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US 5,854,249 AGranted
Opioid diarylmethylpiperazines and piperidines
AssigneeDelta Pharmaceuticals, Inc.
InventorsKwen-Jen Chang, Grady Evan Boswell, Dulce Garrido Bubacz, Mark Allan Collins, Ann Otstot Davis, Robert Walton McNutt, Jr.
Life of this patent
Estimating the term…
Abstract
A method for the treatment or prophylaxis of one or more conditions or disorders selected from the group consisting of physiological pain, diarrhea, urinary incontinence, mental illness, drug and alcohol addiction/overdose, lung edema, depressioysema, apnea, cognitive disorders and gastrointestinal disorders, comprising administration to a subject in need of such treatment or prophylaxis, of a diarylmethylpiperazine or piperidine opioid compound.
Claims22
A method for the treatment or prophylaxis of one or more conditions or disorders selected from the group consisting of diarrhea, urinary incontinence, and gastrointestinal disorders, comprising administration to a subject in need of such treatment or prophylaxis, of an effective amount of a compound of the formula:
- ##STR40## wherein:
- Ar is a 5- or 6-member carbocyclic or heterocyclic aromatic ring having on a first ring carbon atom thereof a substituent Y and on a second ring carbon atom thereof a substituent R.sub.1,
- Y is selected from the group consisting of:
- hydrogen;
- halogen;
- C1-C6 alkyl;
- C1-C6 haloalkyl;
- C3-C6 cycloalkyl;
- C1-C6 alkoxy;
- C3-C6 cycloalkoxy;
- sulfides of the formula SR8 where R8 is C1-C6 alkyl, C3-C6 cycloalkyl, arylalkyl comprising 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 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;
- carboxamides of the formula CONR9R10 where R9 and R10 may be the same or different, and may be hydrogen, C1-C6 alkyl, C2-C6 hydroxyalkyl, C2-C6 methoxyalkyl, C3-C6 cycloalkyl, or C5-C10 aryl, a peptide moiety having from 2 to 30 carbon atoms, or R9 and R10 together may form a ring of 5 or 6 atoms;
- and
- sulfonamides 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;
- and
- amino, and carboxamides and sulfonamides thereof;
- G is carbon or nitrogen;
- R1 is hydrogen, halogen, or C1-C4 alkyl;
- R2 is hydrogen, halogen, or C1-C4 alkyl;
- R3, R4, and R5 may be the same or different, and are independently selected from hydrogen and methyl, subject to the proviso that the total number of methyl groups does not exceed two, or any two of such R3, R4, and R5 substituents together may form a bridge including 1 to 3 carbon atoms;
- R6 is selected from the group consisting of:
- hydrogen;
- C1-C6 alkyl;
- C3-C6 cycloalkyl;
- aralkyl containing C5-C10 aryl and C1-C6 alkyl moieties;
- alkoxyalkyl containing C1-C4 alkoxy and C1-C4 alkyl moieties;
- C1-C4 cyanoalkyl;
- C1-C4 hydroxyalkyl;
- aminocarbonylalkyl containing a C1-C4 alkyl moiety;
- and
- R12COR13, where R12 is C1-C4 alkylene, and R13 is C1-C4 alkyl or C1-C4 alkoxy;
- and
- R7 is hydrogen or fluorine,
- subject to the provisos that:
- (1) R1, R2 and R7 may be fluorine only when Z is --OH;
- and
- (2) when G is carbon, R6 is not aralkyl,
- or a pharmaceutically acceptable ester, or salt thereof.
45 more elements
A method of effecting a receptor-mediated therapeutic treatment of an animal subject in need of such treatment for a condition selected from the group consisting of:
- pain;
- mental, and/or cognitive disorder;
- gastrointestinal disorder;
- alcohol and/or drug abuse and/or overdose;
- cough;
- diarrhea;
- urinary incontinence;
- lung edema;
- depression;
- and respiratory disorders, said method comprising administering to said animal subject an effective amount of a therapeutically effective compound for said treatment, selected from those of the formula:
- ##STR43## wherein:
- Ar is a 5- or 6-member carbocyclic or heterocyclic aromatic ring having on a first ring carbon atom thereof a substituent Y and on a second ring carbon atom thereof a substituent R.sup.1,
- Y is selected from the group consisting of:
- hydrogen;
- halogen;
- C.sub.1 -C.sub.6 alkyl;
- C.sub.1 -C.sub.6 haloalkyl;
- C.sub.3 -C.sub.6 cycloalkyl;
- C.sub.1 -C.sub.6 alkoxy;
- C.sub.3 -C.sub.6 cycloalkoxy;
- sulfides of the formula SR.sup.8 where R.sup.8 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, arylalkyl comprising a C.sub.5 -C.sub.10 aryl moiety and an C.sub.1 -C.sub.6 alkyl moiety, or C.sub.5 -C.sub.10 aryl;
- sulfoxides of the formula SOR.sup.8 where R.sup.8 is the same as above;
- sulfones of the formula SO.sub.2 R.sup.8 where R.sup.8 is the same as above;
- nitrile,
- C.sub.1 -C.sub.6 acyl;
- alkoxycarbonylamino (carbamoyl) of the formula NHCO.sub.2 R.sup.8 where R.sup.8 is the same as above;
- carboxylic acid, or an ester, amide, or salt thereof;
- aminomethyl of the formula CH.sub.2 NR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 may be the same or different, and may be hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 hydroxyalkyl, C.sub.2 -C.sub.6 methoxyalkyl, C.sub.3 -C.sub.6 cycloalkyl, or C5-C.sub.10 aryl, or R.sub.9 and R.sub.10 together may form a ring of 5 or 6 atoms;
- carboxamides of the formula CONR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are the same as above, or C.sub.2 -C.sub.30 peptide conjugates thereof;
- sulfonamides of the formula SO.sub.2 NR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are the same as above;
- and
- Z is selected from the group consisting of:
- hydroxyl, and esters thereof;
- hydroxymethyl, and esters thereof;
- and
- amino, and carboxamides and sulfonamides thereof;
- G is carbon or nitrogen;
- R.sup.1 is hydrogen, halogen, or C.sub.1 -C.sub.4 alkyl;
- R.sup.2 is hydrogen, halogen, or C.sub.1 -C.sub.4 alkyl;
- R.sup.3, R.sup.4, and R.sup.5 may be the same or different, and are independently selected from hydrogen and methyl, subject to the proviso that the total number of methyl groups does not exceed two, or any two of such R.sup.3, R.sup.4, and R.sup.5 substituents together may form a bridge including 1 to 3 carbon atoms;
- R.sup.8 is selected from the group consisting of:
- hydrogen;
- C.sub.1 -C.sub.6 alkyl;
- C.sub.3 --C.sub.6 cycloalkyl;
- aralkyl containing C.sub.5 -C.sub.10 aryl and C.sub.1 -C.sub.6 alkyl moieties;
- alkoxyalkyl containing C.sub.1 -C.sub.4 alkoxy and C.sub.1 -C.sub.4 alkyl moieties;
- C.sub.1 -C.sub.4 cyanoalkyl;
- C.sub.1 -C.sub.4 hydroxyalkyl;
- aminocarbonylalkyl containing a C.sub.1 -C.sub.4 alkyl moiety;
- and
- R.sup.12 COR.sup.13, where R.sup.12 is C.sub.1 -C.sub.4 alkylene, and R13 is C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
- and
- R.sup.7 is hydrogen or fluorine,
- subject to the provisos that:
- (1) R.sup.1, R.sup.2 and R.sup.7 may be fluorine only when Z is --OH;
- and
- (2) when G is carbon, R.sup.8 is not aralkyl,
- or a pharmaceutically acceptable ester, or salt thereof.
55 more elements
Dependencies are inferred from the claim text.