Patents by Inventor William J. Leanza

William J. Leanza has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 5985844
    Abstract: Compounds of the formula: ##STR1## where R is hydrogen, hydroxyl, alkyl or acyl, R' and R" together are oxo, hydroxyimino or alkoxyimino, and R' and R" independently are hydrogen, hydroxyl, acyloxy, or amino substituted by any of hydrogen, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkoxycarbonyl, aralkoxycarbonyl, alkylsulfonyl or arylsulfonyl, and n is 0 or 1, and the pharmaceutically acceptable salts thereof. The compounds are macrolide antibiotics and are also useful as intermediates to the synthesis of other macrolide antibiotics. Pharmaceutical compositions and methods of their use are also provided for.
    Type: Grant
    Filed: March 26, 1992
    Date of Patent: November 16, 1999
    Assignee: Merck & Co., Inc.
    Inventors: James V. Heck, William J. Leanza, Ronald W. Ratcliffe, Thomas N. Salzmann, Kothandaraman Shankaran, Michael J. Szymonifka, Robert R. Wilkening
  • Patent number: 5606030
    Abstract: A novel coconjugate comprising an immunogenic protein or protein complex having a first set of covalent linkages to low molecular weight moieties, --a.sup.--, which have an anionic or polyanionic character at physiological pH, and a second set of covalent linkages to peptides comprising Human Immunodeficiency Virus (HIV) Principal Neutralizing Determinants (PNDs), or peptides immunologically equivalent therewith, is useful for inducing anti-peptide immune responses in mammals, for inducing HIV-neutralizing antibodies in mammals, for formulating vaccines to prevent HIV infection or disease, including the Acquired Immune Deficiency Syndrome (AIDS), or for treating humans afflicted with HIV infection or disease.
    Type: Grant
    Filed: September 14, 1994
    Date of Patent: February 25, 1997
    Assignee: Merck & Co., Inc.
    Inventors: Emilio A. Emini, William J. Leanza, Stephen Marburg, Richard L. Tolman
  • Patent number: 5274122
    Abstract: Homocysteine thiolactone derivatives in which the nitrogen is acylated with groups containing acidic functionalities have been synthesized. These include the succinyl, the carboxymethylglutaryl, the 3-phosphonopropionyl and the 3-sulfopropionyl derivatives. These thiolactones can be used to introduce a thiol functionality into proteins such as the outer membrane protein complex of Neisseria meninioitidis (OMPC) allowing conjugation with electrophilic ligands. This chemistry is similar to known N-acetyl-homocysteine thiolactone chemistry, but the pK.sub.a values are such that at pH 7, concomitant negative charge is introduced into the conjugate. Such negative charge neutralizes excess positive charge introduced when arginine- and lysine-rich peptides are bonded as ligands. In the case of OMPC, introduction of positive charge commonly effects irreversible precipitation of the conjugate. Conjugates prepared with the anionic thiolactones have improved solubility.
    Type: Grant
    Filed: October 15, 1992
    Date of Patent: December 28, 1993
    Assignee: Merck & Co., Inc.
    Inventors: Richard L. Tolman, Stephen Marburg, William J. Leanza
  • Patent number: 4839352
    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
  • Patent number: 4748162
    Abstract: Disclosed are 6-substituted-2-carbamimidoyl-pen-2-em-3-carboxylic acids (I) having the representative structure: ##STR1## wherein R.sup.6, and R.sup.7 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkoxyl, halo, OH, COOH, alkenyl, aryl and aralkyl; A is a direct, single bond connecting the indicated S and C atoms, or A is a cyclic or acyclic connecting group selected, inter alia, from alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl; R.sup.1 and R.sup.2, which define the carbamimidoyl function, are, inter alia, independently selected from hydrogen, alkyl, aryl; additionally, said carbamimidoyl is characterized by cyclic structures achieved by the joinder of the two nitrogen atoms via their substituents and by their joinder to connecting group A; additionally, "carbamimidiums" are disclosed by quarternization of one of the nitrogen atoms of said carbamimidoyl.
    Type: Grant
    Filed: April 30, 1984
    Date of Patent: May 31, 1988
    Assignee: Merck & Co., Inc.
    Inventors: William J. Leanza, Burton G. Christensen, Frank P. DiNinno, Ronald W. Ratcliffe
  • Patent number: 4713451
    Abstract: Crystalline dimethyliminothienamycin having the formula ##STR1## and its preparation are disclosed.
    Type: Grant
    Filed: April 9, 1984
    Date of Patent: December 15, 1987
    Assignee: Merck & Co., Inc.
    Inventors: William J. Leanza, Kenneth J. Wildonger
  • Patent number: 4675317
    Abstract: Disclosed are 6- and 6,6-disubstituted-2-substituted thio-pen-2-em-3-carboxylic acids of the following structure: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from: hydrogen; substituted and unsubstituted: alkyl, cycloalkyl, halo, alkoxyl, alkenyl, aralkyl, aryl, heterocyclyl, heteroaryl, and heterocyclylalkyl; W is an electron withdrawing group, and, for example, is selected from: --COR.sup.5, --CN, SO.sub.2 C.sub.6 H.sub.5 ; R.sup.5 is hydrogen; substituted and unsubstituted: alkyl, aryl, aralkyl, heteroaryl, heterocyclyl, or heterocyclylalkyl; or R.sup.5 may be --OR.sup.6, --NR.sup.7 R.sup.8, and --SR.sup.9 ; wherein R.sup.6 is H; substituted and unsubstituted: alkyl, alkenyl, or a group which defines --CO.sub.2 R.sup.6 as a pharmaceutically acceptable ester wherein R.sup.6 is, for example, phthalidyl, or 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl; R.sup.7 and R.sup.
    Type: Grant
    Filed: January 25, 1983
    Date of Patent: June 23, 1987
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe, David A. Muthard
  • Patent number: 4650794
    Abstract: Disclosed are 6-(1-hydroxyethyl)-2-carbamimidoyl-pen-2-em-3-carboxylic acids (I) having the representative structure: ##STR1## wherein: A is a direct, single bond connecting the indicated S and C atoms, or A is a cyclic or acyclic connecting group selected, inter alia, from alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl; R.sup.1 and R.sup.2, which define the carbamimidoyl function, are, inter alia, independently selected from hydrogen, alkyl, aryl, alkoxy, amino; additionally, said carbamimidoyl is characterized by cyclic structures achieved by the joinder of the two nitrogen atoms via their substituents and by their joinder to connecting group A; additionally, "carbamimidiums" are disclosed by quaternization of one of the nitrogen atoms of said carbamimidoyl. Such compounds as well as their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics.
    Type: Grant
    Filed: April 29, 1982
    Date of Patent: March 17, 1987
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe
  • Patent number: 4610823
    Abstract: Disclosed is a synthesis for preparing substituted 2-thioxopenams which are useful in the synthesis of penem antibiotics 7 which may be conducted in an enantiospecific manner; said process proceeds from azetidinone 1 via the azetidinone acetic ester 2, the 4-metallothiozetidinone 3, and the 4-dithiocarbonylazetidinone 4 to the substituted 2-thioxopenam 5: ##STR1## wherein: R.sup.6 and R.sup.7 are independently selected from: hydrogen; R.sup.6 NH-- (R.sup.6 is acyl or H); substituted and unsubstituted: alkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, and cycloalkenyl; wherein said substituents are, inter alia: halo (chloro, bromo, fluoro, iodo), hydroxyl, cyano, carboxyl, amino, and the above-recited values for R.sup.6 and R.sup.7 ; in functional terms,R.sup.2 is a group which potentially forms a stable carbonium ion, for example: trityl (--C(C.sub.6 H.sub.5).sub.
    Type: Grant
    Filed: January 25, 1983
    Date of Patent: September 9, 1986
    Assignee: Merck & Co., Inc.
    Inventors: Frank P. DiNinno, William J. Leanza, Ronald W. Ratcliffe
  • Patent number: 4397861
    Abstract: Disclosed are N-acyl and carboxyl derivatives of the antibiotic thienamycin, which has the following structure: ##STR1## Such derivatives 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: November 16, 1981
    Date of Patent: August 9, 1983
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, John Hannah, William J. Leanza, David H. Shih
  • Patent number: 4335043
    Abstract: Disclosed are substituted N-methylene derivatives of thienamycin which may be represented by the following structural formula: ##STR1## wherein X and Y are selected from the group consisting of hydrogen, R, OR, SR, and NR.sup.1 R.sup.2 wherein, inter alia, R is substituted or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; R.sup.1 and R.sup.2 are hydrogen or R. Such compounds and their pharmaceutically acceptable salt, ether, 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: October 11, 1979
    Date of Patent: June 15, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza, Kenneth J. Wildonger
  • Patent number: 4311704
    Abstract: Disclosed are substituted N-methylene derivatives of thienamycin having the formula: ##STR1## wherein: (1.) X.dbd.--NR.sup.1 R.sup.2, and Y.dbd.--R'--N.dbd.CRNR.sup.1 R.sup.2, and(2.) X.dbd.R, and Y.dbd.--NR.sup.1 R'N.dbd.CRNR.sup.1 R.sup.2 ; andwherein: R is, inter alia, hydrogen, NH.sub.2, --NHR.sup.1, --NR.sup.1 R.sup.2, R.sup.1 and R.sup.2 ; R.sup.1 and R.sup.2 are independently selected from: hydrogen, substituted, or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; R' is --(CH.sub.2).sub.n.sup.-, n is 1-6, or --(CH.sub.2).sub.m --Q--(CH.sub.2).sub.p.sup.-, m, n.dbd.1-3 and Q is O, S or R' is a carbocyclic or heterocyclic ring. Such compounds and their pharmaceutically acceptable salt, ether, ester and amide derivatives are useful as antibiotics.
    Type: Grant
    Filed: June 16, 1980
    Date of Patent: January 19, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza, David H. Shih, Kenneth J. Wildonger
  • Patent number: 4309438
    Abstract: Disclosed are N-alkyl-N-iminomethyl derivatives of thienamycin which may be represented by the following structural formula: ##STR1## wherein R.sup.5 is, inter alia, alkyl, alkenyl, aryl, or aralkyl, R.sup.6 is selected from R, OR, SR and NR.sup.1 R.sup.2 wherein R is, inter alia, hydrogen and substituted or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; and R.sup.1 and R.sup.2 are hydrogen or R. Such compounds, including their O-- and carboxyl derivatives are useful as antibiotics. Also dislosed 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: March 31, 1980
    Date of Patent: January 5, 1982
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza, Kenneth J. Wildonger
  • Patent number: 4235917
    Abstract: Disclosed are N-alkyl- N-acyl derivatives of the antibiotic thienamycin having the following structural formula: ##STR1## wherein R.sup.1 is, inter alia, alkyl, alkenyl, aryl or aralkyl; and R.sup.2 is acyl. Such compounds, including their 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: May 5, 1977
    Date of Patent: November 25, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza
  • Patent number: 4235920
    Abstract: Disclosed are N-alkylated derivatives of the antibiotic thienamycin, which has the following structure: ##STR1## Such compounds and their pharmaceutically acceptable salt, ester and amide derivatives 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: December 16, 1977
    Date of Patent: November 25, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Raymond A. Firestone, William J. Leanza
  • Patent number: 4232030
    Abstract: Disclosed are substituted N-methylene derivatives of thienamycin sulfoxide (I, n=1) and sulfone (I, n=2) which may be represented by the following structural formula: ##STR1## wherein X and Y are selected from the group consisting of hydrogen, R, OR, SR, and NR.sup.1 R.sup.2 wherein, inter alia, R is substituted or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; R.sup.1 and R.sup.2 are hydrogen or R. Such compounds and their pharmaceutically acceptable salt, ether, 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: September 15, 1977
    Date of Patent: November 4, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza, Kenneth J. Wildonger
  • Patent number: 4226870
    Abstract: Disclosed are O-, N- and substituted carboxyl derivatives of the antibiotic thienamycin, which has the following structure: ##STR1## Such derivatives 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: December 16, 1977
    Date of Patent: October 7, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, John Hannah, William J. Leanza, Ronald W. Ratcliffe, David H. Shih
  • Patent number: 4208330
    Abstract: Disclosed are O- derivatives (esters and ethers of the secondary alcohol group) of the antibiotic thienamycin which has the following structure: ##STR1## Such derivatives 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: December 16, 1977
    Date of Patent: June 17, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza
  • Patent number: 4194047
    Abstract: Disclosed are substituted N-methylene derivatives of thienamycin which may be represented by the following structural formula: ##STR1## wherein X and Y are selected from the group consisting of hydrogen, R, OR, SR, and NR.sup.1 R.sup.2 wherein, inter alia, R is substituted or unsubstituted: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; R.sup.1 and R.sup.2 are hydrogen or R. Such compounds and their pharmaceutically acceptable salt, ether, 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 17, 1977
    Date of Patent: March 18, 1980
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, William J. Leanza, Kenneth J. Wildonger
  • Patent number: 4150145
    Abstract: Disclosed are N-alkylated derivatives of thienamycin sulfoxide (I, n=1) and sulfone (I, n=2): ##STR1## wherein n=1 or 2; and R.sup.5, R.sup.6, and R.sup.7 are, inter alia, hydrogen or alkyl. Such compounds the their pharmaceutically acceptable O- and carboxyl- derivatives 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: September 15, 1977
    Date of Patent: April 17, 1979
    Assignee: Merck & Co., Inc.
    Inventors: Burton G. Christensen, Raymond A. Firestone, William J. Leanza