Claims
- 1. A compound of the formula ##STR1256## or a nontoxic pharmaceutically acceptable salt thereof, wherein D is the residue of a centrally acting drug having at least one reactive hydroxyl functional group, said drug being a steroid sex hormone or antiinflammatory steroid, said residue being characterized by the absence of a hydrogen atom from at least one reactive hydroxyl functional group in said drug; n is a positive integer equal to the number of said functional groups from which a hydrogen atom is absent; and (DHC) is a radical of the formula ##STR1257## wherein the alkylene group can be straight or branched and can contain 1 to 3 carbon atoms; R.sub.0 is hydrogen, methyl, ##STR1258## --CH.sub.2 COOH or --CH.sub.2 CH.sub.2 COOH; p is 1 or 2, provided that, when p is 2, then the alkylene groups can be the same or different and the R.sub.0 radicals can be the same or different; 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 (d') indicates the presence of a double bond in either the 2 or 3 position of the dihydroquinoline ring; R.sub.1 is C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 haloalkyl or C.sub.7 -C.sub.10 aralkyl; the carbonyl-containing grouping in formula (a') can be attached at the 2, 3 or 4 position of the dihydropyridine ring; the carbonyl-containing grouping in formula (d') can be attached at the 2, 3 or 4 position of the dihydroquinoline ring; and the carbonyl-containing grouping in formula (g') can be attached at the 1, 3 or 4 position of the dihydroisoquinoline ring.
- 2. A compound according to claim 1, wherein (DHC) comprises the reduced form of an N-substituted nicotinic acid derivative.
- 3. A compound according to claim 1, wherein (DHC) comprises the reduced form of a trigonelline.
- 4. A compound according to claim 1, wherein n is 1.
- 5. A compound according to claim 1, wherein R.sub.o is hydrogen.
- 6. A compound according to claim 1, wherein p is 1.
- 7. A compound according to claim 1, wherein the steroid is hydrocortisone, betamethasone, dexamethasone, cortisone, flumethasone, fluprednisolone, meprednisone, methylprednisolone, prednisolone, prednisone, triamcinolone, cortodoxone, fludrocortisone, flurandrenolide, paramethasone, testosterone, methyltestosterone, ethinyl estradiol, norgestrel, mestranol, norethindrone, ethisterone, estradiol, estriol, estrone, dimethisterone, allylestrenol, cingestol, ethynerone, lynestrenol, norethynodrel, norgesterone, norvinisterone, ethynodiol, oxogestone, tigestol or quinestrol.
- 8. A compound according to claim 7, wherein the steroid is dexamethasone.
- 9. A compound according to claim 1, wherein the alkylene group has 1 carbon atom.
- 10. A compound according to claim 1, wherein R.sub.0 is hydrogen, methyl, ##STR1259##
- 11. The compound according to claim 1, which has the formula: ##STR1260##
- 12. A compound according to claim 1, wherein R.sub.1 is CH.sub.3.
- 13. A compound according to claim 1, wherein (DHC) has formula (a') wherein the carbonyl-containing grouping is attached at the 3-position of the dihydropyridine ting, or wherein (DHC) has formula (d') wherein the carbonyl-containing grouping is attached at the 3-position of the dihydroquinoline ting, or wherein (DHC) has formula (g') wherein the carbonyl-containing grouping is attached at the 4-position of the dihydroisoquinoline ring.
- 14. A pharmaceutical composition, in unit dosage form, said composition comprising:
- (i) an amount of a compound as claimed in claim 1, or a nontoxic pharmaceutically acceptable salt thereof, sufficient to release a pharmacologically effective amount of a steroid sex hormone or antiinflammatory steroid to the brain; and
- (ii) a nontoxic pharmaceutically acceptable carrier therefor.
- 15. A pharmaceutical composition as claimed in claim 14, said composition being a pharmaceutically acceptable sustained release composition.
- 16. A quaternary salt of the formula ##STR1261## wherein D is the residue of a centrally acting drug having at least one reactive hydroxyl functional group, said drug being a steroid sex hormone or antiinflammatory steroid, said residue being characterized by the absence of a hydrogen atom from at least one reactive hydroxyl functional group in said drug; n is a positive integer equal to the number of said functional groups from which a hydrogen atom is absent; and (QC.sup.+) is a radical of the formula ##STR1262## wherein the alkylene group can be straight or branched and can contain 1 to 3 carbon atoms; R.sub.0 is hydrogen, methyl, ##STR1263## p is 1 or 2, provided that, when p is 2, then the alkylene groups can be the same or different and the R.sub.0 radicals can be the same or different; R.sub.1 is C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 haloalkyl or C.sub.7 -C.sub.10 aralkyl; the carbonyl-containing grouping in formula (a) can be attached at the 2, 3 or 4 position of the pyridinium ring; the carbonyl-containing grouping in formula (d) can be attached at the 2, 3 or 4 position of the quinolinium ring; and the carbonyl-containing grouping in formula (g) can be attached at the 1, 3 or 4 position of the isoquinolinium ring; Y.sup.- is the anion of a pharmaceutically acceptable organic or inorganic acid; t is the valence of the acid anion; and q is the number which when multiplied by t is equal to n.
- 17. A quaternary salt according to claim 16, wherein the steroid is hydrocortisone, betamethasone, dexamethasone, cortisone, flumethasone, fluprednisolone, meprednisone, methylprednisolone, prednisolone, prednisone, triamcinolone, cortodoxone, fludrocortisone, flurandrenolide, paramethasone, testosterone, methyltestosterone, ethinyl estradiol, norgestrel, mestranol, norethindrone, ethisterone, estradiol, estriol, estrone, dimethisterone, allylestrenol, cingestol, ethynerone, lynestrenol, norethynodrel, norgesterone, norvinisterone, ethynodiol, oxogestone, tigestol or quinestrol.
- 18. A quaternary salt according to claim 17, wherein the steroid is dexamethasone.
- 19. A quaternary salt according to claim 16, wherein the alkylene group has 1 carbon atom.
- 20. A quaternary salt according to claim 16, wherein R.sub.0 is hydrogen, methyl, ##STR1264##
- 21. A quaternary salt according to claim 16, wherein (QC.sup.+) comprises the oxidized form of an N-substituted nicotinic acid derivative.
- 22. A quaternary salt according to claim 16, wherein (QC.sup.+) comprises the oxidized form of a trigonelline.
- 23. A quaternary salt according to claim 16, wherein n is 1.
- 24. A quaternary salt according to claim 16, wherein R.sub.0 is hydrogen.
- 25. A quaternary salt according to claim 16, wherein p is 1.
- 26. A quaternary salt according to claim 16, wherein R.sub.1 is CH.sub.3.
- 27. A quaternary salt according to claim 16, wherein (QC.sup.+) has formula (a) wherein the carbonyl-containing grouping is attached at the 3-position of the pyridinium ring, or wherein (QC.sup.+) has formula (d) wherein the carbonyl-containing grouping is attached at the 3-position of the quinolinium ring, or wherein (QC.sup.+) has formula (g) wherein the carbonyl-containing grouping is attached at the 4-position of the isoquinolinium ring.
- 28. The quaternary salt according to claim 16, the cation of which has the formula: ##STR1265##
Priority Claims (2)
Number |
Date |
Country |
Kind |
PCT/US83/00725 |
May 1983 |
WOX |
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428192 |
May 1983 |
CAX |
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a division of application Ser. No. 07/295,663, filed Jan. 11, 1989, now U.S. Pat. No. 5,087,618, which is a division of application Ser. No. 06/666,210, filed Oct. 29, 1984, now U.S. Pat. No. 4,829,070, which is a continuation-in-part of my earlier applications Ser. No. 06/379,316, filed May 18, 1982, now U.S. Pat. No. 4,479,932; Ser. No. 06/461,543, filed Jan. 27, 1983, abandoned in favor of Ser. No. 06/733,463, filed May 13, 1985, now U.S. Pat. No. 4,727,079; Ser. No. 06/475,493, filed Mar. 15, 1983, now U.S. Pat. No. 4,622,218; and Ser. No. 06/516,382, filed Jul. 22, 1983, now U.S. Pat. No. 4,540,564. Each of said earlier copending applications is hereby expressly incorporated by reference in its entirety and relied upon.
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Related Publications (2)
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Date |
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461543 |
Jan 1983 |
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475493 |
Mar 1983 |
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Divisions (2)
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Parent |
295663 |
Jan 1989 |
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Parent |
666210 |
Oct 1984 |
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Continuation in Parts (1)
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379316 |
May 1982 |
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