European Journal of Medicinal Chemistry Impact Factor & Information

Publisher: Elsevier

Journal description

The European Journal of Medicinal Chemistry publishes studies on all aspects of medicinal chemistry: Organic synthesis; Biological behavior; Pharmacological activity; Drug design; QSAR; Molecular Modeling; Drug-receptor interactions; Molecular aspects of drug metabolism; Prodrug synthesis and Drug targeting. The journal accepts papers from any country, European or otherwise, and provides a medium for publication of original papers, laboratory notes, short or preliminary communications, new products and invited reviews.

Current impact factor: 3.43

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 3.432
2012 Impact Factor 3.499
2011 Impact Factor 3.346
2010 Impact Factor 3.193
2009 Impact Factor 3.269
2008 Impact Factor 2.882
2007 Impact Factor 2.301
2006 Impact Factor 2.187
2005 Impact Factor 2.022
2004 Impact Factor 1.673
2003 Impact Factor 1.681
2002 Impact Factor 1.705
2001 Impact Factor 1.077
2000 Impact Factor 1.306
1999 Impact Factor 1.074
1998 Impact Factor 1.116
1997 Impact Factor 0.809
1996 Impact Factor 0.675
1995 Impact Factor 0.746
1994 Impact Factor 0.775
1993 Impact Factor 0.716
1992 Impact Factor 0.624

Impact factor over time

Impact factor
Year

Additional details

5-year impact 3.36
Cited half-life 5.30
Immediacy index 0.61
Eigenfactor 0.01
Article influence 0.70
Website European Journal of Medicinal Chemistry website
Other titles European journal of medicinal chemistry (Online), Eur j med chem
ISSN 1768-3254

Publisher details

Elsevier

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Pre-print allowed on any website or open access repository
    • Voluntary deposit by author of authors post-print allowed on authors' personal website, arXiv.org or institutions open scholarly website including Institutional Repository, without embargo, where there is not a policy or mandate
    • Deposit due to Funding Body, Institutional and Governmental policy or mandate only allowed where separate agreement between repository and the publisher exists.
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months .
    • Set statement to accompany deposit
    • Published source must be acknowledged
    • Must link to journal home page or articles' DOI
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PubMed Central after 12 months
    • Publisher last contacted on 18/10/2013
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aromatase, a cytochrome P450 enzyme complex present in breast tissues, plays a significant role in the biosynthesis of important endogenous estrogens from androgens. The source of estrogen production in breast cancer tissues is intra-tumoral aromatase, and inhibition of aromatase may inhibit the growth stimulation effect of estrogens in breast cancer tissues. Consequently, aromatase is considered a useful therapeutic target in the treatment and prevention of estrogen-dependent breast cancer. Recently, different natural products and synthetic compounds have been rapidly developed, studied, and evaluated for aromatase inhibitory activity. Aromatase inhibitors are classified into two categories on the basis of their chemical structures, i.e., steroidal and nonsteroidal aromatase inhibitors. This review highlights the synthetic steroidal and nonsteroidal aromatase inhibitors reported in the literature in the last few years and will aid medicinal chemists in the design and synthesis of novel and pharmacologically-potent aromatase inhibitors for the treatment of breast cancer.
    European Journal of Medicinal Chemistry 09/2015; 102:375. DOI:10.1016/j.ejmech.2015.08.010
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    ABSTRACT: In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 μg/ml to 0.0156 μg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 μg/ml), as well as its high metabolic stability in human liver microsomes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:471-476. DOI:10.1016/j.ejmech.2015.08.023
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    ABSTRACT: Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a-3d and 5) displayed strong antitumor properties, with IC50 values between 4 and 18 μM. Compound 3c, containing piperidine group at C-28 position, had IC50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 μM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 μM 3c. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102(18):249–255. DOI:10.1016/j.ejmech.2015.08.004
  • Papiya Majumdar · Chandramohan Bathula · Suparna M Basu · Subhendu K Das · Rahul Agarwal · Santanu Hati · Ashutosh Singh · Subhabrata Sen · Benu Brata Das
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    ABSTRACT: DNA opoisomerase I is a potential chemotherapeutic target. Here, we designed and synthesized a library comprising of hydantoin and thiohydantoin derivatives and tested them against human and Leishmania Top1. One of the thiohydantoin compounds with substituted thiophenyl as the central moiety (compound 15) exhibited potent inhibition of human Top1 (HTop1) through stabilization of Top1-DNA cleavage complexes and showed selective anticancer activity against human cervical carcinoma (HeLa) and breast carcinoma (MCF-7) cell lines. Molecular modeling studies with HTop1 rationalized the inhibitory mechanism of compound 15. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:540-551. DOI:10.1016/j.ejmech.2015.08.032
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    ABSTRACT: 17β-Estradiol (E2), the most potent human estrogen, is known to be involved in the etiology of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the last step of E2 biosynthesis and is thus a promising target for the treatment of EDD. The previously described bicyclic substituted hydroxyphenyl methanones (BSHs) display high inhibitory potency towards human 17β-HSD1, but marginal activity towards rodent 17β-HSD1, precluding a proof of principle study in an animal endometriosis model. The aim of this work was to perform structural optimizations in the BSHs class to enhance inhibitory activity against rodent (mouse and rat) 17β-HSD1 while maintaining activity against the human enzyme. The introduction of fluorine atoms on the benzoyl moiety resulted in compounds with the desired properties. Molecular docking and homology modelling were applied to elucidate the binding mode and interspecies differences in activity. Compound 33 is the most potent inhibitor of both human and rat 17β-HSD1 up to date (IC50 = 2 nM and 97 nM, respectively).
    European Journal of Medicinal Chemistry 08/2015; DOI:10.1016/j.ejmech.2015.08.030
  • Giovanna Sociali · Lauretta Galeno · Marco Daniele Parenti · Alessia Grozio · Inga Bauer · Mario Passalacqua · Silvia Boero · Alessandra Donadini · Enrico Millo · Marta Bellotti · [...] · Patrizia Damonte · Alessandra Puddu · Claudia Ferroni · Greta Varchi · Claudio Franceschi · Alberto Ballestrero · Alessandro Poggi · Santina Bruzzone · Alessio Nencioni · Alberto Del Rio
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    ABSTRACT: The NAD(+)-dependent sirtuin SIRT6 is highly expressed in human breast, prostate, and skin cancer where it mediates resistance to cytotoxic agents and prevents differentiation. Thus, SIRT6 is an attractive target for the development of new anticancer agents to be used alone or in combination with chemo- or radiotherapy. Here we report on the identification of novel quinazolinedione compounds with inhibitory activity on SIRT6. As predicted based on SIRT6's biological functions, the identified new SIRT6 inhibitors increase histone H3 lysine 9 acetylation, reduce TNF-α production and increase glucose uptake in cultured cells. In addition, these compounds exacerbate DNA damage and cell death in response to the PARP inhibitor olaparib in BRCA2-deficient Capan-1 cells and cooperate with gemcitabine to the killing of pancreatic cancer cells. In conclusion, new SIRT6 inhibitors with a quinazolinedione-based structure have been identified which are active in cells and could potentially find applications in cancer treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:530-539. DOI:10.1016/j.ejmech.2015.08.024
  • Meng-I Lin · Bo-Han Su · Chia-Hsin Lee · Suz-Ting Wang · Wen-Chun Wu · Prasad Dangate · Shi-Yun Wang · Wen-I Huang · Ting-Jen Cheng · Olivia A Lin · Yih-Shyun E Cheng · Yufeng Jane Tseng · Chung-Ming Sun
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    ABSTRACT: The influenza nucleoprotein (NP) is a single-strand RNA-binding protein and the core of the influenza ribonucleoprotein (RNP) particle that serves many critical functions for influenza replication. NP has been considered as a promising anti-influenza target. A new class of anti-influenza compounds, nucleozin and analogues were reported recently in several laboratories to inhibit the synthesis of influenza macromolecules and prevent the cytoplasmic trafficking of the influenza RNP. In this study, pyrimido-pyrrolo-quinoxalinedione (PPQ) analogues as a new class of novel anti-influenza agents are reported. Compound PPQ-581 was identified as a potential anti-influenza lead with EC50 value of 1 μM for preventing virus-induced cytopathic effects. PPQ produces similar anti-influenza effects as nucleozin does in influenza-infected cells. Treatment with PPQ at the beginning of H1N1 infection inhibited viral protein synthesis, while treatment at later times blocked the RNP nuclear export and the appearance of cytoplasmic RNP aggregation. PPQ resistant H1N1 (WSN) viruses were isolated and found to have a NPS377G mutation. Recombinant WSN carrying the S377G NP is resistant to PPQ in anti-influenza and RNA polymerase assays. The WSN virus with the NPS377G mutation also is devoid of the PPQ-mediated RNP nuclear retention and cytoplasmic aggregation. The NPS377G expressing WSN virus is not resistant to the reported NP inhibitors nucleozin. Similarly, the nucleozin resistant WSN viruses are not resistant to PPQ, suggesting that PPQ targets a different site from the nucleozin-binding site. Our results also suggest that NP can be targeted through various binding sites to interrupt the crucial RNP trafficking, resulting in influenza replication inhibition. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:477-486. DOI:10.1016/j.ejmech.2015.08.016
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    ABSTRACT: A series of new spirooxindole-derived morpholine-fused-1,2,3-triazole derivatives has been synthesized from isatin spiro-epoxides. The protocol involves regiospecific isatin-epoxide ring opening with azide nucleophile followed by sequential O-propargylation, and intramolecular 1,3-dipolar cycloaddition reaction. These compounds have been evaluated for their antiproliferative activity against selected human tumor cell lines of lung (A549), breast (MCF-7), cervical (HeLa), and prostate (DU-145). Among the tested compounds, 6i, 6n and 6p showed potent growth inhibition against A549 cell line with IC50 values in the range of 1.87-4.36 μM, which are comparable to reference standards doxorubicin and 5-flourouracil. The compounds 6i and 6p treated A549 cells displayed typical apoptotic morphological features such as cell shrinkage, nuclear condensation, fragmentation, and decreased migration potential. Flow-cytometry analysis revealed that the compounds arrested the cells in G2/M phase of cell cycle. Hoechst and acridine orange/ethidium bromide staining studies also showed that the cell proliferation was inhibited through induction of apoptosis. Moreover, the compounds treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted in A549 cells. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:413-424. DOI:10.1016/j.ejmech.2015.08.017
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    ABSTRACT: Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:215-222. DOI:10.1016/j.ejmech.2015.08.007
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    ABSTRACT: A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1'-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of anticancer agents, especially for breast cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:303-309. DOI:10.1016/j.ejmech.2015.08.006
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    ABSTRACT: Eight 2-phenylnaphthalenoids (2PNs) (3a-h) and twenty four 2-phenylbenzofuranoids (2PBFs) (4a--4j, 5a-5j, 6a, 6f-6h) were successfully designed, synthesized and their antiproliferative and in vitro DNA topoisomerase inhibitory activities were evaluated. Nine compounds (four 2PNs and five 2PBFs) showed either TopoI or TopoIIα inhibitory activities. Six compounds (four 2PNs and two 2PBFs) exhibited potent cytotoxicity with IC50 values for 72 h exposure ranging from 0.3 to above 20 μM against MDA-MB-231, MDA-MB-435, HepG2 and PC3 cell lines. The two 2PBFs displayed comparable and even better antiproliferative as well as TopoIIα inhibitory activities than 2PNs. Interestingly, the active 2PBFs displayed different mechanisms of TopoIIα inhibition from that of 2PNs, suggesting that the chromophore scaffold replacement may result in a change of the binding site of inhibitors to TopoIIα. Furthermore, the mechanisms of antiproliferation on MDA-MB-231 cells indicate that compounds 5a and 5f are promising for further development of anticancer agents. The results of this study reveal that the evolutionary strategy of medicinal chemistry through scaffold hopping is a promising strategy for structure optimization of TopoIIα inhibitors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:277-287. DOI:10.1016/j.ejmech.2015.07.048
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    ABSTRACT: The androgen receptor (AR) plays important roles in multiple physiological functions, including differentiation, growth, and maintenance of male reproductive organs, and also has effects on hair and skin. In this paper, we report the synthesis of nonsteroidal AR antagonists having a 4-benzyl-1-(2H)-phthalazinone skeleton. Among the synthesized compounds, 11c with two ortho-substituents on the phenyl group potently inhibited SC-3 cell proliferation (IC50: 0.18 μM) and showed high wt AR-binding affinity (IC50: 10.9 μM), comparable to that of hydroxyflutamide (3). Compound 11c also inhibited proliferation of LNCaP cells containing T877A-mutated AR. Docking study of 11c with the AR ligand-binding domain indicated that the benzyl group is important for the antagonism. These phthalazinone derivatives may be useful for investigating potential clinical applications of AR antagonists. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:310-319. DOI:10.1016/j.ejmech.2015.08.002
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    ABSTRACT: A new series of pyrazolo[3,4-h]quinolines, heteroanalogues of angelicin was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular photocytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI50 values reaching the nanomolar level (14.52-0.04 μM). Selected compounds were able to photoinduce a massive cell death with the involvement of mitochondria. Their photodamage cellular targets were proteins and lipids and they did not cause any kind of DNA photodamage. This latter event is of considerable importance in the modulation of long term side effects, generally associated with the use of classical furocoumarins. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:334-351. DOI:10.1016/j.ejmech.2015.08.003
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    ABSTRACT: A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:153-166. DOI:10.1016/j.ejmech.2015.07.050
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    ABSTRACT: The eight novel ivangustin enantiomer analogues possessing α-methylene-γ-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 μM, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 μM. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 08/2015; 102:256-265. DOI:10.1016/j.ejmech.2015.07.051
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    ABSTRACT: Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). The HCV NS5B polymerase, an RNA-dependent RNA polymerase, is essential for HCV replication, which is able to catalyze the synthesis of positive (genomic) and negative (template) strand HCV RNA, but has no functional equivalent in mammalian cells. Therefore, the NS5B polymerase has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). Recently, a growing number of compounds have been reported as the NS5B polymerase inhibitors, some of which especially have been licensed in clinical trials. This review describes recent advances on the synthesis of the NS5B polymerase inhibitors, focusing on the merits and demerits of their synthetic methods. In particular, inspiration from the synthesis and the future direction of the NS5B polymerase inhibitors are highlighted. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 07/2015; 102:188-214. DOI:10.1016/j.ejmech.2015.07.046