Claims
- 1. A compound of the formula: ##STR626## or a pharmaceutically acceptable salt thereof, wherein D-O-- is the residue of a drug having a reactive hydroxyl functional group, said drug being a narcotic analgesic, narcotic antagonist or narcotic agonist/antagonist, the oxygen atom of said functional group being bonded to the phosphorus atom of the ##STR627## moiety; R.sub.1 is C.sub.1-8 alkyl, C.sub.6 -C.sub.10 aryl or C.sub.7 -C.sub.12 aralkyl; R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl, C.sub.4 -C.sub.9 heteroaryl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloheteroalkyl or C.sub.7 -C.sub.12 aralkyl; and R.sub.3 is selected from the group consisting of C.sub.1 -C.sub.8 alkyl; C.sub.2 -C.sub.8 alkenyl having one or two double bonds; (C.sub.3 -C.sub.7 cycloalkyl)-C.sub.r H.sub.2r -- wherein r is zero, one, two or three, the cycloalkyl portion being unsubstituted or bearing 1 or 2 C.sub.1 -C.sub.4 alkyl substituents on the ring portion; (C.sub.6 -C.sub.10 aryloxy)C.sub.1 -C.sub.8 alkyl; 2-, 3- or 4-pyridyl; and phenyl-C.sub.r -H.sub.2r -- wherein r is zero, one, two or three and phenyl is unsubstituted, or is substituted by 1 to 3 alkyl each having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halo, trifluoromethyl, dialkylamino having 2 to 8 carbon atoms or alkanoylamino having 2 to 6 carbon atoms.
- 2. The compound according to claim 1, wherein R.sub.1 is methyl.
- 3. The compound according to claim 1, wherein R.sub.2 is hydrogen.
- 4. The compound according to claim 1, wherein R.sub.3 is C.sub.1 -C.sub.8 alkyl.
- 5. The compound according to claim 4, wherein R.sub.3 is (CH.sub.3).sub.3 C-- or CH.sub.3 (CH.sub.2).sub.4 --.
- 6. The compound according to claim 1, wherein the drug is a narcotic analgesic.
- 7. The compound according to claim 6, wherein the narcotic analgesic is meptazinol, profadol or myfadol.
- 8. The compound according to claim 6, wherein the narcotic analgesic is a morphine derivative.
- 9. The compound according to claim 8, wherein the morphine derivative is hydromorphone, oxymorphone, apomorphine, levorphanol, morphine, metopon, pentazocine, cyclazocine, phenazocine, codeine, oxycodone, drocode or pholcodine.
- 10. The compound according to claim 1, wherein the drug is a narcotic antagonist or narcotic agonist/antagonist.
- 11. The compound according to claim 10, wherein the narcotic antagonist or narcotic agonist/antagonist is nalbuphine, naloxone, nalorphine, buprenorphine, butorphanol, levallorphan, naltrexone, nalmefene, alazocine, oxilorphane or nalmexone.
- 12. The compound according to claim 6, having the formula: ##STR628##
- 13. The compound according to claim 10, having the formula: ##STR629##
- 14. A pharmaceutical composition, in unit dosage form, comprising:
- (i) an amount of a compound as claimed in claim 1 sufficient to release a pharmacologically effective amount of a narcotic analgesic, narcotic antagonist or narcotic agonist/antagonist to the brain; and
- (ii) a nontoxic pharmaceutically acceptable carrier therefor.
- 15. The pharmaceutical composition as claimed in claim 14, said composition being formulated for sustained release.
Parent Case Info
This application is a divisional of application Ser. No. 07/962,504, filed Oct. 16, 1992, now U.S. Pat. No. 5,413,996, which is a divisional of application Ser. No. 07/553,548, filed Jul. 13, 1990, now U.S. Pat. No. 5,177,064 issued Jan. 5, 1993.
US Referenced Citations (12)
Foreign Referenced Citations (1)
Number |
Date |
Country |
0239109 |
Sep 1987 |
EPX |
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Entry |
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Divisions (2)
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Number |
Date |
Country |
Parent |
962504 |
Oct 1992 |
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Parent |
553548 |
Jul 1990 |
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