Tag: M.W=300-400

Hayhow, Thomas G.; Borrows, Rachel E. A.; Diene, Coura R.; Fairley, Gary; Fallan, Charlene; Fillery, Shaun M.; Scott, James S.; Watson, David W. published the artcile< A Buchwald-Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs**>, Safety of Methyl 3-bromo-2-(bromomethyl)benzoate, the main research area is isoindolyl amine preparation; aryl bromide amine Buchwald Hartwig amination palladium catalyst; PEPPSI; PROTAC; amination; cereblon; drug discovery.

A palladium-catalyzed Buchwald-Hartwig amination for lenalidomide-derived aryl bromides was optimized using high throughput experimentation (HTE) to afford isoindolyl amines I [R1 = H, Me; R2 = n-Bu, Ph, 2-MeC6H4, etc.; R1R2 = (CH2)2O(CH2)2, (CH2)2CH(CH2OH)(CH2)2, (CH2)2N(Boc)(CH2)2, etc.]. The substrate scope of the optimized conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodol. allowed access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.

Chemistry – A European Journal published new progress about Amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Safety of Methyl 3-bromo-2-(bromomethyl)benzoate.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Jiang, Xueyang; Zhou, Junting; Wang, Yang; Liu, Xin; Xu, Kaiying; Xu, Jian; Feng, Feng; Sun, Haopeng published the artcile< PROTACs suppression of GSK-3β, a crucial kinase in neurodegenerative diseases>, Category: bromides-buliding-blocks, the main research area is neurodegenerative diseases proteolysis targeting chimera GSK 3beta protein degradation; Glycogen synthase kinase 3β; Neurodegenerative diseases; Proteolysis targeting chimera.

Glycogen synthase kinase 3β (GSK-3β) is involved in a variety of diseases such as neurodegenerative diseases, bipolar disorder, and diabetes. In this study, a series of heterobifunctional small mol. proteolysis targeting chimera (PROTAC) were designed and synthesized based on E3 ubiquitin ligase cereblon (CRBN). Most of PROTACs displayed good inhibitory activity, with the IC50 values at the double-digits nanomolar levels and moderate protein degradation ability against GSK-3β. Western-blot data showed compound PG21(I) can effectively degrade GSK-3β in a dose-dependent manner, which can induce 44.2% protein degradation at 2.8μM. Further pharmacol. experiments revealed that the ability of PG21 to degrade GSK-3β is mediated by the ubiquitin-proteasome system (UPS). In addition, PG21 protects against glutamate-induced cell death in HT-22 cells. As the first PROTAC example to degrade GSK-3β protein, the present study has provided potential candidates for further investigation in the biol. function of GSK-3β protein and its association with diseases.

European Journal of Medicinal Chemistry published new progress about Cereblons Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Category: bromides-buliding-blocks.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Begnini, Fabio; Geschwindner, Stefan; Johansson, Patrik; Wissler, Lisa; Lewis, Richard J.; Danelius, Emma; Luttens, Andreas; Matricon, Pierre; Carlsson, Jens; Lenders, Stijn; Koenig, Beate; Friedel, Anna; Sjoe, Peter; Schiesser, Stefan; Kihlberg, Jan published the artcile< Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1-Nrf2 Protein-Protein Interaction>, Computed Properties of 337536-14-8, the main research area is binding site hydration flexibility Keap1 Nrf2 protein interaction inhibitor.

Upregulation of the transcription factor Nrf2 by inhibition of the interaction with its neg. regulator Keap1 constitutes an opportunity for the treatment of disease caused by oxidative stress. We report a structurally unique series of nanomolar Keap1 inhibitors obtained from a natural product-derived macrocyclic lead. Initial exploration of the structure-activity relationship of the lead, followed by structure-guided optimization, resulted in a 100-fold improvement in inhibitory potency. The macrocyclic core of the nanomolar inhibitors positions three pharmacophore units for productive interactions with key residues of Keap1, including R415, R483, and Y572. Ligand optimization resulted in the displacement of a coordinated water mol. from the Keap1 binding site and a significantly altered thermodn. profile. In addition, minor reorganizations of R415 and R483 were accompanied by major differences in affinity between ligands. This study therefore indicates the importance of accounting both for the hydration and flexibility of the Keap1 binding site when designing high-affinity ligands.

Journal of Medicinal Chemistry published new progress about Biological permeation. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Computed Properties of 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Satz, Alexander Lee; Cai, Jianping; Chen, Yi; Goodnow, Robert; Gruber, Felix; Kowalczyk, Agnieszka; Petersen, Ann; Naderi-Oboodi, Goli; Orzechowski, Lucja; Strebel, Quentin published the artcile< DNA Compatible Multistep Synthesis and Applications to DNA Encoded Libraries>, Recommanded Product: Methyl 3-bromo-2-(bromomethyl)benzoate, the main research area is nitrogen heterocyclic DNA encoded library synthesis high throughput sequencing.

Complex mixtures of DNA encoded small mols. may be readily interrogated via high-throughput sequencing. These DNA encoded libraries (DELs) are commonly used to discover mols. that interact with pharmaceutically relevant proteins. The chem. diversity displayed by the library is key to successful discovery of potent, novel, and drug-like chem. matter. The small mol. moieties of DELs are generally synthesized though a multistep process, and each chem. step is accomplished while it is simultaneously attached to an encoding DNA oligomer. Hence, library chem. diversity is often limited to DNA compatible synthetic reactions. Herein, protocols for 24 reactions are provided that have been optimized for high-throughput production of DELs. These protocols detail the multistep synthesis of benzimidazoles, imidazolidinones, quinazolinones, isoindolinones, thiazoles, and imidazopyridines. Addnl., protocols are provided for a diverse range of useful chem. reactions including BOC deprotection (under pH neutral conditions), carbamylation, and Sonogashira coupling. Last, step-by-step protocols for synthesizing functionalized DELs from trichloronitropyrimidine and trichloropyrimidine scaffolds are detailed.

Bioconjugate Chemistry published new progress about Benzimidazoles Role: SPN (Synthetic Preparation), PREP (Preparation). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Recommanded Product: Methyl 3-bromo-2-(bromomethyl)benzoate.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Choi, Young Lok; Kim, Joa Kyum; Choi, Sang-Un; Min, Yong-Ki; Bae, Myung-Ae; Kim, Bum Tae; Heo, Jung-Nyoung published the artcile< Synthesis of aristolactam analogues and evaluation of their antitumor activity>, Category: bromides-buliding-blocks, the main research area is aristolactam analog library preparation antitumor.

A series of natural aristolactams and their analogs have been prepared and evaluated for antitumor activity against human cancer cells, including multi-drug resistant cell lines. Naturally occurring aristolactams, such as aristolactam BII (cepharanone B), aristolactam BIII, aristolactam FI (piperolactam A), N-Me piperolactam A, and sauristolactam showed moderate antitumor activities in selected cell lines. However, several synthetic aristolactam derivatives (e.g. I) exhibited potent antitumor activities against a broad array of cancer cell lines with GI50 values in the submicromolar range.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Category: bromides-buliding-blocks.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhang, Jingyu; Che, Jinxin; Luo, Xiaomin; Wu, Mingfei; Kan, Weijuan; Jin, Yuheng; Wang, Hanlin; Pang, Ao; Li, Cong; Huang, Wenhai; Zeng, Shenxin; Zhuang, Weihao; Wu, Yizhe; Xu, Yongjin; Zhou, Yubo; Li, Jia; Dong, Xiaowu published the artcile< Structural Feature Analyzation Strategies toward Discovery of Orally Bioavailable PROTACs of Bruton's Tyrosine Kinase for the Treatment of Lymphoma>, Computed Properties of 337536-14-8, the main research area is lymphoma BTR inhibitor PROTACs orally bioavailable.

Bruton’s tyrosine kinase proteolysis-targeting chimeras (BTK-PROTACs) have emerged as a promising approach to address the limitations of BTK inhibitors. However, conducting the rational discovery of orally bioavailable BTK-PROTACs presents significant challenges. In this study, dimensionality reduction anal. and model mol. validation were utilized to identify some key structural features for improving the oral absorption of BTK-PROTACs. The results were applied to optimize the newly discovered BTK-PROTACs B1 and B2. Compound C13 (I) was discovered with improved oral bioavailability, high BTK degradation activity, and selectivity. It exhibited inhibitory effects against different hematol. cancer cells and attenuated the BTK-related signaling pathway. The oral administration of C13 effectively reduced BTK protein levels and suppressed tumor growth. This study led to the discovery of a new orally bioavailable BTK-PROTAC for the treatment of lymphoma, and we hope that the strategy will find wide utility.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Computed Properties of 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Kraszewski, Karol; Tomczyk, Ireneusz; Drabinska, Aneta; Bienkowski, Krzysztof; Solarska, Renata; Kalek, Marcin published the artcile< Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for a Radical-Chain Pathway>, Synthetic Route of 1530-33-2, the main research area is phenol iodine oxidative dearomatization kinetics mechanism; hypervalent iodine; mechanistic investigations; phenol dearomatization; radical-chain pathway; synthetic methods.

The oxidative dearomatization of phenols with the addition of nucleophiles to the aromatic ring induced by hypervalent iodine(III) reagents and catalysts has emerged as a highly useful synthetic approach. However, exptl. mechanistic studies of this important process have been extremely scarce. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of exptl. techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that the transformation proceeds by a radical-chain mechanism, with a phenoxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the phenoxyl radical, the water mol. becomes activated by the interaction with the iodine(III) center, causing the Umpolung of this formally nucleophilic substrate. The radical-chain mechanism allows the rationalization of all existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.

Chemistry – A European Journal published new progress about Activation entropy. 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Synthetic Route of 1530-33-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Ning, Shulin; Zheng, Lianyou; Bai, Ya; Wang, Shutao; Wang, Siyu; Shi, Lingling; Gao, Qiansong; Che, Xin; Zhang, Zhuoqi; Xiang, Jinbao published the artcile< Highly selective electroreductive linear dimerization of electron-deficient vinylarenes>, Formula: C21H22BrP, the main research area is diaryl butane preparation; vinylarene preparation regioselective electroreductive dimerization.

A direct electroreductive dimerization of electron-deficient vinylarenes R1R2C:CR3R4 (R1 = Ph, 4-NCC6H4, pyridin-4-yl, etc., R2 = R3 = R4 = H; R1 = 4-EtO2CC6H4, R2 = Me, Ph, R3 = R4 = H; R1 = 4-MeO2CC6H4, R2 = H, R3 = Me, R4 = H, Me; etc.) for the synthesis of 1,4-diarylbutanes R1R2CH-CR3R4-CR3R4-CHR1R2 as been developed using a simple undivided cell with inexpensive carbon electrodes at room temperature The control and deuterium-labeling experiments of electroreductive dimerization suggest that the hydrogen source comes from the solvent CH3CN. This protocol provides a mild and efficient route for the construction of C-C bond in moderate to good yields with high regioselectivity and broad substrate scope.

Tetrahedron published new progress about Alkylarenes Role: SPN (Synthetic Preparation), PREP (Preparation). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Formula: C21H22BrP.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Tyler, Jasper L.; Noble, Adam; Aggarwal, Varinder K. published the artcile< Strain-Release-Driven Friedel-Crafts Spirocyclization of Azabicyclo[1.1.0]butanes>, Recommanded Product: Isopropyltriphenylphosphonium bromide, the main research area is tertiary butoxy carbonyl azetidino spiro tetralin preparation regioselective DFT; alkylazetidine preparation Friedel Crafts spirocyclization tetrafluoroboric acid etherate catalyst; azabicyclobutane carbinol preparation alkyl halide alkylation; azabicylo[1.1.0]butanes; azetidines; dearomatization; spiro compounds; strained molecules.

The strain-release-driven Friedel-Crafts spirocyclization of azabicyclo[1.1.0]butane-tethered (hetero)aryls I (R = H, Me, Bn, allyl, triethylsilyl; R1 = Ph, 2-naphthyl, benzothiophen-2-yl, etc.) for the synthesis of a unique library of azetidine spiro-tetralins e.g., II was reported. The reaction was discovered to proceed through an unexpected interrupted Friedel-Crafts mechanism, generating a highly complex azabicyclo[2.1.1]hexane scaffold. This dearomatized intermediate, formed exclusively as a single diastereomer, can be subsequently converted to the Friedel-Crafts product upon electrophilic activation of the tertiary amine, or trapped as a Diels-Alder adduct in one-pot. The rapid assembly of mol. complexity demonstrated in these reactions highlights the potential of the strain-release-driven spirocyclization strategy to be utilized in the synthesis of medicinally relevant scaffolds.

Angewandte Chemie, International Edition published new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Recommanded Product: Isopropyltriphenylphosphonium bromide.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Jagot, Fatema; Ntsimango, Songeziwe; Ngwira, Kennedy J.; Fernandes, Manuel A.; de Koning, Charles B. published the artcile< Synthesis of Angucycline/Tetrangulol Derivatives Using Suzuki-Miyaura Cross-Coupling and Ring-Closing Carbonyl-Olefin Metathesis Reactions>, Electric Literature of 1530-33-2, the main research area is angucycline tetrangulol preparation.

Key steps in the synthesis of derivatives of the angucycline, tetrangulol include the use of a palladium catalyzed Suzuki-Miyaura cross-coupling reaction for the assembly of I from 2-iodo-3-methoxy-5-methylbenzaldehyde and II. The biaryl product I was then subjected to an iron-catalyzed ring-closing carbonyl-olefin metathesis reaction to afford 1,7,12-trimethoxy-3-methyltetraphene, which was oxidized to the corresponding quinone III. Late stage oxidation of the quinone III with Ru[Cl2(p-cymene)]2 and an oxidant unexpectedly afforded the chlorinated compounds IV (R = H, OH).

European Journal of Organic Chemistry published new progress about Anthracyclines Role: SPN (Synthetic Preparation), PREP (Preparation). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Electric Literature of 1530-33-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary