104007-09-2Relevant articles and documents
Crystal Packing Modulation of the Strength of Resonance-Assisted Hydrogen Bonds and the Role of Resonance-Assisted Pseudoring Stacking in Geminal Amido Esters: Study Based on Crystallography and Theoretical Calculations
Venkatesan, Perumal,Thamotharan, Subbiah,Percino, M. Judith,Ilangovan, Andivelu
, p. 779 - 798 (2021)
A detailed experimental and theoretical investigation of a series of substituted geminal amido esters (ethyl (2E)-3-(arylamino)-2-(arylcarbamoyl)prop-2-enoate, AME-1-8) leading to the identification of a unique angularly fused pseudotricyclic (S(6),S(6),S(6)) ring system stabilized by an intramolecular resonance-assisted hydrogen bond (RAHB) and a non-RAHB are presented in addition to weak intermolecular interactions. An analysis of X-ray and theoretical models reveals that the strength of the intramolecular RAHB (N1-H1N···O1) varies in a wide range (6.9-11.4 kcal mol-1) due to crystal-packing constraints arising from different aromatic ring substitutions. However, the effect is less significant and the strength differs only in a narrow range (8.2-9.9 kcal mol-1) in the case of non-RAHB. The downfield shift (δ～12.3) observed for the N-Haniline signal in 1H NMR spectra of AME-1-8 is due to the presence of intramolecular RAHB. A PIXEL energy analysis suggests that the molecular dimer formed by stacking of RAHB pseudorings is found to be strong (Etot = -14.4 to -17.9 kcal mol-1), and this dimer forms the basic motif in most of the structures reported herein. A detailed analysis of the isostructurality suggests that the basic motif exists in most of the structural combinations. The weak intermolecular C-H···O, C-H···Cl, and C-H···πinteractions play a vital role in the stabilization of these crystal structures, as evaluated by PIXEL and Bader's quantum theory of atoms in molecules approach (QTAIM). A lattice energy analysis suggests that the Coulombic contribution and total lattice energies are higher in the para-substituted compounds (AME-2, AME-5, and AME-8) in comparison to the other isomeric compounds. Further, the crystal packing of these compounds is analyzed on the basis of the energy frameworks. It shows that most of the crystals show similar 3D topologies, suggesting that these compounds may have similar mechanical behavior.
Synthesis of 6-aryl substituted 4-quinolones via Suzuki cross coupling
Gupta, Sumanta,Ghosh, Prasanjit,Dwivedi, Seema,Das, Sajal
, p. 6254 - 6260 (2014)
A convenient way to introduce aryl functionalization in the 6-position of 4-quinolones is developed via selective bromination and subsequent arylation by Suzuki cross-coupling. Ethyl 4-quinolone 3-carboxylates were subjected to selective bromination at C-6 followed by arylation under microwave irradiation that yielded the desired cross-coupling products within 5 minutes. This approach can expediently be used for library synthesis of the aryl functionalized 4-quinolone derivative, an important class of biologically active compounds.
Synthesis, radiolabeling and evaluation of novel 4-oxo-quinoline derivatives as PET tracers for imaging cannabinoid type 2 receptor
Slavik, Roger,Herde, Adrienne Müller,Bieri, Daniel,Weber, Markus,Schibli, Roger,Kr?mer, Stefanie D.,Ametamey, Simon M.,Mu, Linjing
, p. 554 - 564 (2015)
Our goal is to develop a highly specific and selective PET brain tracer for imaging CB2 expression in patients with neuroinflammatory diseases. Based on our previous findings on a carbon-11 labeled 4-oxoquinoline structure, designated KD2, further structural optimizations were performed, which led to the discovery of N-(1-adamantyl)-1-(2-ethoxyethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide (RS-016). Compared to KD2, RS-016 exhibits a higher binding affinity towards CB2 (Ki = 0.7 nM) with a selectivity over CB1 of >10,000 and lower lipophilicity (logD7.4 = 2.78). [11C]RS-016 was obtained in 99% radiochemical purity and up to 850 GBq/mmol specific radioactivity at the end of synthesis. In vitro autoradiography on rodent spleen tissue showed high specific binding to CB2. [11C]RS-016 was stable in vitro in rodent and human plasma over 40 min, whereas 47% intact compound was found in vivo in rat blood plasma 20 min post injection (p.i.). High specific binding to CB2 was observed in murine spleen tissues and postmortem ALS patient spinal cord tissues in vitro autoradiography, ex vivo biodistribution data confirmed the high and specific uptake of [11C]RS-016 in spleen region in rats. In vivo specificity of [11C]RS-016 could also be shown in brain by PET imaging using a murine neuroinflammation model, which has higher CB2 receptor expression level in the brain induced by lipopolysaccharide (LPS) application.
Discovery of a fluorinated 4-oxo-quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2
Slavik, Roger,Müller Herde, Adrienne,Haider, Ahmed,Kr?mer, Stefanie D.,Weber, Markus,Schibli, Roger,Ametamey, Simon M.,Mu, Linjing
, p. 874 - 886 (2016)
The cannabinoid receptor type 2 (CB2) is part of the endocannabinoid system and has gained growing attention in recent years because of its important role in neuroinflammatory/neurodegenerative diseases. Recently, we reported on a carbon-11 labeled 4-oxo-
Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay
Mori, Shuichi,Iinuma, Hiroto,Manaka, Noriaki,Ishigami-Yuasa, Mari,Murayama, Takashi,Nishijima, Yoshiaki,Sakurai, Akiko,Arai, Ryota,Kurebayashi, Nagomi,Sakurai, Takashi,Kagechika, Hiroyuki
, p. 837 - 848 (2019/07/12)
Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyR1 channel inhibitors.
4-oxo-1,4-dihydroquinoline-3-carboxamide as selective ligand for cannabinoid receptor 2 for diagnosis and therapy
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Paragraph 0063; 0064, (2016/03/18)
The present invention is directed to new compounds selectively binding the cannabinoid 2 receptor. In addition, the invention relates to the use of said compounds for determining cannabinoid receptor 2 (CB2)-selective receptor localization and density, preferably in the central nervous system (CNS), the peripheral nervous system (PNS), heart, liver, gastrointestinal tract, spleen, pancreas, kidney, testis, ovary and/or the prostate. Moreover, the invention pertains to the use of said compounds in the diagnosis, prophylaxis and/or therapy of CB2 receptor-related diseases.
Synthesis and anti-tumor activities of 4-anilinoquinoline derivatives
Liu, Dan,Luan, Tian,Kong, Jian,Zhang, Ying,Wang, Hai-Feng
, (2016/02/05)
Twenty-two 7-fluoro (or 8-methoxy)-4-anilinoquinolines compounds were designed and synthesized as potentially potent and selective antitumor inhibitors. All the prepared compounds were evaluated for their in vitro antiproliferative activities against the HeLa and BGC823 cell lines. Ten compounds (1a-g; 2c; 2e and 2i) exhibited excellent antitumor activity superior to that of gefitinib. Among the ten compounds; seven (1a-c; 1e-1g and 2i) displayed excellent selectivity for BGC823 cells. In particular; 1f and 2i exhibited potent cytotoxic activities against HeLa cells and BGC823 cells with better IC50 values than gefitinib.
Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor
Mistry, Shailesh N.,Valant, Celine,Sexton, Patrick M.,Capuano, Ben,Christopoulos, Arthur,Scammells, Peter J.
, p. 5151 - 5172 (2013/07/26)
Established therapy in Alzheimer's disease involves potentiation of the endogenous orthosteric ligand, acetylcholine, at the M1 muscarinic receptors found in higher concentrations in the cortex and hippocampus. Adverse effects, due to indiscrim
Investigations on the 4-quinolone-3-carboxylic acid motif. 4. Identification of new potent and selective ligands for the cannabinoid type 2 receptor with diverse substitution patterns and antihyperalgesic effects in mice
Pasquini, Serena,De Rosa, Maria,Pedani, Valentina,Mugnaini, Claudia,Guida, Francesca,Luongo, Livio,De Chiaro, Maria,Maione, Sabatino,Dragoni, Stefania,Frosini, Maria,Ligresti, Alessia,Di Marzo, Vincenzo,Corelli, Federico
supporting information; experimental part, p. 5444 - 5453 (2011/09/30)
Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Taking advantage of previous findings on structure-activity/selectivity relationships for a class of 4-quin
Raf inhibitor compounds and methods of use thereof
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Page/Page column 66, (2010/11/26)
Compounds of Formula I are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
