Evaluation of new L-thiocitrulline derivatives as inhibitors of nitric oxide synthase.

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：:We report the discovery of N-((benzo[d][1,3]dioxol-5-yl)methyl)-6-phenylthieno[3,2-d]pyrimidin-4-amine (2a) as an apoptosis inducer using our proprietary cell- and caspase-based ASAP HTS assay, and SAR study of HTS hit 2a which led to the discovery of 4-anilino-N-methylthieno[3,2-d]pyrimidines and 4-anilino-N-methylth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kemnitzer W,Sirisoma N,May C,Tseng B,Drewe J,Cai SX

更新日期：2009-07-01 00:00:00

abstract：:Apparent kinetic constants k(cat) and K(m) were determined for tyrocidine thioesterase (TycC TE) using randomized peptide N-acetylcysteamine thioesters as substrate analogues. The enzyme has been found to be adequately active for the synthesis of positional-scanning libraries for novel antibiotic screening with reduce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xie G,Uttamchandani M,Chen GY,Bu X,Lin SS,Wong KM,Yan W,Yao SQ,Guo Z

更新日期：2002-03-25 00:00:00

abstract：:Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lange JH,van Stuivenberg HH,Veerman W,Wals HC,Stork B,Coolen HK,McCreary AC,Adolfs TJ,Kruse CG

更新日期：2005-11-01 00:00:00

abstract：:Functionalized 1,3-teraryls, synthesized through ring transformation of 6-aryl-3-carbomethoxy-4-methylthio-2H-pyran-2-one from arylketone have been screened for their hepatoprotective activity and of them have demonstrated significant protection in animal model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ram VJ,Goel A,Patnaik GK

更新日期：1998-03-03 00:00:00

abstract：:Alpha-keto ester and amides were found to be potent inhibitors of histone deacetylase. Nanomolar inhibitors against the isolated enzyme and sub-micromolar inhibitors of cellular proliferation were obtained. The alpha-keto amide 30 also exhibited significant anti-tumor effects in an in vivo tumor model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wada CK,Frey RR,Ji Z,Curtin ML,Garland RB,Holms JH,Li J,Pease LJ,Guo J,Glaser KB,Marcotte PA,Richardson PL,Murphy SS,Bouska JJ,Tapang P,Magoc TJ,Albert DH,Davidsen SK,Michaelides MR

更新日期：2003-10-06 00:00:00

abstract：:Small molecule mu agonists based on the 4-phenyl piperidine scaffold were designed and synthesized to further investigate the therapeutic potential of loperamide analogs. The resulting compounds show excellent agonistic activity towards the human mu receptor with interesting SAR trends within the series. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen Z,Davies E,Miller WS,Shan S,Valenzano KJ,Kyle DJ

更新日期：2004-11-01 00:00:00

abstract：:IRAK4 plays a critical role in the IL-1R and TLR signalling, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of permeable N-(1H-pyrazol-4-yl)carboxamides was developed by introducing lipophilic bicyclic cores in place o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim J,Altman MD,Baker J,Brubaker JD,Chen H,Chen Y,Kleinschek MA,Li C,Liu D,Maclean JK,Mulrooney EF,Presland J,Rakhilina L,Smith GF,Yang R

更新日期：2015-11-15 00:00:00

abstract：:Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring form...

journal_title：Bioorganic & medicinal chemistry letters

authors： Glunz PW,Cheng X,Cheney DL,Weigelt CA,Wei A,Luettgen JM,Wong PC,Wexler RR,Priestley ES

更新日期：2015-01-01 00:00:00

abstract：:Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Labeeuw O,Levoin N,Poupardin-Olivier O,Calmels T,Ligneau X,Berrebi-Bertrand I,Robert P,Lecomte JM,Schwartz JC,Capet M

更新日期：2011-09-15 00:00:00

abstract：:Chemical modifications are essential to improve metabolic stability and pharmacokinetic properties of siRNA to enable their systemic delivery. We investigated the effect of combing the phosphorothioate (PS) modification with metabolically stable phosphate analog (E)-5'-vinylphosphonate and GalNAc cluster conjugation o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prakash TP,Kinberger GA,Murray HM,Chappell A,Riney S,Graham MJ,Lima WF,Swayze EE,Seth PP

更新日期：2016-06-15 00:00:00

abstract：:The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and surviva...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yasuda D,Nakajima M,Yuasa A,Obata R,Takahashi K,Ohe T,Ichimura Y,Komatsu M,Yamamoto M,Imamura R,Kojima H,Okabe T,Nagano T,Mashino T

更新日期：2016-12-15 00:00:00

abstract：:Practical, asymmetric total syntheses of the title phospholipids from a readily available myo-inositol derivative as well as short chain and cross-linkable aminoether analogues are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Falck JR,Krishna UM,Capdevila JH

更新日期：2000-08-07 00:00:00

abstract：:Based on the molecular modelling studies, a rational modification of the lead molecule was made to develop highly potent compounds showing anti-cancer activity against human breast cancer cell lines MCF 7, MDA-MB-468 and T-47D. The most potent compounds have Log P and total polar surface area 4.4-5.4 and 59.8 Å, respe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaur M,Singh P

更新日期：2019-01-01 00:00:00

abstract：:The synthesis and anti-angiogenic activities of linomide and its analogues are reported. Three of the analogues are 3.3-69 times more potent than linomide at inhibiting blood vessel formation in the CAM angiogenesis assay. These compounds possessed considerable anti-proliferative activity against isolated HUVEC cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi J,Xiao Z,Ihnat MA,Kamat C,Pandit B,Hu Z,Li PK

更新日期：2003-03-24 00:00:00

abstract：:High throughput screening for β-lactamase inhibitors afforded biphenyl hits such as 1. Hit confirmation and X-ray soaking experiments with Pseudomonas Aeruginosa AmpC enzyme led to the identification of an aryl boronic acid-serine complex 4, which was formed from phenyl boronic acid 8 (an impurity in compound 1) and e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang SW,Pan J,Root Y,Scapin G,Xiao L,Su J

更新日期：2020-01-15 00:00:00

abstract：:The effects of PEGylation of glucose-dependent insulinotropic polypeptide (GIP) on potency and dipeptidyl peptidase IV (DPPIV) stability are reported. N-terminal modification of GIP(1-30) with 40 kDa polyethylene glycol (PEG) abrogates functional activity. In contrast, C-terminal PEGylation of GIP(1-30) maintains full...

journal_title：Bioorganic & medicinal chemistry letters

authors： Salhanick AI,Clairmont KB,Buckholz TM,Pellegrino CM,Ha S,Lumb KJ

更新日期：2005-09-15 00:00:00

abstract：:The use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. Lupeol was anchored to a solid support (Rink amide/Sieber Amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. The resulting polymer linked 3beta-O (resin-al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Srinivasan T,Srivastava GK,Pathak A,Batra S,Raj K,Singh K,Puri SK,Kundu B

更新日期：2002-10-21 00:00:00

abstract：:Analogues of the naturally occurring cyclic hydroxamate dealanylalahopcin, which is an inhibitor of procollagen prolyl-4-hydroxylase, were synthesised and shown to be inhibitors of the human hypoxia-inducible factor prolyl hydroxylases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schlemminger I,Mole DR,McNeill LA,Dhanda A,Hewitson KS,Tian YM,Ratcliffe PJ,Pugh CW,Schofield CJ

更新日期：2003-04-17 00:00:00

abstract：:Based on our earlier reported neuropeptide FF receptors antagonist (RF9), we carried out an extensive structural exploration of the N-terminus part of the amidated dipeptide Arg-Phe-NH(2) in order to establish a structure-activity relationships (SAR) study towards both NPFF receptor subtypes. This SAR led to the disco...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gealageas R,Schneider S,Humbert JP,Bertin I,Schmitt M,Laboureyras E,Dugave C,Mollereau C,Simonnet G,Bourguignon JJ,Simonin F,Bihel F

更新日期：2012-12-15 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H-L (1-5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1-5 and a known compound sinubras...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang CY,Ahmed AF,Su JH,Sung PJ,Hwang TL,Chiang PL,Dai CF,Liaw CC,Sheu JH

更新日期：2017-08-01 00:00:00

abstract：:The synthesis and biological evaluation of novel human A-FABP inhibitors based on the 6-(trifluoromethyl)pyrimidine-4(1H)-one scaffold is described. Two series of compounds, bearing either an amino or carbon substituent in the 2-position of the pyrimidine ring were investigated. Modification of substituents and chain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ringom R,Axen E,Uppenberg J,Lundbäck T,Rondahl L,Barf T

更新日期：2004-09-06 00:00:00

abstract：:Herein, we reported the synthesis of 16 novel steroidal thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides under solvent-free conditions using microwave irradiation. The yields obtained are in the range of 84-96% using microwave method and 46-62% using convention...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Shi Z,Liu M,Liu X

更新日期：2012-12-15 00:00:00

abstract：:The synthesis and biological activity of sordarin oxazepine derivatives are described. The key step features a regioselective oxidation of an unprotected triol followed by double reductive amination to afford the ring-closed products. The spectrum of antifungal activity for these novel derivatives includes coverage of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Serrano-Wu MH,St Laurent DR,Chen Y,Huang S,Lam KR,Matson JA,Mazzucco CE,Stickle TM,Tully TP,Wong HS,Vyas DM,Balasubramanian BN

更新日期：2002-10-07 00:00:00

abstract：:A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Acker BA,Jacobsen EJ,Rogers BN,Wishka DG,Reitz SC,Piotrowski DW,Myers JK,Wolfe ML,Groppi VE,Thornburgh BA,Tinholt PM,Walters RR,Olson BA,Fitzgerald L,Staton BA,Raub TJ,Krause M,Li KS,Hoffmann WE,Hajos M,Hurst RS,

更新日期：2008-06-15 00:00:00

abstract：:In a search of small molecules active against apoptosis-resistant cancer cells, a series of isatin-based heterocyclic compounds were synthesized and found to inhibit proliferation of cancer cell lines resistant to apoptosis. The synthesis of these compounds involved a condensation of commercially available, active met...

journal_title：Bioorganic & medicinal chemistry letters

authors： Evdokimov NM,Magedov IV,McBrayer D,Kornienko A

更新日期：2016-03-15 00:00:00

abstract：:A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2f inhibits TXA2 synthase with an IC50 value of 0.64 microM and the aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cimetière B,Dubuffet T,Landras C,Descombes JJ,Simonet S,Verbeuren TJ,Lavielle G

更新日期：1998-06-02 00:00:00

abstract：:A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bahekar SS,Shinde DB

更新日期：2004-04-05 00:00:00

abstract：:A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

更新日期：2001-06-18 00:00:00