当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis of new N3-substituted dihydropyrimidine derivatives as L-/T- type calcium channel blockers.

Synthesis of new N3-substituted dihydropyrimidine derivatives as L-/T- type calcium channel blockers.

Abstract：

:Cardiovascular diseases (CVDs) are the main cause of deaths worldwide. Up-to-date, hypertension is the most significant contributing factor to CVDs. Recent clinical studies recommend calcium channel blockers (CCBs) as effective treatment alone or in combination with other medications. Being the most clinically useful CCBs, 1,4-dihydropyridines (DHPs) attracted great interest in improving potency and selectivity. However, the short plasma half-life which may be attributed to the metabolic oxidation to the pyridine-counterparts is considered as a major limitation for this class. Among the most efficient modifications of the DHP scaffold, is the introduction of biologically active N3-substituted dihydropyrimidine mimics (DHPMs). Again, some potent DHPMs showed only in vitro activity due to first pass effect through hydrolysis and removal of the N3-substitutions. Herein, the synthesis of new N3-substituted DHPMs with various functionalities linked to the DHPM core via two-carbon spacer to guard against possible metabolic inactivation is described. It was designed to keep close structural similarities to clinically efficient DHPs and the reported lead DHPMs analogues, while attempting to improve the pharmacokinetic properties through better metabolic stability. Applying whole batch clamp technique, five compounds showed promising L- and T- type calcium channel blocking activity and were identified as lead compounds. Structure requirements for selectivity against Cav1.2 as well against Cav3.2 are described.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Teleb M,Zhang FX,Farghaly AM,Aboul Wafa OM,Fronczek FR,Zamponi GW,Fahmy H

doi

10.1016/j.ejmech.2017.03.080

subject

Has Abstract

pub_date

2017-07-07 00:00:00

pages

52-61

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30249-0

journal_volume

134

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Recent advances in the discovery of potent and selective HDAC6 inhibitors.

    abstract：:Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein traffick...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2017.10.040

    authors： Wang XX,Wan RZ,Liu ZP

    更新日期：2018-01-01 00:00:00

  • Synthesis, X-ray crystal structure and anti-tumor activity of calix[n]arene polyhydroxyamine derivatives.

    abstract：:Calixarene-based compounds are highly effective therapeutic agents against cancer. This study aims to prepare a series of calix [n]arene (n = 4, 6, 8) polyhydroxyamine derivatives (3a-3m) and to study their potential antitumor activities. The single crystal structure of calixs[4]arene derivative 3a was determined thro...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.07.016

    authors： An L,Han LL,Zheng YG,Peng XN,Xue YS,Gu XK,Sun J,Yan CG

    更新日期：2016-11-10 00:00:00

  • Tetracyclic indolines as a novel class of β-lactam-selective resistance-modifying agent for MRSA.

    abstract：:Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relatio...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.09.034

    authors： Zhu Y,Cleaver L,Wang W,Podoll JD,Walls S,Jolly A,Wang X

    更新日期：2017-01-05 00:00:00

  • Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer.

    abstract：:In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The ph...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.12.037

    authors： Jha A,Yadav Y,Naidu AB,Rao VK,Kumar A,Parmar VS,MacDonald WJ,Too CK,Balzarini J,Barden CJ,Cameron TS

    更新日期：2015-03-06 00:00:00

  • Norharmane as a potential chemical entity for development of anticancer drugs.

    abstract：:Cancer is a leading cause of death generally, and to overcome this problem the introduction of a new drug developing is a continuous endeavour. An alkaloid, norharmane and its derivatives, which have anticancer activities, widely distributed in several living and synthetic chemical sources. Herewith, the suggested mec...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2018.11.024

    authors： Sahoo CR,Paidesetty SK,Padhy RN

    更新日期：2019-01-15 00:00:00

  • Synthesis, biological investigation and molecular docking study of N-malonyl-1,2-dihydroisoquinoline derivatives as brain specific and shelf-stable MAO inhibitors.

    abstract：:A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.02.039

    authors： Abd El-Gaber MK,Hassan HY,Mahfouz NM,Farag HH,Bekhit AA

    更新日期：2015-03-26 00:00:00

  • Novel imidazole derivatives as heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2) inhibitors and their cytotoxic activity in human-derived cancer cell lines.

    abstract：:Heme oxygenase (HO) is a cytoprotective enzyme that can be overexpressed in some pathological conditions, including certain cancers. In this work, novel imidazole derivatives were designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). In these compounds the imidazole ring, cruci...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.04.003

    authors： Salerno L,Pittalà V,Romeo G,Modica MN,Marrazzo A,Siracusa MA,Sorrenti V,Di Giacomo C,Vanella L,Parayath NN,Greish K

    更新日期：2015-01-01 00:00:00

  • Pyrrolo[1,2-f]phenanthridines and related non-rigid analogues as antiviral agents.

    abstract：:The pyrrolo[1,2-f]phenanthridines 8-22 and the corresponding non-rigid analogues 23-41 were synthesised and their ability to inhibit the replication of HIV-1 was tested. Only the polycyclic derivatives 10, 11, and 13 showed a weak anti-HIV activity, whereas several pyrrolo-phenanthridines (8, 10, 16-18) were found to ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01289-2

    authors： Almerico AM,Mingoia F,Diana P,Barraja P,Montalbano A,Lauria A,Loddo R,Sanna L,Delpiano D,Setzu MG,Musiu C

    更新日期：2002-01-01 00:00:00

  • Design, synthesis and biological evaluation of novel 2-methoxyestradiol analogs as dual selective estrogen receptor modulators (SERMs) and antiangiogenic agents.

    abstract：:2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological evaluation was performed on their anti-proliferative activities a...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.08.016

    authors： Lao K,Wang Y,Chen M,Zhang J,You Q,Xiang H

    更新日期：2017-10-20 00:00:00

  • Design and synthesis of novel SCM-198 analogs as cardioprotective agents: Structure-activity relationship studies and biological evaluations.

    abstract：:SCM-198 (Leonurine) has attracted great attention due to its cardioprotective effects in myocardial infarction (MI). However, no systematic modifications and structure-activity relationship (SAR) studies could be traced so far. In this study, 35 analogs of SCM-198 were designed, synthesized and their cardioprotective ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.112469

    authors： Luo S,Xu S,Liu J,Ma F,Zhu YZ

    更新日期：2020-08-15 00:00:00

  • Amaryllidaceae alkaloids with new framework types from Zephyranthes candida as potent acetylcholinesterase inhibitors.

    abstract：:Three new Amaryllidaceae alkaloids, named zephycandidines I-III (1-3), were isolated from Zephyranthes candida. The structures of 1-3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. T...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.10.057

    authors： Zhan G,Liu J,Zhou J,Sun B,Aisa HA,Yao G

    更新日期：2017-02-15 00:00:00

  • Prodrug strategy for cancer cell-specific targeting: A recent overview.

    abstract：:The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tiss...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2017.08.010

    authors： Zhang X,Li X,You Q,Zhang X

    更新日期：2017-10-20 00:00:00

  • Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds.

    abstract：:Lapachol is an abundant prenyl naphthoquinone occurring in Brazilian Bignoniaceae that was clinically used, in former times, as an antimalarial drug, despite its moderate effect. Aiming to search for potentially better antimalarials, a series of 1,2,3-triazole derivatives was synthesized by chemical modification of la...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.12.051

    authors： Brandão GC,Rocha Missias FC,Arantes LM,Soares LF,Roy KK,Doerksen RJ,Braga de Oliveira A,Pereira GR

    更新日期：2018-02-10 00:00:00

  • Microwave assisted synthesis of fragrant jasmone heterocyclic analogues.

    abstract：:cis-Jasmone, from jasmonoid group, is an important jasmine odor fragrance compound. The syntheses of new heterocyclic analogues of jasmone were described. Five analogues of this compound were prepared under microwave irradiation and the results of the microwave assisted syntheses were compared with classical, thermall...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.09.012

    authors： Pawełczyk A,Zaprutko L

    更新日期：2006-05-01 00:00:00

  • Synthesis and pharmacological evaluation of novel 5-substituted-1-(phenylsulfonyl)-2-methylbenzimidazole derivatives as anti-inflammatory and analgesic agents.

    abstract：:A series of novel 5-substituted-1-(phenylsulfonyl)-2-methylbenzimidazole derivatives have been synthesized. The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass spectral data and elemental analyses. Compounds were evaluated for their anti-inflammatory and analgesic activity as well as gastri...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.01.067

    authors： Gaba M,Singh D,Singh S,Sharma V,Gaba P

    更新日期：2010-06-01 00:00:00

  • QSAR study of heparanase inhibitors activity using artificial neural networks and Levenberg-Marquardt algorithm.

    abstract：:A linear and non-linear quantitative structure-activity relationship (QSAR) study is presented for modeling and predicting heparanase inhibitors' activity. A data set that consisted of 92 derivatives of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid, furanyl-1,3-thiazol-2-yl and benzoxazol-5-yl acetic acids is u...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.04.014

    authors： Jalali-Heravi M,Asadollahi-Baboli M,Shahbazikhah P

    更新日期：2008-03-01 00:00:00

  • Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of L-chicoric acid, as new HIV-1 integrase inhibitors.

    abstract：:Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of HIV DNA copy into the host cell DNA. L-Chicoric acid (1) has been found to be one of the most potent HIV-1 integrase inhibitor. Caffeoylglycolic and caffeoylamino acid derivatives' halfmeric structures of L-chicoric acid 2 were synthesized ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.02.016

    authors： Lee SU,Shin CG,Lee CK,Lee YS

    更新日期：2007-10-01 00:00:00

  • Diminutive effect on T and B-cell proliferation of non-cytotoxic α-santonin derived 1,2,3-triazoles: a report.

    abstract：:α-Santonin derived new series of 1,2,3-triazoles synthesized through Azide-Alkyne Huisgen 1,3-dipolar cycloaddition reaction between substituted aryl azide and a propargylated α-desmotrosantonin were bio-evaluated for their diminutive effect on ConA induced T-cell and LPS induced B-cell proliferation. Interestingly, m...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.12.018

    authors： Chinthakindi PK,Sangwan PL,Farooq S,Aleti RR,Kaul A,Saxena AK,Murthy YL,Vishwakarma RA,Koul S

    更新日期：2013-02-01 00:00:00

  • Structure-activity relationship studies and pharmacological characterization of N5-heteroarylalkyl-substituted-2-(2-furanyl)thiazolo[5,4-d]pyrimidine-5,7-diamine-based derivatives as inverse agonists at human A2A adenosine receptor.

    abstract：:This paper describes the synthesis and characterization of N5-(hetero)arylalkyl-substituted-thiazolo [5,4-d]pyrimidine-5,7-diamine derivatives (4-19) as novel human (h) A2A adenosine receptor (AR) inverse agonists. Competition binding and cyclic AMP assays indicate that the examined compounds behave as hA2A AR inverse...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.06.020

    authors： Varano F,Catarzi D,Vincenzi F,Falsini M,Pasquini S,Borea PA,Colotta V,Varani K

    更新日期：2018-07-15 00:00:00

  • Synthesis and evaluation of xanthine oxidase inhibitory and antioxidant activities of 2-arylbenzo[b]furan derivatives based on salvianolic acid C.

    abstract：:Xanthine oxidase (XO) is the key enzyme in humans which is related to a variety of diseases such as gout, hyperuricemia and cardiovascular diseases. In this work, a series of 2-arylbenzo[b]furan derivatives were synthesized based on salvianolic acid C, and they were evaluated for xanthine oxidase inhibitory and antiox...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.08.019

    authors： Tang HJ,Zhang XW,Yang L,Li W,Li JH,Wang JX,Chen J

    更新日期：2016-11-29 00:00:00

  • Development of novel 4-aminopyridine derivatives as potential treatments for neurological injury and disease.

    abstract：:The amine position of the K+ channel blocker 4-aminopyridine was functionalized to form amide, carbamate and urea derivatives in an attempt to identify novel compounds which restore conduction in injured spinal cord. Eight derivatives were tested in vitro, using a double sucrose gap chamber, for the ability to restore...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.04.017

    authors： Smith DT,Shi R,Borgens RB,McBride JM,Jackson K,Byrn SR

    更新日期：2005-09-01 00:00:00

  • Structural modifications in the distal, regulatory region of histamine H3 receptor antagonists leading to the identification of a potent anti-obesity agent.

    abstract：:A series of 4-pyridylpiperazine derivatives with varying regulatory region substituents proved to be potent histamine H3 receptor (H3R) ligands in the nanomolar concentration range. The most influential modification that affected the affinity toward the H3R appeared by introducing electron-withdrawing moieties into th...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2020.113041

    authors： Szczepańska K,Pockes S,Podlewska S,Höring C,Mika K,Latacz G,Bednarski M,Siwek A,Karcz T,Nagl M,Bresinsky M,Mönnich D,Seibel U,Kuder KJ,Kotańska M,Stark H,Elz S,Kieć-Kononowicz K

    更新日期：2020-11-24 00:00:00

  • Ferrocene-based guanidine derivatives: in vitro antimicrobial, DNA binding and docking supported urease inhibition studies.

    abstract：:Some novel ferrocenyl guanidines 1-8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with bi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.07.109

    authors： Gul R,Rauf MK,Badshah A,Azam SS,Tahir MN,Khan A

    更新日期：2014-10-06 00:00:00

  • Synthetic cinnamylphenol derivatives as cancer chemopreventive agents.

    abstract：:Several substituted cinnamylphenol (1,3-diphenylpropene) derivatives were synthesized and tested for their inhibitory activities against in vitro Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The prenylated cinnamylphenols were found to show remarkably poten...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2006.12.024

    authors： Ito C,Itoigawa M,Kanematsu T,Imamura Y,Tokuda H,Nishino H,Furukawa H

    更新日期：2007-07-01 00:00:00

  • Synthesis of N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines as antiplatelet agents.

    abstract：:A series of novel N(6)-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized, and their human antiplatelet aggregation activities were evaluated by the stimulation of adenosine 5'-diphosphate (ADP). Some of these compounds showed strong activity, among which compound 5b(11) displayed the highest activity with an IC...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.03.047

    authors： Liu G,Xu J,Chen N,Zhang S,Ding Z,Du H

    更新日期：2012-07-01 00:00:00

  • 3-benzylamino-β-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3.

    abstract：:β-carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of β-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-β-carboline, and evaluated their anti-tumo...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.11.044

    authors： Ikeda R,Iwaki T,Iida T,Okabayashi T,Nishi E,Kurosawa M,Sakai N,Konakahara T

    更新日期：2011-02-01 00:00:00

  • Simultaneous tritium labelling of two potent 5-HT4 ligands.

    abstract：:Two potent and selective 5-HT(4) ligands, [(3)H]-5-[(N-propylpiperidin-4-yl)methoxy]-1,2,3,4-tetrahydrobenzo[h][1,6] naphthyridine (1a) and [(3)H]-1-methyl-5-[(N-propylpiperidin-4-yl)methoxy]pyrrolo[1,2-a]thieno[2,3-e]pyrazine (2a) were radiolabelled with tritium. Radioactive labelling was achieved by simultaneous tri...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.12.012

    authors： Sobrio F,Lemaitre S,Hinsberger A,Barré L,Rousseau B,Rault S

    更新日期：2010-03-01 00:00:00

  • Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain.

    abstract：:A series of 3-(4-(aminoalkoxy)benzylidene)-chroman-4-ones 7a-r were designed and synthesized as analogs of homoisoflavonoids which are well known natural products with diverse pharmacological properties related to Alzheimer's disease. The in vitro anti-cholinesterase activity of designed compounds 7a-r against AChE an...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2015.04.055

    authors： Pourshojaei Y,Gouranourimi A,Hekmat S,Asadipour A,Rahmani-Nezhad S,Moradi A,Nadri H,Moghadam FH,Emami S,Foroumadi A,Shafiee A

    更新日期：2015-06-05 00:00:00

  • Neuroprotective effect of synthetic chalcone derivatives as competitive dual inhibitors against μ-calpain and cathepsin B through the downregulation of tau phosphorylation and insoluble Aβ peptide formation.

    abstract：:A series of chalcone derivatives were synthesized and evaluated for their μ-calpain and cathepsin B inhibitory activities. Among the tested chalcone derivatives, two compounds, 7 and 11, showed potent inhibitory activities against μ-calpain and cathepsin B and were selected for further evaluation. Compounds 7 and 11 s...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.06.008

    authors： Jeon KH,Lee E,Jun KY,Eom JE,Kwak SY,Na Y,Kwon Y

    更新日期：2016-10-04 00:00:00

  • Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.

    abstract：:Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylen...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2014.03.035

    authors： Aslam S,Zaib S,Ahmad M,Gardiner JM,Ahmad A,Hameed A,Furtmann N,Gütschow M,Bajorath J,Iqbal J

    更新日期：2014-05-06 00:00:00