71082-34-3Relevant academic research and scientific papers
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; 0065, (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.
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 (2016/11/13)
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-
Regiocontrolled Nitration of 4-Quinolones at Ambient Conditions
Sarkar, Sonali,Ghosh, Prasanjit,Misra, Anirban,Das, Sajal
, p. 2386 - 2393 (2015/10/12)
Regiocontrolled nitration of 4-quinolone, the highly privileged scaffold, has been developed at ambient conditions. The nitro group can selectively be introduced at diverse positions simply by tuning the reactivity of the moiety. Discrimination is being achieved through the selective functionalization of the free N-H group. The functional group has been screened theoretically with the help of Fukui function and local softness calculation. Theoretical predictions are synchronized well with the experimental findings. Finally, this nitration technique allows quick access to the structurally diverse 4-quinolones.
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 (2015/01/30)
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.
Synthesis of 6-aryl substituted 4-quinolones via Suzuki cross coupling
Gupta, Sumanta,Ghosh, Prasanjit,Dwivedi, Seema,Das, Sajal
, p. 6254 - 6260 (2014/01/23)
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 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
SUBSTITUTED PYRIDINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE TO TREAT OXIDATIVE STRESS
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Page/Page column 27-28, (2011/04/13)
Substituted pyridine derivatives, methods of their preparation, pharmaceutical compositions comprising a substituted pyridine derivative, and methods of use in treating inflammation are provided. The substituted pyridine derivatives may control of the act
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
, 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
Microwave-assisted preparation of quinolone and quinoline derivatives
Albrecht, Markus,Osetska, Olga,Rantanen, Toni,Fr?hlich, Roland,Bolm, Carsten
scheme or table, p. 1081 - 1084 (2010/07/02)
Quinolinone derivatives can be obtained in microwave-assisted syntheses by reaction of aniline derivatives with acetylene dicarboxylic esters, a malonic acid diester or -keto ester derivatives. The reaction proceeds under mild conditions in short reaction
