Dihydroquinolines as novel n-NOS inhibitors.

abstract：:Two new cyclic octapeptides, mariannamides A (1) and B (2), have been isolated from Mariannaea elegans NBRC102301, a Pinus densiflora-derived filamentous fungus. Their structures were elucidated to be cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l-Val1-l-Ile2) and cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishiuchi K,Hirose D,Kondo T,Watanabe K,Terasaka K,Makino T

更新日期：2020-02-15 00:00:00

abstract：:Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier N,Clarke B,Cutler L,Demont E,Dingwall C,Dunsdon R,Hawkins J,Howes C,Hubbard J,Hussain I,Maile G,Matico R,Mosley J,Naylor A,O'Brien A,Redshaw S,Rowland P,Soleil V,Smith KJ,Sweitzer S,Theobald P,Vesey D,

更新日期：2009-07-01 00:00:00

abstract：:Potent and selective dipeptidyl boronic acid proteasome inhibitors are described. As compared to peptidyl aldehyde compounds, boronic acids in this series display dramatically enhanced potency. Compounds such as 15 are promising new therapeutics for treatment of cancer and inflammatory diseases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Adams J,Behnke M,Chen S,Cruickshank AA,Dick LR,Grenier L,Klunder JM,Ma YT,Plamondon L,Stein RL

更新日期：1998-02-17 00:00:00

abstract：:Four new lignans, strebluslignanol F (1), (7'R,8'S,7″R,8″S)-erythro-strebluslignanol G (2), isomagnaldehyde (3) and isostrebluslignanaldehyde (4), along with 12 known lignans (5-16) were isolated from the ethyl acetate-soluble part of MeOH extract of the root of Streblus asper. Their structures were elucidated through...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li J,Meng AP,Guan XL,Li J,Wu Q,Deng SP,Su XJ,Yang RY

更新日期：2013-04-01 00:00:00

abstract：:A series of isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones were synthesized as potent inhibitors against Pim-1 and Pim-2 kinases. The structure-activity-relationship studies started from a high-throughput screening hit and was guided by molecular modeling of inhibitors in the active site of Pim-1 kinase. Installing a hyd...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tong Y,Stewart KD,Thomas S,Przytulinska M,Johnson EF,Klinghofer V,Leverson J,McCall O,Soni NB,Luo Y,Lin NH,Sowin TJ,Giranda VL,Penning TD

更新日期：2008-10-01 00:00:00

abstract：:Previously described SAR of benzimidazole-based non-nucleoside finger loop (Thumb Pocket I) inhibitors of HCV NS5B polymerase was expanded. Prospecting studies using parallel synthesis techniques allowed the rapid identification of novel cinnamic acid right-hand sides that provide renewed opportunities for further opt...

journal_title：Bioorganic & medicinal chemistry letters

authors： Goulet S,Poupart MA,Gillard J,Poirier M,Kukolj G,Beaulieu PL

更新日期：2010-01-01 00:00:00

abstract：:Cyclic phosphatidic acid (CPA) is a naturally occurring analog of lysophosphatidic acid (LPA) in which the sn-2 hydroxy group forms a five-membered ring with the sn-3 phosphate. Here, we describe the synthesis of R-3-CCPA and S-3-CCPA along with their pharmacological properties as inhibitors of lysophospholipase D/aut...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gupte R,Siddam A,Lu Y,Li W,Fujiwara Y,Panupinthu N,Pham TC,Baker DL,Parrill AL,Gotoh M,Murakami-Murofushi K,Kobayashi S,Mills GB,Tigyi G,Miller DD

更新日期：2010-12-15 00:00:00

abstract：:Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identificati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cole DC,Stock JR,Kreft AF,Antane M,Aschmies SH,Atchison KP,Casebier DS,Comery TA,Diamantidis G,Ellingboe JW,Harrison BL,Hu Y,Jin M,Kubrak DM,Lu P,Mann CW,Martone RL,Moore WJ,Oganesian A,Riddell DR,Sonnenberg-Reine

更新日期：2009-02-01 00:00:00

abstract：:A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shim HJ,Yang HR,Kim HI,Kang SA,No KT,Jung YH,Lee ST

更新日期：2014-10-01 00:00:00

abstract：:The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2'-methoxyphenyl)-benzylidene)-5-bromo-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]-1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wood ER,Kuyper L,Petrov KG,Hunter RN 3rd,Harris PA,Lackey K

更新日期：2004-02-23 00:00:00

abstract：:A novel series of aminopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bingham AH,Davenport RJ,Gowers L,Knight RL,Lowe C,Owen DA,Parry DM,Pitt WR

更新日期：2004-01-19 00:00:00

abstract：:High-throughput screening of the GSK compound collection against the P2Y(1) receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morales-Ramos AI,Mecom JS,Kiesow TJ,Graybill TL,Brown GD,Aiyar NV,Davenport EA,Kallal LA,Knapp-Reed BA,Li P,Londregan AT,Morrow DM,Senadhi S,Thalji RK,Zhao S,Burns-Kurtis CL,Marino JP Jr

更新日期：2008-12-01 00:00:00

abstract：:Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y

更新日期：2018-08-15 00:00:00

abstract：:As part of our ongoing search for anti-inflammatory compounds from higher plants, we isolated and elucidated two new diterpenoid glycosides, kansuingol A (1) and kansuingol B (2), from the roots of Euphorbia kansui. These structures were elucidated by extensive spectroscopic methods such as NMR and MS. Compounds were ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim YM,Ahn J,Chae HS,Choi YH,Kim J,Chin YW

更新日期：2018-04-15 00:00:00

abstract：:A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is effica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das J,Kimball SD,Hall SE,Han WC,Iwanowicz E,Lin J,Moquin RV,Reid JA,Sack JS,Malley MF,Chang CY,Chong S,Wang-Iverson DB,Roberts DG,Seiler SM,Schumacher WA,Ogletree ML

更新日期：2002-01-07 00:00:00

abstract：:Novel phenothiazine derivatives bearing an amino acid residue were synthesized via peptide chemistry, and evaluated for their inhibitory potential on human farnesyltransferase. The phenothiazine unit proved to be an important bulky unit in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a tyros...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dumitriu GM,Ghinet A,Bîcu E,Rigo B,Dubois J,Farce A,Belei D

更新日期：2014-07-15 00:00:00

abstract：:A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been synthesized and evaluated for their in vitro cytotoxicity against selected human cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference drug. T...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tokala R,Bale S,Janrao IP,Vennela A,Kumar NP,Senwar KR,Godugu C,Shankaraiah N

更新日期：2018-06-01 00:00:00

abstract：:The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modification into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [d-2-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fichna J,do-Rego JC,Janecki T,Staniszewska R,Poels J,Broeck JV,Costentin J,Schiller PW,Janecka A

更新日期：2008-02-15 00:00:00

abstract：:Structures containing the (R)-3-amino-3-methyl piperidine unit as a new pharmacophore moiety have been shown to possess moderate inhibitory activity for DPP-4 with good pharmacokinetics profile. One of these compounds was found to have good oral bioavailability and PK/PD profile in ZF-rat. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishio Y,Kimura H,Tosaki S,Sugaru E,Sakai M,Horiguchi M,Masui Y,Ono M,Nakagawa T,Nakahira H

更新日期：2010-12-15 00:00:00

abstract：:Modulation of DNA repair pathways in oncology has been an area of intense interest in the last decade, not least as a consequence of the promising clinical activity of poly(ADP-ribose) polymerase (PARP) inhibitors. In this review article, we highlight inhibitors of the phosphatidylinositol 3-kinase related kinase (PIK...

journal_title：Bioorganic & medicinal chemistry letters

authors： Finlay MR,Griffin RJ

更新日期：2012-09-01 00:00:00

abstract：:Inhibition of sirtuin 2 (SIRT2) is known to be protective against the toxicity of disease proteins in Parkinson's and Huntington's models of neurodegeneration. Previously, we developed SIRT2 inhibitors based on the 3-(N-arylsulfamoyl)benzamide scaffold, including3-(N-(4-bromophenyl)sulfamoyl)-N-(4-bromophenyl)benzamid...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi SH,Quinti L,Kazantsev AG,Silverman RB

更新日期：2012-04-15 00:00:00

abstract：:We report examples of a series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) analogues 12-15 prepared from a common functionalized building block 11 that can be conveniently synthesized on a large scale and in optically pure form. Isoindoline analogue 15 is the most cytotoxic agent in this series, has the highest D...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masterson LA,Croker SJ,Jenkins TC,Howard PW,Thurston DE

更新日期：2004-02-23 00:00:00

abstract：:A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Regan CF,Guo Z,Chen Y,Huang CQ,Chen M,Jiang W,Rueter JK,Coon T,Chen C,Saunders J,Brown MS,Betz SF,Struthers RS,Yang C,Wen J,Madan A,Zhu YF

更新日期：2008-08-15 00:00:00

abstract：:The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lowe JA 3rd,Qian W,Volkmann RA,Heck S,Nowakowski J,Nelson R,Nolan C,Liston D,Ward K,Zorn S,Johnson C,Vanase M,Faraci WS,Verdries KA,Baxter J,Doran S,Sanders M,Ashton M,Whittle P,Stefaniak M

更新日期：1999-09-06 00:00:00

abstract：:The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P(2) region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure-activity relationship, and selectivity against related proteases are delineated. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sattigeri JA,Andappan MM,Kishore K,Thangathirupathy S,Sundaram S,Singh S,Sharma S,Davis JA,Chugh A,Bansal VS

更新日期：2008-07-15 00:00:00

abstract：:A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. All the intermediates and final molecules were characterised using spectral methods and one of the target comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramprasad J,Nayak N,Dalimba U,Yogeeswari P,Sriram D

更新日期：2015-10-01 00:00:00

abstract：:Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lv PC,Sun J,Luo Y,Yang Y,Zhu HL

更新日期：2010-08-01 00:00:00

abstract：:Gd and Eu complexes of PMN-tetraacetic acid show interesting properties either for MRI or for optical imaging; that is, for the Gd-complex, a high proton relaxivity with favorable water residence time; for the Eu-complex, a luminescence lifetime of 400 micros at room temperature compatible with the use of time-resolve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Laurent S,Vander Elst L,Wautier M,Galaup C,Muller RN,Picard C

更新日期：2007-11-15 00:00:00

abstract：:The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ontoria JM,Bufi LL,Torrisi C,Bresciani A,Giomini C,Rowley M,Serafini S,Bin H,Hao W,Steinkühler C,Jones P

更新日期：2011-09-15 00:00:00

abstract：:It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sukalovic V,Ignjatovic D,Tovilovic G,Andric D,Shakib K,Kostic-Rajacic S,Soskic V

更新日期：2012-06-15 00:00:00