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_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
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 Adoi
10.1016/j.bmcl.2011.04.018subject
Has Abstractpub_date
2011-06-15 00:00:00pages
3818-22issue
12eissn
0960-894Xissn
1464-3405pii
S0960-894X(11)00465-3journal_volume
21pub_type
杂志文章abstract：:Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique str...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.02.064
更新日期：2004-05-17 00:00:00
abstract：:A novel neurokinin-1 receptor antagonist, (+/-)-(1R( *),3S( *),4S( *),5S( *))-4-[(N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-3-phenyl-2-aza-7-oxabicyclo[3.3.0]octane (1), was synthesized stereoselectively using Padwa's intramolecular 1,3-dipolar cycloaddition methodology as the key step. Compound (+/-)-1 showed high...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.10.010
更新日期：2007-12-15 00:00:00
abstract：:Through a systematic modification of the novel angiogenesis inhibitor 4-senecioyloxymethyl-6,7-dimethoxycoumarin (1) we found that a 6,7-dimethoxy moiety is important for bioactivity of 1. Replacement of the lactone functionality in coumarin 1 by an amide decreased its activity. By substitution of the senecioyl chain ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)00392-x
更新日期：2002-09-02 00:00:00
abstract：:3-Phenyl-3.4-dihydro-1-isoquinolinamine is a weak inhibitor of iNOS and nNOS. Structural variation of 5a results in inhibitors with a range of potency and selectivity for the NOS enzymes, including a potent and very selective iNOS inhibitor 5j. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(01)00119-6
更新日期：2001-04-23 00:00:00
abstract：:Ionic liquid ethyl ammonium nitrate is used as an excellent catalyst and solvent for three-component one-pot reaction of an aldehydes, amines and diethylphosphite to form novel α-aminophosphonates at room temperature. Among the various catalysts, the preparation of ethyl ammonium nitrate is an environmental friendly, ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.02.039
更新日期：2011-04-15 00:00:00
abstract：:A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues b...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)01082-x
更新日期：2003-03-10 00:00:00
abstract：:In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 μM. Mecha...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2018.03.017
更新日期：2018-05-01 00:00:00
abstract：:A series of lobelane and GZ-793A analogues that incorporate aromatic 4-hydroxy and 4-(2-fluoroethoxy) substituents were synthesized and evaluated for inhibition of [(3)H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and the dopamine transporter (DAT), and [(3)H]serotonin uptake at the serotonin...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2016.03.119
更新日期：2016-05-15 00:00:00
abstract：:γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-termi...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2014.09.035
更新日期：2014-11-01 00:00:00
abstract：:A series of 5-[(5-aryl-1H-pyrazol-3-yl)methyl]-1H-tetrazoles 3a-h have been synthesized and evaluated for their in vivo antihyperglycemic activity. Some of the synthesized compounds have shown significant glucose lowering activity in male Sprague-Dawley rats in sucrose loaded model. These compounds were also evaluated...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2005.02.060
更新日期：2005-04-15 00:00:00
abstract：:Hydrolysis of beta-lactam antibiotics by beta-lactamases (e.g., metallo-beta-lactamase, mbetal) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. It is shown in this paper tha...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.04.087
更新日期：2010-06-15 00:00:00
abstract：:In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in v...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2012.11.053
更新日期：2013-01-15 00:00:00
abstract：:In the search for plants, containing compounds with α-glucosidase inhibitory activity, we found that a methanolic extract from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen significantly inhibited rat intestinal sucrase in vitro. A phytochemical investigation of the aqueous layer of an A. clypearia ex...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2016.07.044
更新日期：2016-09-01 00:00:00
abstract：:Synthetic array technology was utilized to rapidly synthesize and analyze a diverse set of reductive alkylation analogues of daptomycin. Analysis of the array suggested the use of polar functionality such as sulfonamides or amide or polar spaces such as piperazine would beneficially affect activity. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2003.07.025
更新日期：2003-12-01 00:00:00
abstract：:In search of effective antidiabetic agents having therapeutic effect by inhibiting α-glucosidase and preventive effect by scavenging free radicals, Horsfieldia macrobotrys showed promising bioactivity required for the proposed criteria. Bioassay-guided isolation of the stem bark extract resulted in two new arylalkanon...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2015.08.069
更新日期：2015-10-15 00:00:00
abstract：:High-throughput screening of the GSK compound collection against the P2Y(1) receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2008.09.102
更新日期：2008-12-01 00:00:00
abstract：:A novel series of potent histamine H(3) receptor inverse agonists based on the 3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one scaffold has been discovered. Several compounds display high selectivity over other histamine receptor subtypes and have favorable physicochemical properties, low potential for CYP450 enzyme inhibit...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.08.009
更新日期：2010-10-01 00:00:00
abstract：:A series of novel nikkomycin analogue inhibitors of the chitin synthase of fungal cell wall was synthesized and evaluated for their inhibitory activities. Among them, the compound having a phenanthrene group at the terminal amino acid was found to possess strong anti-chitin synthase activity. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(00)00256-0
更新日期：2000-07-03 00:00:00
abstract：:A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC(50) of 0.033microM against Kv1.5 and is selective against other ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2007.02.052
更新日期：2007-05-15 00:00:00
abstract：:Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.04.004
更新日期：2011-06-01 00:00:00
abstract：:A series of Sordarin derivatives bearing alkyl substituted tetrahydrofuran rings fused to C3'-C4' bond of the sugar moiety have been prepared and their antifungal properties evaluated. Most of them show remarkable antifungal activity against Candida spp and Cryptococcus neoformans. ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(02)00293-7
更新日期：2002-07-08 00:00:00
abstract：:In a continuing study of hybrid compounds containing the alpha-bromoacryloyl moiety as potential anticancer drugs, we synthesized a novel series of hybrids 4a-h, in which this moiety was linked to a 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (4b, 4c, 4e and 4g) demonstrated pronounced, subm...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.03.075
更新日期：2010-05-01 00:00:00
abstract：:In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.01.004
更新日期：2004-04-19 00:00:00
abstract：:4,7-Dichloro-1-benzothien-2-yl sulfonylaminomethyl boronic acid (DSABA, Compound I) was discovered as the first boronic acid-based class D beta-lactamase inhibitor. It exhibited an IC(50) of 5.6 microM against OXA-40. The compound also inhibited class A and C beta-lactamases with sub to low microM IC(50), and synergiz...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2010.02.065
更新日期：2010-04-15 00:00:00
abstract：:Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2018.01.065
更新日期：2018-09-01 00:00:00
abstract：:Structure-activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) receptor antagonists...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2004.04.099
更新日期：2004-07-16 00:00:00
abstract：:[(18)F]-labeled molecular probe for the detection of myocardial perfusion deficit is driving particular interest due to its high clinical applicability. Thus, we synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)triphenylphosphonium salt ([(18)F]3) that specifically accumulates in myocardium according to mitochondrial membr...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2011.11.005
更新日期：2012-01-01 00:00:00
abstract：:Various bis(2-hydroxy-3-chloropropyl)alkylamines were synthesized by coupling primary amine with epichlorohydrin and utilized as a monomer to react with ethylenediamine (EDA), N,N'-dimethylethylenediamine (DMEDA), or tetramethylethylenediamine (TMEDA) to generate a series of lipopolyhydroxylalkyleneamines. The number-...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/j.bmcl.2006.01.120
更新日期：2006-05-01 00:00:00
abstract：:The in vitro evaluation of a series of saturated prostaglandins revealed that compounds with omega chain aromatic rings retain nanomolar potency for the human prostaglandin F receptor (hFP receptor), exemplified by compound 8. In contrast, the double bonds are required for activity in the series with an acyclic omega ...
journal_title：Bioorganic & medicinal chemistry letters
pub_type： 杂志文章
doi：10.1016/s0960-894x(00)00273-0
更新日期：2000-07-17 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
pub_type： 杂志文章
doi：10.1016/j.bmcl.2017.05.068
更新日期：2017-08-01 00:00:00
