Design and synthesis of new bis-pyridinium oxime reactivators for acetylcholinesterase inhibited by organophosphorous nerve agents.

abstract：:Antagonists of the integrin receptor alpha(v)beta(3) are expected to have utility in the treatment of osteoporosis through inhibition of bone resorption. A series of potent, chain-shortened, pyrrolidinone-containing alpha(v)beta(3) receptor antagonists is described. Two sets of diasteromeric pairs of high-affinity ant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perkins JJ,Duong LT,Fernandez-Metzler C,Hartman GD,Kimmel DB,Leu CT,Lynch JJ,Prueksaritanont T,Rodan GA,Rodan SB,Duggan ME,Meissner RS

更新日期：2003-12-15 00:00:00

abstract：:Two natural piperamides (piperlonguminine and refrofractamide A) and their derivatives were synthesized and evaluated for inhibitory activity against histone deacetylases, as well as the HCT-116 human colon cancer cell line. The preliminary structure activity relationship was discussed. Compounds featuring a hydroxami...

journal_title：Bioorganic & medicinal chemistry letters

authors： Luo Y,Liu HM,Su MB,Sheng L,Zhou YB,Li J,Lu W

更新日期：2011-08-15 00:00:00

abstract：:Recent studies have highlighted a key role in regulating gene transcription, in both eukaryotes and prokaryotes, by enzymes that control the acetylation and deacetylation of histones. In particular, inhibitors of histone deacetylases (HDAC-Is) have been shown effective in controlling the development of many parasites,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Giannini G,Battistuzzi G,Vignola D

更新日期：2015-02-01 00:00:00

abstract：:The SAR studies to optimise both potency and rate of clearance in the rat for a series of pyrimidine and pyridine based VLA-4 antagonists are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Porter JR,Archibald SC,Brown JA,Childs K,Critchley D,Head JC,Hutchinson B,Parton TA,Robinson MK,Shock A,Warrellow GJ,Zomaya A

更新日期：2002-06-17 00:00:00

abstract：:A series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives of biological interest have been prepared by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reacti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Keche AP,Hatnapure GD,Tale RH,Rodge AH,Kamble VM

更新日期：2012-11-01 00:00:00

abstract：:Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marwaha A,Goel RK,Mahajan MP

更新日期：2007-09-15 00:00:00

abstract：:Selective σ2 ligands continue to be an active target for medications to attenuate the effects of psychostimulants. In the course of our studies to determine the optimal substituents in the σ2-selective phenyl piperazines analogues with reduced activity at other neurotransmitter systems, we discovered that 1-(3-chlorop...

journal_title：Bioorganic & medicinal chemistry letters

authors： Motel WC,Healy JR,Viard E,Pouw B,Martin K,Matsumoto RR,Coop A

更新日期：2013-12-15 00:00:00

abstract：:A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen TK,Ankersen M,Raun K,Hansen BS

更新日期：2001-07-23 00:00:00

abstract：:A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vullo D,Sai Kumar RS,Scozzafava A,Capasso C,Ferry JG,Supuran CT

更新日期：2013-12-15 00:00:00

abstract：:2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC50=26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F=53%) and long human liver microsome stability (t(1/2)=62 min...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang A,Prouty CP,Pelton PD,Yong M,Demarest KT,Murray WV,Kuo GH

更新日期：2010-02-15 00:00:00

abstract：:Starting from thienobenzopyran HTS hit 1, co-crystallization, molecular modeling and metabolic analysis were used to design potent and metabolically stable inhibitors of PI3-kinase. Compound 15 demonstrated PI3K pathway suppression in a mouse MCF7 xenograft model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Staben ST,Siu M,Goldsmith R,Olivero AG,Do S,Burdick DJ,Heffron TP,Dotson J,Sutherlin DP,Zhu BY,Tsui V,Le H,Lee L,Lesnick J,Lewis C,Murray JM,Nonomiya J,Pang J,Prior WW,Salphati L,Rouge L,Sampath D,Sideris S,

更新日期：2011-07-01 00:00:00

abstract：:A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Soria-Arteche O,Hernández-Campos A,Yépez-Mulia L,Trejo-Soto PJ,Hernández-Luis F,Gres-Molina J,Maldonado LA,Castillo R

更新日期：2013-12-15 00:00:00

abstract：:Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identifica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fader LD,Landry S,Goulet S,Morin S,Kawai SH,Bousquet Y,Dion I,Hucke O,Goudreau N,Lemke CT,Rancourt J,Bonneau P,Titolo S,Amad M,Garneau M,Duan J,Mason S,Simoneau B

更新日期：2013-06-01 00:00:00

abstract：:A series of novel (un)substituted benzotriazolyl oxazolidinone derivatives has been synthesized and tested for in vitro antibacterial activities by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms, some of which are resistant to methicillin and vancomycin. C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dixit PP,Nair PS,Patil VJ,Jain S,Arora SK,Sinha N

更新日期：2005-06-15 00:00:00

abstract：:A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mareddy J,Nallapati SB,Anireddy J,Devi YP,Mangamoori LN,Kapavarapu R,Pal S

更新日期：2013-12-15 00:00:00

abstract：:A series of leinamycin derivatives were synthesized and evaluated for antitumor activity. Modifications at C-8 and C-9 positions revealed a broad structure-activity relationship in vitro and some derivatives showed potent antiproliferative activity against HeLa S3 cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kanda Y,Ashizawa T,Saitoh Y,Saito H,Gomi K,Okabe M

更新日期：1998-04-21 00:00:00

abstract：:The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gilbert EJ,Zhou G,Wong MK,Tong L,Shankar BB,Huang C,Kelly J,Lavey BJ,McCombie SW,Chen L,Rizvi R,Dong Y,Shu Y,Kozlowski JA,Shih NY,Hipkin RW,Gonsiorek W,Malikzay A,Lunn CA,Favreau L,Lundell DJ

更新日期：2010-01-15 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：:Talaromyces stipitatus ATCC 10500 possesses 17 non-reducing polyketide synthase (NR-PKS) genes. During the course of our functional analysis of PKS genes with a C-terminus methyltransferase domain from T. stipitatus, we expressed tspks2, tspks3 and tspks4 genes in the heterologous host Aspergillus oryzae, respectively...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto M,Wakana D,Ueda M,Kobayashi D,Goda Y,Fujii I

更新日期：2015-04-01 00:00:00

abstract：:In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 res...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohkubo M,Nishimura T,Honma T,Nishimura I,Ito S,Yoshinari T,Suda HA,Morishima H,Nishimura S

更新日期：1999-12-06 00:00:00

abstract：:Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker FF,Banik BK

更新日期：1998-10-20 00:00:00

abstract：:Hypoxia is a characteristic feature of solid tumors. Herein, we have developed novel hypoxia-sensitive probes (IM-ACs) for Raman spectroscopic analysis, consisting of nitroimidazole as a hypoxia-targeting unit and acetylene group as the signal-emitting unit. Among IM-ACs synthesized in this study, IM-AC possessing a d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurihara R,Ikemura Y,Tanabe K

更新日期：2016-10-15 00:00:00

abstract：:Several boronic acids were screened for their ability to bind to diols. 3-methoxycarbonyl-5-nitrophenyl boronic acid bound to both a catechol dye as well as fructose with a comparable affinity to that of an ortho-methylamino substituted boronic acid. This work suggests a greater role for appropriately functionalized e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mulla HR,Agard NJ,Basu A

更新日期：2004-01-05 00:00:00

abstract：:Chemoselective purification technologies have seen great success in biomolecule isolation, with a classic example being the genetically-encoded His tag utilized to enrich desired proteins from a crude lysate. We sought to translate this purification tactic into a powerful tool for the isolation of natural products and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trader DJ,Carlson EE

更新日期：2015-11-01 00:00:00

abstract：:We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harada K,Mizukami J,Watanabe T,Mori G,Ubukata M,Suwa K,Fukuda S,Negoro T,Sato M,Inaba T

更新日期：2019-02-01 00:00:00

abstract：:A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infecti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caporuscio F,Tafi A,González E,Manetti F,Esté JA,Botta M

更新日期：2009-11-01 00:00:00

abstract：:Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a nov...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xin Z,Peng H,Zhang A,Talreja T,Kumaravel G,Xu L,Rohde E,Jung MY,Shackett MN,Kocisko D,Chollate S,Dunah AW,Snodgrass-Belt PA,Arnold HM,Taveras AG,Rhodes KJ,Scannevin RH

更新日期：2011-12-15 00:00:00

abstract：:A new series of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridine compounds have been discovered as potent anaplastic lymphoma kinase (ALK) inhibitors. The 4-hydroxyphenyl in the 6-position of 1H-pyrazolo[3,4-b]pyridine were crucial and a fluorine atom substitution could give promising inhibitory activity. The IC50 of compound 9v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Pan P,Deng Z,Wang D,Wu Q,Xu L,Hou T,Cui S

更新日期：2019-04-01 00:00:00

abstract：:An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclospori...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scribner A,Houck D,Huang Z,Mosier S,Peel M,Scorneaux B

更新日期：2010-11-15 00:00:00

abstract：:We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu Q,Liu W,Ding J,Cai J,Duan W

更新日期：2002-05-20 00:00:00