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Showing 1-30 of 293 results for "59356-U" within Papers
Zheyi Hu et al.
PloS one, 10(2), e0116886-e0116886 (2015-02-18)
Multidrug efflux transporter P-glycoprotein (P-gp) is highly expressed on membrane of tumor cells and is implicated in resistance to tumor chemotherapy. HZ08 is synthesized and studied in order to find a novel P-gp inhibitor. MDCK-MDR1 monolayer transport, calcein-AM P-gp inhibition
Min Wu et al.
The European journal of neuroscience, 18(5), 1155-1168 (2003-09-06)
Tonic impulse flow in the septohippocampal GABAergic pathway is essential for normal cognitive functioning and is sustained, in part, by acetylcholine (ACh) that is released locally via axon collaterals of septohippocampal cholinergic neurons. Septohippocampal cholinergic neurons degenerate in Alzheimer's disease
Thomas J Woltering et al.
Bioorganic & medicinal chemistry letters, 18(3), 1091-1095 (2007-12-22)
A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Replacement of a cyano group by a five-membered heterocycle produced compounds inhibiting the binding of [(3)H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both
Yu Luo et al.
Scientific reports, 7, 42064-42064 (2017-02-07)
Halohydrin dehalogenases (HHDHs) are biocatalytically interesting enzymes due to their ability to form C-C, C-N, C-O, and C-S bonds. One of most important application of HHDH was the protein engineering of HheC (halohydrin dehalogenase from Agrobacterium radiobacter AD1) for the
Aaron D Finke et al.
Chemical record (New York, N.Y.), 15(1), 19-30 (2014-10-14)
6,6-Dicyanopentafulvene (DCF) is a fascinating molecular entity that consists of a cyclopentadiene ring conjugated to an exocyclic double bond bearing two cyano groups on its periphery. Herein, we give a brief history of the chemistry of DCFs prior to our
Fan Zhang et al.
European journal of medicinal chemistry, 46(7), 3149-3157 (2011-04-26)
A series of novel 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives were synthesized and their cytotoxic activity against A549, H460, HT-29 and SMMC-7721 cell lines was evaluated in vitro. Among them, ten compounds (10, 11, 14, 16, 17, 26, 27, 29, 30 and 31) displayed
Harry H Wasserman et al.
Current opinion in drug discovery & development, 9(6), 670-699 (2006-11-23)
During recent years, fresh attention has been given to a functional group aggregate in which three carbonyl groups have been assembled in a 1,2,3-vicinal relationship. This vicinal tricarbonyl system represents a potent electrophilic unit, usually stabilized in the form of
Llorente V R Boñaga et al.
Journal of the American Chemical Society, 127(10), 3473-3485 (2005-03-10)
We investigated the formation of macrocycles from alpha,omega-diynes in cobalt-mediated co-cyclotrimerization reactions. Long-chain alpha,omega-diynes underwent metal-mediated [2 + 2 + 2] cycloadditions with nitriles, cyanamides, or isocyanates in the presence of CpCo(CO)2 (Cp = cyclopentadienide) to yield pyridine-containing macrocycles, i.e.
Jijia Li et al.
International journal of cancer, 134(8), 1972-1980 (2013-10-24)
Increasing evidence suggests that the noncanonical IKKs play critical roles in tumor genesis and development, leading to the notion that noncanonical IKKs may be good targets for cancer therapy. Here, we demonstrate that although TBK1 is not overexpressed or constitutively
P C Astles et al.
Journal of medicinal chemistry, 41(15), 2732-2744 (1998-07-21)
The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated.
Jeremy Shonberg et al.
Journal of medicinal chemistry, 58(13), 5287-5307 (2015-06-09)
We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on
Jose María Cid et al.
Journal of medicinal chemistry, 55(5), 2388-2405 (2012-03-01)
The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay
S Ghosh et al.
Acta crystallographica. Section C, Crystal structure communications, 56 ( Pt 10), 1254-1257 (2000-10-12)
The title compounds, 1-cyano-2-hydroxy-N-[4-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI492, 1-cyano-2-hydroxy-N-[3-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI493, and N-[3-bromo-4-(trifluoromethoxy)phenyl]-1-cyano-2-hydroxybut-2-e namide , C(12)H(8)BrF(3)N(2)O(3), PHI495, are potent inhibitors of Bruton's tyrosine kinase (BTK). The molecular structures of these compounds are similar and they display similar hydrogen-bonding networks and crystal packing.
T Fukami et al.
Journal of medicinal chemistry, 39(12), 2313-2330 (1996-06-07)
Continuing studies on modifications of potent cyclic pentapeptide endothelin (ET) receptor antagonists, represented by BQ-123, and potent linear tripeptide derivative ET receptor antagonists, represented by BQ-788, are described herein. The introduction of D-tryptophan analogues with C-2 substituents in these peptidic
Oliver E Hutt et al.
Organic letters, 15(7), 1602-1605 (2013-03-28)
We have applied a diversity-oriented approach for the synthesis of skeletally diverse and stereochemically complex templates for small-molecule library production by performing Beckmann rearrangement and Beckmann fragmentation reactions on the bicyclo[3.2.1]octane rings of steviol and isosteviol, aglycones derived from the
T A Verdoorn et al.
European journal of pharmacology, 269(1), 43-49 (1994-09-15)
The diversity of neuronal glutamate receptors continues to increase with the discovery of multiple subunits and subunit families. The significance of this potential receptor heterogeneity is unknown because pharmacological tools that could clearly distinguish between different structural isoforms have not
Joanna Parkinson et al.
Journal of pharmacological and toxicological methods, 68(3), 357-366 (2013-04-10)
Preclinical assessment of the heart rate corrected QT interval (QTc) is an important component of the cardiovascular safety evaluation in drug discovery. Here we aimed to quantify the translational relationship between QTc prolongation and shortening in the conscious telemetered dog
Ana Suárez-Suárez et al.
Analytica chimica acta, 701(1), 81-85 (2011-07-19)
A high-performance liquid chromatography method was developed for the separation and determination of four cobalamins in seawater. Chromatographic separation was performed on a reversed-phase discovery RP-amide C(16) column with buffer potassium dihydrogenphosphate and acetonitrile as the mobile phases in linear
Yuki Yuza et al.
Cancer biology & therapy, 6(5), 661-667 (2007-05-15)
Targeted cancer therapies impede cancer cell growth by inhibiting the function of activated oncogene products. Patients with non-small cell lung cancer and somatic mutations of EGFR can have a dramatic response to treatment with erlotinib and gefitinib; different somatic mutations
Jun Liang et al.
Journal of medicinal chemistry, 56(11), 4521-4536 (2013-05-15)
Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with lead molecule 3. We used structure-based design to discover 2,6-dichloro-4-cyanophenyl and (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved TYK2 potency and JAK1
Michael C Pirrung et al.
Proceedings of the National Academy of Sciences of the United States of America, 100(22), 12548-12553 (2003-10-15)
A design principle for a two-photon photochemically removable protecting group based on sequential one-photon processes has been established. The expected performance of such groups in spatially directed photoactivation/photodeprotection has been shown by a kinetic analysis. One particular molecular class fitting
Taisuke Uehara et al.
Nature chemical biology, 13(6), 675-680 (2017-04-25)
Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory
K Yoshiizumi et al.
Chemical & pharmaceutical bulletin, 45(12), 2005-2010 (1998-01-20)
In our series of studies on potassium channel openers, several thienylcyanoguanidine derivatives were synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N"-tert-pentylguanidine (4b) and N-(5-bromo-3-thienyl)-N'-cyano-N"-tert-pentylguanidine (4f) exhibited excellent activity which was proved to
Joseph A Buonomo et al.
Chemistry (Weinheim an der Bergstrasse, Germany), 23(58), 14434-14438 (2017-08-26)
Reduction of phosphine oxides to the corresponding phosphines represents the most straightforward method to prepare these valuable reagents. However, existing methods to reduce phosphine oxides suffer from inadequate chemoselectivity due to the strength of the P=O bond and/or poor atom
Craig W Lindsley et al.
ACS chemical neuroscience, 2(8), 471-482 (2011-09-20)
Glutamate is the major excitatory transmitter in the mammalian CNS, exerting its effects through both ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGlus) belong to family C of the G-protein-coupled receptors (GPCRs). The eight mGlus identified to date
Catherine Higgins et al.
Bioorganic & medicinal chemistry letters, 24(11), 2521-2524 (2014-04-30)
This Letter describes the further development and SAR exploration of a novel series of Legumain inhibitors. Based upon a previously identified Legumain inhibitor from our group, we explored the SAR of the carbamate phenyl ring system to probe the P3
Mark Tarleton et al.
European journal of medicinal chemistry, 57, 65-73 (2012-10-11)
We previously reported the discovery of a simple conjugated cyano pharmacophore which had led to the development of (Z)-2-(3,4-dichlorophenyl)-3-(4-nitrophenyl)acrylonitrile, as a selective inhibitor of oestrogen receptor positive (ER+ve) human breast cancer cell line, MCF-7. Further exploration though modification of the
Mei-Jung Lai et al.
Journal of medicinal chemistry, 58(16), 6549-6558 (2015-08-05)
A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4'-cyano-3'-fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI50 value of 57.5
Franz von Nussbaum et al.
ChemMedChem, 10(7), 1163-1173 (2015-06-18)
Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung
Svetlana L Belyanskaya et al.
Chembiochem : a European journal of chemical biology, 18(9), 837-842 (2017-03-11)
DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity
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