Abstract：
:The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.
journal_name
ACS Comb Scijournal_title
ACS combinatorial scienceauthors
Myers SM,Bawn RH,Bisset LC,Blackburn TJ,Cottyn B,Molyneux L,Wong AC,Cano C,Clegg W,Harrington RW,Leung H,Rigoreau L,Vidot S,Golding BT,Griffin RJ,Hammonds T,Newell DR,Hardcastle IRdoi
10.1021/acscombsci.5b00155subject
Has Abstractpub_date
2016-08-08 00:00:00pages
444-55issue
8eissn
2156-8952issn
2156-8944journal_volume
18pub_type
杂志文章abstract：:We report the first example of venting-while-heating microwave-assisted synthesis of a small library of 3-arylthioindoles. Compounds were prepared in excellent isolated yields (90-98%) within 4 min in a closed vessel by treating indoles with disulfides in the presence of sodium hydride in anhydrous N,N-dimethylformami...
journal_title：ACS combinatorial science
pub_type： 信件
doi：10.1021/co200165j
更新日期：2012-04-09 00:00:00
abstract：:Solid-phase synthesis is the method of choice for peptide preparation in both research and industrial settings. The whole synthetic process is governed by the initial functionalization of the resin. Although the literature provides several methods to determine such functionalization, the addition of an Fmoc-amino acid...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00154
更新日期：2019-11-11 00:00:00
abstract：:When isolating binders from yeast displayed combinatorial libraries, a soluble, recombinantly expressed form of the target protein is typically utilized. As an alternative, we describe the use of target proteins displayed as surface fusions on magnetized yeast cells. In our strategy, the target protein is coexpressed ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00147
更新日期：2019-12-09 00:00:00
abstract：:The diversity oriented synthesis of substituted pyridines and dihydro-6H-quinolin-5-ones tethered with aryls and heteroaryls was achieved in very good yields through CeCl(3)·7H(2)O-NaI catalyst via variants of the Bohlmann-Rahtz reaction. β-Enaminones derived from various aryl and heteroaryl methyl ketones were regios...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2000604
更新日期：2011-07-11 00:00:00
abstract：:Adleman's illustration of molecular computing using DNA paved the way toward an entirely new direction of computing (Adleman, L. M. Science 1994, 266, 1021). The exponential time complex combinatorial problem on a traditional computer turns out to be a separation problem involving a polynomial number of steps in DNA c...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00150
更新日期：2020-05-11 00:00:00
abstract：:Solid-phase synthetic strategies toward the generation of libraries of biologically relevant molecules were developed using olefin cross-metathesis as a key step. It is remarkably the formal alkane metathesis based on a one-pot, microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain Csp3-Csp3...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500176b
更新日期：2015-02-09 00:00:00
abstract：:The exploration of new alloys with desirable properties has been a long-standing challenge in materials science because of the complex relationship between composition and microstructure. In this Research Article, we demonstrate a combinatorial strategy for the exploration of composition dependence of microstructure. ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00040
更新日期：2016-10-10 00:00:00
abstract：:Fourteen (hetero-)(arylidene)arylhydrazide derivatives (ABH1-ABH14) were synthesized, and their inhibitory activities against monoamine oxidases (MAOs) and acetylcholinesterase (AChE) were evaluated. Compound ABH5 most potently inhibited MAO-B with an IC50 value of 0.025 ± 0.0019 μM; ABH2 and ABH3 exhibited high IC50 ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00136
更新日期：2020-11-09 00:00:00
abstract：:Thirteen 5-hetarylaminopyrazoles were synthesized in 62-93% yield through the arylation of 1-isopropyl- and 1-phenyl-5-aminopyrazoles with electrophilic hetarylhalides under optimized conditions. Condensation of 5-hetarylaminopyrazoles with carbonyl compounds facilitated by AcOH or Me(3)SiCl furnished 23 pyrazolo[3,4-...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co300063x
更新日期：2012-08-13 00:00:00
abstract：:A novel method of evaluating the enantioselectivity of chiral receptors is investigated. It involves extraction of an ionic guest in racemic form from an ion-exchange resin to the organic solvent, where it is bound by a chiral receptor. The enantioselectivity of the examined receptor is determined simply by measuring ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00075
更新日期：2015-09-14 00:00:00
abstract：:Acetylenic tertiary alcohols are well-known to be compounds that are biologically more stable than their corresponding secondary alcohols. The linkage of an acetylenic compound to a polymer support and further introduction of molecular diversity was found to be an interesting way to generate libraries of hydroxy acety...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co300034y
更新日期：2012-06-11 00:00:00
abstract：:In this article, an original one-pot method is utilized to synthesize a variety of derivatives of naphtho[2,1-b]furan-2(1H)-one via a pseudo-four-component domino reaction of aryl aldehydes, acetic anhydride, hippuric acids, and 2-naphthols catalyzed by HSW@SPIONs. This reaction illustrates an array of attractive feat...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.5b00018
更新日期：2015-08-10 00:00:00
abstract：:The possibility of band gap engineering in graphene opens countless new opportunities for application in nanoelectronics. In this work, the energy gaps of 622 computationally optimized graphene nanoflakes were mapped to topological autocorrelation vectors using machine learning techniques. Machine learning modeling re...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00094
更新日期：2016-11-14 00:00:00
abstract：:A novel and highly efficient three-component reaction of 2-alkynylbenzaldoxime, carbodiimide, with electrophile (bromine or iodine monochloride) is disclosed, which generates 1-(4-haloisoquinolin-1-yl)ureas in good yields under mild conditions. Subsequent palladium-catalyzed Suzuki-Miyaura coupling reaction is introdu...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co100026y
更新日期：2011-03-14 00:00:00
abstract：:Yeast surface display empowers selection of protein binding ligands, typically using recombinant soluble antigens. However, ectodomain fragments of transmembrane targets may fail to recapitulate their true, membrane-bound form. Direct selections against adhered mammalian cells empower enrichment of genuine binders yet...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00036
更新日期：2020-05-11 00:00:00
abstract：:A combination of flow and batch chemistries has been successfully applied to the assembly of a series of trisubstituted drug-like pyrrolidines. This study demonstrates the efficient preparation of a focused library of these pharmaceutically important structures using microreactor technologies, as well as classical par...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2000357
更新日期：2011-07-11 00:00:00
abstract：:This work presents the first use of yeast-displayed protein targets for screening mRNA-display libraries of cyclic and linear peptides. The WW domains of Yes-Associated Protein 1 (WW-YAP) and mitochondrial import receptor subunit TOM22 were adopted as protein targets. Yeast cells displaying WW-YAP or TOM22 were magnet...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.0c00171
更新日期：2020-12-14 00:00:00
abstract：:Retinoic acid (RA) is a key metabolite necessary for embryonic development and differentiation in vertebrates. We demonstrate the utility of genetically encoded, ligand-activatable single-chain bioluminescence probes for detecting RAs from different biological sources. We examined 13 different molecular designs to ide...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.9b00035
更新日期：2019-06-10 00:00:00
abstract：:We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2000218
更新日期：2011-07-11 00:00:00
abstract：:A combination of MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTP(n)) have been successfully utilized for the preparation of a 106-member library of triazole containing benzothiaoxazepine-1,1-dioxides. This report demonstrates the utilization of a suite of soluble OTP(n) reagents for facile (triazo...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co2001839
更新日期：2012-04-09 00:00:00
abstract：:Optical bandgap mapping of Nb-Ti mixed oxides anodically grown on a thin film parent metallic combinatorial library was performed via variable angle spectroscopic ellipsometry (VASE). A wide Nb-Ti compositional spread ranging from Nb-90 at.% Ti to Nb-15 at.% Ti deposited by cosputtering was used for this purpose. The ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.6b00162
更新日期：2017-02-13 00:00:00
abstract：:A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synth...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00119
更新日期：2017-12-11 00:00:00
abstract：:A build/couple/pair strategy for the synthesis of complex and densely functionalized small molecules is presented. The strategy relies on synthetically tractable building blocks (build), that is, diversely substituted hydrazides, α-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (coup...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500091f
更新日期：2015-01-12 00:00:00
abstract：:A series of diverse polycyclic heterocycles containing spirooxindole, pyridine/thiophene, and pyrrolidine/pyrrolizidine/pyrrolothiazole rings have been synthesized through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the condensation of dicarbonyl compounds (isatin or acenaphthenequinone) an...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500085t
更新日期：2014-09-08 00:00:00
abstract：:Protein-protein interactions are generally challenging to target by small molecules. To address the challenge, we have used a multidisciplinary approach to identify small-molecule disruptors of protein-protein interactions that are mediated by SUMO (small ubiquitin-like modifier) proteins. SUMO modifications have emer...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500181b
更新日期：2015-04-13 00:00:00
abstract：:Magnetization using cheap and minimally toxic materials, such as iron oxide nanoparticles can enable easy separation of cells from culture medium and is relevant to several industrial applications. Here, we show that cell surface expression of a mutant protein that binds iron oxide can enable efficient magnetization o...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.8b00084
更新日期：2018-10-08 00:00:00
abstract：:Parallel solution-phase synthesis of combinatorial libraries of dihydroindenoisoquinolines employing a sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation protocol was realized. The scope and limitations of the protocol with respect to the substitution pattern in the aryl ring of the indene core, a...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200027c
更新日期：2011-09-12 00:00:00
abstract：:A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interes...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/acscombsci.7b00172
更新日期：2018-04-09 00:00:00
abstract：:Preparative RP-LCMS is widely used to purify compounds from crude reaction mixtures in drug discovery today. Method development for preparative Liquid Chromatography-Mass Spectrometry (LCMS) consists of finding the right balance between speed and quality, often leading to the use of fast generic gradients (5-95% organ...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co200197b
更新日期：2012-04-09 00:00:00
abstract：:The present investigation reports an easy access to a library of novel spiro-oxindole-pyrrolizine or pyrrolo[1,2-c]thiazole fused coumarin hybrid heterocycles through a one-pot sequential four-component reactions of 2,2-dimethyl-1,3-dioxane-4,6-dione, salicylaldehydes, isatins, and cyclic α-amino acids under ultrasoun...
journal_title：ACS combinatorial science
pub_type： 杂志文章
doi：10.1021/co500092b
更新日期：2014-10-13 00:00:00
