Discovery of novel sphingosine kinase-1 inhibitors. Part 2.

abstract：:Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic aci...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carrigan CN,Patel SA,Cox HD,Bolstad ES,Gerdes JM,Smith WE,Bridges RJ,Thompson CM

更新日期：2014-02-01 00:00:00

abstract：:To overcome the chemical and metabolic instability of the secondary fatty acyl residues in the AGP class of lipid A mimetics, the secondary ether lipid analogs of the potent TLR4 agonist CRX-527 (2) and TLR4 antagonist CRX-526 (3) were synthesized and evaluated along with their ester counterparts for agonist/antagonis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bazin HG,Murray TJ,Bowen WS,Mozaffarian A,Fling SP,Bess LS,Livesay MT,Arnold JS,Johnson CL,Ryter KT,Cluff CW,Evans JT,Johnson DA

更新日期：2008-10-15 00:00:00

abstract：:A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Byun D,Chen X,Doerffler E,Leavitt SA,Sheng XC,Yang CY,Kim CU

更新日期：2012-01-15 00:00:00

abstract：:A new reagent immobilized on solid support allowing for solid-phase synthesis of oligonucleotides with a 3'-terminal phosphorothioate monoester is described. The support is compatible with phosphoramidite chemistry for automated oligonucleotide synthesis. Final deprotection with ammonia under standard conditions leads...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheruvallath ZS,Cole DL,Ravikumar VT

更新日期：2003-01-20 00:00:00

abstract：:Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker FF,Banik BK

更新日期：1998-10-20 00:00:00

abstract：:New polyphenol classes have been tested against amyloid-beta peptide aggregation. We have identified four novel polyphenols which could be efficient fibril inhibitors in Alzheimer's disease: malvidin and its glucoside and curculigosides B and D. We suggest that molecules with the particular C(6)-linkers-C(6) structure...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rivière C,Richard T,Vitrac X,Mérillon JM,Valls J,Monti JP

更新日期：2008-01-15 00:00:00

abstract：:A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pan W,Miao HQ,Xu YJ,Navarro EC,Tonra JR,Corcoran E,Lahiji A,Kussie P,Kiselyov AS,Wong WC,Liu H

更新日期：2006-01-15 00:00:00

abstract：:The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demons...

journal_title：Bioorganic & medicinal chemistry letters

authors： Metcalf MD,Rosicky AD,Hassan HE,Eddington ND,Coop A,Cunningham CW,Mercer SL

更新日期：2014-08-01 00:00:00

abstract：:A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low microM affinity, was prepared by solid-phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO-His-dPhe-Arg-Trp-NH(2), exhibited a K(d) for hMC4R of 9.1+/-1.4 microM, approximatel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu L,Vagner J,Alleti R,Rao V,Jagadish B,Morse DL,Hruby VJ,Gillies RJ,Mash EA

更新日期：2010-04-15 00:00:00

abstract：:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2002-11-04 00:00:00

abstract：:Ligand-protein binding is a complex process that involves the formation of number of non-covalent interactions, e.g. H-bonds and hydrophobic interactions, between the ligand and the protein host. Upon binding, ligand functional groups can act synergistically (positive cooperativity) to improve the overall ligand bindi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Said AM,Hangauer DG

更新日期：2016-08-15 00:00:00

abstract：:We have succeeded in the acquisition of DNA aptamers that recognize chitin using in vitro selection. The obtained DNA aptamers have the stem-loop or bulge loop structures with guanine rich loop clusters and the clockwise B-form stems. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukusaki E,Kato T,Maeda H,Kawazoe N,Ito Y,Okazawa A,Kajiyama S,Kobayashi A

更新日期：2000-03-06 00:00:00

abstract：:5-Ethynyl-2'-deoxyuridine is a common base-modified nucleoside analogue that has served in various applications including selection experiments for potent aptamers and in biosensing. The synthesis of the corresponding triphosphates involves a mild acidic deprotection step. Herein, we show that this deprotection leads ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Röthlisberger P,Levi-Acobas F,Hollenstein M

更新日期：2017-02-15 00:00:00

abstract：:2-(Anilino)imidazolines were identified as novel human 5-HT(1D) receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoline derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prisinzano T,Dukat M,Law H,Slassi A,MacLean N,DeLannoy I,Glennon RA

更新日期：2004-09-20 00:00:00

abstract：:Substituted benzimidazoles were profiled as inhibitors of kinesin spindle protein (KSP), an increasingly important target for the development of anticancer drugs. This series demonstrated the monoastral phenotypic response and was found to be active in both enzymatic and cellular-based assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lahue BR,Ma Y,Shipps GW Jr,Seghezzi W,Herbst R

更新日期：2009-07-01 00:00:00

abstract：:The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin KJ,Koo KD,Yoo KH,Kang YK,Park SW,Kim DJ

更新日期：2001-09-03 00:00:00

abstract：:Mandelate racemase has been studied as a paradigm for enzyme-catalyzed abstraction of a proton from carbon acids with relatively high pKa values. 1,1-Diphenyl-1-hydroxymethylphosphonate is a substrate-intermediate-product analogue and is a modest competitive inhibitor of the enzyme (Ki=1.41+/-0.09 mM), suggesting that...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burley RK,Bearne SL

更新日期：2005-10-01 00:00:00

abstract：:A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hong SS,Lee SA,Kim N,Hwang JS,Han XH,Lee MK,Jung JK,Hong JT,Kim Y,Lee D,Hwang BY

更新日期：2011-02-15 00:00:00

abstract：:The Castagnoli-Cushman reaction between diglycolic anhydride and imines was applied for the synthesis of morpholine derivatives containing a thioamide or an amidino group. Enzyme inhibition assays towards BACE1 revealed an unexpected role of the cyclic thioamide group in providing inhibition in the micromolar range. M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Calugi L,Lenci E,Innocenti R,Trabocchi A

更新日期：2020-07-01 00:00:00

abstract：:Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ray P,Wright J,Adam J,Bennett J,Boucharens S,Black D,Cook A,Brown AR,Epemolu O,Fletcher D,Haunso A,Huggett M,Jones P,Laats S,Lyons A,Mestres J,de Man J,Morphy R,Rankovic Z,Sherborne B,Sherry L,van Straten N,We

更新日期：2011-01-01 00:00:00

abstract：:A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino phosphoramidates have been synthesized and tested in vitro and in vivo for their biological activity. Compared with the parent drug a 10- to 20-fold increase in formation of nucleotide triphosphate in rat and human hepatocytes could be achieve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donghi M,Attenni B,Gardelli C,Marco AD,Fiore F,Giuliano C,Laufer R,Leone JF,Pucci V,Rowley M,Narjes F

更新日期：2009-03-01 00:00:00

abstract：:Methanolic extract of Miliusa balansae Finet et Gagnep exerts an anti-inflammatory effect via inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Three new megastigmane glycosides, milbasides A-C (1-3), together with fifteen known compounds (4-18), were ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thao NP,Luyen BT,Tai BH,Cuong NM,Kim YC,Minh CV,Kim YH

更新日期：2015-09-15 00:00:00

abstract：:4'-Modified noraristeromycin (NAM) analogs, 4'-sulfo-, 4'-sulfamoy, 4'-azido and 4'-amino-NAM, were systematically synthesized. The inhibitory activities of these analogs and related compounds against Plasmodium falciparum and human S-adenosyl-L-homocysteine hydrolase were investigated. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ando T,Kojima K,Chahota P,Kozaki A,Milind ND,Kitade Y

更新日期：2008-04-15 00:00:00

abstract：:A novel class of indomethacin analogs were synthesized wherein a N-difluoromethyl-1,2-dihydropyrid-2-one moiety (5-LOX pharmacophore) was attached at its C-4 or C-5 position via either a CO (14a-b) or CH(2) (19a-b) linker to the indole N(1)-position. In this regard, replacement of the 4-chlorobenzoyl group present in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chowdhury MA,Huang Z,Abdellatif KR,Dong Y,Yu G,Velázquez CA,Knaus EE

更新日期：2010-10-01 00:00:00

abstract：:P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput sc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carter DS,Alam M,Cai H,Dillon MP,Ford AP,Gever JR,Jahangir A,Lin C,Moore AG,Wagner PJ,Zhai Y

更新日期：2009-03-15 00:00:00

abstract：:A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Larget R,Lockhart B,Pfeiffer B,Neudorffer A,Fleury MB,Largeron M

更新日期：1999-10-18 00:00:00

abstract：:The growth inhibition of human cancer cells via T-type Ca(2+) channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca(2+) channel (Cav3.1) blockade and cytotoxicity on three human ovari...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jang SJ,Choi HW,Choi DL,Cho S,Rim HK,Choi HE,Kim KS,Huang M,Rhim H,Lee KT,Lee JY

更新日期：2013-12-15 00:00:00

abstract：:Microwave accelerated reaction system (MARS) technology provided a good method to obtain selective and open isoxazole ligands that bind to and inhibit the Sxc- antiporter. The MARS provided numerous advantages, including: shorter time, better yield and higher purity of the product. Of the newly synthesized series of i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matti AA,Mirzaei J,Rudolph J,Smith SA,Newell JL,Patel SA,Braden MR,Bridges RJ,Natale NR

更新日期：2013-11-01 00:00:00

abstract：:The synthesis and antibacterial activity of a series of nocathiacin I derivatives (4-20) containing polar water solubilizing groups is described. Thiol-Michael adducts containing acidic polar groups have reduced antibacterial activity whereas those with basic polar groups have retained very good antibacterial activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naidu BN,Sorenson ME,Bronson JJ,Pucci MJ,Clark JM,Ueda Y

更新日期：2005-04-15 00:00:00

abstract：:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

更新日期：2015-11-15 00:00:00