当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives.

Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives.

Abstract：

:N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough for the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 A confirmed that a dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: a chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Bartolucci C,Haller LA,Jordis U,Fels G,Lamba D

doi

10.1021/jm901296p

subject

Has Abstract

pub_date

2010-01-28 00:00:00

pages

745-51

issue

2

eissn

0022-2623

issn

1520-4804

journal_volume

53

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents.

    abstract：:Novel classical antifolates (3 and 4) and 17 nonclassical antifolates (11-27) were synthesized as antitumor and/or antiopportunistic infection agents. Intermediates for the synthesis of 3, 4, and 11-27 were 2,4-diamino-5-alkylsubstituted-7H-pyrrolo[2,3-d]pyrimidines, 31 and 38, prepared by a ring transformation/ring a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800244v

    authors： Gangjee A,Jain HD,Queener SF,Kisliuk RL

    更新日期：2008-08-14 00:00:00

  • Binding site detection and druggability index from first principles.

    abstract：:In drug discovery, it is essential to identify binding sites on protein surfaces that drug-like molecules could exploit to exert a biological effect. Both X-ray crystallography and NMR experiments have demonstrated that organic solvents bind precisely at these locations. We show that this effect is reproduced using mo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801385d

    authors： Seco J,Luque FJ,Barril X

    更新日期：2009-04-23 00:00:00

  • 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]-2,4- imidazolidinediones, a new class of skeletal muscle relaxants.

    abstract：:A series of 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]- 2,4-imidazolidinediones (6a-t) was synthesized, and the compounds were evaluated for direct skeletal muscle inhibition in the pithed rat gastrocnemius muscle preparation. The correctness of structural assignment of the new series was verified by alte...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00385a006

    authors： White RL Jr,Wessels FL,Schwan TJ,Ellis KO

    更新日期：1987-02-01 00:00:00

  • Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging.

    abstract：:It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tro...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00059a010

    authors： Meltzer PC,Liang AY,Brownell AL,Elmaleh DR,Madras BK

    更新日期：1993-04-02 00:00:00

  • In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors.

    abstract：:The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01482

    authors： Madia VN,Messore A,Pescatori L,Saccoliti F,Tudino V,De Leo A,Scipione L,Fiore L,Rhoden E,Manetti F,Oberste MS,Di Santo R,Costi R

    更新日期：2019-01-24 00:00:00

  • Discovery of a Thiadiazole-Pyridazine-Based Allosteric Glutaminase 1 Inhibitor Series That Demonstrates Oral Bioavailability and Activity in Tumor Xenograft Models.

    abstract：:Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00260

    authors： Finlay MRV,Anderton M,Bailey A,Boyd S,Brookfield J,Cairnduff C,Charles M,Cheasty A,Critchlow SE,Culshaw J,Ekwuru T,Hollingsworth I,Jones N,Leroux F,Littleson M,McCarron H,McKelvie J,Mooney L,Nissink JWM,Perkins D,

    更新日期：2019-07-25 00:00:00

  • Synthesis and biological evaluation of 14-alkoxymorphinans. 20. 14-phenylpropoxymetopon: an extremely powerful analgesic.

    abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030878b

    authors： Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

    更新日期：2003-09-11 00:00:00

  • Potent inhibition of Grb2 SH2 domain binding by non-phosphate-containing ligands.

    abstract：:Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980388x

    authors： Yao ZJ,King CR,Cao T,Kelley J,Milne GW,Voigt JH,Burke TR Jr

    更新日期：1999-01-14 00:00:00

  • Antagonists of slow-reacting substance of anaphylaxis. 1. Pyrido[2,1-b]quinazolinecarboxylic acid derivatives.

    abstract：:Members of a series of basic amide and ester derivatives of 2-substituted pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated for their ability to prevent slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea. The results indicate that the presence of a branched-cha...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00365a016

    authors： Tilley JW,Levitan P,Welton AF,Crowley HJ

    更新日期：1983-11-01 00:00:00

  • Synthesis and biological activities of novel pleuromutilin derivatives with a substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors.

    abstract：:A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500374c

    authors： Shang R,Pu X,Xu X,Xin Z,Zhang C,Guo W,Liu Y,Liang J

    更新日期：2014-07-10 00:00:00

  • Spirocyclopropyl beta-lactams as mechanism-based inhibitors of serine beta-lactamases. Synthesis by rhodium-catalyzed cyclopropanation of 6-diazopenicillanate sulfone.

    abstract：:Class A-class C mechanism-based beta-lactamase inhibitors were designed on the basis of the intermediacy of an oxycarbenium species capable of cross-linking with amino acids residues in the active site. Penams 24 and 27 were very potent against AmpC in vitro. The MIC values of 24 in combination with piperacillin again...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm034056q

    authors： Sandanayaka VP,Prashad AS,Yang Y,Williamson RT,Lin YI,Mansour TS

    更新日期：2003-06-19 00:00:00

  • Structural studies of metyrapone: a potent inhibitor of cytochrome P-450.

    abstract：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00363a008

    authors： Rossi M

    更新日期：1983-09-01 00:00:00

  • Synthesis, characterization, and comparative in vitro cytotoxicity studies of platinum(II), palladium(II), and gold(III) methylsarcosinedithiocarbamate complexes.

    abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049191x

    authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

    更新日期：2005-03-10 00:00:00

  • Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective agonists.

    abstract：:On the basis of docking studies carried out using the recently published cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, whic...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0603466

    authors： Manera C,Benetti V,Castelli MP,Cavallini T,Lazzarotti S,Pibiri F,Saccomanni G,Tuccinardi T,Vannacci A,Martinelli A,Ferrarini PL

    更新日期：2006-10-05 00:00:00

  • Reversible ketomethylene-based inhibitors of human neutrophil proteinase 3.

    abstract：:Neutrophil serine proteases, proteinase 3 (PR3) and human neutrophil elastase (HNE), are considered as targets for chronic inflammatory diseases. Despite sharing high sequence similarity, the two enzymes have different substrate specificities and functions. While a plethora of HNE inhibitors exist, PR3 specific inhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500782s

    authors： Budnjo A,Narawane S,Grauffel C,Schillinger AS,Fossen T,Reuter N,Haug BE

    更新日期：2014-11-26 00:00:00

  • Development of Potent PfCLK3 Inhibitors Based on TCMDC-135051 as a New Class of Antimalarials.

    abstract：:The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for the survival of blood stage Plasmodium falciparum. We recently validated PfCLK3 as a drug target in malaria that offers prophylactic, transmission blocking, and curative potential. Herein, we descri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00451

    authors： Mahindra A,Janha O,Mapesa K,Sanchez-Azqueta A,Alam MM,Amambua-Ngwa A,Nwakanma DC,Tobin AB,Jamieson AG

    更新日期：2020-09-10 00:00:00

  • Discovery of bishomo(hetero)arylpiperazines as novel multifunctional ligands targeting dopamine D(3) and serotonin 5-HT(1A) and 5-HT(2A) receptors.

    abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100294b

    authors： Butini S,Campiani G,Franceschini S,Trotta F,Kumar V,Guarino E,Borrelli G,Fiorini I,Novellino E,Fattorusso C,Persico M,Orteca N,Sandager-Nielsen K,Jacobsen TA,Madsen K,Scheel-Kruger J,Gemma S

    更新日期：2010-06-24 00:00:00

  • Synthesis and Biological Validation of a Harmine-Based, Central Nervous System (CNS)-Avoidant, Selective, Human β-Cell Regenerative Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) Inhibitor.

    abstract：:Recently, our group identified that harmine is able to induce β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. Since, harmine suffers from a lack of selectivity, both against other kinases and CNS off-targets, we therefore sought to expand structure-activity relationships for harmi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01379

    authors： Kumar K,Wang P,Wilson J,Zlatanic V,Berrouet C,Khamrui S,Secor C,Swartz EA,Lazarus M,Sanchez R,Stewart AF,Garcia-Ocana A,DeVita RJ

    更新日期：2020-03-26 00:00:00

  • Synthesis of fluorinated brassinosteroids based on alkene cross-metathesis and preliminary biological assessment.

    abstract：:Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900495f

    authors： Eignerová B,Slavíková B,Budĕsínský M,Dracínský M,Klepetárová B,St'astná E,Kotora M

    更新日期：2009-09-24 00:00:00

  • Potential antitumor agents: synthesis and biological properties of aliphatic amino acid 9-hydroxyellipticinium derivatives.

    abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00375a013

    authors： Auclair C,Voisin E,Banoun H,Paoletti C,Bernadou J,Meunier B

    更新日期：1984-09-01 00:00:00

  • Potential oxidative pathways of brain catecholamines.

    abstract：:The possibility that catecholamines can be oxidized via aberrant pathways in vivo is open to question, but in vitro oxidation via aerobic manipulations is established. Assuming oxidation does occur, we have examined quantitatively the fast chemical reactions of the initial oxidation products, the o-quinones. The natur...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00223a008

    authors： Tse DC,McCreery RL,Adams RN

    更新日期：1976-01-01 00:00:00

  • 4-Amino-5-arylpyrimidines as antiinflammatory agents.

    abstract：:4-Amino-5-arylpyrimidines were synthesized by a variety of methods and have demonstrated antiinflammatory activity in the carrageenan-induced edema in the rat but displayed little activity against adjuvant-induced arthritis in rats or against uv-induced erythema in guinea pigs. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00240a021

    authors： Lang SA Jr,Cohen E

    更新日期：1975-06-01 00:00:00

  • Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.

    abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01858

    authors： Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

    更新日期：2018-02-22 00:00:00

  • New inhibitors of human renin that contain novel replacements at the P2 site.

    abstract：:A series of renin inhibitors with novel modifications at the P2 site has been prepared. Structure-activity relationships reveal that for a particular P2 fragment the in vitro potency is highly dependent on the nature of the P2' portion in addition to the P1-P1' group. The length of the P2 side chain and choice of epsi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00108a004

    authors： Doherty AM,Kaltenbronn JS,Hudspeth JP,Repine JT,Roark WH,Sircar I,Tinney FJ,Connolly CJ,Hodges JC,Taylor MD

    更新日期：1991-04-01 00:00:00

  • Ibotenic acid analogues. Synthesis and biological and in vitro activity of conformationally restricted agonists at central excitatory amino acid receptors.

    abstract：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00371a005

    authors： Krogsgaard-Larsen P,Nielsen EO,Curtis DR

    更新日期：1984-05-01 00:00:00

  • Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.

    abstract：:We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and sugg...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100249w

    authors： Karlberg T,Markova N,Johansson I,Hammarström M,Schütz P,Weigelt J,Schüler H

    更新日期：2010-07-22 00:00:00

  • Design of potent, selective, and orally bioavailable inhibitors of cysteine protease cathepsin k.

    abstract：:Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies on a series of rever...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030373l

    authors： Tavares FX,Boncek V,Deaton DN,Hassell AM,Long ST,Miller AB,Payne AA,Miller LR,Shewchuk LM,Wells-Knecht K,Willard DH Jr,Wright LL,Zhou HQ

    更新日期：2004-01-29 00:00:00

  • 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-ones--inhibitors of blood platelet cAMP phosphodiesterase and induced aggregation.

    abstract：:A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives was synthesized and evaluated as inhibitors of cAMP hydrolysis by a crude human platelet phosphodiesterase preparation and as inhibitors of ADP- and collagen-induced aggregation of rabbit blood platelets. The parent structure 7a, demonstrated potent i...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00113a033

    authors： Meanwell NA,Roth HR,Smith EC,Wedding DL,Wright JJ,Fleming JS,Gillespie E

    更新日期：1991-09-01 00:00:00

  • Hypolipidemic 2-[4-(1,1-dimethylethyl)phenyl]-4H-3,1-benzoxazin-4-ones. Structure-activity relationships of a novel series of high-density lipoprotein elevators.

    abstract：:The preparation and plasma lipid altering characteristics of a series of 4H-3,1-benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is disp...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00121a047

    authors： Fenton G,Newton CG,Wyman BM,Bagge P,Dron DI,Riddell D,Jones GD

    更新日期：1989-01-01 00:00:00

  • 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 2. Effect of pyrrole-C2 and/or -C4 substitutions on biological activity.

    abstract：:Previous SAR studies (Part 1: Mai, A.; et al. J. Med. Chem. 2003, 46, 512-524) performed on some portions (pyrrole-C4, pyrrole-N1, and hydroxamate group) of 3-(4-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1a) highlighted its 4-phenylacetyl (1b) and 4-cynnamoyl (1c) analogues as more potent compounds in ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030990+

    authors： Mai A,Massa S,Cerbara I,Valente S,Ragno R,Bottoni P,Scatena R,Loidl P,Brosch G

    更新日期：2004-02-26 00:00:00