58198-49-5Relevant articles and documents
Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury
Chen, Lingfeng,Chen, Hongjin,Chen, Pengqin,Zhang, Wenxin,Wu, Chao,Sun, Chuchu,Luo, Wu,Zheng, Lulu,Liu, Zhiguo,Liang, Guang
, p. 22 - 38 (2018/10/23)
Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll-like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases.
Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors
Chiaramonte, Niccolò,Bua, Silvia,Angeli, Andrea,Ferraroni,Picchioni, Ilaria,Bartolucci, Gianluca,Braconi,Dei, Silvia,Teodori, Elisabetta,Supuran, Claudiu T.,Romanelli, Maria Novella
, (2019/08/01)
Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylb
Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease
Huang, Weijun,Wang, Yujun,Li, Jiaming,Zhang, Yanchun,Ma, Xiaodong,Zhu, Panhu,Zhang, Yang
, p. 110 - 122 (2018/12/11)
Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218?nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β-protein 1–42 (Aβ1–42). Among them, 8a showed higher inhibition rate (%Inhibition?=?22.29) than the positive reference Donepezil (%Inhibition?=?17.65).
The synthesis and biological evaluation of novel gardenamide A derivatives as multifunctional neuroprotective agents
Zhang, Zuzhi,Wang, Yujun,Zhang, Yanchun,Li, Jiaming,Huang, Weijun,Wang, Lei
, p. 1180 - 1186 (2019/07/25)
A novel series of gardenamide A derivatives was synthesized as potential anti-Alzheimer's disease agents. The neuroprotective effects of these multifunctional agents against oxygen-glucose deprivation (OGD)-induced neurotoxicity in rat cortical neurons, and hydrogen peroxide (H2O2)- A nd amyloid-β1-42 (Aβ1-42)-induced neurotoxicity in rat hippocampal neurons were evaluated. In vitro studies revealed that these compounds demonstrated moderate to good multifunctional neuroprotective activity. Among the entire series, compounds 10e, 10j, 10n and 10p appeared to be the most active multifunctional neuroprotective agents. Studies indicate that compounds 10e, 10f, 10h, 10i, 10j, 10n and 10p exhibit significant activities against OGD-induced neurotoxicity in rat cortical neurons, and 10e, 10j, 10n and 10p show prominent activities against H2O2- A nd Aβ1-42-induced neurotoxicity in rat hippocampal neurons. Moreover, these derivatives did not exert conspicuous neurotoxicity in rat cortical neurons. Thus, the present study evidently shows that 10e, 10j, 10n and 10p are potent multifunctional neuroprotective agents, which may serve as promising lead candidates for anti-Alzheimer's disease drug development.
Flavonoid derivatives as selective ABCC1 modulators: Synthesis and functional characterization
Obreque-Balboa, José Esteban,Sun, Qiu,Bernhardt, Günther,K?nig, Burkhard,Buschauer, Armin
supporting information, p. 124 - 133 (2016/01/20)
A series of chromones, bearing substituted amino groups or N-substituted carboxamide moieties in position 2, was synthesized and characterized in cellular assays for modulation of the ABC transporters ABCC1 (MDCKII-MRP1 cells), ABCB1 (Kb-V1 cells) and ABCG2 (MCF-7/Topo cells). The most potent ABCC1 modulators identified among these flavonoid-type compounds were comparable to the reference compound reversan regarding potency, but superior in terms of selectivity concerning ABCB1 and ABCG2 (2-[4-(Benzo[c][1,2,5]oxadiazol-5-ylmethyl)piperazin-1-yl]-5,7-dimethoxy-4H-chromen-4-one (51): ABCC1, IC50 11.3-1/4M; inactive at ABCB1 and ABCG2). Compound 51 was as effective as reversan in reverting ABCC1-mediated resistance to cytostatics in MDCKII-MRP1 cells and proved to be stable in mouse plasma and cell culture medium. Modulators, such as compound 51, are of potential value as pharmacological tools for the investigation of the (patho)physiological role of ABCC1.
NEW FYN KINASE INHIBITORS
-
, (2016/10/04)
The invention relates to new selective FYN kinase inhibitors of Formula (I), pharmaceutical compositions containing them, and their use for the pharmacological treatment of pain and arthritis, including osteoarthritis and rheumatoid arthritis.
Synthesis and evaluation of paeonol derivatives as potential multifunctional agents for the treatment of alzheimer's disease
Zhou, An,Wu, Hongfei,Pan, Jian,Wang, Xuncui,Li, Jiaming,Wu, Zeyu,Hui, Ailing
, p. 1304 - 1318 (2015/01/30)
(A.H.); Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder characterized by memory loss, language impairment, personality changes and intellectual decline. Taking into account the key pathological features of AD, such as low levels of acetylcholine, beta-amyloid (Aβ) aggregation, oxidative stress and dyshomeostasis of biometals, a new series of paeonol derivatives 5a-5d merging three different functions, i.e., antioxidant, anti-acetylcholinesterase (AChE) activity, metal chelating agents for AD treatment have been synthesized and characterized. Biological assays revealed that compared with paeonol (309.7 μM), 5a-5d had a lower DPPH IC50 value (142.8-191.6 μM). 5a-5d could significantly inhibit hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay in the concentration range of 5-40 μM. AChE activity was effectively inhibited by 5a-5d, with IC50 values in the range of 0.61-7.04 μM. 5a-5d also exhibited good metal-chelating ability. All the above results suggested that paeonol derivatives may be promising multifunctional agents for AD treatment.
Synthesis and in vitro antitumor activity of novel diaryl urea derivatives
Zhao, Yan-Fang,Liu, Zi-Jian,Zhai, Xin,Ge, Dan-Dan,Huang, Qiang,Gong, Ping
, p. 386 - 388 (2013/07/19)
A series of novel diaryl ureas containing 4-[(2-amino-6-trifluromethyl) pyrimidine-4-yl]piperazine-1-yl group were synthesized and evaluated for their cytotoxic activities in a panel of human cancer cell lines. Compared with the reference drug Sorafenib, some compounds showed more potent and a broader spectrum of anti-cancer activities. Among them, compound 2p demonstrated significant inhibitory activities against MDA-MB-231, HT-29 and MCF-7 cell lines with IC50 values of 0.016, 0.63, 0.001 μmol/L, respectively.
Synthesis and antimalarial activity of hydroxyethylpiperazine derivatives
Cunico, Wilson,Gomes, Claudia R.B.,Moreth, Marcele,Manhanini, Diogo P.,Figueiredo, Isabela H.,Penido, Carmen,Henriques, Maria G.M.O.,Varotti, Fernando P.,Krettli, Antoniana U.
body text, p. 1363 - 1368 (2009/09/27)
The antimalarial activity of hydroxyethylpiperazine derivatives, synthesized from the reaction of (2S,3S)Boc-phenylalanine epoxide with benzylpiperazines in good yields (76-96%), has been evaluated in vitro against the Plasmodium falciparum W2 clone (chlo
Synthesis of an indole containing KDR kinase inhibitor by tandem Sonogashira coupling-5-endo-dig-cyclization as a key step
Palimkar, Sanjay S.,More, Vijaykumar S.,Kumar, P. Harish,Srinivasan, Kumar V.
, p. 12786 - 12790 (2008/03/13)
An efficient synthesis of the potent KDR kinase inhibitor 3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indol-2-yl]quinoline-2-(1H)-one using a Sonogashira coupling-5-endo-dig-cyclization strategy is described.
