5935-29-5

Upstream product

• 106-96-7 propargyl bromide 
• 504-63-2 trimethyleneglycol 
• 18180-30-8 prop-2-ynyloxymethyl-oxirane 
• 775-12-2 diphenylsilane 
• 96-11-7 1,2,3-tribromopropane 
• 488150-84-1 tert-butyl 3-(prop-2-yn-1-yloxy)propanoate 

Downstream Products

• 136196-54-8 4,11-dioxa-6,8-tetradecadiynylene bis(p-toluenesulfonate) 
• 136196-53-7 1,6-bis<3-(3,5-dichlorophenoxy)propoxy>-2,4-hexadiyne 
• 145916-44-5 1-(3,5-dichlorophenoxy)-3-(2-propynyloxy)propane 
• 355150-61-7 (E)-1-Phenylsulfonyl-3-triisopropylsiloxy-5-oxaoct-1-en-7-yne 
• 355150-60-6 (E)-3-Ethoxymethoxy-1-phenylsulfonyl-5-oxaoct-1-en-7-yne 
• 355150-59-3 (E)-1-Phenylsulfonyl-5-oxa-oct-1-en-7-yn-3-ol 
• 145916-42-3 3-(2-propynyloxy)propanol p-toluenesulfonate 

Relevant academic research and scientific papers

Enzyme-like Click Catalysis by a Copper-Containing Single-Chain Nanoparticle

A major challenge in performing reactions in biological systems is the requirement for low substrate concentrations, often in the micromolar range. We report that copper cross-linked single-chain nanoparticles (SCNPs) are able to significantly increase the efficiency of copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions at low substrate concentration in aqueous buffer by promoting substrate binding. Using a fluorogenic click reaction and dye uptake experiments, a structure-activity study is performed with SCNPs of different size and copper content and substrates of varying charge and hydrophobicity. The high catalytic efficiency and selectivity are attributed to a mechanism that involves an enzyme-like substrate binding process. Saturation-transfer difference (STD) NMR spectroscopy, 2D-NOESY NMR, kinetic analyses with varying substrate concentrations, and computational simulations are consistent with a Michaelis-Menten, two-substrate, random-sequential enzyme-like kinetic profile. This general approach may prove useful for developing more-sustainable catalysts and agents for biomedicine and chemical biology.

HSP90-BINDING CONJUGATES AND FORMULATIONS THEREOF

Conjugates of an active agent attached to a targeting moiety, such as an HSP90 binding moiety, via a linker, and formulations comprising such conjugates have been designed. Methods of making and using the conjugates and the formulations thereof are also provided.

Primary Alcohols via Nickel Pentacarboxycyclopentadienyl Diamide Catalyzed Hydrosilylation of Terminal Epoxides

The efficient and regioselective hydrosilylation of epoxides co-catalyzed by a pentacarboxycyclopentadienyl (PCCP) diamide nickel complex and Lewis acid is reported. This method allows for the reductive opening of terminal, monosubstituted epoxides to form unbranched, primary alcohols. A range of substrates including both terminal and nonterminal epoxides are shown to work, and a mechanistic rationale is provided. This work represents the first use of a PCCP derivative as a ligand for transition-metal catalysis.

IRAK DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

The design, synthesis and anti-tumor mechanism study of new androgen receptor degrader

Targeted protein degradation using small molecules is a novel strategy for drug development. In order to solve the problem of drug resistance in the treatment of prostate cancer, proteolysis-targeting chimeras (PROTAC) was introduced into the design of anti-prostate cancer derivatives. In this work, we synthesized two series of selective androgen receptor degraders (SARDs) containing the hydrophobic degrons with different linker, and then investigated the structure-activity relationships of these hybrid compounds. Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Among them, compound A9 displayed potent inhibitory activity against LNCaP prostate cancer cell line with IC50 values of 1.75 μM, as well as excellent AR degradation activity. Primary mechanism studies elucidated compound A9 arrested cell cycle at G0/G1 phase and induced a mild apoptotic response in LNCaP cells. Further study indicated that the degradation of AR was mediated through proteasome-mediated process. For all these reasons, compound A9 held promising potential as anti-proliferative agent for the development of highly efficient SARDs for drug-resistance prostate cancer therapies.

Flavone derivative for treating tumor and application thereof

The invention provides a flavone derivative represented by a formula I and pharmaceutically acceptable salt, hydrate or solvate thereof. In the formula I, R1 H, is 1-4 alkyl, amino or C1-4 acyl; R2 isisopentenyl or 2-hydroxy isopentyl; R3 is H, methyl or deuterated methyl; R4 represents C1-4 alkyl, amino or C1-4 acyl or R5 represents monosaccharide residue or oligosaccharide residue; and L represents polypeptide, C1-C20 straight chain alkyl or derivative thereof, C1-C20 straight chain or branched chain acyl derivative, C1-C20 ethylene glycol or derivative thereof, wherein Y is an integer of 0to 100, b is an integer of 1 to 100, C is an integer of 1 to 10, d is an integer of 0 to 100, and e is an integer of 0 to 100. The flavone derivative has high-efficiency broad-spectrum anticancer activity.

Octahydrocyclopenta[c]pyridine and octahydrocyclopenta[c]pyran analogues as a protease activated receptor 1 (PAR1) antagonist

Protease activated receptor 1 (PAR1) has been considered as a promising antiplatelet target to prevent thrombotic cardiovascular events in patients with prior myocardial infarction or peripheral arterial diseases. Previously, we found a series of octahydroindene analogues to have high potency on PAR1 and no significant cytotoxicity but poor metabolic stability in human and rat liver microsomes. We have designed and synthesized fused 6/5 heterobicycle analogues with octahydrocyclopenta[c]pyridine or octahydrocyclopenta[c]pyran core scaffold by the insertion of heteroatom at C5 of octahydroindene ring aiming to improvement of metabolic stability. Both heterobicycle analogues showed much more improved metabolic stability compared with octahydroindenes without remarkable decrease in activity. Compounds 22 (IC50 = 110 nM) and 33 (IC50 = 50 nM) from this series showed good activity on PAR1 with moderate metabolic stability.

MACROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS FOR THE TREATMENT OF INFLAMMATORY DISEASES

Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R4/s

Mimicking biological membranes with programmable glycan ligands self-assembled from amphiphilic Janus glycodendrimers

An accelerated modular synthesis produced 18 amphiphilic Janus glycodendrimers with three different topologies formed from either two or one carbohydrate head groups or a mixed constellation with a noncarbohydrate hydrophilic arm. By simple injection of their THF solutions into water or buffer, all of the Janus compounds self-assembled into uniform, stable, and soft unilamellar vesicles, denoted glycodendrimersomes. The mixed constellation topology glycodendrimersomes were demonstrated to be most efficient in binding plant, bacterial, and human lectins. This evidence with biomedically relevant receptors offers a promising perspective for the application of such glycodendrimersomes in targeted drug delivery, vaccines, and other areas of nanomedicine.

[6+5] FUSED BICYCLES AS A THROMBIN ANTAGONIST, PROCESS FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE BICYCLES

The present invention relates to the new [6+5] fused bicycle derivatives, pharmaceutically acceptable salts or isomers thereof, processes for preparing the same, and pharmaceutical compositions comprising the same. The [6+5] fused bicycle derivatives can antagonize the thrombin receptor and thus may be effectively used for the treatment and prevention of thrombus, platelet aggregation, atherosclerosis, restenosis, blood coagulation, hypertension, arrhythmia, angina pectoris, heart failure, inflammation and cancer when used alone or with other cardiovascular agents.