121903-71-7Relevant academic research and scientific papers
Application of Off-Rate Screening in the Identification of Novel Pan-Isoform Inhibitors of Pyruvate Dehydrogenase Kinase
Brough, Paul A.,Baker, Lisa,Bedford, Simon,Brown, Kirsten,Chavda, Seema,Chell, Victoria,D’Alessandro, Jalanie,Davies, Nicholas G. M.,Davis, Ben,Le Strat, Loic,Macias, Alba T.,Maddox, Daniel,Mahon, Patrick C.,Massey, Andrew J.,Matassova, Natalia,McKenna, Sean,Meissner, Johannes W. G.,Moore, Jonathan D.,Murray, James B.,Northfield, Christopher J.,Parry, Charles,Parsons, Rachel,Roughley, Stephen D.,Shaw, Terry,Simmonite, Heather,Stokes, Stephen,Surgenor, Allan,Stefaniak, Emma,Robertson, Alan,Wang, Yikang,Webb, Paul,Whitehead, Neil,Wood, Mike
, p. 2271 - 2286 (2017/04/03)
Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro.
RESORCINOL N-ARYL AMIDE COMPOUNDS, FOR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS
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, (2015/04/15)
A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: Y is –CONR1- or optionally substituted arylene or optionally substituted heteroarylene; R1 is H, Cl, F, CH3 or CF3; 10 each R4 is independently H, CH3 or F; R5 is H or CH3; and each R2 and R6 is independently (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X; The compounds of the invention are useful as resorcinol N-aryl amide (NAA) compounds, which are suitable for use as PDK inhibitors, for example for 15 inhibition of cancer cell proliferation.
TETRAHYDROISOQUINOLINE COMPOUNDS AND THEIR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS
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, (2015/04/15)
A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: R1 is H, Cl, F, CH3 or CF3; R2 is H, C1-C6 alkyl or optionally substituted heteroaryl or optionally substituted aryl; and R3 is (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X. The compounds are useful as tetrahydroisoquinoline (THQ) compounds, which are suitable for use as PDK inhibitors, for example for inhibition of cancer cell proliferation.
Total Synthesis of Petrobactin and Its Homologues as Potential Growth Stimuli for Marinobacter hydrocarbonoclasticus, an Oil-Degrading Bacteria
Gardner, Richard Andrew,Kinkade, Rebecca,Wang, Chaojie,Phanstiel IV, Otto
, p. 3530 - 3537 (2007/10/03)
A modular synthesis was developed to access petrobactin, a catechol-containing siderophore isolated from Marinobacter hydrocarbonoclasticus. A range of petrobactin homologues with differing dihydroxybenzamide motifs and in one case an increased number of
Total Synthesis of Polyamine Amide Spider Toxin Argiotoxin-636 by a Practical Reductive Alkylation Strategy
Blagbrough, Ian S.,Moya, Eduardo
, p. 9393 - 9396 (2007/10/02)
Reductive alkylation is a practical strategy for a total synthesis of spider toxin argiotoxin-636, a polyamine amide which is selective glutamate receptor antagonist and may have potential as a neuroprotective agent.Central to this synthesis are a Swern o
The Synthesis of Cyclic Enol Ethers via Molybdenum Alkylidene-Catalyzed Ring-Closing Metathesis
Fujimura, Osamu,Fu, Gregory C.,Grubbs, Robert H.
, p. 4029 - 4031 (2007/10/02)
An efficient method for the construction of five- and six-membered cyclic vinyl ethers from unsaturated esters using stoichiometric titanium reagents to convert the esters to acyclic olefinic enol ethers which are then transformed to the desired products by catalytic ring-closing olefin metathesis with a molybdenum alkylidene complex is described.
Total synthesis of nstx-3, spider toxin of Nephila maculata
Teshima, Tadashi,Matsumoto, Takahiro,Wakamiya, Tateaki,Shiba, Tetsuo,Aramaki, Yoshio,Nakajima, Terumi,Kawai, Nobufumi
, p. 3305 - 3312 (2007/10/02)
A spider toxin NSTX-3 obtained from the venom of Papua New Guinean spider, Nephila maculata was synthesized in order to confirm its proposed structure and to supply the sample for the biological tests. The structure of NSTX-3 is now established as 2,4-dihydroxyphenylacetyl-L-Asn→Cad←Pua←L-Arg, where Cad stands for cadaverine and Pua for putreanine.
Flavonoids from the cultured cells of Glycyrrhiza echinata
Ayabe, Shin-Ichi,Kobayashi, Miyuki,Hikichi, Manabu,Matsumoto, Kazuo,Furuya, Tsutomu
, p. 2179 - 2183 (2007/10/02)
Constituents of the cultured cells of Glycyrrhiza echinata have been investigated. Echinatin (4,4′-dihydroxy-2-methoxychalcone), a biosynthetically unique retrochalcone, and licodione (1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-1,3-propanedione), a dibezoylmethane derivative, which is the possible precursor of echinatin, were obtained. The structures were determined by spectroscopic methods and syntheses. 1H NMR of licodione revealed new features in chemical shifts of protons of diketonic and keto-enolic forms. 7,4′-Dihydroxyflavone, two of its prenyl derivatives and formononetin were also isolated. A discussion on retrochalcone biosynthesis is presented.
