Analgetic and antiinflammatory 7-aroylbenzofuran-5-ylacetic acids and 7-aroylbenzothiophene-5-ylacetic acids.

abstract：:A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clog...

journal_title：Journal of medicinal chemistry

authors： Wang H,Yu N,Chen D,Lee KC,Lye PL,Chang JW,Deng W,Ng MC,Lu T,Khoo ML,Poulsen A,Sangthongpitag K,Wu X,Hu C,Goh KC,Wang X,Fang L,Goh KL,Khng HH,Goh SK,Yeo P,Liu X,Bonday Z,Wood JM,Dymock BW,Kantharaj E,Su

更新日期：2011-07-14 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...

journal_title：Journal of medicinal chemistry

authors： Wright GE,Gambino JJ

更新日期：1984-02-01 00:00:00

abstract：:2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives int...

journal_title：Journal of medicinal chemistry

authors： Frecentese F,Sosic A,Saccone I,Gamba E,Link K,Miola A,Cappellini M,Cattelan MG,Severino B,Fiorino F,Magli E,Corvino A,Perissutti E,Fabris D,Gatto B,Caliendo G,Santagada V

更新日期：2016-03-10 00:00:00

abstract：:Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-2...

journal_title：Journal of medicinal chemistry

authors： Tang G,Ding K,Nikolovska-Coleska Z,Yang CY,Qiu S,Shangary S,Wang R,Guo J,Gao W,Meagher J,Stuckey J,Krajewski K,Jiang S,Roller PP,Wang S

更新日期：2007-07-12 00:00:00

abstract：:The preparation and activity against Plasmodium berghei of derivatives of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine are described. Replacement of the cinnamoyl group was accomplished by acylation or alkylation of 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine. Modifications of the 5-phenyl grou...

journal_title：Journal of medicinal chemistry

authors： Herrin TR,Pauvlik JM,Schuber EV,Geiszler AO

更新日期：1975-12-01 00:00:00

abstract：:Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GA...

journal_title：Journal of medicinal chemistry

authors： Fritch PC,McNaughton-Smith G,Amato GS,Burns JF,Eargle CW,Roeloffs R,Harrison W,Jones L,Wickenden AD

更新日期：2010-01-28 00:00:00

abstract：:A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated. These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions. Structure-activity relationship studies indicate that antib...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Bailey DM,Cornett JB,Dobson RA,Powles RG,Wagner RB

更新日期：1984-09-01 00:00:00

abstract：:Two compounds, analogues of cephalexin with 2- and 4-pyridone groups at C-3, were prepared. Biological evaluation found the compounds to exhibit activity against Gram-positive and Gram-negative organisms in vitro and in vivo. The compounds were only active in vivo on subcutaneous administration. ...

journal_title：Journal of medicinal chemistry

authors： Edwards ML,Erickson RC

更新日期：1979-11-01 00:00:00

abstract：:We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, ...

journal_title：Journal of medicinal chemistry

authors： Berkhout TA,Blaney FE,Bridges AM,Cooper DG,Forbes IT,Gribble AD,Groot PH,Hardy A,Ife RJ,Kaur R,Moores KE,Shillito H,Willetts J,Witherington J

更新日期：2003-09-11 00:00:00

abstract：:HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate immune system. Through structure-based drug design and optimizatio...

journal_title：Journal of medicinal chemistry

authors： Jiang Y,Andrews SW,Condroski KR,Buckman B,Serebryany V,Wenglowsky S,Kennedy AL,Madduru MR,Wang B,Lyon M,Doherty GA,Woodard BT,Lemieux C,Geck Do M,Zhang H,Ballard J,Vigers G,Brandhuber BJ,Stengel P,Josey JA,Beigelm

更新日期：2014-03-13 00:00:00

abstract：:We describe the design, synthesis, and evaluation of novel disubstituted cyclohexanes as potent CCR2 antagonists. Exploratory SAR studies led to the cis-disubstituted derivative 22, which displayed excellent binding affinity for CCR2 (binding IC50 = 5.1 nM) and potent functional antagonism (calcium flux IC50 = 18 nM a...

journal_title：Journal of medicinal chemistry

authors： Cherney RJ,Mo R,Meyer DT,Nelson DJ,Lo YC,Yang G,Scherle PA,Mandlekar S,Wasserman ZR,Jezak H,Solomon KA,Tebben AJ,Carter PH,Decicco CP

更新日期：2008-02-28 00:00:00

abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

journal_title：Journal of medicinal chemistry

authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

更新日期：2008-12-11 00:00:00

abstract：:3alpha-(diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3alpha-[bis(4'-f...

journal_title：Journal of medicinal chemistry

authors： Zou MF,Kopajtic T,Katz JL,Wirtz S,Justice JB Jr,Newman AH

更新日期：2001-12-06 00:00:00

abstract：:A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared h...

journal_title：Journal of medicinal chemistry

authors： Borchardt RT,Reid JR,Thakker DR

更新日期：1976-10-01 00:00:00

abstract：:The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of new selective muscarinic ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized, and their pharmacological profiles at muscarinic receptor subtypes were assessed by fun...

journal_title：Journal of medicinal chemistry

authors： Bolognesi ML,Minarini A,Budriesi R,Cacciaguerra S,Chiarini A,Spampinato S,Tumiatti V,Melchiorre C

更新日期：1998-10-08 00:00:00

abstract：:A series of 4- and 5-[2,3-dihydro-6,7-bis[[(N-alkylcarbamoyl)oxy]methyl]-1H-pyrrol izin-5- yl]-2-halopyridinium iodides were synthesized. The rates of hydrolysis of the alpha-halopyridinium salts to the corresponding pyridones, and the reactivities of the carbamate moieties were studied as a function of pH, buffer com...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Dean DC,Endo T

更新日期：1990-06-01 00:00:00

abstract：:A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioa...

journal_title：Journal of medicinal chemistry

authors： Bailey TR,Rippin SR,Opsitnick E,Burns CJ,Pevear DC,Collett MS,Rhodes G,Tohan S,Huggins JW,Baker RO,Kern ER,Keith KA,Dai D,Yang G,Hruby D,Jordan R

更新日期：2007-04-05 00:00:00

abstract：:We have previously shown that the oral administration of the small molecule hPTHR1 agonist PCO371 and its lead compound, 1 (CH5447240) results in PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. However, 1 was converted to a reactive metabolite in a human liver microsome assay. In this a...

journal_title：Journal of medicinal chemistry

authors： Nishimura Y,Esaki T,Isshiki Y,Furuta Y,Mizutani A,Kotake T,Emura T,Watanabe Y,Ohta M,Nakagawa T,Ogawa K,Arai S,Noda H,Kitamura H,Shimizu M,Tamura T,Sato H

更新日期：2020-05-28 00:00:00

abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...

journal_title：Journal of medicinal chemistry

authors： Butini S,Campiani G,Franceschini S,Trotta F,Kumar V,Guarino E,Borrelli G,Fiorini I,Novellino E,Fattorusso C,Persico M,Orteca N,Sandager-Nielsen K,Jacobsen TA,Madsen K,Scheel-Kruger J,Gemma S

更新日期：2010-06-24 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first smal...

journal_title：Journal of medicinal chemistry

authors： Maga G,Falchi F,Garbelli A,Belfiore A,Witvrouw M,Manetti F,Botta M

更新日期：2008-11-13 00:00:00

abstract：:Virtually all low molecular weight inhibitors of human glutamate carboxypeptidase II (GCPII) are highly polar compounds that have limited use in settings where more lipophilic molecules are desired. Here we report the identification and characterization of GCPII inhibitors with enhanced liphophilicity that are derived...

journal_title：Journal of medicinal chemistry

authors： Plechanovová A,Byun Y,Alquicer G,Skultétyová L,Mlčochová P,Němcová A,Kim HJ,Navrátil M,Mease R,Lubkowski J,Pomper M,Konvalinka J,Rulíšek L,Bařinka C

更新日期：2011-11-10 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：:The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and pot...

journal_title：Journal of medicinal chemistry

authors： Takahashi H,Riether D,Bartolozzi A,Bosanac T,Berger V,Binetti R,Broadwater J,Chen Z,Crux R,De Lombaert S,Dave R,Dines JA,Fadra-Khan T,Flegg A,Garrigou M,Hao MH,Huber J,Hutzler JM,Kerr S,Kotey A,Liu W,Lo HY,Lok

更新日期：2015-02-26 00:00:00

abstract：:We report the activities of 62 bisphosphonates as inhibitors of the Leishmania major mevalonate/isoprene biosynthesis pathway enzyme, farnesyl pyrophosphate synthase. The compounds investigated exhibit activities (IC(50) values) ranging from approximately 100 nM to approximately 80 microM (corresponding to K(i) values...

journal_title：Journal of medicinal chemistry

authors： Sanders JM,Gómez AO,Mao J,Meints GA,Van Brussel EM,Burzynska A,Kafarski P,González-Pacanowska D,Oldfield E

更新日期：2003-11-20 00:00:00

abstract：:The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the min...

journal_title：Journal of medicinal chemistry

authors： Clark ER,Hughes IE,Smith CF

更新日期：1976-05-01 00:00:00

abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

journal_title：Journal of medicinal chemistry

authors： Hulshoff A,Perrin JH

更新日期：1977-03-01 00:00:00

abstract：:SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrat...

journal_title：Journal of medicinal chemistry

authors： Xue CB,He X,Corbett RL,Roderick J,Wasserman ZR,Liu RQ,Jaffee BD,Covington MB,Qian M,Trzaskos JM,Newton RC,Magolda RL,Wexler RR,Decicco CP

更新日期：2001-10-11 00:00:00

abstract：:Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure...

journal_title：Journal of medicinal chemistry

authors： Johnson CN,Ahn JS,Buck IM,Chiarparin E,Day JEH,Hopkins A,Howard S,Lewis EJ,Martins V,Millemaggi A,Munck JM,Page LW,Peakman T,Reader M,Rich SJ,Saxty G,Smyth T,Thompson NT,Ward GA,Williams PA,Wilsher NE,Chessari G

更新日期：2018-08-23 00:00:00

abstract：:Continuing our search for vitamin D analogues, we explored the modification of the steroidal side chain and inserted a methylene moiety in position C-22 together with either lengthening the side chain or introducing a ring at the terminal end. Our conformational studies confirmed that the presence of a methylene group...

journal_title：Journal of medicinal chemistry

authors： Sibilska-Kaminski IK,Sicinski RR,Plum LA,DeLuca HF

更新日期：2020-07-09 00:00:00