US4562201A
Expired / Lapsed
US
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Aminomethyl benzanilides
Assignee: Bristol Myers Squibb Pharma Co
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Filing: 1982-07-26
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Granted: 1985-12-31
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Expires: 2002-07-26
Abstract
Abstract The present invention relates to new compounds of the formula <IMAGE> where X is <IMAGE> +TR <IMAGE> alkylene, or -S- where R1 is hydrogen, alkyl, or aryl; W is hydrogen, hydroxy, amino, alkyloxy, aryloxy, O-alkyl, or O-aralkyl; (Y)A is -CH2NR2R3 where R2 and R3 may be hydrogen, substituted alkyls, aryls, or together with N form a 5 to 7 membered heterocyclic group; and Ar is a substituted or unsubstituted aryl. These compounds are useful in the treatment of various cardiac arrhythmias.
Inventors
- 👤 David M. Stout
- 👤 William L. Matier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 14:19
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/08; C07D295/096; C07D295/10; C07D295/112; C07D295/12; C07D295/135; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/38
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
252 words
A compound of the formula ##STR171## wherein X is ##STR172## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoloweralkyl having the formula --CH 2 NR 2 R 3 where R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine, ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amino, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR173## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, haloloweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
252 words
A compound of the formula ##STR171## wherein X is ##STR172## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoloweralkyl having the formula --CH 2 NR 2 R 3 where R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine, ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amino, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR173## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, haloloweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
9 words
The compound of claim 1 wherein Ar is phenyl.
Claim 4
Dependent Claim
98 words
A compound of the formula ##STR174## wherein x is ##STR175## wherein R 1 is hydrogen or lower alkyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoloweralkyl having the formula --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
98 words
A compound of the formula ##STR174## wherein x is ##STR175## wherein R 1 is hydrogen or lower alkyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoloweralkyl having the formula --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
20 words
A compound of claim 3 wherein R 1 is hydrogen, n and m are each 0, and Ar is phenyl.
Claim 7
Dependent Claim
9 words
A compound according to claim 4 which is N-benzoyl-3,5-bis(N-pyrrolidinylmethyl)-4-hydroxyaniline.
Claim 8
Dependent Claim
9 words
A compound according to claim 4 which is N-([3,5-bis(pyrrolidinylmethyl)-4-hydroxy]benzoyl)-aniline.
Claim 9
Dependent Claim
270 words
A cardiac arrhythmic composition containing an antiarrhythmic-effective amount of the compound having the formula ##STR176## wherein X is ##STR177## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl,; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoalkyl having the formula --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine, ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweroalkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR178## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, haloloweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof; in admixture with a pharmaceutically acceptable carrier or diluent.
Claim 10
Dependent Claim
270 words
A cardiac arrhythmic composition containing an antiarrhythmic-effective amount of the compound having the formula ##STR176## wherein X is ##STR177## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl,; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is an aminoalkyl having the formula --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine, ring, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweroalkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR178## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, haloloweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof; in admixture with a pharmaceutically acceptable carrier or diluent.
Claim 11
Dependent Claim
149 words
A cardiac arrhythmic composition containing an antiarrhythmic-effective amount of the compound having the formula ##STR179## wherein x is ##STR180## wherein R 1 is hydrogen or lower alkyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR181## wherein (Z).sub.β is independently chloro, methyl, nitro or carboxymethyl and β is from 0 to 3; or a pharmaceutically acceptable salt thereof; in admixture with a pharmaceutically acceptable carrier or diluent.
Claim 12
Dependent Claim
149 words
A cardiac arrhythmic composition containing an antiarrhythmic-effective amount of the compound having the formula ##STR179## wherein x is ##STR180## wherein R 1 is hydrogen or lower alkyl; W is hydrogen or hydroxy; (Y) A is positioned ortho to W and is --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR181## wherein (Z).sub.β is independently chloro, methyl, nitro or carboxymethyl and β is from 0 to 3; or a pharmaceutically acceptable salt thereof; in admixture with a pharmaceutically acceptable carrier or diluent.
Claim 13
Dependent Claim
20 words
A composition of claim 8 wherein R 1 is hydrogen, n and m are each 0, and Ar is phenyl.
Claim 14
Dependent Claim
12 words
A composition according to claim 9 wherein the compound is N-benzoyl-3,5-bis(N-pyrrolidinylmethyl)-4-hydroxyaniline composition.
Claim 15
Dependent Claim
11 words
A composition according to claim 9 wherein the compound is N-([3,5-bis(pyrrolidinylmethyl)-4-hydroxy]benzoyl)-aniline.
Claim 16
Independent Claim
269 words
A method of treating cardiac arrhythmias in a patient by administration of an anti-arrhythmic effective amount to such patient of a compound having the formula ##STR182## where x is ##STR183## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl; W is hydrogen, or hydroxy; (Y) A is positioned ortho to W and is --CH 2 --NR 2 R 3 , wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloalkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amino, hydroxy, cyclolowerakyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR184## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, halo- loweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cyclolower-alkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof.
Claim 17
Independent Claim
269 words
A method of treating cardiac arrhythmias in a patient by administration of an anti-arrhythmic effective amount to such patient of a compound having the formula ##STR182## where x is ##STR183## wherein R 1 is hydrogen, lower alkyl, phenyl, or benzyl; W is hydrogen, or hydroxy; (Y) A is positioned ortho to W and is --CH 2 --NR 2 R 3 , wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, unsubstituted or substituted with 1 to 3 substituents each of which is independently halo, lower alkyl, lower alkoxy, haloalkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amino, hydroxy, cyclolowerakyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR184## wherein (Z).sub.β is independently halo, lower alkyl, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; and β is from 0 to 3 with the proviso that when β is 1 and (Z).sub.β is positioned para to --(CH 2 )n--, that (Z).sub.β is halo, lower alkoxy, haloloweralkyl, amino, aminoloweralkyl, nitro, cyano, carbamoyl, amido, hydroxy, cycloloweralkyl, lower alkenyl, lower alkynyl, or phenyl; with the proviso that when β is 3 that (Z).sub.β is halo, lower alkyl, halo- loweralkyl, amino, nitro, cyano, carbamoyl, amido, hydroxy, cyclolower-alkyl, lower alkenyl, lower alkynyl, or phenol; or a pharmaceutically acceptable salt thereof.
Claim 18
Dependent Claim
17 words
The method of claim 12 wherein the compound is administered for suppression of supraventricular or ventricular tachyarrhythmias.
Claim 19
Dependent Claim
21 words
The method of claim 12 wherein the compound is administered for the suppression of premature supraventricular complexes or premature ventricular complexes.
Claim 20
Independent Claim
155 words
A method of treating cardiac arrhythmias in a patient by administration of an anti-arrhythmic effective amount to such patient of a compound having the formula ##STR185## where X is ##STR186## wherein R 1 is hydrogen or loweralkyl; W is hydrogen or loweralkyl; w is hydrogen or hydroxy; (Y) A is positioned ortho to W and is --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR187## wherein (Z).sub.β is independently chloro, methyl, nitro or carboxymethyl and β is from 0 to 3; or a pharmaceutically acceptable salt thereof.
Claim 21
Independent Claim
155 words
A method of treating cardiac arrhythmias in a patient by administration of an anti-arrhythmic effective amount to such patient of a compound having the formula ##STR185## where X is ##STR186## wherein R 1 is hydrogen or loweralkyl; W is hydrogen or loweralkyl; w is hydrogen or hydroxy; (Y) A is positioned ortho to W and is --CH 2 NR 2 R 3 wherein R 2 and R 3 are the same or different and may be lower alkyl or R 2 and R 3 may together with N form a pyrrolidine group, and A is 2; n and m are independently from 0 to 5; and Ar is phenyl or cinnamoyl optionally fused with a phenyl group, with the proviso that when Ar is phenyl that phenyl is represented by the formula ##STR187## wherein (Z).sub.β is independently chloro, methyl, nitro or carboxymethyl and β is from 0 to 3; or a pharmaceutically acceptable salt thereof.
Claim 22
Dependent Claim
26 words
A method of claim 15 in which the compound is one wherein R 1 is hydrogen, n and m are each 0, and Ar is phenyl.
Claim 23
Dependent Claim
12 words
A method according to claim 16 in which the compound is N-benzoyl-3,5-bis(N-pyrrolidinylmethyl)-4-hydroxyaniline.
Claim 24
Dependent Claim
12 words
A method according to claim 16 in which the compound is N-([3,5-bis(pyrrolidinylmethyl)-4-hydroxy]benzoyl)-aniline.
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) | 1988-12-30 | 1989-07-01 | 1989-12-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-12-30 | 1993-07-01 | 1993-12-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-12-30 | 1997-07-01 | 1997-12-31 | $7700.00 | Window Closed / Lapsed |