Tag: M.W=300-400

Zhou, Bing; Hu, Jiantao; Xu, Fuming; Chen, Zhuo; Bai, Longchuan; Fernandez-Salas, Ester; Lin, Mei; Liu, Liu; Yang, Chao-Yie; Zhao, Yujun; McEachern, Donna; Przybranowski, Sally; Wen, Bo; Sun, Duxin; Wang, Shaomeng published the artcile< Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression>, SDS of cas: 337536-14-8, the main research area is preparation degrader bromodomain extra terminal protein cancer.

The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic “”readers”” and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-mol. BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders. One of the most promising compounds, 23, effectively degrades BRD4 protein at concentrations as low as 30 pM in the RS4;11 leukemia cell line, achieves an IC50 value of 51 pM in inhibition of RS4;11 cell growth and induces rapid tumor regression in vivo against RS4;11 xenograft tumors. These data establish that compound 23 (BETd-260/ZBC260) is a highly potent and efficacious BET degrader.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, SDS of cas: 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Brandstatter, Marco; Huwyler, Nikolas; Carreira, Erick M. published the artcile< Gold(I)-catalyzed stereoselective cyclization of 1,3-enyne aldehydes by a 1,3-acyloxy migration/Nazarov cyclization/aldol addition cascade>, COA of Formula: C21H22BrP, the main research area is bicyclooctenone preparation diastereoselective enantioselective; enyne aldehyde propargylic acetate preparation cyclization tandem gold catalyst.

Stereoselective synthesis of bicyclo[3.3.0]octenones I (R = Ph, naphthalen-2-yl, i-Pr, etc.) from chiral 1,3-enyne aldehydes bearing propargylic acetates (R,E/Z)-CH3CH(OC(O)CH3)CCC(R)=CH(CH2)2CHO is described. The method is based on a Au(I)-catalyzed domino sequence with concomitant transfer of chirality involving 1,3-acyloxy migration followed by Nazarov cyclization and an unprecedented aldol addition The method furnishes densely functionalized bicyclic structures in high yields, with up to 97% ee and good diastereoselectivity.

Chemical Science published new progress about Aldol addition catalysts, stereoselective. 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, COA of Formula: C21H22BrP.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Li, Qing; Meng, Liuwei; Zhou, Siru; Deng, Xiaoyan; Wang, Na; Ji, Yi; Peng, Yichun; Xing, Junhao; Yao, Gongmei published the artcile< Rapid generation of novel benzoic acid-based xanthine derivatives as highly potent, selective and long acting DPP-4 inhibitors: scaffold-hopping and prodrug study>, Electric Literature of 337536-14-8, the main research area is diabetes antidiabetes DPP 4 benzoic acid xanthine prodrug pharmacokinetics; Benzoic acid; DPP-4 inhibitor; Prodrug; Scaffold-hopping; Xanthine derivatives.

A series of novel xanthine derivatives 2a-l incorporating benzoic acid moieties were rapidly generated by using strategy of scaffold-hopping from our previously reported scaffold uracil to xanthine, a scaffold of approved drug linagliptin. After systematic structure-activity relationship (SAR) study around benzoic acid moieties, 5 novel DPP-4 inhibitors with low picomolar potency range (IC50 < 1 nM) and excellent selectivity against various DPP-4 homologues were identified, in which the best one, compound 2f(I), with the IC50 value of 0.1 nM for DPP-4, showed 22-fold improvement in inhibitory activity compared to lead compound uracil 1, its activity was 45-fold more potent than alogliptin. 2E, I, 2i(II) and 2k were selected for pharmacokinetic evaluation, and I and II showed the better pharmacokinetic profiles after iv administration, but poor oral bioavailability. To improve the oral pharmacokinetic profile, prodrug design approach was performed around I and II. Esters of I and II were synthesized and evaluated for stability, toxicity and pharmacokinetics. Compound 3e(III), the Me ester of compound I, was identified to demonstrate good stability, low toxicity and improved oral bioavailability, with 3-fold higher blood concentration compared to I in rats. The following in vivo evaluations revealed III provided a sustained pharmacodynamics effect for 48h, and robustly improved glucose tolerance in normal ICR and db/db mice in dose-dependent manner. Chronic treatments investigations demonstrated that III achieved more beneficial effects on fasting blood glucose levels and glucose tolerance than alogliptin in type 2 diabetic db/db mice. The overall results have shown that compound III has the potential to efficacious, safety and long-acting treatment for T2DM. European Journal of Medicinal Chemistry published new progress about Antidiabetic agents. 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

Huang, Zhiliang; Guan, Renpeng; Shanmugam, Muralidharan; Bennett, Elliot L.; Robertson, Craig M.; Brookfield, Adam; McInnes, Eric J. L.; Xiao, Jianliang published the artcile< Oxidative Cleavage of Alkenes by O2 with a Non-Heme Manganese Catalyst>, Application of C21H22BrP, the main research area is alkene oxygen light manganese oxidation catalyst; ketone preparation.

The oxidative cleavage of C=C double bonds with mol. oxygen to produce carbonyl compounds is an important transformation in chem. and pharmaceutical synthesis. In nature, enzymes containing the first-row transition metals, particularly heme and non-heme iron-dependent enzymes, readily activate O2 and oxidatively cleave C=C bonds with exquisite precision under ambient conditions. The reaction remains challenging for synthetic chemists, however. There are only a small number of known synthetic metal catalysts that allow for the oxidative cleavage of alkenes at an atm. pressure of O2, with very few known to catalyze the cleavage of nonactivated alkenes. In this work, we describe a light-driven, Mn-catalyzed protocol for the selective oxidation of alkenes to carbonyls under 1 atm of O2. For the first time, aromatic as well as various nonactivated aliphatic alkenes could be oxidized to afford ketones and aldehydes under clean, mild conditions with a first row, biorelevant metal catalyst. Moreover, the protocol shows a very good functional group tolerance. Mechanistic investigation suggests that Mn-oxo species, including an asym., mixed-valent bis(μ-oxo)-Mn(III,IV) complex, are involved in the oxidation, and the solvent methanol participates in O2 activation that leads to the formation of the oxo species.

Journal of the American Chemical Society published new progress about Aldehydes Role: SPN (Synthetic Preparation), PREP (Preparation). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Application of C21H22BrP.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Garcia-Barrantes, Pedro M.; Cho, Hyekyung P.; Blobaum, Anna L.; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W. published the artcile< Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs>, SDS of cas: 337536-14-8, the main research area is VU0486321 analog preparation mGluR1 pos allosteric modulator pharmacokinetics schizophrenia; Metabotropic glutamate receptor; Positive allosteric modulator (PAM); Schizophrenia; Structure–activity relationship (SAR); mGlu(1).

This Letter describes the further lead optimization of the VU0486321 series of mGlu1 pos. allosteric modulators (PAMs), focused on addressing the recurrent issue of plasma instability of the phthalimide moiety. Here, the authors evaluated a number of phthalimide bioisosteres, and ultimately identified isoindolinones as the ideal replacement that effectively address plasma instability, while maintaining acceptable mGlu1 PAM potency, DMPK profile, CNS penetration and mGluR selectivity.

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

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Ge, Liang; Wang, Ding-Xing; Xing, Renyi; Ma, Di; Walsh, Patrick J.; Feng, Chao published the artcile< Photoredox-catalyzed oxo-amination of aryl cyclopropanes>, Application of C21H22BrP, the main research area is aryl cyclopropane azole iridium photocatalyst ring opening oxidative amination; azolylalkyl ketone regioselective preparation.

A photoredox-coupled ring-opening oxo-amination of electronically unbiased cyclopropanes, which enabled the expedient construction of a host of structurally diverse β-amino ketone derivatives Through one electron oxidation, the relatively inert aryl cyclopropanes were readily converted into reactive radical cation intermediates, which in turn participate in the ensuing ring-opening functionalizations. Based on mechanistic studies, the present oxo-amination was proposed to proceed through an SN2-like nucleophilic attack/ring-opening manifold. This protocol featured wide substrate scope, mild reaction conditions, and use of dioxygen as an oxidant both for catalyst regeneration and oxygen-incorporation. Moreover, a one-pot formal aminoacylation of olefins was described through a sequential cyclopropanation/oxo-amination.

Nature Communications published new progress about Aminoacylation (regioselective). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Application of C21H22BrP.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Tanaka, Yuta; Seto, Masaki; Kakegawa, Keiko; Takami, Kazuaki; Kikuchi, Fumiaki; Yamamoto, Takeshi; Nakamura, Minoru; Daini, Masaki; Murakami, Masataka; Ohashi, Tomohiro; Kasahara, Takahito; Wang, Junsi; Ikeda, Zenichi; Wada, Yasufumi; Puenner, Florian; Fujii, Takahiro; Inazuka, Masakazu; Sato, Sho; Suzaki, Tomohiko; Oak, Jeong-Ho; Takai, Yuichi; Kohara, Hiroshi; Kimoto, Kouya; Oki, Hideyuki; Mikami, Satoshi; Sasaki, Minoru published the artcile< Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore>, Product Details of C9H8Br2O2, the main research area is pyrrolopyridinone preparation glucosylceramide synthase inhibitor SAR.

Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher’s disease and has been suggested as a potential target for treating Parkinson’s disease. Herein, authors report the discovery of novel brain-penetrant GCS inhibitors. Assessment of the structure-activity relationship revealed a unique pharmacophore in this series. The lipophilic ortho-substituent of aromatic ring A and the appropriate directionality of aromatic ring B were key for potency. Optimization of the absorption, distribution, metabolism, elimination, toxicity (ADMETox) profile resulted in the discovery of T-036, a potent GCS inhibitor in vivo. Pharmacophore-based scaffold hopping was performed to mitigate safety concerns associated with I. The ring opening of I resulted in another potent GCS inhibitor with a lower toxicol. risk, II, which reduced glucosylceramide in a dose-dependent manner in the plasma and cortex of mice. Finally, authors discuss the structural aspects of the compounds that impart a unique inhibition mode and lower the cardiovascular risk.

Journal of Medicinal Chemistry published new progress about Enzyme inhibitors (Glucosylceramide Synthase). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Product Details of C9H8Br2O2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Breuers, Christian B. J.; Daniliuc, Constantin G.; Studer, Armido published the artcile< Dearomatizing Cyclization of 2-Iodoindoles by Oxidative NHC Catalysis to Access Spirocyclic Indolenines and Oxindoles Bearing an All Carbon Quaternary Stereocenter>, Related Products of 337536-14-8, the main research area is spirooxindole enantioselective preparation; iodoindolylmethylbenzaldehye NHC catalyst oxidative cyclization.

An intramol. dearomatizing spirocyclization of indoles by oxidative N-heterocyclic carbene catalysis was reported. C2-iodinated indoles are used as substrates in combination with aroyl azolium ions as acceptors, which provides C2-iodinated indolenines containing an all carbon quaternary stereocenter. The products are readily further C2-functionalized and give access to valuable oxindoles by simple hydrolysis in very good overall yields and excellent enantioselectivities.

Organic Letters published new progress about Aralkyl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Related Products of 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhu, Jun; Zhang, Rui; Dong, Guangbin published the artcile< Orthogonal cross-coupling through intermolecular metathesis of unstrained C(aryl)-C(aryl) single bonds>, Electric Literature of 1530-33-2, the main research area is biaryl ruthenium catalyst regioselective orthogonal cross coupling reaction.

Ruthenium-catalyzed reversible C-C single-bond metathesis reaction that allowed redox- and pH-neutral biaryl synthesis. Assisted by directing groups, unstrained homo-biaryl compounds underwent aryl exchanges to generate cross-biaryl products, catalyzed by a well-defined air-stable ruthenium(II) complex. Functional groups reactive under typical cross-coupling reactions, such as halogen, silyl and boronate moieties, were compatible under the metathesis conditions. Mechanistic studies disclosed an intriguing ‘olefin-metathesis-like’ pathway that involved an unexpected heptacoordinated, 18-electron closed-shell intermediate. The distinct reaction mode discovered here is expected to inspire the development of more general C-C single-bond metathesis and orthogonal cross-coupling reactions.

Nature Chemistry published new progress about Biaryls 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, Electric Literature of 1530-33-2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Qin, Pengjin; Wang, Li-An; O’Connor, Joseph M.; Baldridge, Kim K.; Li, Yifan; Tufekci, Burak; Chen, Jiyue; Rheingold, Arnold L. published the artcile< Transition-Metal Catalysis of Triene 6π Electrocyclization: The π-Complexation Strategy Realized>, Application of C21H22BrP, the main research area is triene electrocyclization transition metal pi complexation catalysis; catalysis; cycloaromatization; electrocyclization; transition metals; triene.

Triene 6π electrocyclization, wherein a conjugated triene undergoes a concerted stereospecific cycloisomerization to a cyclohexadiene, is a reaction of great historical and practical significance. In order to circumvent limitations imposed by the normally harsh reaction conditions, chemists have long sought to develop catalytic variants based upon the activating power of metal-alkene coordination. Herein, we demonstrate the first successful implementation of such a strategy by utilizing [(C5H5)Ru(NCMe)3]PF6 as a precatalyst for the disrotatory 6π electrocyclization of highly substituted trienes that are resistant to thermal cyclization. Mechanistic and computational studies implicate hexahapto transition-metal coordination as responsible for lowering the energetic barrier to ring closure. This work establishes a foundation for the development of new catalysts for stereoselective electrocyclizations.

Angewandte Chemie, International Edition published new progress about Alkatrienes Role: PEP (Physical, Engineering or Chemical Process), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), PROC (Process), RACT (Reactant or Reagent), PREP (Preparation). 1530-33-2 belongs to class bromides-buliding-blocks, and the molecular formula is C21H22BrP, Application of C21H22BrP.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary