当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Lobelane analogues containing 4-hydroxy and 4-(2-fluoroethoxy) aromatic substituents: Potent and selective inhibitors of [(3)H]dopamine uptake at the vesicular monoamine transporter-2.

Lobelane analogues containing 4-hydroxy and 4-(2-fluoroethoxy) aromatic substituents: Potent and selective inhibitors of [(3)H]dopamine uptake at the vesicular monoamine transporter-2.

Abstract：

:A series of lobelane and GZ-793A analogues that incorporate aromatic 4-hydroxy and 4-(2-fluoroethoxy) substituents were synthesized and evaluated for inhibition of [(3)H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and the dopamine transporter (DAT), and [(3)H]serotonin uptake at the serotonin transporter (SERT). Most of these compounds exhibited potent inhibition of DA uptake at VMAT2 in the nanomolar range (Ki=30-70nM). The two most potent analogues, 7 and 14, both exhibited a Ki value of 31nM for inhibition of VMAT2. The lobelane analogue 14, incorporating 4-(2-fluoroethoxy) and 4-hydroxy aromatic substituents, exhibited 96- and 335-fold greater selectivity for VMAT2 versus DAT and SERT, respectively, in comparison to lobelane. Thus, lobelane analogues bearing hydroxyl and fluoroethoxy moieties retain the high affinity for VMAT2 of the parent compound, while enhancing selectivity for VMAT2 versus the plasmalemma transporters.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Joolakanti SR,Nickell JR,Janganati V,Zheng G,Dwoskin LP,Crooks PA

doi

10.1016/j.bmcl.2016.03.119

subject

Has Abstract

pub_date

2016-05-15 00:00:00

pages

2422-2427

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30351-1

journal_volume

26

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Inhibition of estrone sulfatase (ES) by derivatives of 4-[(aminosulfonyl)oxy] benzoic acid.

    abstract：:In our search for potent inhibitors of the enzyme estrone sulfatase (ES), we have undertaken the synthesis and biochemical evaluation of a range of straight chain alkyl esters of 4-[(aminosulfonyl)oxy] benzoic acid. The results of the study show that the synthesised compounds possess greater inhibitory activity when c...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00383-9

    authors： Ahmed S,James K,Owen CP

    更新日期：2002-09-02 00:00:00

  • Inhibitory mode of 2-acetoxyphenyl alkyl sulfides against COX-1 and COX-2: QSAR analyses.

    abstract：:Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important strategy in design of potent anti-inflammatory compounds with significantly reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1 inhibit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.08.002

    authors： Jain HK,Mourya VK,Agrawal RK

    更新日期：2006-10-15 00:00:00

  • Potential α-glucosidase inhibitors from thermal transformation of (+)-catechin.

    abstract：:Thermal transformation of the (+)-catechin (1) with heating processing afforded a new oxidation product, gambiriin D (2), along with catechin [6'-8]-catechin (3), and (+)-epicatechin (4). The structure of a new catechin dimer with C-C linkage was determined on the basis of spectroscopic data interpretation. The catech...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.027

    authors： Kim T,Choi HJ,Eom SH,Lee J,Kim TH

    更新日期：2014-03-15 00:00:00

  • From genome to drug lead: identification of a small-molecule inhibitor of the SARS virus.

    abstract：:Virtual screening, a fast, computational approach to identify drug leads [Perola, E.; Xu, K.; Kollmeyer, T. M.; Kaufmann, S. H.; Prendergast, F. G. J. Med. Chem.2000, 43, 401; Miller, M. A. Nat. Rev. Drug Disc.2002, 1 220], is limited by a known challenge in crystallographically determining flexible regions of protein...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.11.018

    authors： Dooley AJ,Shindo N,Taggart B,Park JG,Pang YP

    更新日期：2006-02-15 00:00:00

  • Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors.

    abstract：:A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylsulfonamides has been synthesized and assayed for β-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl substituents ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.09.058

    authors： Bertini S,Ghilardi E,Asso V,Minutolo F,Rapposelli S,Digiacomo M,Saccomanni G,Salmaso V,Sturlese M,Moro S,Macchia M,Manera C

    更新日期：2017-11-01 00:00:00

  • Structural hybridization as a facile approach to new drug candidates.

    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

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2020.127514

    authors： Sampath Kumar HM,Herrmann L,Tsogoeva SB

    更新日期：2020-12-01 00:00:00

  • Essential structure of orexin 1 receptor antagonist YNT-707, Part IV: The role of D-ring in 4,5-epoxymorphinan on the orexin 1 receptor antagonistic activity.

    abstract：:The orexin 1 receptor (OX1R) antagonists carrying a morphinan skeleton such as YNT-707 (2) and YNT-1310 (3) showed potent and extremely high selective antagonistic activity against OX1R. In the course of our study of the essential structure of YNT-707 for high binding affinity against OX1R, we prepared derivatives of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.07.039

    authors： Saitoh T,Seki K,Nakajima R,Yamamoto N,Kutsumura N,Nagumo Y,Irukayama-Tomobe Y,Ogawa Y,Ishikawa Y,Tanimura R,Yanagisawa M,Nagase H

    更新日期：2019-09-15 00:00:00

  • Discovery of two aminoglycoside antibiotics as inhibitors targeting the menin-mixed lineage leukaemia interface.

    abstract：:Menin functions as an oncogenic cofactor of mixed lineage leukaemia (MLL) fusion proteins in leukaemogenesis. The menin-MLL interface is a potential therapeutic target in acute leukaemia cases. In this study, approximately 900 clinical compounds were evaluated and ranked using pharmacophore-based virtual screening, th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.03.055

    authors： Li L,Zhou R,Geng H,Yue L,Ye F,Xie Y,Liu J,Kong X,Jiang H,Huang J,Luo C

    更新日期：2014-05-01 00:00:00

  • Design of selective Cathepsin inhibitors.

    abstract：:A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.06.090

    authors： Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher S

    更新日期：2009-08-15 00:00:00

  • Multidrug resistance-reversal effects of resin glycosides from Dichondra repens.

    abstract：:Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to the isolation of three new resin glycosides dichondrins A-C (1-3), and three known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin glycosides with an acyclic core were evaluated for their multidrug resistance reversal ac...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.12.083

    authors： Song WB,Wang WQ,Zhang SW,Xuan LJ

    更新日期：2015-02-15 00:00:00

  • An additional 2'-ribofuranose residue at a specific position of the DNA primer prevents Its elongation by HIV-1 reverse transcriptase.

    abstract：:Oligodeoxynucleotides containing 2'-O-beta-D-ribofuranosyladenosine were prepared and used as modified primers in RNA-templated DNA synthesis catalyzed by HIV reverse transcriptase. It was shown that the additional 2'-ribofuranose residue in specific position of primer prevents its elongation. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00836-8

    authors： Andreeva OI,Golubeva AS,Kochetkov SN,Van Aerschot A,Herdewijn P,Efimtseva EV,Ermolinsky BS,Mikhailov SN

    更新日期：2002-02-25 00:00:00

  • Synthesis of rigid trichostatin A analogs as HDAC inhibitors.

    abstract：:New inhibitors of histone deacetylase (HDAC) have been synthesized and evaluated for their activity toward non small lung cancer cell line H661. Their design is based on indanone (or tetralone) systems leading to trichostatin A (TSA) analogs with limited conformational mobility. Molecular modelization at the AM1 level...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.07.080

    authors： Charrier C,Bertrand P,Gesson JP,Roche J

    更新日期：2006-10-15 00:00:00

  • Identification of benzofuran central cores for the inhibition of leukotriene A(4) hydrolase.

    abstract：:Leukotrienes (LT's) are known to play a physiological role in inflammatory immune response. Leukotriene A(4) hydrolase (LTA(4)H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA(4) to LTB(4). LTB(4) is a known pro-inflammatory mediator. This paper describes the identification and synthe...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.11.074

    authors： Eccles W,Blevitt JM,Booker JN,Chrovian CC,Crawford S,de Leon AR,Deng X,Fourie AM,Grice CA,Herman K,Karlsson L,Kearney AM,Lee-Dutra A,Liang J,Luna R,Pippel D,Rao N,Riley JP,Santillán A,Savall B,Tanis VM,Xue X,Y

    更新日期：2013-02-01 00:00:00

  • Chroman-3-amides as potent Rho kinase inhibitors.

    abstract：:Inhibition of Rho kinase (ROCK) is an attractive strategy for the treatment of diseases such as hypertension, glaucoma, and cancer. Here we report chroman-3-amides as highly potent ROCK inhibitors with sufficient kinase selectivity, excellent cell activity, good microsomal stability, and desirable pharmacokinetic prop...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.080

    authors： Chen YT,Bannister TD,Weiser A,Griffin E,Lin L,Ruiz C,Cameron MD,Schürer S,Duckett D,Schröter T,LoGrasso P,Feng Y

    更新日期：2008-12-15 00:00:00

  • 2-Aminoalkyl nicotinamide derivatives as pure inverse agonists of the ghrelin receptor.

    abstract：:New inverse agonists of the ghrelin receptor (ghrelinR) were obtained through high-throughput screening and subsequent structural modification of 2-aminoalkyl nicotinamide derivatives. The key structural feature to improve in vitro activity was the introduction of a diazabicyclo ring at the 5-position of the pyridine ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.04.040

    authors： Takahashi B,Funami H,Iwaki T,Maruoka H,Nagahira A,Koyama M,Kamiide Y,Matsuo T,Muto T,Annoura H

    更新日期：2015-07-01 00:00:00

  • Synthesis and biological activity of 4-substituted benzoxazolone derivatives as a new class of sEH inhibitors with high anti-inflammatory activity in vivo.

    abstract：:A series of novel 4-substituted benzoxazolone derivatives was synthesized, characterized and evaluated as human soluble epoxide hydrolase (sEH) inhibitors and anti-inflammatory agents. Some compounds showed moderate sEH inhibitory activities in vitro, and two novel compounds, 3g and 4j, exhibited the highest activitie...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.048

    authors： Tang L,Ma WH,Ma YL,Ban SR,Feng XE,Li QS

    更新日期：2013-04-15 00:00:00

  • Carbonic anhydrase inhibitors. Inhibition of transmembrane isozymes XII (cancer-associated) and XIV with anions.

    abstract：:Metal complexing anions represent an important class of inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The first inhibition study of the transmembrane isozymes CA XII (tumor-associated) and XIV with anions is reported. These isozymes showed inhibition profiles with physiologic/non-physiologic ani...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.12.113

    authors： Innocenti A,Vullo D,Pastorek J,Scozzafava A,Pastorekova S,Nishimori I,Supuran CT

    更新日期：2007-03-15 00:00:00

  • Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta.

    abstract：:The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the act...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.045

    authors： Liu Y,Wu J,Weissig H,Betancort JM,Gai WZ,Leventhal PS,Patricelli MP,Samii B,Szardenings AK,Shreder KR,Kozarich JW

    更新日期：2008-11-15 00:00:00

  • Synthesis and biological evaluation of copper (II) complexes of sterically hindered o-aminophenol derivatives as antimicrobial agents.

    abstract：:Cu(II) complexes with 4,6-di(tert-butyl)-2-aminophenol (I) and 2-anilino-4,6-di(tert-butyl)phenol (II) have been synthesized and characterized by means of elemental analysis, TG/DTA, FT-IR, UV-vis, ESR, and conductance measurements. The compounds I and II can coordinate in their singly deprotonated forms and behave as...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.07.065

    authors： Loginova NV,Koval'chuk TV,Zheldakova RA,Osipovich NP,Sorokin VL,Polozov GI,Ksendzova GA,Glushonok GK,Chernyavskaya AA,Shadyro OI

    更新日期：2006-10-15 00:00:00

  • An alternative synthesis of 4,4-dimethyl-5 alpha-cholesta-8,14,24-trien-3 beta-ol, an intermediate in sterol biosynthesis and a reported activator of meiosis and of nuclear orphan receptor LXR alpha.

    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

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00016-x

    authors： Ruan B,Wilson WK,Schroepfer GJ Jr

    更新日期：1998-02-03 00:00:00

  • Hit-to-lead studies: the discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists.

    abstract：:A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00561-4

    authors： Baxter A,Bennion C,Bent J,Boden K,Brough S,Cooper A,Kinchin E,Kindon N,McInally T,Mortimore M,Roberts B,Unitt J

    更新日期：2003-08-18 00:00:00

  • Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids.

    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

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00029-8

    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

  • Synthesis and antihormonal properties of novel 11β-benzoxazole-substituted steroids.

    abstract：:Early studies led to the identification of 11β-aryl-4',5'-dihydrospiro[estra-4,9-diene-17β,4'-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4'-dimethylaminophenyl group of mifepristone with th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.12.110

    authors： Jin C,Fix SE,Kepler JA,Cook CE

    更新日期：2012-02-15 00:00:00

  • Pyridazines. Part 36: Synthesis and antiplatelet activity of 5-substituted-6-phenyl-3(2H)-pyridazinones.

    abstract：:A convenient and efficient palladium-catalysed retro-ene-assisted method has been developed to prepare a series of 5-substituted-6-phenyl-3(2H)-pyridazinones as potential antiplatelet drugs. The most active compounds were those that contain a 3-phenyl-3-oxo-propenyl fragment or a phenylthio group at position 5 of the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.11.009

    authors： Coelho A,Sotelo E,Fraiz N,Yáñez M,Laguna R,Cano E,Raviña E

    更新日期：2004-01-19 00:00:00

  • Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation.

    abstract：:The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl-3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is described. Through these efforts compound 2 was identified as a potent (cell IC50 = 15 nM) BACE inhibitor with accep...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.01.056

    authors： Low JD,Bartberger MD,Cheng Y,Whittington D,Xue Q,Wood S,Allen JR,Minatti AE

    更新日期：2018-04-01 00:00:00

  • A new selective fluorescent probe based on tamoxifen.

    abstract：:Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiment...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.09.028

    authors： Ho LA,Thomas E,McLaughlin RA,Flematti GR,Fuller RO

    更新日期：2016-10-15 00:00:00

  • Topological estimation of electronic absorption bands of arene absorption spectra as a tool for modeling their toxicity and environmental pollution.

    abstract：:A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.06.094

    authors： Khadikar PV,Singh S,Jaiswal M,Mandloi D

    更新日期：2004-09-20 00:00:00

  • New diarylureas and diarylamides possessing acet(benz)amidophenyl scaffold: design, synthesis, and antiproliferative activity against melanoma cell line.

    abstract：:A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, co...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.03.020

    authors： Kim HJ,Cho HJ,Kim H,El-Gamal MI,Oh CH,Lee SH,Sim T,Hah JM,Yoo KH

    更新日期：2012-05-01 00:00:00

  • New analogue of arenastatin A, a potent cytotoxic spongean depsipeptide, with anti-tumor activity.

    abstract：:Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration diffe...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.02.080

    authors： Murakami N,Tamura S,Koyama K,Sugimoto M,Maekawa R,Kobayashi M

    更新日期：2004-05-17 00:00:00

  • Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors.

    abstract：:A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity ag...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.06.060

    authors： Narva S,Chitti S,Amaroju S,Bhattacharjee D,Rao BB,Jain N,Alvala M,Sekhar KVGC

    更新日期：2017-08-15 00:00:00