Abstract:
:The bromodomain and extra-terminal (BET) bromodomains, particularly BRD4, have been identified as promising therapeutic targets in the treatment of many human disorders such as cancer, inflammation, obesity, and cardiovascular disease. Recently, the discovery of novel BRD4 inhibitors has garnered substantial interest. Starting from scaffold hopping of the reported compound dihydroquinazolinone (PFI-1), a series of coumarin derivatives were designed and synthesised as a new chemotype of BRD4 inhibitors. Interestingly, the representative compounds 13 exhibited potent BRD4 binding affinity and cell proliferation inhibitory activity, and especially displayed a favourable PK profile with high oral bioavailability (F = 49.38%) and metabolic stability (T1/2 = 4.2 h), meaningfully making it as a promising lead compound for further drug development.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Zhang Z,Gu L,Wang B,Huang W,Zhang Y,Ma Z,Zeng S,Shen Zdoi
10.1080/14756366.2019.1587417subject
Has Abstractpub_date
2019-12-01 00:00:00pages
808-817issue
1eissn
1475-6366issn
1475-6374journal_volume
34pub_type
杂志文章abstract::The effect of N'-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the alpha-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of th...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360410001733702
更新日期:2005-02-01 00:00:00
abstract::The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for their inhibitory activity against human MAO-B (hMAO-B). The majorit...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2020.1797711
更新日期:2020-12-01 00:00:00
abstract::The reaction mechanism of glycoside hydrolases belonging to family 1 (GH1) of carbohydrate-active enzymes classification, hydrolysing β-O-glycosidic bonds, is well characterised. This family includes several thousands of enzymes with more than 20 different EC numbers depending on the sugar glycone recognised as substr...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2019.1608198
更新日期:2019-12-01 00:00:00
abstract::Two carbonic anhydrase IX (CA IX) inhibitors were radiolabeled with (18)F, and evaluated for imaging CA IX expression. Despite good affinity for CA IX and excellent plasma stability, uptake of both tracers in CA IX-expressing HT-29 tumor xenografts in mice was low. (18)F-FEC accumulated predominately in the liver and ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2013.773994
更新日期:2014-04-01 00:00:00
abstract::A series of hydroxylic compounds (1-10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068-4003, 0.012-9.9 and 0...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2015.1114930
更新日期:2016-12-01 00:00:00
abstract::The sequence of human urotensin II (UII) has been recently established as H-Glu-Thr-Pro-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH, and it has been reported that UII is the most potent mammalian vasoconstrictor peptide identified so far. A series of UII analogues was synthesized, and the contractile activity of each compound ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/1475636031000093507
更新日期:2003-04-01 00:00:00
abstract::Several (thiazol-2-yl)hydrazone derivatives from 2-, 3- and 4-acetylpyridine were synthesized and tested against human monoamine oxidase (hMAO) A and B enzymes. Most of them had an inhibitory effect in the low micromolar/high nanomolar range, being derivatives of 4-acetylpyridine selective hMAO-B inhibitors also at lo...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2014.987138
更新日期:2015-12-01 00:00:00
abstract::In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazo...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2014.1003213
更新日期:2015-12-01 00:00:00
abstract::The small and highly electronegative fluorine atom can play a remarkable role in medicinal chemistry. Selective installation of fluorine into a therapeutic or diagnostic small molecule candidate can enhance a number of pharmacokinetic and physicochemical properties such as improved metabolic stability and enhanced mem...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1080/14756360701425014
更新日期:2007-10-01 00:00:00
abstract::A small library of phosphorylated sulfamates (N-(O-alkylsulfamoyl)-phosphoramidic acids) incorporating long aliphatic chains (C8-C16) has been synthesized and investigated for their interaction with two physiologically relevant carbonic anhydrase (CA) isozymes. These compounds behaved as very potent inhibitors of both...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360410001689522
更新日期:2004-06-01 00:00:00
abstract::The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new triazoles were synthesized and evaluated for antituberculosis activity. A series of 4-arylidenamino-4H-1,2,4-triazol...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360601178424
更新日期:2007-08-01 00:00:00
abstract::A novel set of 16 hybrids of bromopyrrole alkaloids with aroyl hydrazone were designed, synthesized and evaluated for antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA; ATCC 43866), methicillin-susceptible Staphylococcus aureus (MSSA; ATCC 35556) and Staphylococcus epid...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2013.793183
更新日期:2014-06-01 00:00:00
abstract::The synthesis of new 4-[2-(alkylamino)ethylthio]pyrrolo[1,2-a]quinoxaline derivatives la-1 is described in five or six steps starting from various substituted nitroanilines 2a-e. The bioisostere 5-[2-(alkylamino)ethylthio]pyrrolo[1,2- a]thieno[3,2-e]pyrazine 1m was also prepared. The new derivatives were evaluated as ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360701485406
更新日期:2007-10-01 00:00:00
abstract::Flavonoids, polyphenolic phytochemicals, are ubiquitous in plants and are commonly present in the human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. The present study was designed to evaluate three biomolecules that play important roles in the apoptotic proces...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360601162063
更新日期:2007-08-01 00:00:00
abstract::Adenosine receptors have been considered as potential targets for drug development, but one of the main obstacles to this goal is to selectively inhibit one receptor subtype over the others. This subject is particularly crucial for adenosine A2b receptor antagonists (AdoRA2B). The structure–activity relationships of x...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2013.830113
更新日期:2014-08-01 00:00:00
abstract::Leishmaniasis is considered as one of the major neglected tropical diseases due to its magnitude and wide geographic distribution. Leishmania braziliensis, responsible for cutaneous leishmaniasis, is the most prevalent species in Brazil. Superoxide dismutase (SOD) belongs to the antioxidant pathway of the parasites an...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2018.1550752
更新日期:2019-12-01 00:00:00
abstract::A series of novel benzene sulfonamides (previously evaluated as selective cyclooxygenase-2 inhibitors) has been profiled against human carbonic anhydrases I, II, IV and VII in an attempt to observe the manifestation of the well established "tail" approach for designing potent, isoform-selective inhibitors of carbonic ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2016.1178248
更新日期:2016-01-01 00:00:00
abstract::Phytochemical investigations on the chloroform and ethyl acetate soluble fractions of the roots of Ranunculus repens led to the isolation of methyl 3,4,5-trihydroxybenzoate 1, R(+)- 4-methoxydalbergione 2 and R(+)-dalbergiophenol 3. The structures of these compounds were established through spectral studies including ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360500319210
更新日期:2006-02-01 00:00:00
abstract::The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcin...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2018.1475369
更新日期:2018-12-01 00:00:00
abstract::Three series of sintenin derivatives (compounds 1-14) were designed and prepared and their antioxidative and neuroprotective effects were evaluated. The in vitro models of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, chelating ferrous ions, inhibiting the rat brain homogenates lipid peroxidation, and prot...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360802188214
更新日期:2009-04-01 00:00:00
abstract::The purpose of this study was the evaluation of the xanthine oxidase (XO) inhibition produced by some synthetic 2-styrylchromones. Ten polyhydroxylated derivatives with several substitution patterns were synthesised, and these and a positive control, allopurinol, were tested for their effects on XO activity by measuri...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360290019944
更新日期:2002-02-01 00:00:00
abstract::Ligand-protein docking is one of the most common techniques used in virtual screening campaigns. Despite the large number of docking software available, there is still the need of improving the efficacy of docking-based virtual screenings. To date, only very few studies evaluated the possibility of combining the resul...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2016.1193736
更新日期:2016-01-01 00:00:00
abstract::An array of novel spiro imidazolidine derivatives was synthesized in dry media and was screened for their anti-microbial activities. Structure-activity relationship results revealed that compounds 22, 23 against P.aeruginosa, 24 against S.aureus, 24, 25 against K.pneumonia, 27 against S.aureus, β-H.streptococcus, 29 a...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2010.503611
更新日期:2011-04-01 00:00:00
abstract::For the development of potent novel antileishmanial agents, 3,3'-(arylmethylene)bis(2-hydroxynaphthalene-1,4 dione) derivatives were synthesized from lawsone and evaluated for cytotoxicity on Leishmania donovani promastigotes as well as on leishmanial DNA topoisomerase-I. Enzyme inhibition studies were conducted with ...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2013.765413
更新日期:2014-04-01 00:00:00
abstract::In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a-f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. A...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2015.1022174
更新日期:2016-01-01 00:00:00
abstract::Monoacylglycerol lipase is a serine hydrolase that plays a major role in the degradation of the endocannabinoid neurotransmitter 2-arachidonoylglycerol. A wide number of MAGL inhibitors are reported in literature; however, many of them are characterised by an irreversible mechanism of action and this behavior determin...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756366.2017.1375484
更新日期:2017-12-01 00:00:00
abstract::In the present study we have evaluated the antigenotoxic effects of Farnesol (FL) a 15-carbon isoprenoid alcohol against benzo (a) pyrene [B(a)P] (125 mg kg(- 1).b.wt oral) induced toxicity. B(a)P administration lead to significant induction in Cytochrome P450 (CYP) content and aryl hydrocarbon hydrolase (AHH) activit...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.1080/14756360701448768
更新日期:2008-12-01 00:00:00
abstract::Dithiocarbamates (DTC) are promising compounds with potential applications in antitumoral and glaucoma therapy. Our aim is to understand molecular features affecting DTC interaction with carbonic anhydrases (CAs), zinc-containing enzymes maintaining acid-base balance in blood and other tissues. To this end, we generat...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2012.727410
更新日期:2013-04-01 00:00:00
abstract::This study presents the synthesis and in vitro pharmacological evaluations of novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in vitro antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus,...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2011.592491
更新日期:2012-06-01 00:00:00
abstract::The synthesis, in vitro antimicrobial activities of some novel hydroxy pyridines supported with various pharmacophores is described. Twenty-six out of the tested 58 compounds exhibited variable inhibitory effects on the growth of the tested Gram positive and Gram negative bacteria. The tested compounds revealed better...
journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
doi:10.3109/14756366.2012.694880
更新日期:2013-10-01 00:00:00