Patents Represented by Attorney James Arno

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  • Synthesis of thienamycin from D-glucose
    Patent number: 4384998
    Abstract: Disclosed is a chiral, total synthesis of thienamycin from D-glucose which proceeds via intermediates I, II and III to known aldehyde IV which is known to be useful in the total synthesis of thienamycin (V): ##STR1## wherein: R is lower alkyl having 1-6 carbon atoms or bi-valent alkyl having 2-6 carbon atoms which joins the two sulfur atoms; R.sup.1 is lower alkyl or aralkyl, such as benzyl and the like; and R.sup.2 is hydrogen or a removable protecting group, such as triorganosilyl wherein the organo groups are independently selected from lower alkyl, phenyl and phenylloweralkyl.
    Type: Grant
    Filed: March 30, 1981
    Date of Patent: May 24, 1983
    Assignee: Merck & Co., Inc.
    Inventor: Philippe L. Durette
  • Process for the preparation of 1-carbapenems and intermediates via silyl-substituted dithioacetals
    Patent number: 4383946
    Abstract: Disclosed is a process for the total synthesis of 1-carbapenem antibiotics (I) from L-aspartic acid via central intermediates II and III: ##STR1## wherein R is hydrogen, a pharmaceutically acceptable ester moiety or salt cation, or a readily removable blocking group; R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl; R.sup.1' and R.sup.e are hydrogen, or a readily removable protecting group; R.sup.a, R.sup.b and R.sup.c are selected from alkyl, aryl or aralkyl.
    Type: Grant
    Filed: September 18, 1981
    Date of Patent: May 17, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
  • Process for the preparation of thienamycin and intermediates
    Patent number: 4378315
    Abstract: Disclosed is a process for the total synthesis of thienamycin from L-aspartic acid via intermediate III: ##STR1## R=H, blocking group or salt cation.
    Type: Grant
    Filed: May 11, 1981
    Date of Patent: March 29, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
  • Process for the preparation of 6-hydroxymethyl-2-(.beta.-aminoethylthio)-1-carbadethiapen-2-em-3-carbox ylic acid
    Patent number: 4375433
    Abstract: Disclosed is a process for preparing the antibiotic 6-hydroxymethyl-2-(.beta.-aminoethylthio)-1-carbadethiapen-2-em-3-carboxyl ic acid (I) ##STR1## and its pharmaceutically acceptable salt and ester derivatives. An intermediate for the production of these compounds are compounds of the formula ##STR2## wherein R.sup.5 and R are readily removable protecting groups.
    Type: Grant
    Filed: September 12, 1980
    Date of Patent: March 1, 1983
    Assignee: Merck & Co., Inc.
    Inventors: David G. Melillo, Kenneth M. Ryan
  • Process for the preparation of N-formimidoyl thienamycin and reagents therefor
    Patent number: 4374772
    Abstract: Disclosed is a novel class of substituted and unsubstituted benzyl formimidates, represented in a convenient acid addition salt form (I); and the use of these reagents in the preparation of the antibiotic N-formimidoyl thienamycin (II): ##STR1## wherein A is a non-critical anion such as chloro, bromo, hydrogen sulfate or an alkyl aralkyl or aryl sulfonate, wherein the alkyl moiety has 1-6 carbon atoms and the aryl moiety is phenyl, for example; n is 0, 1 or 2; and X is independently selected from nitro, halo (chloro, bromo, fluoro, and iodo), loweralkyl having from one to six carbon atoms, phenyl, and phenylalkyl having from 7-12 carbon atoms, and --COOR, wherein R is hydrogen or loweralkyl having from one to six carbon atoms.
    Type: Grant
    Filed: March 19, 1981
    Date of Patent: February 22, 1983
    Assignee: Merck & Co., Inc.
    Inventors: George G. Hazen, Ralph P. Volante, Kenneth E. Wilson
  • 6-(1-Hydroxyethyl)cyclonocardicin
    Patent number: 4374848
    Abstract: Disclosed are 6-(1-hydroxyethyl)cyclonocardicins (I) and their pharmaceutically acceptable salts and esters which are useful as antibiotics. ##STR1## 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: September 14, 1981
    Date of Patent: February 22, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, James V. Heck, Michael J. Szymonifka
  • 6-Amidocyclonocardicins
    Patent number: 4374849
    Abstract: Disclosed are 6-amidocyclonocardicins (I) and their pharmaceutically acceptable salts and esters which are useful as antibiotics ##STR1## wherein: R is NH.sub.2, R.sup.1 NH, R.sup.1 is acyl. 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: September 14, 1981
    Date of Patent: February 22, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, James V. Heck
  • 6-, 1- And 2-substituted-thio-1-carbadethiapen-2-em-3-carboxylic acid S-oxides
    Patent number: 4372965
    Abstract: Disclosed are S-oxides of 6-, 1- and 2-substituted-1-carbadethiapen-2-em-3-carboxylic acids having the structure: ##STR1## wherein: n is 1 or 2; and R.sup.1, R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds as well as 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: January 8, 1981
    Date of Patent: February 8, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, David H. Shih
  • 3-Substituted-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylic acid
    Patent number: 4369187
    Abstract: Disclosed are 3-substituted-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylic acids (I): ##STR1## wherein R is, inter alia, acyl, alkyl, and 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: August 8, 1980
    Date of Patent: January 18, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe
  • 2-Substituted thio-6-substituted-carbapen-2-em-3-carboxylic acids
    Patent number: 4361512
    Abstract: Disclosed are 2-substituted thio-6-substituted-carbapen-2-em-3-carboxylic acids (I) and their pharmaceutically acceptable salt, ester and amide derivatives which are useful as antibiotics: ##STR1## wherein: R.sup.5 is CN, ##STR2## (R is alkyl or aryl); R.sup.6 is hydrogen, R.sup.5, alkyl, aryl or heteroaryl; andR.sup.7 and R.sup.8 are, inter alia, hydrogen, alkyl, alkenyl, aryl and aralkyl.
    Type: Grant
    Filed: November 26, 1980
    Date of Patent: November 30, 1982
    Assignee: Merck & Co., Inc.
    Inventor: Ronald W. Ratcliffe
  • Process for the preparation of (2S)-tetrahydro-2.alpha.-methyl-6-oxo-4.beta..alpha.-carboxylic acid
    Patent number: 4360684
    Abstract: Disclosed is a process for preparing (2S)-tetrahydro-2.alpha.-methyl-6-oxo-4.beta.-amino-2H-pyran-3.alpha.-carb oxylic acid (I) which is useful in the synthesis of thienamycin. The process proceeds via a stereospecific reduction of the 2-acetyl-3-(R)-.alpha.-methylbenzylamino-2-pentenedioic acid diester (II). ##STR1## wherein R is, .alpha.-methylbenzyl, and R.sup.1 is lower alkyl having 1-6 carbon atoms or arylalkyl such as benzyl.
    Type: Grant
    Filed: April 8, 1981
    Date of Patent: November 23, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Raymond J. Cvetovich, David G. Melillo, Kenneth M. Ryan, Meyer Sletzinger
  • 7-N-Heterocyclyl cephalosporins
    Patent number: 4358447
    Abstract: Disclosed are antibiotic cephalosporins (I) of the formula: ##STR1## Wherein the stylized radical attached to the 7-amino nitrogen of the cephalosporin moiety represents a nitrogen-containing heterocyclic group (mono- or polycyclic); R is, inter alia, hydrogen, alkyl, heterocyclylalkyl, aryl, alkenyl, aralkyl, --NR.sub.2, --OR, COOR, CONR.sub.2 or CN; A is conventionally known in the cephalosporin art; and R.sup.2 is H, or lower alkoxyl. Also disclosed are the pharmaceutically acceptable salt and ester derivatives of I; 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: April 27, 1979
    Date of Patent: November 9, 1982
    Assignee: Merck & Co., Inc.
    Inventor: John Hannah
  • 1-Azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylic acid
    Patent number: 4357342
    Abstract: Disclosed are the pharmaceutically acceptable salt and ester forms of 1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylic acid (I): ##STR1## Such compounds 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: October 8, 1980
    Date of Patent: November 2, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe
  • 3-(1-Hydroxyethyl)-4-(but-2-ene)-azetidin-2-one and derivatives
    Patent number: 4356120
    Abstract: Disclosed is a process for the total synthesis of thienamycin from substituted 4-allylazetidinone (IIIa) via intermediate III: ##STR1## wherein: R=H, blocking group or a salt cation; and R.degree. is alkyl, aralkyl, cycloalkyl, or cycloalkylalkyl.
    Type: Grant
    Filed: January 5, 1981
    Date of Patent: October 26, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Ronald W. Ratcliffe, Thomas N. Salzmann
  • 6- and 4-Substituted-1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylates
    Patent number: 4350631
    Abstract: Disclosed are 6- and 4-substituted-1-azabicyclo[3.2.0]heptan-3,7-dione-2-carboxylic acid esters and salts (I) which are useful in the preparation of 6-, 1- and 2-substituted carbapenem antibiotics. ##STR1## wherein R.sup.5 is a pharmaceutically acceptable ester moiety or a removable protecting group or an alkali or alkaline earth metal cation such as sodium or potassium and wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, aryl and aralkyl.
    Type: Grant
    Filed: March 18, 1981
    Date of Patent: September 21, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, David H. Shih
  • Intermediate for synthesis of thienamycin via (3SR, 4RS)-3-[1 (SR)-hydroxyethyl]-2-oxo-4-azetidineacetic acid
    Patent number: 4349687
    Abstract: Disclosed is a process for the stereocontrolled total synthesis of thienamycin via intermediates II and IIa: ##STR1## wherein R is a readily removable carboxyl protecting group.
    Type: Grant
    Filed: April 8, 1981
    Date of Patent: September 14, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Thomas M. H. Liu, David G. Melillo, Kenneth M. Ryan, Ichiro Shinkai, Meyer Sletzinger
  • Substituted azetidiones
    Patent number: 4348320
    Abstract: Disclosed are substituted azetidinones (1) which are useful in the preparation of 1-carba-2-penem-3-carboxylic acids (I): ##STR1## wherein R is hydrogen or a blocking group and R.sup.1, R.sup.2 and R.sup.3 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl. Such 1-carba-2-penem-3-carboxylic acids and their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics.
    Type: Grant
    Filed: August 20, 1980
    Date of Patent: September 7, 1982
    Assignee: Merck & Co., Inc.
    Inventors: F. Aileen Bouffard, Burton G. Christensen, David B. R. Johnston
  • Methyl 3-azido-4-C-cyano-2,3,4,6-tetradeoxy-.alpha.-D-arabino-hexopyranoside
    Patent number: 4348325
    Abstract: Disclosed is methyl 3-azido-4-C-cyano-2,3,4,6-tetradeoxy-.alpha.-D-arabino-hexopyranoside and processes for its preparation from methyl 3-azido-2,3,6-trideoxy-.alpha.-D-arabino-hexopyranoside via the 4-bromo-4-deoxy intermediate; wherein the two inversions of configuration at C-4 result in a net retention of the .alpha.-D-arabino stereochemistry.
    Type: Grant
    Filed: March 30, 1981
    Date of Patent: September 7, 1982
    Assignee: Merck & Co., Inc.
    Inventor: Philippe L. Durette
  • 3-Substituted-6-(1'-hydroxyethyl)-7-oxo-1-azabicyc lo[3.2.0]-hept-2-ene-2-carboxylic acid
    Patent number: 4347367
    Abstract: Disclosed are 3-substituted-6-(1'-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-ca rboxylic acids having the structure: ##STR1## wherein R.sup.8 is, inter alia, selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds as well as their pharmaceutically acceptable O- and carboxyl 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: November 14, 1980
    Date of Patent: August 31, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, David B. R. Johnston, Susan M. Schmitt
  • 3 -Substituted-6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxyl ic acid
    Patent number: 4347368
    Abstract: Disclosed are 3- and 6-substituted 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids having the structure: ##STR1## wherein R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds as well as 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: November 14, 1980
    Date of Patent: August 31, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, David B. R. Johnston, Susan M. Schmitt