The present invention provides novel analogs of FR901464, as well as an improved methodology for preparing FR901464 and its analogs. These compounds display an anti-cancer activity and are candidates for therapies against a number of disease states associated with dysfunctional RNA splicing.

There are provided inter alia stable anti-cancer compounds and splice modulators and methods of synthesis and use thereof.

An intermediate compound is prepared and used for the synthesis of halichondrin B, eribulin or an analog thereof, particularly a structural fragment C27-C35 thereof. The starting materials of the synthetic route are readily available, and the optical purity of the starting materials can be ensured, so that the optical purity of the structural fragment C27-C35 in halichondrin B, eribulin or the analog thereof is ensured. Steps for constructing a chiral center of the structural fragment C27-C35 feature higher diastereoselectivity and yield, in particular preparation methods of compounds of formulae (X), (XI), (XVI) and (XV). By-products of partial reactions can be removed only by recrystallization, which results in easy purification and significant reduce in cost.

A process for manufacturing a polybenzoxazine monomer, crosslinking the latter, and using the crosslinked product to form an ablative thermal protection system for a thruster nozzle or atmospheric reentry body.

Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein. In an embodiment, the splicing modulator comprises a pladienolide or a pladienolide derivative.

The present invention provides MDM2 inhibitor compounds of Formula I,

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wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

The present invention provides MDM2 inhibitor compounds of Formula I,

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wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.

A process for manufacturing a polybenzoxazine monomer, crosslinking the latter, and using the crosslinked product to form an ablative thermal protection system for a thruster nozzle or atmospheric reentry body.

A process for manufacturing a polybenzoxazine monomer, crosslinking the latter, and using the crosslinked product to form an ablative thermal protection system for a thruster nozzle or atmospheric reentry body.

The present invention is directed to compounds of the formula [INSERT CHEMICAL STRUCTURE HERE}] wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

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