Arylanthranilodinitriles: a new biaryl class of antileishmanial agents.

abstract：:A series of glutathione derivatives 1-4, modified at the N,S and/or COOH sites, with in vitro antitrypanosomal activity were tested against bloodstream form Trypanosoma brucei 247 wild type and a T. b. brucei 247 strain over-expressing the multiple drug resistance protein (MRPA) by 50-100x to assess the susceptibility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alibu VP,Daunes S,D'Silva C

更新日期：2013-08-01 00:00:00

abstract：:Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

更新日期：2020-04-15 00:00:00

abstract：:The efficient synthesis of an enzyme cleavable biotinylated diazirinyl photoaffinity ligand is described to allow the effective manipulation of the photolabeled biocomponents. The compound contains a glutamic acid gamma-methyl ester, which is a precursor of the substrate for V8 protease, between the diazirinyl photoph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto M,Okamoto S,Nabeta K,Hatanaka Y

更新日期：2004-05-17 00:00:00

abstract：:Inhibition of BCR-ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia (CML). However, drug resistance has quickly arisen in recent clinical trials for STI571 (Gleevec), which is the first approved drug of CML by inhibiting ABL tyrosine kinase. It is desirable to dev...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng H,Huang N,Qi J,Xie P,Xu C,Wang J,Yang C

更新日期：2003-11-03 00:00:00

abstract：:Based on the molecular modelling studies, a rational modification of the lead molecule was made to develop highly potent compounds showing anti-cancer activity against human breast cancer cell lines MCF 7, MDA-MB-468 and T-47D. The most potent compounds have Log P and total polar surface area 4.4-5.4 and 59.8 Å, respe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaur M,Singh P

更新日期：2019-01-01 00:00:00

abstract：:The synthesis and biological properties of a novel water-soluble echinocandin-like lipopeptide, FR131535, are described. This compound displayed potent in vitro and in vivo antifungal activities. The hemolytic activity of FR901379 was reduced by replacing the acyl side chain. This compound showed good water-solubility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujie A,Iwamoto T,Sato B,Muramatsu H,Kasahara C,Furuta T,Hori Y,Hino M,Hashimoto S

更新日期：2001-02-12 00:00:00

abstract：:The designed cytosine-carbohydrate hybrid molecule selectively recognized and stabilized the bulged duplex DNA possessing the complementary bulged DNA base, guanine, while the nucleotide base itself did not exhibit any such ability. It was also found that the assistance of the carbohydrate to stabilize the interaction...

journal_title：Bioorganic & medicinal chemistry letters

authors： Idutsu Y,Sasaki A,Matsumura S,Toshima K

更新日期：2005-10-01 00:00:00

abstract：:The synthesis and biological profile of a novel series of potent and selective inhibitors of cysteine protease cathepsin K (Cat K) are described. Pharmacokinetic evaluation of 12 indicated that some members of this series could be suitable candidates to develop new orally active therapeutic agents for the treatment of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Setti EL,Venkatraman S,Palmer JT,Xie X,Cheung H,Yu W,Wesolowski G,Robichaud J

更新日期：2006-08-15 00:00:00

abstract：:Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the opti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y,Liu XH,Saunders M,Pearce S,Foulks JM,Parnell KM,Clifford A,Nix RN,Bullough J,Hendrickson TF,Wright K,McCullar MV,Kanner SB,Ho KK

更新日期：2014-01-15 00:00:00

abstract：:New inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered using an N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamide scaffold. The series was found to be potent in a porcine TACE (pTACE) assay with IC(50)s typically below 5 nM. For most compounds, selectivity for pTACE relative to MMP-1,-2, and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Lu Z,Xue CB,He X,Seng JL,Roderick JJ,Wasserman ZR,Liu RQ,Covington MB,Magolda RL,Newton RC,Trzaskos JM,Decicco CP

更新日期：2003-06-16 00:00:00

abstract：:The alpha7 subtype of the neuronal nicotinic acetylcholine receptors (nAChRs) was targeted for the design of selective agonists deriving from the quinuclidine scaffold. Arylidene groups at the 3-position and N-methyl quinuclidine were found to be selective agonists with EC(50)s of 1.5 and 40 microM, respectively. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leonik FM,Papke RL,Horenstein NA

更新日期：2007-03-15 00:00:00

abstract：:A new 'naked-eye' quinoline-based 'reactive' ratiometric fluorescent probe was prepared. The reactive stoichiometry of the probe with Hg²⁺ ion was 2:1. The probe exhibited high selectivity towards Hg²⁺ ion to other metal ions with a 410-fold increase in absorbance intensity ratio (A₄₀₂/A₃₄₀) in aqueous solution over a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Yan Y,Chen S,Gao Z,Xu H

更新日期：2014-12-01 00:00:00

abstract：:Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： da Silva SR,Paiva SL,Bancerz M,Geletu M,Lewis AM,Chen J,Cai Y,Lukkarila JL,Li H,Gunning PT

更新日期：2016-09-15 00:00:00

abstract：:Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mochona B,Qi X,Euynni S,Sikazwi D,Mateeva N,Soliman KF

更新日期：2016-06-15 00:00:00

abstract：:Phosphorothioate oligodeoxynucleotides containing CpG motifs have immunostimulatory activity. Appropriate substitution of deoxynucleosides in the flanking region of CpG-containing phosphorothioate oligodeoxynucleotides with 2'-O-methylribonucleosides results in significant decreases or increases in their immunostimula...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Q,Yu D,Agrawal S

更新日期：1999-12-20 00:00:00

abstract：:We disclose a novel series of insulin-like growth factor-1 receptor kinase inhibitors based on the 3-(pyrimidin-4-yl)-imidazo[1,2-a]pyridine scaffold. The influence on the inhibitory activity of substitution on the imidazopyridine and at the C5 position of the pyrimidine is discussed. In the course of this optimizatio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ducray R,Simpson I,Jung FH,Nissink JW,Kenny PW,Fitzek M,Walker GE,Ward LT,Hudson K

更新日期：2011-08-15 00:00:00

abstract：:In this study, five novel triterpenes were isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum and identified as gypensapogenin H (1), gypensapogenin I (2), gypensapogenin L (3), gypensapogenin J (4) and gypensapogenin K (5), three of which (1-3) possess unprecedented ring A. All the isolated comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang XS,Cao JQ,Zhao C,Wang XD,Wu XJ,Zhao YQ

更新日期：2015-08-15 00:00:00

abstract：:A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Larget R,Lockhart B,Pfeiffer B,Neudorffer A,Fleury MB,Largeron M

更新日期：1999-10-18 00:00:00

abstract：:Three novel inosine-based dinuclear platinum complexes have been synthesized via a solid-phase strategy. In these compounds, the metal is linked both to the N-7 of the purine nucleus and to the terminal amine group of a hexylamine side chain installed on N-1. Cis- or trans- diamine as well as ethylenediamine ligands a...

journal_title：Bioorganic & medicinal chemistry letters

authors： D'Errico S,Oliviero G,Piccialli V,Amato J,Borbone N,D'Atri V,D'Alessio F,Di Noto R,Ruffo F,Salvatore F,Piccialli G

更新日期：2011-10-01 00:00:00

abstract：:Potential prodrugs for the TRH-like tripeptide pGlu-Glu-Pro-NH(2) were synthesized either by esterifying the Glu side-chain of the parent peptide in solution with alcohols in the presence of resin-bound dicyclohexylcarbodiimide or by solid-phase peptide chemistry. Affinities of these ester prodrugs to lipid membranes ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prokai-Tatrai K,Nguyen V,Zharikova AD,Braddy AC,Stevens SM,Prokai L

更新日期：2003-03-24 00:00:00

abstract：:In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

更新日期：2015-05-01 00:00:00

abstract：:A one step synthesis of fluorescent 8-aryl-(7-deazaguanines) has been accomplished. Probes exhibit blue to green high quantum yield fluorescence in a variety of organic and aqueous solutions, high extinction coefficients, and large Stokes shifts often above 100 nm. The probes are highly cell permeable, and exhibit sta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhimitruka I,Eubank TD,Gross AC,Khramtsov VV

更新日期：2015-10-15 00:00:00

abstract：:A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerizat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li PK,Xiao Z,Hu Z,Pandit B,Sun Y,Sackett DL,Werbovetz K,Lewis A,Johnsamuel J

更新日期：2005-12-15 00:00:00

abstract：:A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Chen X,Cho A,Delaney WE 4th,Doerffler E,Fardis M,Ji M,Mertzman M,Pakdaman R,Pyun HJ,Rowe T,Yang CY,Sheng XC,Kim CU

更新日期：2011-06-15 00:00:00

abstract：:The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of differen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Denhart DJ,Purandare AV,Catt JD,King HD,Gao A,Deskus JA,Poss MA,Stark AD,Torrente JR,Johnson G,Mattson RJ

更新日期：2004-08-16 00:00:00

abstract：:In order to obtain information regarding the design of selective DPP4 inhibitors, a 3D-QSAR study was conducted using DPP4, DPP8, and DPP9 inhibitors including newly synthesized six- and seven-membered cyclic hydrazine derivatives (KR64300, KR64301), which were evaluated in vitro for their inhibition of DPP4, DPP8, an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang NS,Ahn JH,Kim SS,Chae CH,Yoo SE

更新日期：2007-07-01 00:00:00

abstract：:Synthetic and biological evaluation of novel diphenyloxazole derivatives containing a pyrrolidine ring, as a prostacyclin mimetic without the PG skeleton, are described. Asymmetric reduction of a ketone using a chiral Ru complex and reductive amination by NaBH(4) produces four isomers of the tetrahydronaphthalene ring...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hattori K,Okitsu O,Tabuchi S,Taniguchi K,Nishio M,Koyama S,Seki J,Sakane K

更新日期：2005-07-01 00:00:00

abstract：:A new class of (E)-2-alkyl-2-(4-methanesulfonylphenyl)-1-phenylethenes were designed for evaluation as selective cyclooxygense-2 (COX-2) inhibitors. The target olefins were synthesized, via a Takeda olefination reaction, followed by oxidation of the respective thiomethyl olefinic intermediate. In vitro COX-1/COX-2 inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uddin MJ,Rao PN,Rahim MA,McDonald R,Knaus EE

更新日期：2004-10-04 00:00:00

abstract：:Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baba A,Wakao M,Shinchi H,Chan M,Hayashi T,Yao S,Cottam HB,Carson DA,Suda Y

更新日期：2020-02-01 00:00:00

abstract：:Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Williams PD,Bock MG,Evans BE,Freidinger RM,Gallicchio SN,Guidotti MT,Jacobson MA,Kuo MS,Levy MR,Lis EV,Michelson SR,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Salvatore C,Stauffer KJ,Woyden CJ

更新日期：1999-05-03 00:00:00