18794-97-3Relevant academic research and scientific papers
Regioselective CC bond cleavage in arylhydrazones of 4,4,4-trifluoro-1- (thiophen-2-yl)butane-1,3-diones
Solhnejad, Reza,Aliyeva, Farqana S.,Maharramov, Abel M.,Aliyeva, Rafiga A.,Chyragov, Famil M.,Gurbanov, Atash V.,Mahmudov, Kamran T.,Kopylovich, Maximilian N.
, p. 180 - 184 (2013)
New (Z)-2-(2-(para-substituted phenyl)hydrazono)-4,4,4-trifluoro-1- (thiophen-2-yl)butane-1,3-diones with chloro (1), bromo (2) and carboxy (3) substituents were synthesized and characterized by ESI-MS, IR, 1H and 13C NMR spectroscop
Design, synthesis and biological evaluation of novel N-[4-(2-fluorophenoxy)pyridin-2-yl]cyclopropanecarboxamide derivatives as potential c-Met kinase inhibitors
Chen, Ye,Ding, Shi,Gong, Yilin,Hao, Xuechen,Hou, Yunlei,Liu, Ju,Liu, Yajing,Shi, Jiantao,Wang, Yang,Zhou, Yunpeng
, (2020/03/31)
Three series of novel 4-phenoxypyridine derivatives containing 4-methyl-6-oxo-1,6-dihydropyridazine- 3-carboxamide, 5-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide and 4-methyl-3,5-dioxo-2,3,4,5- tetrahydro-1,2,4-triazine-6-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activitives against c-Met kinase and cytotoxic activitives against A549, H460, HT-29 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activitives. The most promising compound 26a (with c-Met IC50 value of 0.016 μM) showed remarkable cytotoxicity against A549, H460, and HT-29 cell lines with IC50 values of 1.59 μM, 0.72 μM and 0.56 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that 4-methyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxamide was more preferred as linker part, and electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activitives. Furthermore, the colony formation, acridine orange/ethidium bromide (AO/EB) staining, apoptosis, and wound-healing assay of 26a were performed on HT-29 and/or A549 cell lines.
2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile as novel inhibitor of receptor tyrosine kinase and PI3K/AKT/mTOR signaling pathway in glioblastoma
Viswanathan, Anisha,Kute, Dinesh,Musa, Aliyu,Konda Mani, Saravanan,Sipil?, Vili,Emmert-Streib, Frank,Zubkov, Fedor I.,Gurbanov, Atash V.,Yli-Harja, Olli,Kandhavelu, Meenakshisundaram
, p. 291 - 303 (2019/02/07)
Nerve growth factor receptor (NGFR), a member of kinase protein, is emerging as an important target for Glioblastoma (GBM) treatment. Overexpression of NGFR is observed in many metastatic cancers including GBM, promoting tumor migration and invasion. Hydrazones have been reported to effectively interact with receptor tyrosine kinases (RTKs). We report herein the synthesis of 23 arylhydrazones of active methylene compounds (AHAMCs) compounds and their anti-proliferative activity against GBM cell lines, LN229 and U87. Compound R234, 2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile, was identified as the most active anti-neoplastic compound, with the IC50 value ranging 87 μM - 107 μM. Molecular docking simulations of the synthesized compounds into the active site of tyrosine receptor kinase A (TrkA), demonstrated a strong binding affinity with R234 and concurs well with the obtained biological results. R234 was found to be a negative regulator of PI3K/Akt/mTOR pathway and an enhancer of p53 expression. In addition, R234 treated GBM cells exhibited the downregulation of cyclins, cyclin-dependent kinases and other key molecules involved in cell cycle such as CCNE, E2F, CCND, CDK6, indicating that R234 induces cell cycle arrest at G1/S. R234 also exerted its apoptotic effects independent of caspase3/7 activity, in both cell lines. In U87 cells, R234 induced oxidative effects whereas LN229 cells annulled oxidative stress. The study thus concludes that R234, being a negative modulator of RTKs and cell cycle inhibitor, may represent a novel class of anti-GBM drugs.
Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinase inhibitors
Wang, Lin Xiao,Liu, Xiaobo,Xu, Shan,Tang, Qidong,Duan, Yongli,Xiao, Zhen,Zhi, Jia,Jiang, Liwen,Zheng, Pengwu,Zhu, Wufu
, p. 538 - 551 (2017/11/01)
In continue to our previous research, eight series of pyrrolo[2,3-b]pyridine and pyrrolo[2,3-d]pyrimidine derivatives bearing pyridazinone moiety were designed, synthesized, and the in vitro antitumor activity was evaluated against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). Some selected compounds (22f, 22g, 26c and 26e) were evaluated for the activity against c-Met kinase, and according to the results of kinase inhibitory activity, the compound 22g was further evaluated for other four tyrosine kinases (Flt-3, VEGFR-2, c-Kit and EGFR) to test the enzyme-based selectivity. The most promising compound 22g showed excellent activity than lead compound Foretinib against A549, HepG2, MCF-7 and PC-3 cell lines, with the IC50 values of 2.19 ± 0.45 μM, 1.32 ± 0.26 μM, 6.27 ± 1.04 μM and 4.63 ± 0.83 μM. The structure–activity relationships (SARs) and docking studies indicated that the pyrrolo[2,3-b]pyridine derivatives bearing 4-oxo-pyridazinone moiety was superior to the pyrrolo[2,3-d]pyrimidine derivatives bearing 6-oxo-pyridazinone moiety. What's more, the target compounds modified with X and Y (X = H, Y = H) were favorable to the activity. And electron drawing groups (EWGs) of 4-Cl-3CF3 on the aryl group show the best activity.
Synthesis and antidiabetic evaluation of novel pyrazolone derivatives
Kumar, M. Vijay,Revanasiddappa
, p. 169 - 172 (2019/01/16)
Ethyl-2-[diazo(substituted benzene) acetoacetates (2a-h) were treated with benzhydrazide (3) to yield the title compounds pyrazolone derivatives (4a-h). All the new compounds were characterized by IR, 1H-NMR, Mass and elemental analysis. The title compounds were subjected to in-vitro antidiabetic activity by α-amylase and α-glucosidase inhibitory activity. Compounds 4b and 4c showed good antidiabetic activity when compared to the standard drug acarbose.
Microwave assisted synthesis and biological activity of 4-(2-(aryl substituted) hydrazono)-1-(2-(p-tolyloxyacetyl)-3-methyl-1H-pyrazol- 5-one
Jois, H.S. Vidyashree,Kalluraya, Balakrishna,Babu,Bhagya,Chandrashekar
, p. 7 - 10 (2019/01/21)
A novel series of 4-(2-(aryl substituted) hydrazono)-1-(2-(p-tolyloxy) acetyl)-3-methyl- 1H-pyrazol-5-ones 3(a-j) was prepared by the reaction of ethyl-2-arylhydrazono -3- oxobutyrate and p-tolyloxyacethydrazide under microwave irradiation. The structures of the synthesized compounds were established by their spectral and analytical data. All the new compounds were screened for their antibacterial and antifungal activity.
Synthesis and antibacterial activity of some novel 4-aryl hydrazono-2,5-disubstituted-2,4-dihydro-3H-pyrazol-3-ones
Singh, Vipin Kumar
, p. 429 - 432 (2019/01/21)
4-Aryl hydrazono-2,4-dihydro-3H-pyrazol-2,5-disubstituted-3-ones were prepared by the reaction of ethyl-2-arylhydrazono-3-oxybutyrates with substituted hydrazines in the presence of glacial acetic acid at reflux temp. The synthesized compounds have been c
Design, synthesis and structure-activity relationships of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety as potential antitumor agents
Zhou, Shunguang,Liao, Huimin,He, Chao,Dou, Yanan,Jiang, Mingyan,Ren, Lixiang,Zhao, Yanfang,Gong, Ping
, p. 581 - 593 (2014/07/21)
A series of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety were synthesized and evaluated for their in vitro cytotoxic activity against five cancer cell lines (HT-29, H460, A549, MKN-45, and U87MG). Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines. Compounds 15a, 20a, 15b, 15c, 20d, and 16e were further examined for their inhibitory activity against c-Met kinase. The most promising compound 15a (c-Met half-maximal inhibitory concentration [IC50] = 2.15 nM) showed remarkable cytotoxicity against HT-29, H460, and A549 cell lines with IC50 values of 0.10 μM, 0.13 μM, and 0.05 μM, respectively, and thus it was 1.5- to 2.3-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.
Type II diabetes-related enzyme inhibition and molecular modeling study of a novel series of pyrazolone derivatives
Shetty, Shobhitha,Kalluraya, Balakrishna,Nithinchandra,Peethambar,Telkar, Sandeep B.
, p. 2834 - 2846 (2014/05/06)
Inhibitors of alpha-Amylase are targets for the development of novel drugs for the treatment of diabetes and obesity. Alpha amylase is an enzyme which increases the bio availability of glucose in the blood. Hence, the inhibition effects of alpha amylase of 2-[1-(4-isobutylphenyl)ethyl]-5-methyl-4-[2-(aryl- substituted)hydrazinylidene]-2,4-dihydro-3H-pyrazol-3-one (4a-l) were investigated, among them compounds 4d, 4f, 4a, and 4g have displayed good inhibitory activity. The compounds with significant results were further evaluated for their molecular modeling study using in silico method. The new series of compounds were synthesized by solvent-free microwave irradiation method and were characterized by spectral and analytical data.
Phenyl hydrazone bearing pyrazole and pyrimidine scaffolds: Design and discovery of a novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) against HIV-1 and their antibacterial properties
Singh, Udaya Pratap,Bhat, Hans Raj,Verma, Amita,Kumawat, Mukesh Kumar,Kaur, Rajinder,Gupta,Singh, Ramendra K.
, p. 17335 - 17348 (2013/09/24)
A novel series of phenyl hydrazone bearing pyrazole and pyrimidine hybrid compounds has been designed using the molinspiration toolkit based on Lipinski's rule of five and developed via sequential reactions starting from the diazotization of different anilines and further active methylation with acetyl acetone, ethyl acetoacetate and ethyl cyanoacetate to generate hydrazono derivatives. The target hybrid compounds were synthesized on cyclisation of the resulting hydrazono derivatives with hydrazine, phenyl hydrazine and urea. These molecules have been subsequently tested for anti-HIV activity using TZM-bl cell lines. The MTT assay was also carried out for the cytotoxicity determination of the active compounds. Further, to exemplify the key structural features of the molecules, a molecular docking analysis of the most active compounds was performed at the NNIBP of the HIV-RT protein. The antibacterial activity of the target compounds was also determined against a panel of four Gram-positive and four Gram-negative human pathogens. All molecules showed a potent anti-HIV activity along with a prominent inhibition of bacterial organisms.
