S-aryl cysteine S,S-dioxides as inhibitors of mammalian kynureninase.

abstract：:The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu C,Wang L,Zhu Y,Guo ZZ,Liu P,Hu Z,Szewczyk JW,Kang L,Chicchi G,Ehrhardt A,Woods A,Seo T,Woods M,van Heek M,Dingley KH,Pang J,Salituro GM,Powell J,Terebetski JL,Hornak V,Campeau LC,Orr RK,Ujjainwalla F,Mil

更新日期：2017-03-01 00:00:00

abstract：:Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and scr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Temple KJ,Wright EN,Fierke CA,Gibbs RA

更新日期：2016-08-01 00:00:00

abstract：:The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P(2) region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure-activity relationship, and selectivity against related proteases are delineated. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sattigeri JA,Andappan MM,Kishore K,Thangathirupathy S,Sundaram S,Singh S,Sharma S,Davis JA,Chugh A,Bansal VS

更新日期：2008-07-15 00:00:00

abstract：:5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antago...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ladouceur GH,Cook JH,Doherty EM,Schoen WR,MacDougall ML,Livingston JN

更新日期：2002-02-11 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：:(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rodrigues T,Guedes RC,dos Santos DJ,Carrasco M,Gut J,Rosenthal PJ,Moreira R,Lopes F

更新日期：2009-07-01 00:00:00

abstract：:Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Snead AN,Miyakawa M,Tan ES,Scanlan TS

更新日期：2008-11-15 00:00:00

abstract：:A series of human carbonic anhydrase (hCA) IX inhibitors conjugated to various near-infrared fluorescent dyes was synthesized with the aim of imaging hypoxia-induced hCA IX expression in tumor cells in vitro, ex vivo and in vivo. The resulting compounds were profiled for inhibition of transmembrane hCA IX showing a ra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Groves K,Bao B,Zhang J,Handy E,Kennedy P,Cuneo G,Supuran CT,Yared W,Peterson JD,Rajopadhye M

更新日期：2012-01-01 00:00:00

abstract：:Double-stranded RNA has become a ubiquitous tool for inhibition of gene expression in the laboratory. If similar success could be achieved in vivo, duplex RNA might provide a new class of therapeutics capable of treating a broad spectrum of disease. Chemists and biologists developing duplex RNA as a drug have made pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watts JK,Corey DR

更新日期：2010-06-01 00:00:00

abstract：:The in vitro and in vivo activities of a series of (2R,3R)-2-(2,4-difluorophenyl)-3-(substituted indazol-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol as potential antifungal agents are described. In particular, the analog 12j having 5-bromo substitution on the indazole ring exhibited significant antifungal activity again...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park JS,Yu KA,Kang TH,Kim S,Suh YG

更新日期：2007-06-15 00:00:00

abstract：:To improve the DNA hydrolytic activity of the zinc finger nuclease, we have created a new artificial zinc finger nuclease (ZWH4) by connecting two distinct zinc finger domains possessing different types of Zn(II) binding sites (Cys(2)His(2)- and His(4)-types). The overall fold of ZWH4 is similar to that of the wild-ty...

journal_title：Bioorganic & medicinal chemistry letters

authors： Negi S,Umeda Y,Masuyama S,Kano K,Sugiura Y

更新日期：2009-05-15 00:00:00

abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

更新日期：2009-06-15 00:00:00

abstract：:A series of potent and orally bioavailable 3,4-diaminocyclobutenediones with various amide modifications and substitution on the left side phenyl ring were prepared and found to show significant inhibitory activities towards both CXCR2 and CXCR1 receptors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aki C,Chao J,Ferreira JA,Dwyer MP,Yu Y,Chao J,Merritt RJ,Lai G,Wu M,Hipkin RW,Fan X,Gonsiorek W,Fosseta J,Rindgen D,Fine J,Lundell D,Taveras AG,Biju P

更新日期：2009-08-01 00:00:00

abstract：:Potent cyclin dependent kinase inhibitors were prepared using parallel synthesis methodology. Treating advanced intermediate 2 with a variety of hydrazides in DMSO at 80 degrees C for 30 min gave the desired acylsemicarbazides in good to excellent yield. Several compounds were active against cdk4/D1 and cdk2/E in the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nugiel DA,Vidwans A,Dzierba CD

更新日期：2004-11-15 00:00:00

abstract：:A few substituted piperazinylphenyloxazolidinone compounds 6-13 having substitution on the distant nitrogen atom of piperazine ring scaffold have been synthesized and evaluated for their antibacterial activity in Gram-positive bacteria. A few compounds showed superior in vitro antibacterial activity against Staphyloco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lohray BB,Lohray VB,Srivastava BK,Gupta S,Solanki M,Pandya P,Kapadnis P

更新日期：2006-03-15 00:00:00

abstract：:Twenty 13,28-epoxy and related triterpenoid saponins from Ardisia japonica were evaluated for their anti-proliferative activity on human liver cancer cells and normal liver cells. Eight saponins selectively inhibited the growth of liver cancer Bel-7402 and HepG-2 cells without affecting the survival of normal liver HL...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Q,Li W,Hui LP,Zhao CY,He L,Koike K

更新日期：2012-10-01 00:00:00

abstract：:A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity ag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Narva S,Chitti S,Amaroju S,Bhattacharjee D,Rao BB,Jain N,Alvala M,Sekhar KVGC

更新日期：2017-08-15 00:00:00

abstract：:Two series of aminosubstituted coumarins were synthesised and evaluated in vitro as inhibitors of DNA gyrase and as potential antibacterials. Novel novobiocin-like coumarins, 4-(dialkylamino)methylcoumarins and 4-((2-alkylamino)ethoxy)coumarins, were discovered as gyrase B inhibitors with promising antibacterial activ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Laurin P,Ferroud D,Schio L,Klich M,Dupuis-Hamelin C,Mauvais P,Lassaigne P,Bonnefoy A,Musicki B

更新日期：1999-10-04 00:00:00

abstract：:In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric alpha7 channels, we carried out the virtual screening of a test set of potential nicotinic ligands, and adopted a simplified MM-PBSA approach to estimate their relative binding free energy values. By means ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grazioso G,Pomè DY,Matera C,Frigerio F,Pucci L,Gotti C,Dallanoce C,De Amici M

更新日期：2009-11-15 00:00:00

abstract：:In order to improve the analgesic activity of lead compound 7a, two series of dispirocyclopiperazinium (DSPZ) salts 9a-h, 10a-e and compounds 14, 15 were synthesized and evaluated for their in vivo analgesic activity both by acetic acid induced writhing test and hot plate test. Compounds 9h, 14, and 15 exhibited bette...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li A,Wang X,Yue CQ,Ye J,Li CL,Li RT

更新日期：2007-09-15 00:00:00

abstract：:Poly(ADP-ribose)polymerase-I (PARP-1) enzyme is involved in maintaining DNA integrity and programmed cell death. A virtual screening of commercial libraries led to the identification of five novel scaffolds with inhibitory profile in the low nanomolar range. A hit-to-lead optimization led to the identification of a gr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Giannini G,Battistuzzi G,Vesci L,Milazzo FM,De Paolis F,Barbarino M,Guglielmi MB,Carollo V,Gallo G,Artali R,Dallavalle S

更新日期：2014-01-15 00:00:00

abstract：:Here we present first dinucleotide affinity resins for purification of proteins that specifically recognize the 5' end of mRNA. Constructed resins possess either a naturally occurring mono- or trimethylated cap or their analogues resistant towards enzymatic degradation, bearing a CH(2) bridge between β and γ position ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jankowska-Anyszka M,Piecyk K

更新日期：2011-10-15 00:00:00

abstract：:The transcription factor nuclear factor-κB (NF-κB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu DC,Gong GH,Wei CX,Jin XJ,Quan ZS

更新日期：2016-03-15 00:00:00

abstract：:Beauveria bassiana AM278 and Absidia coerulea AM93 converted 8-prenylnaringenin (1) into two glycoside derivatives (7-O-β-D-glucopyranoside) (2) and 7-O-β-D-4'''-O-methylglucopyranoside) (3) in high yields in processes conducted in Saboraud medium. 8-Prenylnaringenin 7-O-β-D-4'''-O-methylglucopyranoside (3) is a new c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bartmańska A,Tronina T,Huszcza E

更新日期：2012-10-15 00:00:00

abstract：:A potent family of spirocyclic nicotinyl aminobenzamide selective HDAC1/HDAC2 inhibitors (SHI-1:2) is profiled. The incorporation of a biaryl zinc-binding motif into a nicotinyl scaffold resulted in enhanced potency and selectivity versus HDAC3, but also imparted hERG activity. It was discovered that increasing polar ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Methot JL,Hamblett CL,Mampreian DM,Jung J,Harsch A,Szewczak AA,Dahlberg WK,Middleton RE,Hughes B,Fleming JC,Wang H,Kral AM,Ozerova N,Cruz JC,Haines B,Chenard M,Kenific CM,Secrist JP,Miller TA

更新日期：2008-12-01 00:00:00

abstract：:This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seo WD,Lee JH,Jia Y,Wu C,Lee SJ

更新日期：2015-11-15 00:00:00

abstract：:Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea in the checkpoint kinase 1 (Chk1) enzyme, we modified R4, and to a lesser extent, R2, and R5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li G,Hasvold LA,Tao ZF,Wang GT,Gwaltney SL 2nd,Patel J,Kovar P,Credo RB,Chen Z,Zhang H,Park C,Sham HL,Sowin T,Rosenberg SH,Lin NH

更新日期：2006-04-15 00:00:00

abstract：:The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical...

journal_title：Bioorganic & medicinal chemistry letters

authors： Côté B,Burch JD,Asante-Appiah E,Bayly C,Bédard L,Blouin M,Campeau LC,Cauchon E,Chan M,Chefson A,Coulombe N,Cromlish W,Debnath S,Deschênes D,Dupont-Gaudet K,Falgueyret JP,Forget R,Gagné S,Gauvreau D,Girardin M,Guir

更新日期：2014-02-01 00:00:00

abstract：:A facile 1,3-dipolar cycloaddition of azomethine ylide generated in situ from the reaction of 1,3-thiazolane-4-carboxylic acid and isatin to 2-arylidene-1,3-indanediones furnished novel dispiro-oxindolylpyrrolothiazoles regio- and stereo-selectively in moderate to good yields (60-92%). In vitro antitubercular screenin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maheswari SU,Balamurugan K,Perumal S,Yogeeswari P,Sriram D

更新日期：2010-12-15 00:00:00

abstract：:Cryptosporidiosis, a gastrointestinal disease caused by protozoans of the genus Cryptosporidium, is a common cause of diarrheal diseases and often fatal in immunocompromised individuals. Bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis (C. hominis) has been a molecular t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mukerjee A,Iyidogan P,Castellanos-Gonzalez A,Cisneros JA,Czyzyk D,Ranjan AP,Jorgensen WL,White AC Jr,Vishwanatha JK,Anderson KS

更新日期：2015-01-01 00:00:00