25983-53-3Relevant academic research and scientific papers
Identification, synthesis and pharmacological evaluation of novel anti-EV71 agents via cyclophilin A inhibition
Yan, Wenzhong,Qing, Jie,Mei, Hanbing,Nong, Junxiu,Huang, Jin,Zhu, Jin,Jiang, Hualiang,Liu, Lei,Zhang, Linqi,Li, Jian
, p. 5682 - 5686 (2015/11/24)
In this work, the relationship between cyclophilin A (CypA) and EV71 prompted us to screen a series of small molecular CypA inhibitors which were previously reported by our group. Among them, compounds 1 and 2 were discovered as non-immunosuppressive anti-EV71 agents with an EC50 values of 1.07 ± 0.17 μM and 3.36 ± 0.45 μM in virus assay, respectively, which were desirably for the further study. The subsequent chemical modifications derived a novel class of molecules, among which compound 11 demonstrated the most potent anti-EV71 activity in virus assay (EC50 = 0.37 ± 0.17 μM), and low cytotoxicity (CC50 > 25 μM). The following CypA enzyme inhibition studies indicated that there was not only the enzyme inhibition activity, undoubtedly important, functioning in the antiviral process, but also some unknown mechanisms worked in combination, and the further study is underway in our laboratory. Nevertheless, to the best of our knowledge, compound 11 was probably the most potent small molecular anti-EV71 agent via CypA inhibitory mechanism to date. Consequently, our study provided a new potential small molecule for curing EV71 infection.
The flavan-isoflavan rearrangement: Bioinspired synthetic access to isoflavonoids via 1,2-shift-alkylation sequence
Nakamura, Kayo,Ohmori, Ken,Suzuki, Keisuke
, p. 7012 - 7014 (2015/04/22)
An approach to 2-substituted isoflavonoids is reported based on the 1,2-shift of the aryl group in the catechin skeleton followed by the in situ alkylation. Synthesis of (-)-equol, a natural isoflavan with estrogenic activities, was achieved.
Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)
Ma, Lei,Yang, Zhengyi,Li, Chenjing,Zhu, Zhiyuan,Shen, Xu,Hu, Lihong
experimental part, p. 643 - 648 (2012/04/10)
According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A-and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC50=0.27 μM).
Water accessibility to the binding cleft as a major switching factor from entropy-driven to enthalpy-driven binding of an alkyl group by synthetic receptors
Matsumoto, Sayaka,Iwamoto, Hiroya,Mizutani, Tadashi
, p. 1163 - 1170 (2011/07/07)
Free energy, enthalpy, and entropy changes in the binding of alkyl pyridines to water-soluble zinc porphyrin receptors with varying accessibility of water to the binding cleft were determined to explain why the driving force of hydrophobic effects is enthalp-ic in some occasions and entropic in others. Zinc porphyrins bearing four alkyl pillars with terminal solubilizing poly(oxyethylene) (POE) chains of molecular weight of 750 (1), with eight alkyl pillars with terminal solubilizing POE chains of molecular weight of 350 (3), and with eight alkyl pillars with POE of molecular weight of 750 (4) had a binding cleft with decreasing water accessibility in this order as revealed by binding selectivity of imidazole/pyridine. Although all these porphyrins showed that the free energy of binding (-ΔG°) increases linearly as the alkyl group of the guest is lengthened (-ΔG° per CH2 was 2.6, 2.8, and 2.6kJmol-1 for 1, 3, and 4, respectively), the origin of the free energy gain was much different. Receptor 1 with the most hydrophilic binding site bound the alkyl group by an enthalpic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔH° = -16.4 kJmol-1), while receptor 4 with the most hydrophobic binding site by an entropic driving force (4-pentylpyridine favored over 4-methylpyridine by ΔΔ5° = 39.6 JK-1mol-1). Receptor 3 showed intermediate behavior: both enthalpic and entropic terms drove the binding of the alkyl group with the en-thalpic driving force being dominant. The binding site of the four-pillared receptor (1) is open and accessible to water molecules, and is more hydro-philic than that of the eight-pillared receptor (4). We propose that the alkyl chains of 1 are exposed to water to produce a room to accommodate the guest to result in enthalpy-driven hy-drophobic binding, whereas 4 can accommodate the guest without such structural changes to lead to entropy-driven hydrophobic binding. Therefore, accessibility of water or exposure of the binding site to the water phase switches the driving force of hydropho-bic effects from an entropic force to an enthalpic force. 2010 Wiley-VCH Verlag GmbH Co. KGaA, Weinheim.
Synthesis and protein kinase inhibitory activity of balanol analogues with modified benzophenone subunits
Lampe, John W.,Jagdmann Jr., G. Erik,Johnson, Mary George,Lai, Yen-Shi,Lowden, Christopher T.,Lynch, Michael P.,Mendoza, José S.,Murphy, Marcia M.,Wilson, Joseph W.,Ballas, Lawrence M.,Carter, Kiyomi,Biggers, Christopher K.,Darges, James W.,Davis, Jefferson E.,Hubbard, Frederick R.,Stamper, Mark L.,Defauw, Jean M.,Foglesong, Robert J.,Hall, Steven E.,Heerding, Julia M.,Hollinshead, Sean P.,Hu, Hong,Hughes, Philip F.
, p. 2624 - 2643 (2007/10/03)
A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure -activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.
Two step synthesis of C2 symmetric 2,6,diarylalkyloxybenzaldehydes - A mitsunobu approach
Smith, John R. Lindsay,O'Brien, Peter,Reginato, Gloriana
, p. 3415 - 3420 (2007/10/03)
A simple two step method for the synthesis of three novel C2 symmetric 2,6-diarylalkyloxybenzaldehydes is described. Starting from resorcinol, the route involves double Mitsunobu reaction with chiral alcohols followed by regiospecific lithiation and formylation.
Synthesis of porphyrins tailored with eight facially-encumbering groups. An approach to solid-state light-harvesting complexes
Wagner,Wagner, Richard W.,Lindsey,Lindsey, Jonathan S.,Turowska-Tyrk,Turowska-Tyrk, Ilona,Scheidt,Scheidt, W. Robert
, p. 11097 - 11112 (2007/10/02)
Synthetic models of the photosynthetic antenna complexes must achieve long-range 3-dimensional order encompassing a large number of porphyrinic pigments with limited direct contact of the pigments. In order to develop solid-state antenna complexes, we have synthesized porphyrins bearing benzyloxy groups projecting over both faces and optionally also around the periphery of the porphyrin. Routes have been established for prefunctionalizing benzaldehydes with various benzyloxy groups. Reaction of 2,6-bis, 3,5-bis, or 2,4,6-tris(benzyloxy)benzaldehydes with pyrrole via the room temperature two-step one-flask porphyrin reaction provides direct access to the facially-encumbered porphyrins. The benzyloxybenzaldehydes react as efficiently as methoxybenzaldehydes, indicating the utility of the -OCH2- unit for introducing large substituents near the face of the porphyrin. The octakis and dodecakis(benzyloxy)porphyrins exhibit characteristic porphyrin absorption and fluorescence properties in solution. The crystal structure of meso-tetrakis[2,6-bis(2,3,4,5,6-pentalfuorobenzyloxy)phenyl]porphyrin has been determined. The pentafluorobenzyloxy substituents provide a cavity on each side of the porphyrin plane which has an approximate cylindrical shape with a diameter of ~7.5 A and a height of ≥4.5 A. The porphyrin core parameters are those obtained for free base derivatives in which the inner hydrogen atoms are ordered. Crystal data: a=14.759 (1) A, b=25.519 (2) A, c=13.100 (1) A, α=100.04 (1), β=99.83 (1), γ=88.25 (1), V=4767.3 (6) A3, all measurements at 127 K, triclinic, space group P1, Z=2 R1(F)=0.097, for 10020 'observed' data, and wR2(F2)=0.275 for 17761 total unique (all) data.
Synthesis and Fluorescence Properties of Selectively Metallated Diporphyrins with Electron-Accepting Moieties
Nagata, Toshi
, p. 3005 - 3016 (2007/10/02)
Synthesis of selectively metallated diporphyrins with electron-accepting moieties is described.Steady-state fluorescence spectra of these compounds showed substantial quenching of the fluorescence of the free-base porphyrin.A possible "superexchange" mechanism of long-range electron transfer is discussed.
Synthesis of facially-encumbered porphyrins. An approach to light-harvesting antenna complexes
Wagner,Ruffing,Breakwell,Lindsey
, p. 1703 - 1706 (2007/10/02)
2,6-di- and 2.4.6-tri-benzyloxybenzaldehydes are converted to the respective octa- and dodeca-benzyloxy porphyrins in 9-52% yields via the two-step one-flask room-temperature porphyrin synthesis.
