Category: 337536-14-8

Lawson, Edward C.; Luci, Diane K.; Ghosh, Shyamali; Kinney, William A.; Reynolds, Charles H.; Qi, Jenson; Smith, Charles E.; Wang, Yuanping; Minor, Lisa K.; Haertlein, Barbara J.; Parry, Tom J.; Damiano, Bruce P.; Maryanoff, Bruce E. published the artcile< Nonpeptide Urotensin-II Receptor Antagonists: A New Ligand Class Based on Piperazino-Phthalimide and Piperazino-Isoindolinone Subunits>, Recommanded Product: Methyl 3-bromo-2-(bromomethyl)benzoate, the main research area is urotensin receptor antagonist preparation structure activity piperazino phthalimide isoindolinone.

We have discovered two related chem. series of nonpeptide urotensin-II (U-II) receptor antagonists based on piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. One of the antagonists exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. In advanced pharmacol. testing, one of the antagonists blocked the effects of U-II in vitro in a rat aortic ring assay and in vivo in a rat ear-flush model. A discussion of U-II receptor antagonist pharmacophores is presented, and a specifically defined model is suggested from tricycle compound, which has a high degree of conformational constraint.

Journal of Medicinal Chemistry published new progress about Biological ion transport, calcium. 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

Curtin, Michael L.; Frey, Robin R.; Heyman, H. Robin; Sarris, Kathy A.; Steinman, Douglas H.; Holmes, James H.; Bousquet, Peter F.; Cunha, George A.; Moskey, Maria D.; Ahmed, Asma A.; Pease, Lori J.; Glaser, Keith B.; Stewart, Kent D.; Davidsen, Steven K.; Michaelides, Michael R. published the artcile< Isoindolinone ureas: a novel class of KDR kinase inhibitors>, Product Details of C9H8Br2O2, the main research area is isoindolinone urea preparation KDR kinase inhibitor.

A series of substituted isoindolinone ureas was prepared and evaluated for enzymic and cellular inhibition of KDR kinase activity. Several of these analogs, such as I, are potent inhibitors of KDR both enzymically (<50 nM) and cellularly (≤100 nM). A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site. Bioorganic & Medicinal Chemistry Letters published new progress about Homo sapiens. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Product Details of C9H8Br2O2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Chen, Dake; Berhane, Ilyas A.; Chemler, Sherry R. published the artcile< Copper-Catalyzed Enantioselective Hydroalkoxylation of Alkenols for the Synthesis of Cyclic Ethers>, Name: Methyl 3-bromo-2-(bromomethyl)benzoate, the main research area is THF phthalan isochroman morpholine enantioselective preparation; copper catalyst enantioselective intramol hydroalkoxylation alkenol.

In the presence of Cu(OTf)2 and a nonracemic bis(oxazoline), terminal and 1,1-disubstituted and 1,2-disubstituted alkenols such as I underwent enantioselective intramol. hydroalkoxylation with 1,4-cyclohexadiene as a reducing agent and either MnO2 or Ag2CO3 as oxidant in PhCF3 to yield nonracemic cyclic ethers such as II. Tetrahydrofurans, phthalans, isochromans, and morpholines were prepared from 4- and 5-alkenols using this method; the substrate scope is complementary to existing enantioselective alkene hydroalkoxylations and is broad with respect to substrate backbone and alkene substitution. The method was used for an enantioselective preparation of the antifungal insecticide furametpyr. A polar/radical mechanism involving enantioselective oxycupration followed by homolysis of the copper-carbon bond and hydrogen atom transfer is proposed.

Organic Letters published new progress about Alkenyl alcohols 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, Name: Methyl 3-bromo-2-(bromomethyl)benzoate.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Yakovenko, Georgiy G.; Yagodkina, Marta S.; Bol’but, Andriy V.; Shishkina, Svitlana V.; Vovk, Mykhailo V. published the artcile< Synthesis of new triazolo[1,5-b][2,4]benzodiazepines via tandem cyclization of o-(azidomethyl)benzoates with cyanoacetamides>, Electric Literature of 337536-14-8, the main research area is crystal mol structure bromo methylpiperazine benzo triazole diazepinone; tandem cyclization azidomethy benzoate cyanoacetamide; triazolo benzodiazepine preparation tandem cyclization.

Based on the tandem anionic cyclization of o-(azidomethyl)benzoates with 2-cyanoacetamides, an efficient synthetic route to the hitherto unknown heterocyclic system, triazolo[1,5-b][2,4]benzodiazepine, has been developed. The optimum reaction conditions have been found which provide 59-74% yields of target compounds Their structural determination has been performed by the IR, LCMS, and NMR spectral methods as well as by X-ray diffraction anal.

Monatshefte fuer Chemie published new progress about Active methylene compounds Role: RCT (Reactant), RACT (Reactant or Reagent). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Electric Literature of 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

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

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

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

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