Claims
- 1. A pharmaceutical composition comprising:
- 2. The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises a diarylmethylpiperazine or a diarylmethylpiperazine compound.
- 3. The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises a diarylmethylpiperazine compound.
- 4.The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises 3290W93.
- 5.The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises BW373U86.
- 6.The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises an agent selected from the group consisting of:
- 7.The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises an agent selected from the group consisting of:
- 8.The pharmaceutical composition of claim 1, in a form suitable for injectable or spinal administration.
- 9.A pharmaceutical composition comprising:
- 10. A pharmaceutical composition comprising an effective amount of a bioactive composition mediating respiratory depression, and an effective amount of a compound for reducing, treating or preventing respiratory depression, of the formula:10.21wherein:Ar is a 5- or 6-member carbocyclic or heterocyclic aromatic ring with atoms selected from the group consisting of carbon, nitrogen, oxygen and sulfur, and having on a first carbon atom thereof a substituent Y and on a second ring carbon thereof a substituent R1;Y is selected from the group consisting of:hydrogen;halogen;C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl;C1-C6 haloalkyl;C1-C6 alkoxy;C3-C6 cycloalkoxy;sulfides of the formula SR8 where R8 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, arylalkyl having a C5-C10 aryl moiety and an C1-C6 alkyl moiety, or C5-C10 aryl;sulfoxides of the formula SOR8 where R8 is the same as above;sulfones of the formula SO2R8 where R8 is the same as above;nitrile;C1-C6 acyl;alkoxycarbonylamino (carbamoyl) of the formula NHCO2R8 where R8 is the same as above;carboxylic acid, or an ester, amide, or salt thereof;aminomethyl of the formula CH2NR9R10 where R9 and R10 may be the same or different, and may be hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 hydroxyalkyl, C2-C6 methoxyalkyl, C3-C6 cycloalkyl, or C5-C10 aryl, or R9 and R10 together may form a ring of 5 or 6 atoms, the ring atoms selected from the group consisting of N and C;carboxamides of the formula CONR9R10 where R9 and R10 are the same as above, or C2-C30 peptide conjugates thereof; andsulfonamides of the formula SO2NR9R10 where R9 and R10 are the same as above;Z is selected from the group consisting of:hydroxyl, and esters thereof;hydroxymethyl, and esters thereof; andamino, and carboxamides and sulfonamides thereof;G is carbon or nitrogen;R1 is hydrogen, halogen, or C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkynyl;R2 is hydrogen, halogen, or C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkynyl;R3, R4 and R5 may be the same or different, and are independently selected from hydrogen and methyl, and wherein at least one of R3, R4 or R5 is not hydrogen, subject to the proviso that the total number of methyl groups does not exceed two, or any two of R3, R4 and R5 together may form a bridge of 1 to 3 carbon atoms;R6 is selected from the group consisting of:hydrogen;C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl;C3-C6 cycloalkyl;arylalkyl having C5-C10 aryl and C1-C6 alkyl moieties;alkoxyalkyl having C1-C4 alkoxy and C1-C4 alkyl moieties;C2-C4 cyanoalkyl;C2-C4 hydroxyalkyl;aminocarbonylalkyl having a C1-C4 alkyl moiety; andR12COR13, where R12 is C1-C4 alkylene, and R13 is C1-C4 alkyl or C1-C4 alkoxy; andR7 is hydrogen or fluorine,or a pharmaceutically acceptable ester or salt thereof.
- 11. The pharmaceutical composition according to claim 10, wherein Ar is a 6-member carbocyclic aromatic (benzene) ring and R1 is hydrogen.
- 12. The pharmaceutical composition according to claim 10, wherein Y is a carboxamide of the formula CONR9R10.
- 13. The pharmaceutical composition according to claim 10, wherein R9 and R10 together form a ring of five or six atoms, thereby forming a pyrrolidinyl or piperidino ring.
- 14. The pharmaceutical composition according to claim 10, wherein R9 and R10 are the same or different and are each independently selected from hydrogen, C1 alkyl and C2 alkyl.
- 15. The pharmaceutical composition according to claim 10, wherein Y is hydrogen.
- 16. The pharmaceutical composition according to claim 10, wherein Y is a sulfone of the formula SO2R8 and R8 is C1-C6 alkyl.
- 17. The pharmaceutical composition according to claim 10, wherein G is N, R7 and R2 are each hydrogen, and Z is hydroxyl.
- 18. The pharmaceutical composition according to claim 10, wherein R6 is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl.
- 19. The pharmaceutical composition according to claim 10, wherein R3, R4 and R5 are hydrogen or methyl, where the total number of methyl groups is one or two.
- 20. The pharmaceutical composition according to claim 10, wherein R3 and R5 are both methyl, and R4 is hydrogen.
- 21. The pharmaceutical composition according to claim 1, wherein the δ receptor activating agent comprises a compound selected from the group consisting of:
- 22. The pharmaceutical composition of claim 1, wherein the δ receptor activating agent comprises
- 23. The pharmaceutical composition of claim 1, wherein the bioactive compound comprises an opiate compound.
- 24.The pharmaceutical composition of claim 1, wherein the bioactive compound comprises an opiate analgesic compound.
- 25. The pharmaceutical composition of claim 1, wherein the bioactive compound comprises a μ opiate compound.
- 26. The pharmaceutical composition of claim 1, wherein the bioactive compound comprises at least one active ingredient selected from the group consisting of alcohol, aldesleukin, alfentanil, bremazocine, buprenorphine, butorphanol, chloropromazine, clozapine, codeine, dantrolene, diazepam, dihydrocodeine, etorphine, fentanyl, flurazepam, heroin, hydrocodone, hydromorphone, ketamine, larazepam, levallorphen, levorphanol, meperidine, methadone, methohexital, mitomycin, morphine, nalbuphine, opium, oxazepam, oxycodone, oxymorphone, pentazocine, phenobarbital, porfimer, propoxyphene, resperidone, sufentanil, temazepam, thiopental, thiorzadine, tramadol, trimethaphan, and zolpidem.
- 27.A pharmaceutical composition comprising:
- 28.A pharmaceutical composition comprising:
- 29.The pharmaceutical composition of claim 28, wherein the δ receptor activating agent comprises a diarylmethylpiperazine or a diarylmethylpiperazine compound.
Cross Reference to Related Applications
[0001] This is a divisional application of United States patent application no. 09/352,308 filed July 12, 1999 and issued October 9, 2001 as U.S. Patent 6,300,332, which claims priority to United States patent application 08/887,312 filed July 3, 1997, which is a continuation-in-part of United States patent application no. 08/658,726, filed June 5, 1996. The disclosures of the following applications are hereby incorporated herein by reference in their entirety: United States patent application no. 08/658,726 filed June 5, 1996; United States patent application no. 08/169,879 filed December 17, 1993; United States patent application no. 08/098,333 filed July 30, 1993; United States patent application no. 08/430,677 filed April 28, 1995; International Patent Application no. PCT/GB93/00216 filed February 2, 1993; Great Britain patent application 9202238.3 filed 3 February 1992; and all applications from which they claim priority, or from which priority is claimed.
Divisions (2)
|
Number |
Date |
Country |
Parent |
09/352,308 |
Jul 1999 |
US |
Child |
09974004 |
Oct 2001 |
US |
Parent |
08/887,312 |
Jul 1997 |
US |
Child |
09/352,308 |
Jul 1999 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08/658,726 |
Jun 1996 |
US |
Child |
08/887,312 |
Jul 1997 |
US |