391211-97-5Relevant articles and documents
Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function
Korkutata, Mustafa,Saitoh, Tsuyoshi,Cherasse, Yoan,Ioka, Shuji,Duo, Feng,Qin, Rujie,Murakoshi, Nobuyuki,Fujii, Shinya,Zhou, Xuzhao,Sugiyama, Fumihiro,Chen, Jiang-Fan,Kumagai, Hidetoshi,Nagase, Hiroshi,Lazarus, Michael
, p. 122 - 132 (2019)
Insomnia is one of the most common sleep problems with an estimated prevalence of 10%–15% in the general population. Although adenosine A2A receptor (A2AR) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous A2AR signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness. In the present study, we found that 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, denoted A2AR positive allosteric modulator (PAM)-1, enhanced adenosine signaling at the A2AR and induced slow wave sleep (SWS) without affecting body temperature in wild-type male mice after intraperitoneal administration, whereas the SWS-inducing effect of this benzoic acid derivative was abolished in A2AR KO mice. In contrast to the A2AR agonist CGS 21680, the A2AR PAM-1 did not affect blood pressure or heart rate. These findings indicate that enhancing A2AR signaling promotes SWS without cardiovascular effects. Therefore, small molecules that allosterically modulate A2ARs could help people with insomnia to fall asleep.
Crystalline solids of MEK inhibitor N-((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide and uses thereof
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Page/Page column 94; 96; 99-101, (2021/08/11)
The present disclosure relates to a) crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide; b) pharmaceutical compositions comprising one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, and, optionally, one or more pharmaceutically acceptable carriers; c) methods of treating a tumor a cancer, or a Rasopathy disorder by administering one or more crystalline forms of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof, and methods of producing essentially pure Form IV of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide.
NOVEL SLOW-WAVE SLEEP INDUCING AGENT
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Paragraph 0065; 0066; 0067; 0068, (2019/07/29)
PROBLEM TO BE SOLVED: To provide a sleep inducing agent that induces slow-wave sleep (SWS) without causing side effects such as a cardiovascular action. SOLUTION: A slow-wave sleep inducing agent is provided that includes a compound represented by formula (I) or pharmaceutically acceptable salt thereof (R1 is a carboxyl group; m R2 independently represent a halogen atom, an alkyl group, a nitro group, an alkoxy group, a cyano group or an aryl group; n R3 independently represent a halogen atom, an alkyl group, a nitro group, an alkoxy group, a cyano group or an aryl group; m is 0, 1 or 2; n is 1 or 2). SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT