A click chemistry approach to pleuromutilin conjugates with nucleosides or acyclic nucleoside derivatives and their binding to the bacterial ribosome.

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 00:00:00

abstract：:A computational methodology is introduced to systematically organize compound analogue series according to substitution sites and identify combinations of sites that determine structure-activity relationships (SARs) and make large contributions to SAR discontinuity. These sites are prime targets for further chemical m...

journal_title：Journal of medicinal chemistry

authors： Peltason L,Weskamp N,Teckentrup A,Bajorath J

更新日期：2009-05-28 00:00:00

abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...

journal_title：Journal of medicinal chemistry

authors： Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JC

更新日期：1994-12-09 00:00:00

abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...

journal_title：Journal of medicinal chemistry

authors： Vaezi MF,Alam M,Sani BP,Rogers TS,Simpson-Herren L,Wille JJ,Hill DL,Doran TI,Brouillette WJ,Muccio DD

更新日期：1994-12-23 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：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...

journal_title：Journal of medicinal chemistry

authors： Smith PA,Sorich MJ,McKinnon RA,Miners JO

更新日期：2003-04-24 00:00:00

abstract：:Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while t...

journal_title：Journal of medicinal chemistry

authors： Fernandes J,Gattass CR

更新日期：2009-02-26 00:00:00

abstract：:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...

journal_title：Journal of medicinal chemistry

authors： Bijelic A,Theiner S,Keppler BK,Rompel A

更新日期：2016-06-23 00:00:00

abstract：:By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor ...

journal_title：Journal of medicinal chemistry

authors： Tung JS,Davis DL,Anderson JP,Walker DE,Mamo S,Jewett N,Hom RK,Sinha S,Thorsett ED,John V

更新日期：2002-01-17 00:00:00

abstract：:The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found to be potent inh...

journal_title：Journal of medicinal chemistry

authors： Yee SW,Jarno L,Gomaa MS,Elford C,Ooi LL,Coogan MP,McClelland R,Nicholson RI,Evans BA,Brancale A,Simons C

更新日期：2005-11-17 00:00:00

abstract：:Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code ) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide i...

journal_title：Journal of medicinal chemistry

authors： Greenidge PA,Mérette SA,Beck R,Dodson G,Goodwin CA,Scully MF,Spencer J,Weiser J,Deadman JJ

更新日期：2003-04-10 00:00:00

abstract：:Lipophilicity/bioavailibility of Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase (SOD) mimics has a major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues but are 10-fold more lipophilic and more planar. Enhanced lipophilicity contrib...

journal_title：Journal of medicinal chemistry

authors： Kos I,Benov L,Spasojević I,Rebouças JS,Batinić-Haberle I

更新日期：2009-12-10 00:00:00

abstract：:Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and ...

journal_title：Journal of medicinal chemistry

authors： Shakya N,Srivastav NC,Desroches N,Agrawal B,Kunimoto DY,Kumar R

更新日期：2010-05-27 00:00:00

abstract：:Transient receptor potential canonical (TRPC) channels are highly homologous, nonselective cation channels that form many homo- and heterotetrameric channels. These channels are highly abundant in the brain and kidney and have been implicated in numerous diseases, such as depression, addiction, and chronic kidney dise...

journal_title：Journal of medicinal chemistry

authors： Sharma S,Hopkins CR

更新日期：2019-09-12 00:00:00

abstract：:A number of 6-sulfenamide, 6-sulfinamide, and 6-sulfonamide derivatives of 2-aminopurine and certain related purine ribonucleosides have been synthesized and evaluated for antileukemic activity in mice. Amination of 6-mercaptopurine ribonucleoside (7a) and 6-thioguanosine (7b) with chloramine solution gave 9-beta-D-ri...

journal_title：Journal of medicinal chemistry

authors： Revankar GR,Hanna NB,Imamura N,Lewis AF,Larson SB,Finch RA,Avery TL,Robins RK

更新日期：1990-01-01 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 26 derivatives of the novel muscarinic antagonist 3-(2-benzofuranyl)quinuclidin-2-ene (1) has been synthesized and evaluated for muscarinic and antimuscarinic properties. The affinity of the compounds was determined by competition experiments in homogenates of cerebral cortex, heart, parotid gland, and uri...

journal_title：Journal of medicinal chemistry

authors： Nordvall G,Sundquist S,Johansson G,Glas G,Nilvebrant L,Hacksell U

更新日期：1996-08-16 00:00:00

abstract：:A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two compounds exhibit ant...

journal_title：Journal of medicinal chemistry

authors： Drakulić BJ,Juranić ZD,Stanojković TP,Juranić IO

更新日期：2005-08-25 00:00:00

abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

journal_title：Journal of medicinal chemistry

authors： Kuhlmann KF,Mosher CW

更新日期：1981-11-01 00:00:00

abstract：:A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl rin...

journal_title：Journal of medicinal chemistry

authors： Mounetou E,Legault J,Lacroix J,C-Gaudreault R

更新日期：2001-03-01 00:00:00

abstract：:There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...

journal_title：Journal of medicinal chemistry

authors： Douat-Casassus C,Borbulevych O,Tarbe M,Gervois N,Jotereau F,Baker BM,Quideau S

更新日期：2010-10-14 00:00:00

abstract：:The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of li...

journal_title：Journal of medicinal chemistry

authors： Ding L,Etemad-Moghadam G,Cros S,Auclair C,Meunier B

更新日期：1991-03-01 00:00:00

abstract：:A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...

journal_title：Journal of medicinal chemistry

authors： Jiang JB,Johnson MG,Defauw JM,Beine TM,Ballas LM,Janzen WP,Loomis CR,Seldin J,Cofield D,Adams L

更新日期：1992-11-13 00:00:00

abstract：:A unique tetrahydrofuran ether class of highly potent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and structure-based drug design. An acyclic lead compound, containing an ether-linked isopropylsulfonamide and biphenyl group, was pharmacologically augmen...

journal_title：Journal of medicinal chemistry

authors： Shaffer CL,Patel NC,Schwarz J,Scialis RJ,Wei Y,Hou XJ,Xie L,Karki K,Bryce DK,Osgood SM,Hoffmann WE,Lazzaro JT,Chang C,McGinnis DF,Lotarski SM,Liu J,Obach RS,Weber ML,Chen L,Zasadny KR,Seymour PA,Schmidt CJ,Haj

更新日期：2015-05-28 00:00:00

abstract：:The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC(50) (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalign...

journal_title：Journal of medicinal chemistry

authors： Schobert R,Seibt S,Mahal K,Ahmad A,Biersack B,Effenberger-Neidnicht K,Padhye S,Sarkar FH,Mueller T

更新日期：2011-09-22 00:00:00

abstract：:The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf splee...

journal_title：Journal of medicinal chemistry

authors： Harriman GC,Poirot AF,Abushanab E,Midgett RM,Stoeckler JD

更新日期：1992-10-30 00:00:00

abstract：:BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited ...

journal_title：Journal of medicinal chemistry

authors： Hu J,Tian CQ,Damaneh MS,Li Y,Cao D,Lv K,Yu T,Meng T,Chen D,Wang X,Chen L,Li J,Song SS,Huan XJ,Qin L,Shen J,Wang YQ,Miao ZH,Xiong B

更新日期：2019-09-26 00:00:00

abstract：:The cyclic somatostatin analogue cyclo[Pro(1)-Phe(2)-D-Trp(3)-Lys(4)-Thr(5)-Phe(6)] (L-363,301) displays high biological activity in inhibiting the release of growth hormone, insulin, and glucagon. According to the sequence of L-363,301, we synthesized a number of cyclic hexa- and pentapeptides containing nonnatural a...

journal_title：Journal of medicinal chemistry

authors： Sukopp M,Schwab R,Marinelli L,Biron E,Heller M,Várkondi E,Pap A,Novellino E,Kéri G,Kessler H

更新日期：2005-04-21 00:00:00

abstract：:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compoun...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Lin S,Aung TT,Lim F,Zou H,Bai Y,Li J,Lin H,Pang LM,Koh WL,Salleh SM,Lakshminarayanan R,Zhou L,Qiu S,Pervushin K,Verma C,Tan DT,Cao D,Liu S,Beuerman RW

更新日期：2015-01-22 00:00:00

abstract：:Ten analogues of the highly mu-receptor selective cyclic opioid peptide H-Tyr-D-Orn-Phe-Asp-NH2 (1) were synthesized by the solid phase method and were characterized in vitro in mu- and delta-receptor representative binding assays and bioassays. These cyclic analogues are structurally related to the linear opioid pept...

journal_title：Journal of medicinal chemistry

authors： Schiller PW,Nguyen TM,Maziak LA,Wilkes BC,Lemieux C

更新日期：1987-11-01 00:00:00