Hetero Ring Is Four-membered Containing Nitrogen And Having Chalcogen Double Bonded Directly To A Ring Carbon Which Is Adjacent To The Ring Nitrogen Patents (Class 540/200)
Heavy metal containing (Class 540/201)
Plural hetero atoms in the hetero ring (Class 540/202)
Polycyclo ring system containing the hetero ring as one of the cyclos (Class 540/203)
Additional chalcogen bonded directly to the hetero ring (Class 540/354)
Halogen attached directly at the 4-position of the hetero ring by nonionic bonding (Class 540/361)
The 4-position of the hetero ring is unsubstituted or alkyl substituted only (Class 540/362)
Nitrogen bonded directly at the 3-position of the hetero ring (Class 540/364)
  • Processes for preparing carbapenem derivatives
    Patent number: 5306816
    Abstract: The invention relates to carbapenem derivatives useful as antimicrobial agents, more particularly to intermediate compounds for the preparations thereof of the formula ##STR1##
    Type: Grant
    Filed: February 12, 1992
    Date of Patent: April 26, 1994
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Masayoshi Murata, Chiyoshi Kasahara, Hideo Tsutsumi, Yoshihiro Murakami
  • Method of enantioselectively inserting a carbene
    Patent number: 5296595
    Abstract: A chiral catalyst is disclosed together with methods of using it for enantioselective syntheses. The chiral catalyst includes a nucleus with two metal atoms that has four bridging ligands oriented radially to the axis of the nucleus. Each of these ligands includes a two complexing atoms each complexed to one of the metal atoms. At least one of the bridging ligands includes a chiral center which is bonded to one of the complexing atoms. Preferably, all four of the bridging ligands include a chiral center bonded to one of the complexing atoms. The catalyst of the invention has been found to be useful in catalyzing carbenoid transformation reactions such as cyclopropanation.
    Type: Grant
    Filed: September 24, 1992
    Date of Patent: March 22, 1994
    Assignee: Research Corporation Technologies
    Inventor: Michael P. Doyle
  • Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines
    Patent number: 5284963
    Abstract: The invention provides a novel method for producing compounds of the formula I: ##STR1## wherein X and R are defined in the specifications. The invention also provides a method for making intermediates useful to produce the compounds of formula I. Utilizing a common intermediate, the novel method efficiently produces compounds of the formula I.
    Type: Grant
    Filed: August 13, 1992
    Date of Patent: February 8, 1994
    Assignee: American Cyanamid Company
    Inventors: Phaik-Eng Sum, Ving J. Lee
  • Benzoquinone compounds
    Patent number: 5283355
    Abstract: Compounds of the Formula (5) and processes for their preparation and use, particularly in the manufacture of unsymmetrical triphenodioxazine dyes: ##STR1## wherein: Y is H, alkyl, substituted alkyl, alkoxy, Cl or Br;R is a group of Formula (3) ##STR2## R.sup.1 and R.sup.2 are each independently alkyl, or R.sup.1 and R.sup.2 together with the carbon atom to which they are attached form an optionally substituted 4, 5 or 6 membered alicyclic or heterocyclic ring;R.sup.3 is H;Z is Cl, Br or A--NH; andA is H or the residue of a primary amine.
    Type: Grant
    Filed: October 22, 1991
    Date of Patent: February 1, 1994
    Assignee: Imperial Chemical Industries PLC
    Inventor: William J. E. Norris
  • Amidinophenylalanine derivatives, process for their preparation, their use and compositions containing them
    Patent number: 5274098
    Abstract: Amidinophenylalanine derivatives, a process for their preparation, their use and pharmaceutical compositions which contain these compounds are described.
    Type: Grant
    Filed: April 7, 1992
    Date of Patent: December 28, 1993
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: StuWerner, Gerhard Dickneite
  • Metal ion porphyrin-containing poly(azine)
    Patent number: 5252698
    Abstract: The present invention relates to porphyrin and metal ion-containing monomers and polymers. The monomers ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from H, alkyl having 1 to 6 carbon atoms, phenyl or phenyl substituted with 1 to 3 alkyl groups each having 1 to 6 carbons or with 1 to 3 halogen atoms and A is a metal atom, are used with a diamine or a dialdehyde respectively to produce a porphyrin polymer or a metal ion containing porphyrin polymer. These polymers are useful as electrical conductors and as liquid crystal polymers.
    Type: Grant
    Filed: October 9, 1992
    Date of Patent: October 12, 1993
    Assignee: SRI International
    Inventors: Tilak R. Bhardwaj, Susanna C. Ventura, Subhash C. Narang
  • Azetidin-2-one derivatives as serine protease inhibitors
    Patent number: 5250677
    Abstract: The present invention relates to new 3-guanidinoalkyl-2-azetidinones of the formula ##STR1## wherein: U and W can be the same or different and are selected from the group consisting of hydrogen and an amino protecting group;n is 1 to 3;X is a member selected from the group consisting of hydrogen, trialkylsilyl, arylsulfonyl, amino substituted arylsulfonyl, alkylsulfonyl, arylaminocarbonyl, alkylcarbonyl and arylcarbonyl; andY is a member selected from the group consisting of hydrogen, arylalkenyl, arylalkyl, formyl, carboxy, alkoxycarbonyl, acyloxy, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, arylaminocarbonyl, the radical ##STR2## in which R is hydrogen, alkyl or arylalkyl, and the radical ##STR3## in which m is 1 to 3 and R' is hydrogen or --CO.sub.2 R" wherein R" is hydrogen, alkyl or arylalkyl.The novel azetidinones of the present invention exhibit anti-thrombin and anti-trypsin activities and are thus useful in controlling blood coagulation and treating pancreatitis.
    Type: Grant
    Filed: October 6, 1992
    Date of Patent: October 5, 1993
    Assignee: Bristol-Myers Squibb Company
    Inventor: William T. Han
  • Process for the preparation of 3-substituted-2-azetidinones
    Patent number: 5250676
    Abstract: Provided is a process for diastereoselectively preparing compounds of the formula ##STR1## which includes the step of subjecting a compound of the formula ##STR2## to a salt whose anion is a nucleophilic base whose conjugate acid has a pKa in the range of between about -7 to about 14, or a silylated derivative of the salt; whereinR.sub.1 is said nucleophile;R is hydrogen, or protected amino,R.sub.2 is R.sub.4 as defined herein below;R.sub.3 is a leaving group; andR.sub.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or a group of the formula--CH.sub.2 --CH.sub.2 --R.sub.6whereinR.sub.6 is 2-furyl, naphthyl, phenyl, phenyl substituted with 1, 2 or 3 substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, nitro, halo, carboxy and amido; orR.sub.6 is a group of the formula--COOR.sub.7or--COSR.sub.7in whichR.sub.7 is selected from C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, benzyl, phenyl, or benzyl or phenyl substituted with 1, 2 or 3 substituents selected from C.sub.
    Type: Grant
    Filed: March 23, 1992
    Date of Patent: October 5, 1993
    Assignee: University of Notre Dame du Lac
    Inventors: Catherine M. Gasparski, Marvin J. Miller, Min Teng
  • Benzthiazolinonyl-substituted alkylamides
    Patent number: 5240919
    Abstract: Compounds of general formula (I): ##STR1## where R, X, A, B and p are defined in the description. Medicinal products useful for treating sleep disorders comprising the same.
    Type: Grant
    Filed: March 9, 1992
    Date of Patent: August 31, 1993
    Assignee: Adir et Compagnie
    Inventors: Said Yous, Isabelle Lesieur, Patrick Depreux, Daniel H. Caignard, Beatrice Guardiola, Gerard Adam, Pierre Renard
  • Heterocyclic compounds and their production
    Patent number: 5231179
    Abstract: A compound of the formula: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each a hydrogen atom, a lower alkyl group, an ar(lower)alkyl group or an aryl group, or R.sub.1 and R.sub.2 may be combined together to form a lower alkylene group and/or R.sub.3 and R.sub.4 are combined together to form a lower alkylene group, or R.sub.1, R.sub.2, R.sub.3 and R.sub.4 may be combined together to form an o-phenylene group, X is a halogen atom and Y is an oxygen atom or a nitrogen atom substituted with lower alkyl or aryl, which is useful as an intermediate in the synthesis of 1.beta.-methylcarbapenem compounds valuable as antibiotics.
    Type: Grant
    Filed: April 12, 1991
    Date of Patent: July 27, 1993
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Shiro Terashima, Yoshio Ito, Takeo Kawabata, Kunikazu Sakai, Tamejiro Hiyama, Yoshikazu Kimura, Makoto Sunagawa, Katsumi Tamoto, Akira Sasaki
  • 4-cyclohexenyl azetidinone derivatives
    Patent number: 5225552
    Abstract: Compounds of formula ##STR1## in which R.sub.1 represents a hydrogen atom or a hydroxyl protecting group; R.sub.2 represents a hydrogen atom or a trialkylsilyl group, and --X--Y-- represents the epoxide group (A) or the alkene group (B). ##STR2## wherein R.sub.3 represents a C.sub.1-6 alkyl group optionally substituted by halogen or an optionally substituted phenyl group, useful as intermediates in the preparation of antibacterially active compound.
    Type: Grant
    Filed: March 6, 1992
    Date of Patent: July 6, 1993
    Assignee: Glaxo SpA
    Inventor: Alcide Perboni
  • Process for preparing (1'R,3S)-3-(1'-hydroxyethyl)-azetidin-2-one and derivatives thereof
    Patent number: 5204461
    Abstract: A process for preparing (1'R,3S)-3-(1'-hydroxyethyl)-azetidin-2-one or a derivative thereof represented by formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom or a hydroxyl-protective group, is disclosed, comprising reacting (2S,3R)-2-aminomethyl-3-hydroxybutyric acid or a derivative thereof represented by formula (II): ##STR2## wherein R.sup.1 is as defined above, with a sulfenamide represented by formula (III): ##STR3## wherein R.sup.2 represents ##STR4## and R.sup.3 and R.sup.4 each represent a hydrogen atom or a cyclic or acyclic hydrocarbon group, provided that they do not simultaneously represent a hydrogen atom, or R.sup.3 and R.sup.4 are taken together with the adjacent nitrogen atom to form a heterocyclic group, and triphenylphosphine. The reaction yield is high, and the sulfenamide (III) used as a lactamization reagent is cheap and can be recovered after the reaction.
    Type: Grant
    Filed: November 8, 1991
    Date of Patent: April 20, 1993
    Assignee: Takasago International Corporation
    Inventors: Toshiyuki Murayama, Takashi Miura, Toyohiko Kobayashi
  • Polysaccharide derivatives as separating agents
    Patent number: 5202433
    Abstract: A polysaccharide derivative prepared by replacing a part or the whole of hydrogen atoms of hydroxyl and/or amino groups of a polysaccharide with one or more atomic groups represented by the following formula (1), (2) or (3) is new and useful for the separation of optical isomers: ##STR1## wherein the number of carbon atoms constituting R is 1 to 30 and R is a group having at least one asymmetric center.
    Type: Grant
    Filed: January 18, 1991
    Date of Patent: April 13, 1993
    Assignee: Daicel Chemical Industries, Ltd.
    Inventors: Yoshio Okamoto, Koichi Hatada
  • 4-cyclohexenyl azetidinones and epoxy derivatives thereof
    Patent number: 5196528
    Abstract: Compounds of formula ##STR1## in which R.sub.1 is hydrogen or a hydroxyl protecting group and --X--Y-- is --CH.dbd.CH-- or ##STR2## useful as intermediates in the preparation of antibacterially active compounds.
    Type: Grant
    Filed: July 12, 1991
    Date of Patent: March 23, 1993
    Assignee: Glaxo S.p.A.
    Inventors: Alcide Perboni, Claudio Bismara, Giorgio Pentassuglia
  • .beta.-lactam compounds and production process thereof
    Patent number: 5191074
    Abstract: A process for producing a .beta.-lactam compound of the formula ##STR1## wherein OR.sup.1 is a protected or unprotected hydroxyl group; R.sup.2 is a C.sub.1 to C.sub.7 alkyl or aryl group; from an azetidinone compound of the formula ##STR2## wherein X is an electronegative group removable through the reaction in three steps in which the second step subjects the .beta.-lactam compound obtained in the first step to silylation to convert the R.sup.2 group to the beta form.
    Type: Grant
    Filed: August 12, 1991
    Date of Patent: March 2, 1993
    Assignees: Yasumitsu Tamura, Shionogi & Co., Ltd.
    Inventors: Yasumitsu Tamura, Junichi Haruta, Nishi Koichi
  • Nitrogen deprotected 4-acyloxyazetidin-2-ones
    Patent number: 5177201
    Abstract: The 4-acyloxyazetidin-2-ones, which are intermediates in the production of carbapenems and penems, are produced from nitrogen deprotected 4-furanylazetidin-2-ones.
    Type: Grant
    Filed: June 21, 1990
    Date of Patent: January 5, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Joseph E. Lynch, William L. Laswell, Ralph P. Volante, Ichiro Shinkai
  • Azetidin-2-one derivatives as serine protease inhibitors
    Patent number: 5175283
    Abstract: The present invention relates to new 3-guanidinoalkyl-2-azetidinones of the formula ##STR1## wherein: U and W can be the same or different and are selected from the group consisting of hydrogen and an amino protecting group;n is 1 to 3;X is a member selected from the group consisting of hydrogen, trialkylsilyl, arylsulfonyl, amino substituted arylsulfonyl, alkylsulfonyl, arylaminocarbonyl, alkylcarbonyl and arylcarbonyl; andY is a member selected from the group consisting of hydrogen, arylalkenyl, arylalkyl, formyl, carboxy, alkoxycarbonyl, acyloxy, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, arylaminocarbonyl, the radical ##STR2## in which R is hydrogen, alkyl or arylalkyl, and the radical ##STR3## in which m is 1 to 3 and R' is hydrogen or --CO.sub.2 R" wherein R" is hydrogen, alkyl or arylalkyl.The novel azetidinones of the present invention exhibit anti-thrombin and anti-trypsin activities and are thus useful in controlling blood coagulation and treating pancreatitis.
    Type: Grant
    Filed: February 11, 1992
    Date of Patent: December 29, 1992
    Assignee: Bristol-Myers Squibb Company
    Inventor: William T. Han
  • Process for producing azetidinone derivatives
    Patent number: 5149802
    Abstract: A process for producing 2-azetidinone derivatives represented by formula ##STR1## wherein R.sup.1 denotes a protecting group of a hydroxyl group,Z denotes a hydrogen atom or a protecting group of an amino group, andQ denotes ##STR2## in which X denotes a halogen atom, Y denotes a halogen atom or OR.sup.2, R.sup.2 denotes a hydrogen atom or a protecting group of a carboxyl group, and Y.sup.2 denotes OR.sup.3 or SR.sup.4 in which R.sup.3 denotes a hydrogen atom, a protecting group of a carboxyl group or an ester residue and R.sup.4 denotes an ester residue.
    Type: Grant
    Filed: July 10, 1991
    Date of Patent: September 22, 1992
    Assignee: Mercian Corporation
    Inventors: Takeo Yoshioka, Ryoichi Miyata, Toshio Tsuchida, Hiroshi Tone, Rokuro Okamoto
  • Stereoselective synthesis of a chiral cis 3-beta hydrogen (3R) 4-aroyloxy azetidinone
    Patent number: 5145957
    Abstract: A process is described for the stereocontrolled synthesis of (3R,4R)-3-[(1R)-1-hydroxyethyl]-4-benzoyloxyazetidin-2-ones and their derivatives by cycloaddition involving an imine and a ketone, generated from 3(S)-hydroxybutyrate which are useful intermediates in the synthesis of carbapenem antibiotics.
    Type: Grant
    Filed: January 9, 1992
    Date of Patent: September 8, 1992
    Assignee: Merck & Co., Inc.
    Inventors: David M. Tschaen, Joseph E. Lynch, William L. Laswell, Ralph P. Volante, Ichiro Shinkai
  • Phosphocholine derivative inhibitors of phospholipase A.sub.2
    Patent number: 5144045
    Abstract: Phospocholine derivatives having the formula: ##STR1## in which W, Z, Q and R are described in the specification are disclosed as useful for inhibiting the enzyme phospholipase A.sub.2. Methods of making and using the compounds are also disclosed.
    Type: Grant
    Filed: November 13, 1990
    Date of Patent: September 1, 1992
    Assignee: American Cyanamid Company
    Inventors: Allan Wissner, Robert E. Schaub, Kenneth E. Green, Philip R. Hamann
  • Process of enantiomeric separation of carbacephem intermediates
    Patent number: 5142038
    Abstract: Enantiomerically pure .beta.-lactam intermediates of the formula (I) ##STR1## are isolated from a haloalkane solvent through precipitation with methyl-t-butyl ether or methanol. The products thus obtained are key intermediates in the synthesis of antibiotic aagents. The process is appropriate for large scale production.
    Type: Grant
    Filed: July 23, 1991
    Date of Patent: August 25, 1992
    Assignee: Eli Lilly and Company
    Inventors: Christopher W. Doecke, Jeffrey N. Levy, Wayne D. Luke, Michael A. Staszak
  • 4-(2-Oxo-cyclohexyl) azetidinones
    Patent number: 5138048
    Abstract: Compounds of the general formula (I) ##STR1## in which: R.sub.1 represents a hydroxyl protecting group; andR.sub.2 represents a hydrogen or halogen atom, an azido group, a C.sub.1-3 alkyl group, a group (CH.sub.2).sub.m OR.sub.3 wherein m is zero or one and R.sub.3 represents a hydrogen atom or a hydroxyl protecting group, an azidoethoxy group, a protected hydroxyethoxy group or a group XR.sub.4 in which X is an oxygen atom or the group S(O).sub.n in which n is zero, 1 or 2 and R.sub.4 represents a C.sub.1-5 alkyl, C.sub.3-7 cycloalkyl or phenyl group or when X is oxygen or sulphur then R.sub.4 may also represent the group AlkNR.sub.5 R.sub.6 in which Alk represents a C.sub.2-6 straight or branched alkylene chain and R.sub.5 and R.sub.6 independently represent a hydrogen atom or C.sub.1-4 alkyl group or R.sub.5 and R.sub.6 together with the nitrogen atom to which they are attached form a pyrrolidino or piperidino ring or the group NR.sub.5 R.sub.6 represents a protected amino group, or R.sub.
    Type: Grant
    Filed: September 7, 1990
    Date of Patent: August 11, 1992
    Assignee: Glaxo S.p.A.
    Inventors: Bruno Tamburini, Alcide Perboni, Tino Rossi, Daniele Donati, Daniele Andreotti, Giovanni Gaviraghi, Stefano Biondi, Claudio Bismara
  • 3(1-hydoxyethyl)azetidinone compounds and their production
    Patent number: 5134231
    Abstract: An amino acid compound of the formula: ##STR1## wherein R is a lower alkyl group, R.sub.1 is a hydrogen atom or a protecting group for carboxyl, R.sub.2 is a hydrogen atom, a protecting group for amino, an optionally substituted allyl group of the formula: ##STR2## (wherein R.sub.3 and R.sub.4 are each a hydrogen atom, a lower alkyl group or an aryl group), a beta-hydroxyethyl group in which the hydroxyl group is optionally protected, a formylmethyl group in which the formyl group is optionally protected, a carboxymethyl group in which the carboxyl group is protected or a 2-furylmethyl group and X is an optionally protected carboxyl group, a hydroxymethyl group in which the hydroxyl group is optionally protected or a substituted mercaptomethyl group of the formula:--CH.sub.2 SR.sub.5(wherein R.sub.5 is an aryl group or an ar(lower)alkyl group), which is a useful intermediate in the synthesis of 1-alkylcarbapenem compounds.
    Type: Grant
    Filed: January 17, 1991
    Date of Patent: July 28, 1992
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Makoto Sunagawa, Yoshihito Nozaki, Akira Sasaki, Haruki Matsumura
  • Beta-lactams
    Patent number: 5112966
    Abstract: A beta-lactam compound of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom, a lower alkyl group or a 1-hydroxy(lower)alkyl group wherein the hydroxyl group is optionally protected, R.sub.2 is a hydrogen atom or a protective group for the nitrogen atom and R.sub.3 is a methyl group, a halomethyl group, a hydroxymethyl group, a protected hydroxymethyl group, a formyl group, a carboxyl group, a lower alkoxycarbonyl group or an ar(lower)alkoxycarbonyl group wherein the aryl group is optionally substituted, or R.sub.2 and R.sub.3 are combined together to form an oxaalkylene group and, when taken together with one nitrogen atom and two carbon atoms adjacent thereto, they represent a six-membered cyclic aminoacetal group, which is useful as a valuable intermediate in the stereospecific production of 1-methylcarbapenem compounds.
    Type: Grant
    Filed: October 31, 1985
    Date of Patent: May 12, 1992
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Makoto Sunagawa, Haruki Matsumura, Tsuneo Yano, Akira Sasaki, Shinzi Takata
  • Process for preparing 4-substituted azetidinones
    Patent number: 5106475
    Abstract: A process for preparing 3-4-cis-.beta.,.beta.-(4)-substituted and 3-4-trans,.beta.,.alpha.-(4)-substituted azetidinones is provided. Also provided are novel 4,4-disubstituted azetidinones.
    Type: Grant
    Filed: October 16, 1990
    Date of Patent: April 21, 1992
    Assignee: Eli Lilly and Company
    Inventors: John M. Morin, Jr., Robert J. Ternansky, David A. Hall
  • Enantioselective process for producing 1-beta-methyl carbapenem antibiotic intermediates
    Patent number: 5104984
    Abstract: A process is described for the stereochemically controlled synthesis of intermediates useful in producing 1-betamethylcarbapenem antibiotic intermediates involving reacting a beta lactam with a chiral thia- or oxazolidinone enolate to preferentially produce a beta-methyl intermediate which can be transformed into a carbapenem antibiotic.
    Type: Grant
    Filed: July 11, 1990
    Date of Patent: April 14, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Thomas N. Salzmann, Lelia M. Fuentes, Ichiro Shinkai
  • 4-benzoyl azetidinones
    Patent number: 5089609
    Abstract: Compounds of the formula ##STR1## wherein each R' is independently hydrogen, one, two or three of halogen, lower alkyl or lower alkoxy and R" is methyl, ethyl, allyl or a phenyl, are described. These compounds are useful as intermediates in preparing penems and carbapenems.
    Type: Grant
    Filed: November 30, 1990
    Date of Patent: February 18, 1992
    Assignee: Schering Corporation
    Inventor: Samuel Chackalamannil
  • 3-alkenyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds
    Patent number: 5081237
    Abstract: The invention relates to novel intermediate compounds for preparation of compounds of high antimicrobial activity, said intermediate compounds being of one of the formulas: ##STR1## wherein R.sup.1 is carboxy or protected carboxy,R.sup.2 is hydroxy(lower)alkyl or protected hyroxy(lower)alkyl,R.sup.3 and R.sup.4 are each hydrogen or lower alkyl,R.sup.5 is a saturated heterocyclic group, andR.sup.6 is aryl or lower alkoxy,or pharmaceutically acceptable salts thereof.
    Type: Grant
    Filed: January 30, 1990
    Date of Patent: January 14, 1992
    Assignee: Fujisawa Pharmaceutical Company, Ltd.
    Inventors: Masayoshi Murata, Toshiyuki Chiba, Akira Yamada
  • .beta.methyl azetidinone derivatives and stereoselective process for preparing the same
    Patent number: 5081238
    Abstract: An azetidinone derivative having the general formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are hydrogen atom or a protective group and R.sup.3 is an alkyl group or hydrogen atom, a process for preparing the same, and a process for preparing an azetidinone derivative having the general formula (II): ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are as above. The azetidinone derivative (I) of the present invention can be converted into an important intermediate of 1.beta.-methylcarbapenem antibiotics of a selective reduction of the double bond.
    Type: Grant
    Filed: June 8, 1990
    Date of Patent: January 14, 1992
    Assignee: Sagami Chemical Research Center
    Inventors: Masakatsu Shibasaki, Takamasa Iimori
  • Chiral 1-.beta.-methyl-carbapenem intermediates
    Patent number: 5075436
    Abstract: A multistep process is described for selectively obtaining 1-.beta.-methylcarbapenem intermediates in high overall yield. The desired 1-.beta.-methyl chirality is obtained through the hydrogenation of certain bicyclic .beta.-lactam ring structures containing an exocyclic methylene double bond alpha to the .beta.-lactam ring, in the presence of a metallic nickel hydrogenation catalyst. The hydrogenation results in a mixture of .alpha.- and .beta.-methyl isomers having a high .beta./.alpha.epimeric molar ratio. New 1-.beta.-methylcarbapenem intermediates containing the exocyclic double bond are also described.
    Type: Grant
    Filed: January 19, 1989
    Date of Patent: December 24, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Ichiro Shinkai, Anthony O. King, Lelia M. Fuentes
  • Beta-lactams and their production via stereospecific hydrogenation
    Patent number: 5075435
    Abstract: A beta-lactam compound of the formula: ##STR1## wherein R.sub.1 is a hydrogen atom, a lower alkyl group or a 1-hydroxy(lower)alkyl group wherein the hydroxyl group is optionally protected, R.sub.2 is a hydrogen atom or a protective group for the nitrogen atom and R.sub.3 is a methyl group, a halomethyl group, a hydroxymethyl group, a protected hydroxymethyl group, a formyl group, a carboxyl group, a lower alkoxycarbonyl group or an ar(lower)alkoxycarbonyl group wherein the aryl group is optionally substituted, or R.sub.2 and R.sub.3 are combined together to form an oxaalkylene group and, when taken together with one nitrogen atom and two carbon atoms adjacent thereto, they represent a six-membered cyclic aminoacetal group, which is useful as a valuable intermediate in the stereospecific production of 1-methylcarbapenem compounds.
    Type: Grant
    Filed: June 12, 1990
    Date of Patent: December 24, 1991
    Assignee: Sumitomo Pharmaceuticals Company, Limited
    Inventors: Makoto Sunagawa, Haruki Matsumura, Tsuneo Yano, Akira Sasaki, Shinzi Takata
  • 3,4-disubstituted-2-azetidinone derivatives and processes for preparation using tin enolates
    Patent number: 5075437
    Abstract: The invention relates to the preparation of 3,4-disubstituted-2-azetidinone compounds of the formula: ##STR1## in which R.sup.1 is hydrogen or amido-protective group, R.sup.2 is hydroxy(lower)alkyl or protected hydroxy(lower)alkyl, R.sup.3 is lower alkyl, and R.sup.4 is 1-(lower)alkyl-1-hydroxy(C.sub.2 -C.sub.6)alkyl, 1-(lower)alkyl-1-(protected hydroxy)-(C.sub.2 -C.sub.6)alkyl or 2-thioxothiazolidin-3-yl, useful as an intermediate for the production of antimicrobial agents by reacting a compound a compound of the formula: ##STR2## in which R.sup.5 is acyl, or salts thereof, with a compound of the formula:R.sup.3 --CH.sub.2 CO--R.sup.4or salts thereof, in the presence of an enolizating agent selected from the group consisting of stannous(lower)alkylsulfonate and stannous perhalo(lower)alkylsulfonate.
    Type: Grant
    Filed: May 4, 1990
    Date of Patent: December 24, 1991
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Takeshi Nakai, Fumiyuki Shirai, Toshiyuki Chiba, Hiroaki Ohtake
  • Dehydrogenative silylation process of organic compounds having active hydrogen
    Patent number: 5047526
    Abstract: A dehydrogenative silylation process of organic compounds having active hydrogen which comprises reacting an organic compound having active hydrogen with t-butyldimethylsilane in the presence of a catalyst which is a metal of Group VIII of the periodic table or its compound. The reaction may be carried out in a solvent. When the organic compound is a strongly acidic compound, the reaction may be carried out without use of any catalyst.
    Type: Grant
    Filed: June 22, 1989
    Date of Patent: September 10, 1991
    Assignee: Shin-Etsu Chemical Co., Ltd.
    Inventor: Keiji Yamamoto
  • Azetidin-2-one derivatives as serine protease inhibitors
    Patent number: 5037819
    Abstract: The present invention relates to new 3-guanidinoalkyl-2-azetidinones of the formula ##STR1## wherein: U and W can be the same or different and are selected from the group consisting of hydrogen and an amino protecting group;n is 1 to 3;X is a member selected from the group consisting of hydrogen, trialkylsilyl, arylsulfonyl, amino substituted arylsulfonyl, alkylsulfonyl, arylaminocarbonyl, alkylcarbonyl and arylcarbonyl; andY is a member selected from the group consisting of hydrogen, arylalkenyl, arylalkyl, formyl, carboxy, alkoxycarbonyl, acyloxy, arylthio, arylsulfinyl, arylsulfonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, arylaminocarbonyl, the radical ##STR2## in which R is hydrogen, alkyl or arylalkyl, and the radical ##STR3## in which m is 1 to 3 and R' is hydrogen or --CO.sub.2 R" wherein R" is hydrogen, alkyl or arylalkyl.The novel azetidinones of the present invention exhibit anti-thrombin and anti-trypsin activities and are thus useful in controlling blood coagulation and treating pancreatitis.
    Type: Grant
    Filed: June 4, 1990
    Date of Patent: August 6, 1991
    Assignee: Bristol-Myers Squibb Company
    Inventor: William T. Han
  • Cyclization process for synthesis of a beta-lactam carbapenem intermediate
    Patent number: 5037974
    Abstract: A process is described for the synthesis of 3(S)-4(R)-3-[1(S)-hydroxyethyl]-4-(alkoxycarbonylmethyl)-azetidin-2-one (II) which is a useful intermediate in the synthesis of carbapenem antibiotics.
    Type: Grant
    Filed: August 14, 1990
    Date of Patent: August 6, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Mallory F. Loewe, Raymond Cvetovich, George G. Hazen
  • 6- and 6,6-disubstituted-3-substituted-1-azabicyclo(3.2.0)hept-2-en-7-one-2-car boxylic acids
    Patent number: 5021566
    Abstract: Disclosed are 6- and 6,6-disubstituted-3-substituted-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carbo xylic acids (I): ##STR1## wherein R.sup.1 and R.sup.2 are, inter alia, independently selected from the group consisting of hydrogen (both are not hydrogen at the same time), substituted and unsubstituted: alkyl, aryl and aralkyl; X is halo, oxygen (the 2-3 bond is saturated and the species I exists as carboxylate salt or ester), or --OR wherein R is, inter alia, acyl, alkyl, or aralkyl. Such compounds and their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
    Type: Grant
    Filed: February 15, 1990
    Date of Patent: June 4, 1991
    Assignee: Merck & Co. Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliff
  • Cerebral function ameliorating agents related to Tan-950 A
    Patent number: 5021439
    Abstract: A compound having the formula (I) or (II) ##STR1## wherein R.sup.1 is a hydrogen atom or an organic residue bonded via a carbon atom, R.sup.2 is a hydrogen atom or a N-protecting group, --COR.sup.3 is an optionally esterified or amidated carboxyl group, R.sup.4 and R.sup.5 are the same or different and respectively a hydrogen atom or an acyl group or a chain or alicyclic hydrocarbon group optionally having an aryl substituent, R.sup.6 is NOH or O, n is an integer of 0 to 3, or R.sup.4 and R.sup.5 together with the adjacent nitrogen atom may form a ring or an optionally substituted benzylidene amino group, which is useful therapeutics of brain dysfunction.
    Type: Grant
    Filed: September 18, 1989
    Date of Patent: June 4, 1991
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Setsuo Harada, Akinobu Nagaoka, Katsumi Itoh, Shinji Terao
  • Preparation of azetidinones via novel protected intermediates
    Patent number: 5008404
    Abstract: A multistep process is disclosed for preparing azetidinone intermediates used in the making penems and carbapenems wherein intermediates containing ##STR1## R' is independently hydrogen or 1, 2 or 3 of lower alkyl or lower alkoxy, preferably hydrogen, wherein R" is methyl, ethyl, a phenyl or alkyl, preferably ethyl, as a readily removable nitrogen protecting group are made.
    Type: Grant
    Filed: March 20, 1990
    Date of Patent: April 16, 1991
    Assignee: Schering Corporation
    Inventor: Samuel Chackalamannil
  • Quinoline-3-carboxylic acid derivatives
    Patent number: 4997943
    Abstract: Compounds of formula (I): ##STR1## (in which R.sup.1 is alkoxy, R is alkyl, haloalkyl, alkylamino, cycloalkyl or optionally substituted phenyl, X is chlorine or fluorine and Y is selected from certain specific heterocycles) have excellent antibacterial activity. They may be prepared by introducing the group represented by Y into the corresponding compound in which Y is replaced by a halogen atom.
    Type: Grant
    Filed: March 31, 1987
    Date of Patent: March 5, 1991
    Assignees: Sankyo Company Limited, Ube Industries Limited
    Inventors: Masayuki Iwata, Tomio Kimura, Yoshimi Fujihara, Tetsushi Katsube
  • Penem derivatives
    Patent number: 4992543
    Abstract: An efficient, multistep process for the synthesis of certain 6-(1-hydroxyethyl) 2-substituted penem antibiotics from 2-[4R-(triphenylmethylthio)-3S-(1R-(dimethyl-t-butylsilyloxy)ethyl)-2-azet idon-1 yl]acetic acid ester.
    Type: Grant
    Filed: July 11, 1989
    Date of Patent: February 12, 1991
    Assignee: Pfizer Inc.
    Inventors: Brian T. O'Neill, Douglas Phillips
  • Process for preparing 4-substituted azetidinones
    Patent number: 4992545
    Abstract: A process for preparing 3-4-cis-.beta.,.beta.-(4)-substituted and 3-4-trans,.beta.,.alpha.- (4)-substituted azetidinones is provided. Also provided are novel 4,4-disubstituted azetidinones.
    Type: Grant
    Filed: September 20, 1989
    Date of Patent: February 12, 1991
    Assignee: Eli Lilly and Company
    Inventors: David A. Hall, deceased, John M. Morin, Jr., Robert J. Ternansky
  • Beta-lactams as anticholesterolemic agents
    Patent number: 4983597
    Abstract: Compounds of formula (I), which are useful as antihypercholesterolemic agents, are disclosed.
    Type: Grant
    Filed: August 31, 1989
    Date of Patent: January 8, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Shu S. Yang, Yuan-Ching P. Chiang, James V. Heck, Michael N. Chang
  • Preparation of azetidinones via novel protected intermediates
    Patent number: 4963670
    Abstract: A multistep process is disclosed for preparing azetidinone intermediates used in the making penems and carbapenems wherein intermediates containing ##STR1## R' is independently hydrogen or 1, 2 or 3 of lower alkyl or lower alkoxy, preferably hydrogen, wherein R" is methyl, ethyl, a phenyl or alkyl, preferably ethyl, as a readily removable nitrogen protecting group are made.
    Type: Grant
    Filed: November 28, 1988
    Date of Patent: October 16, 1990
    Assignee: Schering Corporation
    Inventor: Samuel Chackalamannil
  • Alkenylsilylazetidinone intermediates for carbapenems
    Patent number: 4960880
    Abstract: An intermediate for synthesizing carbapenems is produced through(1) a reaction of 4-(leaving group substituted)-2-azetidinone (I) with (alk-2-enyl)halosilane (II) to afford 4-(leaving group substituted)-1-(alk-2-enyl)silyl-2-azetidinone (III) and then(2) a reaction of the product 4-(leaving group substituted)-1-alk-2-enyl)silyl-2-azetidinone (III) with acid to give the corresponding 4-(alk-2-enyl)-2-azetidinone (IV).
    Type: Grant
    Filed: September 21, 1988
    Date of Patent: October 2, 1990
    Assignee: Shionogi & Co., Ltd.
    Inventor: Shoichiro Uyeo
  • Process for carbapenem intermediates
    Patent number: 4960879
    Abstract: A novel intermediate for synthesizing 1 .beta.-alkyl-1-carbapenem, i.e., 4 .beta.-(1 .beta.-alkyl-2-carboxyprop-2-enyl)azetidin-2-one (II), is prepared stereoselectively by treating 4-(leaving group substituted)azetidin-2-one (I) with trans-2-(leaving group substituted)-methyl-3-alkylacrylic acid (III) and a reducing metal. ##STR1## wherein R.sup.1 is hydrogen, alkyl, or substituted alkyl;R.sup.2 is optionally substituted alkyl;R.sup.3 is hydrogen or a carboxy-protecting group; andR.sup.4 and R.sup.5 each is a leaving group.
    Type: Grant
    Filed: March 3, 1989
    Date of Patent: October 2, 1990
    Assignee: Shionogi & Co., Ltd.
    Inventor: Shoichiro Uyeo
  • 3-(substituted propylidene)-2-azetidinone derivates for blood platelet aggregation
    Patent number: 4952689
    Abstract: A 2-azetizinone derivative represented by the formula: ##STR1## wherein R.sup.1 is a halogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms or an alkoxycarbonyl group in which the alkoxy group has 1 to 4 carbon atoms, R.sup.2 is a group represented by the formula ##STR2## a pyrrolidinyl group or a tetrahydroazepinyl group, and n is an integer of from 2 to 10, and a salt thereof are disclosed. These compounds are useful as blood platelet aggregation inhibiting agent.
    Type: Grant
    Filed: October 10, 1989
    Date of Patent: August 28, 1990
    Assignee: Taisho Pharmaceutical Co., Ltd.
    Inventors: Yutaka Kawashima, Masakazu Sato, Masahiro Kawase, Yoshiaki Watanabe, Katsuo Hatayama
  • Process for preparing azetidinones
    Patent number: 4940788
    Abstract: A process for preparing azetidinones of the formula: ##STR1## wherein R.sup.1 is an amino-protecting group and R.sup.2 is alkyl or aryl, which comprises reacting compounds of the formulae (VIII) and (IX) ##STR2## wherein L is a leaving group. The product azetidinones are intermediates in the preparation of penem and carbapenem antibiotics.
    Type: Grant
    Filed: January 19, 1988
    Date of Patent: July 10, 1990
    Assignee: Imperial Chemical Industries PLC
    Inventors: Ian M. Cunningham, David W. Heaton
  • Process for the preparation of 4-acyloxyazetidin-2-one by singlet oxygen oxidation
    Patent number: 4940520
    Abstract: The 4-acyloxyazetidin-2-ones, which are intermediates in the production of carbapenems and penems, are produced from 4-furanylazetidin-2-ones by singlet oxygen oxidation.
    Type: Grant
    Filed: June 21, 1989
    Date of Patent: July 10, 1990
    Assignee: Merck & Co., Inc.
    Inventors: Joseph E. Lynch, William L. Laswell, Ralph P. Volante, Ichiro Shinkai
  • Optically active azetidinones
    Patent number: 4939248
    Abstract: This invention provides compounds of the formula ##STR1## wherein Y represents an acetyl, 1-hydroxyethyl or 1-fluoroethyl group, R.sub.1 represents a hydrogen atom or an easily splittable amino-protecting group, and R.sub.2 and R.sub.3 are identical or different and each represents a hydrogen atom, a lower alkyl group, a phenyl group, a benzyl group or a diphenylmethyl group, or R.sub.2 and R.sub.3 together represent a lower alkylene group; and processes for production thereof. These compounds are useful as synthesis intermediates for production of various medicines, particulary carbapenam or carbapenem antibiotics, such as a carbapenem antibiotic of the following formula which has excellent antimicrobial activity and relatively good stability to kidney dehydropeptidase.
    Type: Grant
    Filed: August 18, 1988
    Date of Patent: July 3, 1990
    Assignee: Sanraku Incorporated
    Inventors: Takeo Yoshioka, Machiko Watanabe, Yasuo Fukagawa, Tomoyuki Ishikura
  • Novel process for the manufacture of 4-acyloxy-3-hydroxyethyl-azetidinones
    Patent number: 4927507
    Abstract: The invention relates to a novel process for the manufacture of (3R,1'R)-4-acyloxy-3-(1'-hydroxyethyl)-2-azetidinones of formula ##STR1## in which R.sup.1 represents lower alkyl or aryl, by enantioselective reduction of the carbonyl group in a suitable .alpha.-acylaminomethyl-acetoacetic acid ester, cyclization of the resulting .alpha.-acylaminomethyl-.beta.-hydroxybutyric acid ester to a 5,6-dihydro-1,3,4H-oxazine with inversion of the carbon atom carrying the hydroxy group, equilibration to form the preferred trans-substituted dihydrooxazine, recleaving to form the configuratively uniform .alpha.-aminomethyl-.beta.-hydroxybutyric acid, ring-closure to form the .beta.-lactam and oxidative acylation at C(4) of the .beta.-lactam. Compounds of formula I can be used as starting materials for the manufacture of .beta.-lactam antibiotics. The invention relates also to novel intermediates.
    Type: Grant
    Filed: April 27, 1988
    Date of Patent: May 22, 1990
    Assignee: Ciba-Geigy Corporation
    Inventors: Peter Schneider, Gerardo Ramos, Jacques Bersier