1643957-24-7

Basic information

• Product Name: Tos-PEG2-CH2CO2tBu
• Synonyms: Tos-PEG2-CH2CO2tBu;tert-Butyl 2-[2-(tosyloxy)ethoxy]acetate
• CAS NO: 1643957-24-7
• Molecular Formula: C15H22O6S
• Molecular Weight: 330.4
• Mol File: 1643957-24-7.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Tos-PEG2-CH2CO2tBu(CAS DataBase Reference)
• NIST Chemistry Reference: Tos-PEG2-CH2CO2tBu(1643957-24-7)
• EPA Substance Registry System: Tos-PEG2-CH2CO2tBu(1643957-24-7)

Safety Data

• Hazardous Substances Data: 1643957-24-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tos-PEG2-CH2CO2tBu is used as a solubility enhancer for improving the aqueous solubility of drugs, which is crucial for their bioavailability and efficacy. The hydrophilic PEG spacer aids in increasing the solubility of hydrophobic drug molecules, allowing for better absorption and distribution within the body.
Used in Chemical Synthesis:
In the field of chemical synthesis, Tos-PEG2-CH2CO2tBu is used as a protecting group for carboxyl groups during the synthesis of complex molecules. The t-butyl ester can be selectively deprotected under acidic conditions, enabling the controlled release of the carboxyl group at the desired stage of the synthesis.
Used in Bioconjugation:
Tos-PEG2-CH2CO2tBu is used as a bioconjugation agent for the attachment of biologically active molecules, such as peptides, proteins, or nucleic acids, to other molecules or surfaces. The tosyl group facilitates nucleophilic substitution reactions, allowing for the efficient coupling of the biologically active molecule to the desired target.
Used in Drug Delivery Systems:
In the development of drug delivery systems, Tos-PEG2-CH2CO2tBu is used as a component in the design of targeted drug carriers. The PEG linker can be functionalized with targeting ligands, while the t-butyl ester and tosyl group can be utilized for the controlled release of the drug payload in response to specific stimuli, such as pH changes or enzymatic activity.
Used in Material Science:
In material science, Tos-PEG2-CH2CO2tBu is used as a building block for the creation of stimuli-responsive materials. The PEG linker can be incorporated into polymers or hydrogels, where the t-butyl ester and tosyl group can be used to introduce responsiveness to environmental triggers, such as temperature, pH, or light.

Upstream product

• 1309451-06-6 2-(2-(benzyloxy)ethoxy)acetic acid tert-butyl ester 
• 5292-43-3 bromoacetic acid tert-butyl ester 
• 98-59-9 p-toluenesulfonyl chloride 
• 287174-32-7 (2-hydroxyethoxy)acetic acid tert-butyl ester 

Downstream Products

• 1155811-37-2 tert-butyl 2-(2-aminoethoxy)acetate 
• 1820717-35-8 2-azidoethoxyacetic acid tert-butyl ester 

Relevant articles and documents

Protection of all cleavable sites of DNA with the multiple CGCG or continuous CGG sites from the restriction enzyme, indicative of simultaneous binding of small ligands

The anthracenone ligands (1–12) with a keto-phenol and a hydroxamic acid unit were synthesized and evaluated by a restriction enzyme inhibition assay. DNA substrates composed of multiple CGCG or CGG sites are fully hydrolyzed by a restriction enzyme that is selective for each sequence. Under such conditions, the full-length DNA substrate remains only when the ligand binds to all binding sites and protects it from hydrolysis by the restriction enzymes. In the assay using AccII and the 50-mer DNA substrates containing a different number of CGCG sites at different non-binding AT base pair intervals, the more the CGCG sites, the more the full-length DNA increased. Namely, simultaneous binding of the ligand (5) to the CGCG sites increased in the order of (CGCG)5>(CGCG)2>(CGCG)1. Furthermore, the length of the spacer of the hydroxamic acid to the anthracenone skeleton played an important role in the preference for the number of the d(A/T) base pairs between the CGCG sites. The long spacer-ligand (5) showed a preference to the CGCG sites with five AT pairs, and the short spacer-ligand (10) to that with two AT pairs. The ligand (12) with the shortest spacer showed a preference in simultaneous binding to the 54-mer DNA composed of 16 continuous CGG sites in the assay using the restriction enzyme Fnu4HI that hydrolyzes the d(GCGGC)/d(CGCCG) site. Application of these ligands to biological systems including the repeat DNA sequence should be of significant interest.

Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.

Protein degradation targeting chimera for degrading androgen receptor

The invention relates to a novel difunctional molecule compound based on VHL ligand induction and application of the difunctional molecule compound in synthesis of the compounds and pharmaceutical compositions thereof. The compound is shown as a formula I. The compound can selectively induce AR protein degradation and can be used for treating cancers such as prostatic cancer and breast cancer.

Oseltamivir PROTAC compound as well as preparation method and application thereof in anti-influenza virus medicines

The invention discloses an oseltamivir PROTAC compound as well as a preparation method and application thereof in anti-influenza virus medicines, and belongs to the technical field of medicines. The oseltamivir PROTAC compound is shown as a general formula (I) or (II), and in the general formula, E3 ligase is a VHL or CRBN ligand, and Linker is a linking group. The compound provided by the invention can effectively degrade influenza virus neuraminidase so as to exert the activity of inhibiting influenza virus replication, not only has inhibitory activity on wild influenza viruses, but also hasa very good inhibitory effect on oseltamivir drug-resistant strains, and has low toxicity to cells. The compound or the pharmacologically or physiologically acceptable salt thereof can be used for preparing anti-influenza virus medicines.

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 1 PROTEINS

The present invention relates to compounds comprising an interleukin-1 receptor-associated kinase 1 (IRAK1) protein binding moiety and a Von Hippel-Lindau (VHL) E3 ubiquitin ligase binding moiety, and associated methods of use. The compounds are useful as modulators of targeted ubiquitination, especially with respect to IRAK1, which is degraded by the compounds according to the invention.

POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES

The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

AMIDE COMPOUND HAVING BET PROTEOLYSIS-INDUCING ACTION AND MEDICINAL APPLICATION THEREOF

The present invention aims to provide a compound that: has an excellent cytotoxic action on cancer cells, excellent induction of BET protein degradation in cancer cells, and an excellent binding-inhibiting action on BET protein and acetylated histone; and is effective as an anti-cancer agent, a BET protein degradation-inducing agent, or a BET protein inhibiting agent. A compound indicated in general formula (I) or a pharmacologically acceptable salt thereof. {In the formula, each symbol is as outlined in the Description.}

Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation

A series of (E)-3-(4-((2,4-bis(trifluoromethyl)benzyl)oxy)-3-methoxyphenyl)-2-cyanoacrylamide derivatives were designed and synthesized as new estrogen-related receptor α (ERRα) degraders based on the proteolysis targeting chimera (PROTAC) concept. One of the representative compounds 6c is capable of specifically degrading ERRα protein by >80% at a relatively low concentration of 30 nM, becoming one of the most potent and selective ERRα degraders to date. Compound 6c could be utilized as a new powerful research tool for further biological investigation of ERRα.

MODULATORS OF ESTROGEN RECEPTOR PROTEOLYSIS AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF THE ANDROGEN RECEPTOR

The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.