Claims
- 1. A compound having the formula ##STR646## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; and ##STR647## is a radical of the formula ##STR648## wherein the dotted line in formula (a) indicates the presence of a double bond in either the 4 or 5 position of the dihydropyridine ring; the dotted line in formula (b) indicates the presence of a double bond in either the 2 or 3 position of the dihydroquinoline ring system; m is zero or one; n is zero, one or two; p is zero, one or two, provided that when p is one or two, each R in formula (b) can be located on either of the two fused rings; q is zero, one or two, provided that when q is one or two, each R in formula (c) can be located on either of the two fused rings; and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR' " wherein R"'is H or C.sub.1 -C.sub.7 alkyl, and --CNR'R" wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
- 2. A compound according to claim 1, wherein n, m, p or q is one, and wherein R is located in the 3 position of the dihydropyridine ring, in the 3 position of the dihydroquinoline ring system or in the 4 position of the dihydroisoquinoline ring system.
- 3. A compound according to claim 2, wherein R is --CONH.sub.2.
- 4. A compound according to claim 1 having the formula ##STR649## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; the dotted line indicates the presence of a double bond in either the 4 or 5 position of the dihydropyridine ring; n is zero, one or two; and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R"'is H or C.sub.1 -C.sub.7 alkyl, and --CNR'R" wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
- 5. A compound according to claim 4 having the formula ##STR650## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; the dotted line indicates the presence of a double bond in either the 4 or 5 position of the dihydropyridine ring; and R is halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R"'is H or C.sub.1 -C.sub.7 alkyl, and --CNR'R" wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
- 6. A compound according to claim 5 having the formula ##STR651## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; the dotted line indicates the presence of a double bond in either the 4 or 5 position of the dihydropyridine ring; and R is halo, methyl, ethyl, methoxy, ethoxy, ethoxycarbonyl, isopropoxycarbonyl, acetoxy, pivalyloxy, isobutyryloxy, C.sub.1 -C.sub.2 haloalkyl bearing 1 to 3 halogen substituents, methylthio, methylsulfinyl, methylsulfonyl, --CH.dbd.NOH, --CONH.sub.2 or --CON(CH.sub.3).sub.2.
- 7. A compound according to claim 5 having the formula ##STR652## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; the dotted line indicates the presence of a double bond in either the 4 or 5 position of the dihydropyridine ring; and --CONR'R" is --CONH.sub.2 or --CON(CH.sub.3).sub.2.
- 8. A compound according to claim 7 having the formula ##STR653## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; and --CONR'R" is --CONH.sub.2 or --CON(CH.sub.3).sub.2.
- 9. A compound according to claim 8 having the formula ##STR654## or a non-toxic pharmaceutically acceptable salt thereof, wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group.
- 10. A compound according to claim 1, wherein R.sub.b is H.
- 11. A compound according to claim 9, wherein R.sub.b is H.
- 12. A compound according to claim 10, wherein each --OR.sub.a is --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group.
- 13. A compound according to claim 11, wherein each --OR.sub.a is --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group.
- 14. A compound according to claim 12, wherein Y is alkanoyl having 2 to 8 carbon atoms.
- 15. A compound according to claim 13, wherein Y is alkanoyl having 2 to 8 carbon atoms.
- 16. The compound according to claim 15, which is 1-(3,4-dipivaloyloxy)phenethyl-3-carbamoyl -1,4-dihydropyridine.
- 17. A non-toxic pharmaceutically acceptable quaternary salt having the formula ##STR655## wherein each --OR.sub.a is independently --OH or --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group; R.sub.b is H, --COOH or --COOY' wherein Y' is a hydrolytically or metabolically cleavable carboxyl protective group; X.sup.- is the anion of a non-toxic pharmaceutically acceptable acid; and ##STR656## is a radical of the formula ##STR657## wherein n is zero, one or two; p is zero, one or two, provided that when p is one or two, each R in formula (b) can be located on either of the two fused rings; q is zero, one or two, provided that when q is one or two, each R in formula (c) can be located on either of the two fused rings; and each R is independently selected from the group consisting of halo, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.8 alkoxycarbonyl, C.sub.2 -C.sub.8 alkanoyloxy, C.sub.1 -C.sub.7 haloalkyl, C.sub.1 -C.sub.7 alkylthio, C.sub.1 -C.sub.7 alkylsulfinyl, C.sub.1 -C.sub.7 alkylsulfonyl, --CH.dbd.NOR'" wherein R"'is H or C.sub.1 -C.sub.7 alkyl, and --CNR'R" wherein R' and R", which can be the same or different, are each H or C.sub.1 -C.sub.7 alkyl.
- 18. A quaternary salt according to claim 17, having the ##STR658## wherein --OR.sub.a, R.sub.b and X.sup.- are as defined in claim 17.
- 19. A quaternary salt according to claim 18, wherein R.sub.b is H.
- 20. A quaternary salt according to claim 19, wherein each --OR.sub.a is --OY wherein Y is a hydrolytically or metabolically cleavable hydroxyl protective group.
- 21. The quaternary salt according to claim 20, which is 1-(3,4-dipivaloyloxy)phenethyl-3-carbamoylpyridinium trifluoroacetate or 1-(3,4-dipivaloyloxy) phenethyl-3-carbamoylpyridinium chloride.
- 22. A pharmaceutical composition of matter comprising an amount of a compound as claimed in claim 1 sufficient to evoke an effective dopaminergic response and a non-toxic pharmaceutically acceptable carrier therefor.
- 23. A pharmaceutical composition of matter comprising an amount of a compound as claimed in claim 10 sufficient to evoke an effective dopaminergic response and a non-toxic pharmaceutically acceptable carrier therefor.
- 24. A pharmaceutical composition of matter comprising an amount of a compound as claimed in claim 13 sufficient to evoke an effective dopaminergic response and a non-toxic pharmaceutically acceptable carrier therefor.
- 25. A pharmaceutical composition of matter according to claim 17, said composition being formulated as a pharmaceutically acceptable sustained release composition.
- 26. A method for treating Parkinsonism or hyperprolactinemia in an animal in need of such treatment, said method comprising administering to said animal an effective anti-Parkinsonism or anti-hyperprolactinemia amount of a compound as claimed in claim 1.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a division of application Ser. No. 07/208,872, filed Jun. 20, 1988, now U.S. Pat. No. 4,933,438, issued Jun. 12, 1990, which is a division of application Ser. No. 06/785,903, filed as PCT/US85/00236, Feb. 15, 1985, now U.S. Pat. No. 4,771,059, which is a continuation-in-part of applicant's copending application Ser. No. 584,800, filed Feb. 29, 1984, now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4479932 |
Bodor |
Oct 1984 |
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Foreign Referenced Citations (2)
Number |
Date |
Country |
8303968 |
Nov 1983 |
WOX |
822351 |
Oct 1959 |
GBX |
Non-Patent Literature Citations (3)
Entry |
Dean et al., CA 86:16522h. |
Chemical Abstracts, vol. 84, Jun. 7, 1976, p. 447, abstract No. 164580z. |
Chemical Abstracts, vol. 81, Aug. 5, 1974, p. 24, abstract No. 20899a. |
Divisions (2)
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Number |
Date |
Country |
Parent |
208872 |
Jun 1988 |
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Parent |
785903 |
Aug 1985 |
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Continuation in Parts (1)
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Number |
Date |
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Parent |
584800 |
Feb 1984 |
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