Ming-Xia Song,Yuping Huang,Shiben Wang,Zeng-Tao Wang,Xian-Qing Deng
A novel series of benzoxazole derivatives containing 1,2,4-triazolone ( 5a-m ) was designed. These compounds were synthesized in order to screen their anticonvulsant activities by the maximal electroshock seizure (MES) model and the subcutaneous pentylenetetrazole (sc-PTZ) seizure model in mice. The rotarod test was used to evaluate their neurotoxicities. Most of the compounds showed anti-MES activities at 100 and 300 mg/kg. Compound 5f , which showed potential anticonvulsant activity in the MES model with ED 50 values of 22.0 mg/kg, was considered as the most promising one in this study. It exhibited greater safety than that of carbamazepine and valproate regarding neurotoxicity. The efficacy of compound 5f in inhibiting the tonic seizures and death induced by the convulsants 3-mercaptopropionic acid and BIC was also verified. In an enzyme-linked immunosorbent assay, compound 5f and the positive drug phenytoin significantly increased the γ-aminobutyric acid (GABA) level in the mouse brain. Further, pretreatment with an inhibitor of the GABA synthesizing enzyme dramatically raised the ED 50 value of 5f in the MES model. These results confirmed that the compound 5f plays its anticonvulsive action via regulating the GABA function in the brain. Also, a docking study of the compound 5f in the benzodiazepine (BZD) binding site of the GABA A receptor confirmed possible binding of the compound 5f with BZD receptors.
Compared with jagged and rod-like raw products, the spherulitic 3-nitro-1,2,4-triazol-5-one (NTO) crystalline powder is generally superior in the formulation. However, the growth mechanism and corresponding influential factors for NTO spherulites remain to be deeply explored. Herein, the morphological evolutions of NTO crystals in alcohol solvents under a range of maximum supersaturation (Smax) are systematically investigated. It was found that differences in solvent-crystal interface interactions determine the primary morphology of the growing crystals while the magnitude of Smax determines the subsequent polycrystalline evolution. The cooling rate, initial concentration and stirring rate all could affect the crystal morphology by changing the Smax. It is demonstrated that there exists a critical Smax range (1.75–1.88) above which the formation of spherulites is kinetically favorable. Face indexing tests suggest that the (0 0 1) plane of NTO is mostly prone to twinning at low supersaturation, which is because that the molecular layers on the (0 0 1) surface are prone to twisting and the energy difference before and after is only 8.77 kJ mol−1. Then, the interfacial growth theory is employed to explain how a growing crystal plane develops from smooth to rough with non-crystallographic sub-individuals as the crystallization driving force increases. The change of morphology has a positive consequence in improving the safety performance of NTO crystalline powder under drop-weight impact. These findings would forward the understanding of the spherulitic crystallization process for energetic crystals.
危险品化学品经营许可证（带存储）