Sequential cytotoxicity: a theory examined using a series of 3,5-bis(benzylidene)-1-diethylphosphono-4-oxopiperidines and related phosphonic acids.

abstract：:KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang S,Lu D,Ouyang P

更新日期：2018-09-15 00:00:00

abstract：:Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hou W,Huang ZX,Xu HG,Lin J,Zhang DM,Peng QL,Lin H,Chang YQ,Wang LH,Yao Z,Sun PH,Chen WM

更新日期：2018-11-01 00:00:00

abstract：:A series of 114 SIRT inhibitor candidates was assembled using 'click chemistry', by reacting two alkynes bearing 2-anilinobenzamide pharmacophore with 57 azide building blocks in the presence of Cu(I) catalyst. Screening identified two SIRT2-selective inhibitors, which were more SIRT2-selective than AGK2, a known SIRT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tatum PR,Sawada H,Ota Y,Itoh Y,Zhan P,Ieda N,Nakagawa H,Miyata N,Suzuki T

更新日期：2014-04-15 00:00:00

abstract：:A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 00:00:00

abstract：:The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim YJ,Jeon Y,Kim T,Lim WC,Ham J,Park YN,Kim TJ,Ko H

更新日期：2017-02-15 00:00:00

abstract：:We report an efficient approach for the chemical synthesis of Rhesus θ-defensin-1 (RTD-1) using Fmoc-based solid-phase peptide synthesis in combination with an intramolecular version of native chemical ligation. The corresponding linear thioester precursor was cyclized and folded in a one-pot reaction using reduced gl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aboye TL,Li Y,Majumder S,Hao J,Shekhtman A,Camarero JA

更新日期：2012-04-15 00:00:00

abstract：:Nine new monoterpene glycosides (1-9), together with 18 known compounds were obtained from the n-butanol soluble fraction of ethanol extract from Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectroscopic data. The inhibitory effects of these compounds (except com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ding L,Zhao F,Chen L,Jiang Z,Liu Y,Li Z,Qiu F,Yao X

更新日期：2012-12-01 00:00:00

abstract：:Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies direc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebsack AD,Rech JC,Branstetter BJ,Hawryluk NA,Merit JE,Allison B,Rynberg R,Buma J,Rizzolio M,Swanson N,Ao H,Maher MP,Herrmann M,Freedman J,Scott BP,Luo L,Bhattacharya A,Wang Q,Chaplan SR,Wickenden AD,Breitenbucher

更新日期：2010-12-01 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：:Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matveev SV,Kwiatkowski S,Sviripa VM,Fazio RC,Watt DS,LeVine H 3rd

更新日期：2014-12-01 00:00:00

abstract：:PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody dr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holte D,Lyssikatos JP,Valdiosera AM,Swinney Z,Sisodiya V,Sandoval J,Lee C,Aujay MA,Tchelepi RB,Hamdy OM,Gu C,Lin B,Sarvaiya H,Pysz MA,Laysang A,Williams S,Jun Lee D,Holda MK,Purcell JW,Gavrilyuk J

更新日期：2020-12-15 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

abstract：:The synthesis and pharmacological profile of a novel series of 7-methoxy-furo[2,3-c]pyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buckley GM,Cooper N,Davenport RJ,Dyke HJ,Galleway FP,Gowers L,Haughan AF,Kendall HJ,Lowe C,Montana JG,Oxford J,Peake JC,Picken CL,Richard MD,Sabin V,Sharpe A,Warneck JB

更新日期：2002-02-11 00:00:00

abstract：:Some ergostane triterpenoids from Taiwanofungus camphoratus have been shown to exhibit anti-inflammatory activity in vitro. However, the effect of ergostane triterpenoids on the immune response remains unknown. In this study, we elucidated that ergostane triterpenoids significantly decreased the cytokines and chemokin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin MK,Lee MS,Chang WT,Chen HY,Chen JF,Li YR,Lin CC,Wu TS

更新日期：2015-10-15 00:00:00

abstract：:Biflorin 1 is a biologically active quinone, isolated from Capraria biflora. Five new biflorin-based nitrogen derivatives were synthesized, of which two were mixtures of (E)- and (Z)- isomers: (Z)-2a, (Z)-2b, (Z)-3a, (Z)- and (E)-3b, (Z)- and (E)-3c. The antibacterial activity was investigated using the microdilution ...

journal_title：Bioorganic & medicinal chemistry letters

authors： da S Souza LG,Almeida MCS,Lemos TLG,Ribeiro PRV,de Brito ES,Silva VLM,Silva AMS,Braz-Filho R,Costa JGM,Rodrigues FFG,Barreto FS,de Moraes MO

更新日期：2016-01-15 00:00:00

abstract：:Several substituted quinolin-4-amines and heteroaromatic analogs were synthesized and evaluated for interaction with triplex polydA.2polydT and duplex polydA.polydT by using UV-thermal melting experiments. Excellent triple-helix DNA ligands with high affinity toward T.A.T triplets and triple/duplex selectivity were de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Strekowski L,Hojjat M,Wolinska E,Parker AN,Paliakov E,Gorecki T,Tanious FA,Wilson WD

更新日期：2005-02-15 00:00:00

abstract：:Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45nM. The in vivo effects of these compounds in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elokdah HM,Friedrichs GS,Chai SY,Harrison BL,Primeau J,Chlenov M,Crandall DL

更新日期：2002-08-05 00:00:00

abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

更新日期：2009-04-15 00:00:00

abstract：:An asymmetric synthesis of alpha-amino acids with novel beta-branched side chains has been implemented. The syntheses feature a p-toluenesulfinylimine induced chiral Strecker approach and were found to be applicable to the introduction of both aliphatic and aromatic beta-branched sidechains for preparation of previous...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang M,Porte A,Diamantidis G,Sogi K,Kubrak D,Resnick L,Mayer SC,Wang Z,Kreft AF,Harrison BL

更新日期：2007-05-01 00:00:00

abstract：:Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Loh VM Jr,Cockcroft XL,Dillon KJ,Dixon L,Drzewiecki J,Eversley PJ,Gomez S,Hoare J,Kerrigan F,Matthews IT,Menear KA,Martin NM,Newton RF,Paul J,Smith GC,Vile J,Whittle AJ

更新日期：2005-05-02 00:00:00

abstract：:Exogenous short-chain nucleic acids undergo rapid import into the nucleus. Fluorescence-labeled dT1-13 DNA microinjected into the cytoplasm domain of a HeLa cell was rapidly imported into the nucleus domain within 1min. This is much more rapid than what has been observed for intracellular diffusion of small molecules....

journal_title：Bioorganic & medicinal chemistry letters

authors： Kitagawa M,Okamoto A

更新日期：2016-10-01 00:00:00

abstract：:Cyclic phosphatidic acid (CPA) is a naturally occurring analog of lysophosphatidic acid (LPA) in which the sn-2 hydroxy group forms a five-membered ring with the sn-3 phosphate. Here, we describe the synthesis of R-3-CCPA and S-3-CCPA along with their pharmacological properties as inhibitors of lysophospholipase D/aut...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gupte R,Siddam A,Lu Y,Li W,Fujiwara Y,Panupinthu N,Pham TC,Baker DL,Parrill AL,Gotoh M,Murakami-Murofushi K,Kobayashi S,Mills GB,Tigyi G,Miller DD

更新日期：2010-12-15 00:00:00

abstract：:Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ando M,Sekino E,Haga Y,Moriya M,Ito M,Ito J,Iwaasa H,Ishihara A,Kanatani A,Ohtake N

更新日期：2009-09-01 00:00:00

abstract：:The potency and selectivity of a series of 5-hetero-2-iminohexahydroazepines were examined as inhibitors of the three human NOS isoforms. The effect of ring substitution of the 5-carbon for a heteroatom is presented. Potencies (IC(50)'s) for these inhibitors are in the low micromolar range for hi-NOS with some example...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moormann AE,Metz S,Toth MV,Moore WM,Jerome G,Kornmeier C,Manning P,Hansen DW Jr,Pitzele BS,Webber RK

更新日期：2001-10-08 00:00:00

abstract：:Chromatography of the ethanol extract of the medicinal fruit Stauntonia hexaphylla resulted in the purification of 26 compounds (1-26), including two undescribed triterpene saponins 1 and 2 (hexaphylosides A and B). Their structures were confirmed by spectroscopic data, including IR, HR QTOF MS, 1H, 13C NMR, COSY, HMQ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ba Vinh L,Jang HJ,Viet Phong N,Dan G,Won Cho K,Ho Kim Y,Young Yang S

更新日期：2019-08-15 00:00:00

abstract：:A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory a...

journal_title：Bioorganic & medicinal chemistry letters

authors： He H,Wang X,Shi L,Yin W,Yang Z,He H,Liang Y

更新日期：2016-07-15 00:00:00

abstract：:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key anal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

更新日期：2012-01-01 00:00:00

abstract：:The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environm...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nguyen TT,Ryu HJ,Lee SH,Hwang S,Breton V,Rhee JH,Kim D

更新日期：2011-05-15 00:00:00

abstract：:Anions represent the second class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), in addition to sulfonamides, which possess clinical applications. The first inhibition study of the zinc and cobalt gamma-class enzyme from the archaeon Methanosarcina thermophila (Cam) with anions is reported here....

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Zimmerman S,Ferry JG,Scozzafava A,Supuran CT

更新日期：2004-06-21 00:00:00

abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

更新日期：2009-11-01 00:00:00