Whole structure-activity relationships of the fat-accumulation inhibitor (-)-ternatin: recognition of the importance of each amino acid residue.

abstract：:The protein kinase C (PKC) family of serine/threonine kinases is implicated in a wide variety of cellular processes. The PKC theta (PKCtheta) isoform is involved in TCR signal transduction and T cell activation and regulates T cell mediated diseases, including lung inflammation and airway hyperresponsiveness. Thus inh...

journal_title：Journal of medicinal chemistry

authors： Cole DC,Asselin M,Brennan A,Czerwinski R,Ellingboe JW,Fitz L,Greco R,Huang X,Joseph-McCarthy D,Kelly MF,Kirisits M,Lee J,Li Y,Morgan P,Stock JR,Tsao DH,Wissner A,Yang X,Chaudhary D

更新日期：2008-10-09 00:00:00

abstract：:The AAA+ ATPase, p97, also referred to as VCP, plays an essential role in cellular homeostasis by regulating endoplasmic reticulum-associated degradation (ERAD), mitochondrial-associated degradation (MAD), chromatin-associated degradation, autophagy, and endosomal trafficking. Mutations in p97 have been linked to a nu...

journal_title：Journal of medicinal chemistry

authors： Huryn DM,Kornfilt DJP,Wipf P

更新日期：2020-03-12 00:00:00

abstract：:Treatment of 14 beta-nitrocodeinone with sodium borohydride gave the codeine derivative which was reduced with zinc dust in acetic anhydride-acetic acid solution to give 14 beta-acetamidocodeine 6-acetate. 14 beta-Thiocyanatocodeinone was obtained from the reaction of thebaine with thiocyanogen and was reduced to 14 b...

journal_title：Journal of medicinal chemistry

authors： Osei-Gyimah P,Archer S

更新日期：1980-02-01 00:00:00

abstract：:Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid ...

journal_title：Journal of medicinal chemistry

authors： Van Zandt MC,Jones ML,Gunn DE,Geraci LS,Jones JH,Sawicki DR,Sredy J,Jacot JL,Dicioccio AT,Petrova T,Mitschler A,Podjarny AD

更新日期：2005-05-05 00:00:00

abstract：:The design and synthesis of 3-amino-2-oxo-4-phenylbutanoic acid amides (alpha-keto amides), a new class of aminopeptidase inhibitor, are described. These compounds, illustrated by the Phe-Leu analogue 2, are effective inhibitors of arginyl aminopeptidase (Ki = 1.5 microM), cytosol aminopeptidase (Ki = 1.0 microM), and...

journal_title：Journal of medicinal chemistry

authors： Ocain TD,Rich DH

更新日期：1992-02-07 00:00:00

abstract：:The E and Z isomers of 2-[2-(3-chlorophenyl)-1-phenyl-1-propenyl]pyridine (2a,b) and 2-[2-(3-chlorophenyl)-1-(4-hydroxyphenyl)-1-propenyl]pyridine (4a,b) were synthesized and separated as possible metabolites of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1a). Following administration of 1a to rats, a ...

journal_title：Journal of medicinal chemistry

authors： Kokosa JM,Sinsheimer JE,Wade DR,Drach JC,Burckhalter JH

更新日期：1978-02-01 00:00:00

abstract：:We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activit...

journal_title：Journal of medicinal chemistry

authors： Flouret G,Mahan K,Majewski T

更新日期：1992-02-21 00:00:00

abstract：:A potent new class of inhibitors of phenylalanyl-tRNA synthetase from Escherichia coli B is described. N-Benzyl-2-phenylethylamine is a competitive inhibitor with respect to L-phenylalanine and appears to possess the structural features required for near-optimal binding. Hydrophobic substituents at the ortho position ...

journal_title：Journal of medicinal chemistry

authors： Anderson RT Jr,Santi DV

更新日期：1976-11-01 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Although recognized in small molecules for quite some time, the implications of halogen bonding in biomolecular systems are only now coming to light. In this study, several systems of proteins in complex with halogenated ligands have been investigated by using a two-layer QM/MM ONIOM methodology. In all cases, the hal...

journal_title：Journal of medicinal chemistry

authors： Lu Y,Shi T,Wang Y,Yang H,Yan X,Luo X,Jiang H,Zhu W

更新日期：2009-05-14 00:00:00

abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...

journal_title：Journal of medicinal chemistry

authors： Wilman DE,Cox PJ,Goddard PM,Hart LI,Merai K,Newell DR

更新日期：1984-07-01 00:00:00

abstract：:Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior h...

journal_title：Journal of medicinal chemistry

authors： Saavedra JE,Southan GJ,Davies KM,Lundell A,Markou C,Hanson SR,Adrie C,Hurford WE,Zapol WM,Keefer LK

更新日期：1996-10-25 00:00:00

abstract：:4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 microM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prost...

journal_title：Journal of medicinal chemistry

authors： Meanwell NA,Rosenfeld MJ,Trehan AK,Wright JJ,Brassard CL,Buchanan JO,Federici ME,Fleming JS,Gamberdella M,Zavoico GB

更新日期：1992-09-18 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 00:00:00

abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

journal_title：Journal of medicinal chemistry

authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

更新日期：2005-03-10 00:00:00

abstract：:The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corres...

journal_title：Journal of medicinal chemistry

authors： Rosati RL,Kapili LV,Morrissey P,Retsema JA

更新日期：1990-01-01 00:00:00

abstract：:Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an ...

journal_title：Journal of medicinal chemistry

authors： Chuang S,Velkov T,Horne J,Porter CJ,Scanlon MJ

更新日期：2008-07-10 00:00:00

abstract：:Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)met...

journal_title：Journal of medicinal chemistry

authors： Lesiak K,Watanabe KA,Majumdar A,Powell J,Seidman M,Vanderveen K,Goldstein BM,Pankiewicz KW

更新日期：1998-02-12 00:00:00

abstract：:A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required...

journal_title：Journal of medicinal chemistry

authors： Doherty EM,Fotsch C,Bannon AW,Bo Y,Chen N,Dominguez C,Falsey J,Gavva NR,Katon J,Nixey T,Ognyanov VI,Pettus L,Rzasa RM,Stec M,Surapaneni S,Tamir R,Zhu J,Treanor JJ,Norman MH

更新日期：2007-07-26 00:00:00

abstract：:Tethered dimers incorporating natural alpha-amino acid end groups were synthesized, including examples in which the previously reported esterase-sensitive ester linker was replaced with more stable amide or ether linkers. These compounds remained effective both as inhibitors of NAD synthetase and as potent antibacteri...

journal_title：Journal of medicinal chemistry

authors： Velu SE,Mou L,Luan CH,Yang ZW,DeLucas LJ,Brouillette CG,Brouillette WJ

更新日期：2007-05-31 00:00:00

abstract：:The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We h...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Barrett K,Chen Y,DeVoss J,Eigenbrot C,Goldsmith R,Ismaili MH,Lau K,Lin Z,Ortwine DF,Zarrin AA,McEwan PA,Barker JJ,Ellebrandt C,Kordt D,Stein DB,Wang X,Chen Y,Hu B,Xu X,Yuen PW,Zhang Y,Pei Z

更新日期：2015-05-14 00:00:00

abstract：:Thrombin is a serine protease responsible for blood coagulation. Since thrombin inhibitors appear to be effective in the treatment and prevention of thrombotic and embolic disorders, considerable attention has been focused on the structure and interactions of this enzyme. In this work, to evaluate the relative free en...

journal_title：Journal of medicinal chemistry

authors： Guimarães CR,Bicca de Alencastro R

更新日期：2002-11-07 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional re...

journal_title：Journal of medicinal chemistry

authors： Perrone R,Nadai M,Frasson I,Poe JA,Butovskaya E,Smithgall TE,Palumbo M,Palù G,Richter SN

更新日期：2013-08-22 00:00:00

abstract：:New analogues of flavone-8-acetic acid were synthesized, bearing an alkoxy group in position 3 and different substituents on the benzene ring in position 2 of the flavone nucleus. The compounds were tested for direct cytotoxicity against four human tumor cell lines and for indirect antitumor effects by measuring their...

journal_title：Journal of medicinal chemistry

authors： Gobbi S,Rampa A,Bisi A,Belluti F,Piazzi L,Valenti P,Caputo A,Zampiron A,Carrara M

更新日期：2003-08-14 00:00:00

abstract：:Selenosemicarbazones show marked antitumor activity. However, their mechanism of action remains unknown. We examined the medicinal chemistry of the selenosemicarbazone, 2-acetylpyridine 4,4-dimethyl-3-selenosemicarbazone (Ap44mSe), and its iron and copper complexes to elucidate its mechanisms of action. Ap44mSe demons...

journal_title：Journal of medicinal chemistry

authors： Al-Eisawi Z,Stefani C,Jansson PJ,Arvind A,Sharpe PC,Basha MT,Iskander GM,Kumar N,Kovacevic Z,Lane DJ,Sahni S,Bernhardt PV,Richardson DR,Kalinowski DS

更新日期：2016-01-14 00:00:00

abstract：:Developing methods to incorporate protein flexibility into structure-based drug design is an important challenge. Our approach uses multiple protein structures (MPS) to create a receptor-based pharmacophore model of the desired target. We have previously demonstrated the success of the method by applying it to human i...

journal_title：Journal of medicinal chemistry

authors： Meagher KL,Lerner MG,Carlson HA

更新日期：2006-06-15 00:00:00

abstract：:To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...

journal_title：Journal of medicinal chemistry

authors： Brown DG,May-Dracka TL,Gagnon MM,Tommasi R

更新日期：2014-12-11 00:00:00

abstract：:Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systema...

journal_title：Journal of medicinal chemistry

authors： Nazaré M,Will DW,Matter H,Schreuder H,Ritter K,Urmann M,Essrich M,Bauer A,Wagner M,Czech J,Lorenz M,Laux V,Wehner V

更新日期：2005-07-14 00:00:00

abstract：:A series of novel 2-[(4-phenylpiperazin-1-yl)methyl]imidazoazines and aza-analogues were prepared and screened at selected dopamine, serotonin, and adrenergic receptor subtypes. 2-Substituted imidazopyridines and pyridazines presented high affinities and selectivities for D4 dopamine receptors. Whereas functional expe...

journal_title：Journal of medicinal chemistry

authors： Enguehard-Gueiffier C,Hübner H,El Hakmaoui A,Allouchi H,Gmeiner P,Argiolas A,Melis MR,Gueiffier A

更新日期：2006-06-29 00:00:00