Synthesis and Determination of Physicochemical Properties of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Alkoxyethoxybenzoates

Abstract

Abstract:Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log k w ) and dissociation constant (pK a ) were experimentally determined and compared to the software calculated data. The lipophilicity index was determined by means of reversed-phase high performance liquid chromatography (RP-HPLC). The pK a values were determined by means of capillary zone electrophoresis. The "drug-likeness" properties according to the Lipinski Rule of Five and prediction of possible blood-brain barrier penetration were computed and discussed.

An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors

“…2-(2,6-Dimethoxyphenoxy)ethanamine was prepared via Gabriel synthesis (see Scheme 5) from 2-[2-(2,6-dimethoxyphenoxy)ethyl]-1 H -isoindole-1,3(2 H )-dione in two-step synthesis starting from 2,6-dimethoxyphenol that gave 2-(2-bromoethoxy)-1,3-dimethoxybenzene with 1,2-dibromoethane.Then the 2-(2-bromoethoxy)-1,3-dimethoxybenzene was reacted with potassium phthalimide [61]. The main synthesis was carried out as described by Marvanova et al [62]. 4-(2-Methoxy)ethoxybenzoic acid ( 14a ) was prepared from ethyl 4-hydroxybenzoate via reaction with 2-methoxyethyl 4-methylbenzenesulfonate and following hydrolysis of the ester.…”

Three-Step Synthesis of a Less-Aggregated Water-Soluble Poly(p-phenylene ethynylene) with Meta Side Chains via Palladium/Norbornene Cooperative Catalysis

“…We anticipated that placing side chains at the 2,6-positions ( meta side chains) could effectively break aggregation due to their intrinsically less-ordered packing, which may consequently allow much simpler side chains to be used (Figure b). In particular, the piperazine moiety is expected to serve as attractive side chains because, as a common structural motif found in drugs − and pH-responsive acryloyl-type polymers, piperazine features high water solubility through double protonations of both nitrogen sides (p K a1 = 6.3, p K a2 = 8.8) under acidic conditions. Herein, we describe our development of a three-step synthesis of a highly water-soluble PPE that contain piperazine meta side chains through palladium/norbornene (Pd/NBE)-catalyzed AB–C-type polymerization.…”