Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Thomas J Lanza, Jr

William K Hagmann

Philippe L Durette

Soumya P Sahoo

Shrenik K Shah

Richard L Tolman

Gary H Rasmusson

Derek J Von Langen

Bruce E Witzel

Ping Liu

Ravindra N Guthikonda

Linus S Lin

Linda L Chang

James Patrick Jewell

Hongbo Qi

Helen M Armstrong

Sander G Mills

Malcolm MacCoss

Tsung-Ying Shen

Paul E Finke

Conrad P Dorn

Jeffrey John Hale

James B Doherty

Arsenio A Pessolano

Robert L Clark

Allan N Tischler

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

Substituted amides

Substituted pyridyoxy amides

16-substituted-4-aza-androstane 5-&agr;-reductase isozyme 1 inhibitors

Compounds of the Formula I ##STR1## are inhibitors of the 5.alpha.-reductase 1 isozyme, and are useful alone, or in combination with a 5.alpha.-reductase 2 inhibitor, for the treatment of androgenic sensitive disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.

16-pyrazinyl-substituted-4-aza-androstane 5-.alpha.-reductase isozyme 1

Disclosed herein are compounds of Formula (I) ##STR1## and pharmaceutically acceptable salts thereof which have been found useful in the treatment of nitric oxide synthase mediated diseases and disorders, including neurodegenerative disorders, disorders of gastrointestinal motility and inflammation. These disease and disorders include hypotension, septic shock, toxic shock syndrom, hemodialysis, IL-2 therapy such as in cancer patients, cachexia, immnunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn or psoriasis and respiratory conditions such as bronchitis, asthma, and acure respiratory distress (ARDS), myocarditis, heart failure, atherosclerosis, arthritis, rheumatoid arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis. Compounds of Formula I are also useful in the treatment of hypoxia, hyperbaric oxygen convulsions and toxicity, dementia, Sydenham's chorea, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, Korsakoffs disease, imbecility related to cerebral vessel disorder, ischemic brain edema, sleeping disorders, schizophrenia, depression, PMS, anxiety, drug addiction, pain, migraine, immune complex disease, as immunosupressive agents and for preventing or reversing tolerance to opiates and diazepines.

Substituted saturated aza heterocycles as inhibitors of nitric oxide

Substituted azetidinones are herein disclosed for use in the treatment of various elastase-mediated diseases.

Substituted azetidiones as anti-inflammatory and antidegenerative agents

16-substituted-4-aza-3-oxo-androstane as 5-alpha-reductase isozyme 1

16-substituted-4-aza-androstane 5-alpha-reductase isozyme 1 inhibitors

New substituted azetidinones of the general Formula (I) which have been found to be potent elastase inhibitors and thereby useful anti-inflammatory and antidegenerative agents are described. ##STR1## wherein R.sub.4 is (a) ##STR2## or (b) ##STR3## where R.sub.x is carboxy C.sub.1-6 alkyl, benzyloxycarbonylC.sub.1-3 alkyl, or t-butoxycarbonylC.sub.1-3 alkyl, wherein

Substituted azetidinones as anti-inflammatory and antidegenerative agents

3-Hydroxybenzo[b]thiophene-2-carboxamide derivatives have been prepared by:

5-methylthio-3-hydroxybenzo [b]thiophene-2-carboxamide derivatives as

3-hydroxybenzo[b]thiophene-2-sulfide derivatives have been prepared by ring closure of an appropriately substituted 2--R.sup.1 SCH.sub.2 S-- benzoic acid ester in the presence of a strong base. These compounds have been found to be specific inhibitors of 5-lipoxygenase and thereby useful in the treatment of inflammation, pain and fever associated with inflammation, arthritic conditions, asthma, allergic disorders such as allergic rhinitis and chronic bronchitis, skin diseases like psoriasis and atopic exzema, cardiovascular or vascular disorders, and other leukotriene mediated diseases. Furthermore, these compounds have been found to exhibit cytoprotective activity which does not involve the inhibition of gastric acid secretion but can be used at relatively low dosages for increasing the resistance of gastro-intestinal mucosa to strong irritants.

3-hydroxybenzo[b]thiophene-2-sulfide derivatives compositions, and

The various isomers of oxazolo- and thiazolopyridines having utility as antiinflammatory, antipyretic and analgesic agents are prepared by condensation of an appropriate amino-hydroxypyridine or amino-mercaptopyridine with a carboxylic acid, halide or anhydride.

Anti-inflammatory oxazolo [5,4-b]pyridines

Anti-inflammatory oxazole[4,5-b]pyridines

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Edison, NJ, United States of America

Thomas J Lanza, Jr