Tag: 200-300

The author of 《Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression》 were Li, Yangbing; Yang, Jiuling; Aguilar, Angelo; McEachern, Donna; Przybranowski, Sally; Liu, Liu; Yang, Chao-Yie; Wang, Mi; Han, Xin; Wang, Shaomeng. And the article was published in Journal of Medicinal Chemistry in 2019. Recommanded Product: tert-Butyl (5-aminopentyl)carbamate The author mentioned the following in the article:

Human murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53 and has been pursued as an attractive cancer therapeutic target. Several potent, nonpeptide, small-mol. inhibitors of MDM2 are currently in clin. development. In this paper, we report our design, synthesis, and evaluation of small-mol. MDM2 degraders based on the proteolysis targeting chimera (PROTAC) concept. The most promising compound (MD-224, I) effectively induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells. It achieves an IC50 value of 1.5 nM in inhibition of growth of RS4;11 cells and also low nanomolar IC50 values in a panel of leukemia cell lines. MD-224 (I) achieves complete and durable tumor regression in vivo in the RS4;11 xenograft tumor model in mice at well-tolerated dose schedules. MD-224 (I) is thus a highly potent and efficacious MDM2 degrader and warrants extensive evaluations as a new class of anticancer agent. In the experiment, the researchers used tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3Recommanded Product: tert-Butyl (5-aminopentyl)carbamate)

Some of the reported applications of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3) include: synthesis of of a supermacrocycle that self-assemble to form organic nanotubes., preparation of water-soluble unsymmetrical sulforhodamine fluorophores from monobrominated sulfoxanthene dye, synthesis of functionalized porphyrins as biocompatible carrier system for photodynamic therapy (PDT).Recommanded Product: tert-Butyl (5-aminopentyl)carbamate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

The author of 《Discovery of a Potent Kelch-Like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Protein-Protein Interaction Inhibitor with Natural Proline Structure as a Cytoprotective Agent against Acetaminophen-Induced Hepatotoxicity》 were Lu, Meng-Chen; Zhang, Xian; Wu, Feng; Tan, Shi-Jie; Zhao, Jing; You, Qi-Dong; Jiang, Zheng-Yu. And the article was published in Journal of Medicinal Chemistry in 2019. Recommanded Product: H-Trp-OMe.HCl The author mentioned the following in the article:

The transcription factor Nrf2 is a key regulator of cytoprotective system, and enhancing Nrf2 activity can protect cells from various insults and threats. Directly disrupting Keap1-Nrf2 protein-protein interactions has been regarded as a promising way to activate Nrf2. We reported here the first identification of amino acids as preferred substituents to design potent Keap1-Nrf2 inhibitors. Comprehensive structure-activity anal. identified Pro as a preferred substituent, obtaining a potent inhibitor 35 with an IC50 of 43 nM in the competitive fluoresce polarization (FP) assay and a Kd value of 53.7 nM for Keap1 protein in the isothermal titration calorimetry (ITC) assay. The Pro analog 35 exhibited tight and prolonged Keap1 binding in vitro and in cells, and treatment with 35 activated Nrf2-regulated cytoprotective response and antagonized acetaminophen-induced liver injury both in cellular and in vivo models. This work not only provides a useful tool to further explore the therapeutic potential of Keap1-Nrf2 inhibition but also enriches the diversity of chem. structures suitable for the Keap1-Nrf2 interface. After reading the article, we found that the author used H-Trp-OMe.HCl(cas: 7524-52-9Recommanded Product: H-Trp-OMe.HCl)

H-Trp-OMe.HCl(cas:7524-52-9) is one of amino acid derivatives. Amino acid derivatives represent an important category of skin penetration promoters. These compounds possess hydrophobic chains attached to an amino acid headgroup via a biodegradable ester bond. Due to the amphiphilic nature of these derivatives, it is possible for them to enter into the SC lipid barrier and significantly disorganize skin membrane lipids.Recommanded Product: H-Trp-OMe.HCl

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

The author of 《Biomimetic Enantioselective Total Synthesis of (-)-Robustanoids A and B and Analogues》 were Liu, Zhan-Jiang; Huang, Pei-Qiang. And the article was published in Journal of Organic Chemistry in 2019. Safety of H-Trp-OMe.HCl The author mentioned the following in the article:

We report a step-economical, enantioselective total synthesis of (-)-robustanoid B, I (R = MeO), and (-)-robustanoid A, I (R = OH), and four novel natural product-like compounds Our strategy relied on our biosynthetic hypothesis and on a novel complexity generation methodol., namely, the one-pot hydroxylative double cyclization reaction. The latter consists of a modified 3,3-dimethyldioxirane-triggered epoxidation-epoxide-ring-opening cyclization reaction cascade and Trost’s regioselectivity umpolung methodol. (“”anti-Michael addition””). In the experiment, the researchers used many compounds, for example, H-Trp-OMe.HCl(cas: 7524-52-9Safety of H-Trp-OMe.HCl)

H-Trp-OMe.HCl(cas:7524-52-9) is one of amino acid derivatives. Amino acid derivatives represent an important category of skin penetration promoters. These compounds possess hydrophobic chains attached to an amino acid headgroup via a biodegradable ester bond. Due to the amphiphilic nature of these derivatives, it is possible for them to enter into the SC lipid barrier and significantly disorganize skin membrane lipids.Safety of H-Trp-OMe.HCl

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

In 2019,ACS Medicinal Chemistry Letters included an article by Peng, Lijie; Zhang, Zhensheng; Lei, Chong; Li, Shan; Zhang, Zhang; Ren, Xiaomei; Chang, Yu; Zhang, Yan; Xu, Yong; Ding, Ke. Recommanded Product: 51644-96-3. The article was titled 《Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation》. The information in the text is summarized as follows:

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 I 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 I could be utilized as a new powerful research tool for further biol. investigation of ERRα. The results came from multiple reactions, including the reaction of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3Recommanded Product: 51644-96-3)

Some of the reported applications of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3) include: synthesis of of a supermacrocycle that self-assemble to form organic nanotubes., preparation of water-soluble unsymmetrical sulforhodamine fluorophores from monobrominated sulfoxanthene dye, synthesis of functionalized porphyrins as biocompatible carrier system for photodynamic therapy (PDT).Recommanded Product: 51644-96-3

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Product Details of 51644-96-3In 2020 ,《Discovery of novel small molecule induced selective degradation of the bromodomain and extra-terminal (BET) bromodomain protein BRD4 and BRD2 with cellular potencies》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Jiang, Fei; Wei, Qingyun; Li, Huili; Li, Hongmei; Cui, Yong; Ma, Yu; Chen, Haifang; Cao, Peng; Lu, Tao; Chen, Yadong. The article conveys some information:

The BET proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation and can be degraded by proteolysis-targeting chimeras (PROTACs) for BET proteins. However, the lack of intra-BET proteins selectivity limits the scope of current degraders as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We describe herein the design, synthesis, and evaluation of PROTAC BET degraders, based on the BET inhibitor with selectivity for the first Bromodomain benzo[cd]indole-2-one, alkylamide linker and cereblon ligand thalidomide. Compound 15 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 and BRD2 over BRD3, which not only effectively inhibits cell growth in human acute leukemia cell lines, but also very effective in inhibiting solid tumors with low cytotoxic effect in the cell profiles of NCI 60 cell lines. Remarkable dependency on linker length was observed for BRD4-degrading and c-Myc-driven antiproliferative activities in acute myeloid leukemia cell line MV4-11. The small-mol. 15 represents a novel, potent, and selective class of BRD4 and BRD2 degraders for the development of therapeutics to treat cancers. The results came from multiple reactions, including the reaction of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3Product Details of 51644-96-3)

Some of the reported applications of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3) include: synthesis of of a supermacrocycle that self-assemble to form organic nanotubes., preparation of water-soluble unsymmetrical sulforhodamine fluorophores from monobrominated sulfoxanthene dye, synthesis of functionalized porphyrins as biocompatible carrier system for photodynamic therapy (PDT).Product Details of 51644-96-3

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Xie, Shaowen; Sun, Yuan; Liu, Yulin; Li, Xinnan; Li, Xinuo; Zhong, Wenyi; Zhan, Feiyan; Zhu, Jingjie; Yao, Hong; Yang, Dong-Hua; Chen, Zhe-Sheng; Xu, Jinyi; Xu, Shengtao published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Development of Alectinib-Based PROTACs as Novel Potent Degraders of Anaplastic Lymphoma Kinase (ALK)》.Computed Properties of C11H24N2O2 The article contains the following contents:

A series of novel anaplastic lymphoma kinase (ALK) degraders were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technol. by linking two alectinib analogs (I and II) with pomalidomide through linkers of different lengths and types. The most promising degrader III possessed a high ALK-binding affinity and potent antiproliferative activity in the ALK-dependent cell lines and did not exhibit obvious cytotoxicity in ALK fusion-neg. cells. More importantly, the efficacy of compound III in a Karpas 299 xenograft mouse model was further evaluated based on its ALK-sustained degradation ability in vivo. The reduction in tumor weight in the compound III-treated group (10 mg/kg/day, I.V.) reached 75.82%, while alectinib reduced tumor weight by 63.82% at a dose of 20 mg/kg/day (P.O.). Taken together, our findings suggest that alectinib-based PROTACs associated with the degradation of ALK may have promising beneficial effects for treating ALK-driven malignancies. The experimental process involved the reaction of N-Boc-1,6-Diaminohexane(cas: 51857-17-1Computed Properties of C11H24N2O2)

N-Boc-1,6-Diaminohexane(cas: 51857-17-1) can be used as a linear hexyl spacer (C6-spacer) to synthesize biodegradable poly(disulfide amine)s for gene delivery, a multifunctional dendrimer for theranostics and so on.Computed Properties of C11H24N2O2

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

《Synthesis and Applications of Cinchona Squaramide-Modified Poly(Glycidyl Methacrylate) Microspheres as Recyclable Polymer-Grafted Enantioselective Organocatalysts》 was written by Nagy, Sandor; Feher, Zsuzsanna; Karpati, Levente; Bagi, Peter; Kisszekelyi, Peter; Koczka, Bela; Huszthy, Peter; Pukanszky, Bela; Kupai, Jozsef. Name: N-Boc-1,6-Diaminohexane And the article was included in Chemistry – A European Journal in 2020. The article conveys some information:

This work presents the immobilization of cinchona squaramide organocatalysts on poly(glycidyl methacrylate) solid supports. Preparation of the well-defined monodisperse polymer microspheres was facilitated by comprehensive parameter optimization. By exploiting the reactive epoxy groups of the polymer support, three amino-functionalized cinchona derivatives I [R = Me, 2-aminoethyl; R1 = Me, 1-((4-(aminomethyl)phenyl)methyl)-1H-1,2,3-triazol-4-yl; R2 = 3,5-bis(trifluoromethyl)phenyl, 6-aminohexyl] were immobilized on this carrier. To explore the effect of the amino linker, these structurally varied precatalysts were synthesized by modifying the cinchona skeleton at different positions. The catalytic activities of the immobilized organocatalysts were tested in the Michael addition of pentane-2,4-dione and trans-β-nitrostyrene with excellent yields (up to 98%) and enantioselectivities (up to 96% ee). Finally, the catalysts were easily recovered five times by centrifugation without loss of activity. In the experiment, the researchers used N-Boc-1,6-Diaminohexane(cas: 51857-17-1Name: N-Boc-1,6-Diaminohexane)

N-Boc-1,6-Diaminohexane(cas: 51857-17-1) is a compound useful in organic synthesis used in the preparation of mixed self-assembled monolayers (SAMs) that resist adsorption of proteins using the reaction of amines with a SAM that presents interchain carboxylic anhydride groupsName: N-Boc-1,6-Diaminohexane

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

《Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach》 was written by Huang, Fubao; Hu, Hangchen; Wang, Kai; Peng, Chengyuan; Xu, Wenwei; Zhang, Yu; Gao, Jing; Liu, Yishen; Zhou, Hu; Huang, Ruimin; Li, Minjun; Shen, Jianhua; Xu, Yechun. Quality Control of tert-Butyl (5-aminopentyl)carbamate And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:

Covalent ligands are of great interest as therapeutic drugs or biochem. tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, resp., compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3Quality Control of tert-Butyl (5-aminopentyl)carbamate)

Some of the reported applications of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3) include: synthesis of of a supermacrocycle that self-assemble to form organic nanotubes., preparation of water-soluble unsymmetrical sulforhodamine fluorophores from monobrominated sulfoxanthene dye, synthesis of functionalized porphyrins as biocompatible carrier system for photodynamic therapy (PDT).Quality Control of tert-Butyl (5-aminopentyl)carbamate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

The author of 《Fluorine-19 NMR spectra of substituted pentafluorobenzenes》 were Pushkina, L. N.; Stepanov, A. P.; Zhukov, V. S.; Naumov, A. D.. And the article was published in Zhurnal Organicheskoi Khimii in 1972. Reference of Ethyl 2,3,4,5,6-pentafluorobenzoate The author mentioned the following in the article:

The value and sign of the meta spin-spin interaction constants in the 19F NMR spectra of 65 C6F5R correlated with the chem. shifts of the resp. F atoms. The experimental part of the paper was very detailed, including the reaction process of Ethyl 2,3,4,5,6-pentafluorobenzoate(cas: 4522-93-4Reference of Ethyl 2,3,4,5,6-pentafluorobenzoate)

Ethyl 2,3,4,5,6-pentafluorobenzoate(cas: 4522-93-4) belongs to esters. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. Reference of Ethyl 2,3,4,5,6-pentafluorobenzoate

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adonin, N. Yu.; Starichenko, V. F. published an article on January 31 ,2000. The article was titled 《Regioselective ortho-hydrodefluorination of pentafluorobenzoic acid by low-valent nickel complexes》, and you may find the article in Journal of Fluorine Chemistry.Quality Control of Ethyl 2,3,4,5,6-pentafluorobenzoate The information in the text is summarized as follows:

2,3,4,5-Tetrafluorobenzoic and 3,4,5-trifluorobenzoic acids were prepared in high yields by reaction of C6F5COOH with zinc in the presence of NiCl2-2′-bipyridine (or 1,10-phenanthroline) complexes. In the experimental materials used by the author, we found Ethyl 2,3,4,5,6-pentafluorobenzoate(cas: 4522-93-4Quality Control of Ethyl 2,3,4,5,6-pentafluorobenzoate)

Ethyl 2,3,4,5,6-pentafluorobenzoate(cas: 4522-93-4) belongs to esters. Esters are more polar than ethers but less polar than alcohols. Quality Control of Ethyl 2,3,4,5,6-pentafluorobenzoate They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics