3660-90-0Relevant articles and documents
Bis(iminopyridyl)phthalazine as a sterically hindered compartmental ligand for an M2 (M = Co, Ni, Fe, Zn) centre; Applications in ethylene oligomerisation
Savjani, Nicky,Singh, Kuldip,Solan, Gregory A.
, p. 184 - 194 (2015)
Abstract The new bis(iminopyridyl)phthalazine ligand, 1,4-{(2,6-i-Pr2C6H3)N=CMe)C5H3N}2C8H4N2 (L), has been prepared in good yield using a combination of palladium-mediated cross coupling and condensation strategies. Reaction of L with three equivalents of CoX2 (X = Cl, Br) in n-BuOH at elevated temperature generates, on crystallisation from bench acetonitrile, the paramagnetic tetrahalocobaltate salts [(L)Co2X(μ-X)(NCMe)m(OH2)n](CoX4) (X = Cl, m = 2, n = 1 1a; X = Br, m = 2, n = 0 1b) as acetonitrile or mixed acetonitrile/aqua adducts; a similar product is obtained from the reaction of FeCl2 with L and has been tentatively assigned as [(L)Fe2Cl(μ-Cl)(OH2)3](FeCl4) (2). By contrast, reaction of L with NiX2(DME) (X = Cl, Br; DME = 1,2-dimethoxyethane), under similar reaction conditions, affords the halide salts [(L)Ni2X2(μ-X)(OH2)2](X) (X = Cl 3a, X = Br 3b) as aqua adducts. Structural determinations on 1 and 3 reveal L to adopt a bis(tridentate) bonding mode allowing the halide-bridged metal centres to assemble in close proximity (M...M range: 3.437-3.596 ?). Unexpectedly, on reaction of L with ZnCl2, the neutral bimetallic [(L)Zn2Cl4] (4b) complex is formed in which the ZnCl2 units fill inequivalent binding sites within L (viz. the Nphth,Npy,Nim and Npy,Nim pockets). Complex 4b could also be obtained by the sequential addition of ZnCl2 to L to form firstly monometallic [(L)ZnCl2] (4a) and then on further ZnCl2 addition 4b; the fluxional behaviour of diamagnetic 4a and 4b is also reported. On activation with excess methylaluminoxane (MAO), 1-3 display modest activities for ethylene oligomerisation forming low molecular weight waxes with methyl-branched products predominating for the nickel systems (3). On the other hand, the iron catalyst (2) gives exclusively α-olefins while the cobalt systems (1) are much less selective affording equal mixtures of α-olefins and internal olefins along with lower levels of vinylidenes and tri-substituted alkenes. Single crystal X-ray structures are reported for L, 1a, 1b, 3a, 3b and 4.
Synthesis and biological evaluation of 2,4-disubstituted phthalazinones as Aurora kinase inhibitors
Wang, Wei,Feng, Xiu,Liu, Huan-Xiang,Chen, Shi-Wu,Hui, Ling
, p. 3217 - 3226 (2018/05/04)
A series of 2,4-disubstituted phthalazinones were synthesized and their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects were evaluated. Among them, N-cyclohexyl-4-((4-(1-methyl-1H-pyrazol-4-yl)-1-oxophthalazin-2(1H)-yl) methyl) benzamide (12c) exhibited the most potent antiproliferation against five carcinoma cell lines (HeLa, A549, HepG2, LoVo and HCT116 cells) with IC50 values in range of 2.2–4.6 μM, while the IC50 value of reference compound VX-680 was 8.5–15.3 μM. Moreover, Aurora kinase assays exhibited that compound 12c was potent inhibitor of AurA and AurB kinase with the IC50 values were 118 ± 8.1 and 80 ± 4.2 nM, respectively. Molecular docking studies indicated that compound 12c forms better interaction with both AurA and AurB. Furthermore, compound 12c induced G2/M cell cycle arrest in HeLa cells by regulating protein levels of cyclinB1 and cdc2. These results suggested that 12c is a promising pan-Aurora kinase inhibitor for the potential treatment of cancer.
Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship
Gao, Rui,Liao, Sha,Zhang, Chen,Zhu, Weilong,Wang, Liyan,Huang, Jin,Zhao, Zhenjiang,Li, Honglin,Qian, Xuhong,Xu, Yufang
, p. 597 - 604 (2013/05/09)
In this study, starting from a lead compound discovered by virtual screening, a series of novel heterocyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inh
