US4414213A
Expired / Lapsed
US
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Dihydropyridyl cyclic imidate esters and their pharmaceutical use
Assignee: Mead Johnson and Co LLC
•
Filing: 1982-03-22
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Granted: 1983-11-08
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Expires: 2002-03-22
Abstract
Abstract A series of 1,4-dihydropyrid-5-yl cyclic imidate esters have been prepared possessing the general formula ##STR1## wherein R and R 1 are independently selected from hydrogen, lower alkyl or alkoxyalkyl groups; R 2 is lower alkyl, aryl, or hetaryl; R 3 is cycloalkyl, aryl or hetaryl, generally with electron-withdrawing substituents; R 4 is lower alkyl, alkoxyalkyl, aminoalkyl, haloalkyl, or dialkylaminoalkyl; R 5 is lower alkyl or aryl; m is 0 or 1; and n is 0, 1, or 2. Compounds of this series demonstrate blockage of calcium ion flux in tissue preparations in vitro and vasodilation in animal testing in vivo.
Inventors
- 👤 Graham S. Poindexter
- 👤 David L. Temple, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 02:16
CPC Classifications
C; C07; C07D; C07D413/00; C07D413/14; A; A61; A61P; A61P3/00; A61P43/00; A61P9/00; A61P9/08; A61P9/10; A61P9/12; C07C; C07C205/00; C07C205/49; C07C205/56; C07C255/00; C07C317/00; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/18; C07D211/00; C07D211/04; C07D211/80; C07D211/84; C07D211/90; C07D213/00; C07D213/02; C07D213/04; C07D213/24; C07D213/54; C07D213/55; C07D263/00; C07D263/02; C07D263/08; C07D263/10; C07D263/14; C07D263/16; C07D263/28; C07D265/00; C07D265/04; C07D265/06; C07D265/08; C07D307/00; C07D307/02; C07D307/04; C07D307/10; C07D307/16; C07D307/34; C07D307/38; C07D307/54; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/24; C07D413/02; C07D413/04; C07D413/06
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
128 words
A compound having the formula ##STR10## and the pharmaceutically acceptable acid addition salts thereof wherein R and R 1 are independently selected from hydrogen, lower (C 1 -C 4 ) alkyl or lower alkoxy-lower alkyl groups; R 2 is lower alkyl, phenyl, or thienyl; R 3 is cycloalkyl of 5 to 7 carbon atons, bicycloalkenyl of 7 to 9 carbon atoms, furanyl, indolyl, pyridyl, thienyl, phenyl, naphthyl, or substituted phenyl with the substituents comprising acetamino, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, halogen, hydroxyl, nitro, trifluoromethyl, trifluoromethylsulfonyl, and methylsulfonyl; R 4 is lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, halo-lower alkyl, or di-lower alkylamino-lower alkyl; R 5 is lower alkyl or aryl; m is 0 or 1; and n is 0, 1, or 2.
Claim 2
Dependent Claim
128 words
A compound having the formula ##STR10## and the pharmaceutically acceptable acid addition salts thereof wherein R and R 1 are independently selected from hydrogen, lower (C 1 -C 4 ) alkyl or lower alkoxy-lower alkyl groups; R 2 is lower alkyl, phenyl, or thienyl; R 3 is cycloalkyl of 5 to 7 carbon atons, bicycloalkenyl of 7 to 9 carbon atoms, furanyl, indolyl, pyridyl, thienyl, phenyl, naphthyl, or substituted phenyl with the substituents comprising acetamino, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, cyano, halogen, hydroxyl, nitro, trifluoromethyl, trifluoromethylsulfonyl, and methylsulfonyl; R 4 is lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, halo-lower alkyl, or di-lower alkylamino-lower alkyl; R 5 is lower alkyl or aryl; m is 0 or 1; and n is 0, 1, or 2.
Claim 3
Dependent Claim
22 words
The compound of claim 1 wherein R 2 is lower alkyl, R 3 is 3-nitrophenyl, m is 0, and n is 1.
Claim 4
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 5
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-4-(2-furanyl)-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 6
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(4-nitrophenyl)-3-pyridinecarboxylate.
Claim 7
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-phenyl-3-pyridinecarboxylate.
Claim 8
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-4-(2-fluorophenyl)-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 9
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-1,4-dihydro-2-methyl-6-(1-methylethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 10
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-(1,1-dimethylethyl)-1,4-dihydro-2-methyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 11
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-phenyl-3-pyridinecarboxylate.
Claim 12
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-6-(2-thienyl)-3-pyridinecarboxylate.
Claim 13
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-5-phenyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 14
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(2-chloro-5-nitrophenyl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 15
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(3-chlorophenyl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 16
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-[3-(trifluoromethyl)phenyl]-3-pyridinecarboxylate.
Claim 17
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(2-thienyl)-3-pyridinecarboxylate.
Claim 18
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-4-(4-hydroxy-3-methoxyphenyl)-2-methyl-3-pyridinecarboxylate.
Claim 19
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-methylphenyl)-3-pyridinecarboxylate.
Claim 20
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(1-naphthalenyl)-3-pyridinecarboxylate.
Claim 21
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-pyridinyl)-3-pyridinecarboxylate.
Claim 22
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(2-chlorophenyl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 23
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(3-cyanophenyl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 24
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-4-(2-methoxyphenyl)-2-methyl-3-pyridinecarboxylate.
Claim 25
Dependent Claim
7 words
The compound of claim 1, ethyl 4-(bicyclo[2.2.1]hept-5-en-2-yl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 26
Dependent Claim
7 words
The compound of claim 1, ethyl 4-cyclohexyl-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 27
Dependent Claim
7 words
The compound of claim 1, ethyl 4-[4-(acetylamino)phenyl]-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-3-pyridinecarboxylate.
Claim 28
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-4-(3-hydroxy-4-nitrophenyl)-2-methyl-3-pyridinecarboxylate.
Claim 29
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-4-(1H-indol-3-yl)-2-methyl-3-pyridinecarboxylate.
Claim 30
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-6-ethyl-1,4-dihydro-4-(4-hydroxy-3-nitrophenyl)-2-methyl-3-pyridinecarboxylate.
Claim 31
Dependent Claim
7 words
The compound of claim 1, methyl 5-(4,5-dihydro-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 32
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 33
Dependent Claim
7 words
The compound of claim 1, ethyl 5-[4,5-dihydro-4-(methoxymethyl)-4-methyl-2-oxazolyl]-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 34
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 35
Dependent Claim
7 words
The compound of claim 1, ethyl 5-(5,6-dihydro-4,4,6-trimethyl-4H-1,3-oxazin-2-yl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 36
Dependent Claim
7 words
The compound of claim 1, 1-methylethyl 5-(4,5-dihydro-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 37
Dependent Claim
7 words
The compound of claim 1, 2-methoxyethyl 5-(4,5-dihydro-2-oxazolyl)-6-ethyl-1,4-dihydro-2-methyl-4-(3-nitrophenyl)-3-pyridinecarboxylate.
Claim 38
Dependent Claim
36 words
A pharmaceutical composition for the treatment of cardiovascular disease such as angina or hypertension comprising from 5 to 500 mg of a compound claimed in claim 1 in combination with a pharmaceutically acceptable, non-toxic inert carrier.
Claim 39
Dependent Claim
41 words
The method of exerting a vasodilating effect in a mammalian host which comprises administering to a mammal having a condition in which therapeutic benefit is derived from vasodilation, a non-toxic effective vasodilating dose of a compound as claimed in claim 1.
Claim 40
Dependent Claim
24 words
The antihypertensive method which comprises administering to a mammalian host having hypertension a non-toxic antihypertensive effective dose of a compound claimed in claim 1.
Claim 41
Dependent Claim
26 words
The anti-ischemia method which comprises administering to a mammalian host, subject to ischemic attack, a non-toxic anti-ischemia effective dose of a compound claimed in claim 1.
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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) | 1986-11-07 | 1987-05-09 | 1987-11-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-11-07 | 1991-05-09 | 1991-11-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-11-07 | 1995-05-09 | 1995-11-08 | $7700.00 | Window Closed / Lapsed |