202604-70-4Relevant academic research and scientific papers
Synthesis and biological evaluation of new 4-arylpiperidines and 4-aryl-4-piperidinols: dual Na+ and Ca2+ channel blockers with reduced affinity for dopamine D2 receptors
Annoura, Hirokazu,Nakanishi, Kyoko,Uesugi, Mayumi,Fukunaga, Atsuko,Imajo, Seiichi,Miyajima, Atsuko,Tamura-Horikawa, Yoshiko,Tamura, Shigeki
, p. 371 - 383 (2002)
A series of novel 4-arylpiperidines and 4-aryl-4-piperidinols (2a-f, 3a-f and 4a-f) was synthesized and evaluated for blocking effects on both neuronal Na+ and T-type Ca2+ channels and binding affinity for dopamine D2 receptors. Most of the compounds blockaded both ion channels with potency greater than or equal to flunarizine 1a which was adopted as a reference standard. In addition, these compounds had significantly reduced affinity for dopamine D2 receptors which is common in this class of structure. Compounds 2a-f, 3a-f and 4a-f exhibited potent anticonvulsant effects following systemic (ip) administration on audiogenic seizures in DBA/2 mice, indicating their excellent brain permeability. The neuroprotective activity of 2a, 3a and 4a was also assessed in a transient middle cerebral artery occlusion (MCAO) model. These compounds significantly reduced neuronal damage without affecting ischemic hyperthemia, while flunarizine 1a produced only minor reductions. In particular, 4a had 1.7-fold the potency in this MCAO method but only 1/20 the affinity for dopamine D2 receptor of 1a. The superposition of 2a, 3a and 4a on the basis of analyses of systematic conformation and similar structure has revealed that the cinnamyl, phenacyl and phenoxypropanol groups are likely to be structurally and biologically equivalent. Moreover, the superposition of 2a and 2f shows that diphenyl ether and biphenyl groups occupy a similar space, suggesting that both groups act as a bioisostere for the blockade of ion channels; however, this is not the case for dopamine D2 receptors since only biphenyl compounds such as 2f had high affinitity similar to flunarizine 1a. Compound 4a (SUN N5030) has a good pharmacological profile and may be useful in the alleviation and treatment of ischemic diseases. Copyright
ANTHELMINTIC AGENTS AND THEIR USE
-
Page/Page column 148, (2010/11/03)
This invention is directed to compounds and salts that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds and salts, pharmaceut
ANTHELMINTIC AGENTS AND THEIR USE
-
Page/Page column 61-62, (2009/07/18)
This invention is directed to compounds and salts that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds and salts, pharmaceut
