131885-99-9Relevant academic research and scientific papers
Design and synthesis of novel 7-heterocycle-6-trifluoromethyl-3- oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group as superior AMPA receptor antagonists with good physicochemical properties
Takano, Yasuo,Shiga, Futoshi,Asano, Jun,Hori, Wataru,Fukuchi, Kazunori,Anraku, Tsuyoshi,Uno, Takashi
, p. 776 - 792 (2007/10/03)
We describe the design, synthesis, and physicochemical and biological properties of a novel series of 7-heterocycle-6-trifluoromethyl-3- oxoquinoxaline-2-carboxylic acids bearing a substituted phenyl group joined through a urethane or urea linkage to the heterocycle at the 7 position. Introduction of the trifluoromethyl group at the 6 position conferred good biological activity, including neuroprotective effects, as well as good physicochemical properties. In terms of α-amino-3-hydroxy-5- methylisoxazole propionate receptor (AMPA-R) affinity, a urea linkage was equivalent to a urethane linkage and a pyrrole ring at the 7 position reduced affinity in comparison with an imidazole ring. Among this series, compound 14h (KRP-199), which has a 4-carboxyphenyl group joined through a urethane linkage to a 7-imidazolyl heterocycle, was found to possess high potency and selectivity for the AMPA-R in vitro and to exhibit good neuroprotective effects in vivo. Furthermore, the compound showed good physicochemical properties, including stability to light and good solubility in aqueous solutions.
Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl group and improved its good physicochemical properties by introduced CF3 group
Takano, Yasuo,Shiga, Futoshi,Asano, Jun,Hori, Wataru,Anraku, Tsuyosi,Uno, Takashi
, p. 5107 - 5111 (2007/10/03)
We describe the synthesis, physicochemical and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group. Among them, compound 9k (KRP-199) was found to possess high potency and selectivity for the AMPA-R and to exhibit good neuroprotective effects in vivo, and also showed good physicochemical properties by introduced trifluoromethyl group at the C-6 position.
6-(1H-imidazol-1-yl)-7-nitro-2,3 (1H,4H)-quinoxalinedione hydrochloride (YM90K) and related compounds: Structure-activity relationships for the AMPA- type non-NMDA receptor
Ohmori,Sakamoto,Kubota,Shimizu-Sasamata,Okada,Kawasaki,Hidaka,Togami,Furuya,Murase
, p. 467 - 475 (2007/10/02)
A novel series of quinoxalinediones possessing imidazolyl and related heteroaromatic substituents was synthesized and evaluated for their activity to inhibit [3H]AMPA binding from rat whole brain. From the structure- activity relationships, it was found that the 1H-imidazol-1-yl moiety could function as a bioisostere for the cyano and nitro groups, and that 6-(1H- imidazol-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione (11) showed the most potent activity for the AMPA receptor. Compound 11 was evaluated for selectivity versus other excitatory amino acid receptors, and its action against AMPA at its receptor in the rat striatum was characterized. These data showed that compound 11 was a selective antagonist for the AMPA receptor with a K(i) value of 0.084 μM, being approximately equipotent with 2,3-dihydro-6-nitro- 7-sulfamoylbenzo(f)quinoxaline (3) (NBQX; K(i) = 0.060 μM). Compound 11 was also found to give protection against sound-induced seizure on DBA/2 mice at the minimum effective dose of 3 mg/kg ip (3; 10 mg/kg ip).
Cardiotonic Agents. Synthesis and Cardiovascular Properties of Novel 2-Arylbenzimidazoles and Azabenzimidazoles
Guengoer, Timur,Fouquet, Andre,Teulon, Jean-Marie,Provost, Daniel,Cazes, Michele,et al.
, p. 4455 - 4463 (2007/10/02)
Novel 2-arylbenzimidazoles and azabenzimidazoles were synthesized, and their inotropic action was evaluated.Changes in left ventricular pressure, dP/dt max, were measured as an index of cardiac contractility.The structural features that impart optimal inotropic activity are presented.The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers.To investigate the mechanism of action, the most potent compounds were tested for their calcium-sensitizing properties and their potential for the inhibition of phosphodiesterase.Two compounds, 1 and 41, showed interesting in vitro and oral activity without side effects.They have a more potent calcium-sensitizing effect than MCI-154 and are under further investigation.
