51359-78-5Relevant articles and documents
Cationic N-confused porphyrin derivative as a better molecule scaffold for G-quadruplex recognition
Du, Yuhao,Zhang, Dan,Chen, Wei,Zhang, Ming,Zhou, Yangyang,Zhou, Xiang
, p. 1111 - 1116 (2010)
One N-confused porphyrin derivative was prepared and its first observation that it could stabilize G-quadruplex and possessed high selectivity over duplex DNA was made, furthermore, it was also proved to possess the capacity to induce a structural transition from the antiparallel to the mixed-type hybrid G-quadruplex structure.
Synthesis and evaluation of novel α-aminoamides containing benzoheterocyclic moiety for the treatment of pain
Cheng, Jingchao,He, Junlin,Ren, Fengxia,Ren, Fengzhi,Shi, Weiguo,Tong, Kun,Yu, Zixing,Zhang, Ruotian,Zhang, Tao,Zhang, Yatong
, (2021)
Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav 1.7 and anti-Nav 1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.
A Chemoselective and Modular Post-Synthetic Multi-Functionalization of NHC-Platinum Complexes
Dahm, Georges,Borré, Etienne,Guichard, Gilles,Bellemin-Laponnaz, Stéphane
, p. 1665 - 1668 (2015)
We report oxime ligation in combination with metal ligand exchange as a novel orthogonal and practical approach to the multifunctionalization of NHC-platinum complexes. This strategy, which enables strong diversity enhancement of metallodrug candidates, could also be applied to selective bioconjugation. We report oxime ligation in combination with metal ligand exchange as a novel orthogonal and practical approach to the multi-functionalization of NHC-platinum complexes.
Self-Assembly of a "cationic-cage": Via the formation of Ag-carbene bonds followed by imine condensation
Modak, Ritwik,Mondal, Bijnaneswar,Howlader, Prodip,Mukherjee, Partha Sarathi
, p. 6711 - 6714 (2019)
A new strategy for the synthesis of a "cationic-cage" (CC-Ag) has been developed via metal-carbene (M-CNHC) bond formation followed by imine bond condensation. Reaction of a trigonal trisimidazolium salt H3L(PF6)3 functionalized with three flexible N-phenyl-Aldehyde pendants with silver oxide yielded a trinuclear tricationic organometallic cage (OC-Ag). Subsequent treatment of the organometallic cage (OC-Ag) with 1,4-diaminobutane links the two tris-NHC ligands via imine bond condensation, which thus generates a 3D 'cationic-cage' (CC-Ag). Furthermore, post-synthetic replacement of the Ag(i) with Au(i) leading to the formation of CC-Au was achieved via trans-metalation, with the retention of the molecular architecture.
Discovery of novel CA-4 analogs as dual inhibitors of tubulin polymerization and PD-1/PD-L1 interaction for cancer treatment
Yang, Xuchao,Cheng, Binbin,Xiao, Yao,Xue, Mingming,Liu, Ting,Cao, Hao,Chen, Jianjun
, (2021)
A series of novel CA-4 analogs as dual inhibitors of tubulin polymerization and PD-1/PD-L1 were designed, synthesized and bio-evaluated. Among them, compound TP5 exhibited strongest inhibitory effects against five cancer cell lines with an IC50 value of 800 nM in HepG2 cells. In addition, mechanism studies revealed that TP5 could effectively inhibit tubulin polymerization, suppress HepG2 cells migration and colony formation, and cause cell arrest at G2/M phase and induce apoptosis. Furthermore, TP5 exhibited moderate anti-PD-1/PD-L1 activity with IC50 values of 48.76 μM in a homogenous time-resolved fluorescence (HTRF) assay. In vivo efficacy studies indicated that TP5 could significantly suppress tumor growth in an immune checkpoint humanized mouse model with a Tumor Growth Suppression (TGI) of 57.9% at 100 mg/kg without causing significant toxicity. Moreover, TP5 did not cause in vivo cardiotoxicity in BALB/c mice. These results suggest that the novel CA-4 analogs may serve as a starting point for developing more potent dual inhibitors of tubulin polymerization and PD-1/PD-L1.
Rotationally Restricted 1,1′-Bis(phenylethynyl)ferrocene Subunits in Macrocycles
Hoffmann, Viktor,Jenny, Nicolas,H?ussinger, Daniel,Neuburger, Markus,Mayor, Marcel
, p. 2187 - 2199 (2016)
The synthesis of macrocycles comprising a 1,1′-bis(phenylethynyl)ferrocene subunit was developed to increase the structural control over the spatial arrangement of the two cyclopentadienyl ligands of the ferrocene junction. The target structures were obtained through a modular strategy that enables the assembly of varying ring sizes from a common precursor. In particular, macrocycles were either formed by an ether formation reaction or by ring-closing metathesis reactions. The macrocycles were obtained in reasonable isolated yields, which allowed their thorough characterization by one- and two-dimensional NMR spectroscopy experiments, and the identity of one macrocycle was corroborated by single-crystal X-ray diffraction.
Synthesis and evaluation of novel α-aminoamides containing an indole moiety for the treatment of neuropathic pain
Li, Haotian,Fan, Shiyong,Cheng, Jingchao,Zhang, Ping,Zhong, Bohua,Shi, Weiguo
, (2016)
The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted.
A Bifunctional Photosensitizer for Enhanced Fractional Photodynamic Therapy: Singlet Oxygen Generation in the Presence and Absence of Light
Turan, Ilke Simsek,Yildiz, Deniz,Turksoy, Abdurrahman,Gunaydin, Gurcan,Akkaya, Engin U.
, p. 2875 - 2878 (2016)
The photosensitized generation of singlet oxygen within tumor tissues during photodynamic therapy (PDT) is self-limiting, as the already low oxygen concentrations within tumors is further diminished during the process. In certain applications, to minimize photoinduced hypoxia the light is introduced intermittently (fractional PDT) to allow time for the replenishment of cellular oxygen. This condition extends the time required for effective therapy. Herein, we demonstrated that a photosensitizer with an additional 2-pyridone module for trapping singlet oxygen would be useful in fractional PDT. Thus, in the light cycle, the endoperoxide of 2-pyridone is generated along with singlet oxygen. In the dark cycle, the endoperoxide undergoes thermal cycloreversion to produce singlet oxygen, regenerating the 2-pyridone module. As a result, the photodynamic process can continue in the dark as well as in the light cycles. Cell-culture studies validated this working principle in vitro.
Novel quinolone-based potent and selective HDAC6 inhibitors: Synthesis, molecular modeling studies and biological investigation
Relitti, Nicola,Saraswati, A. Prasanth,Chemi, Giulia,Brindisi, Margherita,Brogi, Simone,Herp, Daniel,Schmidtkunz, Karin,Saccoccia, Fulvio,Ruberti, Giovina,Ulivieri, Cristina,Vanni, Francesca,Sarno, Federica,Altucci, Lucia,Lamponi, Stefania,Jung, Manfred,Gemma, Sandra,Butini, Stefania,Campiani, Giuseppe
, (2020/11/24)
In this work we describe the synthesis of potent and selective quinolone-based histone deacetylase 6 (HDAC6) inhibitors. The quinolone moiety has been exploited as an innovative bioactive cap-group for HDAC6 inhibition; its synthesis was achieved by applying a multicomponent reaction. The optimization of potency and selectivity of these products was performed by employing computational studies which led to the discovery of the diethylaminomethyl derivatives 7g and 7k as the most promising hit molecules. These compounds were investigated in cellular studies to evaluate their anticancer effect against colon (HCT-116) and histiocytic lymphoma (U9347) cancer cells, showing good to excellent potency, leading to tumor cell death by apoptosis induction. The small molecules 7a, 7g and 7k were able to strongly inhibit the cytoplasmic and slightly the nuclear HDAC enzymes, increasing the acetylation of tubulin and of the lysine 9 and 14 of histone 3, respectively. Compound 7g was also able to increase Hsp90 acetylation levels in HCT-116 cells, thus further supporting its HDAC6 inhibitory profile. Cytotoxicity and mutagenicity assays of these molecules showed a safe profile; moreover, the HPLC analysis of compound 7k revealed good solubility and stability profile.
COMPOUNDS AND PHOTORESPONSIVE RELEASE CONTROL AGENTS
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Paragraph 0057; 0058, (2020/10/14)
PROBLEM TO BE SOLVED: To provide compounds having a photoreleasing protecting group which has excellent photoresponsivity to long-wavelength light and can release molecules to be time- and space-controlled even by one-photon excitation. SOLUTION: The compounds are represented by any of the formulas (1) to (3) in the figure. In the formulas (1) to (3), X is a pigment-containing group; Y is a releasable molecule-containing group; and R1, R2 and R3 are each independently a hydrogen atom or alkyl group. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPO&INPIT
