Bristol-myers Company

Bristol-myers Squibb Compnay

Bristol-myers

Murray A Kaplan

Alphonse P Granatek

William J Gottstein

Joseph B Bogardus

Robert K Perrone

Robert A Lipper

Dolatrai M Vyas

Thomas W Hudyma

Susan D Boettger

Kun M Shih

John F Kadow

John K Thottathil

Koji Tomita

Mark D Wittman

John J Wright

Henry S Wong

James A Matson

Wen-Sen Li

Jacqueline M Mattei

Daniel Bouzard

Abraham Weber

Jerzy Golik

John E Leet

Jacques Stemer

Munir N Nassar

Claude Perol

Kin S Lam

Gary M Lim

Rajesh Babulal Gandhi

Shreeram N Agharkar

Lawan Phusanti

Elizabeth A Garofalo

Sheeram N Agharkar

Edward C Shinal

Ismat Ullah

Scott R Stenberg

Peter M Garofalo

Timothy R Marr

Kenneth W Douglas, Sr

Solomon J Nachfolger

Richard G Corrao

Gururaj Bykadi

Nagaswara R Palepu

Chih-Ming J Chen

Edward J Bara

Michael W Lovell

Nageswara R Palepu

King S Lam

Kenneth J Wilcox

The present invention concerns antitumor compounds. More particularly, the invention provides novel taxane derivatives, pharmaceutical compositions thereof, and their use as antitumor agents.

Phosphonooxymethyl ethers of taxane derivatives

Provided are very highly water soluble, stable, crystalline salts of 2&prime;,3&prime;-dideoxy-2&prime;,3&prime;-didehydrothymidine (&ldquo;d4T&rdquo;), 2&prime;,3&prime;-dideoxyinosine (&ldquo;ddI&rdquo;), and 2&prime;,3&prime;-dideoxy-2&prime;-fluoroinosine (&ldquo;F-ddI&rdquo;). Such salts are useful as intermediates or as antiviral agents.

Antiviral, highly water soluble, stable, crystalline salts of 2&prime;, 3&prime;-dideoxyinosine, 2&prime;, 3&prime;-dideoxy-2&prime;, 3&prime;-didehydrothymidine and 2&prime;, 3&prime;-dideoxy-2&prime;-fluoroinosine

The present invention concerns a novel process using controlled cooling for obtaining d.sub.4 T polymorphic Form I from a mixture containing one or more of polymorphic Forms I, II and III. Compound d.sub.4 T has been approved for use in the treatment of AIDS.

d.sub.4 T polymorphic Form 1 process

Solutions of carboplatin and other malonato platinum(II) antitumor agents are prepared containing stabilizing amounts of 1,1-cyclobutanedicarboxylic acid or salt at pH 4-8. The stabilizers inhibit unacceptable discoloration and precipitation. The solutions may also be stabilized by purging the carrier with air or oxygen and, optionally, blanketing the headspace with air or oxygen.

Stabilized solutions of platinum(II) antitumor agents

The present invention provides physical admixtures of a new crystalline dihydrochloride dihydrate salt of the cephalosporin antibiotic, cefepime with a pharmaceutically acceptable non-toxic organic or inorganic base. In particular, this invention provides physical admixtures having a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having a specific X-ray powder diffraction pattern as described herein.

Injectable compositions of a cephalosporin dihydrate salt

The present invention relates to a new crystalline dihydrochloride dihydrate salt of the cephalosporin antibiotic, cefepime. In particular, this invention provides a temperature and moisture stable crystalline dihydrochloride dihydrate form of cefepime having enhanced stability and a specific x-ray powder diffraction pattern as described herein.

Crystalline dihydrate of a cephalosporin salt

Crystalline sulfuric, di-nitric, mono-hydrochloric, di-hydrochloric, and di- and sesqui-orthosphosphoric acid addition salts of 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(Z)-methoxyiminoacetamido]-3-[(1- methyl-1-pyrrolidinio)methyl]-3-cephem-4-carboxylate are stable even at elevated temperatures. The crystalline sulfuric acid addition salt is made by forming an admixture of (a) at least one molar equivalent of sulfuric acid with (b) zwitterion in an amount so as to be present in the admixture at a concentration of greater than 25 milligrams/ml, causing crystallization, separating the crystals, washing and drying. The crystalline monohydrochloride, dihydrochloride, and orthophosphate salts are prepared by dissolving the zwitterion in the appropriate amount of acid, causing crystallization by adding acetone and isolating the crystals. Physical admixtures of the salts with certain bases in proportions to give a pH ranging from about 3.5 to about 7 on dilution with water provide injectable compositions on dilution.

Injectable compositions of cefepime dihydrochloride hydrate

Platinum complexes are disclosed in which the formula is ##STR1## wherein A and B are each independently ammine or monodentate amine, or A and B taken together represent a bidentate amine, and A and B are coordinated to the platinum atom through their nitrogen atom; X and Y are each independently halogen; R' is C.sub.1 -C.sub.20 alkanoyl, aroyl, heteroaroyl, or a group selected from the group consisting of ##STR2## wherein u' is an integer from 1 to 5; and R' is hydrogen with the proviso that A, B, X, and Y are structually equatorial substituents with respect to OR'--Pt--OR'. These platinum complexes show antitumor activity with relatively lower kidney or bone marrow toxicity.

Water and solvent soluble axial hydroxy and mono- and di- carboxylic

A stable, amorphous, lyophilized dihydrochloride salt of 7-[.alpha.-(2-aminothiazol-4-yl)-.alpha.-(z)-methoxyiminoacetamido]-3-[(1- methyl-1-pyrrolidinium) methyl]-3-cephem-4-carboxylate is described. This lyophilized salt is more easily prepared than the crystalline counterpart and can be reconstituted in effective concentrations for intramuscular and intravenous injection utilizing suitable organic and inorganic bases to pH 3-7.0.

Lyophilized cefepime dihydrochloride for parenteral use

A new antitumor antibiotic designated BMY-40800 is produced by fermentation of Streptomyces hygroscopicus ATCC 53653. The new compound inhibits the growth of tumors in experimental animals.

BMY-40800 antitumor antibiotics

This invention relates to novel compositions of the antitumor agent [4'-9-(acridinylamino) methanesulfon-m-anisidide], (m-AMSA). Acid salts of m-AMSA are dissolved in 1-methyl-2-pyrrolidinone to provide highly stable solutions. The solutions may be diluted with Sterile Water for Injection, U.S.P. to provide stable, non-precipitating solutions for intravenous use.

Stable, water soluble salt compositions of M-AMSA in

Cephalosporin salts and injectable compositions

The invention relates to chemically stable, concentrated solutions of cis-diamminedinitratoplatinum which are pH-stabilized with nitric acid and are readily convertible to parenteral cisplatin solutions by addition of sources of chloride ion.

Concentrated, stabilized cis-diamminedinitratoplatinum solutions for

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Syracuse, NY, United States of America

Murray A Kaplan