Abstract: Derivatives of Penicillin, their sulfoxides and sulfones are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Type:
Grant
Filed:
October 16, 1986
Date of Patent:
July 11, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Kevan R. Thompson, Paul E. Finke, James B. Doherty
Abstract: 5-Amino or substituted amino 1,2,3-triazoles are disclosed as a new class of antiproliferative agents useful in the treating and managing of psoriasis, inflammatory bowel syndrome, cutaneous leishmanilisis and certain types of cancer.
Type:
Grant
Filed:
August 20, 1987
Date of Patent:
July 11, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Donald Hupe, Lawrence Argenbright, Nancy Behrens, Barbara A. Azzolina
Abstract: Tetrazolyl derivatives of .beta.-lactams are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Type:
Grant
Filed:
June 5, 1987
Date of Patent:
July 4, 1989
Assignee:
Merck & Co., Inc.
Inventors:
James B. Doherty, William K. Hagmann, Paul E. Finke, Shrenik K. Shah
Abstract: .beta.-Lactam derivatives and analogs are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Type:
Grant
Filed:
July 16, 1987
Date of Patent:
January 10, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, Morris Zimmerman, James B. Doherty, Bonnie M. Ashe, Conrad P. Dorn
Abstract: N-Alkenyl-2-hydroxybenzo[b]thiophene-3-carboxamide derivatives are prepared via treatment of the corresponding unsubstituted carboxamide with appropriate agents, such as aldehydes, ketones, enol ethers, epoxides, acetals or ketals.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, asthma, allergic disorders, skin diseases, cardiovascular disorders, psoriasis, inflammatory bowel disease, glaucoma or other prostaglandins and/or leukotriene mediated diseases.
Abstract: Substituted cinnamyl-2,3-dihydrobenzofurans and analogs were prepared from the nucleophlic substitution of a cinnamylhalide with a 2,3-dihydrobenzofuran anion or an analog thereof. These compounds were found to be potent topical anti-inflammatory agents.
Type:
Grant
Filed:
April 17, 1987
Date of Patent:
October 18, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Michael N. Chang, Norman P. Jensen, Milton L. Hammond, Robert A. Zambias, John McDonald, Kathleen M. Rupprecht
Abstract: Phenylalkyl-2,3-dihydrobenzofurans and analogs were prepared by (1) nucleophilic substitution involving an appropriately substituted 2,3-dihydrobenzofuranol (or 2,3-dihydrobenzopyranol) and a cinnamylhalide followed by reduction; or (2) by Wittig reaction involving a halomethyl derivative of 2,3-dihydrobenzofuran (or 2,3-dihydrobenzopyran and an aryl or a heteroaryl aldehyde followed by reduction. These compounds were found to be potent anti-inflammatory agents.
Type:
Grant
Filed:
May 4, 1987
Date of Patent:
October 4, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Michael N. Chang, David A. Boulton, Kathryn L. Thompson
Abstract: 3-Hydroxyazabenzo[b]thiophene derivatives having optionally 2-aryl, 2-aralkyl, 2-alkyl or 2-alkenyl substituents were prepared by, among other methods, ring closure of an appropriately substituted benzylthio-alkoxycarbonyl-pyridine. These compounds are found to be useful in the treatment of pain, fever, inflammation, arthritic conditions, asthma, allergic disorders, skin diseases such as psoriasis and atopic eczema, cardiovascular disorders, inflammatory diseases and other leukotriene mediated diseases.
Type:
Grant
Filed:
January 30, 1987
Date of Patent:
August 30, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Robert K. Baker, Kathleen M. Rupprecht, Arsenio A. Pessolano, Philippe L. Durette
Abstract: There are disclosed phospholipid analogs which are useful as PAF synthesis inhibitors. These compounds inhibit PAF (platelet-activating factor) biosynthesis and are thereby useful in the treatment of various diseases or disorders mediated by the PAF such as, for example, pain, fever, inflammation, cardiovascular disorder, asthma, lung edema, allergic disorders, skin diseases, psoriasis, and adult respiratory distress syndrome.
Type:
Grant
Filed:
July 1, 1985
Date of Patent:
August 2, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Robert L. Bugianesi, Mitree M. Ponpipom, Kathleen M. Rupprecht
Abstract: N-Alkenyl-3-hydroxybenzo[b]thiophene-2-carboxamide derivatives have been prepared by:(1) treating a substituted 2-halobenzoate with thioacetamide followed by N-alkenylation with appropriate agents, such as aldehydes, ketones, enol ethers, epoxides, acetals or ketals;(2) treating a substituted thiosalicylate with an appropriately substituted haloacetamide, followed by dehydration; and(3) further synthetic modification of compounds prepared above.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, asthma, allergic disorders, skin diseases, cardiovascular disorders, psoriasis, inflammatory bowel disease, glaucoma or other prostaglandins and/or leukotriene mediated diseases.
Type:
Grant
Filed:
February 27, 1985
Date of Patent:
July 26, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Allan N. Tischler, Bruce E. Witzel, Philippe L. Durette, Kathleen M. Rupprecht, Timothy F. Gallagher, Debra L. Allison, Marvin M. Goldenberg
Abstract: Analogs of 2,5-Diaryl tetrahydrothiophenes which were substituted or unsubstituted on 3,4-positions were prepared.These compounds are found to be leukotriene inhibitors and potent and specific PAF (Platelet Activating Factor) antagonists. They are therefore useful in the treatment of various diseases or disorders mediated by the leukotriene and/or PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, adult respiratory distress syndrome, pain, and aggregation of platelets.
Abstract: Thiazole derivatives have been made, for example, by reacting a 2-aryl-2,2-dialkoxyethylamine with an appropriately substituted aryl acetyl halide followed by treating the resulting amide with diphosphoryl pentasulfide. The thiazole derivatives are found to be effective immunoregulants.
Type:
Grant
Filed:
March 26, 1987
Date of Patent:
May 24, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Charles G. Caldwell, Ihor Kopka, Milton L. Hammond, Robert A. Zambias
Abstract: Substituted 2-benzyl-mercapto-imidazoles and analogs were prepared from the nucleophlic substitution of an appropriately substituted benzoxyacetate with a 2-imidazole mercapto anion or an analog thereof. These compounds were found to be anti-inflammatory agents.
Abstract: 2-Benzyl-4-(4-pyridyl)thiazoles and derivatives thereof have been made from converting a benzyl cyanide to the corresponding thioamide followed by condensation with a 4-bromoacetylpyridine. The thiazole derivatives are found to be effective immunoregulants.
Type:
Grant
Filed:
August 21, 1986
Date of Patent:
February 16, 1988
Assignee:
Merck & Co., Inc.
Inventors:
David A. Boulton, Vernon L. Moore, Ihor E. Kopka, Arsenio A. Pessolano
Abstract: 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.
Type:
Grant
Filed:
August 2, 1985
Date of Patent:
January 19, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Bruce E. Witzel, Allan N. Tischler, Debra L. Allison
Abstract: Substituted 1-oxa-dethiacephalosporins are found to be effective elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Abstract: 6-Hydroxy-2-(2-hydroxy-4-methoxyphenyl)benzofuran derivatives and related pharmaceutical compositions and methods of treatment are disclosed. The compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, they are useful therapuetic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation.
Abstract: Phenylalkyl-2,3-dihydrobenzofurans and analogs were prepared by (1) nucleophilic substitution involving an appropriately substituted 2,3-dihydrobenzofuranol (or 2,3-dihydrobenzopyranol) and a cinnamylhalide followed by reduction; or (2) by Wittig reaction involving a halomethyl derivative of 2,3-dihydrobenzofuran (or 2,3-dihydrobenzopyran and an aryl or a heteroaryl aldehyde followed by reduction. These compounds were found to be potent anti-inflammatory agents.
Type:
Grant
Filed:
April 25, 1985
Date of Patent:
December 15, 1987
Assignee:
Merck & Co., Inc.
Inventors:
Michael N. Chang, Kathryn L. Thompson, David A. Boulton
Abstract: .beta.-Lactam derivatives and analogs are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.
Type:
Grant
Filed:
July 2, 1984
Date of Patent:
December 8, 1987
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, James B. Doherty, Morris Zimmerman, Bonnie M. Ashe, Conrad P. Dorn
Abstract: A water-soluble combination of sodium sulindac and an appropriate base, for example, tromethamine or sodium bicarbonate, has been found to exhibit unexpectedly improved onset of activity relative to conventional water-soluble formulations containing sodium sulindac.