Volkova T V, Terekhova I V, Silyukov O I, Proshin A N, Bauer-Brandl A, Perlovich G L
Department of Physical Chemistry of Drugs , Krestov's Institute of Solution Chemistry, Russian Academy of Sciences , 153045 Akademicheskaya str. 1 , Ivanovo , Russia . Email:
Institute of Physiologically Active Compounds , Russian Academy of Sciences , 142432 , Chernogolovka , Russia.
Medchemcomm. 2016 Oct 28;8(1):162-175. doi: 10.1039/c6md00545d. eCollection 2017 Jan 1.
Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized and identified. Their ability to inhibit the glutamate stimulated Ca uptake was investigated. The solubility of thiadiazoles was measured in a buffer solution (pH 7.4) at 298 K. The distribution coefficients in 1-octanol/buffer (pH 7.4) and 1-hexane/buffer (pH 7.4) immiscible phases as model systems imitating the gastrointestinal tract epithelium and the blood-brain barrier were determined. Permeation experiments the new Permeapad™ barrier using Franz diffusion cells were conducted and the apparent permeability coefficients were obtained. The influence of the compound structure on the physicochemical properties determining the bioavailability of drug-like substances was revealed. Solubility-permeability interplay has been assessed to evaluate potential bioavailability of the compounds studied.
合成并鉴定了新型1,2,4-噻二唑衍生物作为有效的神经保护剂。研究了它们抑制谷氨酸刺激的钙摄取的能力。在298K下于缓冲溶液（pH 7.4）中测量噻二唑的溶解度。测定了在模拟胃肠道上皮和血脑屏障的模型体系1-辛醇/缓冲液（pH 7.4）和1-己烷/缓冲液（pH 7.4）不混溶相中的分配系数。使用Franz扩散池对新型Permeapad™屏障进行渗透实验，并获得表观渗透系数。揭示了化合物结构对决定类药物物质生物利用度的物理化学性质的影响。评估了溶解度-渗透性相互作用以评价所研究化合物的潜在生物利用度。
