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

We describe the synthesis, physicochemical, and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group attached through a urethane linkage at the C-7 position. We found that the introduction of trifluoromethyl group at th...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-10, Vol.14 (20), p.5107-5111
Main Authors: TAKANO, Yasuo, SHIGA, Futoshi, ASANO, Jun, HORI, Wataru, ANRAKU, Tsuyosi, UNO, Takashi
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Ischemia - drug therapy
Brain Ischemia - pathology
Disease Models, Animal
Glutamatergic system (aspartate and other excitatory aminoacids)
Imidazoles - chemical synthesis
Imidazoles - chemistry
Imidazoles - pharmacology
In Vitro Techniques
Infusions, Intravenous
Medical sciences
Miscellaneous
Neuropharmacology
Neuroprotective agent
Neuroprotective Agents - chemical synthesis
Neuroprotective Agents - chemistry
Neuroprotective Agents - pharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Quinoxalines - chemical synthesis
Quinoxalines - chemistry
Quinoxalines - pharmacology
Rats
Receptors, AMPA - antagonists & inhibitors
Solubility
Structure-Activity Relationship
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Summary:We describe the synthesis, physicochemical, and biological properties of a novel series of 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acids with a substituted phenyl group attached through a urethane linkage at the C-7 position. We found that the introduction of trifluoromethyl group at the C-6 position brought about good biological activity and physicochemical properties. Among them, compound 9k (KRP-199), which has a 4-carboxyphenyl group, 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 such as stability to light and good solubility in aqueous solutions.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.07.093