Category: 337536-14-8

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

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

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

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

Tanaka, Yuta; Kurasawa, Osamu; Yokota, Akihiro; Klein, Michael G.; Saito, Bunnai; Matsumoto, Shigemitsu; Okaniwa, Masanori; Ambrus-Aikelin, Geza; Uchiyama, Noriko; Morishita, Daisuke; Kimura, Hiromichi; Imamura, Shinichi published the artcile< New Series of Potent Allosteric Inhibitors of Deoxyhypusine Synthase>, HPLC of Formula: 337536-14-8, the main research area is allosteric deoxyhypusine synthase inhibitor preparation pharmacokinetics SAR.

In this work, a new chem. series possessing fused ring scaffolds designed from high-throughput screening hit compounds was synthesized, discovering a 5,6-dihydrothieno[2,3-c]pyridine derivative I [R = (R)-i-Bu] with potent inhibitory activity. Furthermore, the X-ray crystallog. anal. of the DHPS complex with I [R = (R)-i-Bu] demonstrated a distinct allosteric binding mode compared to a previously reported inhibitor. These findings could be significantly useful in the functional anal. of conformational changes in DHPS as well as the structure-based design of allosteric inhibitors.

ACS Medicinal Chemistry Letters published new progress about Allosteric modulators. 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, HPLC of Formula: 337536-14-8.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Wang, Siyuan; Zhou, Yangkun; Huang, Hanmin published the artcile< Palladium-Catalyzed Tandem Carbonylative Diels-Alder Reaction for Construction of Bridged Polycyclic Skeletons>, Category: bromides-buliding-blocks, the main research area is aldehyde halomethylaryl diastereoselective regioselective carbonylative Diels Alder alkene; bridged bicyclic lactone stereoselective preparation.

A palladium-catalyzed tandem carbonylative lactonization and Diels-Alder cycloaddition reaction between aldehyde-tethered benzyl halides I (R1 = H, X = Cl, Br; R1 = 4-Cl, 3-Br, 5-MeO, etc., X = Br) and alkenes R2R3C:CHR4 [R2 = H, n-BuO, ClCH2CH2O, BocNH, Ph, 2-MeC6H4, 4-ClC6H4, etc., R3 = R4 = H; R2 = Ph, R3 = Me, R4 = H; R2R4 = OCH2CH2, (CH2)3, (CH2)6; etc.] has been developed. A range of alkenes and aldehyde-tethered benzyl halides bearing different substituents can be successfully transformed into the corresponding bridged polycyclic compounds II in good yields. This strategy provides a unique approach to complex lactone-containing bridged polycyclic compounds

Organic Letters published new progress about Aldehydes, halo Role: RCT (Reactant), RACT (Reactant or Reagent). 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< Correction to DNA Compatible Multistep Synthesis and Applications to DNA Encoded Libraries>, COA of Formula: C9H8Br2O2, the main research area is nitrogen heterocyclic DNA encoded library synthesis high throughput sequencing; erratum.

This correction fixes the connection between the DNA sequence and the chem. structure in Scheme 1, which is currently published as a hydrazide, but is actually an amide in both Scheme 1a and b.

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, COA of Formula: C9H8Br2O2.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary