Abstract:
:By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52+/-7.25% to 90.94+/-11.97%, which were significantly higher than that ranged from 12.27+/-9.56% to 17.71+/-7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3+/-8.0 s to 119.6+/-7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7+/-7.5s to 119.1+/-8.7s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10(-7) M) was treated with the solution of 2a-t in NS (final concentration, 5 x 10(-3) M) only lower percentage inhibitions ranged from 6.63+/-2.72% to 46.28+/-2.63% were recorded. Relatively higher concentration of 2a-t (5 x 10(-3) M) and relatively lower percentage inhibitions (13 of 20 less than 23.27+/-3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Zhao M,Li Z,Peng L,Tang YR,Wang C,Zhang Z,Peng Sdoi
10.1016/j.ejmech.2007.07.007subject
Has Abstractpub_date
2008-05-01 00:00:00pages
1048-58issue
5eissn
0223-5234issn
1768-3254pii
S0223-5234(07)00297-8journal_volume
43pub_type
杂志文章abstract::The article presents the synthesis of 5-ene-4-thiazolidinone derivatives with pyrazole core linked by enamine group. The structure and purity of compounds were confirmed by analytical and spectral data including X-ray analysis. Target compounds were screened for their anticancer activity and selective antileukemic act...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.03.089
更新日期:2016-07-19 00:00:00
abstract::A series of sulfapyridine-polyhydroxyalkylidene (or arylidene)-imino derivatives (Schiff's bases) 2a-c and 4a-e were prepared by condensation of 4-amino-N-pyridin-2-ylbenzenesulfonamide (1) with different monosaccharides or with aromatic aldehydes. Treatment of 2a-c with thioglycolic acid led to the formation of the C...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.10.044
更新日期:2010-02-01 00:00:00
abstract::Six series of 2-substituted 4-aminobutanamide derivatives were synthesized and evaluated for their ability to inhibit GABA transport proteins mGAT1-4 stably expressed in HEK-293 cell lines. The pIC50 values determined were in the range 4.23-5.23. Two compounds (15b and 15c) were selected for further in vitro studies. ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.024
更新日期:2014-08-18 00:00:00
abstract::Novel Biginelli dihydropyrimidines of biological interest were prepared using p-toluene sulphonic acid as an efficient catalyst. All the thirty-two synthesised dihydropyrimidines were evaluated for their in vitro antioxidant activity using DPPH method. Only, compounds 28 and 29 exhibited reasonably good antioxidant ac...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.05.014
更新日期:2009-10-01 00:00:00
abstract::Intestinal parasites delay mental and physical development in children. Infection with these parasites can result in complications during pregnancy and alter the health of newborns, which has long-term effects on educational attainment and economic productivity. The appearance of resistance against classical drug trea...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.02.005
更新日期:2017-03-31 00:00:00
abstract::Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly sel...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.08.053
更新日期:2018-09-05 00:00:00
abstract::Here we report the design, synthesis, and molecular modeling of new potent and selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested compounds showed a good inhibitor activity with IC50 values in the low micromolar...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.02.007
更新日期:2018-03-25 00:00:00
abstract::The efficient synthesis of novel azetidin-2-ones 6 has been established. Thus, condensation of 5-[(2-methyl-1H-benzimidazol-1-yl)methyl]-1,3,4-thiadiazol-2-amine 4 with various aromatic aldehydes afforded 5-[(2-methyl-1H-benzimidazol-1-yl)methyl]-N-[(substituted) phenylmethylidene]-1,3,4-thiadiazol-2-amine 5 which on ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.01.022
更新日期:2009-05-01 00:00:00
abstract::A series of novel, heteroaryl carboxylic acid conjugates of the sesquiterpene melampomagnolide-B (MMB, 3) has been evaluated as antitumor agents against an NCI panel of 64 human hematopoetic and solid tumor cell lines. The indole-3-acrylic acid conjugate 7j and the indole-3-carboxylic acid conjugate 7k were found to b...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.05.031
更新日期:2017-08-18 00:00:00
abstract::New anti-tubercular agents, imidazo[1,2-a]pyridine-2-carboxamide derivatives (5a-q) have been designed and synthesized. The structural considerations of the designed molecules were further supported by the docking study with a long-chain enoyl-acyl carrier protein reductase (InhA). The chemical structures of the new c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.10.079
更新日期:2015-01-07 00:00:00
abstract::We describe the synthesis and characterization of a novel bioconjugate, consisting of an octaarginine cell-penetrating peptide and a highly DNA-affine doxorubicin dimer. The linkage between the two components is composed of a cleavable disulfide bond, which enables the efficient intracellular delivery of the cytotoxic...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.02.056
更新日期:2017-04-21 00:00:00
abstract::A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.08.012
更新日期:2017-10-20 00:00:00
abstract::5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a novel anticancer agent with a number of unique activities, and is in clinical trial. The current synthesis of DMXAA involves six steps, beginning with a heterogeneous reaction to form an isonitrosoacetanilide, and gives an overall yield of 11% from 2,3-dimethylaniline....
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(02)01406-x
更新日期:2002-10-01 00:00:00
abstract::Malignant tumor cells have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential antitumor therapy. In this study, the 7-ethyl-10-boronic acid camptothecin (B1) was synthesize...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.03.063
更新日期:2016-06-30 00:00:00
abstract::Two series with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitrile were synthesized through one pot reaction of the appropriate acetophenone, aldehyde, ammonium acetate with ethyl cyanoacetate or malononitrile, respectiv...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.09.029
更新日期:2010-01-01 00:00:00
abstract::A series of novel pyridone conjugated monobactams with various substituents at the (4) position were synthesized and evaluated for their antibacterial activities against a panel of multidrug-resistant (MDR) Gram-negative bacteria in vitro. Compounds 46d, 54 and 75e displayed good to moderate activities against P. aeru...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.03.058
更新日期:2018-05-10 00:00:00
abstract::Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multist...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.111588
更新日期:2019-11-15 00:00:00
abstract::Glycogen synthase kinase 3β (GSK-3β) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitor...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.12.014
更新日期:2013-02-01 00:00:00
abstract::Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifunga...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.02.037
更新日期:2012-05-01 00:00:00
abstract::A guaiane framework was scaffolded by photochemical rearrangement reactions using α-santonin 1 as a starting material. Then, using a series of reactions, we synthesized the guaiane-type sesquiterpene lactone 5 in high yield. The inhibitory activities of compound 5 and of a series of derivatives on nitric oxide (NO) re...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.043
更新日期:2014-08-18 00:00:00
abstract::A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a-g and 7a-g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a-g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.01.053
更新日期:2015-03-06 00:00:00
abstract::Novel ester prodrugs (II, III and IV) of ibuprofen (I) were synthesized using alpha-methyl, ethyl and propyl glucopyranoside as promoieties and tested for their anti-inflammatory, analgesic and ulcerogenic activities. Study of their chemical hydrolysis in aqueous buffer (pH 3.0-10.0) showed that these compounds acted ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2006.05.014
更新日期:2006-11-01 00:00:00
abstract::Several prenylflavonoids have been synthesised and tested against human tumour cell lines. The prenyl unit has been geranyl or a labdane diterpene. These labdane-flavonoids have been synthesised for the first time. The antitumour activity increase with the prenylation at C-8 position. Twenty-three C and O-prenylated a...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.06.025
更新日期:2010-09-01 00:00:00
abstract::The target phosphoramidates 5a-e were prepared in one step from 3-hydroxypropyl derivatives 3a-e of nonsteroidal anti-inflammatory drugs (fenoprofen, ketoprofen, ibuprofen, indomethacin, diclofenac). The products 3a-e and 5a-e were evaluated for their cytostatic and antiviral activity against malignant tumour cell lin...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.03.037
更新日期:2009-01-01 00:00:00
abstract::A series of novel aliphatic amido-quaternary ammonium salts were synthesized and evaluated for their anticancer effects involving induction of RhoB. Most of these compounds, featuring open-ring forms of aliphatic amido-quaternary ammonium salts, exhibited potent anti-proliferative activities in human cancer cell lines...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.12.063
更新日期:2013-05-01 00:00:00
abstract::Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.04.034
更新日期:2014-06-10 00:00:00
abstract::Herein we report the straightforward preparation of novel conformationally-restricted steroids from trans-androsterone and estrone, decorated with spiranic oxazolidin-2-one or 2-aminooxazoline motifs at C-17 as potential antiproliferative agents. Such unprecedented pharmacophores were accessed using an aminomethylalco...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.10.063
更新日期:2018-01-01 00:00:00
abstract::O-Perbenzoylated 5-(β-D-glucopyranosyl)tetrazole was reacted with N-benzyl carboximidoyl chlorides to give the corresponding 4-benzyl-3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles. Removal of the O-benzoyl and N-benzyl protecting groups by base catalysed transesterification and catalytic hydrogenation, respecti...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.02.041
更新日期:2014-04-09 00:00:00
abstract::Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endo...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.05.035
更新日期:2016-10-04 00:00:00
abstract::Some new ethyl 2-[3-(4-unsubstituted or 4-substituted phenylsufonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylates 3a-c, 2-[3-(phenylsulfonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbohydrazides 4a-f, 3-phenylsulfonyl-6,7,8,9-tetrahydro-5H-cyclohepta[1',2':4,5]thieno[2,3-d]pyrimi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.11.014
更新日期:2010-02-01 00:00:00