The present invention belongs to the field of medical technology and relates to a class of functional small molecules targeting proteolysis pathways, a preparation and an application thereof. Specifically, the present invention relates to functional small molecules represented by formula (M) and pharmaceutically acceptable salts thereof, as well as the application of said compounds and pharmaceutical compositions thereof in the preparation of tumor-treating drugs. The functional small molecules are obtained by means of linking a compound containing a peroxide bridge linkage and a substrate of an E3 ubiquitin ligase complex. The related functional molecules can promiscuously target and bind to multiple proteins comprising functional proteins in the proteolysis pathway and have anti-tumor biological activity.

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The present invention provides compounds of formula I: ##STR00001##
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

The present invention provides compounds of formula I: ##STR00001##
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds, and methods of using such compounds for treatment of joint damage or joint injury in a mammal, and for inducing differentiation of mesenchymal stem cells into chondrocytes.

A general and modular mechanophore platform that efficiently releases a cargo molecule via a mechanically triggered cascade reaction is described, along with methods of synthesis and use thereof. The mechanophore platform comprises a stable Diels-Alder adduct mechanophore comprising a 2-furylcarbinol derivative as its diene component, wherein the 2-furylcarbinol derivative is, in turn, pre-loaded with a covalently attached cargo molecule, and wherein the Diels-Alder adduct mechanophore is embedded into a polymer chain or polymer network, such that the mechanophore platform undergoes the retro [4+2] cycloaddition reaction under mechanical force to reveal the unstable 2-furylcarbinol derivative, which, in turn, easily decomposes under mild conditions to release its molecule cargo.

A general and modular mechanophore platform that efficiently releases a cargo molecule via a mechanically triggered cascade reaction is described, along with methods of synthesis and use thereof. The mechanophore platform comprises a stable Diels-Alder adduct mechanophore comprising a 2-furylcarbinol derivative as its diene component, wherein the 2-furylcarbinol derivative is, in turn, pre-loaded with a covalently attached cargo molecule, and wherein the Diels-Alder adduct mechanophore is embedded into a polymer chain or polymer network, such that the mechanophore platform undergoes the retro [4+2] cycloaddition reaction under mechanical force to reveal the unstable 2-furylcarbinol derivative, which, in turn, easily decomposes under mild conditions to release its molecule cargo.

The invention relates to a crosslinking compound of formula (I) ##STR00001##
In particular, the present invention relates to a liquid composition comprising a monomer, a (meth)acrylic polymer and at least one crosslinking compound of formula (I). This liquid composition may be used in the form of a syrup and in particular in the form of a syrup for impregnating fibers or fibrous material. The invention also relates to a pseudo-thermoplastic material obtained after polymerization of the liquid composition being at least partially crosslinked. The invention also relates to a process for manufacturing such a liquid composition. The invention also relates to a process for impregnating a long-fiber fibrous substrate with said liquid composition. The invention also relates to a fibrous substrate impregnated with said liquid composition which is useful for manufacturing composite parts. The present invention also relates to a process for manufacturing mechanical parts or structural elements made of composite material and to mechanical parts or structural elements made of composite material obtained via a process using such a liquid composition.

The invention relates to a crosslinking compound of formula (I) ##STR00001##
In particular, the present invention relates to a liquid composition comprising a monomer, a (meth)acrylic polymer and at least one crosslinking compound of formula (I). This liquid composition may be used in the form of a syrup and in particular in the form of a syrup for impregnating fibers or fibrous material. The invention also relates to a pseudo-thermoplastic material obtained after polymerization of the liquid composition being at least partially crosslinked. The invention also relates to a process for manufacturing such a liquid composition. The invention also relates to a process for impregnating a long-fiber fibrous substrate with said liquid composition. The invention also relates to a fibrous substrate impregnated with said liquid composition which is useful for manufacturing composite parts. The present invention also relates to a process for manufacturing mechanical parts or structural elements made of composite material and to mechanical parts or structural elements made of composite material obtained via a process using such a liquid composition.

The present disclosure relates to compounds suitable for the inhibition of protein arginine methyl-transferase (PRMT), in particular PRMT5. These compounds may be for use as therapeutic agents, in particular, agents for use in the treatment and/or prevention of proliferative diseases, such as cancer.

Bifunctional chimeric heterocyclic compounds of formula (I) is effective for targeted degradation of androgen receptors and use thereof. The compound of formula (I) also has an isotopic compound, an optical isomer, a tautomer, pharmacologically acceptable salt, a prodrug thereof, or a solvate. In formula (I), ARB is an androgen receptor recognition/binding part, L is a link part, and U is a ubiquitin protease recognition/binding part; and the three parts are connected by means of chemical bonds. The compound can perform targeted degradation on androgen receptors in prostate cancer cells, and suppress proliferation of the prostate cancer cells, and also show good metabolic stability and pharmacokinetic properties. The compound has good application prospect in preparation of targeted chimeras for protein degradation of androgen receptors and in the preparation of drugs for treating related diseases regulated by the androgen receptors.

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Bifunctional chimeric heterocyclic compounds of formula (I) is effective for targeted degradation of androgen receptors and use thereof. The compound of formula (I) also has an isotopic compound, an optical isomer, a tautomer, pharmacologically acceptable salt, a prodrug thereof, or a solvate. In formula (I), ARB is an androgen receptor recognition/binding part, L is a link part, and U is a ubiquitin protease recognition/binding part; and the three parts are connected by means of chemical bonds. The compound can perform targeted degradation on androgen receptors in prostate cancer cells, and suppress proliferation of the prostate cancer cells, and also show good metabolic stability and pharmacokinetic properties. The compound has good application prospect in preparation of targeted chimeras for protein degradation of androgen receptors and in the preparation of drugs for treating related diseases regulated by the androgen receptors.

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