当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > 3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes.

3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes.

Abstract：

:A series of 3,4-dihydroquinazoline derivatives consisting of the selected compounds from our chemical library on the diversity basis and the new synthetic compounds were in vitro tested for their inhibitory activities for both acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) enzymes. It was discovered that most of the compounds displayed weak AChE and strong BuChE inhibitory activities. In particular, compound 8b and 8d were the most active compounds in the series against BChE with IC50 values of 45nM and 62nM, as well as 146- and 161-fold higher affinity to BChE, respectively. To understand the excellent activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of 3,4-dihydroquinazoline derivatives. As expected, compound 8b and 8d bind to both catalytic anionic site (CAS) and peripheral site (PS) of BChE with better interaction energy values than AChE, in agreement with our experimental data. Furthermore, the non-competitive/mixed-type inhibitions of both compounds further confirmed their dual binding nature in kinetic studies.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Park B,Nam JH,Kim JH,Kim HJ,Onnis V,Balboni G,Lee KT,Park JH,Catto M,Carotti A,Lee JY

doi

10.1016/j.bmcl.2017.01.068

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

1179-1185

issue

5

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30080-X

journal_volume

27

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Lithospermic acid derivatives from Lithospermum erythrorhizon increased expression of serine palmitoyltransferase in human HaCaT cells.

    abstract：:A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.01.052

    authors： Thuong PT,Kang KW,Kim JK,Seo DB,Lee SJ,Kim SH,Oh WK

    更新日期：2009-03-15 00:00:00

  • Design and synthesis of potent macrocyclic renin inhibitors.

    abstract：:Two types of P1-P3-linked macrocyclic renin inhibitors containing the hydroxyethylene isostere (HE) scaffold just outside the macrocyclic ring have been synthesized. An aromatic or aliphatic substituent (P3sp) was introduced in the macrocyclic ring aiming at the S3 subpocket (S3sp) in order to optimize the potency. A ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.140

    authors： Sund C,Belda O,Wiktelius D,Sahlberg C,Vrang L,Sedig S,Hamelink E,Henderson I,Agback T,Jansson K,Borkakoti N,Derbyshire D,Eneroth A,Samuelsson B

    更新日期：2011-01-01 00:00:00

  • Detection of NAD(P)H-dependent enzyme activity by time-domain ratiometry of terbium luminescence.

    abstract：:NAD(P)H-dependent oxidoreductases play important roles in biology. Recently, we reported that the luminescence lifetime of some Tb(3+) complexes is sensitive to NAD(P)H, and we used this phenomenon to detect activities of these enzymes. However, conventional time-resolved luminescence assays are susceptible to static ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.03.038

    authors： Terai T,Ito H,Hanaoka K,Komatsu T,Ueno T,Nagano T,Urano Y

    更新日期：2016-05-01 00:00:00

  • 2,3-Diaminopyridine as a platform for designing structurally unique nonpeptide bradykinin B1 receptor antagonists.

    abstract：:A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.077

    authors： Feng DM,Wai JM,Kuduk SD,Ng C,Murphy KL,Ransom RW,Reiss D,Chang RS,Harrell CM,MacNeil T,Tang C,Prueksaritanont T,Freidinger RM,Pettibone DJ,Bock MG

    更新日期：2005-05-02 00:00:00

  • d(TGGGAG) with 5'-nucleobase-attached large hydrophobic groups as potent inhibitors for HIV-1 envelop proteins mediated cell-cell fusion.

    abstract：:The Hotoda's sequence substituted with TBDPS via 5'-end nucleobase existed as parallel quadruplex structure and exhibited inhibitory activities in an HIV-1 envelop proteins mediated cell-cell fusion assay. This result demonstrated that the 5'-aromatic groups of the Hotoda's sequence are allowed to have a large spatial...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.007

    authors： Chen W,Xu L,Cai L,Zheng B,Wang K,He J,Liu K

    更新日期：2011-10-01 00:00:00

  • Urokinase-type plasminogen activator expression and Rac1/WAVE-2/Arp2/3 pathway are blocked by pterostilbene to suppress cell migration and invasion in MDA-MB-231 cells.

    abstract：:Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects o...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.115

    authors： Ko HS,Kim JS,Cho SM,Lee HJ,Ahn KS,Kim SH,Lee EO

    更新日期：2014-02-15 00:00:00

  • Ligand binding cooperativity: Bioisosteric replacement of CO with SO2 among thrombin inhibitors.

    abstract：:Ligand-protein binding is a complex process that involves the formation of number of non-covalent interactions, e.g. H-bonds and hydrophobic interactions, between the ligand and the protein host. Upon binding, ligand functional groups can act synergistically (positive cooperativity) to improve the overall ligand bindi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.07.024

    authors： Said AM,Hangauer DG

    更新日期：2016-08-15 00:00:00

  • Syntheses and evaluation of quinoline derivatives as novel retinoic acid receptor alpha antagonists.

    abstract：:In the course of studies on novel retinoids, we have designed and synthesized a series of quinoline derivatives. One of them, 4-[5-[8-(1-methylethyl)-4-phenyl-2-quinolinyl]-1H-2-pyrrolyl]benzoic acid (12f) shows potent RARalpha-selective antagonistic activity. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00177-9

    authors： Kikuchi K,Tagami K,Hibi S,Yoshimura H,Tokuhara N,Tai K,Hida T,Yamauchi T,Nagai M

    更新日期：2001-05-07 00:00:00

  • Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1).

    abstract：:Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.12.051

    authors： El-Ayache NC,Li SH,Warnock M,Lawrence DA,Emal CD

    更新日期：2010-02-01 00:00:00

  • The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives.

    abstract：:In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.05.086

    authors： Yasuno T,Ohe T,Takahashi K,Nakamura S,Mashino T

    更新日期：2015-08-15 00:00:00

  • Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of some chrysene derivatives.

    abstract：:Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00520-4

    authors： Becker FF,Banik BK

    更新日期：1998-10-20 00:00:00

  • Synthesis and biological evaluation of N9-cis-cyclobutylpurine derivatives for use as cyclin-dependent kinase (CDK) inhibitors.

    abstract：:A novel 6-aminopurine scaffold bearing an N9-cis-cyclobutyl moiety was designed using structure-based molecular design based on two known CDK inhibitors, dinaciclib and Cmpd-27. A series of novel 6-aminopurine compounds was prepared for structure-activity relationship (SAR) studies of CDK2 and CDK5 inhibitors. Among t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.08.018

    authors： Park SJ,Kim E,Yoo M,Lee JY,Park CH,Hwang JY,Ha JD

    更新日期：2017-09-15 00:00:00

  • Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents.

    abstract：:A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines was prepared and tested for its in vitro cytotoxic activity against a panel of 12 human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity and were further tested for their in vivo efficacy in the HT-29 human colon ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.10.020

    authors： Sharma VM,Adi Seshu KV,Chandra Sekhar V,Madan S,Vishnu B,Babu PA,Vamsee Krishna C,Sreenu J,Ravi Krishna V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Kumar TS

    更新日期：2004-01-05 00:00:00

  • Discovery of 5-hydroxyalkyl-4-phenylpyridines as a new class of glucagon receptor antagonists.

    abstract：:5-Hydroxyalkyl-4-phenylpyridines have been identified as a novel class of glucagon antagonists with potential utility for the treatment of diabetes. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of a potent antago...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00766-1

    authors： Ladouceur GH,Cook JH,Doherty EM,Schoen WR,MacDougall ML,Livingston JN

    更新日期：2002-02-11 00:00:00

  • New antibacterial isocoumarin glycosides from a wetland soil derived fungal strain Metarhizium anisopliae.

    abstract：:Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.01.074

    authors： Tian JF,Li PJ,Li XX,Sun PH,Gao H,Liu XZ,Huang P,Tang JS,Yao XS

    更新日期：2016-03-01 00:00:00

  • Microbial transformation of acetyl-11-keto-β-boswellic acid and their inhibitory activity on LPS-induced NO production.

    abstract：:The capabilities of 20 strains of fungi to transform acetyl-11-keto-β-boswellic (AKBA) were screened. And biotransformation of AKBA by Cunninghamella blakesleana AS 3.970 afforded five metabolites (1-5), while two metabolites (6, 7) were isolated from biotransformation of Cunninghamella elegans AS 3.1207. The chemical...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.12.086

    authors： Sun Y,Liu D,Xi R,Wang X,Wang Y,Hou J,Zhang B,Wang C,Liu K,Ma X

    更新日期：2013-03-01 00:00:00

  • Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004.

    abstract：:New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.07.080

    authors： Raeppel F,Raeppel SL,Therrien E

    更新日期：2015-09-15 00:00:00

  • Synthesis and fluorescent study of 5-phenyl furocoumarin derivatives as vasodilatory agents.

    abstract：:Two series of 5-phenyl furocoumarin derivatives were designed and prepared based on our previous research. All new compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Furthermore, they were screened for their vasodilatory activity on the mesenteric artery of Sprague-Dawley rats, and they all presente...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.056

    authors： Wang C,Wang T,Huang L,Lu W,Zhang J,He H

    更新日期：2016-01-15 00:00:00

  • Discovery of medium ring thiophosphorus based heterocycles as antiproliferative agents.

    abstract：:Hydrogen sulfide (H2S) has been investigated for its potential in therapy. Recently, we reported novel H2S donor molecules based on a thiophosphorus core, which slowly release H2S and have improved anti-proliferative activity in cancer cell lines compared to the most widely studied H2S donor GYY4137 (1). Herein, we ha...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.12.079

    authors： Feng W,Novera W,Peh K,Neo D,Ramanujulu PM,Moore PK,Deng LW,Dymock BW

    更新日期：2017-02-15 00:00:00

  • Ganglioside GM1 mimics: lipophilic substituents improve affinity for cholera toxin.

    abstract：:Ganglioside GM1 mimics including (R)-2-hydroxy-3-cyclohexylpropionic acid or (R)-2-hydroxy-3-phenylpropionic acid as replacements for NeuAc are stronger cholera toxin binders than the parent ligand 2, which includes (R)-2-hydroxy-propionic acid. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.07.007

    authors： Arosio D,Baretti S,Cattaldo S,Potenza D,Bernardi A

    更新日期：2003-11-03 00:00:00

  • Activation of antibacterial prodrugs by peptide deformylase.

    abstract：:5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the defo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00167-0

    authors： Wei Y,Pei D

    更新日期：2000-05-15 00:00:00

  • Potent and selective oxytocin receptor agonists without disulfide bridges.

    abstract：:Oxytocin (OT) is a neuropeptide involved in a wide variety of physiological actions, both peripherally and centrally. Many human studies have revealed the potential of OT to treat autism spectrum disorders and schizophrenia. OT interacts with the OT receptor (OTR) as well as vasopressin 1a and 1b receptors (V1aR, V1bR...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.04.030

    authors： Adachi Y,Sakimura K,Shimizu Y,Nakayama M,Terao Y,Yano T,Asami T

    更新日期：2017-06-01 00:00:00

  • Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands.

    abstract：:1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I(2) imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I(2) imidazoline receptors (K(i)=6.2 nM) and with exceptional (> or =1000-fold) selectivity relativ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.033

    authors： Chang-Fong J,Tyacke RJ,Lau A,Westaway J,Hudson AL,Glennon RA

    更新日期：2004-02-23 00:00:00

  • Synthesis and antibacterial activity of novel (un)substituted benzotriazolyl oxazolidinone derivatives.

    abstract：:A series of novel (un)substituted benzotriazolyl oxazolidinone derivatives has been synthesized and tested for in vitro antibacterial activities by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms, some of which are resistant to methicillin and vancomycin. C...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.04.045

    authors： Dixit PP,Nair PS,Patil VJ,Jain S,Arora SK,Sinha N

    更新日期：2005-06-15 00:00:00

  • Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.

    abstract：:The affinity of a series of 2', 3'- and 5-modified thymidine analogues for Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) was evaluated. The affinities of several non-phosphorylated analogues are in the same order of magnitude as those of their phosphorylated congeners. In view of drug delivery pro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00643-7

    authors： Vanheusden V,Van Rompaey P,Munier-Lehmann H,Pochet S,Herdewijn P,Van Calenbergh S

    更新日期：2003-09-15 00:00:00

  • Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoprotein.

    abstract：:Installation of a C2-aminopropyl side chain to the 2,4-diaryl-2,5-dihydropyrrole series of kinesin spindle protein (KSP) inhibitors results in potent, water soluble compounds, but the aminopropyl group induces susceptibility to cellular efflux by P-glycoprotein (Pgp). We show that by carefully modulating the basicity ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.03.006

    authors： Cox CD,Breslin MJ,Whitman DB,Coleman PJ,Garbaccio RM,Fraley ME,Zrada MM,Buser CA,Walsh ES,Hamilton K,Lobell RB,Tao W,Abrams MT,South VJ,Huber HE,Kohl NE,Hartman GD

    更新日期：2007-05-15 00:00:00

  • Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN

    abstract：:A structure-activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.03.113

    authors： Engers DW,Frist AY,Lindsley CW,Hong CC,Hopkins CR

    更新日期：2013-06-01 00:00:00

  • Synthesis of [1,2,4]triazolo[1,5-a]pyrazines as adenosine A2A receptor antagonists.

    abstract：:Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.07.052

    authors： Dowling JE,Vessels JT,Haque S,Chang HX,van Vloten K,Kumaravel G,Engber T,Jin X,Phadke D,Wang J,Ayyub E,Petter RC

    更新日期：2005-11-01 00:00:00

  • Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease.

    abstract：:A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the protease-bound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.107

    authors： Clarke MO,Byun D,Chen X,Doerffler E,Leavitt SA,Sheng XC,Yang CY,Kim CU

    更新日期：2012-01-15 00:00:00

  • Structure-activity relationships in a series of NPY Y5 antagonists: 3-amido-9-ethylcarbazoles, core-modified analogues and amide isosteres.

    abstract：:Beginning with carbazole 1a, the amide and alkyl substituents were optimized to maintain potency while adding solubilizing groups. Efforts to replace the 3-amino-9-ethylcarbazole core, a known carcinogen, used the SAR generated in the carbazole series for guidance and led to the synthesis of a number of core-modified ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00329-9

    authors： Hammond M,Elliott RL,Gillaspy ML,Hager DC,Hank RF,LaFlamme JA,Oliver RM,DaSilva-Jardine PA,Stevenson RW,Mack CM,Cassella JV

    更新日期：2003-06-16 00:00:00