Tag: M.W=200-250

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

Li, Xu; Chen, Xiaolan; Yuan, Jinwei; Qu, Lingbo; Zhu, Haisheng; Bi, Wenzhu; Zhao, Yufen published the artcile< Synthesis and Characterization of Phosphoramide Piperazine Analogs of Paeonol>, COA of Formula: C9H19ClN2O2, the main research area is phosphoramide piperazine analog paeonol preparation.

Based on the phosphorylated reaction, an efficient general synthetic approach that provide facile, rapid and cheap access to a wide range of novel phosphoramide derivatives of paeonol has been developed. These analogs of paeonol are synthesized in high yields and elucidated by IR, HR MS, and NMR.

Phosphorus, Sulfur and Silicon and the Related Elements published new progress about Phosphoramides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, COA of Formula: C9H19ClN2O2.

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

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

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

Chen, Xiaolan; Yuan, Jinwei; Qu, Lingbo; Qu, Zhibo; Xu, Shaohua; Wang, Fujun; Zhao, Yufen published the artcile< Synthesis and Spectroscopic Characterization of Some New Piperazine Phosphoramide Derivatives of 4-Hydroxycoumarin>, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride, the main research area is piperazine phosphoramide hydroxycoumarin preparation.

A series of new piperazine phosphoramide derivatives of 4-hydroxycoumarin were synthesized through a facile phosphorylating reaction starting from 4-hydroxycoumarin and various phosphorylating agents. The title compounds were characterized by IR, NMR, electrospray ionization-mass spectrometry, and high-resolution mass spectrometry, and their spectroscopic data were further analyzed to feature the related spectroscopic characteristics of the compounds of this class.

Phosphorus, Sulfur and Silicon and the Related Elements published new progress about Phosphorylation. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, Recommanded Product: tert-Butyl piperazine-1-carboxylate hydrochloride.

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

Donnell, Andrew F.; Zhang, Yong; Stang, Erik M.; Wei, Donna D.; Tebben, Andrew J.; Perez, Heidi L.; Schroeder, Gretchen M.; Pan, Chin; Rao, Chetana; Borzilleri, Robert M.; Vite, Gregory D.; Gangwar, Sanjeev published the artcile< Macrocyclic pyrrolobenzodiazepine dimers as antibody-drug conjugate payloads>, Electric Literature of 229009-40-9, the main research area is macrocyclic pyrrolo benzodiazepine dimer preparation antibody drug conjugate mesothelin; Antibody-drug conjugates; Macrocycles; Pyrrolobenzodiazepines.

Macrocyclic pyrrolobenzodiazepine dimers were designed and evaluated for use as antibody-drug conjugate payloads. Initial structure-activity exploration established that macrocyclization could increase the potency of PBD dimers compared with non-macrocyclic analogs. Further optimization overcame activity-limiting solubility issues, leading to compounds with highly potent (picomolar) activity against several cancer cell lines. High levels of in vitro potency and specificity were demonstrated with an anti-mesothelin conjugate.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 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

Rudolf, Klaus; Eberlein, Wolfgang; Engel, Wolfhard; Pieper, Helmut; Entzeroth, Michael; Hallermayer, Gerhard; Doods, Henri published the artcile< Development of Human Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists. Potent and Selective Small Molecule CGRP Antagonists. 1-[N2-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1- piperidinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)piperazine: The First CGRP Antagonist for Clinical Trials in Acute Migraine>, Computed Properties of 76535-74-5, the main research area is oxoquinazolinpiperazine derivative preparation CGRP receptor antagonist antimigraine migraine.

Although the triptans have greatly improved the acute treatment of migraine headache, there are yet many shortcomings. Therefore, new strategies for the treatment of migraine are needed which offer advantages over current therapy, e.g. triptans. Our novel approach was based on the hypothesis that the release of calcitonin gene-related peptide (CGRP) could play a causative role in migraine headache. Thus the authors initiated a program aimed at the design and synthesis of small mol. CGRP receptor antagonists. High throughput screening led to the identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but unequivocal binding to the human CGRP receptor. Lead optimization afforded highly potent CGRP antagonists, the prototype being compound (I) (BIBN4096). This compound exhibiting a favorable biol. profile was selected for initial clin. trials. A proof of concept study indicated that i.v. application of I was effective in the treatment of acute migraine headache. This finding strongly supports our initial working hypothesis that CGRP plays an important role in the pathophysiol. of migraine.

Journal of Medicinal Chemistry published new progress about Antimigraine agents. 76535-74-5 belongs to class piperazines, and the molecular formula is C9H19ClN2O2, Computed Properties of 76535-74-5.

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