Target specific virtual screening: optimization of an estrogen receptor screening platform.

abstract：:Various 2',3'-dideoxy-L-cytidine,2',3'-dideoxy-L-uridine, and 3'-deoxy-L-thymidine analogues have been synthesized and evaluated in vitro as potential anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of 5-fluorocytosine, cytosi...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Luo MZ,Liu MC,Pai SB,Dutschman GE,Cheng YC

更新日期：1994-03-18 00:00:00

abstract：:An alpha-sialoside linked to acrylamide by a short connector (5-acetamido-2-O-(N-acryloyl-8-amino-5-oxaoctyl)-2,6-anhydro-3,5-d ideoxy-D-galacto-alpha-nonulopyranosonoic acid, 1) was prepared. Compound 1 formed high molecular weight copolymers with acrylamide, derivatives of acrylamide, and/or vinylpyrrolidone upon ph...

journal_title：Journal of medicinal chemistry

authors： Lees WJ,Spaltenstein A,Kingery-Wood JE,Whitesides GM

更新日期：1994-09-30 00:00:00

abstract：:A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in ...

journal_title：Journal of medicinal chemistry

authors： Clark CR,Lin CM,Sansom RT

更新日期：1986-08-01 00:00:00

abstract：:Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this se...

journal_title：Journal of medicinal chemistry

authors： Mao J,Yuan H,Wang Y,Wan B,Pieroni M,Huang Q,van Breemen RB,Kozikowski AP,Franzblau SG

更新日期：2009-11-26 00:00:00

abstract：:A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characte...

journal_title：Journal of medicinal chemistry

authors： Micheli F,Cavanni P,Andreotti D,Arban R,Benedetti R,Bertani B,Bettati M,Bettelini L,Bonanomi G,Braggio S,Carletti R,Checchia A,Corsi M,Fazzolari E,Fontana S,Marchioro C,Merlo-Pich E,Negri M,Oliosi B,Ratti E,Read K

更新日期：2010-07-08 00:00:00

abstract：:A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys....

journal_title：Journal of medicinal chemistry

authors： Houlihan WJ,Gogerty JH,Ryan EA,Schmitt G

更新日期：1985-01-01 00:00:00

abstract：:Variation of the bridge linking the heterocyclic ring and p-aminobenzoyl-L-glutamate portions of our previously described classical 2,4-diaminofuro[2,3-d]pyrimidines 1 and 2 are reported as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) and as antitumor agents. Specifically -CH2CH2- and -CH...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Devraj R,McGuire JJ,Kisliuk RL

更新日期：1995-09-15 00:00:00

abstract：:(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...

journal_title：Journal of medicinal chemistry

authors： Wu YJ,Boissard CG,Greco C,Gribkoff VK,Harden DG,He H,L'Heureux A,Kang SH,Kinney GG,Knox RJ,Natale J,Newton AE,Lehtinen-Oboma S,Sinz MW,Sivarao DV,Starrett JE Jr,Sun LQ,Tertyshnikova S,Thompson MW,Weaver D,Wong HS

更新日期：2003-07-17 00:00:00

abstract：:Spatial correspondence between apomorphine, a prototype dopaminergic (DA) drug, and ergoline and some of its (partial) analogues were derived by matching their molecular electrostatic potential (MEP) patterns surrounding the aromatic moieties with respect to the coincident aliphatic N atoms. The MEP patterns were calc...

journal_title：Journal of medicinal chemistry

authors： Kocjan D,Hodoscek M,Hadzi D

更新日期：1986-08-01 00:00:00

abstract：:The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and C...

journal_title：Journal of medicinal chemistry

authors： Hardcastle IR,Arris CE,Bentley J,Boyle FT,Chen Y,Curtin NJ,Endicott JA,Gibson AE,Golding BT,Griffin RJ,Jewsbury P,Menyerol J,Mesguiche V,Newell DR,Noble ME,Pratt DJ,Wang LZ,Whitfield HJ

更新日期：2004-07-15 00:00:00

abstract：:As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, o...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Duan W,Cohen DJ,Bidlack JM

更新日期：2000-09-21 00:00:00

abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

更新日期：1979-06-01 00:00:00

abstract：:Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtain...

journal_title：Journal of medicinal chemistry

authors： Scapecchi S,Nesi M,Matucci R,Bellucci C,Buccioni M,Dei S,Guandalini L,Manetti D,Martini E,Marucci G,Romanelli MN,Teodori E,Cirilli R

更新日期：2008-07-10 00:00:00

abstract：:Inhibition of inducible T-cell kinase (ITK), a nonreceptor tyrosine kinase, may represent a novel treatment for allergic asthma. In our previous reports, we described the discovery of sulfonylpyridine (SAP), benzothiazole (BZT), indazole (IND), and tetrahydroindazole (THI) series as novel ITK inhibitors and how comput...

journal_title：Journal of medicinal chemistry

authors： Heifetz A,Trani G,Aldeghi M,MacKinnon CH,McEwan PA,Brookfield FA,Chudyk EI,Bodkin M,Pei Z,Burch JD,Ortwine DF

更新日期：2016-05-12 00:00:00

abstract：:The synthetic pentasaccharide (1) corresponding to the heparin sequence which binds to, and activates, antithrombin III (AT III) is a potent antithrombotic compound in several animal models of venous thrombosis. We describe here the preparation and the pharmacological properties of 34, an analogue of oligosaccharide 1...

journal_title：Journal of medicinal chemistry

authors： Petitou M,Duchaussoy P,Jaurand G,Gourvenec F,Lederman I,Strassel JM,Bârzu T,Crépon B,Hérault JP,Lormeau JC,Bernat A,Herbert JM

更新日期：1997-05-23 00:00:00

abstract：:Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A(1) and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside deri...

journal_title：Journal of medicinal chemistry

authors： Jacobson KA,Gao ZG,Tchilibon S,Duong HT,Joshi BV,Sonin D,Liang BT

更新日期：2005-12-29 00:00:00

abstract：:Chemical investigations leading to the construction of bis(bioreductive) alkylating agents having both conformationally restricted and mobile spacer regions are described. Two targets having the conformationally mobile ethylene spacer group, namely, 2,2'-ethylenebis[6-(hydroxymethyl)-p-benzoquinone] diacetate (3b) and...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kamat PL,Allison DL,Liebowitz SM,Glaser R,Holliday JE,Moeschberger ML,Schaller JP

更新日期：1983-12-01 00:00:00

abstract：:A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Abeta plaques. 6-Ethylthio- (12h), 6-cyano- (12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI < 10...

journal_title：Journal of medicinal chemistry

authors： Cai L,Cuevas J,Temme S,Herman MM,Dagostin C,Widdowson DA,Innis RB,Pike VW

更新日期：2007-09-20 00:00:00

abstract：:Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzym...

journal_title：Journal of medicinal chemistry

authors： Seidler J,McGovern SL,Doman TN,Shoichet BK

更新日期：2003-10-09 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

abstract：:A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...

journal_title：Journal of medicinal chemistry

authors： Andersen KE,Braestrup C,Grønwald FC,Jørgensen AS,Nielsen EB,Sonnewald U,Sørensen PO,Suzdak PD,Knutsen LJ

更新日期：1993-06-11 00:00:00

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 00:00:00

abstract：:A series of four structurally related carbocyclic nucleosides (6a, 6b, 10a, and 10b) were synthesized and evaluated for their ability to inhibit tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) production from human primary macrophages. These compounds had little effect...

journal_title：Journal of medicinal chemistry

authors： Borcherding DR,Peet NP,Munson HR,Zhang H,Hoffman PF,Bowlin TL,Edwards CK 3rd

更新日期：1996-06-21 00:00:00

abstract：:This paper describes the chemical synthesis and CCK-B and CCK-A receptor binding affinities of a series of compounds in which the central amide bond of the CCK-B "dipeptoid" ligand tricyclo[3.3.1.1(3,7)]dec-2-yl [R-(R*,S*)]-[2-[[1-(hydroxymethyl)- 2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethyl]carb amate (4) ...

journal_title：Journal of medicinal chemistry

authors： Fincham CI,Higginbottom M,Hill DR,Horwell DC,O'Toole JC,Ratcliffe GS,Rees DC,Roberts E

更新日期：1992-04-17 00:00:00

abstract：:The 2S,3S and 2R,3S diastereoisomers of the hydroxy amino acid 3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA) were synthesized and substituted for the leucyl residues of Leu-Leu-Val-Phe-OCH3 to yield the following analogues: AHMHA-Leu-Val-Phe-OCH3, AHMHA-Val-Phe-OCH3, and Leu-AHMHA-Val-Phe-OCH3. These analogues were ...

journal_title：Journal of medicinal chemistry

authors： Johnson RL

更新日期：1982-05-01 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：:Small molecule protein kinase inhibitors are widely employed as biological reagents and as leads in the design of drugs for a variety of diseases. One of the hardest challenges in kinase inhibitor design is achieving target selectivity. By utilizing X-ray structural information for four promiscuous inhibitors, we prop...

journal_title：Journal of medicinal chemistry

authors： Aronov AM,Murcko MA

更新日期：2004-11-04 00:00:00

abstract：:A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in n...

journal_title：Journal of medicinal chemistry

authors： Van Overmeire I,Boldin SA,Dumont F,Van Calenbergh S,Slegers G,De Keukeleire D,Futerman AH,Herdewijn P

更新日期：1999-07-15 00:00:00

abstract：:Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds, including an AZT analogue, show modest antivirial activity against HIV-1 and HIV-2 r...

journal_title：Journal of medicinal chemistry

authors： Okruszek A,Olesiak M,Balzarini J

更新日期：1994-10-28 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