Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists.

abstract：:We previously reported on the monobody E1, which specifically targets the tumor marker hEphA2. In this study, we labeled NOTA-conjugated E1 with 64Cu (64Cu-NOTA-E1) and evaluated biologic characteristics. The uptake of 64Cu-NOTA-E1 in PC3 cells (a human prostate cancer cell line) with high expression of hEphA2 increas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pyo A,You SH,Sik Kim H,Young Kim J,Min JJ,Kim DY,Hong Y

更新日期：2020-07-15 00:00:00

abstract：:The synthesis of two C-1 analogues of pancratistatin has been accomplished in 17 steps from bromobenzene. The key steps involved the enzymatic dihydroxylation, regioselective opening of epoxyaziridine 9 with the alane derived from 8, a solid-state silica-gel-catalyzed intramolecular opening of aziridine to produce phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Scattolon J,Hudlicky T,Romero AE,Kornienko A

更新日期：2011-08-15 00:00:00

abstract：:The structure-activity relationships of 5,6-positions of aminopyridine carboxamide-based c-Jun N-terminal Kinase (JNK) inhibitors were explored to expand interaction with the kinase specificity and ribose-binding pockets. The syntheses of analogues and the impact of structural modification on in vitro potency and cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu G,Zhao H,Liu B,Xin Z,Liu M,Kosogof C,Szczepankiewicz BG,Wang S,Clampit JE,Gum RJ,Haasch DL,Trevillyan JM,Sham HL

更新日期：2006-11-15 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of the metabolic syndrome. Especially a combination of PPARα and PPARγ agonistic activity seems worthwhile to be pursued. Herein we present the design and synthesis of a series of pirinixic acid derivatives as potent PPARα par...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lamers C,Dittrich M,Steri R,Proschak E,Schubert-Zsilavecz M

更新日期：2014-08-15 00:00:00

abstract：:A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hagmann WK,Caldwell CG,Chen P,Durette PL,Esser CK,Lanza TJ,Kopka IE,Guthikonda R,Shah SK,MacCoss M,Chabin RM,Fletcher D,Grant SK,Green BG,Humes JL,Kelly TM,Luell S,Meurer R,Moore V,Pacholok SG,Pavia T,Williams H

更新日期：2000-09-04 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

authors： Tan Q,Ogawa AM,Painter RE,Park YW,Young K,DiNinno FP

更新日期：2010-04-15 00:00:00

abstract：:The Hotoda's sequence substituted with TBDPS via 5'-end nucleobase existed as parallel quadruplex structure and exhibited inhibitory activities in an HIV-1 envelop proteins mediated cell-cell fusion assay. This result demonstrated that the 5'-aromatic groups of the Hotoda's sequence are allowed to have a large spatial...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen W,Xu L,Cai L,Zheng B,Wang K,He J,Liu K

更新日期：2011-10-01 00:00:00

abstract：:The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited informa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu J,Wang X,Chen L,Huang M,Tang W,Zuo J,Liu YC,Shi Z,Liu R,Shen J,Xiong B

更新日期：2016-02-01 00:00:00

abstract：:Two series of triamino pyrimidines and a series of triamino pyridines have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. Small structural changes in these three hetereoaromatic cores influenced the functional activi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meduna SP,Savall BM,Cai H,Edwards JP,Thurmond RL,McGovern PM

更新日期：2011-05-15 00:00:00

abstract：:The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tremblay MR,Simard J,Poirier D

更新日期：1999-10-04 00:00:00

abstract：:The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein-protein interaction. Here we report on the identification of fragments that bind to a C-terminal sub-pock...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu S,Gochin M

更新日期：2013-09-15 00:00:00

abstract：:In the screening search for Hepatitis B virus inhibitory agents from medicinal plants, the ethanol extract of Piper longum Linn. was found to possess superior anti-HBV activity in vitro. Bioassay-guided fractionation coupled with repeated purification resulted in the isolation of four new compounds, involving two new ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZY,Liu WF,Zhang XM,Luo J,Ma YB,Chen JJ

更新日期：2013-04-01 00:00:00

abstract：:Gram positive (Bacillus cereus, B. subtilis), Gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria, and Candida albicans as a representative of fungi were used for screening the in vitro antimicrobial activity of diarylamines in the 2,3,5-trimethylbenzo[b]thiophene series bearing different substituents, s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ferreira IC,Calhelha RC,Estevinho LM,Queiroz MJ

更新日期：2004-12-06 00:00:00

abstract：:This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trujillo JI,Huang W,Hughes RO,Rogier DJ,Turner SR,Devraj R,Morton PA,Xue CB,Chao G,Covington MB,Newton RC,Metcalf B

更新日期：2011-03-15 00:00:00

abstract：:A series of novel pyrimidone analogues have been designed and synthesized as HIV-1 integrase (IN) inhibitors. This study demonstrated that introducing a substituent in the N1-position of the pyrimidone scaffold does not significantly influence IN inhibitory activity. Molecular docking studies showed these compounds co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu S,Sanchez TW,Liu Y,Yin Y,Neamati N,Zhao G

更新日期：2013-11-15 00:00:00

abstract：:The structure-activity relationships for semicarbazide-sensitive amine oxidase (SSAO) inhibitors based on arylpropynylamines was investigated using solution-phase combinatorial Sonogashira coupling. The results suggest that binding to the active site occurs by coordination of the amine to the proximal copper(II) and f...

journal_title：Bioorganic & medicinal chemistry letters

authors： Conn C,Shimmon R,Cordaro F,Hargraves TL,Ibrahim P

更新日期：2001-10-08 00:00:00

abstract：:We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martín-Gago P,Ramón R,Aragón E,Fernández-Carneado J,Martin-Malpartida P,Verdaguer X,López-Ruiz P,Colás B,Cortes MA,Ponsati B,Macias MJ,Riera A

更新日期：2014-01-01 00:00:00

abstract：:Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 microM, respectively. It exhibited a s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Giroux A,Boulet L,Brideau C,Chau A,Claveau D,Côté B,Ethier D,Frenette R,Gagnon M,Guay J,Guiral S,Mancini J,Martins E,Massé F,Méthot N,Riendeau D,Rubin J,Xu D,Yu H,Ducharme Y,Friesen RW

更新日期：2009-10-15 00:00:00

abstract：:Recent studies have found that phthalonitrile derivatives are remarkably potent inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to further determine the structure-activity relationships (SARs) for MAO inhibition by this class of compounds and to discover novel potent MAO inhibitors, the present stud...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chirkova ZV,Kabanova MV,Filimonov SI,Abramov IG,Petzer A,Petzer JP,Firgang SI,Suponitsky KY

更新日期：2015-03-15 00:00:00

abstract：:A number of compounds bearing a quaternary ammonium moiety were found to be antagonists with nanomolar binding affinity for the chemokine receptor-2. The structure-activity relationships in the series are described herein along with some detailed characterization of the interesting compounds. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lagu B,Gerchak C,Pan M,Hou C,Singer M,Malaviya R,Matheis M,Olini G,Cavender D,Wachter M

更新日期：2007-08-01 00:00:00

abstract：:A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Espinoza-Moraga M,Singh K,Njoroge M,Kaur G,Okombo J,De Kock C,Smith PJ,Wittlin S,Chibale K

更新日期：2017-02-01 00:00:00

abstract：:A new synthesis of (R,S)-PPG (4-phosphonophenylglycine) and the separation of the protected enantiomers leading after deprotection to (+)- and (-)-PPG are described. Pharmacological characterization at the group III metabotropic glutamate receptors hmGluR4a and hmGluR7b revealed (+)-PPG as the active enantiomer. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gasparini F,Inderbitzin W,Francotte E,Lecis G,Richert P,Dragic Z,Kuhn R,Flor PJ

更新日期：2000-06-05 00:00:00

abstract：:Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints and key transcriptional events in response to extracellular and intracellular signals leading to proliferation. Significant clinical activity for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sánchez-Martínez C,Lallena MJ,Sanfeliciano SG,de Dios A

更新日期：2019-10-15 00:00:00

abstract：:A new triterpenoid saponin, julibroside J(28) (1), was isolated from the stem bark of Albizia julibrissin Durazz (Leguminosae) by using chromatographic method. The structure of 1 was established by spectroscopic methods. 1 displayed significant antitumor activity in vitro against PC-3M-1E8, Bel-7402, and HeLa cancer c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang H,Tong WY,Zhao YY,Cui JR,Tu GZ

更新日期：2005-10-15 00:00:00

abstract：:Catalytic disulfenylation reaction of alkenes by common Lewis acids has been investigated in detail. While reactions by FeCl(3) were feasible with cycloalkenes and other simple alkenes, much faster and excellent conversions were possible by AlCl(3) even with the substrates less reactive toward FeCl(3). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamagiwa N,Suto Y,Torisawa Y

更新日期：2007-11-15 00:00:00

abstract：:We have designed and synthesized a novel series of 3-biphenylamino acid amides as cathepsin K inhibitors based on compound I. In these inhibitors, we have discovered 4-aminophenoxyacetic acids 43 and 47 with good IC(50) values, although lipophilic groups are favorable for the hydrophobic S1' pocket. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shinozuka T,Shimada K,Matsui S,Yamane T,Ama M,Fukuda T,Taki M,Naito S

更新日期：2006-03-15 00:00:00

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:Double-stranded RNA has become a ubiquitous tool for inhibition of gene expression in the laboratory. If similar success could be achieved in vivo, duplex RNA might provide a new class of therapeutics capable of treating a broad spectrum of disease. Chemists and biologists developing duplex RNA as a drug have made pro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watts JK,Corey DR

更新日期：2010-06-01 00:00:00

abstract：:The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Powell CE,Groendyke BJ,Gero TW,Feru F,Feutrill J,Chen B,Li B,Szabo H,Gray NS,Scott DA

更新日期：2020-10-01 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