SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors.

abstract：:A unique bicyclic peptide, moroidin (1), from the seeds of Celosia argentea (Amaranthaceae) strongly inhibited the polymerization of tubulin. The stereostructure of moroidin (1) was reinvestigated by spectroscopic data, chemical degradation, and molecular dynamics simulation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita H,Shimbo K,Shigemori H,Kobayashi J

更新日期：2000-03-06 00:00:00

abstract：:A facile synthesis of 7-epi-(-)-goniofufurone as well as the first synthesis of (-)-crassalactone C was achieved starting from D-xylose. A comparison of their in vitro antitumour activities with those observed for the corresponding naturally occurring enantiomers was provided. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Popsavin V,Benedeković G,Srećo B,Popsavin M,Francuz J,Kojić V,Bogdanović G

更新日期：2008-10-01 00:00:00

abstract：:A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

更新日期：1998-06-16 00:00:00

abstract：:Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC...

journal_title：Bioorganic & medicinal chemistry letters

authors： Williams IS,Joshi P,Gatchie L,Sharma M,Satti NK,Vishwakarma RA,Chaudhuri B,Bharate SB

更新日期：2017-08-15 00:00:00

abstract：:A series of methoxycarbonyl group modified nidulalin A analogs were synthesized to improve stability against esterases. The amide derivatives showed cytotoxic activity along with inhibitory activity against DNA topoisomerase II. Among the analogs, amide 9a exhibited antitumor activity in Colon 26 murine tumor model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato S,Suga Y,Yoshimura T,Nakagawa R,Tsuji T,Umemura K,Andoh T

更新日期：1999-09-20 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 series of 1-(quinoliloxypropyl)-4-aryl-piperazines has been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypic behaviour in mice. The 8-hydroxyquinoline ether derivative 14 has emerged as an important lead compound showing a potenti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bali A,Malhotra S,Dhir H,Kumar A,Sharma A

更新日期：2009-06-01 00:00:00

abstract：:A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerizat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li PK,Xiao Z,Hu Z,Pandit B,Sun Y,Sackett DL,Werbovetz K,Lewis A,Johnsamuel J

更新日期：2005-12-15 00:00:00

abstract：:Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SK,Reddy PG,Rao KS,Lohray BB,Misra P,Rajjak SA,Rao YK,Venkateswarlu A

更新日期：2004-01-19 00:00:00

abstract：:3-O-tert-Butyldimethylsilyl-17 alpha-(6-mesyloxyhexynyl)estradiol was converted to the azide in 60-70% yield with NaN3/DMPU, then reduced to the corresponding amine (> 95% yield). Acylation with the N-hydroxysuccinimide esters of biotin, 5-carboxyfluorescein and 10-(3-sulfopropyl)-N-tosyl-N-(3- carboxypropyl)acridiniu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adamczyk M,Chen YY,Moore JA,Mattingly PG

更新日期：1998-06-02 00:00:00

abstract：:Bacterial resistance is rapidly growing, necessitating the need to discover new agents. Novel bacterial topoisomerase inhibitors (NBTIs) are new class of broad-spectrum antibacterial agents targeting bacterial DNA gyrase and topoisomerase IV. This class of inhibitors binds to an alternative binding site relative to fl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh SB,Kaelin DE,Wu J,Miesel L,Tan CM,Meinke PT,Olsen DB,Lagrutta A,Wei C,Peng X,Wang X,Fukuda H,Kishii R,Takei M,Shibata T,Ohata K,Takano H,Kurasaki H,Takeuchi T,Nishimura A,Fukuda Y

更新日期：2015-06-01 00:00:00

abstract：:Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoyama Y,Konoike T,Kanda A,Naya N,Nakajima M

更新日期：2001-07-09 00:00:00

abstract：:The search for novel, potent Kv1.5 blockers based on an anthranilic amide scaffold employing a pharmacophore-based virtual screening approach is described. The synthesis and structure-activity relationships (SAR) with respect to inhibition of the Kv1.5 channel are discussed. The most potent compounds display sub-micro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peukert S,Brendel J,Pirard B,Strübing C,Kleemann HW,Böhme T,Hemmerle H

更新日期：2004-06-07 00:00:00

abstract：:Two novel α-linked sialyltrisaccharide imidazolium-type probes (ITags) based on the structures of biologically relevant 6'-sialyllactosamine and 3'-sialyllactosamine were efficiently and stereoselectively prepared using a chemo-enzymatic approach. The apparent kinetic parameters for the enzyme catalyzed transformation...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sittel I,Galan MC

更新日期：2015-10-01 00:00:00

abstract：:A series of alpha,beta-unsaturated-gamma-lactone-free nitrogen-containing heterocyclic analogues of solamin, a natural mono-THF acetogenin, have been synthesized and their cytotoxicity was investigated against 39 tumor cell lines. One of them, 1-methylpyrazol-5-yl derivative, showed selective increase of cytotoxicity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kojima N,Fushimi T,Maezaki N,Tanaka T,Yamori T

更新日期：2008-03-01 00:00:00

abstract：:A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)-antagonists. The most potent compounds were found in the class of (piperazine-1-yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau JF,Jeppesen CB,Rimvall K,Hohlweg R

更新日期：2006-10-15 00:00:00

abstract：:Structure-activity studies on the oxytocin antagonist 1 (L-371,257) have identified a new series of high affinity, receptor-selective OT antagonists in which the N-acetyl-4-piperidinyl ether terminus in 1 has been replaced with a 1-(aryl)ethoxy group. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuo MS,Bock MG,Freidinger RM,Guidotti MT,Lis EV,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Williams PD,Woyden CJ

更新日期：1998-11-03 00:00:00

abstract：:A novel fluorescein-based fluorescent probe for nitroxyl (HNO) based on the reductive Staudinger ligation of HNO with an aromatic phosphine was prepared. This probe reacts with HNO derived from Angeli's salt and 4-bromo Piloty's acid under physiological conditions without interference by other biological redox species...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miao Z,Reisz JA,Mitroka SM,Pan J,Xian M,King SB

更新日期：2015-01-01 00:00:00

abstract：:A significant increase in plasma glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase was observed 6 h after intraperitoneal administration of D-galactosamine (D-Galn). Three hours after administration of D-Galn, the vitamin C concentration in the liver decreased significantly compared to that in a ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishioka H,Kishioka T,Iida C,Fujii K,Ichi I,Kojo S

更新日期：2006-06-01 00:00:00

abstract：:Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antiba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vatmurge NS,Hazra BG,Pore VS,Shirazi F,Chavan PS,Deshpande MV

更新日期：2008-03-15 00:00:00

abstract：:GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2012-02-15 00:00:00

abstract：:Neuropeptide Y is one of the most potent appetite stimulating hormones known. Novel thiophene and benzo[b]thiophene hydrazide derivatives were synthetized and evaluated biologically as NPY Y(1) and Y(5) receptor subtype antagonists. They were found to have nanomolar binding affinities for human NPY Y(5) receptor, obta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Galiano S,Erviti O,Pérez S,Moreno A,Juanenea L,Aldana I,Monge A

更新日期：2004-02-09 00:00:00

abstract：:Several unnatural derivatives of narciclasine were prepared in which the C-7 carbon was replaced with nitrogen. The 7-aza derivative and its N-oxide were prepared by the coupling of iodopicolinic acid with a conduramine unit derived chemoenzymatically from bromobenzene. Intramolecular Heck reaction was used to constru...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Reisenauer MR,Rogelj S,Hudlicky T

更新日期：2014-09-01 00:00:00

abstract：:Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang W,Li J,Zhang W,Zhou Y,Xie C,Luo Y,Li Y,Wang J,Li J,Lu W

更新日期：2006-04-01 00:00:00

abstract：:The design, synthesis, and IMPDH inhibitory activity of a series of phosphonic acid-containing analogues of mycophenolic acid are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watkins WJ,Chen JM,Cho A,Chong L,Collins N,Fardis M,Huang W,Hung M,Kirschberg T,Lee WA,Liu X,Thomas W,Xu J,Zeynalzadegan A,Zhang J

更新日期：2006-07-01 00:00:00

abstract：:The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang N,Wang QH,Wang WQ,Wang J,Li F,Tan SP,Cheng MS

更新日期：2012-01-01 00:00:00

abstract：:Novel arylthiomethyl morpholines are potent selective norepinephrine reuptake inhibitors (NERIs) and dual serotonin/norepinephrine reuptake inhibitors (SRI/NERIs). The target compounds were prepared using a stereochemically versatile synthesis featuring an aldol condensation as the key step. One enantiomer of the 2-me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boot J,Cases M,Clark BP,Findlay J,Gallagher PT,Hayhurst L,Man T,Montalbetti C,Rathmell RE,Rudyk H,Walter MW,Whatton M,Wood V

更新日期：2005-02-01 00:00:00

abstract：:We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes SJ,Millan DS,Kilty IC,Lewthwaite RA,Mathias JP,O'Reilly MA,Pannifer A,Phelan A,Stühmeier F,Baldock DA,Brown DG

更新日期：2011-11-01 00:00:00

abstract：:The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Siu M,Pastor R,Liu W,Barrett K,Berry M,Blair WS,Chang C,Chen JZ,Eigenbrot C,Ghilardi N,Gibbons P,He H,Hurley CA,Kenny JR,Cyrus Khojasteh S,Le H,Lee L,Lyssikatos JP,Magnuson S,Pulk R,Tsui V,Ultsch M,Xiao Y,Zh

更新日期：2013-09-01 00:00:00

abstract：:A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hattori K,Kohchi Y,Oikawa N,Suda H,Ura M,Ishikawa T,Miwa M,Endoh M,Eda H,Tanimura H,Kawashima A,Horii I,Ishitsuka H,Shimma N

更新日期：2003-03-10 00:00:00