当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Synthetic studies on selective adenosine A2A receptor antagonists. Part II: synthesis and structure-activity relationships of novel benzofuran derivatives.

Synthetic studies on selective adenosine A2A receptor antagonists. Part II: synthesis and structure-activity relationships of novel benzofuran derivatives.

Abstract：

:Based on the previously reported lead compound, a series of benzofuran derivatives were prepared to study their antagonistic activities to A(2A) receptor. The replacement of the phenyl group at the 4-position with a heterocyclic ring improved the PK profile and aqueous solubility. From these studies, we discovered a potent new A(2A) antagonist, 12a, which has both a good oral bioavailability and in vivo efficacy on motor disability in MPTP-treated common marmosets.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Saku O,Saki M,Kurokawa M,Ikeda K,Uchida S,Takizawa T,Uesaka N

doi

10.1016/j.bmcl.2010.04.058

subject

Has Abstract

pub_date

2010-06-15 00:00:00

pages

3768-71

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)00528-7

journal_volume

20

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Synthesis and cytotoxic evaluation of novel paraconic acid analogs.

    abstract：:A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.09.092

    authors： Le Floch C,Le Gall E,Léonel E,Martens T,Cresteil T

    更新日期：2011-12-01 00:00:00

  • An alternative to Western blot analysis using RNA aptamer-functionalized quantum dots.

    abstract：:To make full use both of optical properties of quantum dots (QDs) and of specific interactions between aptamers and their ligands of interest, we employed QD-conjugated RNA aptamer interactions with histidine tag. QDs offer revolutionary fluorescence performance due to their long-term photostability, brilliant colors,...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.04.040

    authors： Shin S,Kim IH,Kang W,Yang JK,Hah SS

    更新日期：2010-06-01 00:00:00

  • Biotransformations of 6',7'-dihydroxybergamottin and 6',7'-epoxybergamottin by the citrus-pathogenic fungi diminish cytochrome P450 3A4 inhibitory activity.

    abstract：:Penicillium digitatum, as well as five other citrus pathogenic species, (Penicillium ulaiense Link, Geotrichum citri Link, Botrytis cinerea P. Micheli ex Pers., Lasiodiplodia theobromae (Pat.) Griffon & Maubl., and Phomopsis citri (teleomorph Diaporthe citri)) were observed to convert 6',7'-epoxybergamottin (1) into 6...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.01.081

    authors： Myung K,Manthey JA,Narciso JA

    更新日期：2012-03-15 00:00:00

  • In vitro efficacy of 7-benzylamino-1-isoquinolinamines against Plasmodium falciparum related to the efficacy of chalcones.

    abstract：:A series of 1,7-diaminoisoquinolinamines, that are expected to mediate antimalarial activity by the same mechanism employed by the chalcones, were produced. Six 7-benzylamino-1-isoquinolinamines were found to be submicromolar inhibitors in vitro of drug-resistant Plasmodium falciparum, with the best possessing activit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.11.099

    authors： Gutteridge CE,Hoffman MM,Bhattacharjee AK,Milhous WK,Gerena L

    更新日期：2011-01-15 00:00:00

  • In vitro SAR of pyrrolidine-containing histamine H3 receptor antagonists: trends across multiple chemical series.

    abstract：:Structure-activity relationships (SAR) were analyzed within a library of diverse yet simple compounds prepared as histamine H3 antagonists. The libraries were constructed with a variety of low molecular weight pyrrolidines, selected from (R)-2-methylpyrrolidine, (S)-2-methylpyrrolidine, and pyrrolidine. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.10.067

    authors： Nersesian DL,Black LA,Miller TR,Vortherms TA,Esbenshade TA,Hancock AA,Cowart MD

    更新日期：2008-01-01 00:00:00

  • Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation.

    abstract：:The optimisation of affinity and selectivity in a novel series of dual 5-HT5A/5-HT7 receptor ligands is described. Brain penetrant 2-aminodihydroquinazolines with low nanomolar affinities were identified. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.10.080

    authors： Peters JU,Lübbers T,Alanine A,Kolczewski S,Blasco F,Steward L

    更新日期：2008-01-01 00:00:00

  • 2-Aryl-3-(6-trifluoromethoxy)benzo[d]thiazole-based thiazolidinone hybrids as potential anti-infective agents: Synthesis, biological evaluation and molecular docking studies.

    abstract：:The search for new antimicrobial agents is greater than ever due to the perpetual threat of multidrug resistance in known pathogens and the relentless emergence of new infections. In this manuscript, ten thiazole-based thiazolidinone hybrids bearing a 6-trifluoromethoxy substituent on the benzothiazole core were synth...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127718

    authors： Haroun M,Tratrat C,Petrou A,Geronikaki A,Ivanov M,Ciric A,Sokovic M

    更新日期：2021-01-15 00:00:00

  • Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5.

    abstract：:This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did n...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.09.057

    authors： Seo WD,Lee JH,Jia Y,Wu C,Lee SJ

    更新日期：2015-11-15 00:00:00

  • PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

    abstract：:Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.06.071

    authors： Marwaha A,Goel RK,Mahajan MP

    更新日期：2007-09-15 00:00:00

  • Evaluation of steroidal amines as lipid raft modulators and potential anti-influenza agents.

    abstract：:The influenza A virus (IFV) possesses a highly ordered cholesterol-rich lipid envelope. A specific composition and structure of this membrane raft envelope are essential for viral entry into cells and virus budding. Several steroidal amines were investigated for antiviral activity against IFV. Both, a positively charg...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.07.015

    authors： Agarwal S,Schroeder C,Schlechtingen G,Braxmeier T,Jennings G,Knölker HJ

    更新日期：2013-09-15 00:00:00

  • Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists.

    abstract：:In the design of potent and selective sphingosine-1-phosphate receptor agonists, we were able to identify two series of molecules based on phenylamide and phenylimidazole analogs of FTY-720. Several designed molecules in these scaffolds have demonstrated selectivity for S1P receptor subtype 1 versus 3 and excellent in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.11.072

    authors： Evindar G,Bernier SG,Kavarana MJ,Doyle E,Lorusso J,Kelley MS,Halley K,Hutchings A,Wright AD,Saha AK,Hannig G,Morgan BA,Westlin WF

    更新日期：2009-01-15 00:00:00

  • The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection.

    abstract：:A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the M...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00240-8

    authors： Hewawasam P,Fan W,Knipe J,Moon SL,Boissard CG,Gribkoff VK,Starrett JE

    更新日期：2002-07-08 00:00:00

  • Aryl sulfonamido indane inhibitors of the Kv1.5 ion channel.

    abstract：:A collection of aryl sulfonamido indanes based on the lead compound 1 was synthesized and evaluated for Kv1.5 inhibitory activity. Kv1.5 inhibitors have the potential to be atrium-selective agents for treatment of atrial fibrillation. (1R,2R)-1 has an IC(50) of 0.033microM against Kv1.5 and is selective against other ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.02.052

    authors： Gross MF,Beaudoin S,McNaughton-Smith G,Amato GS,Castle NA,Huang C,Zou A,Yu W

    更新日期：2007-05-15 00:00:00

  • Structure-activity relationships of neuropeptide Y Y1 receptor antagonists related to BIBP 3226.

    abstract：:Analogues of BIBP 3226, (R)-N(alpha)-diphenylacetyl-N-(4-hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity. Combination with a N(G)...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00292-4

    authors： Aiglstorfer I,Hendrich I,Moser C,Bernhardt G,Dove S,Buschauer A

    更新日期：2000-07-17 00:00:00

  • Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.

    abstract：:Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions we...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.027

    authors： Glunz PW,Zhang X,Zou Y,Delucca I,Nirschl AH,Cheng X,Weigelt CA,Cheney DL,Wei A,Anumula R,Luettgen JM,Rendina AR,Harpel M,Luo G,Knabb R,Wong PC,Wexler RR,Priestley ES

    更新日期：2013-09-15 00:00:00

  • Design, synthesis and in vitro antimalarial activity of an acylhydrazone library.

    abstract：:A library of acylhydrazone iron chelators was synthesized and tested for its ability to inhibit the growth of a chloroquine-resistant strain of Plasmodium falciparum. Some of these new compounds are significantly more active than desferrioxamine DFO, the iron chelator in widespread clinical use and also than the most ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.09.058

    authors： Melnyk P,Leroux V,Sergheraert C,Grellier P

    更新日期：2006-01-01 00:00:00

  • A combinatorial approach to chemical modification of subtilisin Bacillus lentus.

    abstract：:The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00415-6

    authors： Plettner E,Khumtaveeporn K,Shang X,Jones JB

    更新日期：1998-09-08 00:00:00

  • Synthesis and anti-breast cancer activities of substituted quinolines.

    abstract：:Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.024

    authors： Shi A,Nguyen TA,Battina SK,Rana S,Takemoto DJ,Chiang PK,Hua DH

    更新日期：2008-06-01 00:00:00

  • Discovery of benzamides as potent human β3 adrenergic receptor agonists.

    abstract：:The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human β3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From libr...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.030

    authors： Zhu C,Kar NF,Li B,Costa M,Dingley KH,Di Salvo J,Ha SN,Hurley AL,Li X,Miller RR,Salituro GM,Struthers M,Weber AE,Hale JJ,Edmondson SD

    更新日期：2016-01-01 00:00:00

  • Identification of Darmstoff analogs as selective agonists and antagonists of lysophosphatidic acid receptors.

    abstract：:Darmstoff describes a family of gut smooth muscle-stimulating acetal phosphatidic acids initially isolated and characterized from the bath fluid of stimulated gut over 50 years ago. Despite similar structural and biological profiles, Darmstoff analogs have not previously been examined as potential LPA mimetics. Here, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.08.096

    authors： Gududuru V,Zeng K,Tsukahara R,Makarova N,Fujiwara Y,Pigg KR,Baker DL,Tigyi G,Miller DD

    更新日期：2006-01-15 00:00:00

  • Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.002

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

    更新日期：2004-02-23 00:00:00

  • 1-[(Benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles - potent competitive inhibitors of aromatase.

    abstract：:The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles is described. The compounds were tested for human placental aromatase inhibition in vitro, using [1beta-3H]-androstenedione as the substrate for the aromatase enzyme, the percentage inhibition and IC50 data is included. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00328-5

    authors： Vinh TK,Ahmadi M,Delgado PO,Perez SF,Walters HM,Smith HJ,Nicholls PJ,Simons C

    更新日期：1999-07-19 00:00:00

  • Synthesis and antiproliferative activity of benzocyclobutacarbazol derivatives. A new class of potential antitumor agents.

    abstract：:Several benzocyclobutacarbazol derivatives were synthesized and evaluated for their potential cytotoxic properties. A number of these compounds exhibited significant antiproliferative activity with concomitant interaction with the cell cycle and represent a new class of potential anticancer agents. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00532-1

    authors： Graf-Christophe S,Kuehm-Caubère C,Renard P,Pfeiffer B,Pierré A,Léonce S,Caubère P

    更新日期：2000-12-04 00:00:00

  • Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters.

    abstract：:Over the past 15years there have been extensive efforts to understand and reduce the high attrition rates of drug candidates with an increased focus on physicochemical properties. The fruits of this labor have been the generation of numerous efficiency indices, metric-based rules and visualization tools to help guide ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.08.029

    authors： Shultz MD

    更新日期：2013-11-01 00:00:00

  • The synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel opener targeted for urge urinary incontinence.

    abstract：:A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using iso...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00099-9

    authors： Hewawasam P,Erway M,Thalody G,Weiner H,Boissard CG,Gribkoff VK,Meanwell NA,Lodge N,Starrett JE Jr

    更新日期：2002-04-08 00:00:00

  • 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.

    abstract：:We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.08.050

    authors： Haffner CD,McDougald DL,Reister SM,Thompson BD,Conlee C,Fang J,Bass J,Lenhard JM,Croom D,Secosky-Chang MB,Tomaszek T,McConn D,Wells-Knecht K,Johnson PR

    更新日期：2005-12-01 00:00:00

  • Design and synthesis of Pfmrk inhibitors as potential antimalarial agents.

    abstract：:The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a Plasmodium falciparum cyclin-dependent protein kinase, are described. The most potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18 microM. It is the first compound reported to inhibit Pfmrk at the micro molar rang...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00578-9

    authors： Xiao Z,Waters NC,Woodard CL,Li Z,Li PK

    更新日期：2001-11-05 00:00:00

  • 10-Hydroxy-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-diones: potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors with activity against integrase mutants.

    abstract：:A series of 10-hydroxy-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-diones was synthesized and tested for their inhibition of HIV-1 replication in cell culture. Structure-activity studies indicated that high antiviral potency against wild-type virus as well as viruses containing integrase mutation...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.07.037

    authors： Wiscount CM,Williams PD,Tran LO,Embrey MW,Fisher TE,Sherman V,Homnick CF,Donnette Staas D,Lyle TA,Wai JS,Vacca JP,Wang Z,Felock PJ,Stillmock KA,Witmer MV,Miller MD,Hazuda DJ,Day AM,Gabryelski LJ,Ecto LT,Schleif WA

    更新日期：2008-08-15 00:00:00

  • Antiproliferative and apoptotic effects of the oxidative dimerization product of methyl caffeate on human breast cancer cells.

    abstract：:Caffeic acid derivatives are increasingly regarded as potential oncoprotective that could inhibit both the initiation and progression of cancer. Here we have synthesized seven 1-arylnaphthalene lignans and related compounds and tested their impact on breast cancer cell growth in tissue culture. The product of the oxid...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.11.009

    authors： Bailly F,Toillon RA,Tomavo O,Jouy N,Hondermarck H,Cotelle P

    更新日期：2013-01-15 00:00:00

  • The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-RafV600E kinase.

    abstract：:Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.015

    authors： Ren L,Ahrendt KA,Grina J,Laird ER,Buckmelter AJ,Hansen JD,Newhouse B,Moreno D,Wenglowsky S,Dinkel V,Gloor SL,Hastings G,Rana S,Rasor K,Risom T,Sturgis HL,Voegtli WC,Mathieu S

    更新日期：2012-05-15 00:00:00