Austalides V and W, new meroterpenoids from the fungus Aspergillus ustus and their antitumor activities.

abstract：:This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhong M,Peng E,Huang N,Huang Q,Huq A,Lau M,Colonno R,Li L

更新日期：2014-12-15 00:00:00

abstract：:Esculentoside A (EsA) has been reported to possess anti-inflammatory activity and selective inhibitory activity towards cyclooxygenase-2. A series of derivatives of EsA were synthesized by converting the C-28 carboxylic acid group into amides. The haemolytic activity and inhibitory activity towards cyclooxygenase-2 we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu F,Yi Y,Sun P,Zhang D

更新日期：2007-12-01 00:00:00

abstract：:The selective inhibition of coagulation factor Xa has emerged as an attractive strategy for the discovery of novel antithrombotic agents. Here we describe highly potent benzamidine factor Xa inhibitors based on a vicinally-substituted heterocyclic core. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fevig JM,Pinto DJ,Han Q,Quan ML,Pruitt JR,Jacobson IC,Galemmo RA Jr,Wang S,Orwat MJ,Bostrom LL,Knabb RM,Wong PC,Lam PYS,Wexler RR

更新日期：2001-03-12 00:00:00

abstract：:Several novel series of nitrile-containing fluoroquinolones with weakly basic amines are reported which have reduced potential for hERG (human ether-a-go-go gene) channel inhibition as measured by the dofetilide assay. The new fluoroquinolones are potent against both Gram-positive and fastidious Gram-negative strains,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murphy ST,Case HL,Ellsworth E,Hagen S,Huband M,Joannides T,Limberakis C,Marotti KR,Ottolini AM,Rauckhorst M,Starr J,Stier M,Taylor C,Zhu T,Blaser A,Denny WA,Lu GL,Smaill JB,Rivault F

更新日期：2007-04-15 00:00:00

abstract：:Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith DG,Gribble AD,Haigh D,Ife RJ,Lavery P,Skett P,Slingsby BP,Stacey R,Ward RW,West A

更新日期：1999-11-01 00:00:00

abstract：:We report the discovery of the pyrimido-diazepine scaffolds as novel adenine mimics. Structure-based design led to the discovery of analogs with potent inhibitory activity against receptor tyrosine kinases, such as KDR, Flt3 and c-Kit. Compound 14 exhibited low nanomolar KDR enzymatic and cellular potencies (IC(50)=9 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gracias V,Ji Z,Akritopoulou-Zanze I,Abad-Zapatero C,Huth JR,Song D,Hajduk PJ,Johnson EF,Glaser KB,Marcotte PA,Pease L,Soni NB,Stewart KD,Davidsen SK,Michaelides MR,Djuric SW

更新日期：2008-04-15 00:00:00

abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

更新日期：2006-05-15 00:00:00

abstract：:The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines is described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA-0008 demonstra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park CH,Choe H,Jang IY,Kwon SY,Latif M,Lee HK,Lee HJ,Yang EH,Yun JI,Chae CH,Cho SY,Choi SU,Ha JD,Jung H,Kim HR,Kim P,Lee CO,Yun CS,Lee K

更新日期：2013-11-15 00:00:00

abstract：:Two well-defined oxidative chlorination-cyclization processes have been developed for the stereoselective synthesis of a variety of 4-amido-isothiazolidinone oxide derivatives. The stereochemistry of the cyclization products was confirmed by X-ray crystallography. These new compounds were designed as bacterial serine ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Z,Demuth TP Jr,Wireko FC

更新日期：2001-08-20 00:00:00

abstract：:Low-temperature NMR experiments and molecular modeling have been used to characterize the conformational behavior of a covalently cross-linked DNA base pair model. The data suggest that Watson-Crick or reverse Watson-Crick hydrogen bonding geometries have similar energies and can interconvert at low temperatures. This...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jensen EA,Allen BD,Kishi Y,O'Leary DJ

更新日期：2008-11-15 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim HS,Oh YS,Suh PG,Chung SK

更新日期：2003-01-20 00:00:00

abstract：:This Letter details our efforts to discover structurally unique M4 PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Temple KJ,Engers JL,Long MF,Watson KJ,Chang S,Luscombe VB,Jenkins MT,Rodriguez AL,Niswender CM,Bridges TM,Conn PJ,Engers DW,Lindsley CW

更新日期：2020-02-01 00:00:00

abstract：:Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verheijen JC,van Roon AM,Meeuwenoord NJ,Stuivenberg HR,Bayly SF,Chen L,van der Marel GA,Torrence PF,van Boom JH

更新日期：2000-04-17 00:00:00

abstract：:A series of novel hybrid molecules 4a-y containing thiazole and benzotriazole templates were designed and synthesized. The structures of the synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity (zone of inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gaikwad ND,Patil SV,Bobade VD

更新日期：2012-05-15 00:00:00

abstract：:4-Thiazolidinone derivatives were synthesized using T3P®-DMSO media as a cyclodehydrating agent. All the molecules were tested for their cytotoxicity against leukemic cell lines. The compound 3-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)thiazolidin-4-one (4e) with electron donating substituent at para position of phen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharath Kumar KS,Hanumappa A,Vetrivel M,Hegde M,Girish YR,Byregowda TR,Rao S,Raghavan SC,Rangappa KS

更新日期：2015-09-01 00:00:00

abstract：:A uHTS campaign led to the discovery of a 5-(5-furan-2-ylpyrazol-1-yl)-1H-benzimidazole series that inhibits assembly of HIV-1 capsid. Synthetic manipulations at N1, C2 and C16 positions improved the antiviral potency by a . The X-ray structure of 33 complexed with the capsid N-terminal domain allowed identification o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tremblay M,Bonneau P,Bousquet Y,DeRoy P,Duan J,Duplessis M,Gagnon A,Garneau M,Goudreau N,Guse I,Hucke O,Kawai SH,Lemke CT,Mason SW,Simoneau B,Surprenant S,Titolo S,Yoakim C

更新日期：2012-12-15 00:00:00

abstract：:A series of novel arylsulfonylpropargylglycinamide derivatives was investigated as thrombin inhibitors in which the SAR was focused on substituents at the acetylenic terminus. Several compounds in this series were identified as potent thrombin inhibitors (Ki up to 5 nM) that are highly selective over trypsin and other...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee K,Hwang SY,Park CW

更新日期：1999-04-05 00:00:00

abstract：:Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han W,Hu Z,Jiang X,Decicco CP

更新日期：2000-04-17 00:00:00

abstract：:Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Breslin MJ,Duggan ME,Halczenko W,Fernandez-Metzler C,Hunt CA,Leu CT,Merkle KM,Naylor-Olsen AM,Prueksaritanont T,Stump G,Wallace A,Rodan SB,Hutchinson JH

更新日期：2003-05-19 00:00:00

abstract：:This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chrom...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian Y,Jin J,Wang C,Lv W,Li X,Che X,Gong Y,Li Y,Li Q,Hou J,Wang PG,Shen J

更新日期：2016-05-15 00:00:00

abstract：:4-Anilino-3-cyanoquinolines were reported to have irreversible binding to epidermal growth factor receptor kinase (EGFRK) by forming a covalent linkage to C773. Our initial docking studies gave results inconsistent with the in vitro data and showed two different binding modes. To perceive the exact mode of binding of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Akula N,Bhalla J,Sridhar J,Pattabiraman N

更新日期：2004-07-05 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：:In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan YM,Dai HQ,Du Y,Schneider B,Guo H,Li DP,Zhang LX,Fu H,Dong XP,Cheng YX

更新日期：2012-06-15 00:00:00

abstract：:A quantitative structure-activity relationship (QSAR) modeling of the antimold activity of cinnamaldehyde analogues against of Aspergillus niger and Paecilomyces variotii was presented. The molecular descriptors of cinnamaldehyde analogues were calculated by the CODESSA program, and these descriptors were selected by ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Y,Li S,Kong X

更新日期：2013-03-01 00:00:00

abstract：:We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abbott L,Betschmann P,Burchat A,Calderwood DJ,Davis H,Hrnciar P,Hirst GC,Li B,Morytko M,Mullen K,Yang B

更新日期：2007-03-01 00:00:00

abstract：:A series of paclitaxel analogues possessing a macrocyclic structure between the 7 and 10 positions has been prepared. These compounds possess in vitro activity against a paclitaxel resistant cell line and have in vivo activity comparable to paclitaxel. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tarrant JG,Cook D,Fairchild C,Kadow JF,Long BH,Rose WC,Vyas D

更新日期：2004-05-17 00:00:00

abstract：:The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Linder MR,Heckeroth AR,Najdrowski M,Daugschies A,Schollmeyer D,Miculka C

更新日期：2007-08-01 00:00:00

abstract：:A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC(50) values for inhibition of 5-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen FK,Khankischpur M,Tolaymat I,Mesaros R,Dannhardt G,Geffken D

更新日期：2012-08-01 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:Mammalian target of rapamycin (mTOR) is a promising target for the development of anticancer medicines. Here, we report the first example for a successful application of the structure-based virtual screening to identify new mTOR inhibitors. Using the scoring function improved by implementing the ligand solvation effec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park H,Choe H,Hong S

更新日期：2014-02-01 00:00:00