US4284634A
Expired / Lapsed
US
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1,4-Dihydropyridine derivatives, and pharmaceutical method of the same
Assignee: Astellas Pharma Inc
•
Filing: 1979-05-17
•
Granted: 1981-08-18
•
Expires: 1999-05-17
Abstract
Abstract 1,4-dihydropyridine derivatives of the general formula <IMAGE> having vasodilating and anti-hypertensive activity, processes for preparing same, and pharmaceutical compositions thereof for treating cardiovascular diseases.
Inventors
- 👤 Yoshinari Satu
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 08:15
CPC Classifications
C; C07; C07D; C07D401/00; C07D401/02; C07D401/04; C07C; C07C205/00; C07C205/49; C07C205/56; C07D211/00; C07D211/04; C07D211/80; C07D211/84; C07D211/90; C07D213/00; C07D213/02; C07D213/04; C07D213/24; C07D213/54; C07D213/55; C07D307/00; C07D307/02; C07D307/34; C07D307/38; C07D307/54; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/24; C07D405/00; C07D405/02; C07D405/04; C07D405/06; C07D409/00; C07D409/02; C07D409/04; C07D471/00; C07D471/02; C07D471/04
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
83 words
A compound of the formula: ##STR35## wherein R 1 is unsubstituted phenyl, phenyl monosubstituted with halogen, nitro, hydroxy, halo(lower)alkyl, lower alkyl, lower alkoxy, lower alkenyloxy, cyano, lower alkoxycarbonyl or lower alkylsulfamoyl, and disubstituted phenyls selected from 2-chloro-5-nitro, 2-3 and 3-4 dichloros and 3-4 dimethoxy, R 2 and R 3 are lower alkoxycarbonyl, halo(lower)alkoxycarbonyl, hydroxy(lower)alkoxycarbonyl, lower alkoxy(lower)alkoxycarbonyl, phenyl(lower)alkoxycarbonyl, phenyl(lower)alkoxy(lower)alkoxycarbonyl, phenoxy(lower)alkoxycarbonyl, N,N-(di)-(lower)alkylamino(lower)alkoxycarbonyl and N-lower alkyl-N-phenyl(lower)alkylamino(lower)alkoxycarbonyl, R 4 is hydroxy(lower)alkyl or gem-di(lower)alkoxy(lower)alkyl, and R 5 is hydrogen, lower alkyl, or the same as R 4 .
Claim 2
Dependent Claim
83 words
A compound of the formula: ##STR35## wherein R 1 is unsubstituted phenyl, phenyl monosubstituted with halogen, nitro, hydroxy, halo(lower)alkyl, lower alkyl, lower alkoxy, lower alkenyloxy, cyano, lower alkoxycarbonyl or lower alkylsulfamoyl, and disubstituted phenyls selected from 2-chloro-5-nitro, 2-3 and 3-4 dichloros and 3-4 dimethoxy, R 2 and R 3 are lower alkoxycarbonyl, halo(lower)alkoxycarbonyl, hydroxy(lower)alkoxycarbonyl, lower alkoxy(lower)alkoxycarbonyl, phenyl(lower)alkoxycarbonyl, phenyl(lower)alkoxy(lower)alkoxycarbonyl, phenoxy(lower)alkoxycarbonyl, N,N-(di)-(lower)alkylamino(lower)alkoxycarbonyl and N-lower alkyl-N-phenyl(lower)alkylamino(lower)alkoxycarbonyl, R 4 is hydroxy(lower)alkyl or gem-di(lower)alkoxy(lower)alkyl, and R 5 is hydrogen, lower alkyl, or the same as R 4 .
Claim 3
Dependent Claim
41 words
A compound according to claim 1, wherein R 1 is phenyl, nitrophenyl, halophenyl, halo- and nitro-disubstituted phenyl, trifluoromethylphenyl, lower alkylphenyl, lower alkoxyphenyl, hydroxyphenyl, lower alkenyloxyphenyl, cyanophenyl, lower alkoxycarbonylphenyl or lower alkylsulfamoylphenyl, R 2 is lower alkoxycarbonyl, and R 4 is gem-di(lower)alkoxy(lower)alkyl.
Claim 4
Dependent Claim
55 words
A compound according to claim 1, wherein R 1 is phenyl, nitrophenyl, halophenyl, halo- and nitro-di-substituted phenyl, trifluoromethylophenyl, lower alkyl-phenyl, lower alkoxyphenyl, hydroxyphenyl, lower alkenyloxyphenyl, cyanophenyl, lower alkoxycarbonylphenyl or lower alkylsulfamoylphenyl, R 2 is lower alkoxycarbonyl, R 3 is lower alkoxycarbonyl, hydroxy(lower)alkoxycarbonyl, lower alkoxy(lower)alkoxycarbonyl, phenyl(lower) alkoxycarbonyl, phenyl(lower)alkoxy(lower)alkoxycarbonyl or N-(lower)alkyl-N-phenyl(lower) alkylamino(lower)alkoxycarbonyl, and R 4 is hydroxy(lower)alkyl.
Claim 5
Dependent Claim
22 words
A method for effecting vasodilation in humans and mammals which comprises administering thereto an effective amount of the compound of claim 1.
Claim 6
Dependent Claim
34 words
A method for effecting vasodilation in humans and mammals which comprises administering thereto an oral daily dose of 0.1 to 500 mg. or 10 to 25% thereof intravenously of the compound of claim 1.
Claim 7
Dependent Claim
34 words
A method for effecting vasodilation in humans and mammals which comprises administering thereto an oral daily dose of 1 to 50 mg. or 10 to 25% thereof intravenously of the compound of claim 1.
Claim 8
Dependent Claim
35 words
A method for effecting vasodilation in humans and mammals which comprises administering thereto an oral daily dose of 1 μg to 10 mg/kg. or 10 to 25% thereof intravenously of the compound of claim 1.
Claim 9
Dependent Claim
34 words
A method for effecting vasodilation in humans and mammals which comprises administering thereto an oral daily dose of 0.5 to 5 mg/kg or 10 to 25% thereof intravenously of the compound of claim 1.
Claim 10
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2,6-bis(diethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 11
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-chlorophenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 12
Dependent Claim
10 words
A compound according to claim 2 that is dimethyl 2-methyl-4-(2-chlorophenyl)-6-(1,1-dimethoxyethyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 13
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-trifluoromethylphenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 14
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-methoxyphenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 15
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(3-hydroxyphenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 16
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-nitrophenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 17
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(3-nitrophenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 18
Dependent Claim
34 words
A compound according to claim 2 wherein R 1 is 2-nitrophenyl, R 2 is ethoxycarbonyl, R 3 is 2-ethoxyethoxycarbonyl, 2-chloroethoxycarbonyl, 2-hydroxyethoxycarbonyl, benzyloxycarbonyl, 2-benzyloxyethoxycarbonyl or 2-phenoxyethoxycarbonyl, R 4 is diethoxymethyl and R 5 is methyl.
Claim 19
Dependent Claim
33 words
A compound according to claim 2 wherein R 1 is 3-nitrophenyl, R 2 is ethoxycarbonyl, R 3 is 2-ethoxyethoxycarbonyl, 2-chloroethoxycarbonyl, 2-hydroxyethoxycarbonyl, 2-(N,N-diethylamino)ethoxycarbonyl or 2-(N-methyl-N-benzylamino)ethoxycarbonyl, R 4 is diethoxymethyl and R 5 is methyl.
Claim 20
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-chloro-5-nitrophenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 21
Dependent Claim
10 words
A compound according to claim 2 that is methyl 4-(2-chlorophenyl)-5-ethoxycarbonyl-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 22
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-(2-allyloxyphenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 23
Dependent Claim
10 words
A compound according to claim 2 that is dimethyl 2-methyl-4-(2-nitrophenyl)-6-dimethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 24
Dependent Claim
10 words
A compound according to claim 2 that is ethyl 2-methyl-4-(2-nitrophenyl)-5-methoxycarbonyl-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 25
Dependent Claim
10 words
A compound according to claim 2 that is isopropyl 2-methyl-4-(2-nitrophenyl)-5-methoxycarbonyl-6-dimethoxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 26
Dependent Claim
10 words
A compound according to claim 2 that is dimethyl 2-methyl-4-(3-nitrophenyl)-6-dimethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 27
Dependent Claim
10 words
A compound according to claim 2 that is 2-benzyloxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-diethoxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 28
Dependent Claim
10 words
A compound according to claim 2 that is dimethyl 2-methyl-4-(2-cyanophenyl)-6-dimethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 29
Dependent Claim
10 words
A compound according to claim 2 that is diethyl 2-methyl-4-(2-methoxycarbonylphenyl)-6-diethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 30
Dependent Claim
10 words
A compound according to claim 2 that is dimethyl 2-methyl-4-(2-N-methylsulfamoylphenyl)-6-dimethoxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 31
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2,6-dihydroxymethyl-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 32
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-4-(2-chlorophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 33
Dependent Claim
10 words
A compound according to claim 3 that is dimethyl 2-methyl-4-(2-chlorophenyl)-6-(1-hydroxyethyl)-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 34
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-4-(2-trifluoromethylphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 35
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-4-(2-methoxyphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 36
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-4-(3-hydroxyphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 37
Dependent Claim
30 words
A compound according to claim 3, wherein R 1 is nitrophenyl, R 2 and R 3 are each lower alkoxycarbonyl, R 4 is lower alkyl and R 5 is hydroxy(lower)alkyl.
Claim 38
Dependent Claim
30 words
A compound according to claim 3 wherein R 1 is 2-nitrophenyl, R 2 is ethoxycarbonyl, R 3 is 2-hydroxyethoxycarbonyl, or benzyloxycarbonyl, R 4 is hydroxymethyl and R 5 is methyl.
Claim 39
Dependent Claim
30 words
A compound according to claim 3 wherein R 1 is 3-nitrophenyl, R 2 is ethoxycarbonyl, R 3 is 2-ethoxyethoxycarbonyl or 2-(N-methyl-N-benzylamino)ethoxycarbonyl, R 4 is hydroxymethyl and R 5 is methyl.
Claim 40
Dependent Claim
10 words
A compound according to claim 3 that is methyl 4-(2-chlorophenyl)-5-ethoxycarbonyl-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 41
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-(2-allyloxyphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 42
Dependent Claim
10 words
A compound according to claim 3 that is dimethyl 2-methyl-4-(2-cyanophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 43
Dependent Claim
10 words
A compound according to claim 3 that is diethyl 2-methyl-4-(2-methoxycarbonylphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 44
Dependent Claim
10 words
A compound according to claim 3 that is dimethyl 2-methyl-4-(2-methylsulfamoylphenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 45
Dependent Claim
10 words
A compound according to claim 3 that is 2-benzyloxyethyl 2-methyl-4-(2-nitrophenyl)-5-ethoxy-carbonyl-6-hydroxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 46
Dependent Claim
10 words
A compound according to claim 3 that is 2-benzyloxyethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-hydroxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 47
Dependent Claim
10 words
A compound according to claim 36 that is diethyl 2-methyl-4-(2-nitrophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 48
Dependent Claim
10 words
A compound according to claim 36 that is diethyl 2-methyl-4-(3-nitrophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 49
Dependent Claim
9 words
A compound according to claim 36 that is dimethyl-2-methyl-4-(2-nitrophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
Claim 50
Dependent Claim
10 words
A compound according to claim 36 that is isopropyl 2-methyl-4-(2-nitrophenyl)-5-methoxycarbonyl-6-hydroxymethyl-1,4-dihydropyridine-3-carboxylate.
Claim 51
Dependent Claim
10 words
A compound according to claim 36 that is dimethyl 2-methyl-4-(3-nitrophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate.
References Cited (Backward Citations)
US3974278A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-08-17 | 1985-02-16 | 1985-08-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-08-17 | 1989-02-16 | 1989-08-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-08-17 | 1993-02-16 | 1993-08-18 | $7700.00 | Window Closed / Lapsed |