Category: 229009-40-9

Liu, Xuesong; Wang, Beilei; Chen, Cheng; Qi, Ziping; Zou, Fengming; Wang, Junjie; Hu, Chen; Wang, Aoli; Ge, Juan; Liu, Qingwang; Yu, Kailin; Hu, Zhenquan; Jiang, Zongru; Wang, Wei; Wang, Li; Wang, Wenchao; Ren, Tao; Bai, Mingfeng; Liu, Qingsong; Liu, Jing published the artcile< Discovery of (E)-N1-(3-Fluorophenyl)-N3-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)malonamide (CHMFL-KIT-033) as a Novel c-KIT T670I Mutant Selective Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)>, Reference of 229009-40-9, the main research area is CHMFL KIT033 preparation cKIT T670I kinase inhibitor gastrointestinal tumor.

Gain-of-function mutations of c-KIT kinase play crucial pathol. roles for the gastrointestinal stromal tumors (GISTs). Despite the success of imatinib as the first-line treatment of GISTs, dozens of drug-acquired resistant mutations emerge, and c-KIT T670I is one of the most common mutants among them. Although several kinase inhibitors are capable of overcoming the T670I mutant, none of them can achieve the selectivity over the c-KIT wild-type (wt), which also plays important roles in a variety of physiol. functions such as hematopoiesis. Starting from axitinib, through fragment hybrid type II kinase inhibitor design approach, we have discovered a novel inhibitor 24, which not only exhibits potent activity to c-KIT T670I mutant but also achieves 12-fold selectivity over c-KIT weight Compound 24 displays good antiproliferative effects against c-KIT T670I mutant-driven GIST cell lines (GIST-T1/T670I and GIST-5R) and also exhibits suitable in vivo pharmacokinetic profiles as well as dose-dependent antitumor efficacy. This study provides a proof of concept for developing a c-KIT mutant selective inhibitor that theor. can render a better therapeutic window.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Reference of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ivashchenko, Andrey A.; Ivanenkov, Yan A.; Aladinskiy, Vladimir A.; Karapetian, Ruben N.; Koryakova, Angela G.; Ryakhovskiy, Alexey A.; Mitkin, Oleg D.; Kravchenko, Dmitry V.; Savchuk, Nikolai P.; Zagribelnyy, Bogdan A.; Ivashchenko, Alexander V. published the artcile< Synthesis, biological evaluation and in silico modeling of novel pan-genotypic NS5A inhibitors>, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is peptide linked bisimidazole preparation NS5A inhibitor mol modeling SAR; Combinatorial synthesis; HCV; In silico modeling; Medicinal chemistry; NS5A inhibitors.

A series of novel small-mol. pan-genotypic hepatitis C virus (HCV) NS5A inhibitors with picomolar activity containing 2-[(2S)-pyrrolidin-2-yl]-5-[4-(4-{2-[(2S)-pyrrolidin-2-yl]-1H-imidazol-5-yl}buta-1,3-diyn-1-yl)aryl]-1H-imidazole core was designed based on mol. modeling study and SAR anal. The constructed in silico model and docking study provide a deep insight into the binding mode of this type of NS5A inhibitors. Based on the predicted binding interface authors have prioritized the most crucial diversity points responsible for improving antiviral activity. The synthesized mols. were tested in a cell-based assay, and compound I exhibited an EC50 value in the range of 2.9-34 pM against six genotypes of NS5A HCV, including gT3a, and demonstrated favorable pharmacokinetic profile in rats. This lead compound can be considered as an attractive candidate for further clin. evaluation.

Bioorganic & Medicinal Chemistry published new progress about Alkadiynes Role: PAC (Pharmacological Activity), PKT (Pharmacokinetics), PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Safety of 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Zhou, Min; Ni, Chuanfa; Zeng, Yuwen; Hu, Jinbo published the artcile< Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent>, Application In Synthesis of 229009-40-9, the main research area is trifluoromethyl benzoate versatile trifluoromethoxylation reagent; trifluoromethoxylation halogenation aryne.

Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source. The synthetic potency of TFBz is demonstrated by trifluoromethoxylation-halogenation of arynes, nucleophilic substitution of alkyl (pseudo)halides, cross-coupling with aryl stannanes, and asym. difunctionalization of alkenes. The unprecedented trifluoromethoxylation-halogenation of arynes proceeds smoothly at room temperature with the aid of a crown ether-complexed potassium cation, which significantly stabilizes the trifluoromethoxide anion derived from TFBz.

Journal of the American Chemical Society published new progress about Alkynes, arynes Role: RCT (Reactant), RACT (Reactant or Reagent). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Application In Synthesis of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

He, Chunxian; Preiss, Laura; Wang, Bin; Fu, Lei; Wen, Hui; Zhang, Xiang; Cui, Huaqing; Meier, Thomas; Yin, Dali published the artcile< Structural Simplification of Bedaquiline: the Discovery of 3-(4-(N,N-Dimethylaminomethyl)phenyl)quinoline-Derived Antitubercular Lead Compounds>, Synthetic Route of 229009-40-9, the main research area is quinoline dimethylaminomethyl phenyl preparation antitubercular activity; ATP synthase; Mycobacterium tuberculosis; bedaquiline; multidrug resistance; pulmonary tuberculosis.

Bedaquiline (BDQ) is a novel and highly potent last-line antituberculosis drug that was approved by the US FDA in 2013. Owing to its stereo-structural complexity, chem. synthesis and compound optimization are rather difficult and expensive. This study describes the structural simplification of bedaquiline while preserving antitubercular activity. The compound’s structure was split into fragments and reassembled in various combinations while replacing the two chiral carbon atoms with an achiral linkage instead. Four series of analogs were designed; these candidates retained their potent antitubercular activity at sub-microgram per mL concentrations against both sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC-ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results provide a basis for the development of chem. less complex, lower-cost bedaquiline derivatives and describe the identification of two derivatives with antitubercular activity against non-ATP synthase related targets.

ChemMedChem published new progress about ATPase inhibitors. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Synthetic Route of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Casalvieri, Kimberly A.; Matheson, Christopher J.; Warfield, Becka M.; Backos, Donald S.; Reigan, Philip published the artcile< N-Substituted pyrrolopyrimidines and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors>, Electric Literature of 229009-40-9, the main research area is pyrrolopyrimidine preparation antitumor RSK2 inhibition SAR; purine preparation antitumor RSK2 inhibition SAR; Inhibitor; Kinase; RSK; Structure-activity relationship.

In the current study, a series of pyrrolopyrimidines and purines were developed to replace the pteridinone ring of BI-D1870, with a range of N-substituents that extended to the substrate binding site to probe complementary interactions, while retaining the 2,6-difluorophenol-4-amino group to maintain interactions with the hinge domain and the DFG motif. Several compounds inhibited cellular RSK2 activity and compounds that uncoupled cellular RSK2 inhibition from potent cytotoxicity in the MOLM-13 AML cell line were identified . These N-substituted probes revealed an opportunity to further examine substituents that extend from the ATP- to the substrate-binding site may confer improved RSK potency and selectivity.

Bioorganic & Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Electric Literature of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ensan, Deeba; Smil, David; Zepeda-Velazquez, Carlos A.; Panagopoulos, Dimitrios; Wong, Jong Fu; Williams, Eleanor P.; Adamson, Roslin; Bullock, Alex N.; Kiyota, Taira; Aman, Ahmed; Roberts, Owen G.; Edwards, Aled M.; O’Meara, Jeff A.; Isaac, Methvin B.; Al-Awar, Rima published the artcile< Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma>, Product Details of C11H17BN2O2, the main research area is diffuse intrinsic pontine glioma ALK2 inhibitor brain potassium channel.

Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Anal. of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant. Initial efforts resulted in the discovery of M4K2009 (I), an analog of the previously reported ALK2 inhibitor LDN-214117. Although highly selective for ALK2 over the TGF-βR1 receptor ALK5, M4K2009 is also moderately active against the hERG potassium channel. Varying the substituents of the trimethoxyphenyl moiety gave rise to an equipotent benzamide analog M4K2149 (II) with reduced off-target affinity for the ion channel. Addnl. modifications yielded 2-fluoro-6-methoxybenzamide derivatives (26a(III)-c), which possess high inhibitory activity against ALK2, excellent selectivity, and superior pharmacokinetic profiles.

Journal of Medicinal Chemistry published new progress about Activin receptor ACVRLK2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitor). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Product Details of C11H17BN2O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Wang, Lan; Stanley, Mark; Boggs, Jason W.; Crawford, Terry D.; Bravo, Brandon J.; Giannetti, Anthony M.; Harris, Seth F.; Magnuson, Steven R.; Nonomiya, Jim; Schmidt, Stephen; Wu, Ping; Ye, Weilan; Gould, Stephen E.; Murray, Lesley J.; Ndubaku, Chudi O.; Chen, Huifen published the artcile< Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors>, Quality Control of 229009-40-9, the main research area is fragment identification pyrrolo triazine MAP4K4 inhibitor; Fragment-based lead discovery; Kinase inhibitors; MAP4K4; P-loop conformation; Pyrrolotriazine.

MAP4K4 has been shown to regulate key cellular processes that are tied to disease pathogenesis. In an effort to generate small mol. MAP4K4 inhibitors, a fragment-based screen was carried out and a pyrrolotriazine fragment with excellent ligand efficiency was identified. Further modification of this fragment guided by X-ray crystal structures and mol. modeling led to the discovery of a series of promising compounds with good structural diversity and physicochem. properties. These compounds exhibited single digit nanomolar potency and compounds 35 and 44 achieved good in vivo exposure.

Bioorganic & Medicinal Chemistry Letters published new progress about Crystal structure. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Quality Control of 229009-40-9.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Eddie, Sharon L.; Gregson, Aaron; Graham, Emma; Burton, Stephanie; Harrison, Timothy; Burden, Roberta; Scott, Christopher J.; Mullan, Paul B.; Williams, Rich published the artcile< Identification and SAR exploration of a novel series of Legumain inhibitors>, Name: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid, the main research area is Legumain mall mol inhibitor SAR dipeptide; Legumain; SAR; Small molecule inhibitor.

This letter describes the development of a series of potent and selective small mol. Legumain inhibitors suitable as chem. probes for in vitro experiments Our previous research had identified a dipeptide inhibitor utilizing a semi-reversible cyano warhead that generated 2, a cell active inhibitor. This work explores an alternative P2-P3 linker and further SAR exploration of the P3 group which led to the identification of 16i, a highly potent inhibitor with excellent physiochem. properties.

Bioorganic & Medicinal Chemistry Letters published new progress about Dipeptides Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (dipeptide Legumain inhibitors). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Name: 4-(4-Methyl-1-piperazinyl)phenylboronic Acid.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Xie, Fuchun; Zhao, Hongbing; Li, Dewen; Chen, Hong; Quan, Haitian; Shi, Xiaojing; Lou, Liguang; Hu, Youhong published the artcile< Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors>, Product Details of C11H17BN2O2, the main research area is pyrimidine derivative preparation SAR tubulin polymerization inhibitor antiproliferative activity.

Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine I, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC50 = 0.79 μM) and to display significantly high antiproliferative activities against several cancer cell lines with IC50 values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G2/M phase of the cell cycle (EC50 = 20 nM). In addition, I was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity.

Journal of Medicinal Chemistry published new progress about Antimitotic agents. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Product Details of C11H17BN2O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Sung, Dan-Bi; Mun, Bohyun; Park, Sol; Lee, Hyi-Seung; Lee, Jihoon; Lee, Yeon-Ju; Shin, Hee Jae; Lee, Jong Seok published the artcile< Synthesis, Molecular Engineering, and Photophysical Properties of Fluorescent Thieno[3,2-b]pyridine-5(4H)-ones>, Formula: C11H17BN2O2, the main research area is thienopyridinone synthesis regioselective aza cycloaddition aminothiophene unsaturated carboxylic acid; fluorescent thienopyridinone synthesis.

We describe a synthetic approach for a set of fluorescent thieno[3,2-b]pyridine-5(4H)-one derivatives and their photophys. properties. These fluorophores are prepared by a series of reactions employing the Suzuki-Miyaura cross-coupling reaction and a regioselective aza-[3 + 3] cycloaddition of 3-aminothiophenes with α,β-unsaturated carboxylic acids. Our findings revealed that the photophys. properties are chem. tunable by an appropriate choice of functional group on the thieno[3,2-b]pyridine-5(4H)-one scaffold.

Journal of Organic Chemistry published new progress about [3+3] Cycloaddition reaction (regioselective aza-[3 + 3] cycloaddition). 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Formula: C11H17BN2O2.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics