Abstract：
:HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well as mechanistically different. Herein, a series of quinazolinones were designed and synthesized as novel HIV-1 inhibitors. The new synthetic route provides a practical method for the preparation of 5-hydroxy quinazolinones. Primary bioassay results indicated that most of the quinazolinones possess anti-HIV activity, especially for compound 11b with 77.5% inhibition rate at 10 μM emerged as a new active lead. Most of the synthesized compounds were also found to exhibit good anti-TMV activity, of which compo und 9a showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin. This work provides a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration and optimization of previously reported antiviral agents.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Wang Z,Wang M,Yao X,Li Y,Tan J,Wang L,Qiao W,Geng Y,Liu Y,Wang Qdoi
10.1016/j.ejmech.2012.04.010subject
Has Abstractpub_date
2012-07-01 00:00:00pages
275-82eissn
0223-5234issn
1768-3254pii
S0223-5234(12)00230-9journal_volume
53pub_type
杂志文章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：:The synthesis of 7α-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltesto...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.04.027
更新日期：2013-06-01 00:00:00
abstract：:NQO1 is a dimeric flavoprotein which intimately associated with cancer and overexpressed in the cytosol of numerous human tumor cells. Given that the cellular environment is quite dynamic and versatile, further investigation of the function of NQO1 depends on tools for specific detection of it. Currently, several acti...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.10.062
更新日期：2017-02-15 00:00:00
abstract：:A phytochemical investigation of Inula falconeri, a plant endemic to the Himalayas, afforded 10 new sesquiterpenoids and 26 known sesquiterpene lactones, including those bearing guaiane, pseudoguaiane, xanthane, eudesmane, germacrane, rare secocaryophyllane, chromolaevane, and carabrane frameworks. The structures were...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.08.047
更新日期：2011-11-01 00:00:00
abstract：:We recently discovered that 5, 8-O-dimethyl acylshikonin derivatives displayed the selectivity towards MCF-7 and no toxicity to normal cells. Herein, a series of the corresponding 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized starting from shikonin. In vitro evidence of the cytotoxicities indi...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.05.006
更新日期：2011-08-01 00:00:00
abstract：:Breast cancer, a most common malignancy in women, was known to be associated with steroid hormone estrogen. The discovery of estrogen receptor (ER) gave us not only a powerful predictive and prognostic marker, but also an efficient target for the treatment of hormone-dependent breast cancer with various estrogen ligan...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.ejmech.2019.05.023
更新日期：2019-09-01 00:00:00
abstract：:Isocombretastatins are the not isomerizable 1,1-diarylethene isomers of combretastatins. Both families of antimitotics are poorly soluble and new analogs with improved water solubility are needed. The ubiquitous 3,4,5-trimethoxyphenyl ring and most of its replacements contribute to the solubility problem. 39 new compo...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112933
更新日期：2021-01-01 00:00:00
abstract：:The Cannabinoid 2 receptor, CB2R, belonging to the endocannabinoid system, ECS, is involved in the first steps of neurodegeneration and cancer evolution and progression and thus its modulation may be exploited in the therapeutic and diagnostic fields. However, CB2Rs distribution and signaling pathways in physiological...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112037
更新日期：2020-02-15 00:00:00
abstract：:New series of phosphorus-containing dendrimers, having one quaternary ammonium salt as core and carboxylic acid terminal groups have been synthesized from generation 0 (3 carboxylic acid terminal groups) to generation 2 (12 carboxylic acid terminal groups). These dendrimers react with the neutral form of carteolol (an...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.10.017
更新日期：2010-01-01 00:00:00
abstract：:A series of C-cinnamoyl glycosides has been synthesized in good yield by the BF3·OEt2 catalyzed aldol condensation of C-glycosylated acetone derivative with a variety of aromatic aldehydes. The synthesized compounds were evaluated for their potential as anti-filarial agents against bovine filarial parasite Setaria cer...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2016.03.001
更新日期：2016-05-23 00:00:00
abstract：:A series of Lapatinib derivatives were designed and prepared by changing the straight alkyl side chain of Lapatinib into a branched one. ELISA assay and western blot analysis showed that these derivatives can significantly inhibit HER1/HER2 as well as their downstream signal transduction proteins. In vitro cytotoxicit...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2014.10.006
更新日期：2014-11-24 00:00:00
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
更新日期：2019-01-15 00:00:00
abstract：:Covalent drugs play corresponding bioactivities by forming covalent bonds with the target, which possess many significant pharmacological advantages including high potency, ligand efficiency, and long-lasting effects. However, development of covalent inhibitors is a challenge due to their presumed indiscriminate react...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112896
更新日期：2021-01-01 00:00:00
abstract：:A series of N-substituted aminomethylphenol derivatives was synthesized by reductive amination. To study the inhibitory potency of the target compounds at the murine GABA transporters (mGAT1-mGAT4), a [(3)H]GABA uptake test system in a 96-well format based on HEK cells stably expressing mGAT1-mGAT4 was established and...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.01.005
更新日期：2008-11-01 00:00:00
abstract：:Two new series of quinoline incorporated benzimidazole derivatives (4a-i and 8a-f) were synthesized from substituted aniline and isatin through multi-step reaction. 6-substituted-4-carboxyquinolines (3a,b and 7) were synthesized by multi component one pot reactions (via Doebner reaction and Pfitzinger reaction respect...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2012.05.027
更新日期：2012-08-01 00:00:00
abstract：:9-cis-Retinal thiosemicarbazone and its Co(III), Ni(II) and Cu(II) complexes are synthesized and characterized. Central Co(III) atom is in an octahedral environment while Ni(II) and Cu(II) atoms are in a square planar environment. DNA binding constants and spectroscopic data show an intercalative behavior for the nick...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2006.12.019
更新日期：2007-05-01 00:00:00
abstract：:A new series of indolo[1,2-c]quinazoline derivatives were prepared in good yield through reaction of 2-(o-aminophenyl)indole with a variety of arylaldehydes. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and mass spectral studies and elemental analysis. All the title compo...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2009.11.038
更新日期：2010-03-01 00:00:00
abstract：:Axl is a new promising molecular target for antineoplastic therapies. A series of quinolone antibiotic derivatives were designed and synthesized as new selective Axl inhibitors. One of the most promising compound 8i bound tightly to Axl with a Kd value of 1.1 nM, and inhibited its kinase activity with an IC50 value of...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.01.065
更新日期：2019-03-15 00:00:00
abstract：:N(6)-Monoalkylated, N(6)-dialkylated and N(6)-acylated (R(P))-adenosine 3',5'-cyclic phosphorothioic acids have been prepared by stereoselective syntheses from cAMP for a study of protein kinase A antagonist activity. The antagonist activity of the parent primary 6-amino cAMP derivative was reduced after N-monoalkylat...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.10.003
更新日期：2011-12-01 00:00:00
abstract：:In the last decades phenolic compounds have gained enormous interest because of their beneficial health effects such as anti-inflammatory, anticancer, or antiviral activities. The pharmacological effects of phenolic compounds are mainly due to their antioxidant activity and their inhibition of certain enzymes. This an...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2011.12.030
更新日期：2012-03-01 00:00:00
abstract：:Protein-protein interactions are attractive targets because they control numerous cellular processes. In oncology, apoptosis regulating Bcl-2 family proteins are of particular interest. Apoptotic cell death is controlled via PPIs between the anti-apoptotic proteins hydrophobic groove and the pro-apoptotic proteins BH3...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2018.10.003
更新日期：2018-11-05 00:00:00
abstract：:Inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer and other diseases, and lots of efforts have been put into the development of organic compounds as more potent PARP-1 inhibitors. Here we describe a strategy to conveniently obtain metal-based PARP-1 inhib...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.10.062
更新日期：2014-01-01 00:00:00
abstract：:(S)-Blebbistatin is a widely used research tool to study myosin II, an important regulator of many motility based diseases. Its potency is too low to be of clinical relevance, but identification of analogs with enhanced potency could deliver leads for targeted pharmacotherapeutics. This, however, requires a profound i...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2017.04.072
更新日期：2017-08-18 00:00:00
abstract：:The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO b...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2013.07.007
更新日期：2013-10-01 00:00:00
abstract：:Preparation, characterization and drug release behavior of loaded polybutyl adipate (PBA) nanocapsules with penicillin-G are described here. The nanocapsules were produced using a double emulsion solvent evaporation technique, using dichloromethane as an organic solvent and Tween and Span as surfactants. In this proce...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2008.09.045
更新日期：2009-06-01 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：:Alzheimer's disease (AD) is associated with multifactorial neuropathological conditions, which include cholinergic deficit, amyloid-beta plaques formation, loss of neuronal plasticity and neuronal death. Treating such multifactorial conditions with a single target directed approach is considered to be inadequate. Acco...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2019.111613
更新日期：2019-11-15 00:00:00
abstract：:A series of 10-substituted hydroxy-10H-acridin-9-ones were synthesized and studied as potential antipsoriatic agents. The antiproliferative activity of the novel derivatives, which can be considered as aza-analogues of the antipsoriatic drug anthralin, was determined using the human keratinocyte cell line HaCaT. Struc...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2010.08.059
更新日期：2010-11-01 00:00:00
abstract：:Five newly synthesised original compounds were investigated for acute toxicity, influence on hexobarbital sleeping time, effect on the locomotor activity, and brain antihypoxic activity. Two of the compounds were tested in a model of glutamate induced neurotoxicity in the brain cell culture using a cell viability test...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0223-5234(00)01172-7
更新日期：2000-10-01 00:00:00
abstract：:Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B ...
journal_title：European journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.ejmech.2020.112589
更新日期：2020-10-01 00:00:00
