Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity.

abstract：:We studied the structure-activity relationships of a series of 2'-fluoro-2',3'-unsaturated D-nucleosides against HIV-1 in human peripheral blood mononuclear (PBM) cells. The target compounds 10-21 and 28-33 were prepared by N-glycosylation of the acetate 4, which was readily prepared from 2,3-O-isopropylidene-D-glycer...

journal_title：Journal of medicinal chemistry

authors： Lee K,Choi Y,Gumina G,Zhou W,Schinazi RF,Chu CK

更新日期：2002-03-14 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：:Two isomeric series of new thieno-fused 7-deazapurine ribonucleosides (derived from 4-substituted thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidines and thieno[3',2':4,5]pyrrolo[2,3-d]pyrimidines) were synthesized by a sequence involving Negishi coupling of 4,6-dichloropyrimidine with iodothiophenes, nucleophilic azidation, a...

journal_title：Journal of medicinal chemistry

authors： Tichý M,Smoleń S,Tloušt'ová E,Pohl R,Oždian T,Hejtmánková K,Lišková B,Gurská S,Džubák P,Hajdúch M,Hocek M

更新日期：2017-03-23 00:00:00

abstract：:The interaction between β-catenin and B-cell CLL/lymphoma 9 (BCL9), critical for the transcriptional activity of β-catenin, is mediated by a helical segment from BCL9 and a large binding groove in β-catenin. Design of potent, metabolically stable BCL9 peptides represents an attractive approach to inhibit the activity ...

journal_title：Journal of medicinal chemistry

authors： Kawamoto SA,Coleska A,Ran X,Yi H,Yang CY,Wang S

更新日期：2012-02-09 00:00:00

abstract：:Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca(2+) stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the subs...

journal_title：Journal of medicinal chemistry

authors： Natarajan A,Guo Y,Harbinski F,Fan YH,Chen H,Luus L,Diercks J,Aktas H,Chorev M,Halperin JA

更新日期：2004-10-07 00:00:00

abstract：:The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...

journal_title：Journal of medicinal chemistry

authors： Green J,Cao J,Bandarage UK,Gao H,Court J,Marhefka C,Jacobs M,Taslimi P,Newsome D,Nakayama T,Shah S,Rodems S

更新日期：2015-06-25 00:00:00

abstract：:A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u...

journal_title：Journal of medicinal chemistry

authors： Saari WS,Freedman MB,Hartman RD,King SW,Raab AW,Randall WC,Engelhardt EL,Hirschmann R,Rosegay A,Ludden CT,Scriabine A

更新日期：1978-08-01 00:00:00

abstract：:The synthesis and biological evaluation of a series of novel 1-(aryloxy)-2-propanolamines and several related deshydroxy analogues are described. Compounds 4-29 were prepared and investigated for their class III electrophysiological activity in isolated canine Purkinje fibers and in anesthetized open-chest dogs. None ...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Spinelli W,Anantharaman V,Marcopulos N,Parsons RW,Moubarak IF,Cullinan C,Bagli JF

更新日期：1991-11-01 00:00:00

abstract：:The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...

journal_title：Journal of medicinal chemistry

authors： Granberg KL,Yuan ZQ,Lindmark B,Edman K,Kajanus J,Hogner A,Malmgren M,O'Mahony G,Nordqvist A,Lindberg J,Tångefjord S,Kossenjans M,Löfberg C,Brånalt J,Liu D,Selmi N,Nikitidis G,Nordberg P,Hayen A,Aagaard A,Hansson E

更新日期：2019-02-14 00:00:00

abstract：:A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...

journal_title：Journal of medicinal chemistry

authors： Nishikawa Y,Shindo T,Ishii K,Nakamura H,Kon T,Uno H

更新日期：1989-03-01 00:00:00

abstract：:HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimizatio...

journal_title：Journal of medicinal chemistry

authors： Jiang Y,Andrews SW,Condroski KR,Buckman B,Serebryany V,Wenglowsky S,Kennedy AL,Madduru MR,Wang B,Lyon M,Doherty GA,Woodard BT,Lemieux C,Geck Do M,Zhang H,Ballard J,Vigers G,Brandhuber BJ,Stengel P,Josey JA,Beigelm

更新日期：2014-03-13 00:00:00

abstract：:Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0....

journal_title：Journal of medicinal chemistry

authors： Debnath AK,Hansch C,Kim KH,Martin YC

更新日期：1993-04-16 00:00:00

abstract：:Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibit...

journal_title：Journal of medicinal chemistry

authors： Zhang Y,Feng J,Jia Y,Wang X,Zhang L,Liu C,Fang H,Xu W

更新日期：2011-04-28 00:00:00

abstract：:Vacuolar type ATPase (V-ATPase) has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with archazolids, complex polyketide macrolides, which present the most potent V-ATPase inhibitors known to date. Herein, we report a biomimetic, one-step preparation of archazoli...

journal_title：Journal of medicinal chemistry

authors： Scheeff S,Rivière S,Ruiz J,Abdelrahman A,Schulz-Fincke AC,Köse M,Tiburcy F,Wieczorek H,Gütschow M,Müller CE,Menche D

更新日期：2020-02-27 00:00:00

abstract：:A structure-activity study was performed to examine the role of position 14 of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) in activating the CGRP receptor. Interestingly, position 14 of h-alpha-CGRP contains a glycyl residue and is part of an alpha-helix spanning residues 8-18. Analogues [Ala14]-h-alpha...

journal_title：Journal of medicinal chemistry

authors： Li J,Matsuura JE,Waugh DJ,Adrian TE,Abel PW,Manning MC,Smith DD

更新日期：1997-09-12 00:00:00

abstract：:The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

journal_title：Journal of medicinal chemistry

authors： Kumari S,Carmona AV,Tiwari AK,Trippier PC

更新日期：2020-11-12 00:00:00

abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...

journal_title：Journal of medicinal chemistry

authors： Conejo-García A,Campos JM,Sánchez-Martín RM,Gallo MA,Espinosa A

更新日期：2003-08-14 00:00:00

abstract：:A simple pharmacophore point filter has been developed that discriminates between drug-like and nondrug-like chemical matter. It is based on the observation that nondrugs are often underfunctionalized. Therefore, a minimum count of well-defined pharmacophore points is required to pass the filter. The application of th...

journal_title：Journal of medicinal chemistry

authors： Muegge I,Heald SL,Brittelli D

更新日期：2001-06-07 00:00:00

abstract：:In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pre...

journal_title：Journal of medicinal chemistry

authors： Valcavi U,Corsi B,Caponi R,Innocenti S,Martelli P

更新日期：1975-12-01 00:00:00

abstract：:A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition...

journal_title：Journal of medicinal chemistry

authors： Shengule SR,Loa-Kum-Cheung WL,Parish CR,Blairvacq M,Meijer L,Nakao Y,Karuso P

更新日期：2011-04-14 00:00:00

abstract：:The synthesis of 15 compounds related either to the benz[c]acridine or to the benz[a]acridine series is reported. Spectral data, i.e., NMR and EI fragmentation, are given. These compounds were tested for carcinogenic activity in mice of the XVIInc/Z strain by subcutaneous injection. Only three weak carcinogens were de...

journal_title：Journal of medicinal chemistry

authors： Croisy-Delcey M,Croisy A,Zajdela F,Lhoste JM

更新日期：1983-02-01 00:00:00

abstract：:A series of novel 2-substituted acetylenic pyrrolidines and piperidines related to oxotremorine (1) were prepared and evaluated in vitro as muscarinic cholinergic agents at brain M1 and M2 receptors. One analogue, 3-(2-oxo-1-pyrrolidinyl)-1-[2(R)-pyrrolidinyl]-1-propyne hydrogen oxalate (6a), was found to be a partial...

journal_title：Journal of medicinal chemistry

authors： Garvey DS,Wasicak JT,Chung JY,Shue YK,Carrera GM,May PD,McKinney MM,Anderson D,Cadman E,Vella-Rountree L

更新日期：1992-05-01 00:00:00

abstract：:When cephalosporins exert their biological activity by reacting with bacterial enzymes, opening of the beta-lactam ring can lead to expulsion of the 3'-substituent. A series of cephalosporins was prepared in which antibacterial quinolones were linked to the 3'-position through a quaternary nitrogen. Like the 3'-ester-...

journal_title：Journal of medicinal chemistry

authors： Albrecht HA,Beskid G,Christenson JG,Durkin JW,Fallat V,Georgopapadakou NH,Keith DD,Konzelmann FM,Lipschitz ER,McGarry DH

更新日期：1991-02-01 00:00:00

abstract：:A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactiva...

journal_title：Journal of medicinal chemistry

authors： Yang BV,Weinstein DS,Doweyko LM,Gong H,Vaccaro W,Huynh T,Xiao HY,Doweyko AM,McKay L,Holloway DA,Somerville JE,Habte S,Cunningham M,McMahon M,Townsend R,Shuster D,Dodd JH,Nadler SG,Barrish JC

更新日期：2010-12-09 00:00:00

abstract：:Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure...

journal_title：Journal of medicinal chemistry

authors： Johnson CN,Ahn JS,Buck IM,Chiarparin E,Day JEH,Hopkins A,Howard S,Lewis EJ,Martins V,Millemaggi A,Munck JM,Page LW,Peakman T,Reader M,Rich SJ,Saxty G,Smyth T,Thompson NT,Ward GA,Williams PA,Wilsher NE,Chessari G

更新日期：2018-08-23 00:00:00

abstract：:The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [ cyclo(-d-Tyr-l-Arg...

journal_title：Journal of medicinal chemistry

authors： Sekiguchi H,Kuroyanagi T,Rhainds D,Kobayashi K,Kobayashi Y,Ohno H,Heveker N,Akaji K,Fujii N,Oishi S

更新日期：2018-04-26 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine...

journal_title：Journal of medicinal chemistry

authors： Chwang TL,Wood WF,Parkhurst JR,Nesnow S,Danenberg PV,Heidelberger C

更新日期：1976-05-01 00:00:00

abstract：:A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around th...

journal_title：Journal of medicinal chemistry

authors： Judd WR,Slattum PM,Hoang KC,Bhoite L,Valppu L,Alberts G,Brown B,Roth B,Ostanin K,Huang L,Wettstein D,Richards B,Willardsen JA

更新日期：2011-07-28 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 00:00:00