N-[(2,6-Dimethylphenoxy)alkyl] aminoalkanols-their physicochemical and anticonvulsant properties

作者：Waszkielewicz Anna M^*; Cegla Marek; Zeslawska Ewa; Nitek Wojciech; Sloczynska Karolina; Marona Henryk

来源：Bioorganic & Medicinal Chemistry, 2015, 23(15): 4197-4217.

DOI：10.1016/j.bmc.2015.06.045

• 6 Hz
• Ames test
• Aminoalkanols
• Anticonvulsant activity
• Crystal structure
• DSC
• MES
• Mutagenicity
• Rotarod
• Seizures
• TG
• TOX

Twenty four new N-[(dimethylphenoxy) alkyl] aminoalkanols have been synthesized and evaluated for anticonvulsant activity in a series of in vivo tests: the maximum electroshock (MES), 6 Hz, and subcutaneous metrazole (ScMet). The compounds were also evaluated for possible neurotoxicity in the rotarod test. The majority of the achieved compounds exhibit quantified anticonvulsant activity. The most active compound 4: R-(-)-2N-[(2,6-dimethylphenoxy) ethyl] aminopropan-1-ol is active in MES with ED50 = 5.34 (male mice, ip), 22.28 (female mice, ip), 51.19 (male mice, po), 7.43 (rats, ip), and 28.60 (rats, po). Thermal analysis proved that its hydrochloride (4a) can exist in polymorphic forms. The compound binds to sigma, 5-HT1A, and alpha(2) receptors as well as 5-HT transporter and it does not exhibit mutagenic properties.

• 出版日期2015-8-1