Identification of a novel series of selective 5-HT7 receptor antagonists.

abstract：:Zoanthamines are a family of marine alkaloids that have complex heptacyclic structures and are reported to be interleukin-6 modulators. While the structure of zoanthamines, especially the ABC-ring portion, is similar to that of steroids, the CDEFG-ring portion, composed of aminoacetal and lactone core, is a unique str...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hirai G,Oguri H,Hayashi M,Koyama K,Koizumi Y,Moharram SM,Hirama M

更新日期：2004-05-17 00:00:00

abstract：:Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Q,Woods KW,Thomas S,Zhu GD,Packard G,Fisher J,Li T,Gong J,Dinges J,Song X,Abrams J,Luo Y,Johnson EF,Shi Y,Liu X,Klinghofer V,Des Jong R,Oltersdorf T,Stoll VS,Jakob CG,Rosenberg SH,Giranda VL

更新日期：2006-04-01 00:00:00

abstract：:In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Girault S,Davioud-Charvet E,Salmon L,Berecibar A,Debreu MA,Sergheraert C

更新日期：1998-05-19 00:00:00

abstract：:Regio- and/or chemo-selective reductions of taxinine (1a), a taxane diterpenoid readily obtainable from the needles of a Japanese yew (Taxus cuspidata), at the 5-O-cinnamoyl and 4-exo-methylene moieties have been accomplished by the catalytic hydrogenation over Pd/C or Rh/C to obtain 5-O-phenylpropionylated taxinine A...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sako M,Suzuki H,Yamamoto N,Hirota K

更新日期：1999-12-20 00:00:00

abstract：:A series of carboxamide derivatives of 5'-amino-2',5'-dideoxy-5-ethyluridine has been prepared as inhibitors of HSV-TK (herpes simplex virus thymidine kinase). The most potent compounds were derived from xanthene, thioxanthene and dihydroanthracene carboxylic acids. The lead compounds show subnanomolar IC(50) values a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martin JA,Lambert RW,Merrett JH,Parkes KE,Thomas GJ,Baker SJ,Bushnell DJ,Cansfield JE,Dunsdon SJ,Freeman AC,Hopkins RA,Johns IR,Keech E,Simmonite H,Walmsley A,Wong Kai-In P,Holland M

更新日期：2001-07-09 00:00:00

abstract：:A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rambabu D,Mulakayala N,Ismail,Kumar KR,Kumar GP,Mulakayala C,Kumar CS,Kalle AM,Rao MV,Oruganti S,Pal M

更新日期：2012-11-01 00:00:00

abstract：:Beauveria bassiana AM278 and Absidia coerulea AM93 converted 8-prenylnaringenin (1) into two glycoside derivatives (7-O-β-D-glucopyranoside) (2) and 7-O-β-D-4'''-O-methylglucopyranoside) (3) in high yields in processes conducted in Saboraud medium. 8-Prenylnaringenin 7-O-β-D-4'''-O-methylglucopyranoside (3) is a new c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bartmańska A,Tronina T,Huszcza E

更新日期：2012-10-15 00:00:00

abstract：:The biological activity for a set of melanocortin-4 receptor (MC4R) agonists containing a piperazine core with an ortho-substituted aryl sulfonamide is described. Compounds from this set had binding and functional activities at MC4R less than 30 nM. The most selective compound in this series was >25,000-fold more pote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fotsch C,Han N,Arasasingham P,Bo Y,Carmouche M,Chen N,Davis J,Goldberg MH,Hale C,Hsieh FY,Kelly MG,Liu Q,Norman MH,Smith DM,Stec M,Tamayo N,Xi N,Xu S,Bannon AW,Baumgartner JW

更新日期：2005-03-15 00:00:00

abstract：:The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H(3) receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Turner SC,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2003-07-07 00:00:00

abstract：:New A-ring modified betulinic acid derivatives having small steric hindrance were prepared and tested for cytotoxic activity on 3 cancer cell lines: 10 compounds showed stronger cytotoxic activity than betulinic acid. Especially, the compounds bearing 1-ene-3-oxo with electron-withdrawing groups at C2 showed strong cy...

journal_title：Bioorganic & medicinal chemistry letters

authors： You YJ,Kim Y,Nam NH,Ahn BZ

更新日期：2003-10-06 00:00:00

abstract：:A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang T,Duncan L,Gu W,O'Dowd H,Wei Y,Perola E,Parsons J,Gross CH,Moody CS,Arends SJ,Charifson PS

更新日期：2012-06-01 00:00:00

abstract：:Forty-seven 2-benzoylaminobenzoic esters were synthesized and evaluated in anti-platelet aggregation, inhibition of superoxide anion generation, and inhibition of neutrophil elastase release assays. Most 2-benzoylamino-4-chlorobenzoic acid derivatives showed selective inhibitory effects on arachidonic acid (AA)-induce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsieh PW,Hwang TL,Wu CC,Chiang SZ,Wu CI,Wu YC

更新日期：2007-03-15 00:00:00

abstract：:The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhai W,Flynn N,Longhi DA,Tino JA,Murphy BJ,Slusarchyk D,Gordon DA,Pendri A,Shi S,Stoffel R,Ma B,Sofia MJ,Gerritz SW

更新日期：2008-09-15 00:00:00

abstract：:Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a nov...

journal_title：Bioorganic & medicinal chemistry letters

authors： Daher SS,Franklin KP,Scherzi T,Dunman PM,Andrade RB

更新日期：2020-11-01 00:00:00

abstract：:A series of alpha(v)beta(3) antagonists based on a thiophene scaffold were synthesized via two routes and evaluated for in vitro biological activity. We have identified several structurally similar antagonists with different selectivities towards alpha(IIb)beta(3), alpha(v)beta(5) and alpha(5)beta(1) at the cellular l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bubenik M,Meerovitch K,Bergeron F,Attardo G,Chan L

更新日期：2003-02-10 00:00:00

abstract：:New inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered using an N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamide scaffold. The series was found to be potent in a porcine TACE (pTACE) assay with IC(50)s typically below 5 nM. For most compounds, selectivity for pTACE relative to MMP-1,-2, and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Lu Z,Xue CB,He X,Seng JL,Roderick JJ,Wasserman ZR,Liu RQ,Covington MB,Magolda RL,Newton RC,Trzaskos JM,Decicco CP

更新日期：2003-06-16 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

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：:γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II) dependent oxygenase that catalyses an essential step during carnitine biosynthesis in animals. BBOX is inhibited by ejection of structural zinc by a set of selenium containing analogues. Previous structural analyses indicated that an undisrupted N-termi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rydzik AM,Brem J,Struwe WB,Kochan GT,Benesch JL,Schofield CJ

更新日期：2014-11-01 00:00:00

abstract：:The X-ray crystallographic structure for the adduct of an activator with human carbonic anhydrase isozyme I (hCA I) is reported. L-Histidine binds deep within the enzyme active site, participating in a network of hydrogen bonds involving its carboxylate moiety and the zinc-bound water molecule, as well as the imidazol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Temperini C,Scozzafava A,Supuran CT

更新日期：2006-10-01 00:00:00

abstract：:Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arai Y,Inuki S,Fujimoto Y

更新日期：2018-05-15 00:00:00

abstract：:The worldwide increase in antibiotic resistance has led to search of alternatives anti-microbial therapies such as photodynamic inactivation. The aim of this paper was to evaluate the photodynamic activity in vitro of a neutral and two cationic Zn phthalocyanines. Their photokilling activity was tested on Escherichia ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miretti M,Clementi R,Tempesti TC,Baumgartner MT

更新日期：2017-09-15 00:00:00

abstract：:A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lackey K,Cory M,Davis R,Frye SV,Harris PA,Hunter RN,Jung DK,McDonald OB,McNutt RW,Peel MR,Rutkowske RD,Veal JM,Wood ER

更新日期：2000-02-07 00:00:00

abstract：:Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic aci...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carrigan CN,Patel SA,Cox HD,Bolstad ES,Gerdes JM,Smith WE,Bridges RJ,Thompson CM

更新日期：2014-02-01 00:00:00

abstract：:A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to tho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Simic M,Paunovic N,Boric I,Randjelovic J,Vojnovic S,Nikodinovic-Runic J,Pekmezovic M,Savic V

更新日期：2016-01-01 00:00:00

abstract：:4,4-dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol, a sterol of current biological interest, has been synthesized in six steps from 3 beta-acetoxy-4,4-dimethyl-5 alpha-cholest-8(14)-en-15-one. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruan B,Wilson WK,Schroepfer GJ Jr

更新日期：1998-02-03 00:00:00

abstract：:Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patouret R,Doebelin C,Garcia-Ordonez RD,Chang MR,Ruiz C,Cameron MD,Griffin PR,Kamenecka TM

更新日期：2018-04-15 00:00:00

abstract：:Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith DG,Gribble AD,Haigh D,Ife RJ,Lavery P,Skett P,Slingsby BP,Stacey R,Ward RW,West A

更新日期：1999-11-01 00:00:00

abstract：:In our search for a new agent, human neutrophil elastase (HNE) inhibitor, for the treatment of acute respiratory failure, we rationally designed and synthesized a series of peptide-based carboxylic acid-containing transition-state inhibitors. The presence of valyl moiety is found to be essential for potent in vitro in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato F,Inoue Y,Omodani T,Imano K,Okazaki H,Takemura T,Komiya M

更新日期：2002-02-25 00:00:00

abstract：:A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

更新日期：2016-04-01 00:00:00