Vion Pharmaceuticals, Inc.

Yale University

Nanotherapeutics, Inc.

Ivan C King

Xu Kevin Lin

Michael Belcourt

David Gordon Bermudes

Terrence W Doyle

Mario Sznol

Caroline A Clairmont

Yung-Chi Cheng

Alan C Sartorelli

Stanley L Lin

Terrance W Doyle

Li-Mou Zheng

Michael F Belcourt

The present invention relates to simple, safe, high-yield methods of synthesizing VNP40101M, 1,2-bis(methylsulfonyl)-2-(2-chloroethyl)-2-(methylaminocarbonyl)hydrazine, an anti-neoplasia agent. One particularly preferred method uses methyl chloroformamide in a one-pot reaction at elevated temperatures to provide VNP40101M in high yield.

Process for the synthesis of anti-neoplasia agent VNP40101M

This invention provides a method for treating tumor in a subject comprising administering to the subject an effective amount of: (1) VNP40101M, or its equivalent; and (2) a nucleoside, or a nucleoside analog. This invention also provides a method for inhibiting tumor cell growth comprising contacting the tumor cell with effective amounts of: (1) VNP40101M, or its equivalent; and (2) a nucleoside, or a nucleoside analog. The present invention relates to the treatment of cancer, comprising administering to a subject in need thereof an effective amount of VNP40101M in combination with a nucleoside.

Combination therapy comprising cloretazine

The present application discloses the preparation and use of attenuated tumor-targeted bacteria vectors for the delivery of one or more primary effector molecule(s) to the site of a solid tumor. The primary effector molecule(s) of the invention is used in the methods of the invention to treat a solid tumor cancer such as a carcinoma, melanoma, lymphoma, or sarcoma. The invention relates to the surprising discovery that effector molecules, which may be toxic when administered systemically to a host, can be delivered locally to tumors by attenuated tumor-targeted bacteria with reduced toxicity to the host. The application also discloses to the delivery of one or more optional effector molecule(s) (termed secondary effector molecules) which may be delivered by the attenuated tumor-targeted bacteria in conjunction with the primary effector molecule(s).

Compositions and methods for tumor-targeted delivery of effector molecules

Novel phosphate-bearing prodrugs of sulfonyl hydrazines have the formula presented below. Pharmaceutical compositions and uses thereof in the treatment of cancer are claimed. The aforementioned prodrugs include enantiomers, stereoisomers and tautomers thereof, as well as pharmaceutically acceptable salts or solvates and metabolites from all stages. The aforementioned prodrugs are preferentially activated in hypoxic tumors and can be given either alone, or in combination with other anticancer agents or with phototheraphy or radiotherapy. where R is C-Calkyl or haloalkyl;

Phosphate-bearing prodrugs of sulfonyl hydrazines as hypoxia-selective antineoplastic agents

This invention provides a method to determine alkylguanyltransferase activity in a sample, comprising steps of placing the sample in an appropriate condition so that the AGT is functional; contacting the sample with an AGT Detector under conditions permitting the binding of AGT and AGTD to produce a signal; and measuring the signal, thereby determining the AGT activity in said sample. This invention provides different uses of this method.

Alkylguanyltransferase assays

The present invention relates to methods of treating viral or fungal infections using 3-aminopyridine-2-carboxyaldehyde thiosemicarbazone (3-AP) and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone (3-AMP) and its prodrug forms and to pharmaceutical compositions comprising these compounds.

Antiviral agents and methods of treating viral infections

The present invention relates to compounds according to the structure (I):Where R is &#x2014;CHor &#x2014;CHCHCl; R' is C-Calkyl or &#x2014;CHCHCl; Ror Ris OPOH, NO, OCO(Glu-OH), NHCO(Glu-OH), NHRand unassigned groups of R, R, R, Rand Rare, independently H, F, Cl, Br, I, OH, OPOH, OCH, CF, OCF, NO, CN, SOCH, SOCF, COCH, COOCH, SCH, SF, NH, NHR, N(CH), OPOH, or a C1-C7 alkyl group with the proviso that when any two of unassigned groups of R, R, R, Ror Rare other than H, the other two of unassigned groups of R, R, R, Ror Rare H. Ris H or polyglutamyl as described. Phosphoric acid and glutamic acid can be a free acid or pharmaceutically acceptable salt thereof.

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New Haven, CT, United States of America

Ivan C King