Abstract: Disclosed herein are compounds of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6). These compounds are useful in methods for the targeted degradation of CDK4 and/or CDK6 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK4 and/or CDK6 which can be utilized in the treatment of disorders modulated by CDK4 and/or CDK6.

Abstract: The present disclosure relates to bifunctional compounds that serve as degraders (and/or inhibitors) of Bruton's tyrosine kinase (BTK). In the present disclosure, the bifunctional compounds, which contain a target protein (BTK) binding moiety and a E3 ubiquitin ligase (CRBN) binding moiety, are directed to bind to both the BTK and CRBN, such that the BTK is placed in close proximity to the E3 ligase to mediate ubiquitylation of the target protein followed by degradation of the target protein by the proteasome. The present disclosure provides methods for synthesizing the herein disclosed bifunctional compounds, and their pharmacological activities associated with degradation or inhibition of the target protein.

Abstract: The present disclosure relates to bifunctional compounds that serve as degraders (and/or inhibitors) of the estrogen receptor (target protein). In the present disclosure, the bifunctional compounds, which contain a target protein (estrogen receptor) binding moiety and a E3 ubiquitin ligase (CRBN) binding moiety, are directed to bind to both estrogen receptor and CRBN, such that the ER is placed in close proximity to the E3 ligase to mediate ubiquitylation of the target protein followed by degradation of the target protein by the proteasome. The present disclosure provides methods for synthesizing the herein disclosed bifunctional compounds, and their pharmacological activities associated with degradation or inhibition of the target protein. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases, including cancer, particularly breast cancer, and especially ER+ breast cancer.

Abstract: Disclosed is a method for preparing optically pure (+)-ambrisentan and (+)-darusentan, comprising: firstly catalyzing the asymmetric epoxidation of a ?-unsaturated alkene using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to an epoxy compound ring-opening reaction and substitution reaction successively to obtain optically pure (+)-ambrisentan and (+)-darusentan.

Abstract: Disclosed in the present invention is a method for preparing a (?)-clausenamide compound of formula (I), comprising: firstly, catalyzing the asymmetrical epoxidation of trans-cinnamate using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to amidation, oxidation, cyclization and reduction successively to finally obtain the optically pure (?)-clausenamide compound of formula (I).

Abstract: Disclosed is a method for preparing optically pure (+)-ambrisentan and (+)-darusentan, comprising: firstly catalyzing the asymmetric epoxidation of a ?-unsaturated alkene using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to an epoxy compound ring-opening reaction and substitution reaction successively to obtain optically pure (+)-ambrisentan and (+)-darusentan.

Abstract: Disclosed in the present invention is a method for preparing a (?)-clausenamide compound of formula (I), comprising: firstly, catalyzing the asymmetrical epoxidation of trans-cinnamate using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to transesterification, oxidation, cyclization and reduction successively to finally obtain the optically pure (?)-clausenamide compound of formula (I).