Claims
- 1. A compound of the formula
- D"'(--Q").sub.n"
- wherein D"' is the residue of a narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist having at least one --OH functional group, said residue being formed by removal of a hydrogen atom from at least one of the --OH functional groups in the narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist; n" is a positive integer equal to the number of said --OH functional groups from which a hydrogen atom has been removed; and --Q" is a radical of the formula ##STR1602## wherein the dotted line in formulas (a*), (b*), (c*), (d*) and (e*) indicates the presence of the double bond in either the 4 or 5 position of the dihydropyridine ring; the dotted line in formulas (g*), (i*), (k*), (l*) and (n*) 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; R.sub.3 is C.sub.1 to C.sub.3 alkylene; X is --CONR'R" wherein R' and R", which are the same or different, are each H or C.sub.1 -C.sub.7 alkyl, or X is --CH=NOR"' wherein R"' is H or
- C.sub.1 -C.sub.7 alkyl; the ##STR1603## groupings in formulas (a*), (b*), (c*) and (e*) and the X substituent in formula (d*) are each attached at the 2, 3 or 4 position of the dihydropyridine ring; the ##STR1604## groupings in formulas (g*), (i*), (k*) and (n*) and the X substituent in formula (l*) are each attached at the 2, 3 or 4 position of the dihydroquinoline ring; and the ##STR1605## groupings in formulas (f*), (h*), (j*) and (o*) and the X substituent in formula (m*) are each attached at the 1, 3 or 4 position of the dihydroisoquinoline ring;
- or a non-toxic pharmaceutically acceptable salt thereof.
- 2. The compound according to claim 1, wherein D"' is the residue of a narcotic antagonist or narcotic agonist-antagonist.
- 3. The compound according to claim 1, wherein the narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist is codeine, naloxone, oxycodone, hydromorphone, oxymorphone, nalorphine, morphine, levorphanol, metopon, drocode, buprenorphine, nalbuphine, butorphanol, levallorphan, naltrexone, oxilorphan or nalmexone.
- 4. The compound according to claim 2, wherein the narcotic antagonist or agonist-antagonist is nalorphine, naloxone, buprenorphine, nalbuphine, butorphanol, levallorphan, naltrexone, oxilorphan or nalmexone.
- 5. The compound according to claim 4, wherein the narcotic antagonist or agonist-antagonist is buprenorphine.
- 6. The compound according to claim 1, wherein n is 1.
- 7. The compound according to claim 1, wherein --Q" is a radical of the formula ##STR1606## wherein the structural variables are as defined in claim 1.
- 8. The compound according to claim 7, wherein --Q" is a radical of the formula ##STR1607## wherein the ##STR1608## substituent is in the 2-, 3- or 4-position on the ring and R.sub.1 is C.sub.1 -C.sub.7 alkyl or C.sub.7 -C.sub.10 aralkyl.
- 9. The compound according to claim 8, wherein --Q" is a radical of the formula ##STR1609##
- 10. The compound according to claim 9, which has the formula ##STR1610## wherein R' is H or ##STR1611## wherein R' is H or ##STR1612##
- 11. The compound according to claim 10, which has the formula ##STR1613## wherein R' is H or ##STR1614##
- 12. The compound according to claim 11, wherein R' is H.
- 13. A quaternary salt having the formula
- D"' (--Q".sup..sym.).sub.n" Y.sup..crclbar..sub.n"
- wherein D"' is the residue of a narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist having at least one --OH functional group, said residue being formed by removal of a hydrogen atom from at least one of the --OH functional groups in the narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist; n" is a positive integer equal to the number of said --OH functional groups from which a hydrogen atom has been removed; Y.sup..crclbar. is the anion of a non-toxic pharmaceutically acceptable acid; and --Q".sup..sym. has the formula ##STR1615## wherein 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; R.sub.3 is C.sub.1 to C.sub.3 alkylene; X is --CONR'R" wherein R' and R", which are the same or different, are each H or C.sub.1 -C.sub.7 alkyl, or X is --CH=NOR"' wherein R"' is H or C.sub.1 -C.sub.7 alkyl; the ##STR1616## groupings in formulas (aa*), (bb*), (cc*) and (ee*) and the X substituent in formula (dd*) are each attached at the 2, 3 or 4 position of the pyridinium ring; the ##STR1617## groupings in formulas (gg*), (ii*), (kk*) and (nn*) and the X substituent in formula (11') are each attached at the 2, 3 or 4 position of the quinolinium ring; and the ##STR1618## groupings in formulas (if*), (hh*), (jj*) and (oo*) and the X substituent in formula (mm*) are each attached at the 1, 3 or 4 position of the isoquinolinium ring.
- 14. The salt according to claim 13, wherein D"' is the residue of a narcotic antagonist or narcotic agonist-antagonist.
- 15. The salt according to claim 13, wherein the narcotic analgesic, narcotic antagonist or narcotic agonist-antagonist is codeine, naloxone, oxycodone, hydromorphone, oxymorphone, nalorphine, morphine, levorphanol, metopon, drocode, buprenorphine, nalbuphine, butorphanol, levallorphan, naltrexone, oxilorphan or nalmexone.
- 16. The salt according to claim 14, wherein the narcotic antagonist or agonist-antagonist is nalorphine, naloxone, buprenorphine, nalbuphine, butorphanol, levallorphan, naltrexone, oxilorphan or nalmexone.
- 17. The salt according to claim 16, wherein the narcotic antagonist or agonist-antagonist is buprenorphine.
- 18. The salt according to claim 13, wherein --Q".sup..sym. has the formula ##STR1619## wherein the structural variables are as defined in claim 13.
- 19. The salt according to claim 18, wherein --Q".sup..sym. has the formula ##STR1620## wherein the ##STR1621## substituent is in the 2-, 3- or 4-position on the ring and R.sub.1 is C.sub.1 -C.sub.7 alkyl or C.sub.7 -C.sub.10 aralkyl.
- 20. The salt according to claim 19, wherein --Q".sup..sym. has the formula ##STR1622##
- 21. The salt according to claim 20, the cation of which has the formula ##STR1623## wherein R is H or ##STR1624## wherein R is H or ##STR1625##
- 22. The salt according to claim 21, the cation of which has the formula ##STR1626## wherein R is H or ##STR1627##
- 23. A pharmaceutical composition comprising an effective analgesic or narcotic antagonistic amount of a compound as claimed in claim 1 and a non-toxic pharmaceutically acceptable carrier therefor.
- 24. A composition according to claim 23, wherein D"' is the residue of a narcotic antagonist or narcotic agonist-antagonist.
- 25. The composition according to claim 24, wherein the narcotic antagonist or agonist-antagonist is nalorphine, naloxone, buprenorphine, nalbuphine, butorphanol, levallorphan, naltrexone, oxilorphan or nalmexone.
- 26. The composition according to claim 25, wherein the narcotic antagonist or agonist-antagonist is buprenorphine.
- 27. The composition according to claim 23, comprising an effective analgesic or narcotic antagonistic amount of the compound of the formula ##STR1628## wherein R' is H or ##STR1629## wherein R' is H or ##STR1630## and a non-toxic pharmaceutically acceptable carrier therefor.
- 28. The composition according to claim 27, comprising an effective analgesic or narcotic antagonistic amount of the compound of the formula ##STR1631## wherein R' is H or ##STR1632## and a non-toxic pharmaceutically acceptable carrier therefor.
- 29. The composition according to claim 28, wherein R' is H.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US83/00725 |
May 1983 |
WOX |
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a division of application Ser. No. 07/639,283, filed on Jan. 10, 1991, now U.S. Pat. No. 5,187,158; which is a division of application Ser. No. 07/295,938, filed Jan. 11, 1989, now U.S. Pat. No. 5,008,257; which is a division of application Ser. No. 06/665,940, filed Oct. 29, 1984, now U.S. Pat. No. 4,824,850; 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.
US Referenced Citations (11)
Foreign Referenced Citations (2)
Number |
Date |
Country |
428192 |
May 1983 |
CAX |
900812 |
Jul 1990 |
WOX |
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Entry |
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Related Publications (3)
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Date |
Country |
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461543 |
Jan 1983 |
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475493 |
Mar 1983 |
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516382 |
Jul 1983 |
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Divisions (3)
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Number |
Date |
Country |
Parent |
639283 |
Jan 1991 |
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Parent |
295938 |
Jan 1989 |
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Parent |
665940 |
Oct 1984 |
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Continuation in Parts (1)
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Number |
Date |
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Parent |
379316 |
May 1982 |
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