrheal amount of a pharmaceutical composition comprising a compound of claim 5 in combination with one or more pharmaceutically acceptable carriers.
Claim 12
Dependent Claim
59 words
A method of inhibiting gastric acid secretion in a mammal which comprises administering to a mammal in need thereof an effective gastric acid secretion inhibiting amount of a compound of claim 3 or an effective gastric acid secretion inhibiting amount of a pharmaceutical composition comprising a compound of claim 3 in combination with one or more pharmaceutically acceptable carriers.
Claim 13
Dependent Claim
56 words
A method of treating calmodulin mediated gastrointestinal secretory disorders in a mammal which comprises administering to a mammal in need thereof an effective gastrointestinal secretion inhibiting amount of a compound of claim 3 or an effective amount of a pharmaceutical composition comprising a compound of claim 3 in combination with one or more pharmaceutically acceptable carriers.
Claim 14
Dependent Claim
54 words
A method of inhibiting calmodulin activity in a mammal which comprises administering to a mammal in need thereof an effective calmodulin inhibiting amount of a compound of claim 1 or an effective calmodulin inhibiting amount of a pharmaceutical composition comprising a compound of claim 1 in combination with one or more pharmaceutically acceptable carriers.
Claim 15
Dependent Claim
103 words
A compound of the formula ##STR15## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; and X represents hydroxy; or a compound of the formula ##STR16## wherein n, R 1 , R 2 and R 3 have meaning as defined above; or a compound of the formula ##STR17## or a reactive ester selected from lower alkyl or phenyl ester wherein n, R 1 , R 2 and R 3 have the meaning as defined above.
Claim 16
Dependent Claim
103 words
A compound of the formula ##STR15## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; and X represents hydroxy; or a compound of the formula ##STR16## wherein n, R 1 , R 2 and R 3 have meaning as defined above; or a compound of the formula ##STR17## or a reactive ester selected from lower alkyl or phenyl ester wherein n, R 1 , R 2 and R 3 have the meaning as defined above.
Claim 17
Dependent Claim
87 words
A compound of the formula ##STR18## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; R 4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl-piperazino in which aryl represents phenyl or phenyl monosubstituted by lower alkyl or halogen, pyrrolidino, piperidino or substituted piperidino selected from ##STR19## in which R 5 represents hydrogen, halogen or lower alkyl.
Claim 18
Dependent Claim
87 words
A compound of the formula ##STR18## wherein n represents the integer 1, 2, 3 or 4; R 1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R 2 represents hydrogen or lower alkyl; R 3 represents hydrogen, lower alkyl or halogen; R 4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl-piperazino in which aryl represents phenyl or phenyl monosubstituted by lower alkyl or halogen, pyrrolidino, piperidino or substituted piperidino selected from ##STR19## in which R 5 represents hydrogen, halogen or lower alkyl.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-07-19 | 1992-01-18 | 1992-07-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-07-19 | 1996-01-18 | 1996-07-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-07-19 | 2000-01-18 | 2000-07-19 | $7700.00 | Window Closed / Lapsed |