The Ring Nitrogen Is Shared By A Five-membered Ring Patents (Class 540/302)
The five-membered ring contains an additional hetero atom (Class 540/303)
The ring system is 4-aza-bicyclo(3.2.0)heptane (including unsaturated) and has sulfur bonded directly at the 2-position (Class 540/350)
  • Process for preparing carbapenem compounds
    Patent number: 5204459
    Abstract: Novel amino acid derivatives of the formula ##STR1## wherein R.sup.1 is a protecting group removable under reducing or acid conditions, and R.sup.2 and R.sup.5 are hydrogen or carboxylic protecting groups, are useful as intermediates in preparing stereospecific carbapenam/carbapenem derivatives. R.sup.1 is removed under reducing conditions to form a pyrrolidine derivative, which is further cyclized from the R.sup.5 =H compound to form a .beta.-lactam ring. Stereospecificity at the 6-position is achieved by treatment with lithium diisopropylamide (LDA) and quenching at different temperatures. Compound (I) can be prepared by treating R.sup.1 -protected R.sup.3 -pyrrolidone carboxylic acid R.sup.2 -ester with a lithium enolate of the formula R.sup.4 CHLiCO.sub.2 R.sup.5. The lithium enolate can be formed from R.sup.4 CH.sub.2 CO.sub.2 R.sup.5 by treatment with LDA.
    Type: Grant
    Filed: March 17, 1992
    Date of Patent: April 20, 1993
    Assignee: Ajinomoto Co., Inc.
    Inventors: Shigeo Nozoe, Tomihisa Ohta
  • 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
  • 2-biphenyl-carbapenem antibacterial agents
    Patent number: 5192758
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: February 28, 1992
    Date of Patent: March 9, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Kevin D. Dykstra, James V. Heck
  • 4-substituted azetidinones as precursors to 2-substituted-3-carboxy carbapenem antibiotics and a method of producing them
    Patent number: 5189158
    Abstract: New 4-substituted azetidinones having the formulea I and II: ##STR1## with R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X defined hereafter, which are intermediates for the preparation of carbapenem and carbacephem antibacterials and processes for producing such antibacterials through the utilization of an acid mediated ring closure reaction.
    Type: Grant
    Filed: March 20, 1991
    Date of Patent: February 23, 1993
    Assignee: American Cyanamid Company
    Inventors: Gregg B. Feigelson, William V. Curran, Carl B. Ziegler
  • 2-biphenyl-carbapenems intermediates
    Patent number: 5182385
    Abstract: Carbapenems of the formula: ##STR1## are useful intermediates to antibacterial agents.
    Type: Grant
    Filed: October 9, 1990
    Date of Patent: January 26, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Thomas N. Salzmann
  • 2-benzocoumarinyl carbapenems
    Patent number: 5182384
    Abstract: Carbapenems of the formula ##STR1## are useful intermediates to antibacterial agents.
    Type: Grant
    Filed: May 24, 1991
    Date of Patent: January 26, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Thomas A. Rano, Mark L. Greenlee
  • Antimicrobial quinolonyl lactam esters
    Patent number: 5180719
    Abstract: Antimicrobial quinolonyl lactam esters comprising a lactam-containing moiety linked, by an ester group, to the 3-carboxy group of a quinolone moiety. These compounds are of the formula: ##STR1## wherein (1) R.sup.3, R.sup.4, and R.sup.5, together with bonds "a" and "b", form certain lactam-containing moieties similar to those known in the art to have antimicrobial activity; and(2) A.sup.2, A.sup.2, A.sup.3, R.sup.7, R.sup.8, and R.sup.9 form any of a variety of quinolone or naphthyridine structures similar to those known in the art to have antimicrobial activity.
    Type: Grant
    Filed: April 29, 1991
    Date of Patent: January 19, 1993
    Assignee: Norwich Eaton Pharmaceuticals, Inc.
    Inventors: Ronald E. White, Thomas P. Demuth, Jr.
  • 2-phenanthrenyl-carbapenems
    Patent number: 5177202
    Abstract: Carbapenems of the formula ##STR1## are useful intermediates to antibacterial agents.
    Type: Grant
    Filed: October 9, 1990
    Date of Patent: January 5, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Mark L. Greenlee, Thomas N. Salzmann
  • 2-benzocoumarinyl carbapenems
    Patent number: 5162314
    Abstract: Carbapenems of the formula ##STR1## with E as ##STR2## are useful antibacterial agents.
    Type: Grant
    Filed: May 24, 1991
    Date of Patent: November 10, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Mark L. Greenlee, Thomas A. Rano
  • 2-phenanthridonyl carbapenems having cationizeable substituents
    Patent number: 5157033
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: April 16, 1991
    Date of Patent: October 20, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Mark L. Greenlee, Thomas A. Rano
  • 2-benzocoumarinyl-carbapenems
    Patent number: 5153186
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: May 24, 1991
    Date of Patent: October 6, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Thomas A. Rano, Mark L. Greenlee
  • 2-phenanthridonyl carbapenems
    Patent number: 5153185
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: April 16, 1991
    Date of Patent: October 6, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank DiNinno, Mark L. Greenlee, Thomas A. Rano
  • Intermediates for preparing 2-(substituted-dibenzofuranyl and dibenzothienyl) carbapenem antibacterial agents
    Patent number: 5151512
    Abstract: Carbapenem intermediates having the formula: ##STR1## where Z is; ##STR2## M is a removable protecting group for carboxy and P' is a removable protecting group for hydroxy are useful intermediates for preparing antibacterial agents, especially with respect to activity against methicillin resistant Staphylococcus aureus (MRSA).
    Type: Grant
    Filed: October 15, 1990
    Date of Patent: September 29, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Mark L. Greenlee, Thomas N. Salzmann
  • 2-(9-fluorenonyl)-carbapenem intermediates
    Patent number: 5144028
    Abstract: Carbapenems of the formula ##STR1## are useful intermediates in the preparation of 2-(9-fluorenonyl)-carbapenem antibacterial agents.
    Type: Grant
    Filed: October 9, 1990
    Date of Patent: September 1, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Mark L. Greenlee, Frank P. DiNinno, Lovji D. Cama, James V. Heck
  • 2-heteroarylphenyl-carbapenem antibacterial agents
    Patent number: 5143914
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 25, 1991
    Date of Patent: September 1, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Ravindra N. Guthikonda, Susan M. Schmitt
  • 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids
    Patent number: 5140030
    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 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: August 16, 1990
    Date of Patent: August 18, 1992
    Assignee: Merck
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
  • 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
  • 6-amido-1-methyl carbapenems
    Patent number: 5138050
    Abstract: New antibacterial 6-amido-1-methylcarbapenems and process for their synthesis involving new azetidinone intermediates.
    Type: Grant
    Filed: March 7, 1991
    Date of Patent: August 11, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Ravindra N. Guthikonda, Frank P. DiNinno, Thomas N. Salzmann
  • Intermediates for preparing 2-(substituted-dibenzo-furanyl and dibenzothienyl) carbapenem antibacterial agents
    Patent number: 5132420
    Abstract: Carbapenem intermediates having the formula: ##STR1## where Z is ##STR2## M is a removable protecting group for carboxy and P' is a removable protecting group for hydroxy, are useful intermediates for preparing antibacterial agents, especially with respect to activity against methicillin resistant Staphylococcus aureus (MRSA).
    Type: Grant
    Filed: October 11, 1990
    Date of Patent: July 21, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Mark L. Greenlee, Thomas N. Salzmann
  • 2-naphthyl-carbapenem intermediates
    Patent number: 5132421
    Abstract: Carbapenems of the formula ##STR1## are useful intermediates to antibacterial agents.
    Type: Grant
    Filed: October 9, 1990
    Date of Patent: July 21, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Mark L. Greenlee
  • 2-naphthyl-carbapenem intermediates
    Patent number: 5132422
    Abstract: Carbapenems of the formula ##STR1## are useful intermediates to antibacterial agents.
    Type: Grant
    Filed: October 9, 1990
    Date of Patent: July 21, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Mark L. Greenlee
  • 2-heteroarylphenyl-carbapenem antibacterial agents
    Patent number: 5128335
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: October 15, 1990
    Date of Patent: July 7, 1992
    Assignee: Merck & Co., Inc.
    Inventors: Ravindra N. Guthikonda, Susan M. Schmitt, Frank P. Dininno
  • 2-(quinoliniumalkyl and isoquinoliniumalkyl) phenyl carbapenem antibacterial agents
    Patent number: 5124323
    Abstract: Carbapenems having the formula: ##STR1## In which Q.sup.+ is quinolinium or isoquinolinium, are useful antibacterial agents.
    Type: Grant
    Filed: July 17, 1991
    Date of Patent: June 23, 1992
    Assignee: Merck
    Inventors: Frank P. DiNinno, Thomas N. Salzmann, David A. Muthard
  • 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds
    Patent number: 5102877
    Abstract: 1-Azabicyclo[3.2.0]hept-2-ene-2-carboxyic acids having antimicrobial activity have been prepared.
    Type: Grant
    Filed: April 12, 1990
    Date of Patent: April 7, 1992
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Masayoshi Murata, Toshiyuki Chiba, Hideo Tsutsumi, Kohji Hattori, Satoru Kuroda, Hiroaki Ohtake, Fumiyuki Shirai
  • Novel 2-substituted alkyl-3-carboxy carbapenems as antibiotics and a method of producing them
    Patent number: 5068232
    Abstract: The invention relates to new 2-substituted alkyl-3-carboxy carbapenems having the formula: ##STR1## with R.sup.1, R.sup.2, R.sup.3, X and Y defined hereafter as antibiotics and beta lactamase inhibitors produced by a novel Michael addition-elimination reaction of a substituted allyl azetidinone in the reaction shown: ##STR2## with R.sup.1, R.sup.2, Q, X and Y defined hereafter.
    Type: Grant
    Filed: April 10, 1990
    Date of Patent: November 26, 1991
    Assignee: American Cyanamid Company
    Inventors: Carl B. Ziegler, Jr., William V. Curran, Gregg Feigelson
  • Process for producing halomethylcarbapenems
    Patent number: 5064954
    Abstract: A functionallized intermediate for antibacterial carbapenems, 2-halomethylcarbapenem (III) is effectively synthesized by treating 2-hydroxymethylcarbapenem (I) with a phosphorylating reagent to give 2-phosphoryloxymethylcarbapenem (II) and then treating this product with a halogenating reagent. Some carbapenems derived from the intermediate are also disclosed. ##STR1## wherein, R.sup.1 is hydrogen or substituted or unsubstituted alkyl;R.sup.2 is hydrogen or substituted or unsubstituted alkyl;R.sup.3, R.sup.4 is halogen or substituted or unsubstituted alkoxy or aryloxy;R.sup.5 is hydrogen or carboxy protecting group; andHal is halogen.
    Type: Grant
    Filed: October 10, 1990
    Date of Patent: November 12, 1991
    Assignee: Shionogi & Co., Ltd.
    Inventors: Shoichiro Uyeo, Mitsuru Imuta, Hisao Ona, Hikaru Itani
  • Process for preparing 1-carba-2-penem-3-carboxylic acid
    Patent number: 5055573
    Type: Grant
    Filed: August 24, 1990
    Date of Patent: October 8, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Lovji D. Cama, Burton G. Christensen
  • Rhodium catalyzed cyclization process for bicyclic .beta.-lactams
    Patent number: 5051502
    Abstract: 1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkxoy)-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a temperature between about 15.degree. C. and about 85.degree.0 C. The 1-carba bicyclic .beta.-lactams are intermediates for preparing antibiotics.
    Type: Grant
    Filed: June 6, 1990
    Date of Patent: September 24, 1991
    Assignee: University of Notre Dame du Lac
    Inventors: Marvin J. Miller, Matthew A. Williams
  • Carbapenem antibacterial agents
    Patent number: 5037820
    Abstract: Carbapenems having the formula: ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 29, 1990
    Date of Patent: August 6, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Eugene D. Thorsett, Thomas N. Salzmann
  • 2-(9-fluorenonyl)-carbapenem antibacterial agents
    Patent number: 5034384
    Abstract: Carbapenems of the formula ##STR1## wherein either the 2-fluoren-9-one or 3-fluoren-9-one is attached at the 2-position of the carbapenem are useful antibacterial agents.
    Type: Grant
    Filed: August 1, 1990
    Date of Patent: July 23, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Mark L. Greenlee, Frank P. DiNinno, Lovji D. Cama, James V. Heck
  • 2-(heteroarylsubstituted)phenyl carbapenem antibacterial agents
    Patent number: 5034385
    Abstract: Carbapenems having the formula: ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 26, 1990
    Date of Patent: July 23, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Thomas N. Salzmann, David H. Shih
  • 2-naphthyl-carbapenem antibacterial agents
    Patent number: 5032587
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: July 11, 1990
    Date of Patent: July 16, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Mark L. Greenlee
  • 2-(substituted-dibenzofuranyl and dibenzothienyl) carbapenem antibacterial agents
    Patent number: 5025008
    Abstract: Carbapenems having the formula: ##STR1## where Z is; ##STR2## where X is O or S(O).sub.0-2 ; are useful antibacterial agents, especially with respect to activity against methicillin resistant Staphylococcus aureus (MRSA).
    Type: Grant
    Filed: May 24, 1990
    Date of Patent: June 18, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Thomas N. Salzmann, Mark L. Greenlee
  • 2-biphenyl-carbapenem antibacterial agents
    Patent number: 5025006
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 26, 1990
    Date of Patent: June 18, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Thomas N. Salzmann
  • 2-(9-fluorenonyl)-carbapenem antibacterial agents
    Patent number: 5025007
    Abstract: Carbapenems of the formula ##STR1## wherein either the 2-fluoren-9-one or 3-fluoren-9-one is attached at the 2-position of the carbapenem are useful antibacterial agents.
    Type: Grant
    Filed: August 1, 1990
    Date of Patent: June 18, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Mark L. Greenlee, Frank P. DiNinno, Lovji D. Cama, James V. Heck
  • 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
  • Novel 2-substituted alkyl carbapenem antibacterials
    Patent number: 5021565
    Abstract: Described is a new process for producing new 2-substituted alkyl-3-carboxycarbapenems, involving condensation of a 2-oxocarbapenam-3-carboxylic ester with a stabilized ylide followed by ester deblocking. The resulting carbapenem compounds, which are not readily available from other known synthetic routes, show interesting antibacterial activity.
    Type: Grant
    Filed: June 21, 1990
    Date of Patent: June 4, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Ronald W. Ratcliffe, Mary F. Woods
  • 2-naphthyl-carbapenem antibacterial agents
    Patent number: 5006519
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: July 11, 1990
    Date of Patent: April 9, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Mark L. Greenlee
  • 2-phenanthrenyl carbapenem antibacterial agents
    Patent number: 5004739
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 26, 1990
    Date of Patent: April 2, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Mark L. Greenlee, Thomas N. Salzmann
  • 2-phenanthrenyl-carbapenem antibacterial agents
    Patent number: 5004740
    Abstract: Carbapenems of the formula ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: June 26, 1990
    Date of Patent: April 2, 1991
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. Dininno, Thomas N. Salzmann, Mark L. Greenlee
  • 2-(Heteroaryliumalkyl)phenyl carbapenem antibacterial agents
    Patent number: 4978659
    Abstract: Carbapenems having the formula: ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: August 21, 1989
    Date of Patent: December 18, 1990
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, David A. Muthard, Thomas N. Salzmann
  • 2-(Heterocyclylalkyl)phenyl carbapenem antibacterial agents
    Patent number: 4962101
    Abstract: Carbapenems having the formula: ##STR1## are useful antibacterial agents.
    Type: Grant
    Filed: August 21, 1989
    Date of Patent: October 9, 1990
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, Thomas N. Salzmann
  • 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-Alkenyl-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid compounds
    Patent number: 4923857
    Abstract: The invention relates to an antimicrobial compound of the formula: ##STR1## in which R.sup.1 is carboxy or protected carboxy,R.sup.2 is hydroxy(lower)alkyl or protected hydroxy(lower)alkyl,R.sup.3 and R.sup.4 are each hydrogen or lower alkyl, andR.sup.
    Type: Grant
    Filed: February 17, 1989
    Date of Patent: May 8, 1990
    Assignee: Fujisawa Pharmaceutical Company, Ltd.
    Inventors: Masayoshi Murata, Toshiyuki Chiba, Akira Yamada
  • Oxadiazines
    Patent number: 4849516
    Abstract: Compounds of the formula (V): ##STR1## wherein R.sup.1 is certain optionally substituted alkyl groups, R.sup.2 is hydrogen, alkyl or optionally substituted phenyl and R.sup.3 and R.sup.4 are independently alkyl or optionally substituted phenyl, or together form a C.sub.4-7 cycloalkyl ring; are described as useful intermediates in the preparation of carbapenem and penem antibiotics. Processes for their preparation are described as are certain oxadiazine intermediates.
    Type: Grant
    Filed: October 14, 1987
    Date of Patent: July 18, 1989
    Assignee: Imperial Chemical Industries PLC
    Inventor: Michael B. Gravestock
  • 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids
    Patent number: 4833167
    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
  • 6-(disubstituted amino)carbapenam compounds
    Patent number: 4812563
    Abstract: A compound represented by the formula ##STR1## wherein R.sub.1 represents a lower alkyl group or a lower haloalkyl group; R.sub.2 represents a lower alkyl group, a lower haloalkyl group, an aralkyl group, or a group of the formula --COOR.sub.4 or --SO.sub.2 R.sub.5 in which R.sub.4 represents an alkyl group or a substituted or unsubstituted aralkyl group and R.sub.5 represents an alkyl group or a substituted or unsubstituted aryl group; and R.sub.3 represents a hydrogen atom or a carboxyl protecting group which can be easily split off. This compound is useful in the production of a 6-(disubstituted amino)carbapenem-series antibiotic.
    Type: Grant
    Filed: March 10, 1987
    Date of Patent: March 14, 1989
    Assignee: Sanraku Incorporated
    Inventors: Takeo Yoshioka, Noritaka Chida, Azuma Watanabe, Yasuo Fukagawa, Tomoyuki Ishikura
  • 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids
    Patent number: 4783453
    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 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: September 8, 1987
    Date of Patent: November 8, 1988
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, John C. Chabala
  • 2-aza-substituted 1-carbadethiapen-2-em-3 carboxylic acids
    Patent number: 4782051
    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, trizolyl, 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: August 17, 1987
    Date of Patent: November 1, 1988
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, John C. Chabala, Ronald W. Ratcliffe
  • Carbapenems and 1-methylcarbapenems having an externally alkylated mono- or bicyclic 2-quaternary heteroarylalkyl substituent
    Patent number: 4729993
    Abstract: Carbapenems having the formula: ##STR1## wherein ##STR2## is mono- or bicyclic quaternary heteroaryl, their preparation and antibiotic use are disclosed.
    Type: Grant
    Filed: December 13, 1984
    Date of Patent: March 8, 1988
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, James V. Heck, Thomas N. Salzmann, David H. Shih