119022-51-4Relevant articles and documents
REGIOSELECTIVE SYNTHESIS OF 1-METHYL-3-HYDROXY-5-PERFLUOROALKYLPYRAZOLES BY THE ADDITION OF METHYLHYDRAZINE TO PERFLUOROALKYLACETYLENIC ESTERS
Hamper, Bruce C.
, p. 123 - 131 (1990)
A regioselective route to 1-methyl-3-hydroxy-5-perfluoroalkyl(1H,3H)pyrazoles has been developed.Treatment of perfluoroalkylacetylenic esters with methylhydrazine in methanol-water at 0 deg C or in methylene chloride at low temperature leads to 1-methyl-3-hydroxy-5-perfluoroalkyl(1H,3H)pyrazoles in a regioselective manner.Structural assignments of the regioisomers are based on 13C nmr chemical shifts, long range carbon-fluorine and carbon-proton coupling.The effect of the acetylene structure on the regioselectivity of the reaction is discussed.
STUDY OF THE REACTION OF FLUOROALKYL β-KETOESTERS WITH METHYLHYDRAZINE BY 1H and 19F NMR SPECTROSCOPY
Saloutin, V. I.,Kodess, M. I.,Fomin, A. N.,Selivanov, S. I.,Ershov, B. A.,Pashkevich, K. I.
, p. 318 - 321 (1988)
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Identification of 5-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)thiophene-2-Carboxamides as Novel and Selective Monoamine Oxidase B Inhibitors Used to Improve Memory and Cognition
Kaplan, Alan P.,Keenan, Terence,Scott, Roderick,Zhou, Xianbo,Bourchouladze, Rusiko,McRiner, Andrew J.,Wilson, Mark E.,Romashko, Darlene,Miller, Regina,Bletsch, Matthew,Anderson, Gary,Stanley, Jennifer,Zhang, Adia,Lee, Dong,Nikpur, John
, p. 2746 - 2758 (2017/12/26)
Initial work in Drosophila and mice demonstrated that the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) is a master control gene for memory formation. The relationship between CREB and memory has also been found to be true in other species, including aplysia and rats. It is thus well-established that CREB activation plays a central role in memory enhancement and that CREB is activated during memory formation. On the basis of these findings, a phenotypic high-throughput screening campaign utilizing a CRE-luciferase (CRE-Luci) SK-N-MC cell line was performed to identify compounds that enhance transcriptional activation of the CRE promoter with a suboptimal dose of forskolin. A number of small-molecule hits of unknown mechanisms of action were identified in the screening campaign, including HT-0411. Follow-up studies suggested that the CREB activation by HT-0411 is attributed to its specific and selective inhibition of monoamine oxidase B (MAO-B). Further, HT-0411 was shown to improve 24 h memory in rodents in a contextual fear conditioning model. This report describes the lead optimization of a series of 5-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl) thiophene-2-carboxamides that were identified as novel, potent, and selective inhibitors of MAO-B. Extensive SAR studies and in vivo behavioral evaluations of this and other related analogue series identified a number of potential clinical development candidates; ultimately, compound 8f was identified as a candidate molecule with high selectivity toward MAO-B (29-56 nM) over MAO-A (19% inhibition at a screening concentration of 50 μM), an excellent profile against a panel of other enzymes and receptors, good pharmacokinetic properties in rodents and dogs, and efficacy in multiple rodent memory models.
