US4806536A
Expired / Lapsed
US
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Piperazinyl-substituted pyridine and imidazole anti-arrhythmic agents
Assignee: Pfizer Inc
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Filing: 1987-02-02
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Granted: 1989-02-21
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Expires: 2007-02-02
Abstract
Abstract A series of novel 4-substituted piperazinyl-pyridine and 4-substituted piperazinyl-imidazole compounds have been prepared, including their pharmaceutically acceptable salts, wherein the 4-substituent is a lower phenylalkyl group or a derivative thereof further substituted on the phenyl moiety by a sulphamoyl or sulphonylamino group or by a nitro, amino or acetamido group. These particular compounds are useful in therapy as highly effective anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrythmias. The most preferred member compound of the series is N-{4-[1-hydroxy-2-(4-[4-pyridinyl]-1-piperazinyl)ethyl]phenyl} methanesulphonamide. Methods for preparing all these compounds from known starting materials are provided.
Inventors
- 👤 Peter E. Cross
- 👤 Roger P. Dickinson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 20:14
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/04; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/72; C07D213/74; A; A61; A61P; A61P9/00; A61P9/06
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
192 words
A piperazinyl-substituted pyridine or imidazole compound of the formula: ##STR68## or a pharmaceutically acceptable salt thereof, wherein "Het 1 " is selected from (a) a 3- or 4-pyridinyl group optionally substituted by one or two substituents each independently selected from C 1 -C 4 alkyl and amino, (b) a 2-pyridinyl group substituted by an amino group and (c) a 2-imidazolyl group optionally substituted by one or two C 1 -C 4 alkyl groups; R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; and X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three.
Claim 2
Dependent Claim
192 words
A piperazinyl-substituted pyridine or imidazole compound of the formula: ##STR68## or a pharmaceutically acceptable salt thereof, wherein "Het 1 " is selected from (a) a 3- or 4-pyridinyl group optionally substituted by one or two substituents each independently selected from C 1 -C 4 alkyl and amino, (b) a 2-pyridinyl group substituted by an amino group and (c) a 2-imidazolyl group optionally substituted by one or two C 1 -C 4 alkyl groups; R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; and X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three.
Claim 3
Dependent Claim
47 words
A compound as claimed in claim 1 wherein "Het 1 " is selected from (a) a 3- or 4-pyridinyl group optionally substituted by an amino or methyl group, (b) a 2-pyridinyl group substituted by an amino group and (c) a 2-imidazolyl group substituted by a methyl group.
Claim 4
Dependent Claim
21 words
A compound as claimed in claim 2 wherein "Het 1 " is 3-pyridinyl, 4-amino-3-pyridinyl, 4-pyridinyl, 2-methyl-4-pyridinyl, 3-methyl-4-pyridinyl, 2-amino-4-pyridinyl, 4-amino-2-pyridinyl or 1-methyl-imidazol-2-yl.
Claim 5
Dependent Claim
16 words
A compound as claimed in claim 3 wherein "Het 1 " is 4-pyridinyl, 2-amino-4-pyridinyl or 4-amino-2-pyridinyl.
Claim 6
Dependent Claim
57 words
A compound as claimed in claim 1 wherein R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl or --N(C 1 -C 4 alkyl) 2 , (b) --SO 2 NHR 1 where R 1 is hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido.
Claim 7
Dependent Claim
48 words
A compound as claimed in claim 5 wherein R is --NHSO 2 CH 3 , --NHSO 2 CH 2 H 5 , --NHSO 2 N(CH 3 ) 2 , --SO 2 NH 2 , --SO 2 NHCH 3 , --NO 2 , --NH 2 or --NHCOCH 3 .
Claim 8
Dependent Claim
25 words
A compound as claimed in claim 6 wherein R is --NHSO 2 CH 3 , --SO 2 NH 2 or --SO 2 NHCH 3 .
Claim 9
Dependent Claim
35 words
A compound as claimed in claim 1 wherein X is --CH 2 --, --(CH 2 ) 2 --, --COCH 2 --, --CO(CH 2 ) 2 --, --CH(OH)CH 2 -- or --CH(OH)(CH 2 ) 2 --.
Claim 10
Dependent Claim
17 words
A compound as claimed in claim 8 wherein X is --COCH 2 -- or --CH(OH)CH 2 --.
Claim 11
Dependent Claim
123 words
A compound as claimed in claim 1 wherein "Het 1 " is selected from (a) a 3- or 4-pyridinyl group optionally substituted by an amino or methyl group, (b) a 2-pyridinyl group substituted by an amino group and (c) 2-imidazolyl group substituted by a methyl group; R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl or --N(C 1 -C 4 ) 2 , (b) --SO 2 NHR 1 where R 1 is hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; and X is --CH 2 --, --(CH 2 ) 2 --, --COCH 2 --, --CO(CH 2 ) 2 --, --CH(OH)CH 2 -- or CH(OH)(CH 2 ) 2 --.
Claim 12
Dependent Claim
71 words
A compound as claimed in claim 10 wherein "Het 1 " is 3-pyridinyl, 4-amino-3-pyridinyl, 4-pyridinyl, 2-methyl-4-pyridinyl, 3-methyl-4-pyridinyl, 2-amino-4-pyridinyl, 4-amino-2-pyridinyl or 1-methyl-imidazol-2-yl; R is --NHSO 2 CH 3 , --NHSO 2 C 2 H 5 , --NHSO 2 N--(CH 3 ) 2 , --SO 2 NH 2 , --SO 2 NHCH 3 , --NO 2 , --NH 2 or --NHCOCH 3 ; and X is --COCH 2 -- or --CH(OH)CH 2 --.
Claim 13
Dependent Claim
16 words
A compound as claimed in claim 11 wherein "Het 1 " is 4-pyridinyl, 2-amino-4-pyridinyl or 4-amino-2-pyridinyl.
Claim 14
Dependent Claim
25 words
A compound as claimed in claim 11 wherein R is --NHSO 2 CH 3 , --SO 2 NH 2 or --SO 2 NHCH 3 .
Claim 15
Dependent Claim
152 words
A compound as claimed in claim 1 wherein "Het 1 " is a 3- or 4-pyridinyl group optionally substituted by one or two substituents each independently selected from C 1 -C 4 alkyl and amino; R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro and (d) amino; and X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three.
Claim 16
Dependent Claim
15 words
A compound as claimed in claim 14 wherein "Het 1 " is 4-pyridinyl or 2-amino-4-pyridinyl.
Claim 17
Dependent Claim
45 words
A compound as claimed in claim 14 wherein R is --NHSO 2 CH 3 , --NHSO 2 C 2 H 5 , --NHSO 2 N(CH 3 ) 2 , --SO 2 NH 2 , --SO 2 NHCH 3 , NO 2 or NH 2 .
Claim 18
Dependent Claim
25 words
A compound as claimed in claim 16 wherein R is --NHSO 2 CH 3 , --SO 2 NH 2 or --SO 2 NHCH 3 .
Claim 19
Dependent Claim
34 words
A compound as claimed in claim 14 wherein X is --CH 2 --, --(CH 2 ) 2 --, --COCH 2 --, --CO(CH 2 ) 2 , --CH(OH)CH 2 or --CH(OH)(CH 2 ) 2 --.
Claim 20
Dependent Claim
17 words
A compound as claimed in claim 18 wherein X is --COCH 2 -- or --CH(OH)CH 2 --.
Claim 21
Dependent Claim
80 words
A compound as claimed in claim 14 wherein "Het 1 " is 4-pyridinyl or 2-amino-4-pyridinyl; R is --NHSO 2 CH 3 , --NHSO 2 C 2 H 5 , --NHSO 2 N(CH 3 ) 3 , --SO 2 NH 2 , --SO 2 NHCH 3 , NO 2 or NH 2 ; and X is --CH 2 --, --(CH 2 ) 2 --, --COCH 2 --, --CO(CH 2 ) 2 --, --CH(OH)CH 2 -- or --CH(OH)(CH 2 ) 2 --.
Claim 22
Dependent Claim
35 words
A compound as claimed in claim 20 wherein R is --NHSO 2 CH 3 , --SO 2 NH 2 or --SO 2 NHCH 3 , and X is --COCH 2 -- or --CH(OH)CH 2 --.
Claim 23
Dependent Claim
1 words
N-{4-[1-Hydroxy-2-(4-[4-pyridinyl]-1-piperazinyl)ethyl]phenyl}methanesulphonamide.
Claim 24
Dependent Claim
1 words
N-{4-[1-Hydroxy-2-(4-[4-pyridinyl]-1-piperazinyl)ethyl]phenyl}methanesulphonamide.
Claim 25
Dependent Claim
23 words
A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and an effective anti-arrhythmic amount of a compound as claimed in claim 1.
Claim 26
Dependent Claim
39 words
A method for preventing or reducing cardiac arrythmias in the treatment of a subject afflicted with an impaired cardiac pump function, which comprises administering to said subject an effective anti-arrhythmic amount of a compound as claimed in claim 1.
Claim 27
Dependent Claim
168 words
A piperazinyl-substituted pyridine compound of the formula: ##STR69## wherein "Het 2 " is a 2-, 3- or 4-pyridinyl group substituted by a nitro group, or an N-oxide derivative thereof, or a 2-, 3- or 4-pyridinyl group substituted by a group of the formula --NHCOO(C 1 -C 4 alkyl); R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 L wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; and X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three.
Claim 28
Dependent Claim
168 words
A piperazinyl-substituted pyridine compound of the formula: ##STR69## wherein "Het 2 " is a 2-, 3- or 4-pyridinyl group substituted by a nitro group, or an N-oxide derivative thereof, or a 2-, 3- or 4-pyridinyl group substituted by a group of the formula --NHCOO(C 1 -C 4 alkyl); R is selected from (a) --NHSO 2 R 3 where R 3 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 L wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; and X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three.
Claim 29
Dependent Claim
16 words
A compound as claimed in claim 25 wherein "Het 2 " is 4-nitro-1-oxido-3-pyridinyl, 2-ethoxycarbonylamino-4-pyridinyl or 4-nitro-2-pyridinyl.
Claim 30
Dependent Claim
136 words
A 4-substituted piperazine compound of the formula: ##STR70## wherein R is selected from (a) --NHSO 2 R 3 where R 3 L is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three; and Y is hydrogen or an amino-protecting group.
Claim 31
Dependent Claim
136 words
A 4-substituted piperazine compound of the formula: ##STR70## wherein R is selected from (a) --NHSO 2 R 3 where R 3 L is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl or --NR 1 R 2 wherein R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (b) --SO 2 NR 1 R 2 where R 1 and R 2 are each independently hydrogen or C 1 -C 4 alkyl, (c) nitro, (d) amino and (e) acetamido; X is a group of the formula --(CH 2 ) m -- where m is an integer of from one to four, inclusive, or it is --CO(CH 2 ) n -- or --CH(OH)(CH 2 ) n -- where n is one, two or three; and Y is hydrogen or an amino-protecting group.
Claim 32
Dependent Claim
16 words
A compound as claimed in claim 27 wherein the amino-protecting group is acetyl, formyl or benzyl.
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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) | 1992-02-21 | 1992-08-22 | 1993-02-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-02-21 | 1996-08-22 | 1997-02-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-02-21 | 2000-08-22 | 2001-02-21 | $7700.00 | Window Closed / Lapsed |