90993-49-0Relevant academic research and scientific papers
New DNA-Interactive Manganese(II) Complex of Amidooxime: Crystal Structure, DFT Calculation, Biophysical and Molecular Docking Studies
Saha, Urmila,Dolai, Malay,Kumar, Gopinatha Suresh,Butcher, Ray J.,Konar, Saugata
, p. 5393 - 5404 (2020)
A manganese(II) complex [MnII(HL1)2(Cl)(CH3COO)](1) based on the amidooxime ligand was synthesized and characterized by single-crystal X-ray diffraction studies, elemental analysis, UV-vis, and IR spectroscopy. The structural and spectral parameters were further supported using DFT/B3LYP. The complex (1) is mononuclear, having an octahedral geometry. The interaction of 1 with calf thymus DNA was investigated by spectroscopic and calorimetric techniques. The complex was found to interact with DNA through the groove-binding mode. From the isothermal titration calorimetry experiment, the binding constant between 1 and DNA was estimated to be (4.39 ± 0.01) × 105 M-1. The negative standard molar Gibbs energy change (δG0) and positive entropy (TδS0) values obtained from the calorimetry study confirmed the spontaneity of 1-DNA complexation. Thermodynamic parameters also suggested that the process of interaction of 1 with DNA was entropy-driven. The molecular docking study revealed that 1 binds at G30, C29, T31, A14, and G13 base pairs of the DNA chain in the minor groove.
Structural variation from trinuclears to 1D chains: Syntheses, structures and properties
Yin, Xiu-Ju,Zhu, Long-Guan
, (2019)
Five complexes [Co3(Hpmad)6]·(4-sb)2·(CH3COO)2·(H2O)2 (1), [Co3(Hpmad)6]·(3-sb)2·(CH3COO)2·(H2O)0.5 (2), [Co(Hpmad)2(4-sb)]n (3), [Co(Hpmad)2(3-sb)]n (4) and {[Co(Hpmad)(SO4)(H2O)2]·H2O}n (5) [Hpmad is 2-pyrimidineamidoxime, H2(4-sb) is 4-sulfobenzoic acid and H2(3-sb) is 3-sulfobenzoic acid], were prepared at room temperature. Complexes 1–5 were characterized by elemental analyses, single crystal X-ray diffractions, powder X-ray diffractions, infrared spectra, thermogravimetric analyses, fluorescence spectra and magnetic susceptibility measurements. Complexes 1 and 2 possess the linear trinuclear Co2+ structures. Complexes 3 and 4 exhibit similar one-dimensional (1D) chains. Complex 5 comprises the 1D helical chain. The change of anion in cobalt salt from CH3COO? to Cl? to SO42? leads to the structural evolution from the linear trinuclear Co2+ structure to the 1D chain to the 1D helical chain. Complexes 1–5 exhibit the Hpmad-based emissions. The magnetic properties of 1–5 were also investigated.
Structure-activity and structure-property relationships of novel Nrf2 activators with a 1,2,4-oxadiazole core and their therapeutic effects on acetaminophen (APAP)-induced acute liver injury
Xu, Li-Li,Wu, Yu-Feng,Wang, Lei,Li, Cui-Cui,Li, Li,Di, Bin,You, Qi-Dong,Jiang, Zheng-Yu
, p. 1376 - 1394 (2018/09/13)
The antioxidant function induced by Nrf2 protects the liver from damage. We found a novel Nrf2 activator named compound 25 via structural modification of compound 1 we previously reported. In vitro, compound 25 induced Nrf2 transport into the nucleus and protected hepatocyte L02 cells from APAP-induced cytotoxicity via activating the Nrf2-ARE signaling pathway. In vivo, 25 exhibited therapeutic effects in a mouse model of acute liver injury induced by acetaminophen (APAP) by up-regulating Nrf2-dependent antioxidases and down-regulating liver injury markers in serum. Together, these results indicated that 25 is a potent Nrf2/ARE activator both in vitro and in vivo. The drug-like properties of compound 25 further revealed its potential for development as a therapeutic drug against acute liver injury.
CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
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Paragraph 1427, (2018/04/17)
Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors
Ozcan, Sevil,Kazi, Aslamuzzaman,Marsilio, Frank,Fang, Bin,Guida, Wayne C.,Koomen, John,Lawrence, Harshani R.,Sebti, Sa?d M.
supporting information, p. 3783 - 3805 (2013/06/27)
Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.
COMPOUNDS HAVING AN ETHR INHIBITING ACTIVITY - USE OF SAID COMPOUNDS AS DRUGS - PHARMACEUTICAL COMPOSITION AND PRODUCT CONTAINING SAID COMPOUNDS
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Page/Page column 10, (2013/05/21)
The present invention relates to compounds of Formula (I), wherein R1 is chosen among the following radicals : (II); (III); (IV), (V), (VI) (VII) and n= 1 or 2 and m=1 or 2 with the proviso that m=2 when R1 is (VIII). The present invention also relates to the use thereof as drugs, more particularly in the treatment of mycobacterial infections and more particularly in the treatment of tuberculosis.
PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS
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Page/Page column 70, (2012/10/08)
Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)
Synthesis and antibacterial activity of 6-O-(heteroaryl-isoxazolyl)propynyl 2-fluoro ketolides
Sugimoto, Tomohiro,Shimazaki, Yoichi,Manaka, Akira,Tanikawa, Tetsuya,Suzuki, Keiko,Nanaumi, Kayoko,Kaneda, Yoshie,Yamasaki, Yukiko,Sugiyama, Hiroyuki
supporting information; experimental part, p. 5739 - 5743 (2012/10/07)
Macrolide antibiotics are widely prescribed for the treatment of respiratory tract infections; however, the increasing prevalence of macrolide-resistant pathogens is a public health concern. Therefore, the development of new macrolide derivatives with act
Ethionamide boosters. 2. Combining bioisosteric replacement and structure-based drug design to solve pharmacokinetic issues in a series of potent 1,2,4-oxadiazole EthR inhibitors
Flipo, Marion,Desroses, Matthieu,Lecat-Guillet, Nathalie,Villemagne, Baptiste,Blondiaux, Nicolas,Leroux, Florence,Piveteau, Catherine,Mathys, Vanessa,Flament, Marie-Pierre,Siepmann, Juergen,Villeret, Vincent,Wohlk?nig, Alexandre,Wintjens, René,Soror, Sameh H.,Christophe, Thierry,Jeon, Hee Kyoung,Locht, Camille,Brodin, Priscille,Déprez, Benoit,Baulard, Alain R.,Willand, Nicolas
experimental part, p. 68 - 83 (2012/03/10)
Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic.
Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl] piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors
Ontoria, Jesus M.,Bufi, Laura Llauger,Torrisi, Caterina,Bresciani, Alberto,Giomini, Claudia,Rowley, Michael,Serafini, Sergio,Bin, Hu,Hao, Wu,Steinkühler, Christian,Jones, Philip
scheme or table, p. 5274 - 5282 (2011/10/02)
The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway.
