A bivalent ligand (KMN-21) antagonist for mu/kappa heterodimeric opioid receptors.

abstract：:A series of N6,2-disubstituted adenosine analogues have been synthesized and their functional activity measured against A2a and A1 receptors. Examples of compounds with both a lipophilic N6-substituent and amino-functionalized 2-position were highly active at the A2a receptor on the human neutrophil. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keeling SE,Albinson FD,Ayres BE,Butchers PR,Chambers CL,Cherry PC,Ellis F,Ewan GB,Gregson M,Knight J,Mills K,Ravenscroft P,Reynolds LH,Sanjar S,Sheehan MJ

更新日期：2000-02-21 00:00:00

abstract：:A series of analogs of GLP-1(7-36) amide containing a Nepsilon-(2-[2-[2-(3-maleimidopropylamido)ethoxy]ethoxy]acetyl)lysine has been synthesized and the resulting derivatives were bioconjugated to Cys34 of human serum albumin (HSA). The GLP-1-HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Léger R,Thibaudeau K,Robitaille M,Quraishi O,van Wyk P,Bousquet-Gagnon N,Carette J,Castaigne JP,Bridon DP

更新日期：2004-09-06 00:00:00

abstract：:The iridium(III)-catalyzed ortho-C-H amidation of benzoic acids with sulfonyl azides is described. These transformations allow the facile generation of N-sulfonyl anthranilic acids, which are known as crucial scaffolds found in biologically active molecules. In addition, all synthetic products were evaluated for in vi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han SH,Suh HS,Jo H,Oh Y,Mishra NK,Han S,Kim HS,Jung YH,Lee BM,Kim IS

更新日期：2017-05-15 00:00:00

abstract：:A series of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 3d exhibited potentially high activity against human gastric cancer cell SGC-7901 with IC(50) value of 2.69 ± 0.60 μg/mL. All title compounds were assa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu XH,Liu HF,Chen J,Yang Y,Song BA,Bai LS,Liu JX,Zhu HL,Qi XB

更新日期：2010-10-01 00:00:00

abstract：:Model reactions offer a chemical mechanism by which formation of a sulfenyl amide residue at the active site of the redox-regulated protein tyrosine phosphatase PTP1B protects the cysteine redox switch in this enzyme against irreversible oxidative destruction. The results suggest that 'overoxidation' of the sulfenyl a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sivaramakrishnan S,Cummings AH,Gates KS

更新日期：2010-01-15 00:00:00

abstract：:A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is effica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das J,Kimball SD,Hall SE,Han WC,Iwanowicz E,Lin J,Moquin RV,Reid JA,Sack JS,Malley MF,Chang CY,Chong S,Wang-Iverson DB,Roberts DG,Seiler SM,Schumacher WA,Ogletree ML

更新日期：2002-01-07 00:00:00

abstract：:The successfully application of some metallodrugs such as salvarsan, silver sulfadiazine and cisplatin in modern medicine launched the biological investigation of organometallic and metal-organic complexes. The availability and tunability of various ligands including N-heterocycles, phosphines, N-heterocyclic carbenes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Balcıoğlu S,Olgun Karataş M,Ateş B,Alıcı B,Özdemir İ

更新日期：2020-01-15 00:00:00

abstract：:The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Henry JR,Rupert KC,Dodd JH,Turchi IJ,Wadsworth SA,Cavender DE,Schafer PH,Siekierka JJ

更新日期：1998-12-01 00:00:00

abstract：:Developing efficient controlled release system of insecticide can facilitate the better use of insecticide. We described here a first example of photo-controlled release of an insecticide by linking fipronil with photoresponsive coumarin covalently. The generated coumarin-fipronil (CF) precursor could undergo cleavage...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao Z,Yuan P,Wang D,Xu Z,Li Z,Shao X

更新日期：2017-06-01 00:00:00

abstract：:5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antago...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ladouceur GH,Cook JH,Doherty EM,Schoen WR,MacDougall ML,Livingston JN

更新日期：2002-02-11 00:00:00

abstract：:GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput sc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bhuniya D,Umrani D,Dave B,Salunke D,Kukreja G,Gundu J,Naykodi M,Shaikh NS,Shitole P,Kurhade S,De S,Majumdar S,Reddy SB,Tambe S,Shejul Y,Chugh A,Palle VP,Mookhtiar KA,Cully D,Vacca J,Chakravarty PK,Nargund RP,W

更新日期：2011-06-15 00:00:00

abstract：:Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

更新日期：2013-05-01 00:00:00

abstract：:Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synt...

journal_title：Bioorganic & medicinal chemistry letters

authors： Addla D,Jallapally A,Gurram D,Yogeeswari P,Sriram D,Kantevari S

更新日期：2014-01-01 00:00:00

abstract：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00

abstract：:Novel bicyclic tetrahydropyrano[3,2-d]oxazolones derivatives, analogues of Fumagillin, were synthesised via a stereocontrolled oxidative-rearrangement of furylcarbinols and subsequent treatment with the appropriate isocyanate. These compounds demonstrated potent antiangiogenic activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perron-Sierra FM,Pierré A,Burbridge M,Guilbaud N

更新日期：2002-06-03 00:00:00

abstract：:A series of isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones were synthesized as potent inhibitors against Pim-1 and Pim-2 kinases. The structure-activity-relationship studies started from a high-throughput screening hit and was guided by molecular modeling of inhibitors in the active site of Pim-1 kinase. Installing a hyd...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tong Y,Stewart KD,Thomas S,Przytulinska M,Johnson EF,Klinghofer V,Leverson J,McCall O,Soni NB,Luo Y,Lin NH,Sowin TJ,Giranda VL,Penning TD

更新日期：2008-10-01 00:00:00

abstract：:Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Velentza AV,Wainwright MS,Zasadzki M,Mirzoeva S,Schumacher AM,Haiech J,Focia PJ,Egli M,Watterson DM

更新日期：2003-10-20 00:00:00

abstract：:The same two major CYP mediated metabolites of DG-051 were produced in the presence of rat, dog, monkey and human liver microsomes. Their respective structures were hypothesized based on mass spectrometry data correlated with the parent structure and confirmed by comparison with authentic synthetic samples. The number...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enache LA,Zhang J,Sullins DW,Kennedy I,Onua E,Zembower DE,Muellner FW,Singh J,Kiselyov AS

更新日期：2009-11-15 00:00:00

abstract：:Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naka T,Hattori Y,Takenaka H,Ohta Y,Kirihata M,Tanimori S

更新日期：2019-03-01 00:00:00

abstract：:The proprotein convertases PCSK8 and PCSK4 are, respectively, the 8th and 4th members of Ca(+2)-dependent serine endoprotease of Proprotein Convertase Subtilisin Kexin (PCSK) super family structurally related to the bacterial subtilisin and yeast kexin. The membrane bound PCSK8 (also called SKI-1 or S1P) is implicated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Goswami M,Rajkumar A,Mitra T,Majumdar S,O'Reilly P,Bdour HM,Trudeau VL,Basak A

更新日期：2015-01-01 00:00:00

abstract：:A new cytotoxic oxysterol, 16beta-hydroxy-5alpha-cholestane-3,6-dione was isolated from the red alga Jania rubens. Its structure was established by spectroscopic method. The ID50 value was 0.5 microg/mL. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ktari L,Blond A,Guyot M

更新日期：2000-11-20 00:00:00

abstract：:Ubiquitin-dependent proteolysis of cellular proteins is one of the major pathways to regulate protein function posttranslationally. Here we demonstrate a potentially general method of degrading any targeted proteins by the ubiquitin-dependent proteolysis in living cells, using small-molecule proteolysis inducer (SMPI)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang D,Baek SH,Ho A,Kim K

更新日期：2004-02-09 00:00:00

abstract：:Alkyl parabens are used as antimicrobial preservatives in cosmetics, food, and pharmaceutical products. However, the mode of action of these chemicals has not been assessed thoroughly. In this study, we determined the effects of alkyl parabens on plant pathogenic fungi. All the fungi tested, were susceptible to parabe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ito S,Yazawa S,Nakagawa Y,Sasaki Y,Yajima S

更新日期：2015-04-15 00:00:00

abstract：:Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tseng WR,Huang CY,Tsai YY,Lin YS,Hwang TL,Su JH,Sung PJ,Dai CF,Sheu JH

更新日期：2016-07-15 00:00:00

abstract：:A vitamin D analogue containing an affinity and a photoaffinity probe (affinity-driven cross-linker, Double Label) was synthesized. An unknown factor, associated with vitamin D receptor (VDR), was isolated from rat liver nuclear extract using a GST-VDR-ligand-binding domain fusion protein (GST-VDR-LBD), affinity label...

journal_title：Bioorganic & medicinal chemistry letters

authors： Swamy N,Addo JK,Ray R

更新日期：2000-02-21 00:00:00

abstract：:We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents ba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shimizu H,Yasumatsu I,Hamada T,Yoneda Y,Yamasaki T,Tanaka S,Toki T,Yokoyama M,Morishita K,Iimura S

更新日期：2011-02-01 00:00:00

abstract：:Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against gram-pos...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kutterer KM,Davis JM,Singh G,Yang Y,Hu W,Severin A,Rasmussen BA,Krishnamurthy G,Failli A,Katz AH

更新日期：2005-05-16 00:00:00

abstract：:New indole-porphyrin hybrid molecules were isolated from Escherichia coli harboring metagenomic DNA from the Japanese marine sponge Discodermia calyx. The indole was appended to the reactive vinyl substituent of the harderoporphyrin chromophore, encoded by the insert DNA. Thus, the chimeric pathway between the heterol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang XL,Wakimoto T,Takeshige Y,He R,Egami Y,Awakawa T,Abe I

更新日期：2013-07-01 00:00:00

abstract：:Telomerase and telomere maintenance are emerging targets for the treatment of human cancers. We report here on the targeting of the telomere-telomerase complex with a series of small molecules based on an acridine platform. A series of 3,6-bisamidoacridines with extended 9-anilino sidechains were designed and synthesi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schultes CM,Guyen B,Cuesta J,Neidle S

更新日期：2004-08-16 00:00:00

abstract：:The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacok...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lynch CL,Willoughby CA,Hale JJ,Holson EJ,Budhu RJ,Gentry AL,Rosauer KG,Caldwell CG,Chen P,Mills SG,MacCoss M,Berk S,Chen L,Chapman KT,Malkowitz L,Springer MS,Gould SL,DeMartino JA,Siciliano SJ,Cascieri MA,Carella

更新日期：2003-01-06 00:00:00