Synta Pharmaceuticals Corporation

Washington State University

Zhi-Qiang Xia

Shoujun Chen

Lijun Sun

Keizo Koya

Mitsunori Ono

Noriaki Tatsuta

Elena Kostik

Guiqing Liang

Jun Jiang

Takayo Inoue

Farid Vaghefi

Yu Xie

Yaming Wu

Junyi Zhang

Zachary Demko

David James

Hao Li

Christopher Borella

Teresa Kowalczyk-Przewloka

Stefan M Schweizer

Gary Bohnert

Norman G Lewis

Laurence B Davin

Chih-Yi Yu

Keizo Kova

Michael A Costa

The invention relates to compounds of structural formulas (I) and (XVI): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein X, X, Z, L, L, R, R, R, R, n, q, and t are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Thiophene compounds for inflammation and immune-related uses

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein Y, L, X, X, Z, R, R, and n are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Pyridylphenyl compounds for inflammation and immune-related uses

The present invention is directed to compounds represented by structural formula (I), or a pharmaceutically acceptable salt or a transition metal chelate, coordinate or complex thereof or a transition metal chelate, coordinate or complex of a deprotonated form of the compound. Pharmaceutical composition and method of use for these compounds are also included. 

Sulfonylhydrazide compounds for treating proliferative disorders

The invention relates to compounds of structural formulas (I), (VII) and (XI): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof, wherein X, X, X, Y, Z, L, R, R, R, Rand n are defined herein. These compounds are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

Compounds for inflammation and immune-related uses

Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier.

Compounds for treating proliferative disorders

Disclosed are bis(thio-hydrazide amide) disalts and pharmaceutical compositions thereof. Also disclosed are methods of using bis(thio-hydrazide amide) disalts to treat cancer.

Bis(thio-hydrazide amide) salts for treatment of cancers

Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I):  Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R-Rare independently &#x2014;H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or Rand Rtaken together with the carbon and nitrogen atoms to which they are bonded, and/or Rand Rtaken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is &#x2014;O or &#x2014;S. Mis a pharmaceutically acceptable monovalent cation and Mis a pharmaceutically acceptable divalent cation. Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I):  Also, disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt described above.

One embodiment of the present invention is a compound represented by the Structural Formula (I):  Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent.

Paclitaxel enhancer compound

A method of preparing a bis(thio-hydrazide amide) disalt includes the steps of combining a neutral bis(thio-hydrazide amide), an organic solvent and a base to form a bis(thio-hydrazide amide) solution; and combining the solution and methyl tert-butyl ether, thereby precipitating a disalt of the bis(thio-hydrazide amide). In some embodiments, a method of preparing a bis(thio-hydrazide amide) disalt includes the steps of combining a neutral bis(thio-hydrazide amide) and an organic solvent selected from methanol, ethanol, acetone, and methyl ethyl ketone to make a mixture; adding at least two equivalents of a base selected from sodium hydroxide, potassium hydroxide, sodium methoxide, potassium methoxide, sodium ethoxide and potassium ethoxide to the mixture, thereby forming a solution; and combining the solution and methyl tert-butyl ether to precipitate the disalt of the bis(thio-hydrazide amide). The disclosed methods do not require lyophilization and the solvents used in the process can be more readily removed to low levels consistent with pharmaceutically acceptable preparation.

Synthesis of bis(thio-hydrazide amide) salts

Disclosed is a method of preparing a thiohydrazide product compound from a hydrazide starting compound. The hydrazide starting compound is represented by Structural Formula (I): The thiohydrazide product compound is represented by Structural Formula (II): In Structural Formulas (I)-(II), Rand Rare independently an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or Rand Rtaken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. When Ris an aryl group or a substituted aryl group, then Ris a hydrazine protecting group; and when Ris an aliphatic or substituted aliphatic group, then Ris &#x2014;H or a hydrazine protecting group. Ris &#x2014;H or a substituted or unsubstituted alkyl group. The method comprising the step of reacting the starting compound with a thionylating reagent.

Synthesis of taxol enhancers

Disclosed herein are methods of purifying a bis(thio-hydrazide amides) compounds of the following structural formula: wherein R, R, R, R, R, R, Z, and Y are defined herein.

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Acton, MA, United States of America

Zhi-Qiang Xia