N-[(2,6-Dimethylphenoxy)alkyl]aminoalkanols-their physicochemical and anticonvulsant properties
Anna M Waszkielewicz1, Marek Cegła2, Ewa Żesławska3
1Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
Abstract:
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 σ, 5-HT1A, and α2 receptors as well as 5-HT transporter and it does not exhibit mutagenic properties.
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