Discovery of core-structurally novel PTP1B inhibitors with specific selectivity containing oxindole-fused spirotetrahydrofurochroman by one-pot reaction.

abstract：:The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Uchiyama M,Ito H,Takahashi H,Yoshizumi T,Sakoh H,Nagatomi Y,Asai M,Miyazoe H,Tsujita T,Hirayama M,Ozaki S,Tani T,Ishii Y,Ohta H,Okamoto O

更新日期：2009-07-01 00:00:00

abstract：:Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-meth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andersen VL,Hansen HD,Herth MM,Dyssegaard A,Knudsen GM,Kristensen JL

更新日期：2015-03-01 00:00:00

abstract：:A series of 2-phenylpyrimidine coumarin derivatives with potential telomerase-inhibiting activity was designed and synthesized. All of the compounds were screened for antiproliferative activity against CNE2, KB, and Cal27 cell lines in vitro. The results showed that most of the derivatives had a favorable effect on re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv N,Sun M,Liu C,Li J

更新日期：2017-10-01 00:00:00

abstract：:A series of pyrazole and triazole derivatives containing 5-phenyl-2-furan functionality were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. The bioassay results showed that title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Meanwh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li YS,Tian H,Zhao DS,Hu DK,Liu XY,Jin HW,Song GP,Cui ZN

更新日期：2016-08-01 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：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-04-07 00:00:00

abstract：:To continue our study of 2-morpholino-benzoxazine based compounds, which show useful activity against PI3K family enzymes or antiplatelet activity, we designed and synthesized a series of linear 6.7-fused, 5,6-angular fused and 7,8-angular fused-aryl-morpholino-naphth-oxazines. The compounds were prepared from substit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morrison R,Zheng Z,Jennings IG,Thompson PE,Al-Rawi JMA

更新日期：2016-11-15 00:00:00

abstract：:Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeffrey SC,Nguyen MT,Andreyka JB,Meyer DL,Doronina SO,Senter PD

更新日期：2006-01-15 00:00:00

abstract：:A new series of potential inhibitors of DNA topoisomerase II were synthesized from facile materials (aromatic aldehydes, Meldrum's acid and 2-hydroxynaphthalene-1,4-dione) under microwave irradiation. The method provides a valuable tool in designing new and more potent cytotoxic analogues. This procedure is advantageo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei P,Zhang X,Tu S,Yan S,Ying H,Ouyang P

更新日期：2009-02-01 00:00:00

abstract：:A novel cys-annexin A5 with a single cysteine-residue at its concave side has been developed by site-directed mutagenesis to allow conjugation through thiol-chemistry without affecting its apoptotic cell binding properties and was derivatized with HYNIC in a 1:1 stoichiometry. Similar to that of the 1st generation 99m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fonge H,de Saint Hubert M,Vunckx K,Rattat D,Nuyts J,Bormans G,Ni Y,Reutelingsperger C,Verbruggen A

更新日期：2008-07-01 00:00:00

abstract：:A novel class of phenylacetic acid regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore attached to its C-2, C-3 or C-4 position was designed for evaluation as anti-inflammatory (AI) agents. A number of compounds exhibited a combination of potent in vitro cyclooxygenase-2 (COX-2) and 5-lipox...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu G,Chowdhury MA,Abdellatif KR,Dong Y,Praveen Rao PN,Das D,Velázquez CA,Suresh MR,Knaus EE

更新日期：2010-02-01 00:00:00

abstract：:Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZD,Jensen PR,Fenical W

更新日期：1999-07-19 00:00:00

abstract：:A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhance...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leese MP,Newman SP,Purohit A,Reed MJ,Potter BV

更新日期：2004-06-21 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：:A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3-triazol-4-yl-/5-yl moieties were synthesized by employing click chemistry. The new sulfocoumarins incorporated cycloalkyl, tert-butyl and substituted aryl moieties at the triazole ring, and were investigated for the inhibition of four human (h) c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grandane A,Tanc M,Zalubovskis R,Supuran CT

更新日期：2014-03-01 00:00:00

abstract：:Current techniques for the identification of DNA adduct-inducing and DNA interstrand crosslinking agents include electrophoretic crosslinking assays, electrophoretic gel shift assays, DNA and RNA stop assays, mass spectrometry-based methods and 32P-post-labelling. While these assays provide considerable insight into t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Medan J,Sleebs BE,Lackovic K,Watson KG,Evison BJ,Phillips DR,Cutts SM

更新日期：2021-01-21 00:00:00

abstract：:We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SB,Park YI,Dong MS,Gong YD

更新日期：2010-10-01 00:00:00

abstract：:Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Cule...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bandyopadhyay P,Sathe M,Tikar SN,Yadav R,Sharma P,Kumar A,Kaushik MP

更新日期：2014-07-01 00:00:00

abstract：:A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park B,Nam JH,Kim JH,Kim HJ,Onnis V,Balboni G,Lee KT,Park JH,Catto M,Carotti A,Lee JY

更新日期：2017-03-01 00:00:00

abstract：:Pyrazolopyrimidines were discovered as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. In addition to its intrinsic activity, compound 9n significantly enhances nicotinic acid binding to the receptor, thereby potentiating the functional efficacy of nicotinic acid. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen HC,Taggart AK,Wilsie LC,Waters MG,Hammond ML,Tata JR,Colletti SL

更新日期：2008-09-15 00:00:00

abstract：:Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D(2) (2), butyl lucidenate E(2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mas...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tung NT,Cuong TD,Hung TM,Lee JH,Woo MH,Choi JS,Kim J,Ryu SH,Min BS

更新日期：2013-03-01 00:00:00

abstract：:A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yadav DK,Gautam AK,Kureel J,Srivastava K,Sahai M,Singh D,Chattopadhyay N,Maurya R

更新日期：2011-01-15 00:00:00

abstract：:Bacterial quorum sensing is mediated by autoinducers, small signaling molecules generated by bacteria. It has been proposed that the LuxS enzyme converts S-ribosyl-L-homocysteine to 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2 (AI-2). We report here a chemical synthesis of S-ribosyl-L-homocysteine an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao G,Wan W,Mansouri S,Alfaro JF,Bassler BL,Cornell KA,Zhou ZS

更新日期：2003-11-17 00:00:00

abstract：:A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antoszczak M,Maj E,Stefańska J,Wietrzyk J,Janczak J,Brzezinski B,Huczyński A

更新日期：2014-04-01 00:00:00

abstract：:The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fournier PA,Arbour M,Cauchon E,Chen A,Chefson A,Ducharme Y,Falgueyret JP,Gagné S,Grimm E,Han Y,Houle R,Lacombe P,Lévesque JF,MacDonald D,Mackay B,McKay D,Percival MD,Ramtohul Y,St-Jacques R,Toulmond S

更新日期：2012-04-15 00:00:00

abstract：:A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Z,Min Q,Huang H,Liu R,Zhu Y,Zhu Q

更新日期：2018-05-15 00:00:00

abstract：:A novel series of amide derivatives of lomefloxacin were synthesized and evaluated for their topoisomerase I and II inhibitory activity as well as cytotoxicity against a panel of five human cancer cell lines. Of the compounds prepared compounds 9d and 9g exhibited strong inhibition against topoisomerase II at 100μM. I...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou Y,Xu X,Sun Y,Wang H,Sun H,You Q

更新日期：2013-05-15 00:00:00

abstract：:We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selective JAK2 inhibitors. High throughput screening of our in-house compound library led to the identification of hit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors. Adva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Forsyth T,Kearney PC,Kim BG,Johnson HW,Aay N,Arcalas A,Brown DS,Chan V,Chen J,Du H,Epshteyn S,Galan AA,Huynh TP,Ibrahim MA,Kane B,Koltun ES,Mann G,Meyr LE,Lee MS,Lewis GL,Noguchi RT,Pack M,Ridgway BH,Shi X,

更新日期：2012-12-15 00:00:00

abstract：:An artificial neural network based approach using Atomic5 fragmental descriptors has been developed to predict the octanol-water partition coefficient (logP). We used a pre-selected set of organic molecules from PHYSPROP database as training and test sets for a feedforward neural network. Results demonstrate the super...

journal_title：Bioorganic & medicinal chemistry letters

authors： Molnár L,Keseru GM,Papp A,Gulyás Z,Darvas F

更新日期：2004-02-23 00:00:00

abstract：:An α-carbonic anhydrase (CA, EC 4.2.1.1) isolated from the living fossil sponge Astrosclera willeyana, Astrosclerin, was investigated for its inhibition profile with simple inorganic anions, complex anions and other small molecules known to interact with these zinc enzymes. Astrosclerin is a catalytically highly effic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohradanova A,Vullo D,Pastorekova S,Pastorek J,Jackson DJ,Wörheide G,Supuran CT

更新日期：2012-02-01 00:00:00