Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-02-10
1999-10-19
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540524, 540544, 544 60, 544 62, 544130, 544141, 544364, 544372, 544373, 546187, 546196, 546201, 546205, 546208, 546212, 546216, 5483147, 548455, 548466, 548467, 548518, 548950, A61K 31445, A61K40106, A61K41314, A61K45102
Patent
active
059689234
DESCRIPTION:
BRIEF SUMMARY
This invention relates to lactams. More particularly, this invention relates to azetidinylalkyllactam derivatives and to processes for the preparation of, intermediates used in the preparation of, compositions containing and uses of, such derivatives.
The present azetidinylalkyllactam derivatives are antagonists of tachykinins, including NKA, NKB and Substance P, acting at the human neurokinin-1 (NK.sub.1), neurokinin-2 (NK.sub.2) or neurokinin-3 (NK.sub.3) receptor, or a combination thereof. The derivatives are therefore useful for preventing or treating an inflammatory disease such as arthritis, psoriasis, asthma or inflammatory bowel disease, a central nervous system (CNS) disorder such as anxiety, depression, dementia or psychosis, a gastro-intestinal (GI) disorder such as functional bowel disease, irritable bowel syndrome, gastro-oesophageal reflux, faecal incontinence, colitis or Crohn's disease, an urogenital tract disorder such as incontinence, hyperreflexia or cystitis, a pulmonary disorder such as chronic obstructive airways disease, an allergy such as eczema, contact dermatitis or rhinitis, a hypersensitivity disorder such as poison ivy, a vasospastic disease such as angina or Reynaud's disease, a fibrosing or collagen disease such as scleroderma or eosinophillic fascioliasis, reflux sympathetic dystrophy such as shoulder/hand syndrome, an addiction disorder such as alcoholism, a stress-related somatic disorder, a peripheral neuropathy such as diabetic neuropathy, neuralgia, causalgia, painful neuropathy, a burn, herpetic neuralgia or post-herpetic neuralgia, a neuropathological disorder such as Alzheimer's disease or multiple sclerosis, a disorder related to immune enhancement or suppression such as systemic lupus erythematosis, a rheumatic disease such as fibrositis or emesis, cough, acute or chronic pain or migraine. The present derivatives are particularly potent and selective antagonists of achykinins, including NKA, NKB and Substance P, acting at the human NK.sub.2 eceptor. They are particularly useful for treating or preventing an inflammatory isease such as arthritis, psoriasis, asthma or inflammatory bowel disease, a entral nervous system (CNS) disorder such as anxiety, depression, dementia or psychosis, a gastrointestinal (GI) disorder such as functional bowel disease, irritable bowel syndrome, gastro-oesophageal reflux, faecal incontinence, colitis or Crohn's disease, an urogenital tract disorder such as incontinence or cystitis, a pulmonary disorder such as chronic obstructive airways disease, an allergy such as eczema, contact dermatitis or rhinitis, a hypersensitivity disorder such as poison ivy, a peripheral neuropathy such as diabetic neuropathy, neuralgia, causalgia, painful neuropathy, a burn, herpetic neuralgia or post-herpetic neuralgia, cough or acute or chronic pain.
The present invention provides compounds of the formula: ##STR2## and the pharmaceutically acceptable salts thereof, wherein R is C.sub.3 -C.sub.7 cycloalkyl, aryl or C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl being optionally substituted by fluoro, --COOH, --COO(C.sub.1 -C.sub.4 alkyl), C.sub.3 -C.sub.7 cycloalkyl, adamantyl, aryl or het.sup.1, and said C.sub.3 -C.sub.7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, fluoro, fluoro(C.sub.1 -C.sub.4)alkyl and fluoro(C.sub.1 -C.sub.4)alkoxy; optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo and trifluoromethyl; -C.sub.7 cycloalkyl), --NR (C.sub.2 -C.sub.5 alkanoyl), --NR.sup.3 R.sup.4, --NR.sup.5 CONR.sup.5 R.sup.6, (C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl)R.sup.5 N--, (C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl).sub.2 N--, --NR.sup.5 COCF.sub.3, --NR.sup.5 SO.sub.2 CF.sub.3, --NR.sup.5 (SO.sub.2 C.sub.1 -C.sub.4 alkyl), --NR.sup.5 SO.sub.2 NR.sup.5 R.sup.6, --NR.sup.5 (SO.sub.2 aryl), --N(aryl)(SO.sub.2 C.sub.1 -C.sub.4
REFERENCES:
patent: 5340822 (1994-08-01), Edmonds -Alt et al.
patent: 5472958 (1995-12-01), Gunn et al.
patent: 5534510 (1996-07-01), Abe et al.
patent: 5565474 (1996-10-01), Baroni et al.
MacKenzie Alexander Roderick
Marchington Allan Patrick
Meadows Sandra Dora
Middleton Donald Stuart
Appleman Jolene W.
Coleman Brenda
Ginsburg Paul H.
Pfizer Inc.
Raymond Richard L.
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