Synthesis of novel orthoalkylaminophenol derivatives as potent neuroprotective agents in vitro.

abstract：:We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shaghafi MB,Barrett DG,Willard FS,Overman LE

更新日期：2014-02-15 00:00:00

abstract：:Transglutaminase 2 (TG2) is a ubiquitously expressed, Ca(2+)-activated extracellular enzyme in mammals that is maintained in a catalytically dormant state by multiple mechanisms. Although its precise physiological role in the extracellular matrix remains unclear, aberrantly up-regulated TG2 activity is a hallmark of s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yi MC,Palanski BA,Quintero SA,Plugis NM,Khosla C

更新日期：2015-11-01 00:00:00

abstract：:Aminobenzyloxyarylamide derivatives 1a-i and 2a-t were designed and synthesized as novel selective κ opioid receptor (KOR) antagonists. The benzoyl amide moiety of LY2456302 was changed into N-hydroxybenzamide and benzisoxazole-3(2H)-one to investigate whether it could increase the binding affinity or selectivity for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： He G,Song Q,Wang J,Xu A,Peng K,Zhu Q,Xu Y

更新日期：2020-07-01 00:00:00

abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

更新日期：1998-05-05 00:00:00

abstract：:Homology modeling of candida lanosterol C-14 demethylase, synthesis and in vitro antifungal activities of cyclohexyl analogs of restricticin are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsukuda T,Shiratori Y,Watanabe M,Ontsuka H,Hattori K,Shirai M,Shimma N

更新日期：1998-07-21 00:00:00

abstract：:Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

更新日期：2017-10-15 00:00:00

abstract：:Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Glunz PW,Zhang X,Zou Y,Delucca I,Nirschl AH,Cheng X,Weigelt CA,Cheney DL,Wei A,Anumula R,Luettgen JM,Rendina AR,Harpel M,Luo G,Knabb R,Wong PC,Wexler RR,Priestley ES

更新日期：2013-09-15 00:00:00

abstract：:Replacement of the C-terminal carboxylic acid functionality of peptide inhibitors of hepatitis C virus (HCV) NS3 protease (complexed with NS4A peptide cofactor) by activated carbonyl groups does not produce any substantial increase in potency. These latter inhibitors also inhibit a variety of other serine and cysteine...

journal_title：Bioorganic & medicinal chemistry letters

authors： Llinàs-Brunet M,Bailey M,Déziel R,Fazal G,Gorys V,Goulet S,Halmos T,Maurice R,Poirier M,Poupart MA,Rancourt J,Thibeault D,Wernic D,Lamarre D

更新日期：1998-10-06 00:00:00

abstract：:Indolopropellane 2 was reported to show almost no binding affinity to the δ opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagase H,Nakajima R,Yamamoto N,Hirayama S,Iwai T,Nemoto T,Gouda H,Hirono S,Fujii H

更新日期：2014-07-01 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：:New antimicrobial compounds are of major importance because of the growing problem of bacterial resistance and antimicrobial peptides have been gaining a lot of interest. Their mechanism of action, however, is often obscure. Here a set of non-peptidic compounds with antimicrobial activity are presented that have been ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Appelt C,Schrey AK,Söderhäll JA,Schmieder P

更新日期：2007-04-15 00:00:00

abstract：:Bromofluoroacetophenone derivatives which produce fluorine substituted phenyl radicals that cleave DNA upon excitation were investigated as a novel photonuclease. Pyrrolecarboxamide-conjugated bromofluoroacetophenones; 4'-bromo-2'-fluoroacetophenone and 2'-bromo-4'-fluoroacetophenone were synthesized and their DNA cle...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wender PA,Jeon R

更新日期：2003-05-19 00:00:00

abstract：:ADX88178 (1) has been recently developed as a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4). The aim of this study was to develop [(11)C]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [(11)C]1 was efficie...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujinaga M,Yamasaki T,Nengaki N,Ogawa M,Kumata K,Shimoda Y,Yui J,Xie L,Zhang Y,Kawamura K,Zhang MR

更新日期：2016-01-15 00:00:00

abstract：:A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antoszczak M,Maj E,Stefańska J,Wietrzyk J,Janczak J,Brzezinski B,Huczyński A

更新日期：2014-04-01 00:00:00

abstract：:β-carbolines from various natural and synthetic sources have been known to show diverse biological activities. As a part of our current ongoing project to search for potent natural product-derived anti-leishmanial compounds, we have synthesized a series of substituted 1-aryl-β-carboline derivatives. A total of 22 comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gohil VM,Brahmbhatt KG,Loiseau PM,Bhutani KK

更新日期：2012-06-15 00:00:00

abstract：:New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raeppel F,Raeppel SL,Therrien E

更新日期：2015-09-15 00:00:00

abstract：:A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HJ,Cho HJ,Kim H,El-Gamal MI,Oh CH,Lee SH,Sim T,Hah JM,Yoo KH

更新日期：2012-05-01 00:00:00

abstract：:A new series of quinoline ether inhibitors, which potently and selectively inhibit PDGFR tyrosine kinases, is described in this Letter. Compounds 23 and 33 are selective, low nanomolar inhibitors of PDGFRα and β, display good pharmacokinetics in rat and dog and are active in vivo at low doses when given orally twice d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Plé PA,Jung F,Ashton S,Hennequin L,Laine R,Lambert-van der Brempt C,Morgentin R,Pasquet G,Taylor S

更新日期：2012-05-01 00:00:00

abstract：:Four new lignans, strebluslignanol F (1), (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5-16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li J,Meng AP,Guan XL,Li J,Wu Q,Deng SP,Su XJ,Yang RY

更新日期：2013-04-01 00:00:00

abstract：:Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoyama Y,Konoike T,Kanda A,Naya N,Nakajima M

更新日期：2001-07-09 00:00:00

abstract：:Novel quinolone-macrocycle conjugates displayed submicromolar antibacterial activity against Escherichia coli and Staphylococcus aureus bacterial strains. An analogous open-chain structure was not active at 100 microM against the same pathogenic strains. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jefferson EA,Swayze EE,Osgood SA,Miyaji A,Risen LM,Blyn LB

更新日期：2003-05-19 00:00:00

abstract：:8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a potential D(4)-receptor ligand was synthesized using oxidative iodo-destannylation reaction. The preliminary biodistribution studies of radioiodinated iozapine have shown that the compound is taken up in the brains of mice and rabbits. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joshua AV,Sharma SK,Strelkov A,Scott JR,Martin-Iverson MT,Abrams DN,Silverstone PH,McEwan AJ

更新日期：2007-07-15 00:00:00

abstract：:We designed and synthesized novel δ opioid receptor (DOR) agonists 3a-i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watanabe Y,Hayashida K,Saito D,Takahashi T,Sakai J,Nakata E,Kanda T,Iwai T,Hirayama S,Fujii H,Yamakawa T,Nagase H

更新日期：2017-08-01 00:00:00

abstract：:Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O-β-d-glycopyranosyl ester (1), 23-O-4'-epi-neochebuloylarjungenin (2), and 23-O-galloylpinfaenoic acid 28-O-β-d-glucopyranosyl ester (17) were isolated from the fruits of Terminalia chebula Retz. along with fourteen known ones. Their struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee DY,Yang H,Kim HW,Sung SH

更新日期：2017-01-01 00:00:00

abstract：:Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation,  a phenomenon termed as "austerity". Search for the new agents that eliminate the toler...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tawila AM,Sun S,Kim MJ,Omar AM,Dibwe DF,Ueda JY,Toyooka N,Awale S

更新日期：2020-08-15 00:00:00

abstract：:The efficient synthesis of an enzyme cleavable biotinylated diazirinyl photoaffinity ligand is described to allow the effective manipulation of the photolabeled biocomponents. The compound contains a glutamic acid gamma-methyl ester, which is a precursor of the substrate for V8 protease, between the diazirinyl photoph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto M,Okamoto S,Nabeta K,Hatanaka Y

更新日期：2004-05-17 00:00:00

abstract：:Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer's disease (AD). The potency of the compounds were assessed in the inhibition of Aβ self-assembly (fibril and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bag S,Tulsan R,Sood A,Cho H,Redjeb H,Zhou W,LeVine H 3rd,Török B,Török M

更新日期：2015-02-01 00:00:00

abstract：:The SmI(2)-promoted three-component coupling reaction of thiophene-2-carboxylate, indole-2-carbaldehyde and acetophenone provides an expedient route to a series of tetracyclic carbazolothiophene compounds bearing the indole and thiophene rings. Among these samples, 9-benzyl-4-methyl-4-(4-hydroxyphenyl)-10-oxo-4,10-dih...

journal_title：Bioorganic & medicinal chemistry letters

authors： Babu G,Yu HM,Yang SM,Fang JM

更新日期：2004-03-08 00:00:00

abstract：:γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-termi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rydzik AM,Brem J,Struwe WB,Kochan GT,Benesch JL,Schofield CJ

更新日期：2014-11-01 00:00:00

abstract：:A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou G,Wu D,Hermel E,Balogh E,Gochin M

更新日期：2010-03-01 00:00:00