Merck + Co., Inc.

Kothandaraman Shankaran

Shrenik K Shah

Sander G Mills

Malcolm MacCoss

Charles G Caldwell

Lihu Yang

William K Hagmann

Ravindra N Guthikonda

Karla L Furman

Ronald W Ratcliffe

Philippe L Durette

Alexander Pasternak

Thomas N Salzmann

Dong-Ming Shen

Changyou Zhou

Jeffrey John Hale

Robert R Wilkening

James V Heck

Malcolm Maccoss

Christopher L Lynch

Dooseop Kim

Gabor Butora

Kevin Tyler Chapman

William J Leanza

Stephen D Goble

Christopher Alan Willoughby

Jennifer L Loebach

Michael J Szymonifka

Stephan K Grant

(wherein n, R, R, R, R, R, R, R, R, R, R, R, R, R, R, Y and Z are defined herein) which are modulators of chemokine receptor activity and are useful in the prevention or treatment of certain inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which chemokine receptors are involved.

3,3-disubstituted tetrahydropyranyl cyclopentyl amide modulators of chemokine receptor activity

The present invention is directed to compounds of the formula (I) (wherein R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, X, m, n and the dashed line are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2 

Tetrahydropyranyl cyclopentyl benzylamide modulators of chemokine receptor activity

Hexahydro-5-imino-1,4-1,4-thiazepine derivatives as inhibitors of nitric oxide synthases

The present invention is directed to pyrrolidine compounds of the formula I:

Pyrrolidine modulators of chemokine receptor activity

Disclosed herein are compounds of Formula I 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 diseases and disorders include hypotension, septic shock, toxic shock syndrome, hemodialysis, IL-2 therapy such as in in cancer patients, cachexia, immunosuppression such as in transplant therapy, autoimmune and/or inflammatory indications including sunburn, eczema or psoriasis and respiratory conditions such as bronchitis, asthma, oxidant-induced lung injury and acute respiratory distress (ARDS), glomerulonephritis, restenosis, inflammatory sequelae of viral infections, myocarditis, heart failure, atherosclerosis, osteoarthritis, rheumatoid arthritis, septic arthritis, chronic or inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic lupus erythematosis (SLE), ocular conditions such as ocular hypertension, retinitis and uveitis, type 1 diabetes, insulin-dependent diabetes mellitus and cystic fibrosis.

Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric

Compounds of the formula: ##STR1## where R is hydrogen, hydroxyl, alkyl or acyl, R' and R' together are oxo, hydroxyimino or alkoxyimino, and R' and R' independently are hydrogen, hydroxyl, acyloxy, or amino substituted by any of hydrogen, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkoxycarbonyl, aralkoxycarbonyl, alkylsulfonyl or arylsulfonyl, and n is 0 or 1, and the pharmaceutically acceptable salts thereof. The compounds are macrolide antibiotics and are also useful as intermediates to the synthesis of other macrolide antibiotics. Pharmaceutical compositions and methods of their use are also provided for.

Homoerythromycin A derivatives modified at the 4'-and 8A-positions

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, immunosuppression 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 usful in the treatment of hypoxia, hyperbaric oxygen convulsions and toxicity, dementia, Sydenham's chorea, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, mulitple sclerosis, Korsakoff's 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.

Cyclic amidine analogs as inhibitors of nitric oxide synthase

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Kendall Park, NJ, United States of America

Kothandaraman Shankaran