Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors.

abstract：:A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cel...

journal_title：Journal of medicinal chemistry

authors： Han G,Quillan JM,Carlson K,Sadée W,Hruby VJ

更新日期：2003-02-27 00:00:00

abstract：:Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I i...

journal_title：Journal of medicinal chemistry

authors： Ioanoviciu A,Antony S,Pommier Y,Staker BL,Stewart L,Cushman M

更新日期：2005-07-28 00:00:00

abstract：:The mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) is currently in clinical trial as an anticancer drug. A series of acridine-substituted analogues were prepared, using a new synthetic route to substituted acridine-4-carboxylic acids (conversion of substituted diphenylamine ...

journal_title：Journal of medicinal chemistry

authors： Spicer JA,Gamage SA,Atwell GJ,Finlay GJ,Baguley BC,Denny WA

更新日期：1997-06-06 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...

journal_title：Journal of medicinal chemistry

authors： Batra S,Srivastava P,Roy K,Pandey VC,Bhaduri AP

更新日期：2000-09-07 00:00:00

abstract：:A series of 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter (DAT). The in vitro affinity (Ki) for the DAT of the 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl) methyl]tropane analogues was determined by inhibition...

journal_title：Journal of medicinal chemistry

authors： Lomenzo SA,Izenwasser S,Katz JL,Terry PD,Zhu N,Klein CL,Trudell ML

更新日期：1997-12-19 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：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:This paper describes an extended structure-activity relationships study of aminotetralin-piperazine-based hybrid molecules developed earlier for dopamine D2/D3 receptors. Various analogues as positional isomers have been developed where location of the phenolic hydroxyl group has been varied on the aromatic ring. Betw...

journal_title：Journal of medicinal chemistry

authors： Biswas S,Zhang S,Fernandez F,Ghosh B,Zhen J,Kuzhikandathil E,Reith ME,Dutta AK

更新日期：2008-01-10 00:00:00

abstract：:New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affin...

journal_title：Journal of medicinal chemistry

authors： Crosignani S,Prêtre A,Jorand-Lebrun C,Fraboulet G,Seenisamy J,Augustine JK,Missotten M,Humbert Y,Cleva C,Abla N,Daff H,Schott O,Schneider M,Burgat-Charvillon F,Rivron D,Hamernig I,Arrighi JF,Gaudet M,Zimmerli SC,Jui

更新日期：2011-10-27 00:00:00

abstract：:Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the...

journal_title：Journal of medicinal chemistry

authors： Gao M,Duan L,Luo J,Zhang L,Lu X,Zhang Y,Zhang Z,Tu Z,Xu Y,Ren X,Ding K

更新日期：2013-04-25 00:00:00

abstract：:An endogenous heptadecapeptide, nociceptin/orphanin FQ (N/OFQ), and a G-protein-coupled receptor, N/OFQ peptide (NOP) receptor [or opioid-receptor-like-1 (ORL1) receptor], have been described in terms of its structure, distribution, and pharmacology. Thus, the N/OFQ and NOP receptor are located in the central nervous ...

journal_title：Journal of medicinal chemistry

authors： Hayashi S,Hirao A,Imai A,Nakamura H,Murata Y,Ohashi K,Nakata E

更新日期：2009-02-12 00:00:00

abstract：:By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor ...

journal_title：Journal of medicinal chemistry

authors： Tung JS,Davis DL,Anderson JP,Walker DE,Mamo S,Jewett N,Hom RK,Sinha S,Thorsett ED,John V

更新日期：2002-01-17 00:00:00

abstract：:4,5-Diphenyl-4-isoxazolines (13a-k) possessing a variety of substituents (H, F, MeS, MeSO2) at the para position of one of the phenyl rings were synthesized for evaluation as analgesic and selective cyclooxygenase-2 (COX-2) inhibitory antiinflammatory (AI) agents. Although the 4,5-phenyl-4-isoxazolines (13a-d,f), whic...

journal_title：Journal of medicinal chemistry

authors： Habeeb AG,Praveen Rao PN,Knaus EE

更新日期：2001-08-30 00:00:00

abstract：:Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the clinic for PDE4 inhibitors, primarily due to PDE4 mediated side effe...

journal_title：Journal of medicinal chemistry

authors： Felding J,Sørensen MD,Poulsen TD,Larsen J,Andersson C,Refer P,Engell K,Ladefoged LG,Thormann T,Vinggaard AM,Hegardt P,Søhoel A,Nielsen SF

更新日期：2014-07-24 00:00:00

abstract：:A number of new 4(1H)-quinazolinones were synthesized and evaluated in the carrageenin-induced paw edema test. Most of the compounds were obtained by the cyclization of the appropriately substituted anthranilamides with acid chlorides, followed by further chemical transformation. Structure-activity data suggest that 2...

journal_title：Journal of medicinal chemistry

authors： Ozaki K,Yamada Y,Oine T,Ishizuka T,Iwasawa Y

更新日期：1985-05-01 00:00:00

abstract：:The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, res...

journal_title：Journal of medicinal chemistry

authors： Blake JF,Burkard M,Chan J,Chen H,Chou KJ,Diaz D,Dudley DA,Gaudino JJ,Gould SE,Grina J,Hunsaker T,Liu L,Martinson M,Moreno D,Mueller L,Orr C,Pacheco P,Qin A,Rasor K,Ren L,Robarge K,Shahidi-Latham S,Stults J,S

更新日期：2016-06-23 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...

journal_title：Journal of medicinal chemistry

authors： Patel S,Cohen F,Dean BJ,De La Torre K,Deshmukh G,Estrada AA,Ghosh AS,Gibbons P,Gustafson A,Huestis MP,Le Pichon CE,Lin H,Liu W,Liu X,Liu Y,Ly CQ,Lyssikatos JP,Ma C,Scearce-Levie K,Shin YG,Solanoy H,Stark KL,Wa

更新日期：2015-01-08 00:00:00

abstract：:The retinoid 6-[3'-(1-adamantyl)-4'-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) and its active analogues induce cell-cycle arrest and programmed cell death (apoptosis) in cancer cells independently of retinoic acid receptor (RAR) interaction. Its analogue, (E)-4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-(3'-acetami...

journal_title：Journal of medicinal chemistry

authors： Dawson MI,Harris DL,Liu G,Hobbs PD,Lange CW,Jong L,Bruey-Sedano N,James SY,Zhang XK,Peterson VJ,Leid M,Farhana L,Rishi AK,Fontana JA

更新日期：2004-07-01 00:00:00

abstract：:In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding assays in CHO c...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Antonello A,Cavalli A,Bolognesi ML,Minarini A,Marucci G,Poggesi E,Leonardi A,Melchiorre C

更新日期：2003-11-06 00:00:00

abstract：:The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the va...

journal_title：Journal of medicinal chemistry

authors： Dyckman AJ

更新日期：2017-07-13 00:00:00

abstract：:Histone deacetylase 6 (HDAC6) removes the acetyl group from lysine residues in a number of non-histone substrates and plays important roles in microtubule dynamics and chaperone activities. There is growing interest in identifying HDAC6-selective inhibitors as chemical biology tools and ultimately as new therapeutic a...

journal_title：Journal of medicinal chemistry

authors： Lin X,Chen W,Qiu Z,Guo L,Zhu W,Li W,Wang Z,Zhang W,Zhang Z,Rong Y,Zhang M,Yu L,Zhong S,Zhao R,Wu X,Wong JC,Tang G

更新日期：2015-03-26 00:00:00

abstract：:A number of fatty acyl derivatives of (-)-2',3'-dideoxy-3'-thiacytidine (lamivudine, 3TC, 1) were synthesized and evaluated for their anti-HIV activity. The monosubstituted 5'-O-fatty acyl derivatives of 3TC (EC(50) = 0.2-2.3 μM) were more potent than the corresponding monosubstituted N(4)-fatty acyl (EC(50) = 0.4-29....

journal_title：Journal of medicinal chemistry

authors： Agarwal HK,Chhikara BS,Hanley MJ,Ye G,Doncel GF,Parang K

更新日期：2012-05-24 00:00:00

abstract：:Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug ta...

journal_title：Journal of medicinal chemistry

authors： Monti E,Gariboldi M,Maiocchi A,Marengo E,Cassino C,Gabano E,Osella D

更新日期：2005-02-10 00:00:00

abstract：:Human G93A-superoxide dismutase-1 (G93AhSOD1) mutation causes amyotrophic lateral sclerosis (ALS) in rodents and humans. Recent observations indicate gain of interaction of G93AhSOD1 with cytosolic malate dehydrogenase (MDH1) and subsequent impairment in the malate aspartate shuttle which is vital to neurons. Using fl...

journal_title：Journal of medicinal chemistry

authors： Mali Y,Zisapel N

更新日期：2009-09-10 00:00:00

abstract：:A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies...

journal_title：Journal of medicinal chemistry

authors： Morales P,Gómez-Cañas M,Navarro G,Hurst DP,Carrillo-Salinas FJ,Lagartera L,Pazos R,Goya P,Reggio PH,Guaza C,Franco R,Fernández-Ruiz J,Jagerovic N

更新日期：2016-07-28 00:00:00

abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...

journal_title：Journal of medicinal chemistry

authors： Costantino V,D'Esposito M,Fattorusso E,Mangoni A,Basilico N,Parapini S,Taramelli D

更新日期：2005-11-17 00:00:00

abstract：:Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated clinical efficacy in the treatment of acute migraine. Herein, we describe the design, synthesis, and preclinical characterization of a highly potent, oral CGRP receptor antagonist BMS-927711 (8). Compound 8 has good oral bioavailability in r...

journal_title：Journal of medicinal chemistry

authors： Luo G,Chen L,Conway CM,Denton R,Keavy D,Signor L,Kostich W,Lentz KA,Santone KS,Schartman R,Browning M,Tong G,Houston JG,Dubowchik GM,Macor JE

更新日期：2012-12-13 00:00:00

abstract：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...

journal_title：Journal of medicinal chemistry

authors： Monte AP,Marona-Lewicka D,Cozzi NV,Nichols DE

更新日期：1993-11-12 00:00:00

abstract：:A new quadruplex motif located in the promoter of the human KRAS gene, within a nuclease hypersensitive element (NHE), has been characterized. Oligonucleotides mimicking this quadruplex are found to compete with a DNA-protein complex between NHE and a nuclear extract from pancreatic cancer cells. When modified with (R...

journal_title：Journal of medicinal chemistry

authors： Cogoi S,Paramasivam M,Filichev V,Géci I,Pedersen EB,Xodo LE

更新日期：2009-01-22 00:00:00