Shanghaitech University

Chinese Academy of Sciences

Dupont Pharmaceuticals Company

Zhongke Yigong (xiamen) Chemical Technology Co., Ltd.

Zhongke Yigong (shanghai) Chemical Technology Co., Ltd.

Shanghai Cas Advanced Research Institute

Ratiopharm Gmbh

Biao Jiang

Ning Sun

Ying Kong

Chaowei Ren

Xiaobao Yang

Jinju Chen

Yan Li

Xiaoling Song

Xing Qiu

Jia Cheng Liu

Jinguang Zhong

Renhong Sun

Qianqian Yin

Quanju Zhao

Guang Yang

Philip Ma

Yunqi Liu

Daoben Zhu

Yuedong Zhou

Peixiang Ma

Linyi Liu

Yugui Si

Hongxiang Li

Chong-an Di

Xike Gao

Haifan Lin

Jianshui Zhang

Xiao-Long Zhao

Wan-Jun Sioc-Shanghai Institute Of Organic Chemistry Wang

Jia-Jia Dong

A compound of general formula (I), a compound of general formula (III) and anti-tumor applications thereof. A series of compounds designed and synthesized have a wide range of pharmacological activities, have the function of degrading specific proteins and/or inhibiting activity, and can be used in related tumor and cancer treatments.

ALK protein regulator and anti-tumor application thereof

The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.

Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates

A compound of formula (I) and its antitumor application are disclosed. The compounds of formula (I) have degradation and inhibitory effects on ALK target proteins. They are mainly composed of four parts: the first part, ALK-TKI, being compounds with ALK tyrosine kinase inhibitory activity; the second part, LIN, being different kinds of linker (Linker); the third part, the ULM, being a small molecule ligand (ULM, ubiquitin ligase binding moiety) with ubiquitination of VHL, CRBN or other proteases; and the fourth part, the group A, being a carbonyl group or absent, which covalently bond ALK-TKI to LIN, wherein LIN and ULM are covalently bonded. A series of compounds designed and synthesized by the present disclosure have wide pharmacological activities, have functions of degrading ALK protein and inhibiting ALK activity, and can be used for related tumor treatment.

ALK protein degradation agent and anti-tumor application thereof

Provided are chimeric polypeptides that include one or more zinc finger motifs fused to a therapeutic peptide such as botulinum neurotoxins (BoNTs). The zinc finger motif may be located at the C-terminal side of the BoNT and the chimeric polypeptide can optionally include two or more such zinc finger motifs. It said the disclosed chimeric polypeptides can be efficiently delivered to a subject transdermally.

Topical compositions and uses

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor. 

Compounds targeting and degrading BCR-ABL protein and its antitumor application

Provided are amino acid sequences capable of binding to and inhibiting a Cas protein's ability to bind to a nucleic acid molecule, thereby inhibiting the Cas protein's function in genome editing. Such Cas protein inhibitors, which can be comprised of a major coat protein (G8P), an extracellular region of the G8P (G8P), or a biological equivalent, are useful in improving the specificity of Cas protein-based genome editing procedures.

Composition and use of Cas protein inhibitors

Provided is a method for preparing vinyl chloride with acetylene and dichlorethane for large-scale industrial production. Acetylene, dichlorethane vapor and hydrogen chloride gas at a molar ratio of 1:(0.3-1.0):(0-0.20) are mixed; the raw mixed gas is preheated; the preheated raw mixed gas passes through a reactor containing a catalyst and reacts; the resultant mixed gas is cooled to 30-50&#xb0; C. and pressurized to 0.4-1.0 MPa, and then cooled to ambient temperature, and further frozen to &#x2212;25-15&#xb0; C. for liquefaction isolation, and unliquefied gas is recycled and reused; liquefied liquid is sent to a rectifying tower for rectification, and vinyl chloride monomers meeting polymerization requirements are obtained. The present invention has the advantages of eliminating mercury contamination completely, simplifying the reactor structure, recycling hydrogen chloride and acetylene, reducing waterwash process, avoiding mass production of waste acid and improving utilization of chlorine.

Method for preparing vinyl chloride from acetylene and dichlorethane

The present invention discloses a catalyst used in preparing vinyl chloride, its method of preparation, and its applications. Said catalyst used in making vinyl chloride comprises activated carbon as a support, a barium compound and a phosphorus compound supported thereon. The barium compound accounts for 0.2% to 20% of the total mass of the catalyst and the phosphorus compound accounts for 0% to 10% of the total mass of the catalyst based on the mass percentage. A water-soluble barium compound, a water-soluble phosphorus compound, an aqueous polymer monomer, and water are mixed to form a solution or emulsion A. The activated carbon is added into the solution or emulsion A. The activated carbon is removed from water after impregnation, spin-dried, and then the monomers are polymerized. The activated carbon, after polymerization step, is heated to remove water and to decompose and carbonize the polymer. The catalyst after carbonization was activated to obtain a catalyst used in making vinyl chloride.

Catalyst for preparing vinyl chloride, methods of preparation and application thereof

Sulfur containing heterocycle-fused naphthalenetetracarboxylic acid diimide derivatives represented by formula (I) are disclosed, in which, Rand Rare C-Cand C-Clinear alkyl or branched alkyl, respectively; Ris H or halogen atom. The preparation method of the derivatives and the use thereof in manufacture of organic thin film field effect transistor or organic solar batteries are also disclosed.

Sulfur containing heterocycle-fused naphthalene tetracarboxylic acid diimide derivatives, preparation method and use thereof

The invention disclosed a new process of asymmetric alkynylation of ketone or ketimine, involving the chiral ligand-mediated asymmetric addition of zinc or copper acetylide to a trifluoromethyl ketone or ketimine intermediate to give a chiral tertiary proparglic alcohols or amines. The adduct compounds include the key precursors to the potent HIV reverse transcriptase inhibitor Efavirenz (DMP 266), DPC 961 and DPC 083. The invention also disclosed a novel chiral amino alcohol ligand.

Amino alcohol ligand and its use in preparation of chiral proparglic tertiary alcohols and tertiary amines via enantioselective addition reaction

A novel process for making compounds of Formula I, ##STR1## wherein X is a leaving group selected from the group Br, Cl, TsO, MsO, and TfO and R is a 1,2-diol, from a compound of Formula II: ##STR2## is described.

Method for preparing .alpha.-chloroboronic acids from mannitol

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