Improved scoring of ligand-protein interactions using OWFEG free energy grids.

abstract：:Rebeccamycin analogues containing uncommon sugars and substitutions on the imide nitrogen have been synthesized. Their cytotoxicities were tested in colon cancer and leukemia cells. Their ability to target topoisomerase I was examined using the in vivo complex of the topoisomerase bioassay in Hela cells. Compared with...

journal_title：Journal of medicinal chemistry

authors： Zhang G,Shen J,Cheng H,Zhu L,Fang L,Luo S,Muller MT,Lee GE,Wei L,Du Y,Sun D,Wang PG

更新日期：2005-04-07 00:00:00

abstract：:The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...

journal_title：Journal of medicinal chemistry

authors： Hess S,Linde Y,Ovadia O,Safrai E,Shalev DE,Swed A,Halbfinger E,Lapidot T,Winkler I,Gabinet Y,Faier A,Yarden D,Xiang Z,Portillo FP,Haskell-Luevano C,Gilon C,Hoffman A

更新日期：2008-02-28 00:00:00

abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

journal_title：Journal of medicinal chemistry

authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

更新日期：1995-02-17 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：:A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at...

journal_title：Journal of medicinal chemistry

authors： Shaw DE,Baig F,Bruce I,Chamoin S,Collingwood SP,Cross S,Dayal S,Drückes P,Furet P,Furminger V,Haggart D,Hussey M,Konstantinova I,Loren JC,Molteni V,Roberts S,Reilly J,Saunders AM,Stringer R,Sviridenko L,Thomas M,

更新日期：2016-09-08 00:00:00

abstract：:Pyrrolo[1,2-a]benzimidazole(PBI)-based aziridinyl quinones cleave DNA under reducing conditions specifically at G + A bases without any significant cleavage at C + T bases. The postulated mechanisms involve phosphate alkylation by the reductively activated aziridine to afford a hydrolytically labile phosphotriester as...

journal_title：Journal of medicinal chemistry

authors： Skibo EB,Schulz WG

更新日期：1993-10-15 00:00:00

abstract：:Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotropic glutamate receptor ...

journal_title：Journal of medicinal chemistry

authors： Lucas S,Poulsen MH,Nørager NG,Barslund AF,Bach TB,Kristensen AS,Strømgaard K

更新日期：2012-11-26 00:00:00

abstract：:We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-h...

journal_title：Journal of medicinal chemistry

authors： de Medina P,Paillasse MR,Payré B,Silvente-Poirot S,Poirot M

更新日期：2009-12-10 00:00:00

abstract：:Novel classical antifolates (3 and 4) and 17 nonclassical antifolates (11-27) were synthesized as antitumor and/or antiopportunistic infection agents. Intermediates for the synthesis of 3, 4, and 11-27 were 2,4-diamino-5-alkylsubstituted-7H-pyrrolo[2,3-d]pyrimidines, 31 and 38, prepared by a ring transformation/ring a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Jain HD,Queener SF,Kisliuk RL

更新日期：2008-08-14 00:00:00

abstract：:A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on ...

journal_title：Journal of medicinal chemistry

authors： Naylor MA,Stephens MA,Cole S,Threadgill MD,Stratford IJ,O'Neill P,Fielden EM,Adams GE

更新日期：1990-09-01 00:00:00

abstract：:We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure-activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-...

journal_title：Journal of medicinal chemistry

authors： Zhang Z,Wu G,Xie F,Song T,Chang X

更新日期：2011-02-24 00:00:00

abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...

journal_title：Journal of medicinal chemistry

authors： van Vliet LA,Tepper PG,Dijkstra D,Damsma G,Wikström H,Pugsley TA,Akunne HC,Heffner TG,Glase SA,Wise LD

更新日期：1996-10-11 00:00:00

abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...

journal_title：Journal of medicinal chemistry

authors： Ding B,Xiao Y,Zhou H,Zhang X,Qu C,Xu F,Deng Z,Cheng Z,Hong X

更新日期：2019-02-28 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：:Diarylpyrimidine derivatives (DAPYs) exhibit robust anti-HIV-1 potency, although they have been compromised by E138K variant and severe side-effects and been suffering from poor water solubility. In the present work, hydrophilic morpholine or methylsulfonyl and sulfamide-substituted piperazine/piperidines were introdu...

journal_title：Journal of medicinal chemistry

authors： Huang B,Chen W,Zhao T,Li Z,Jiang X,Ginex T,Vílchez D,Luque FJ,Kang D,Gao P,Zhang J,Tian Y,Daelemans D,De Clercq E,Pannecouque C,Zhan P,Liu X

更新日期：2019-02-28 00:00:00

abstract：:Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease se...

journal_title：Journal of medicinal chemistry

authors： Crocetti L,Schepetkin IA,Cilibrizzi A,Graziano A,Vergelli C,Giomi D,Khlebnikov AI,Quinn MT,Giovannoni MP

更新日期：2013-08-08 00:00:00

abstract：:Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase ...

journal_title：Journal of medicinal chemistry

authors： Irwin N,O'Harte FP,Gault VA,Green BD,Greer B,Harriott P,Bailey CJ,Flatt PR

更新日期：2006-02-09 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：:The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV G...

journal_title：Journal of medicinal chemistry

authors： Biggadike K,Boudjelal M,Clackers M,Coe DM,Demaine DA,Hardy GW,Humphreys D,Inglis GG,Johnston MJ,Jones HT,House D,Loiseau R,Needham D,Skone PA,Uings I,Veitch G,Weingarten GG,McLay IM,Macdonald SJ

更新日期：2007-12-27 00:00:00

abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...

journal_title：Journal of medicinal chemistry

authors： Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson ME

更新日期：1985-02-01 00:00:00

abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

journal_title：Journal of medicinal chemistry

authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

更新日期：2000-11-16 00:00:00

abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...

journal_title：Journal of medicinal chemistry

authors： Yang SP,Zhang XW,Ai J,Gan LS,Xu JB,Wang Y,Su ZS,Wang L,Ding J,Geng MY,Yue JM

更新日期：2012-09-27 00:00:00

abstract：:G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A se...

journal_title：Journal of medicinal chemistry

authors： Setoh M,Ishii N,Kono M,Miyanohana Y,Shiraishi E,Harasawa T,Ota H,Odani T,Kanzaki N,Aoyama K,Hamada T,Kori M

更新日期：2014-06-26 00:00:00

abstract：:Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a m...

journal_title：Journal of medicinal chemistry

authors： Shimshoni JA,Bialer M,Wlodarczyk B,Finnell RH,Yagen B

更新日期：2007-12-13 00:00:00

abstract：:As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate subst...

journal_title：Journal of medicinal chemistry

authors： Schiffler MA,Antonysamy S,Bhattachar SN,Campanale KM,Chandrasekhar S,Condon B,Desai PV,Fisher MJ,Groshong C,Harvey A,Hickey MJ,Hughes NE,Jones SA,Kim EJ,Kuklish SL,Luz JG,Norman BH,Rathmell RE,Rizzo JR,Seng TW,Thi

更新日期：2016-01-14 00:00:00

abstract：:Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides...

journal_title：Journal of medicinal chemistry

authors： Souto JA,Vaz E,Lepore I,Pöppler AC,Franci G,Alvarez R,Altucci L,de Lera AR

更新日期：2010-06-24 00:00:00

abstract：:A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imagin...

journal_title：Journal of medicinal chemistry

authors： Pirmettis IC,Papadopoulos MS,Chiotellis E

更新日期：1997-08-01 00:00:00

abstract：:The synthesis and biological activities of a series of N-substituted cis-4a,5,6,7,8,8a-hexa- and cis-4a,5,8,8a-tetrahydro-2H-phthalazin-1-ones are described. It was found that compounds bearing a cycloalkyl group at the 2-position exhibit the highest PDE4 inhibitory activities (pIC(50) = 8.6-9.4). The N-cycloheptyl- a...

journal_title：Journal of medicinal chemistry

authors： Van der Mey M,Boss H,Hatzelmann A,Van der Laan IJ,Sterk GJ,Timmerman H

更新日期：2002-06-06 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engin...

journal_title：Journal of medicinal chemistry

authors： Barkey NM,Tafreshi NK,Josan JS,De Silva CR,Sill KN,Hruby VJ,Gillies RJ,Morse DL,Vagner J

更新日期：2011-12-08 00:00:00