DNA-templated click chemistry for creation of novel DNA binding molecules.

abstract：:Indolinonic hydroxylamines (IH), representing a new type of antioxidants, are comparative to alpha-tocopherol to protect lipids from oxidation. To elucidate the structure-activity relationship for IH, B3LYP/6-31G(d, p) method was employed to calculate the O-H bond dissociation enthalpy (BDE), a theoretical parameter t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang HY,Wang LF

更新日期：2002-01-21 00:00:00

abstract：:Corticotropin-releasing factor (CRF), a 41 amino acid peptide neurohormone synthesised by specific hypothalamic nuclei in the brain, is implicated in stress-related function. Antagonism of CRF(1) receptors is an attractive therapeutic approach for the treatment of depression and anxiety. Unsaturated tetrahydrotriazaac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gentile G,Di Fabio R,Pavone F,Sabbatini FM,St-Denis Y,Zampori MG,Vitulli G,Worby A

更新日期：2007-09-15 00:00:00

abstract：:MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barf T,Kaptein A,de Wilde S,van der Heijden R,van Someren R,Demont D,Schultz-Fademrecht C,Versteegh J,van Zeeland M,Seegers N,Kazemier B,van de Kar B,van Hoek M,de Roos J,Klop H,Smeets R,Hofstra C,Hornberg J,Oubrie A

更新日期：2011-06-15 00:00:00

abstract：:A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphen...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin CH,Krishnaiah M,Sreenu D,Subrahmanyam VB,Rao KS,Mohan AV,Park CY,Son JY,Sheen YY,Kim DK

更新日期：2011-10-15 00:00:00

abstract：:We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fox BM,Natero R,Richard K,Connors R,Roveto PM,Beckmann H,Haller K,Golde J,Xiao SH,Kayser F

更新日期：2011-04-15 00:00:00

abstract：:The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masaki Y,Yamamoto K,Inde T,Yoshida K,Maruyama A,Nagata T,Tanihata J,Takeda S,Sekine M,Seio K

更新日期：2019-01-15 00:00:00

abstract：:The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'-(N,N-d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao ZG,Joshi BV,Klutz AM,Kim SK,Lee HW,Kim HO,Jeong LS,Jacobson KA

更新日期：2006-02-01 00:00:00

abstract：:The peptidomimetic, LLP2A, is a specific, high-affinity ligand for α4β1 integrin receptors. Previously, several PEGylated LLP2A conjugates were evaluated in vivo as imaging agents for the detection of lymphoma, leukemia, multiple myeloma and melanoma tumours via NIR-fluorescence, 111In-SPECT, and 64Cu- and 68Ga-PET im...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walker D,Li Y,Roxin Á,Schaffer P,Adam MJ,Perrin DM

更新日期：2016-10-15 00:00:00

abstract：:Two series (4 and 5) of diarylpyridine derivatives were designed, synthesized, and evaluated for anti-HIV-1 activity. The most promising compound, 5e, inhibited HIV-1 IIIB, NL4-3, and RTMDR1 with low nanomolar EC50 values and selectivity indexes of >10,000. The results of this study indicate that diarylpyridine can be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian X,Qin B,Lu H,Lai W,Jiang S,Lee KH,Chen CH,Xie L

更新日期：2009-09-15 00:00:00

abstract：:The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhai W,Flynn N,Longhi DA,Tino JA,Murphy BJ,Slusarchyk D,Gordon DA,Pendri A,Shi S,Stoffel R,Ma B,Sofia MJ,Gerritz SW

更新日期：2008-09-15 00:00:00

abstract：:Steroidal derivatives as IL-1 beta release inhibitors are discussed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： He W,Huang FC,Morytko M,Jariwala N,Yu KT

更新日期：1998-10-20 00:00:00

abstract：:Phosphorodiamidate morpholino oligonucleotides (PMOs) have been extensively applied in antisense strategies for gene regulation because of their high stability in serum and low toxicity. However, chain elongation of PMOs requires long reaction time because few efficient methods have been developed for the formation of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harakawa T,Tsunoda H,Ohkubo A,Seio K,Sekine M

更新日期：2012-02-01 00:00:00

abstract：:A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewawasam P,Fan W,Knipe J,Moon SL,Boissard CG,Gribkoff VK,Starrett JE

更新日期：2002-07-08 00:00:00

abstract：:We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca(2+) channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca(2+) channels and N-type Ca(2+) channels. Among them, 5b (KYS05044, IC(50)=0.56+/-0.10 microM) was identified as potent T-type C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rhim H,Lee YS,Park SJ,Chung BY,Lee JY

更新日期：2005-01-17 00:00:00

abstract：:A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhance...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leese MP,Newman SP,Purohit A,Reed MJ,Potter BV

更新日期：2004-06-21 00:00:00

abstract：:Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nabika R,Suyama TL,Hau AM,Misu R,Ohno H,Ishmael JE,McPhail KL,Oishi S,Fujii N

更新日期：2015-01-15 00:00:00

abstract：:We report the discovery of a novel, chiral azetidine urea inhibitor of Fatty Acid Amide Hydrolase (FAAH,) and describe the surprising species selectivity of VER-156084 versus rat and human FAAH and also hCB1. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hart T,Macias AT,Benwell K,Brooks T,D'Alessandro J,Dokurno P,Francis G,Gibbons B,Haymes T,Kennett G,Lightowler S,Mansell H,Matassova N,Misra A,Padfield A,Parsons R,Pratt R,Robertson A,Walls S,Wong M,Roughley S

更新日期：2009-08-01 00:00:00

abstract：:A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang C,Corte JR,Rossi KA,Bozarth JM,Wu Y,Sheriff S,Myers JE Jr,Luettgen JM,Seiffert DA,Wexler RR,Quan ML

更新日期：2017-09-01 00:00:00

abstract：:Several analogues of the potent anthelmintic praziquantel were prepared with variation in the aromatic ring. The biological activity of these analogues was evaluated and compared against known analogues. Amination of the ring was tolerated while other variations were not. These results have important implications for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ronketti F,Ramana AV,Chao-Ming X,Pica-Mattoccia L,Cioli D,Todd MH

更新日期：2007-08-01 00:00:00

abstract：:The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C-N bond formation/reduction/diazotizat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marepu N,Yeturu S,Pal M

更新日期：2018-11-01 00:00:00

abstract：:The synthesis of novel C6-aryl substituted derivatives of 3-(dimethylamino)chroman is described. The novel derivatives display 5-HT(7) receptor affinities that varies from nM to muM, indicating that this small set of derivatives constitute a novel and interesting starting point for further structure-serotonin 5-HT(7) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holmberg P,Tedenborg L,Rosqvist S,Johansson AM

更新日期：2005-02-01 00:00:00

abstract：:Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin GH,Lee HJ,Gim HJ,Ryu JH,Jeon R

更新日期：2012-05-01 00:00:00

abstract：:Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang LY,Wang JD,Zhang J,Xue CY,Zhang H,Wang XJ,Xiang WS

更新日期：2013-10-15 00:00:00

abstract：:Hypericin monocarboxylic acid was synthesized in an overall yield of 25% in four steps and radiolabelled with iodine-123 in good yield (>75%). The resulting mono-[(123)I]iodohypericin monocarboxylic acid was evaluated in normal mice and in rats with ethanol induced liver necrosis. In this model, tracer concentration i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fonge H,Jin L,Wang H,Ni Y,Bormans G,Verbruggen A

更新日期：2007-07-15 00:00:00

abstract：:We describe an efficient method for the synthesis of alkyl lysophosphatidic acid (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor agonist activity using a cell migration assay for LPA(1) activation in cancer cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y,Tanaka M,Arai H,Aoki J,Prestwich GD

更新日期：2004-11-01 00:00:00

abstract：:Recently, we had identified an unexplored pocket adjacent to the known binding site of allosteric MEK inhibitors which allowed us to design highly potent and in vivo efficacious novel inhibitors. We now report that our initial preclinical candidate, featuring a phenoxy side chain with a sulfamide capping group, displa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartung IV,Hammer S,Hitchcock M,Neuhaus R,Scholz A,Siemeister G,Bohlmann R,Hillig RC,Pühler F

更新日期：2016-01-01 00:00:00

abstract：:A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ma Z,Pan Y,Huang W,Yang Y,Wang Z,Li Q,Zhao Y,Zhang X,Shen Z

更新日期：2014-01-01 00:00:00

abstract：:Synthesis of a symmetrically branched diglycerol (BGL002, involving one iminodiacetic residue) as a G2 dendron, and the tetradecaglycerol (BGL014, involving one iminodiacetic residue) as a G4 dendron, is described. Several members of the BGL family of G2-G4 dendrons were assembled, with G2 bearing four hydroxyl groups...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nemoto H,Ishihara A,Araki T,Katagiri A,Kamiya M,Matsushita T,Hattori H,Mimura Y,Tomoda Y,Yamasaki M

更新日期：2011-08-15 00:00:00

abstract：:Polysulfides typically react readily with thiols, thus, reactions of endogenous cellular thiols with the polysulfide linkage in naturally-occuring pentathiepin cytotoxins are likely to be an important aspect of their biological chemistry. Here, it is reported that the reaction of thiols with the pentathiepin ring syst...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chatterji T,Gates KS

更新日期：2003-04-07 00:00:00

abstract：:Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zeng Y,Rademacher C,Nycholat CM,Futakawa S,Lemme K,Ernst B,Paulson JC

更新日期：2011-09-01 00:00:00