Merck + Co., Inc.

Debra L Allison

Bruce E Witzel

Kathleen M Rupprecht

Allan N Tischler

Philippe L Durette

Timothy Francis Gallagher

James B Doherty

Marvin M Goldenberg

Tsung-Ying Shen

Paul E Finke

Conrad P Dorn

Charles G Caldwell

Method for increasing resistance to gastro-intestinal irritation, and for the treatment of pain, fever, inflammation, arthritic conditions, asthma, allergic disorders, skin diseases, cardiovascular disorders, psoriasis, inflammatory bowel disease, glaucoma or other prostaglandin and/or leukotriene mediated diseases comprising the administration to a subject in need of such treatment, a non-toxic therapeutically effective amount of compound of formula I: ##STR1##

N-alkenyl-3-hydroxybenzo[b]thiophene-2-carboxamide derivatives as dual

Aryl substituted thiophenes 3-ols, its dihydro derivatives, 1-oxide and 1,1-dioxide analogs, as well as aryl substituted furans, are 5-lipoxygenase inhibitors useful in the treatment of inflammation and other leukotriene-mediated diseases.

Aryl-substituted thiophene 3-ols, derivatives and analogs useful as

N-Alkenyl-3-hydroxybenzo[b]thiophene-2-carboxamide derivatives have been prepared by:

N-substituted fused-heterocyclic carboxamide derivatives, for example, N-(2,2-diphenylethenyl)-3-hydroxythieno[3,2-b]thiophene-2-carboxamide can be prepared by ring closure between an appropriately substituted halo-thiophene ester, e.g., methyl 3-bromo-thiophene-2-carboxylate, and mercaptoacetamide followed by condensation with diphenylacetaldehyde. Alternatively, the ring closure can be carried out between an appropriately substituted mercaptothiophene ester, e.g., methyl 3-mercaptothiophene-2-carboxylate and a haloacetamide to afford the fused-heterocyclic intermediate, 3-hydroxythieno[3,2-b]thiophene-2-carboxamide. N-alkenylation of the intermediate will then lead to the final products. These compounds have been found to be effective inhibitors of both cyclooxygenase and lipoxygenase and thereby useful in the treatment of pain, fever, inflammation, arthritic conditions, eye inflammation caused by glaucoma or other eye diseases, asthma, allergic disorders, skin diseases, cardiovascular disorders, psoriasis, inflammatory bowel disease, or other prostaglandin and/or leukotriene mediated diseases.

N-substituted fused-heterocyclic carboxamide derivatives as dual

Tricyclic derivatives of substituted pyrrole acids, e.g., substituted 4,10-dihydro-10-oxo-1H-[1]benzoxepino[4,3-b]pyrrole-2-acetic acids or the 5-thia analogs thereof have been prepared via hydrolysis of a precursor or decarboxylation of a precursor-diacid. These tricyclic compounds are found to have high analgesic and anti-inflammatory activities but low ulcerogenic side effects.

Tricyclic derivatives of substituted pyrrole acids as analgesic and

Improved yields of Benzoxepino- or Benzthiapino[4,3-b]pyrrole-2-acetic acids have been achieved from processes based on modifications performed on a pyrrole carboxylic ester rather than on a pyrrole-.alpha.-oxoacetate.

Process for preparing Benzoxepino- or

Zomepirac and its analogs have been prepared from a 5-aroyl-3-hydroxycarbonyl-4-substituted pyrrole-2-acetic acid via acidic decarboxylation.

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Scotch Plains, NJ, United States of America

Debra L Allison