4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part I: synthesis and pharmacological evaluation.

abstract：:Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimizati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu L,Lu K,Desai M,Packiarajan M,Joshi A,Marzabadi MR,Jubian V,Andersen K,Chandrasena G,Boyle NJ,Walker MW

更新日期：2011-09-15 00:00:00

abstract：:A series of 1H-1,2,3-triazole/acylhydrazide-tethered tetrahydro-β-carboline-4-aminoquinoline conjugates was synthesized with an aim to study their anti-plasmodial structure-activity relationship. The presence of 1H-1,2,3-triazole-core along with a flexible alkyl chain length on aminoquinoline core has favourable influ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma B,Kaur S,Legac J,Rosenthal PJ,Kumar V

更新日期：2020-01-15 00:00:00

abstract：:Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimida...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zawawi NK,Rajput SA,Taha M,Ahmat N,Ismail NH,Abdullah N,Khan KM,Choudhary MI

更新日期：2015-10-15 00:00:00

abstract：:We have synthesized a series of 4H,6H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleoside and their anti-vesicular stomatitis virus (VSV) activities in Wish cell were also investigated in vitro. It was found that most compounds showed obvious anti-VSV activities and compound 9 with ribofuranoside improved ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu X,Wang J,Yao Q

更新日期：2015-01-15 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：:A set of trimeric and tetrameric derivatives 6-11 of the influenza virus neuraminidase inhibitor zanamivir 1 have been synthesized by coupling a common monomeric zanamivir derivative 3 onto various multimeric carboxylic acid core groups. These discrete multimeric compounds are all significantly more antiviral than zan...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watson KG,Cameron R,Fenton RJ,Gower D,Hamilton S,Jin B,Krippner GY,Luttick A,McConnell D,MacDonald SJ,Mason AM,Nguyen V,Tucker SP,Wu WY

更新日期：2004-03-22 00:00:00

abstract：:The structural modification of the benzylic ether region of oxime 1 has resulted in the identification of several novel aryl amides as selective or dual NK(1)/NK(2) antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shih NY,Albanese M,Anthes JC,Carruthers NI,Grice CA,Lin L,Mangiaracina P,Reichard GA,Schwerdt J,Seidl V,Wong SC,Piwinski JJ

更新日期：2002-01-21 00:00:00

abstract：:Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki K,Shimizu T,Nakata T

更新日期：1998-08-18 00:00:00

abstract：:An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sleeman MC,MacKinnon CH,Hewitson KS,Schofield CJ

更新日期：2002-02-25 00:00:00

abstract：:Inhibition of the newest isoform of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), CA XV, with a series of phenols was investigated. Murine CA XV showed an inhibition profile by phenols distinct of those of the cytosolic human isoforms CA I and II. Phenol and some of its 2-, 3-, and 4-substituted derivatives i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Hilvo M,Scozzafava A,Parkkila S,Supuran CT

更新日期：2008-06-15 00:00:00

abstract：:The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dreef-Tromp CM,Basten JE,Broekhoven MA,van Dinther TG,Petitou M,van Boeckel CA

更新日期：1998-08-18 00:00:00

abstract：:The structure activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1'-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee J,Kang SU,Kim SY,Kim SE,Kang MK,Jo YJ,Kim S

更新日期：2001-04-23 00:00:00

abstract：:A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nantermet PG,Barrow JC,Selnick HG,Homnick CF,Freidinger RM,Chang RS,O'Malley SS,Reiss DR,Broten TP,Ransom RW,Pettibone DJ,Olah T,Forray C

更新日期：2000-08-07 00:00:00

abstract：:Based on a screening lead from a yeast-based assay to identify Src family kinase inhibitors, a series of 4-anilino-7-thienyl-3-quinolinecarbonitriles was prepared. When the thiophene ring was substituted with a water-solubilizing group in a 2,5-, 3,5- or 2,4-pattern, potent inhibition of Src kinase activity was observ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boschelli DH,Wang DY,Ye F,Yamashita A,Zhang N,Powell D,Weber J,Boschelli F

更新日期：2002-08-05 00:00:00

abstract：:Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conj...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Y,Zhu L,Ma Y,Niu G,Chen X

更新日期：2011-02-15 00:00:00

abstract：:In order to elucidate the essential structural features for KDR kinase inhibitors, three-dimensional pharmacophore hypotheses were built on the basis of a set of known KDR kinase inhibitors selected from the literature with CATALYST program. Several methods tools used in validation of pharmacophore hypothsis were pres...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu H,Wang Z,Zhang L,Zhang J,Huang Q

更新日期：2007-04-15 00:00:00

abstract：:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DS,Pezzuto JM,Pisha E

更新日期：1998-07-07 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

abstract：:A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dai L,Zang C,Tian S,Liu W,Tan S,Cai Z,Ni T,An M,Li R,Gao Y,Zhang D,Jiang Y

更新日期：2015-01-01 00:00:00

abstract：:A new family of bioactive bromotyrosine derivatives, termed mololipids, was recently isolated from a Hawaiian sponge, but could not be resolved into individual components by chromatography. To complete their structural characterization and better understand structure-activity relationships, the first pure samples of d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schoenfeld RC,Lumb JP,Fantini J,Ganem B

更新日期：2000-12-04 00:00:00

abstract：:An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilson KJ,Witter DJ,Grimm JB,Siliphaivanh P,Otte KM,Kral AM,Fleming JC,Harsch A,Hamill JE,Cruz JC,Chenard M,Szewczak AA,Middleton RE,Hughes BL,Dahlberg WK,Secrist JP,Miller TA

更新日期：2008-03-15 00:00:00

abstract：:Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaiya T,Aoyama S,Kohda K

更新日期：1999-04-05 00:00:00

abstract：:In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric alpha7 channels, we carried out the virtual screening of a test set of potential nicotinic ligands, and adopted a simplified MM-PBSA approach to estimate their relative binding free energy values. By means ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grazioso G,Pomè DY,Matera C,Frigerio F,Pucci L,Gotti C,Dallanoce C,De Amici M

更新日期：2009-11-15 00:00:00

abstract：:A series of sesquiterpene compounds possessing both eudesmane and eremophilane skeletons were tested as gastric cytoprotective agents on male Wistar rats. The presence of an alpha,beta-unsaturated aldehyde on the C-7 side chain together with a hydroxyl group at C-4 is the requirement for the observed antiulcerogenic a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donadel OJ,Guerreiro E,María AO,Wendel G,Enriz RD,Giordano OS,Tonn CE

更新日期：2005-08-01 00:00:00

abstract：:Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of thi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith G,Ruhland T,Mikkelsen G,Andersen K,Christoffersen CT,Alifrangis LH,Mørk A,Wren SP,Harris N,Wyman BM,Brandt G

更新日期：2004-08-02 00:00:00

abstract：:Starting from a weak omeprazole screening hit, replacement of the pyridine with a 1,3-benzodioxole moiety, modification of the thioether linkage, and substitution of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3 agonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carlton DL,Collin-Smith LJ,Daniels AJ,Deaton DN,Goetz AS,Laudeman CP,Littleton TR,Musso DL,Morgan RJ,Szewczyk JR,Zhang C

更新日期：2008-10-15 00:00:00

abstract：:Backbone-modified DNA analogs were synthesized in good yields by the boranophosphotriester method on a solid support. The oligodeoxyribonucleoside boranophosphates, protected with 2-(azidomethyl)benzoyl groups for nucleobases, were converted into DNA and its backbone-modified analogs via the corresponding H-phosphonat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawanaka T,Shimizu M,Shintani N,Wada T

更新日期：2008-07-01 00:00:00

abstract：:Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Horikawa M,Shigeri Y,Yumoto N,Yoshikawa S,Nakajima T,Ohfune Y

更新日期：1998-08-04 00:00:00

abstract：:Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and P...

journal_title：Bioorganic & medicinal chemistry letters

authors： Parmenon C,Guillard J,Caignard DH,Hennuyer N,Staels B,Audinot-Bouchez V,Boutin JA,Dacquet C,Ktorza A,Viaud-Massuard MC

更新日期：2009-05-15 00:00:00

abstract：:Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii K,Morita D,Onoda K,Kuroda T,Miyachi H

更新日期：2016-05-01 00:00:00