Abstract: The invention provides compounds of the formulas ##STR1## which are useful as intermediates for the preparation of 6-demethyl-6-deotetracycline antibiotic agents.
Type:
Grant
Filed:
December 8, 1994
Date of Patent:
March 23, 1999
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Joseph J. Hlavka, Raymond T. Testa
Abstract: New 4-substituted azetidinones having the formulae I and II: ##STR1## wherein X is oxygen, sulfur or a moiety of the formula NR.sup.6 where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are 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:
April 12, 1995
Date of Patent:
December 23, 1997
Assignee:
American Cyanamid Company
Inventors:
Gregg Brian Feigelson, William V. Curran, Carl Bernard Ziegler
Abstract: The invention provides a method for selectively extracting a compound of formula I: ##STR1## wherein: R is hydrogen or --NR.sub.3 R.sub.4 ; and when R=--NR.sub.3 R.sub.4, R.sub.3 and R.sub.4 may be the same or different and are selected from hydrogen and straight or branched (C.sub.1 -C.sub.4)alkyl; R.sub.1 and R.sub.2 may be the same or different and are selected from straight or branched (C.sub.1 -C.sub.6)alkyl; from an aqueous mixture containing a compound of Formula I, its C-4 epimer and its oxidative degradation by-products by adding methylene at a concentration of 2-4 ml of methylene chloride per gram of compound of Formula I and at a pH between pH 6.5-8.0; and obtaining an extract containing methylene chloride, a compound of Formula I, and its C-4 epimer, said epimer being present in an amount of less than 3% of the amount of the compound of Formula I.
Type:
Grant
Filed:
November 16, 1994
Date of Patent:
October 7, 1997
Assignee:
American Cyanamid Company
Inventors:
Lalitha Krishnan, Richard A. Leese, Raghavan Krishnan
Abstract: Compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.12, R.sup.16 and R.sup.17 are defined in the specification are provided. These compounds are useful as intermediates for the preparation of carbapenem antibacterials.
Type:
Grant
Filed:
August 24, 1994
Date of Patent:
August 12, 1997
Assignee:
American Cyanamid Company
Inventors:
Gregg Brian Feigelson, William V. Curran, Carl Bernard Ziegler
Abstract: Carbapenem antibiotic compounds of the general formula: ##STR1## wherein the moiety ##STR2## is a 4, 5 or 6 membered mono, di- or tri- substituted oxygen or sulfur containing ring; wherein Z is oxygen, sulfur, sulfoxide and sulfone, pharmaceutical compositions thereof useful for the treatment of bacterial infections, processes for preparing the compounds and new intermediates useful in the process.
Type:
Grant
Filed:
January 26, 1994
Date of Patent:
February 11, 1997
Assignee:
American Cyanamid Company
Inventors:
Yang-I Lin, Panayota Bitha, Subas Sakya, Timothy W. Strohmeyer, Karen Bush, Carl B. Ziegler, Gregg B. Feigelson
Abstract: The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-halogen-9-[hydrogen or [(substituted glycyl)amido]]-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein X and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.
Type:
Grant
Filed:
December 13, 1994
Date of Patent:
November 12, 1996
Assignee:
American Cyanamid Company
Inventors:
Joseph M. Backer, Peter Bohlen, Phaik-Eng Sum
Abstract: The invention provides a method for prevention, treatment or control of bacterial infections in warm blooded animals by administering a pharmacologically effect amount of a compound of the formula: ##STR1## wherein R, R.sup.1 and W are defined in the specification.
Type:
Grant
Filed:
May 18, 1995
Date of Patent:
October 22, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Raymond T. Testa
Abstract: The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-(hydrogen or di (C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ine of Formula I: ##STR1## wherein R, X and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.
Type:
Grant
Filed:
December 13, 1994
Date of Patent:
October 22, 1996
Assignee:
American Cyanamid Company
Inventors:
Joseph M. Backer, Peter Bohlen, Phaik-Eng Sum
Abstract: The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein W, R.sub.2 and R.sub.3 are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.
Abstract: The disclosure is drawn to a method of using novel 7-substituted-9-(substituted amino)-6-demethyl-6-deoxytetracycline compounds to treat infections caused by a wide spectrum of bacterial organisms, including those which are resistant to tetracycline.
Type:
Grant
Filed:
May 31, 1995
Date of Patent:
June 25, 1996
Assignee:
American Cyanamid Company
Inventors:
Joseph J. Hlavka, Phaik-Eng Sum, Yakov Gluzman, Ving J. Lee, Adma A. Ross
Abstract: The disclosure is drawn to novel 7-substituted-9-(substituted amino)-6-demethyl-6-deoxytetracycline compounds. These compounds are useful to treat infections caused by a wide spectrum of bacterial organisms, including those which are resistant to tetracycline.
Type:
Grant
Filed:
May 31, 1995
Date of Patent:
June 25, 1996
Assignee:
American Cyanamid Company
Inventors:
Joseph J. Hlavka, Phaik-Eng Sum, Yakov Gluzman, Ving J. Lee, Adma A. Ross
Abstract: The invention provides compounds of formula ##STR1## wherein X, R and R.sup.1 are defined in the specification. These compounds are useful as antibiotic agents.
Type:
Grant
Filed:
May 31, 1995
Date of Patent:
April 30, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Joseph J. Hlavka, Raymond T. Testa
Abstract: The invention provides compounds of the formula: ##STR1## wherein R, R.sup.1 and Y are defined in the specification. The compounds are useful for the production of 6-demethyl-6-deoxytracycline derivatives.
Type:
Grant
Filed:
September 1, 1994
Date of Patent:
February 27, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Raymond T. Testa
Abstract: The invention provides compounds of the formulas ##STR1## which are useful as intermediates for the preparation of 6-demethyl-6-deotetracycline antibiotic agents.
Type:
Grant
Filed:
December 8, 1994
Date of Patent:
February 27, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Joseph J. Hlavka, Raymond T. Testa
Abstract: The invention is drawn to 7-substituted-9-(substituted amino)-6-demethyl-6-deoxytetracycline compounds of the formula ##STR1## wherein R, X, R.sup.5 and R.sup.6 are defined in the specification. The compounds of the invention are useful as broad spectrum antibiotics.
Type:
Grant
Filed:
August 4, 1994
Date of Patent:
February 27, 1996
Assignee:
American Cyanamid Company
Inventors:
Joseph J. Hlavka, Phaik-Eng Sum, Yakov Gluzman, Ving J. Lee, Adma A. Ross
Abstract: The invention provides a process for the production of compounds of the formula: ##STR1## wherein, R, R.sup.3, R.sup.4, X and W are defined in the specification in which a compound of the following formula: ##STR2## is reacted with a nucleophile of the formula WH in an inert atmosphere in the presence of a polar-protic or a polar-aprotic solvent. The resulting compounds are useful as antibiotics.
Type:
Grant
Filed:
September 27, 1994
Date of Patent:
February 27, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Joseph J. Hlavka, Raymond T. Testa
Abstract: The invention provides a process for the production of compounds of the formula: ##STR1## wherein R, R.sup.3, R.sup.4 and W are defined in the specification in which a compound of the following formula: ##STR2## is reacted with a nucleophile of the formula WH in an inert atmosphere in the presence of a polar aprotic solvent. The resulting compounds are useful as antibiotics.
Type:
Grant
Filed:
September 13, 1994
Date of Patent:
February 27, 1996
Assignee:
American Cyanamid Company
Inventors:
Phaik-Eng Sum, Ving J. Lee, Raymond T. Testa