Synthesis and calculated log P correlation of imidooxy anticonvulsants

Abstract

Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss structure activity and the Craig plot analytical approaches as well as a semiempirical method. CLOG P analysis was also applied to this series after experimentally determining the NOR fragment. All compounds were minimized and these physicochemical parameters correlated to anticonvulsant activity. Several interesting substituted benzyloxy compounds emerged from this study: the 2',4'-dichloro (2b), 4'-(trifluoromethyl) (2c), 2'-bromo (2d), 3'-chloro (2o), 2'-chloro (2r), 2'-fluoro (2p), and 3'-fluoro (2w) analogs, all of which had comparable, or better activity than the parent unsubstituted analog (2a). X-ray crystal analysis of the active 2a versus inactive N-benzyl-2-azaspiro[4.4]nonane-1,3-dione (10) is discussed.

Antidepressant, Analgesic Activity and SAR Studies of Substituted Benzimidazoles

“…Theoretical Log P was calculated by using the software ChemOffice 6.0 (Table 1). The experimental Log P values were determined between octanol and phosphate buffer at room temperature [19]. The theoretical Log P values were compared with experimental values.…”

Triazole incorporated thiazoles as a new class of anticonvulsants: Design, synthesis and in vivo screening

“…The partition coefficient between octanol and phosphate buffer was determined at room temperature (29 C) using a procedure described elsewhere [20]. 10 mL of octanol and 10 mL phosphate buffer (pH ¼ 7.4) were taken in a glass stoppered graduated tube and 5 mg of accurately weighed drug was added.…”

Synthesis and Evaluation of New 2-(Substituted Phenyl)- 3-[5'-(2'-Oxo-2H-chromen-3'-yl)-1,3,4-Oxadiazol-2-yl]-1, 3-Thiazolidin-4-Ones as Anticonvulsants

“…Physical data of compounds (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) a Elemental analysis for C, H, N and S were within 0.4% and 0.3% respectively of the theoretical values. b Eluents used in TLC were Toluene: Ethyl acetate: Formic acid (5:4:1) for compounds.…”

“…The anticonvulsant activity of different types of compounds was reported to be correlated with lipophilicity 12 . The experimental log P values were determined using octanol-water method 13 for compounds, which showed significant protection. The compound 12 and 13 had log P value of 1.0 and 1.65 respectively, which were near to optimum log P value of ± 2.…”