Patent US4167567A successfully refreshed from Google Patents.
US4167567A
Expired / Lapsed
US
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Antihypertensive 4-aminoquinolines
Assignee: Pharmacia and Upjohn Co
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Filing: 1978-05-05
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Granted: 1979-09-11
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Expires: 1998-05-05
Abstract
Abstract Antihypertensive compounds of the formula ll ##STR1## wherein X is chloro or trifluoromethyl; wherein R is an aromatic heterocyclic radical selected from the group consisting of triazinyl, pyrazinyl, pyridinyl, pyrimidinyl or the above radicals substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, or 1 to 4 halo atoms for pyridine, or combinations of substituents, in which alkyl and alkoxy are each of 1 to 3 carbon atoms, inclusive, and halo is fluoro, bromo or chloro, or R is the group ##STR2## in which R 1 is phenyl, phenyl-substituted with one or two halogens, trifluoromethylphenyl, phenyl-substituted with one or two alkoxy or alkyl groups, or alkylphenylsulfonyl, in which alkyl, alkoxy, and halo are defined as above; or R is the group SO 2 R 2 , in which R 1 is dialkylamino, phenyl, phenyl-substituted with one or two halogens, alkyl, trifluoromethyl or alkoxy groups, in which alkyl, alkoxy and halo are defined as hereinabove, are prepared from compounds of the formula ##STR3## WHEREIN X has the significance as above, by reaction with the selected cyclic amine or by reaction of ##STR4## wherein X is defined as above and a selected R 2 -sulfonyl chloride or R 1 -isocyanate. The compounds of formula ll and their pharmacologically acceptable acid addition salts are hypotensive agents which are useful for the treatment of hypertension in mammals, including man.
Inventors
- 👤 John M. McCall
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 16:45
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/16; C07D295/18; C07D295/182; C07D295/192; A; A61; A61P; A61P9/00; A61P9/12; C07D215/00; C07D215/02; C07D215/16; C07D215/38; C07D215/42; C07D215/44
Claims Analysis
Total Claims: 43
Claim 1
Independent Claim
157 words
A compound of the formula II ##STR15## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR16## wherein R 1 is phenyl, phenyl subsituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 2
Dependent Claim
157 words
A compound of the formula II ##STR15## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR16## wherein R 1 is phenyl, phenyl subsituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 3
Dependent Claim
106 words
A compound according to claim 1 of the formula IIA ##STR17## wherein X is chloro or trifluoromethyl; wherein R 5 is (a) pyrimidinyl or pyrazinyl or the alkylthio-, alkyl-, halo- or alkoxy-substituted derivatives thereof, wherein halo is chloro or fluoro and alkyl and alkoxy are of 1 to 3 carbon atoms, (b) halopyridinyl; (c) --SO 2 R 6 , wherein R 6 is phenyl, alkylphenyl, halophenyl, alkoxyphenyl, in which alkoxy, alkyl and halo are defined as above; or (d) ##STR18## wherein R 7 is phenyl, alkylphenyl, halophenyl, trifluoromethylphenyl, or alkylphenylsulfonyl, wherein halo and alkyl are defined as above; or the pharmacologically acceptable acid addition salts thereof.
Claim 4
Dependent Claim
71 words
A compound according to claim 1 of the formula IIB ##STR19## wherein R 8 is (a) pyrimidinyl and pyrazinyl or these groups substituted with methyl, methylthio, methoxy or chloro; (b) halopyridinyl; (c) --SO 2 R 9 , wherein R 9 is ##STR20## p-tolyl, p-chlorophenyl or p-fluorophenyl; or (d) ##STR21## wherein R 10 is halophenyl, phenyl or trifluoromethylphenyl, wherein halo is chloro or fluoro; or the pharmacologically acceptable acid addition salts thereof.
Claim 5
Dependent Claim
21 words
The compound according to claim 2, wherein R 5 is ##STR22## wherein R 7 is m-chlorophenyl and X is trifluoromethyl; 1-[[(3-chlorophenyl)amino]carbonyl]-4-[4-[[(7-trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 6
Dependent Claim
17 words
A compound according to claim 3, wherein R 8 is ##STR23## and R 10 is (m-trifluoromethyl)phenyl; 1-[[[3-(trifluoromethyl)phenyl]amino]carbonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 7
Dependent Claim
12 words
A compound according to claim 3, wherein R 8 is 2,6-dimethoxy-4-pyrimidinyl; 1-(2,6-dimethoxy-4-pyrimidinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 8
Dependent Claim
21 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is ##STR24## wherein R 7 is p-tolyl; 1-[[(4-methylphenyl)amino]carbonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 9
Dependent Claim
12 words
A compound according to claim 3, wherein R 8 is 2,3,5,6-tetrachloropyridinyl; 1-(2,3,5,6-tetrachloro-4-pyridinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 10
Dependent Claim
25 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is p-chlorophenyl; 1-[(4-chlorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 11
Dependent Claim
25 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is p-tolylsulfonyl; 1-[[[(4-methylphenyl)sulfonyl]amino]carbonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 12
Dependent Claim
25 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is p-fluorophenyl; 1-[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 13
Dependent Claim
25 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is dimethylamino; 1-[(dimethylamino)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 14
Dependent Claim
25 words
A compound according to clam 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is p-methoxyphenyl; 1-[(4-methoxyphenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 15
Dependent Claim
25 words
A compound according to clam 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 , wherein R 6 is p-methoxyphenyl; 1-[(4-methoxyphenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 16
Dependent Claim
12 words
A compound according to claim 3, wherein R 8 is 2-pyrazine; 1-(2-pyrazinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 17
Dependent Claim
12 words
A compound according to claim 3, wherein R 8 is 2-pyrimidinyl; 1-[(2-pyrimidinyl)]-4-[4-[[7-trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 18
Dependent Claim
25 words
A compound according to claim 2, wherein X is trifluoromethyl and R 5 is --SO 2 R 6 ; wherein R 6 is 4-methylphenyl; 1-[(4-methylphenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 19
Dependent Claim
16 words
A compound according to claim 2, wherein X is trifluoromethyl and R 8 is 2-methylthio-4-pyrimidinyl; 1-[4-(2-methylthio)-pyrimidinyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 20
Dependent Claim
175 words
A pharmaceutical dosage unit form for systemic administration to alleviate hypertension consisting essentially of an effective non-toxic amount of a compound of the formula ##STR25## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR26## wherein R 1 is phenyl, phenyl substituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 21
Dependent Claim
175 words
A pharmaceutical dosage unit form for systemic administration to alleviate hypertension consisting essentially of an effective non-toxic amount of a compound of the formula ##STR25## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR26## wherein R 1 is phenyl, phenyl substituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 22
Dependent Claim
116 words
The composition according to claim 18, wherein the compound used in effective non-toxic amount is that of the formula IIA ##STR27## wherein X is chloro or trifluoromethyl; wherein R 5 is (a) pyrimidinyl or pyrazinyl or the alkylthio-, alkyl-, halo- or alkoxy-substituted derivatives thereof, wherein halo is chloro or fluoro and alkyl and alkoxy are of 1 to 3 carbon atoms, (b) halopyridinyl; (c) --SO 2 R 6 , wherein R 6 is phenyl, alkylphenyl, halophenyl, alkoxyphenyl, in which alkoxy, alkyl and halo are defined as above; or (d) ##STR28## wherein R 7 is phenyl, alkylphenyl, halophenyl, trifluoromethylphenyl, or alkylphenylsulfonyl, wherein halo and alkyl are defined as above; or the pharmacologically acceptable acid addition salts thereof.
Claim 23
Dependent Claim
80 words
The composition according to claim 18, wherein the compound used in effective non-toxic amount is that of formula IIB ##STR29## wherein R 8 is (a) pyrimidinyl and pyrazinyl or these groups substituted with methyl, methylthio, methoxy or chloro; (b) halopyridinyl; (c) --SO 2 R 9 , wherein R 9 is ##STR30## p-tolyl, p-chlorophenyl or p-fluorophenyl; or (d) ##STR31## wherein R 10 is halophenyl, phenyl or trifluoromethylphenyl, wherein halo is chloro or fluoro; or the pharmacologically acceptable acid addition salts thereof.
Claim 24
Dependent Claim
16 words
The composition according to claim 19, wherein the compound used in effective non-toxic amount is 1-(2,6-dimethoxy-4-pyrimidinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 25
Dependent Claim
16 words
The composition according to claim 19, wherein the compound used in effective non-toxic amount is 1-(2-pyrimidinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 26
Dependent Claim
16 words
The composition according to claim 19, wherein the compound used in effective non-toxic amount is 1-(2-pyrazinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 27
Dependent Claim
16 words
The composition according to claim 20, wherein the compound used in effective non-toxic amount is 1-[(4-methylphenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 28
Dependent Claim
16 words
The composition according to claim 20, wherein the compound used in effective non-toxic amount is 1-[(4-chlorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 29
Dependent Claim
16 words
The composition according to claim 20, wherein the compound used in effective non-toxic amount is 1-[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 30
Dependent Claim
16 words
The composition according to claim 20, wherein the compound used in effective non-toxic amount is 1-[[(3-chlorophenyl(amino]carbonyl]-4-[4-[[(7-trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 31
Dependent Claim
16 words
The composition according to claim 20, wherein the compound used in effective non-toxic amount is 1-[[[3-(trifluoromethyl)phenyl]amino]carbonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 32
Independent Claim
189 words
A method of obtaining antihypertensive effects in a mammal which consists essentially of administering systemically to the mammal a pharmaceutical dosage unit form supplying an effective non-toxic amount for hypertensive effects of a compound of the formula II ##STR32## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR33## wherein R 1 is phenyl, phenyl substituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 33
Independent Claim
189 words
A method of obtaining antihypertensive effects in a mammal which consists essentially of administering systemically to the mammal a pharmaceutical dosage unit form supplying an effective non-toxic amount for hypertensive effects of a compound of the formula II ##STR32## wherein X is chloro or trifluoromethyl; wherein R is (a) triazinyl; (b) pyrazinyl; (c) pyrimidinyl; (d) triazinyl, pyrazinyl, or pyrimidinyl substituted by one or two trifluoromethyl, alkyl, alkoxy, dialkylamino, alkylthio, or halo, wherein halo is fluoro, bromo, or iodo, wherein alkyl is of one to 3 carbon atoms, and wherein alkoxy is of one to 3 carbon atoms; (e) halopyridinyl of 1 to 4 halo atoms; (f) ##STR33## wherein R 1 is phenyl, phenyl substituted with one or two halo or trifluoromethylphenyl, phenyl substituted with one or two alkoxy, alkylphenyl, or alkylphenylsulfonyl, wherein alkyl, alkoxy and halo are as defined above; or (g) --SO 2 R 2 , wherein R 2 is dialkylamino, phenyl substituted with one or two halo, alkylphenyl, phenyl, or trifluoromethylphenyl, or phenyl substituted with one or two alkoxy groups; wherein alkyl, alkoxy, and halo are as defined above; or the pharmacologically acceptable acid addition salts thereof.
Claim 34
Dependent Claim
110 words
A method according to claim 29, wherein the compound is of the formula IIA ##STR34## wherein X is chloro or trifluoromethyl; wherein R 5 is (a) pyrimidinyl or pyrazinyl or the alkylthio-, alkyl-, halo- or alkoxy-substituted derivatives thereof, wherein halo is chloro or fluoro and alkyl and alkoxy are of 1 to 3 carbon atoms, (b) halopyridinyl; (c) --SO 2 R 6 , wherein R 6 is phenyl, alkylphenyl, halophenyl, alkoxyphenyl, in which alkoxy, alkyl and halo are defined as above; or (d) ##STR35## wherein R 7 is phenyl, alkylphenyl, halophenyl, trifluoromethylphenyl, or alkylphenylsulfonyl, wherein halo and alkyl are defined as above; or the pharmacologically acceptable acid addition salts thereof.
Claim 35
Dependent Claim
75 words
A method according to claim 29, wherein the compound is of the formula IIB ##STR36## wherein R 8 is (a) pyrimidinyl and pyrazinyl or these groups substituted with methyl, methylthio, methoxy or chloro; (b) halopyridinyl; (c) --SO 2 R 9 , wherein R 9 is ##STR37## p-tolyl, p-chlorophenyl or p-fluorophenyl; or (d) ##STR38## wherein R 10 is halophenyl, phenyl or trifluoromethylphenyl, wherein halo is chloro or fluoro; or the pharmacologically acceptable acid addition salts thereof.
Claim 36
Dependent Claim
11 words
A method according to claim 30, wherein the compound is 1-(2,6-dimethoxy-4-pyrimidinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 37
Dependent Claim
11 words
A method according to claim 30, wherein the compound is 1-(2-pyrazinyl)-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]-piperazine.
Claim 38
Dependent Claim
11 words
A method according to claim 30, wherein the compound is 1-[(2-pyrimidinyl)]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 39
Dependent Claim
11 words
A method according to claim 31, wherein the compound is 1-[(4-methylphenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 40
Dependent Claim
11 words
A method according to claim 31, wherein the compound is 1-[(4-chlorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 41
Dependent Claim
11 words
A method according to claim 31, wherein the compound is 1-[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluorometyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 42
Dependent Claim
11 words
A method according to claim 31, wherein the compound is 1-[[(3-chlorophenyl)amino]carbonyl]-4-[4-[[7-trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
Claim 43
Dependent Claim
11 words
A method according to claim 31, wherein the compound is 1-[[(3-trifluoromethylphenyl)amino]carbonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine.
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) | 1982-09-10 | 1983-03-12 | 1983-09-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-09-10 | 1987-03-12 | 1987-09-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-09-10 | 1991-03-12 | 1991-09-11 | $7700.00 | Window Closed / Lapsed |