In silico multi-filter screening approaches for developing novel beta-secretase inhibitors.

abstract：:Selective metabotropic glutamate receptor 2 (mGluR2) inhibitors have been demonstrated to show therapeutic effects by improving alleviating symptoms of schizophrenic patients in clinical studies. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography (PET) tracer origin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumata K,Zhang Y,Ogawa M,Kurihara Y,Mori W,Hu K,Fujinaga M,Nengaki N,Zhang MR

更新日期：2020-12-01 00:00:00

abstract：:Novel 8-aryl and 8-aroyl substituted derivatives of 3-(dipropylamino)chroman are described. The compounds have been prepared by a palladium catalyzed reaction of iodoarenes and a stannylated derivative of [eta6-3-(dipropylamino)chroman]Cr(CO)3. Several of the compounds have high affinity for 5-HT1A receptors whereas t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldirola P,Chowdhury R,Unelius L,Mohell N,Hacksell U,Johansson AM

更新日期：1999-06-07 00:00:00

abstract：:In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent...

journal_title：Bioorganic & medicinal chemistry letters

authors： Almeida LE,Pereira EF,Camara AL,Maelicke A,Albuquerque EX

更新日期：2004-04-19 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：:Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester as a potent and selective mGluR1 non-competitive antagonist, the use of a doubly (13)C-labeled analogue to identify, and consequently prevent, metabolically labile positions is reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Micheli F,Cavanni P,Di Fabio R,Donati D,Hamdan M,Provera S,Tranquillini ME,Vitulli G

更新日期：2007-02-15 00:00:00

abstract：:Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic acids initially isolated and characterized from the bath fluid of stimulated gut over 50 years ago. Despite similar structural and biological profiles, Darmstoff analogs have not previously been examined as potential LPA mimetics. Here, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gududuru V,Zeng K,Tsukahara R,Makarova N,Fujiwara Y,Pigg KR,Baker DL,Tigyi G,Miller DD

更新日期：2006-01-15 00:00:00

abstract：:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2002-11-04 00:00:00

abstract：:A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hong SS,Lee SA,Kim N,Hwang JS,Han XH,Lee MK,Jung JK,Hong JT,Kim Y,Lee D,Hwang BY

更新日期：2011-02-15 00:00:00

abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

更新日期：2006-05-15 00:00:00

abstract：:Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to impr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brown MF,Marfat A,Antognoli G,Chambers RJ,Cheng JB,Damon DB,Liston TE,McGlynn MA,O'Sullivan SP,Owens BS,Pillar JS,Shirley JT,Watson JW

更新日期：1998-09-22 00:00:00

abstract：:Symmetrically and asymmetrically substituted 1,2,4,5-tetraoxanes were synthesized by the oxidative system H(2)O(2)/TFE in presence of MeReO(3) as a catalyst. All of the synthesized compounds were characterized spectroscopically, and evaluated for cytotoxicity, and antimalarial activity. Several of these tetraoxanes ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Atheaya H,Khan SI,Mamgain R,Rawat DS

更新日期：2008-02-15 00:00:00

abstract：:Imidazo[1,2-a]pyrimidines and imidazo[1,2-b][1,2,4]triazines are ligands for the benzodiazepine binding site of GABA(A) receptors that are functionally selective for the alpha2/alpha3 subtypes over the alpha1 subtype. SAR studies to optimise this functional selectivity, pharmacokinetic and behavioural data are describ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jennings AS,Lewis RT,Russell MG,Hallett DJ,Street LJ,Castro JL,Atack JR,Cook SM,Lincoln R,Stanley J,Smith AJ,Reynolds DS,Sohal B,Pike A,Marshall GR,Wafford KA,Sheppard WF,Tye SJ

更新日期：2006-03-15 00:00:00

abstract：:Two series of 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles were synthesized and their affinities for the cannabinoid CB(1) and CB(2) receptors were determined. In the 2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A second series of 23 1-pentyl-2-aryl-4-(1-naphthoyl)-pyrroles (6) was also prepar...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huffman JW,Padgett LW,Isherwood ML,Wiley JL,Martin BR

更新日期：2006-10-15 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：:In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

更新日期：2015-05-01 00:00:00

abstract：:Regioselective synthesis of a number of highly functionalized 3-benzylpyrimidino chromen-2-ones (4) were accomplished in a one pot three component reaction in acetic acid and determined their anti-microbial and anti-biofilm activities. Compounds 4o and 4p showed an excellent anti-microbial activity against Micrococcus...

journal_title：Bioorganic & medicinal chemistry letters

authors： Emmadi NR,Atmakur K,Bingi C,Godumagadda NR,Chityal GK,Nanubolu JB

更新日期：2014-01-15 00:00:00

abstract：:O6-Benzylguanine (O6-BG) is a substrate of O6-methylguanine-DNA methyltransferase (MGMT), which is involved in drug resistance of chemotherapy in the majority of glioblastoma multiform. For clinical diagnosis, it is hoped that the MGMT expression level could be determined by a noninvasive method to understand the deta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koyama H,Ikenuma H,Toda H,Kondo G,Hirano M,Kato M,Abe J,Yamada T,Wakabayashi T,Ito K,Natsume A,Suzuki M

更新日期：2017-05-01 00:00:00

abstract：:The syntheses and SAR investigations of novel CB(1) receptor antagonists based on a 1,2-diaryl piperidine core have been described. Optimization of this core afforded a compound with robust in vivo potency by reducing food intake in a mouse DIO model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scott JD,Li SW,Wang H,Xia Y,Jayne CL,Miller MW,Duffy RA,Boykow GC,Kowalski TJ,Spar BD,Stamford AW,Chackalamannil S,Lachowicz JE,Greenlee WJ

更新日期：2010-02-01 00:00:00

abstract：:A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar-NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar-NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The synthetic compounds exhibite...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tang H,Ning FX,Wei YB,Huang SL,Huang ZS,Chan AS,Gu LQ

更新日期：2007-07-01 00:00:00

abstract：:The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guerrini R,Rizzi D,Zucchini M,Tomatis R,Regoli D,Calo' G,Salvadori S

更新日期：2003-02-10 00:00:00

abstract：:This article describes the syntheses and SAR of a series of imidazolopyrimidine derivatives, which are evaluated as inhibitors of PI3-Kinase (PI3K) and mTOR. These compounds were found to be ATP competitive with good tumor cell growth inhibition, and suppression of pathway specific biomakers such as phosphorylation of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Venkatesan AM,Dehnhardt CM,Chen Z,Santos ED,Dos Santos O,Bursavich M,Gilbert AM,Ellingboe JW,Ayral-Kaloustian S,Khafizova G,Brooijmans N,Mallon R,Hollander I,Feldberg L,Lucas J,Yu K,Gibbons J,Abraham R,Mansour TS

更新日期：2010-01-15 00:00:00

abstract：:Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and development of arteriosclerosis. Previous attempts aimed at developing proanthocya...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mizuno M,Nakanishi I,Matsumoto KI,Fukuhara K

更新日期：2017-11-15 00:00:00

abstract：:A novel series of diphenyl lactam containing calcium channel blockers is described. Extensive SAR studies resulted in compounds with low molar activity and good plasma exposure after oral dosing. Compounds 2, 6 and 7 demonstrated significant efficacy in the capsaicin model of secondary hyperalgesia following oral admi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Doherty GA,Bhatia P,Vortherms TA,Marsh KC,Wetter JM,Mack H,Scott VE,Jarvis MF,Stewart AO

更新日期：2012-02-15 00:00:00

abstract：:Some novel oxazolidinone derivatives with benzotriazole as pendant have been synthesized and tested for antibacterial activity. Linearly attached benzotriazole derivative showed more potency compared to angular one in vitro. Out of E/Z-isomers of angularly attached derivatives E-isomer was found to be more potent than...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das J,Rao CV,Sastry TV,Roshaiah M,Sankar PG,Khadeer A,Kumar MS,Mallik A,Selvakumar N,Iqbal J,Trehan S

更新日期：2005-01-17 00:00:00

abstract：:The 1',6'-isomer of neplanocin A possesses biological properties that have not been optimised through rationally conceived analogues. In that direction, this Letter reports the use of the Ullmann reaction to achieve enantiomeric 3-deaza-1',6'-isoneplanocin and 3-bromo-3-deaza-1',6'-isoneplanocin. These four compounds ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu C,Chen Q,Schneller SW

更新日期：2016-02-01 00:00:00

abstract：:The stereochemistry of the tubulin inhibitors taltobulin HTI-286 (2) and HTI-042 (3) was determined by utilizing the DPFGSE 1D NOE experiment. Single crystal X-ray diffraction analysis further confirmed the absolute configuration of these two compounds, which carry the (S,S,S)-configuration necessary for biological ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niu C,Ho DM,Williamson RT,Zask A,Ayral-Kaloustian S

更新日期：2010-03-01 00:00:00

abstract：:Isodesmosine and desmosine are crosslinking amino acids that are present only in elastin. They are useful biomarkers for the degradation of elastin, which occurs during the progression of chronic obstructive pulmonary disease (COPD) and related diseases. This Letter describes the synthesis of [(13)C3,(15)N1]-labeled i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tanigawa T,Komatsu A,Usuki T

更新日期：2015-01-01 00:00:00

abstract：:We previously identified o-carborane bisphenol BE360 (4) as a selective estrogen receptor modulator (SERM), which ameliorated bone loss without inducing estrogenic action in uterus of OVX and ORX mice. Here, we synthesized a fluorinated derivative, B-fluorinated o-carborane bisphenol BE310 (5) by means of S(N)Ar react...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2012-07-15 00:00:00

abstract：:The design and synthesis of new 1alpha,25-dihydroxy-19-norvitamin D(3) analogues 3a-c, which have an amide bond in the molecule instead of the diene, are described. The A-ring moiety was constructed by a (3S,5S)-3,5-dihydroxypiperidine derivative (9, 11, or 13) prepared from D-mannose, and a CD-ring carboxylic acid 16...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suhara Y,Kittaka A,Ono K,Kurihara M,Fujishima T,Yoshida A,Takayama H

更新日期：2002-12-16 00:00:00

abstract：:A one step synthesis of fluorescent 8-aryl-(7-deazaguanines) has been accomplished. Probes exhibit blue to green high quantum yield fluorescence in a variety of organic and aqueous solutions, high extinction coefficients, and large Stokes shifts often above 100 nm. The probes are highly cell permeable, and exhibit sta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhimitruka I,Eubank TD,Gross AC,Khramtsov VV

更新日期：2015-10-15 00:00:00