Development of new simple molecular probes of DNA bulged structures.

abstract：:Silybin is the major flavonolignan of silymarin and it displays a plethora of biological effects, generally ascribed to its antioxidant properties. Herein we shall describe an efficient synthetic strategy to obtain a variety of new and more water-soluble silybin and 2,3-dehydrosilybin (DHS) derivatives in which the 23...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zarrelli A,Sgambato A,Petito V,De Napoli L,Previtera L,Di Fabio G

更新日期：2011-08-01 00:00:00

abstract：:A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Engers DW,Frist AY,Lindsley CW,Hong CC,Hopkins CR

更新日期：2013-06-01 00:00:00

abstract：:Current techniques for the identification of DNA adduct-inducing and DNA interstrand crosslinking agents include electrophoretic crosslinking assays, electrophoretic gel shift assays, DNA and RNA stop assays, mass spectrometry-based methods and 32P-post-labelling. While these assays provide considerable insight into t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Medan J,Sleebs BE,Lackovic K,Watson KG,Evison BJ,Phillips DR,Cutts SM

更新日期：2021-01-21 00:00:00

abstract：:West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. Thes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sidique S,Shiryaev SA,Ratnikov BI,Herath A,Su Y,Strongin AY,Cosford ND

更新日期：2009-10-01 00:00:00

abstract：:Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combinat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weng Z,Xu G,Chen D,Yang Y,Song G,Shen W,Zhang S,Wang L,Yang W,Zuo Z

更新日期：2020-01-15 00:00:00

abstract：:Endothelial lipase (EL) inhibitors have been shown to elevate HDL-C levels in pre-clinical murine models and have potential benefit in prevention and treatment of cardiovascular diseases. Modification of the 1-ethyl-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one (DHP) lead, 1, led to the discovery of a series of potent tetrahy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu CH,Wang TC,Qiao JX,Haque L,Chen AYA,Taylor DS,Ying X,Onorato JM,Galella M,Shen H,Huang CS,Toussaint N,Li YX,Abell L,Adam LP,Gordon D,Wexler RR,Finlay HJ

更新日期：2018-12-15 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

authors： Sharon A,Pratap R,Tiwari P,Srivastava A,Maulik PR,Ram VJ

更新日期：2005-04-15 00:00:00

abstract：:To understand the species selectivity in a series of alpha-methyl-alpha-phenoxy carboxylic acid PPARalpha/gamma dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARalpha. This study suggested that interaction of both 4-phenoxy and phenyloxa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Winneroski LL,Ardecky RJ,Babine RE,Brooks DA,Etgen GJ,Hutchison DR,Kauffman RF,Kunkel A,Mais DE,Montrose-Rafizadeh C,Ogilvie KM,Oldham BA,Peters MK,Rito CJ,Rungta DK,Tripp AE,Wilson SB,Xu Y,Zink RW,McCarthy

更新日期：2004-12-20 00:00:00

abstract：:A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi J,Zhu J,Liu X,Ding L,Zheng C,Han G,Lv J,Zhou Y

更新日期：2011-10-01 00:00:00

abstract：:A novel type of caspase inhibitor prodrug that improves systemic exposure after oral administration in rats has been designed. Such a prodrug, based on a 6,6a-dihydrofuro[3,2-d]oxazol-5(3aH)-one motif, has the advantage of rapidly liberating the active inhibitor without producing any cleavage by-product. Prodrugs 6-8,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier JD,Durrant SJ,Studley J,Lawes L,Weber P

更新日期：2012-01-01 00:00:00

abstract：:Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mochona B,Qi X,Euynni S,Sikazwi D,Mateeva N,Soliman KF

更新日期：2016-06-15 00:00:00

abstract：:A novel series of triazole tethered coumarin-benzotriazole hybrids based on donepezil skeleton has been designed and synthesized as multifunctional agents for the treatment of Alzheimer's disease (AD). Among the synthesized compounds 13b showed most potent acetylcholinesterase (AChE) inhibition (IC50 = 0.059 μΜ) with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh A,Sharma S,Arora S,Attri S,Kaur P,Kaur Gulati H,Bhagat K,Kumar N,Singh H,Vir Singh J,Mohinder Singh Bedi P

更新日期：2020-10-15 00:00:00

abstract：:In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramnauth J,Surman MD,Sampson PB,Forrest B,Wilson J,Freeman E,Manning DD,Martin F,Toro A,Domagala M,Awrey DE,Bardouniotis E,Kaplan N,Berman J,Pauls HW

更新日期：2009-09-15 00:00:00

abstract：:A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, resp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Palmer WS,Alam M,Arzeno HB,Chang KC,Dunn JP,Goldstein DM,Gong L,Goyal B,Hermann JC,Hogg JH,Hsieh G,Jahangir A,Janson C,Jin S,Ursula Kammlott R,Kuglstatter A,Lukacs C,Michoud C,Niu L,Reuter DC,Shao A,Silva T,Tr

更新日期：2013-03-01 00:00:00

abstract：:There is tremendous interest in developing activator artificial transcription factors that functionally mimic endogenous transcriptional activators for use as mechanistic probes, as components of synthetic cell circuitry, and in transcription-targeted therapies. Here, we demonstrate that a phage display selection agai...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majmudar CY,Labut AE,Mapp AK

更新日期：2009-07-15 00:00:00

abstract：:The synthesis and biological profile of a novel series of potent and selective inhibitors of cysteine protease cathepsin K (Cat K) are described. Pharmacokinetic evaluation of 12 indicated that some members of this series could be suitable candidates to develop new orally active therapeutic agents for the treatment of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Setti EL,Venkatraman S,Palmer JT,Xie X,Cheung H,Yu W,Wesolowski G,Robichaud J

更新日期：2006-08-15 00:00:00

abstract：:Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv PC,Li DD,Li QS,Lu X,Xiao ZP,Zhu HL

更新日期：2011-09-15 00:00:00

abstract：:We demonstrate the synthesis and selective binding of two novel furan based tricyclic homo-oligopeptides to G-quadruplex and using Real Time PCR show its repressive effect on c-MYC transcription. CD spectroscopy and FRET melting studies show that these ligands can induce G-quadruplex structures in the G rich 22 mer c-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Agarwal T,Roy S,Chakraborty TK,Maiti S

更新日期：2010-08-01 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：:Twenty three side chain analogs of the crambescidin alkaloids were prepared from the corresponding pentacyclic zwitterionic core acid. In the crambescidin 800 and 657 series, potency increased with increasing chain length. In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aron ZD,Pietraszkiewicz H,Overman LE,Valeriote F,Cuevas C

更新日期：2004-07-05 00:00:00

abstract：:Novel bendazac analogues and their salts have been designed and prepared. The resulting compounds (13c-d, 15c, 17c) showed very good aqueous solubility (>100 mg/mL). An in vitro assay showed that most of the resulting compounds had potent protective activity against the oxidative damage. Particularly, compound 13d was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen H,Gou S,Shen J,Zhu Y,Zhang Y,Chen X

更新日期：2010-04-01 00:00:00

abstract：:A new abietane, namely, 20-hydroxyferruginol (1), together with known ferruginol (2), 18-hydroxyferruginol (3), sugiol (4), and 6alpha-hydroxysugiol (5), were isolated from the cones of Sequoia sempervirens. Their structures were elucidated through spectral data. Compounds 1 and 5 strongly inhibited colon, lung, and b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Son KH,Oh HM,Choi SK,Han DC,Kwon BM

更新日期：2005-04-15 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：:Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roth J,Minond D,Darout E,Liu Q,Lauer J,Hodder P,Fields GB,Roush WR

更新日期：2011-12-01 00:00:00

abstract：:To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yabunaka H,Abe M,Kenmochi A,Hamada T,Nishioka T,Miyoshi H

更新日期：2003-07-21 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：:Oxygen dependent degradation of hypoxia-inducible factor (HIF)-1α is triggered with hydroxylation by proline hydroxylase domain 2 (PHD2) under normoxic conditions. Some of previously developed PHD2 inhibitors show a considerable potency against factor inhibiting HIF (FIH), the HIF asparagine hydroxylase. For specific ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kwon HS,Choi YK,Kim JW,Park YK,Yang EG,Ahn DR

更新日期：2011-07-15 00:00:00

abstract：:A computational approach was utilized to study the relative binding modes of diospyrin (bisnaphthoquinonoid) with the crystal structure of human DNA-TopoI and the recently reported Leishmania donavani DNA-TopoI. Additionally, the binding site interactions of amino derivatives of diospyrin with human TopoI were studied...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chhabra S,Sharma P,Ghoshal N

更新日期：2007-08-15 00:00:00

abstract：:A series of optically pure phenyl-and non-phenyl-substituted 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines was synthesized and their binding affinity for dopamine transporter (DAT) was investigated. The analogues with a hydroxyl group in the S configuration were more selective for the DAT over...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsin LW,Prisinzano T,Wilkerson CR,Dersch CM,Horel R,Jacobson AE,Rothman RB,Rice KC

更新日期：2003-02-10 00:00:00

abstract：:Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding. CypA is the most prevalent of the ~19 human Cyps, and plays a crucial role in viral infectivity, most notably for HIV-1 and HCV. Cyclophilins have been shown to play key role...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peel M,Scribner A

更新日期：2013-08-15 00:00:00