Novel synthesis, cytotoxic evaluation, and structure-activity relationship studies of a series of alpha-alkylidene-gamma-lactones and lactams.

abstract：:3',5'-Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger that regulates numerous biological processes under physiological and pathological conditions, including cancer, diabetes, heart failure, inflammation, and neurological disorders. In the past, all effects of cAMP were initially believed to be med...

journal_title：Journal of medicinal chemistry

authors： Chen H,Wild C,Zhou X,Ye N,Cheng X,Zhou J

更新日期：2014-05-08 00:00:00

abstract：:The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rea...

journal_title：Journal of medicinal chemistry

authors： Dorey G,Dubois L,Prodo de Carvalho LP,Potier P,Dodd RH

更新日期：1995-01-06 00:00:00

abstract：:Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design...

journal_title：Journal of medicinal chemistry

authors： Carolan CG,Dillon GP,Khan D,Ryder SA,Gaynor JM,Reidy S,Marquez JF,Jones M,Holland V,Gilmer JF

更新日期：2010-02-11 00:00:00

abstract：:The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-don...

journal_title：Journal of medicinal chemistry

authors： Martinez A,Gil C,Abasolo MI,Castro A,Bruno AM,Perez C,Prieto C,Otero J

更新日期：2000-08-24 00:00:00

abstract：:Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoi...

journal_title：Journal of medicinal chemistry

authors： Hilpert K,Ackermann J,Banner DW,Gast A,Gubernator K,Hadváry P,Labler L,Müller K,Schmid G,Tschopp TB

更新日期：1994-11-11 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining the crystallographic binding mode. By selection of a small set of representatives, the experimentally observed binding mode can be...

journal_title：Journal of medicinal chemistry

authors： Källblad P,Mancera RL,Todorov NP

更新日期：2004-06-17 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:The HIV-1 central nervous system infection leads to the onset of neurological impairments called AIDS dementia complex (ADC). PAF plays an important role in this pathology, as it is an HIV-1-induced neurotoxin produced by infected or activated macrophages and microglia, in the brain. We previously reported that PAF-an...

journal_title：Journal of medicinal chemistry

authors： Serradji N,Martin M,Bensaid O,Cisternino S,Rousselle C,Dereuddre-Bosquet N,Huet J,Redeuilh C,Lamouri A,Dong CZ,Clayette P,Scherrmann JM,Dormont D,Heymans F

更新日期：2004-12-02 00:00:00

abstract：:5-Oxo-ETE is the most powerful eosinophil chemoattractant among lipid mediators. Eosinophil infiltration into the lungs of asthmatics may be responsible for the late phase of inflammatory asthma. We have designed and synthesized a 5-oxo-ETE receptor antagonist, the purpose of which is to prevent eosinophil migration t...

journal_title：Journal of medicinal chemistry

authors： Gore V,Patel P,Chang CT,Sivendran S,Kang N,Ouedraogo YP,Gravel S,Powell WS,Rokach J

更新日期：2013-05-09 00:00:00

abstract：:We present the first report of the application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to hydroxy-containing drug derivatives. In particular, we applied this strategy to the highly lipophilic antiviral drug family of bicyclic furanopyrimidine nucleoside analogues (BCNA) in order to improve t...

journal_title：Journal of medicinal chemistry

authors： Diez-Torrubia A,Balzarini J,Andrei G,Snoeck R,De Meester I,Camarasa MJ,Velázquez S

更新日期：2011-03-24 00:00:00

abstract：:Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the...

journal_title：Journal of medicinal chemistry

authors： Löber S,Hübner H,Utz W,Gmeiner P

更新日期：2001-08-16 00:00:00

abstract：:The observed structure-activity relationship of three distinct ATP noncompetitive With-No-Lysine (WNK) kinase inhibitor series, together with a crystal structure of a previously disclosed allosteric inhibitor bound to WNK1, led to an overlay hypothesis defining core and side-chain relationships across the different se...

journal_title：Journal of medicinal chemistry

authors： Yamada K,Levell J,Yoon T,Kohls D,Yowe D,Rigel DF,Imase H,Yuan J,Yasoshima K,DiPetrillo K,Monovich L,Xu L,Zhu M,Kato M,Jain M,Idamakanti N,Taslimi P,Kawanami T,Argikar UA,Kunjathoor V,Xie X,Yagi YI,Iwaki Y,Ro

更新日期：2017-08-24 00:00:00

abstract：:SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrat...

journal_title：Journal of medicinal chemistry

authors： Xue CB,He X,Corbett RL,Roderick J,Wasserman ZR,Liu RQ,Jaffee BD,Covington MB,Qian M,Trzaskos JM,Newton RC,Magolda RL,Wexler RR,Decicco CP

更新日期：2001-10-11 00:00:00

abstract：:Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...

journal_title：Journal of medicinal chemistry

authors： Sall DJ,Kaiser RE Jr

更新日期：1993-08-06 00:00:00

abstract：:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting...

journal_title：Journal of medicinal chemistry

authors： Hübner H,Haubmann C,Utz W,Gmeiner P

更新日期：2000-02-24 00:00:00

abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...

journal_title：Journal of medicinal chemistry

authors： Weet JF,Lenz GR

更新日期：1985-02-01 00:00:00

abstract：:Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding m...

journal_title：Journal of medicinal chemistry

authors： Xiao Z,Chen D,Song S,van der Vlag R,van der Wouden PE,van Merkerk R,Cool RH,Hirsch AKH,Melgert BN,Quax WJ,Poelarends GJ,Dekker FJ

更新日期：2020-10-22 00:00:00

abstract：:3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the ph...

journal_title：Journal of medicinal chemistry

authors： Cervetto L,Demontis GC,Giannaccini G,Longoni B,Macchia B,Macchia M,Martinelli A,Orlandini E

更新日期：1998-12-03 00:00:00

abstract：:Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluor...

journal_title：Journal of medicinal chemistry

authors： Galante E,Okamura T,Sander K,Kikuchi T,Okada M,Zhang MR,Robson M,Badar A,Lythgoe M,Koepp M,Årstad E

更新日期：2014-02-13 00:00:00

abstract：:A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration proces...

journal_title：Journal of medicinal chemistry

authors： Pasquini S,Mugnaini C,Tintori C,Botta M,Trejos A,Arvela RK,Larhed M,Witvrouw M,Michiels M,Christ F,Debyser Z,Corelli F

更新日期：2008-08-28 00:00:00

abstract：:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a po...

journal_title：Journal of medicinal chemistry

authors： Xu J,Cole DC,Chang CP,Ayyad R,Asselin M,Hao W,Gibbons J,Jelinsky SA,Saraf KA,Park K

更新日期：2008-07-24 00:00:00

abstract：:Hydroxylated, methoxylated, and/or chlorinated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines were generally synthesized out of substituted 2-phenylethylamines and isochromanones by Bischler-Napieralski cyclization of the resulting benzamides to dibenzoquinolizines and the quaternization and cleavage of the centra...

journal_title：Journal of medicinal chemistry

authors： Mohr P,Decker M,Enzensperger C,Lehmann J

更新日期：2006-03-23 00:00:00

abstract：:Dequalinium (4) is a potent and selective blocker of small conductance Ca2+-activated K+ channels, an important but relatively little studied class. The 4-NH2 group of dequalinium has been shown to contribute significantly to blocking potency. In this study, we have investigated further the role of the 4-NH2 group. Re...

journal_title：Journal of medicinal chemistry

authors： Galanakis D,Calder JA,Ganellin CR,Owen CS,Dunn PM

更新日期：1995-09-01 00:00:00

abstract：:Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mi...

journal_title：Journal of medicinal chemistry

authors： Akcan M,Stroud MR,Hansen SJ,Clark RJ,Daly NL,Craik DJ,Olson JM

更新日期：2011-02-10 00:00:00

abstract：:Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthe...

journal_title：Journal of medicinal chemistry

authors： Barthel BL,Rudnicki DL,Kirby TP,Colvin SM,Burkhart DJ,Koch TH

更新日期：2012-07-26 00:00:00

abstract：:Aberrant RET kinase signaling plays critical roles in several human cancers such as thyroid carcinoma. The gatekeeper mutants (V804L or V804M) of RET are resistant to currently approved RET inhibitors such as cabozantinib and vandetanib. We, for the first time, report a highly selective and extremely potent RET inhibi...

journal_title：Journal of medicinal chemistry

authors： Yoon H,Kwak Y,Choi S,Cho H,Kim ND,Sim T

更新日期：2016-01-14 00:00:00

abstract：:The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic...

journal_title：Journal of medicinal chemistry

authors： Biswas K,Peterkin TA,Bryan MC,Arik L,Lehto SG,Sun H,Hsieh FY,Xu C,Fremeau RT,Allen JR

更新日期：2011-10-27 00:00:00

abstract：:In a continuation of studies directed toward characterizing the hydrophilic pocket within the aromatic ring binding region of the active site of phenylethanolamine N-methyltransferase (PNMT), 5-, 6-, 7-, and 8-hydroxy-1,2,3,4-tetrahydroisoquinoline were prepared and evaluated as substrates and inhibitors of PNMT. In o...

journal_title：Journal of medicinal chemistry

authors： Sall DJ,Grunewald GL

更新日期：1987-12-01 00:00:00

abstract：:Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such stud...

journal_title：Journal of medicinal chemistry

authors： Brouwer C,Jenko K,Zoghbi SS,Innis RB,Pike VW

更新日期：2014-07-24 00:00:00