OBJECTIVE To synthesize bivalent γ-carboline derivatives and determine their acetylcholinesterase inhibition activity. METHODS The key intermediate γ-carboline was synthesized by Fischer method using N-acetyl- 3-bromo-4-piperidone and phenylhydrazine as starting materials. The γ-carboline synthesized was then reacted with ω,ω’- dibromoalkanes in the presence of NaH to form bivalent γ-carboline derivatives. Methylation of γ-carboline derivative with iodomethane in methanol yielded its quaternary ammonium salt. The acetylcholinesterase activity was measured by Ellman method with slight modification. RESULTS Seven novel carboline derivatives were synthesized and their structures were characterized by IR, 1H-NMR, 13C-NMR and ESI-MS. The results of pharmacological experiments indicated that all the target compounds showed inhibition activity against the acetylcholinesterase. Compound 4g exhibited inhibitory activity similar to that of the positive control donepezil. CONCLUSION Bivalent γ-carboline derivatives have inhibition activity against the acetylcholinesterase. The length of the connecting chain has an impact on the activity. It shows the best activity with chain length of eight carbon atoms, and the quaternization of tertiary nitrogen in the structure is beneficial for raising the inhibitory activity.

OBJECTIVE To explore the course construction and teaching reform of solid preparation with the aim of cultivating high-quality technical and skilled talents. METHODS Teaching objectives were set according to the post requires of solid preparation. Examples from pharmaceutical companies were used and the teaching content was reorganized by integrating professional courses and certificates. School and enterprise cooperation was deepened, information-based and multi-scenario learning resources were built, and high-quality curriculum politics teaching resources were created. Professional education and ideological education, knowledge imparting and value guidance were fully integrated. Based on the project-driving method, the integration of "Theoretical-Virtual-Real" and online and offline blended teaching was carried out. The evaluation method was "three comprehensive evaluation". RESULTS AND CONCLUSION Through the practice of course construction and teaching reform, students’ grades significantly increased and their skills become proficient. Their recognition of their profession significantly improved, and their awareness of quality and responsibility was significantly enhanced. Good reform effects had been achieved.