Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa receptor antagonists.

abstract：:A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewis TA,Young MA,Arrington MP,Bayless L,Cai X,Collart P,Eckman JB,Ellis JL,Ene DG,Libertine L,Nicolas JM,Scannell RT,Wels BF,Wenberg K,Wypij DM

更新日期：2004-11-15 00:00:00

abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

更新日期：2009-06-15 00:00:00

abstract：:5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu CF,Battah S,Kong X,Reeder BJ,Hider RC,Zhou T

更新日期：2015-02-01 00:00:00

abstract：:The discovery and optimization of a new class of non-peptidyl, pyridazinone derived melanocortin subtype-4 receptor agonists is disclosed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ujjainwalla F,Warner D,Walsh TF,Wyvratt MJ,Zhou C,Yang L,Kalyani RN,MacNeil T,Van der Ploeg LH,Rosenblum CI,Tang R,Vongs A,Weinberg DH,Goulet MT

更新日期：2003-12-15 00:00:00

abstract：:Resveratrol (Rsv) is widely reported to possess anticarcinogenic properties in a plethora of cellular and animal models having limited toxicity toward normal cells. In the molecular level, Rsv can act as a suppressive agent for several impaired signaling pathways on cancer cells. However, Fukuhara and Miyata have show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andrade Volkart P,Benedetti Gassen R,Mühlen Nogueira B,Nery Porto B,Eduardo Vargas J,Arigony Souto A

更新日期：2017-08-01 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：:Seventy-two novel 1,3,4-oxadiazole thioether derivatives containing different flexible-chain moieties were designed and synthesized. The nematicidal activities of all the title compounds were evaluated, and some compounds showed excellent nematicidal activities against citrus nematodes. The compounds 15, 16, 18, 27, 4...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen J,Wei C,Wu S,Luo Y,Wu R,Hu D,Song B

更新日期：2020-04-15 00:00:00

abstract：:A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, (1)H NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Prelimina...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu YR,Luo JZ,Duan PP,Shao J,Zhao BX,Miao JY

更新日期：2012-11-15 00:00:00

abstract：:The design and synthesis of a novel series of non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) based on a pyrazole template is described. These compounds are active against wild type reverse transcriptase (RT) and retain activity against clinically important mutants. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mowbray CE,Burt C,Corbau R,Perros M,Tran I,Stupple PA,Webster R,Wood A

更新日期：2009-10-01 00:00:00

abstract：:'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gibbons S,Zloh M

更新日期：2010-07-15 00:00:00

abstract：:The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Raubo P,Andrews DM,McKelvie JC,Robb GR,Smith JM,Swarbrick ME,Waring MJ

更新日期：2015-08-15 00:00:00

abstract：:A series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2- and Nck-interacting kinase (TNIK) activity are described. These compounds were used as tools to test the importance of TNIK kinase activity in signaling and proliferation in Wnt-activated colorec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho KK,Parnell KM,Yuan Y,Xu Y,Kultgen SG,Hamblin S,Hendrickson TF,Luo B,Foulks JM,McCullar MV,Kanner SB

更新日期：2013-01-15 00:00:00

abstract：:The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this gener...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun W,Chu T

更新日期：2015-10-15 00:00:00

abstract：:Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1) benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deaton DN,Gao EN,Graham KP,Gross JW,Miller AB,Strelow JM

更新日期：2008-01-15 00:00:00

abstract：:Four N-Fmoc protected polyoxyethylene-based amino acid type linkers were designed and synthesized for peptide derivatization in solid phase. Three of them were obtained in a crystalline form. The crystallized linkers can be stored at 4 degrees C for 2 years without significant decomposition. Protocols for biotinylatio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song A,Wang X,Zhang J,Marík J,Lebrilla CB,Lam KS

更新日期：2004-01-05 00:00:00

abstract：:Methylation of the carbon atom C of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gulini U,Angeli P,Marucci G,Buccioni M,Giardinà D,Antolini L,Franchini S,Sorbi C,Brasili L

更新日期：2001-01-22 00:00:00

abstract：:Macrocarpins A (1), B (2), C (3) and D (4), four new nor-triterpenes, have been isolated from the roots of Maytenus macrocarpa. The structures were established by spectroscopic examinations. Natural compounds 1, 2, 4 and the acetyl derivative 1a are cytotoxic against four tumoral cell lines with IC50 values ranging be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chávez H,Rodríguez G,Estévez-Braun A,Ravelo AG,Estévez-Reyes R,González AG,Fdez-Puente JL,García-Grávalos D

更新日期：2000-04-17 00:00:00

abstract：:Ureas derived from two substituted 3-aminopyrrolidine subunits were prepared as constrained analogs of a linear lead compound and tested as antagonists of the MCH(1) receptor. The series was optimized for substitution and stereochemistry to generate a functional antagonist with a K(i) of 3.3 nM and IC(50) of 12 nM (GT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grey J,Dyck B,Rowbottom MW,Tamiya J,Vickers TD,Zhang M,Zhao L,Heise CE,Schwarz D,Saunders J,Goodfellow VS

更新日期：2005-02-15 00:00:00

abstract：:The human epidermal growth factor receptor (EGFR) family is known to be involved in cell signaling pathways. The extracellular domain of EGFR consists of four domains, of which domain II and domain IV are known to be involved in the dimerization process. Overexpression of these receptors is known to play a significant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naik H,Gauthier T,Singh S,Jois S

更新日期：2018-12-01 00:00:00

abstract：:The esterase, phosphatase, and sulfatase activities of carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I, II, and XIII with 4-nitrophenyl esters as substrates was investigated. These enzymes show esterase activity with 4-nitrophenyl acetate as substrate, with second order rate constants in the range of 753-7706M(-1)s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Scozzafava A,Parkkila S,Puccetti L,De Simone G,Supuran CT

更新日期：2008-04-01 00:00:00

abstract：:Chelerythrine, an isoquinoline alkaloid isolated from the herbaceous perennial Chelidonium majus, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A) with an IC50 value of 0.55 µM. Chelerythrine was a reversible competitive MAO-A inhibitor (Ki = 0.22 µM) with a pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baek SC,Ryu HW,Kang MG,Lee H,Park D,Cho ML,Oh SR,Kim H

更新日期：2018-08-01 00:00:00

abstract：:In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent eff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan X,Wang Z,Sudom A,Cardozo M,DeGraffenreid M,Di Y,Fan P,He X,Jaen JC,Labelle M,Liu J,Ma J,McMinn D,Miao S,Sun D,Tang L,Tu H,Ursu S,Walker N,Ye Q,Powers JP

更新日期：2010-12-01 00:00:00

abstract：:Mirror-image screening using d-proteins is a powerful approach to provide mirror-image structures of chiral natural products for drug screening. During the course of our screening study for novel MDM2-p53 interaction inhibitors, we identified that NPD6878 (R-(-)-apomorphine) inhibited both the native l-MDM2-l-p53 inte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishiba H,Noguchi T,Shu K,Ohno H,Honda K,Kondoh Y,Osada H,Fujii N,Oishi S

更新日期：2017-06-01 00:00:00

abstract：:In continuation of our efforts to find new antimicrobial compounds, series of fatty N-acyldiamines were prepared from fatty methyl esters and 1,2-ethylenediamine, 1,3-propanediamine or 1,4-butanediamine. The synthesized compounds were screened for their antibacterial activity against Gram-positive bacteria (Staphyloco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ferreira BDS,de Almeida AM,Nascimento TC,de Castro PP,Silva VL,Diniz CG,Le Hyaric M

更新日期：2014-10-01 00:00:00

abstract：:This paper documents a serious problem met during the testing of Gi protein-activating properties of a new series of synthetic compounds by measuring the induced binding of [(35)S]GTPgammaS to different subtypes of Gi protein. The problem arose from the strong affinity between [(35)S]GTPgammaS and the tested compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： Manetti D,Di Cesare Mannelli L,Dei S,Guandalini L,Martini E,Banchelli M,Ghelardini C

更新日期：2009-04-15 00:00:00

abstract：:We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fuchi N,Iura Y,Kaneko H,Nitta A,Suyama K,Ueda H,Yamaguchi S,Nishimura K,Fujii S,Sekiya Y,Yamada M,Takahashi T

更新日期：2012-07-01 00:00:00

abstract：:A new series of 2-(benzyloxy)benzamides are presented that are potent functional antagonists of TRPM8 and possess improved LipE and LE compared to the original lead. They were discovered through a series of compound libraries and we present a powerful visualization method for the chemical space explored with each libr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brown A,Ellis D,Favor DA,Kirkup T,Klute W,MacKenny M,McMurray G,Stennett A

更新日期：2013-11-15 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：:A new support for solid-phase combinatorial organic synthesis has been developed, which we term a regio-reactive resin (R(3)-resin). The resin is based on a unique hydroxyl-functionalized cross-linker readily synthesized in two steps starting from 4-hydroxybenzaldehyde. The cross-linker's ease of synthesis and high pu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dickerson TJ,Reed NN,Janda KD

更新日期：2001-06-18 00:00:00

abstract：:A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to tho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Simic M,Paunovic N,Boric I,Randjelovic J,Vojnovic S,Nikodinovic-Runic J,Pekmezovic M,Savic V

更新日期：2016-01-01 00:00:00