Progress in the discovery of small molecule modulators of the Cys-loop superfamily receptors.

abstract：:From our modulator library an interesting inhibitor of breast cancer resistance protein (BCRP) was identified. Due to its high inhibitory potency, this compound may serve as a promising novel lead for the design of new and potent modulators. This adds a new structural class to the few known highly active BCRP inhibito...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pick A,Müller H,Wiese M

更新日期：2010-01-01 00:00:00

abstract：:We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee S,Kwon OS,Lee CS,Won M,Ban HS,Ra CS

更新日期：2017-07-01 00:00:00

abstract：:Herein we report the preparation of a combinatorial library of compounds with potent CCR5 binding affinity. The library design was aided by SAR generated in a traditional medicinal chemistry effort. Compounds with novel combinations of subunits were discovered that have high binding affinity for the CCR5 receptor. A p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Willoughby CA,Berk SC,Rosauer KG,Degrado S,Chapman KT,Gould SL,Springer MS,Malkowitz L,Schleif WA,Hazuda D,Miller M,Kessler J,Danzeisen R,Holmes K,Lineberger J,Carella A,Carver G,Emini EA

更新日期：2001-12-17 00:00:00

abstract：:The methylendioxyphenyl group, present in a number of potent endothelin receptor antagonists, could have undesirable metabolic interactions with cytochrome P450 in vivo. Using a self-organizing neural network we analysed the features of molecular electrostatic potentials of several endothelin receptor ligands. A libra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anzali S,Mederski WW,Osswald M,Dorsch D

更新日期：1998-01-06 00:00:00

abstract：:EZH2 is the core subunit of Polycomb repressive complex 2 catalyzing the methylation of histone H3 lysine-27 and closely involved in tumorigenesis. To discover small molecule inhibitors for EZH2 methyltransferase activity, we performed an inhibitor screen with catalytically active EZH2 protein complex and identified t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Woo J,Kim HY,Byun BJ,Chae CH,Lee JY,Ryu SY,Park WK,Cho H,Choi G

更新日期：2014-06-01 00:00:00

abstract：:cis-4-Amino-L-proline derivatives 1 and 2 derived from quinazolinone and pyrazolo pyrimidone respectively were designed as novel lipid lowering agents. A preliminary in vivo screening indicates that 1b and 2a have moderate triglyceride lowering activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das SK,Narasimha Rao Krovvidi VL,Jagadheshan H,Iqbal J

更新日期：2002-12-16 00:00:00

abstract：:RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat cau...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guan L,Luo Y,Ja WW,Disney MD

更新日期：2018-09-01 00:00:00

abstract：:Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang W,Devasthale P,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Li YX,Zahler R,Kirby MS,Hamann LG

更新日期：2011-11-15 00:00:00

abstract：:The human epidermal growth factor receptor (EGFR) family is known to be involved in cell signaling pathways. The extracellular domain of EGFR consists of four domains, of which domain II and domain IV are known to be involved in the dimerization process. Overexpression of these receptors is known to play a significant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naik H,Gauthier T,Singh S,Jois S

更新日期：2018-12-01 00:00:00

abstract：:QSAR models represent the relationship of biological activity with either physicochemical parameters or structural indices. QSAR study was performed on some arylpiperazines as 5-HT(1A)/alpha(1)-adrenergic receptor antagonists using E-state indices to identify the pharmacophoric requirements. It was found that some of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Debnath B,Samanta S,Naskar SK,Roy K,Jha T

更新日期：2003-09-01 00:00:00

abstract：:We have synthesized a series of 4H,6H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleoside and their anti-vesicular stomatitis virus (VSV) activities in Wish cell were also investigated in vitro. It was found that most compounds showed obvious anti-VSV activities and compound 9 with ribofuranoside improved ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu X,Wang J,Yao Q

更新日期：2015-01-15 00:00:00

abstract：:A non-methionine FT inhibitor lead structure (1) was designed through computer modeling of the peptidomimetic FT inhibitor ABT839. Optimization of this lead resulted in compounds 2e and 2g, with FT IC(50) values of 1.3 and 1.8 nM, GGT IC(50) of 1400 nM, and EC(50) (Ras processing) values of 13 and 11 nM, respectively....

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang GT,Wang X,Wang W,Hasvold LA,Sullivan G,Hutchins CW,O'Conner S,Gentiles R,Sowin T,Cohen J,Gu WZ,Zhang H,Rosenberg SH,Sham HL

更新日期：2005-01-03 00:00:00

abstract：:The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) inf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Varela MT,Dias RZ,Martins LF,Ferreira DD,Tempone AG,Ueno AK,Lago JH,Fernandes JP

更新日期：2016-02-15 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：:A series of aromatic sulfonamides incorporating indane moieties were prepared starting from commercially available 1- and 2-indanamine, and their activity as inhibitors of two carbonic anhydrase (CA, EC 4.2.1.1) isozymes, hCA I and II was studied. The new sulfonamides incorporating acetamido, 4-chloro-benzoyl, valproy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chazalette C,Masereel B,Rolin S,Thiry A,Scozzafava A,Innocenti A,Supuran CT

更新日期：2004-12-06 00:00:00

abstract：:Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antiba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vatmurge NS,Hazra BG,Pore VS,Shirazi F,Chavan PS,Deshpande MV

更新日期：2008-03-15 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：:Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujishiro S,Dodo K,Iwasa E,Teng Y,Sohtome Y,Hamashima Y,Ito A,Yoshida M,Sodeoka M

更新日期：2013-02-01 00:00:00

abstract：:An efficient and simple polymer-assisted approach has been developed to biotinylate multifunctional compounds bearing an amino functionality. Biotin was immobilized on aminomethylated polystyrene via the Kenner safety catch linker, activated and subsequently transferred to the amino function of the target compounds ch...

journal_title：Bioorganic & medicinal chemistry letters

authors： Golisade A,Herforth C,Wieking K,Kunick C,Link A

更新日期：2001-07-09 00:00:00

abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-04-07 00:00:00

abstract：:Several oximes of triterpenes with a 17-beta hydroxyl and abietane derivatives are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 micromol/kg. However, the mechanism ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aicher TD,Damon RE,Koletar J,Vinluan CC,Brand LJ,Gao J,Shetty SS,Kaplan EL,Mann WR

更新日期：1999-08-02 00:00:00

abstract：:We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved t...

journal_title：Bioorganic & medicinal chemistry letters

authors： McComas C,Cohen J,Huselton C,Marella M,Melenski E,Mugford C,Slayden O,Winneker R,Wrobel J,Yudt MR,Fensome A

更新日期：2012-12-01 00:00:00

abstract：:Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(β-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gutiérrez B,Muñoz C,Osorio L,Fehér K,Illyés TZ,Papp Z,Kumar AA,Kövér KE,Sagua H,Araya JE,Morales P,Szilágyi L,González J

更新日期：2013-06-15 00:00:00

abstract：:A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction betwe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasantha K,Basavarajaswamy G,Vaishali Rai M,Boja P,Pai VR,Shruthi N,Bhat M

更新日期：2015-04-01 00:00:00

abstract：:The objective of this report is to introduce the novel concept of utilizing sulfenamides as prodrugs for compounds containing an NH-acidic functionality, particularly weakly acidic amide-type functionalities (amides, ureas, carbamates, etc.). Included are the syntheses and physicochemical characterizations of some mod...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guarino VR,Karunaratne V,Stella VJ

更新日期：2007-09-01 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 nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang LY,Wang JD,Zhang J,Xue CY,Zhang H,Wang XJ,Xiang WS

更新日期：2013-10-15 00:00:00

abstract：:A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang C,Corte JR,Rossi KA,Bozarth JM,Wu Y,Sheriff S,Myers JE Jr,Luettgen JM,Seiffert DA,Wexler RR,Quan ML

更新日期：2017-09-01 00:00:00

abstract：:A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I(Kur)) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vaccaro W,Huynh T,Lloyd J,Atwal K,Finlay HJ,Levesque P,Conder ML,Jenkins-West T,Shi H,Sun L

更新日期：2008-12-15 00:00:00

abstract：:The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Monte FL,Kramer T,Boländer A,Plotkin B,Eldar-Finkelman H,Fuertes A,Dominguez J,Schmidt B

更新日期：2011-09-15 00:00:00