Potent 3-spiropiperidine growth hormone secretagogues.

abstract：:A virtual screening system based on one-class classification with molecular fingerprints as descriptors is developed and tested on a series of 1226 inhibitors and 209 noninhibitors of glycogen synthase kinase 3β (GSK-3β). The suggested system outperforms the ones based on pharmacophore hypothesis and molecular docking...

journal_title：Bioorganic & medicinal chemistry letters

authors： Karpov PV,Osolodkin DI,Baskin II,Palyulin VA,Zefirov NS

更新日期：2011-11-15 00:00:00

abstract：:A series of novel cyclic analogues of curcumin were synthesized and analyzed for in vitro cytostatic activity. Condensation of 2-acetylcycloalkanones with a variety of aromatic aldehydes resulted in the formation of 2-arylidene-6-(3-arylacryoyl)-cycloalkanone derivatives. A number of these analogues were found to have...

journal_title：Bioorganic & medicinal chemistry letters

authors： Youssef D,Nichols CE,Cameron TS,Balzarini J,De Clercq E,Jha A

更新日期：2007-10-15 00:00:00

abstract：:Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting ana...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park CH,Lee C,Yang JS,Joe BY,Chun K,Kim H,Kim HY,Kang JS,Lee JI,Kim MH,Han G

更新日期：2014-06-15 00:00:00

abstract：:Novel quinolone-macrocycle conjugates displayed submicromolar antibacterial activity against Escherichia coli and Staphylococcus aureus bacterial strains. An analogous open-chain structure was not active at 100 microM against the same pathogenic strains. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jefferson EA,Swayze EE,Osgood SA,Miyaji A,Risen LM,Blyn LB

更新日期：2003-05-19 00:00:00

abstract：:Structure-activity studies on benzamide 1 obtained from library screening led to the discovery of a novel series of potent and selective glycine transporter type-2 inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ho KK,Appell KC,Baldwin JJ,Bohnstedt AC,Dong G,Guo T,Horlick R,Islam KR,Kultgen SG,Masterson CM,McDonald E,McMillan K,Morphy JR,Rankovic Z,Sundaram H,Webb M

更新日期：2004-01-19 00:00:00

abstract：:In order to investigate the relationship between tyrosine phosphorylation of β-catenin and transcriptional activity of β-catenin in Hela and Bcap-37 cells, genistein (a tyrosine kinase inhibitor) was used to inhibit tyrosine phosphorylation in cells. Our results showed the total β-catenin protein levels were mainly eq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qian HY,Zhang DG,Wang HW,Pei DS,Zheng JN

更新日期：2014-06-01 00:00:00

abstract：:Benzalacetone synthase (BAS) and chalcone synthase (CHS) are plant-specific type III polyketide synthases (PKSs), sharing 70% amino acid sequence identity and highly homologous overall protein structures. BAS catalyzes the decarboxylative coupling of 4-coumaroyl-CoA with malonyl-CoA to produce the diketide benzalaceto...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shimokawa Y,Morita H,Abe I

更新日期：2010-09-01 00:00:00

abstract：:Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The cu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ellsworth BA,Meng W,Patel M,Girotra RN,Wu G,Sher PM,Hagan DL,Obermeier MT,Humphreys WG,Robertson JG,Wang A,Han S,Waldron TL,Morgan NN,Whaley JM,Washburn WN

更新日期：2008-09-01 00:00:00

abstract：:In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma H,Sanchez TW,Neamati N,Detorio M,Schinazi RF,Cheng X,Buolamwini JK

更新日期：2013-11-15 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：:Optimisation of affinity, chemical stability, metabolic stability and solubility led from a chemically labile HTS hit 1 to mGlu5 receptor antagonists (24-26) with high affinity for the allosteric MPEP binding site, improved microsomal metabolic stability and anxiolytic-like activity in vivo as assessed by the Vogel co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Büttelmann B,Peters JU,Ceccarelli S,Kolczewski S,Vieira E,Prinssen EP,Spooren W,Schuler F,Huwyler J,Porter RH,Jaeschke G

更新日期：2006-04-01 00:00:00

abstract：:A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee W,Ortwine DF,Bergeron P,Lau K,Lin L,Malek S,Nonomiya J,Pei Z,Robarge KD,Schmidt S,Sideris S,Lyssikatos JP

更新日期：2013-09-15 00:00:00

abstract：:The design and synthesis of a new series of c-Jun N-terminal kinase-3 (JNK3) inhibitors with selectivity against JNK1 are reported. The novel series of substituted 2'-anilino-4,4'-bipyridines were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of compound...

journal_title：Bioorganic & medicinal chemistry letters

authors： Swahn BM,Xue Y,Arzel E,Kallin E,Magnus A,Plobeck N,Viklund J

更新日期：2006-03-01 00:00:00

abstract：:Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian JF,Li PJ,Li XX,Sun PH,Gao H,Liu XZ,Huang P,Tang JS,Yao XS

更新日期：2016-03-01 00:00:00

abstract：:Structural hybridization of preclinically and clinically validated pharmacologically active molecules has emerged as a promising tool to develop new generations of safe and highly efficient drug candidates against various diseases including microbial infections, virus infections and cancer. Strategies of drug-drug com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sampath Kumar HM,Herrmann L,Tsogoeva SB

更新日期：2020-12-01 00:00:00

abstract：:Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kashyap M,Das D,Preet R,Mohapatra P,Satapathy SR,Siddharth S,Kundu CN,Guchhait SK

更新日期：2012-04-01 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of the metabolic syndrome. Especially a combination of PPARα and PPARγ agonistic activity seems worthwhile to be pursued. Herein we present the design and synthesis of a series of pirinixic acid derivatives as potent PPARα par...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lamers C,Dittrich M,Steri R,Proschak E,Schubert-Zsilavecz M

更新日期：2014-08-15 00:00:00

abstract：:Amino-1,2,5-trideoxy-2,5-imino-D-mannitol was fluorescently tagged by reaction with dansyl chloride at N-1 or by attachment of a dansyl amide bearing spacer to this centre. Compounds obtained are highly potent inhibitors of beta-glucosidase exhibiting Ki values in the single figure nanomolar range. The 1-N-dansyl subs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hermetter A,Scholze H,Stütz AE,Withers SG,Wrodnigg TM

更新日期：2001-05-21 00:00:00

abstract：:Novel 8-aryl and 8-aroyl substituted derivatives of 3-(dipropylamino)chroman are described. The compounds have been prepared by a palladium catalyzed reaction of iodoarenes and a stannylated derivative of [eta6-3-(dipropylamino)chroman]Cr(CO)3. Several of the compounds have high affinity for 5-HT1A receptors whereas t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldirola P,Chowdhury R,Unelius L,Mohell N,Hacksell U,Johansson AM

更新日期：1999-06-07 00:00:00

abstract：:A series of substituted biphenyl ethylene ether compounds has been designed to target the gp41N-trimer in order to inhibit formation of the six-helical bundle that represents the end state of gp41-mediated viral fusion. A size exclusion HPLC based helical bundle formation (HBF) assay was developed to evaluate in vitro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu B,Joseph RW,Dorsey BD,Schiksnis RA,Northrop K,Bukhtiyarova M,Springman EB

更新日期：2009-10-01 00:00:00

abstract：:A series of tripeptidic acylsulfonamide inhibitors of HCV NS3 protease were prepared that explored structure-activity relationships (SARs) at the P4 position, and their in vitro and in vivo properties were evaluated. Enhanced potency was observed in a series of P4 ureas; however, the PK profiles of these analogues wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Venables BL,Sin N,Wang AX,Sun LQ,Tu Y,Hernandez D,Sheaffer A,Lee M,Dunaj C,Zhai G,Barry D,Friborg J,Yu F,Knipe J,Sandquist J,Falk P,Parker D,Good AC,Rajamani R,McPhee F,Meanwell NA,Scola PM

更新日期：2018-06-01 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：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

更新日期：2009-04-15 00:00:00

abstract：:Utilizing a combination of high-throughput and multi-step synthesis, SAR in a novel series of M(1) acetylcholine receptor antagonists was rapidly established. The efforts led to the discovery the highly potent M(1) antagonists 6 (VU0431263), and 8f (VU0433670). Functional Schild analysis and radioligand displacement e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Poslusney MS,Sevel C,Utley TJ,Bridges TM,Morrison RD,Kett NR,Sheffler DJ,Niswender CM,Daniels JS,Conn PJ,Lindsley CW,Wood MR

更新日期：2012-11-15 00:00:00

abstract：:JNK2 and p38alpha are closely related mitogen-activated protein kinases that regulate various cellular activities and are considered drug targets for inflammatory diseases. We have determined the X-ray crystal structure of the clinical phase II p38alpha inhibitor BIRB796 bound to its off-target JNK2. This shows for th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuglstatter A,Ghate M,Tsing S,Villaseñor AG,Shaw D,Barnett JW,Browner MF

更新日期：2010-09-01 00:00:00

abstract：:The synthesis and receptor binding of novel adenosine receptor antagonists is described. We found that non-xanthine 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives may have high affinity and substantial selectivity for the adenosine A(1) receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： van Tilburg EW,van der Klein PA,de Groote M,Beukers MW,IJzerman AP

更新日期：2001-08-06 00:00:00

abstract：:A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 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：:The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the tw...

journal_title：Bioorganic & medicinal chemistry letters

authors： Menchise V,De Simone G,Di Fiore A,Scozzafava A,Supuran CT

更新日期：2006-12-15 00:00:00

abstract：:The synthesis and SAR of benzylamine side chain analogs of the NK-1 receptor antagonist CP-99,994 are described. The 5-trifluoromethoxy analog, CP-122,721, shows superior in vivo blockade of NK-1 receptor mediated responses. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rosen TJ,Coffman KJ,McLean S,Crawford RT,Bryce DK,Gohda Y,Tsuchiya M,Nagahisa A,Nakane M,Lowe JA 3rd

更新日期：1998-02-03 00:00:00