Abstract: A process is described for the synthesis of E-2-methyl-.alpha.,.beta.-unsaturated aldehydes, which are useful as intermediates in the synthesis of the macrolide structure of the immunosuppressant FK-506. These compounds are also useful as ultraviolet radiation absorbers.
Type:
Grant
Filed:
February 27, 1989
Date of Patent:
April 3, 1990
Assignee:
Merck & Co., Inc.
Inventors:
Richard Desmond, Sander G. Mills, Ralph P. Volante, Ichiro Shinkai
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 benzylthioalkoxycarbonyl-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 disease and other leukotriene mediated diseases.
Type:
Grant
Filed:
April 28, 1988
Date of Patent:
February 27, 1990
Assignee:
Merck & Co., Inc.
Inventors:
Robert K. Baker, Kathleen M. Rupprecht, Arsenio A. Pessolano, Philippe L. Durette
Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of 1 from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.
Type:
Grant
Filed:
January 19, 1989
Date of Patent:
January 9, 1990
Assignee:
Merck & Co., Inc.
Inventors:
Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
Abstract: Substituted 3-nitropyridines are disclosed to have activity in increasing the sensitivity of hypoxic tumor cells to therapeutic radiation. Also disclosed are methods of preparing such compounds by amination of the corresponding chloro-3-nitropyridine with 2,3-dihydroxypropylamine and pharmaceutical compositions including such compounds.
Abstract: A novel antibacterial drug combination is provided, one component being a 2-substituted penem, and the other component is a dipeptidase (E.C.3.4.13.11) inhibitor. The dual-component combination is formulated so that 1 to 3 parts by weight of the penem are employed for 30 to 1 parts by weight of the inhibitor compound.
Abstract: Compounds are disclosed of the structural formula: ##STR1## wherein R.sup.2 is independently selected from hydrogen, linear or branched C.sub.1 -C.sub.3 alkyl, which can be substituted with fluoro, hydroxy, or protected hydroxy, R.sup.3 is hydrogen or a protecting group, X is sulfur or selenium, Q is hydroxymethyl, carboxy or C.sub.1 -C.sub.4 alkoxycarbonyl, and R.sup.1 is C.sub.1 -C.sub.4 alkyl, C.sub.6 -C.sub.10 aryl, or pyridyl which can be substituted with C.sub.1 -C.sub.4 alkyl, alkoxy and nitro; such compound are useful for selectively obtaining 1-.beta.-methylcarbapenem intermediates.
Type:
Grant
Filed:
February 6, 1989
Date of Patent:
October 10, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Burton G. Christensen, Lovji D. Cama, Susan M. Schmitt
Abstract: A process for producing arylglyoxal arylimine intermediates, by the DMSO/HBr oxidation of arylmethylketones. The imine compounds are intermediates in the synthesis of carbapenem antibiotics, i.e. imipenem.
Type:
Grant
Filed:
March 18, 1988
Date of Patent:
October 3, 1989
Assignee:
Merck & Company Incorporated
Inventors:
Richard Desmond, Sander G. Mills, Ralph P. Volante, Ichiro Shinkai
Abstract: Disclosed are specific dipeptidyl 4-0, 6-0-acyl-2-amino-2-deoxy-D-glucose derivatives which, either alone, or in combination with an anti-AIDS drug, e.g. azidothymidine, protect against opportunistic bacterial, fungal and viral infection in a human host immunocompromised by an AIDS-related virus, as well as help to suppress the AIDS-related virus itself.
Abstract: Disclosed are specific dipeptidyl 2-amino-1,2-dideoxy-D-glucoses which, either alone, or in combintion with an anti-AIDS drug, e.g. azidothymidine, protect an immunocompromised human host, resulting from an AIDS-related virus, against opportunistic, bacterial, fungal and viral infections, as well as help to suppress the AIDS-related virus itself.
Abstract: Disclosed are specific dipeptidyl saccharide derivatives which alone, or in combination with an anti-AIDS drug, e.g. azidothymidine, provide protection against opportunistic infection in human individuals whose resistance to infection has been specifically suppressed by an AIDS-related (HIV) virus, as well as help to suppress the AIDS-related infection itself.
Abstract: Disclosed are specific dipeptidyl 5-0, 6-0-Acyl-2-amino-2-deoxy-D-glucofuranoses, which, either alone, or in combination with an anti-AIDS drug, e.g. azidothymidine, provide protection in human individuals whose resistance to infection has been specifically suppressed by an AIDS-related (HIV) virus, as well as help to suppress the AIDS-related infection itself.
Abstract: Disclosed are N-acyl derivatives of the antibiotic thienamycin having the following structural formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen and acyl. Such derivatives and their pharmaceutically acceptable salts, are useful as antibiotics. Also disclosed are processes for the preparation of such derivatives, pharmaceutical compositions comprising such derivatives, and methods of treatment comprising administering such derivatives and compositions when an antibiotic effect is indicated.
Type:
Grant
Filed:
August 27, 1987
Date of Patent:
June 13, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Louis Barash, Burton G. Christensen, John Hannah, William J. Leanza, David H. Shih
Abstract: Disclosed are specific aminoalkyl naphthalenediol derivatives that enhance natural human host resistance to viral infectious organisms and particularly AIDS-related viruses. Such agents are also administered prophylactically to individuals whose resistance to infection has been specifically immunocompromised by an AIDS-related (HIV) virus.
Abstract: Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, diaklylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: ##STR1## wherein R.sup.16 is H or CH.sub.3, preferably beta-methyl; R.sup.6, and R.sup.7 are independently hydrogen, linear, branched or cyclic C.sub.1 -C.sub.5 alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino wherein R.sup.6 and R.sup.7 taken together can also be C.sub.2 -C.sub.4 alkylidene, similarly substituted; with the proviso that both R.sup.6 and R.sup.7 are not unsubstituted alkyl, R.sup.1 and R.sup.
Type:
Grant
Filed:
June 10, 1985
Date of Patent:
May 23, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Burton G. Christensen, John C. Chabala, Ronald W. Ratcliffe
Abstract: A process for isomerizing an alpha methylated azetidinone alkyl ester to the corresponding beta-methyl isomer, which is an intermediate in the synthesis of 1-beta-methylcarbapenem antibacterial agents. The process involves treating the dianion of structure I, being the alpha isomer, with a P-H or S-H containing organic protic acid, organometallic Sn or Pb hydride, metallic cation salt or trialkyl borane, followed by quenching with an OH protic organic acid or mineral acid.
Type:
Grant
Filed:
December 16, 1987
Date of Patent:
March 28, 1989
Assignee:
Merck & Co., Inc.
Inventors:
Dean R. Bender, Ichiro Shinkai, Anthony M. De Marco, James A. McCauley
Abstract: A stereospecific process for preparing 3-trans-R-trisubstituted silyloxyethyl substituted azetidinones useful as intermediates for preparing penems and carbapenems is provided wherein a 3-unsubstituted azetidinone is treated with a strong base and a trisubstituted silylmethyl ketone to form 3-trans-S-[1-trisubstituted silyl-1-hydroxy]ethylazetidinone followed by rearrangement of this resulting carbinol by treatment with an alkali metal alkoxide and a proton source.
Abstract: Described bare 3-halovinylglycines and their amino acid dipeptide and oligopeptide conjugates, a new class of efficient antibacterial agents, pharmaceutical compositions containing them as active ingredients, and methods of synthesis. The compounds are thought to interfere in bacterial cell wall synthesis.
Type:
Grant
Filed:
November 12, 1987
Date of Patent:
February 21, 1989
Assignee:
Merck & Co., Inc.
Inventors:
David Taub, Robert H. Abeles, Arthur A. Patchet
Abstract: A process is described for the stereochemically controlled synthesis of intermediates useful in producing 1-betamethylcarbapenem antibiotics.
Type:
Grant
Filed:
May 4, 1987
Date of Patent:
December 13, 1988
Assignee:
Merck & Co., Inc.
Inventors:
Thomas N. Salzmann, Lelia M. Fuentes, Ichiro Shinkai