Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.

abstract：:A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease...

journal_title：Journal of medicinal chemistry

authors： Gehlhaar DK,Moerder KE,Zichi D,Sherman CJ,Ogden RC,Freer ST

更新日期：1995-02-03 00:00:00

abstract：:Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. This paper reports the synthesis, characterization, and biological evaluation of a novel class of MMP inhibit...

journal_title：Journal of medicinal chemistry

authors： Breuer E,Salomon CJ,Katz Y,Chen W,Lu S,Röschenthaler GV,Hadar R,Reich R

更新日期：2004-05-20 00:00:00

abstract：:Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered thietane ring was efficiently synthesized by the cyclization of 1-thioacetyl-3-mesylate (4/38) under basic conditions. Condensation with various heterocyclic bases was conducted via Pummerer-type rearrangement to afford va...

journal_title：Journal of medicinal chemistry

authors： Choo H,Chen X,Yadav V,Wang J,Schinazi RF,Chu CK

更新日期：2006-03-09 00:00:00

abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...

journal_title：Journal of medicinal chemistry

authors： Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

更新日期：2011-07-28 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:A short series of the title compounds was prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. All but the two N-methylated derivatives were active in this screen by the intravenous route, the most potent being the symmetrical dimethyl compound, 4,9-dihydro-6,7-dimethyl-4,9...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Smith H,Spicer BA,Tedder JM

更新日期：1983-05-01 00:00:00

abstract：:In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...

journal_title：Journal of medicinal chemistry

authors： Posner GH,McRiner AJ,Paik IH,Sur S,Borstnik K,Xie S,Shapiro TA,Alagbala A,Foster B

更新日期：2004-02-26 00:00:00

abstract：:We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-su...

journal_title：Journal of medicinal chemistry

authors： Ohmori J,Kubota H,Shimizu-Sasamata M,Okada M,Sakamoto S

更新日期：1996-03-15 00:00:00

abstract：:Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities. Key transformations include metalation at the 4-C-position of 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine (5) and its coupling with benzyl bromide or benzaldehyde deriv...

journal_title：Journal of medicinal chemistry

authors： Dollé V,Nguyen CH,Legraverend M,Aubertin AM,Kirn A,Andreola ML,Ventura M,Tarrago-Litvak L,Bisagni E

更新日期：2000-10-19 00:00:00

abstract：:The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline (HHII) scaffold as a surrogate for the steroidal A-B ring system is described. The structure-activity relationships of the analogs derived from this scaffold show that the basic imidazole moiety is tolerated by the glucocorticoid receptor (G...

journal_title：Journal of medicinal chemistry

authors： Xiao HY,Wu DR,Malley MF,Gougoutas JZ,Habte SF,Cunningham MD,Somerville JE,Dodd JH,Barrish JC,Nadler SG,Dhar TG

更新日期：2010-02-11 00:00:00

abstract：:The design, synthesis, and biological profile of several indole melatonin analogues with a conformationally restricted C3 amidoethane side chain are presented. Examination of the accessible conformations of the melatonin side chain led us to explore some of its fully or partially restricted analogues, 2-12, the bindin...

journal_title：Journal of medicinal chemistry

authors： Spadoni G,Balsamini C,Diamantini G,Di Giacomo B,Tarzia G,Mor M,Plazzi PV,Rivara S,Lucini V,Nonno R,Pannacci M,Fraschini F,Stankov BM

更新日期：1997-06-20 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulf...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Xu SP,Zhu LY,Cosby LA,Sartorelli AC

更新日期：1989-07-01 00:00:00

abstract：:Human melanocortin receptors (hMCRs) have been challenging targets to develop ligands that are explicitly selective for each of their subtypes. To modulate the conformational preferences of the melanocortin ligands and improve the biofunctional agonist/antagonist activities and selectivities, we have applied a backbon...

journal_title：Journal of medicinal chemistry

authors： Cai M,Marelli UK,Bao J,Beck JG,Opperer F,Rechenmacher F,McLeod KR,Zingsheim MR,Doedens L,Kessler H,Hruby VJ

更新日期：2015-08-27 00:00:00

abstract：:Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...

journal_title：Journal of medicinal chemistry

authors： Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

更新日期：2007-03-22 00:00:00

abstract：:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active aga...

journal_title：Journal of medicinal chemistry

authors： Bolognese A,Correale G,Manfra M,Lavecchia A,Novellino E,Pepe S

更新日期：2006-08-24 00:00:00

abstract：:The C-terminal "address" sequences of prodynorphin-derived opioid peptides contain an unusually high proportion of basic residues, which are known to be crucial for conferring high activity and selectivity for kappa-opioid receptors. In an effort to investigate the possibility that the polycationic "tails" may be invo...

journal_title：Journal of medicinal chemistry

authors： Jacobson AR,Tam SW,Sayre LM

更新日期：1991-09-01 00:00:00

abstract：:Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of...

journal_title：Journal of medicinal chemistry

authors： Hagiwara D,Miyake H,Morimoto H,Murai M,Fujii T,Matsuo M

更新日期：1992-08-21 00:00:00

abstract：:Structure-activity studies have been carried out on a series of imidazo[4,5-f]quinoline derivatives reported to have potent in vivo immunostimulatory activity. This activity has been confirmed, and subtle structure-activity relationships have been uncovered which resulted in the identification of novel analogs (pyrazo...

journal_title：Journal of medicinal chemistry

authors： Moyer MP,Weber FH,Gross JL

更新日期：1992-11-27 00:00:00

abstract：:The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation. Among the variety of diseases in which the leukotrienes may play a symptomatic or causative role is the dermatological condition psoriasis,...

journal_title：Journal of medicinal chemistry

authors： Hammond ML,Zambias RA,Chang MN,Jensen NP,McDonald J,Thompson K,Boulton DA,Kopka IE,Hand KM,Opas EE

更新日期：1990-03-01 00:00:00

abstract：:Edelfosine (ET-18-OCH3), a synthetic antitumor ether lipid, is taken up by malignant but not by normal cells, triggering apoptosis in a large variety of human tumor cells. The synthesis of the first fluorescent edelfosine analogue (6), with apoptotic activity comparable to that of the parent drug, is described. Fluore...

journal_title：Journal of medicinal chemistry

authors： Quesada E,Delgado J,Gajate C,Mollinedo F,Acuña AU,Amat-Guerri F

更新日期：2004-10-21 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：:A novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform o...

journal_title：Journal of medicinal chemistry

authors： Hayashi Y,Skwarczynski M,Hamada Y,Sohma Y,Kimura T,Kiso Y

更新日期：2003-08-28 00:00:00

abstract：:Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing al...

journal_title：Journal of medicinal chemistry

authors： Sharma AK,Sharma A,Desai D,Madhunapantula SV,Huh SJ,Robertson GP,Amin S

更新日期：2008-12-25 00:00:00

abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...

journal_title：Journal of medicinal chemistry

authors： Li X,Li Z,Wu X,Xiong Z,Yang T,Fu Z,Liu X,Tan X,Zhong F,Wan X,Wang D,Ding X,Yang R,Hou H,Li C,Liu H,Chen K,Jiang H,Zheng M

更新日期：2020-08-27 00:00:00

abstract：:Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergol...

journal_title：Journal of medicinal chemistry

authors： Crider AM,Lu CK,Floss HG,Cassady JM,Clemens JA

更新日期：1979-01-01 00:00:00

abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Teller S,Pongratz H,Hufsky H,Sellmer A,Botzki A,Uecker A,Beckers T,Baasner S,Schächtele C,Uberall F,Kassack MU,Dove S,Böhmer FD

更新日期：2002-02-28 00:00:00

abstract：:Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...

journal_title：Journal of medicinal chemistry

authors： Fliri AF,Loging WT,Thadeio PF,Volkmann RA

更新日期：2005-11-03 00:00:00

abstract：:The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to...

journal_title：Journal of medicinal chemistry

authors： Yoshimoto M,Hansch C

更新日期：1976-01-01 00:00:00

abstract：:A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells. Through the use of the structure-activity relationships within this series of compounds and computational chemistry techniques, a binding conformation is prop...

journal_title：Journal of medicinal chemistry

authors： Wyatt PG,Bethell RC,Cammack N,Charon D,Dodic N,Dumaitre B,Evans DN,Green DV,Hopewell PL,Humber DC

更新日期：1995-05-12 00:00:00