Anticonvulsant and analgesic in neuropathic pain activity in a group of new aminoalkanol derivatives

Design, Synthesis and Anticonvulsant Activity of New Phenoxyalkyl, Phenoxyethoxyethyl and Phenoxyacetyl Derivatives of Aminoalkanols

“…The design of new compounds was based on structure-activity relationship analysis for previously synthesized and tested compounds. [10][11][12][13][14][15][16][17][18][19][20][21] All designed structures were analogues or homologs of reference compounds I-VI (Figure 1) and are presented in Table 1. There were three sites of structural modifications: (1) substitution of aromatic ring, (2) linker and (3) aminoalkanol moiety.…”

“…Moreover, substitution of phenoxy ring with three methyl groups in positions 2, 3 and 5 was indicated as a structural alert for potential mutagenic properties (in silico simulations using Osiris Property Explorer software). [11] As active compounds substituted in the aromatic ring with a methyl group and chlorine were also obtained in the course of the research, the currently presented study focused on this structural modification. Structure-activity analysis of previously obtained compounds showed that among amine derivatives, the use of an ethylene or ethoxyethyl linker seems to be advantageous in terms of both anticonvulsant activity and protective index.…”

“…Structure-activity analysis of previously obtained compounds showed that among amine derivatives, the use of an ethylene or ethoxyethyl linker seems to be advantageous in terms of both anticonvulsant activity and protective index. [11] For that reason, these two linkers dominated in the structures of newly designed compounds. Additionally, butylene and acetyl linkers were incorporated in case of several compounds.…”

“…This reagent offers the possibility of fast and chemoselective oxidation of alcohols to carbonyl compounds in mild conditions. Structures of noradrenaline, propranolol, mexiletine and reference compounds I, [10] II, [11] III, [16] IV, [13] V [14] and VI. [15] MES -maximal electroshock seizure test; STZ -streptozotocin-induced neuropathy; OXA -oxaliplatin-induced neuropathy.…”

“…Previous studies conducted by our group brought interest to a group of phenoxyalkyl, phenoxyethoxyethyl and phenoxyacetyl derivatives of aminoalkanols. [10][11][12][13][14][15][16][17][18][19][20][21] The research resulted in the development of centrally active compounds (selected of which are presented in Figure 1), related in chemical structure to neurotransmitters (such as noradrenaline) and antiarrhythmic drugs with proven anticonvulsant activity (e. g. propranolol and mexiletine). The compounds were characterized by anticonvulsant activity in vivo, while some of them showed also analgesic activity in neuropathic pain.…”