4521-61-3Relevant articles and documents
Synthesis and biological evaluation of rigid polycyclic derivatives of the Diels-Alder adduct tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione
Ito, Felicia Megumi,Petroni, Jacqueline Marques,De Lima, Denis Pires,Beatriz, Adilson,Marques, Maria Rita,De Moraes, Manoel Odorico,Costa-Lotufo, Leticia Veras,Montenegro, Raquel Carvalho,Magalhaes, Hemerson Iury Ferreira,Do O Pessoa, Claudia
, p. 271 - 282 (2007)
Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformati
Synthesis of 3,4-diaminobenzoyl derivatives as factor Xa inhibitors
Yang, Jiabin,Su, Guoqiang,Ren, Yu,Chen, Yang
, p. 41 - 51 (2015)
Abstract The coagulation factor Xa (FXa) plays a central role in the blood coagulation cascade. Recent studies have shown that FXa is a particularly attractive target for the development of oral antithrombotic agents. In view of the excellent pharmaceutical properties of 1,2-phenylenediamine-based FXa inhibitors and the reported structureeactivity relationship (SAR) analysis of FXa inhibitors, we designed and synthesized a series of 3,4-diaminobenzoyl-based FXa inhibitors. Intensive SAR studies on this new series led to the discovery of 3,4-dimethoxyl substituted compound 7b. 7b is a highly potent, selective, direct FXa inhibitor with excellent in vivo antithrombotic activity.
Unusual C-H...π interactions in the structure of 3,4,5-trimethoxy-N-p-tolylbenzamide
Saeed, Aamer,Simpson, Jim
, p. 51 - 57 (2013)
3,4,5-trimethoxy-N-p-tolylbenzamide, C17H19NO 4, (1), is a benzanilide derivative derived from p-toluidine and 3,4,5-trimethoxybenzoyl chloride. The structure was identified from spectroscopic and elemental analysis data a
Micellar Catalysis for Sustainable Hydroformylation
Calamante, Massimo,Dei, Filippo,Maramai, Samuele,Migliorini, Francesca,Petricci, Elena
, p. 2794 - 2806 (2021/05/03)
It is here reported a fully sustainable and generally applicable protocol for the regioselective hydroformylation of terminal alkenes, using cheap commercially available catalysts and ligands, in mild reaction conditions (70 °C, 9 bar, 40 min). The process can take advantages from both micellar catalysis and microwave irradiation to obtain the linear aldehydes as the major or sole regioisomers in good to high yields. The substrate scope is largely explored as well as the application of hydroformylation in tandem with intramolecular hemiacetalization thus demonstrating the compatibility with a broad variety of functional groups. The reaction is efficient even in large scale and the catalyst and micellar water phase can be reused at least 5 times without any impact in reaction yields. The efficiency and sustainability of this protocol is strictly related to the in situ transformation of the aldehyde into the corresponding Bertagnini's salt that precipitates in the reaction mixture avoiding organic solvent mediated purification steps to obtain the final aldehydes as pure compounds.
Tubulin inhibitors: Discovery of a new scaffold targeting extra-binding residues within the colchicine site through anchoring substituents properly adapted to their pocket by a semi-flexible linker
AbdelHafez, El-Shimaa M. N.,Abdelhamid, Dalia,Aly, Omar M.,Maklad, Raed M.
, (2020/04/22)
Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between α- and β-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by ‘anchor groups’ which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these ‘extra-binding’ properties through reliving ligands’ strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of ?62.362 kcal/mol (extra-binding to Arg α:221, Thr β:353 & Lys β:254); 34% NCI-H522 cells’ death (at 10 μM), IC50 = 0.073 μM (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.
Probing the effects of the number and positions of –OCH3 and –CN substituents on color tuning of Ir(III) complex derivatives through a joint computational and experimental study
Qin, Xiao,Li, Ming,Xiang, Minghui,Luo, Yi,Jiao, Yan,Yuan, Rongao,Wang, Ning,Lu, Zhiyun,Pu, Xumei
, p. 470 - 481 (2019/06/03)
We performed a joint theoretical and experimental study on sixteen Ir(III) complexes bearing a similar molecular platform of bis(2-phenylbenzothiozolato-N,C2’) iridium(III) (acetylacetonate) by grafting – OCH3 group and/or – CN group on different positions of the C-related arene moiety of the C^N ligand (Cring). Our results reveal that the introduction of – CN renders an overall drop in the FMO energy levels while a reverse increase is observed for – OCH3. The ortho- and para-sites of the C-ring are more effective substitution positions to modulate the HOMO energy level due to the fact that the electronic density of HOMO mainly locates at them while the meta-site would induce a stronger impact on LUMO since the electronic density of LUMO mainly distributes over the position. Utilizing the synergistic effects of the substituents and the substituted positions, a wide color-tuning range from 479 nm to 637 nm was achieved, which covers nearly the whole window of visible spectrum. In particular, the tri-substituted Ir35mo4cn complex (λemmax=637 nm) may be a potential candidate for high efficiency red OLEDs materials due to its greatly enhanced absorption processes, relatively higher3MLCT (%), lower ΔES1–T1, enlarged separation between3MLCT/π–π* and3MC d–d states, and good hole and particle-transporting performances. Finally, six representative complexes were synthesized and their spectra were determined, which confirm the reliability of our computational strategy.
Pd(II)-Catalyzed asymmetric oxidative annulation of N-alkoxyheteroaryl amides and 1,3-dienes
Zhang, Tao,Shen, Hong-Cheng,Xu, Jia-Cheng,Fan, Tao,Han, Zhi-Yong,Gong, Liu-Zhu
, p. 2048 - 2051 (2019/03/29)
The first Pd(II)-catalyzed asymmetric oxidative annulation of N-alkoxyaryl amides and 1,3-dienes is reported, which features particular applicability for quick assembly of different types of chiral heterocycles with high yields and enantioselectivities. A novel chiral pyridine-oxazoline bearing a methoxyl group at the C-5 position and a gem-dimethyl group on the oxazoline moiety was found to be crucial for conversion.
Synthesis, biological evaluation and molecular docking studies of novel trimethoxy-ring derivatives as BRD4 inhibitors
Yang, Yan,Yao, Zhiyi
, p. 1319 - 1328 (2018/11/01)
Background: Bromodomain-containing protein 4 (BRD4) inhibitors synthesized with trimethoxy-ring refer to a new series of small molecular inhibitors. Currently, BRD4 offers the potential for research as a cancer therapeutic target. Based on previous studies, 17 trimethoxy-ring derivatives were designed as novel BRD4 inhibitors. Methods: All these new compounds were synthesized via the amide reaction. Their structures were identified by 1H NRM,13C NRM spectra and HRMS. In vitro antitumor activities of the new compounds were evaluated by MTT. Molecular docking studies were conducted to explain the binding interactions of these compounds with BRD4 protein. Results: A series of novel trimethoxy-ring derivatives were synthesized as BRD4 inhibitors and screened by testing their inhibition against HCT116, MCF-7, K562 and KMS-1 cell lines. Most of the newly synthesized compounds exhibited moderate-to-good inhibitory activity against HCT116, MCF-7, and K562 cell lines, whereas some showed inhibitory activity against the KMS-1 cell line. Conclusion: Compound 3g demonstrated the most potent anti-tumor activity against breast (MCF-7), leukemia (K562), multiple myeloma (KMS-1), and colon cancer (HCT116) cell lines.
Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents
Semenova, Marina N.,Demchuk, Dmitry V.,Tsyganov, Dmitry V.,Chernysheva, Natalia B.,Samet, Alexander V.,Silyanova, Eugenia A.,Kislyi, Victor P.,Maksimenko, Anna S.,Varakutin, Alexander E.,Konyushkin, Leonid D.,Raihstat, Mikhail M.,Kiselyov, Alex S.,Semenov, Victor V.
, p. 700 - 721 (2019/01/03)
A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure-activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diarylpyrazoles. Isoxazoles 3 with 3,4,5-trimethoxy-substituted ring A and 3-hydroxy-4-methoxy-substituted ring B were more active than the respective pyrazoles 1. Of the azoles substituted with the same set of other aryl pharmacophores, diarylpyrazoles 1, 4,5-diarylisoxazoles 3, and 4,5-diaryl-1,2,3-triazoles 7 displayed similar strongest antimitotic antitubulin effect followed by 3,4-diarylisoxazoles 5, 1,5-diaryl-1,2,3-triazoles 8, and pyrroles 10 that showed the lowest activity. Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazoles, whereas potency of the respective 3,4-diarylisoxazoles was increased.
Benzoylsalicylic acid derivatives as defense activators in tobacco and Arabidopsis
Kamatham, Samuel,Pallu, Reddanna,Pasupulati, Anil Kumar,Singh, Surya Satyanarayana,Gudipalli, Padmaja
, p. 160 - 169 (2017/08/29)
Systemic acquired resistance (SAR) is a long lasting inducible whole plant immunity often induced by either pathogens or chemical elicitors. Salicylic acid (SA) is a known SAR signal against a broad spectrum of pathogens in plants. In a recent study, we have reported that benzoylsalicylic acid (BzSA) is a SAR inducer in tobacco and Arabidopsis plants. Here, we have synthesized BzSA derivatives using SA and benzoyl chlorides of various moieties as substrates. The chemical structures of BzSA derivatives were elucidated using Infrared spectroscopy (IR), Nuclear magnetic spectroscopy (NMR) and High-resolution mass spectrometer (HRMS) analysis. The bioefficacy of BzSA derivatives in inducing defense response against tobacco mosaic virus (TMV) was investigated in tobacco and SA abolished transgenic NahG Arabidopsis plants. Interestingly, pre-treatment of local leaves of tobacco with BzSA derivatives enhanced the expression of SAR genes such as NPR1 [Non-expressor of pathogenesis-related (PR) genes 1], PR and other defense marker genes (HSR203, SIPK, WIPK) in systemic leaves. Pre-treatment of BzSA derivatives reduced the spread of TMV infection to uninfected areas by restricting lesion number and diameter both in local and systemic leaves of tobacco in a dose-dependent manner. Furthermore, pre-treatment of BzSA derivatives in local leaves of SA deficient Arabidopsis NahG plants induced SAR through AtPR1 and AtPR5 gene expression and reduced leaf necrosis and curling symptoms in systemic leaves as compared to BzSA. These results suggest that BzSA derivatives are potent SAR inducers against TMV in tobacco and Arabidopsis.
