Indazole Derivative

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform

Eduardo Villamor - One of the best experts on this subject based on the ideXlab platform.

Francisco Perezvizcaino - One of the best experts on this subject based on the ideXlab platform.

Prasanta Ghosh - One of the best experts on this subject based on the ideXlab platform.

  • A Redox-Active Cascade Precursor: Isolation of a Zwitterionic Triphenylphosphonio–Hydrazyl Radical and an Indazolo–Indazole Derivative
    Inorganic chemistry, 2017
    Co-Authors: Sandip Mondal, Suvendu Maity, Prasanta Ghosh
    Abstract:

    A redox-active [ML] unit (M = CoII and MnII; LH2 = N′-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide) defined as a cascade precursor that undergoes a multicomponent redox reaction comprising of a C–N bond formation, tautomerization, oxidation, C–C coupling, demetalation, and affording 6,14-dibenzoylbenzo[f]benzo[5,6]indazolo[3a,3-c]Indazole-5,8,13,16-tetraone (IndL2) is reported. Conversion of LH2 → IndL2 in air is overall a (6H++6e) oxidation reaction, and it opens a route for the syntheses of bioactive diarylindazolo[3a,3-c]Indazole Derivatives. The reaction occurs via a radical coupling reaction, and the radical intermediate was isolated as a triphenylphosphonio adduct. In presence of PPh3 the [ML] unit promotes a reaction that involves a C–P bond formation, tautomerization, and oxidation to yield a stable zwitterionic triphenylphosphonio-hydrazyl radical (PPh3L±•). Conversion of LH2 → PPh3L±• is a (3H++3e) oxidation reaction. To authenticate the [ML] unit, in addition to the IndL2, a zinc(II) co...

  • a redox active cascade precursor isolation of a zwitterionic triphenylphosphonio hydrazyl radical and an indazolo Indazole Derivative
    Inorganic Chemistry, 2017
    Co-Authors: Sandip Mondal, Suvendu Maity, Prasanta Ghosh
    Abstract:

    A redox-active [ML] unit (M = CoII and MnII; LH2 = N′-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide) defined as a cascade precursor that undergoes a multicomponent redox reaction comprising of a C–N bond formation, tautomerization, oxidation, C–C coupling, demetalation, and affording 6,14-dibenzoylbenzo[f]benzo[5,6]indazolo[3a,3-c]Indazole-5,8,13,16-tetraone (IndL2) is reported. Conversion of LH2 → IndL2 in air is overall a (6H++6e) oxidation reaction, and it opens a route for the syntheses of bioactive diarylindazolo[3a,3-c]Indazole Derivatives. The reaction occurs via a radical coupling reaction, and the radical intermediate was isolated as a triphenylphosphonio adduct. In presence of PPh3 the [ML] unit promotes a reaction that involves a C–P bond formation, tautomerization, and oxidation to yield a stable zwitterionic triphenylphosphonio-hydrazyl radical (PPh3L±•). Conversion of LH2 → PPh3L±• is a (3H++3e) oxidation reaction. To authenticate the [ML] unit, in addition to the IndL2, a zinc(II) co...

  • A Redox-Active Cascade Precursor: Isolation of a Zwitterionic Triphenylphosphonio–Hydrazyl Radical and an Indazolo–Indazole Derivative
    2017
    Co-Authors: Sandip Mondal, Suvendu Maity, Prasanta Ghosh
    Abstract:

    A redox-active [ML] unit (M = CoII and MnII; LH2 = N′-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)­benzohydrazide) defined as a cascade precursor that undergoes a multicomponent redox reaction comprising of a C–N bond formation, tautomerization, oxidation, C–C coupling, demetalation, and affording 6,14-dibenzoylbenzo­[f]­benzo­[5,6]­indazolo­[3a,3-c]­Indazole-5,8,13,16-tetraone (IndL2) is reported. Conversion of LH2 → IndL2 in air is overall a (6H++6e) oxidation reaction, and it opens a route for the syntheses of bioactive diarylindazolo­[3a,3-c]­Indazole Derivatives. The reaction occurs via a radical coupling reaction, and the radical intermediate was isolated as a triphenylphosphonio adduct. In presence of PPh3 the [ML] unit promotes a reaction that involves a C–P bond formation, tautomerization, and oxidation to yield a stable zwitterionic triphenylphosphonio-hydrazyl radical (PPh3L±•). Conversion of LH2 → PPh3L±• is a (3H++3e) oxidation reaction. To authenticate the [ML] unit, in addition to the IndL2, a zinc­(II) complex, [(L3)­ZnII(H2O)­Cl]·2MeOH (1·2MeOH), was successfully isolated (L3H = a pyridazine Derivative of 1,4 naphthoquinone) from a reaction of LH2 with hydrated ZnCl2. Conversion of 3LH2 → 1 is also a multicomponent (6H++6e) oxidation reaction promoted by zinc­(II) ion via a radical intermediate. Facile oxidation of [L2–] to [L•–] that was considered as an intermediate of these conversions was confirmed by isolating a 1,4 naphthoquinone-benzhydrazyl radical (LH•) complex, [(LH•)­ZnII(H2O)­Cl2] (2H•). The intermediates of LH2 → IndL2, LH2 → PPh3L±•, and 3LH2 → 1 conversions were analyzed by electrospray ionization mass spectroscopy. The molecular and electronic structures of PPh3L±•, IndL2, 1·2MeOH, and 2H• were confirmed by single-crystal X-ray crystallography, electron paramagnetic resonance spectroscopy, and density functional theory calculations

Jih-hwa Guh - One of the best experts on this subject based on the ideXlab platform.

  • the Indazole Derivative yd 3 specifically inhibits thrombin induced angiogenesis in vitro and in vivo
    Shock, 2010
    Co-Authors: Chieh Yu Peng, Jih-hwa Guh, Shiow Lin Pan, Hui Chen Pai, An Chi Tsai, Ya Ling Chang, Shengchu Kuo, Fang Yu Lee, Cheming Teng
    Abstract:

    ABSTRACT Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and the inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to examine the antiangiogenic efficacy of YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-Indazole], a selective thrombin inhibitor, on thrombin-induced endothelial cell proliferation and neoangiogenesis in a murine Matrigel model. First, the effect of YD-3 on angiogenesis was evaluated in vivo using the mouse Matrigel implant model. Plugs treated with 1 and 10 μM of YD-3 inhibited neovascularization induced by thrombin, protease-activated receptor (PAR) 1, and PAR-4, but not by vascular endothelial growth factor, in a concentration-dependent manner over 7 days. These results indicate that YD-3 has specific antiangiogenic activity on thrombin. YD-3 also inhibited (in a concentration-dependent manner) the ability of thrombin, PAR-1, and PAR-4, but not PAR-2, to induce the proliferation of human umbilical vascular endothelial cells, using a [3H]thymidine incorporation assay. YD-3 predominantly inhibited thrombin-induced vascular endothelial growth factor receptor 2 (Flk-1) expression, but not extracellular signal-regulated kinase 1/2 phosphorylation, using Western blot analysis. YD-3 may have benefit in elucidating pathophysiology induced by thrombin-induced angiogenesis.

  • the Indazole Derivative yd 3 inhibits thrombin induced vascular smooth muscle cell proliferation and attenuates intimal thickening after balloon injury
    Thrombosis and Haemostasis, 2004
    Co-Authors: Chieh Yu Peng, Jih-hwa Guh, Shiow Lin Pan, Ya Ling Chang, Shengchu Kuo, Fang Yu Lee, Yi Nan Liu, Cheming Teng
    Abstract:

    Proliferation of vascular smooth muscle cells (VSMCs) is postulated to be one of the key events in the pathogenesis of atherosclerosis and restenosis.We investigated whether YD-3, a lowmolecular weight, non-peptide compound, could modulate proliferation of VSMCs in vitro and restenosis after balloon angioplasty in vivo. We examined the effect of YD-3 on thrombininduced VSMC proliferation by [3H]thymidine incorporation assay. The data demonstrated that YD-3 inhibited VSMC proliferation in a concentration-dependent manner. To define the mechanisms of YD-3 action,we found that YD-3 showed a profound inhibition on thrombin-induced Ras and ERK1/2 activities by using Western blotting analysis. Furthermore, oral adminis tration of YD-3 exhibited a marked reduction in neointimal thickness using the carotid injury model in rats. Using immunochemical detection, our experiments also revealed that YD-3 significantly suppressed expression of the PAR-1 receptor, and markedly inhibited PAR-1-activating peptide (SFLLRN)-induced VSMC proliferation in a concentration-dependent manner. These results suggest that YD-3 inhibits thrombin-induced VSMC growth via the Ras- and ERK1/2-mediated signaling pathway. Moreover, YD-3 also shows a developmental potential in the treatment of atherosclerosis and restenosis after vascular injury.

  • Mechanism of anti-proliferation caused by YC-1, an Indazole Derivative, in cultured rat A10 vascular smooth-muscle cells
    Biochemical Journal, 1995
    Co-Authors: Z J Cheng, Jih-hwa Guh, F Y Lee, S C Kuo
    Abstract:

    An Indazole Derivative, YC-1, was identified in this study to be capable of reversibly and effectively inhibiting proliferation of rat A10 vascular smooth-muscle cells (VSMCs) in vitro. YC-1 (1-100 microM) dose-dependently inhibited [3H]thymidine incorporation into DNA in rat A10 VSMCs that were synchronized by serum depletion and then restimulated by addition of 10% foetal calf serum (FCS), whereas FCS-induced [3H]thymidine incorporation into rat synchronized endothelial cells was unaffected by this agent. The dose of YC-1 required to cause inhibition of FCS-induced proliferation was similar to that necessary for the formation of cellular cyclic GMP (cGMP). Guanylate cyclase activity in soluble fractions of VSMCs was activated by YC-1 (1-100 microM), whereas cGMP-specific phosphodiesterase activity was unaffected by this compound. The anti-proliferative effect of YC-1 was mimicked by 8-bromo-cGMP, a membrane-permeable cGMP analogue, and was antagonized by KT 5823 (0.2 microM), a selective inhibitor of protein kinase G. The anti-proliferative effect of YC-1 was also antagonized by Methylene Blue (50 microM), a guanylate cyclase inhibitor, and was potentiated by 3-isobutyl-1-methylxanthine (500 microM), a phosphodiesterase inhibitor. These results verified that YC-1 is a direct soluble guanylate cyclase activator in A10 VSMCs, and the anti-proliferative effect of YC-1 is mediated by cGMP. YC-1 still inhibited FCS-induced DNA synthesis even when added 10-18 h after restimulation of the serum-deprived A10 VSMCs with 10% FCS. Flow cytometry in synchronized populations revealed an acute blockage of FCS-inducible cell-cycle progression at a point in the G1/S-phase in YC-1 (100 microM)-treated cells. The inhibition of proliferation by YC-1 was demonstrated to be independent of cell damage, as documented by several criteria of cell viability. In conclusion, YC-1 reversibly and effectively inhibited the proliferation of VSMCs, suggesting that it has potential as a therapeutic agent in the prevention of vascular diseases.

Gema Esther Gonzalezluis - One of the best experts on this subject based on the ideXlab platform.

Related terms

Indazole Derivative - 15 days free trial to Access Experts & Abstracts