New diterpene furanoids from the Antarctic lichen Huea sp.

abstract：:Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K(+) channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hua Z,Lvov A,Morin TJ,Kobertz WR

更新日期：2011-09-01 00:00:00

abstract：:Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bass JY,Caldwell RD,Caravella JA,Chen L,Creech KL,Deaton DN,Madauss KP,Marr HB,McFadyen RB,Miller AB,Parks DJ,Todd D,Williams SP,Wisely GB

更新日期：2009-06-01 00:00:00

abstract：:Three new iridoid glycosides, 6"-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (2), genipin 1-O-α-D-xylopyranosyl (1→6)-β-D-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known ir...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng K,Yang L,Zhao S,Chen L,Zhao F,Qiu F

更新日期：2013-02-15 00:00:00

abstract：:In general, serine protease chymase inhibitors readily decompose in plasma. We previously found that thiazolidine-2,4-dione and thiadiazole derivatives are also unstable. Using a pharmacophore-based database search, we identified a benzo[b]thiophen-2-sulfonamide derivative as a stable chymase inhibitor. Finding a lead...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koide Y,Tatsui A,Hasegawa T,Murakami A,Satoh S,Yamada H,Kazayama S,Takahashi A

更新日期：2003-01-06 00:00:00

abstract：:A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)-antagonists. The most potent compounds were found in the class of (piperazine-1-yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau JF,Jeppesen CB,Rimvall K,Hohlweg R

更新日期：2006-10-15 00:00:00

abstract：:This study examined the neuroprotective effects of kobophenol A (kob A), oligomeric stillbene, and a resveratrol tetramer. Neuronal death induced by the withdrawal of tropic support was ameliorated by kob A. The protective effect of kob A against nitrosative/oxidative or mitochondrial damages resulted in the inhibitio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SR,Kwak JH,Kim HJ,Pyo S

更新日期：2007-04-01 00:00:00

abstract：:We have optimized 2-aminomethylphenylamine derivative as a factor Xa inhibitor. Several polar functional groups were introduced in the central phenyl ring, and we focused on zwitter ionic compound showing continuous inhibitory activity in oral administration test. In vitro and oral activities were improved by optimiza...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mochizuki A,Nagata T,Kanno H,Takano D,Kishida M,Suzuki M,Ohta T

更新日期：2011-12-15 00:00:00

abstract：:Prostate-specific membrane antigen (PSMA) is an important biological target for therapy and diagnosis of prostate cancer. In this study, novel multivalent PSMA inhibitors with glutamate-urea-lysine structures were designed to improve inhibition characteristics. Precursors of the novel inhibitors were prepared from glu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kwon YD,Chung HJ,Lee SJ,Lee SH,Jeong BH,Kim HK

更新日期：2018-02-15 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：:A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thuong PT,Kang KW,Kim JK,Seo DB,Lee SJ,Kim SH,Oh WK

更新日期：2009-03-15 00:00:00

abstract：:Novel fused 1H-benzo[f]chromen-indole derivatives were synthesized regioselectivly in good to high yields by triethyl amine catalyzed condensation of 3-cyanoacetylindoles, β-naphthol and aryl aldehydes in methanol under ultrasounic irradiations and conventional conditions. The easy work-up of the products, rapidity, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hossein nia R,Mamaghani M,Tabatabaeian K,Shirini F,Rassa M

更新日期：2012-09-15 00:00:00

abstract：:We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes AD,Chin KH,Dunham SL,Jasper JR,King KE,Lee TW,Mammen M,Martin J,Steinfeld T

更新日期：2011-03-01 00:00:00

abstract：:Pradimicins are a group of antiviral and antifungal natural products from Actinomadura hibisca. Two putative O-methyltransferase genes, pdmF and pdmT, are present in the pradimicin biosynthetic gene cluster. However, there is only one methoxy group (11-OCH3) in pradimicins. Through heterologous expression and in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu F,Napan K,Zhang S,Gladwin T,Takemoto J,Zhan J

更新日期：2017-08-01 00:00:00

abstract：:Stereoselective total synthesis of bioactive marine natural product crucigasterin A has been accomplished from commercially available and inexpensive L-(-)-malic acid as a starting material. Julia olefination and chelation controlled Grignard additions are the key steps involved in the present synthesis. Cytotoxic pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar JN,Reddy PR,Das B,Kumar CG,Sujitha P

更新日期：2013-09-15 00:00:00

abstract：:We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies le...

journal_title：Bioorganic & medicinal chemistry letters

authors： He S,Ye Z,Dobbelaar PH,Bakshi RK,Hong Q,Dellureficio JP,Sebhat IK,Guo L,Liu J,Jian T,Lai Y,Franklin CL,Reibarkh M,Holmes MA,Weinberg DH,MacNeil T,Tang R,Tamvakopoulos C,Peng Q,Miller RR,Stearns RA,Chen HY,Chen

更新日期：2010-11-15 00:00:00

abstract：:Using clonogenic survival assays, we demonstrated that a new platinum-acridine hybrid agent, PT-ACRAMTU, is cytotoxic in SNB19 and U87MG glioblastoma cells at low-micromolar concentrations. PT-ACRAMTU is more cytotoxic than ACRAMTU (the platinum-free acridine), acts in a time and dose dependent manner, and appears to ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hess SM,Anderson JG,Bierbach U

更新日期：2005-01-17 00:00:00

abstract：:A series of potent non-acetylinic negative allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 NAMs) was developed starting from HTS screening hit 1. Potency was improved via iterative SAR, and physicochemical properties were optimized to deliver orally bioavailable compounds acceptable for in vivo t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duvey G,Perry B,Le Poul E,Poli S,Bonnet B,Lambeng N,Charvin D,Donovan-Rodrigues T,Haddouk H,Gagliardi S,Rocher JP

更新日期：2013-08-15 00:00:00

abstract：:Previously, potent factor Xa inhibitors were described based on a pyrazole core. Modifications of the pyrazole core have provided additional novel, highly potent factor Xa inhibitors. This manuscript will describe the synthesis and biological activity of factor Xa inhibitors containing the 1H-pyrazolo[4,3-d]pyrimidin-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fevig JM,Cacciola J,Buriak J Jr,Rossi KA,Knabb RM,Luettgen JM,Wong PC,Bai SA,Wexler RR,Lam PY

更新日期：2006-07-15 00:00:00

abstract：:SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC(50) value of 34 nM. [(11)C]SB-216763 (3-(2,4-dichlorophenyl)-4-(1-[(11)C]methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay cor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Hutchins GD,Zheng QH

更新日期：2011-01-01 00:00:00

abstract：:The stereoselective synthesis and biological activity of NPS 1407 (4a), (S)-(-)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate (4) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moe ST,Smith DL,DelMar EG,Shimizu SM,Van Wagenen BC,Balandrin MF,Chien YE,Raszkiewicz JL,Artman LD,White HS,Mueller AL

更新日期：2000-11-06 00:00:00

abstract：:Chimeric oligonucleotides comprised of alternating residues of 2'-deoxy-2'-fluoro-D-arabinonucleic acid (2'F-ANA) and DNA were synthesized and evaluated for an important antisense property-the ability to elicit ribonuclease H (RNase H) degradation of complementary RNA. Experiments used both human RNase HII and Escheri...

journal_title：Bioorganic & medicinal chemistry letters

authors： Min KL,Viazovkina E,Galarneau A,Parniak MA,Damha MJ

更新日期：2002-09-16 00:00:00

abstract：:Previously, 4-tosylanthra[1,2-c][1,2,5]thiadiazole-6,11-dione (1) was identified as a novel non-camptothecin topoisomerase I (Top1) inhibitor by structure-based virtual screening. Herein, a series of 4-substituted derivatives were designed and synthesized. Most of them showed potent Top1 inhibitory activity. Their in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dong G,Fang Y,Liu Y,Liu N,Wu S,Zhang W,Sheng C

更新日期：2017-05-01 00:00:00

abstract：:To design artificial restriction enzymes, synthetic catalytic centers that effectively hydrolyze linear double-stranded polydeoxyribonucleotides are needed. The Co(III) complex of cyclen (CoCyc) attached to polystyrene derivatives hydrolyzes linearized pUC18 DNA with half-lives as short as 30 min at 25 degrees C. The ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeung CS,Song JB,Kim YH,Suh J

更新日期：2001-12-03 00:00:00

abstract：:The 5,5-bicycles cis-6-oxo-hexahydro-2-oxa-1,4-diazapentalene 3 and cis-6-oxo-hexahydropyrrolo[3,2-c]pyrazole 4 were designed as rotationally restricted templates towards the preparation of inhibitors of CAC1 cysteinyl proteinases. The design strategy was exemplified through the solution and solid phase preparation of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Benn A,Flinn N,Monk T,Ramjee M,Watts J,Quibell M

更新日期：2005-03-01 00:00:00

abstract：:Prostate specific membrane antigen (PSMA) is recognized as an attractive molecular target for the development of radiopharmaceuticals to image and potentially treat metastatic prostate cancer. A series of novel (99m)Tc/Re-tricarbonyl radiolabeled PSMA inhibitors were therefore synthesized by the attachment of glutamat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu G,Maresca KP,Hillier SM,Zimmerman CN,Eckelman WC,Joyal JL,Babich JW

更新日期：2013-03-01 00:00:00

abstract：:[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglut...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kato H,Yashiro A,Mizuno A,Nishida Y,Kobayashi K,Shinohara H

更新日期：2001-11-19 00:00:00

abstract：:N-13C-methyl-deoxynojirimycin was synthesized and used in isotope-edited NMR studies to probe the binding site of an alpha-glucosidase. Results from this analysis led to the design and preparation of a novel alpha-glucosidase inhibitor, N-glycyl deoxynojirimycin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hines JV,Chang H,Gerdeman MS,Warn DE

更新日期：1999-05-03 00:00:00

abstract：:We report the synthesis and biochemical evaluation of new competitive inhibitors of the cytosolic (NADH-dependent) glycerophosphate dehydrogenase. The best tested compound, phosphono-propionohydroxamic acid, with a Ki of 6 microM, might be of interest as an anti-obesity drug. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fonvielle M,Therisod H,Hemery M,Therisod M

更新日期：2007-01-15 00:00:00

abstract：:A new series of Proteolysis Targeting Chimeras (PROTACs) targeting Bruton's Tyrosine Kinase (BTK) was synthesized, with the goal of improving the pharmacokinetic properties of our previously reported PROTAC, MT802. We recently described the ability of MT802 to induce degradation of both wild-type and C481S mutant BTK ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jaime-Figueroa S,Buhimschi AD,Toure M,Hines J,Crews CM

更新日期：2020-02-01 00:00:00

abstract：:A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over bindi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Kato T,Yamamoto I,Shimizu A,Mizutani S,Asai M,Kawamoto H,Ito S,Yoshizumi T,Hirayama M,Ozaki S,Ohta H,Okamoto O

更新日期：2009-06-01 00:00:00