Design, Synthesis, and Antidepressant Activity Study of Novel Aryl Piperazines Targeting Both 5-HT1A and Sigma-1 Receptors

A total of 20 novel aryl piperazine derivatives were designed and synthesized, and their structures were confirmed by mass spectrometry and nuclear magnetic resonance analyses. Their 5-HT1A and sigma-1 receptor affinities were determined, and six of them showed high affinities (K i < 20 nmol/L) to both 5-HT1A and sigma-1 targets. Then, metabolic stability (T 1/2) tests of six compounds in rat and human liver microsomes were performed. Our data indicated that compound 27 has both high affinity for 5-HT1A and sigma-1 receptors (5-HT1A: K i = 0.44 nmol/L; sigma-1: K i = 0.27 nmol/L), and good metabolic stability (T 1/2 values are 21.7 and 24.6 minutes, respectively). Interestingly, results from the forced swimming test, mouse tail suspension test, and preliminary pharmacokinetic test suggested the marked antidepressant activity, good pharmacokinetic characteristics, and low toxicity of compound 27 in the two models. In conclusion, compound 27 has great value of further study as an active molecule of antidepressant drugs.

Rapid Targeted Method of Detecting Abused Piperazine Designer Drugs

Piperazine derivatives belong to the popular psychostimulating compounds from the group of designer drugs. They are an alternative to illegal drugs such as ecstasy and amphetamines. They are being searched by consumers for recreational use due to their stimulating and hallucinogenic effects. Many NPS-related poisonings and deaths have been reported where piperazines have been found. However, a major problem is the potential lack of laboratory confirmation of the involvement of piperazine derivatives in the occurrence of poisoning. Although many methods have been published, piperazine derivatives are not always included in a routine analytical approach or targeted toxicological analysis. There is an increasing need to provide qualitative evidence for the presence of piperazine derivatives and to ensure reproducible quantification. This article describes a new rapid method of detecting piperazine derivatives in biological material, using LC-MS. All target analytes were separated in a 15 min run time and identified based on the precursor ion, at least two product ions, and the retention time. Stable isotopically labeled (SIL) internal standards: BZP-D7, mCPP-D8 and TFMPP-D4 were used for analysis, obtaining the highest level of confidence in the results. The proposed detection method provides the analytical confirmation of poisoning with piperazine designer drugs.

Synthesis And Biological Activity of Amide Derivatives Derived From Natural Product Waltherione F

Structural optimization based on natural products has become an effective way to develop new green fungicides, which provide important guiding significance for practicing the new development concept and promoting the green development of pesticides. In this project, combined with the fungicidal amide lead compound X-I-4 discovered in our previous work and fungicidal piperazine derivatives reported in literatures, the target compounds containing 4-quinolone and piperazine substructures based on waltherione F were designed, synthesized and screened for their biological activity. The bioassay results indicated that compounds I-3, I-5, II-3, II-7, II-10, II-11 and II-13 displayed higher inhibition rates against Rhizoctonia solani than other tested compounds. The in vitro cellular cytotoxicity assay revealed the compounds II-6 and II-11 exhibited higher cytotoxicity against HepG2 than other tested compounds. The fluorescence characteristics investigation showed that the absolute fluorescence QY value of the methanol solution of the compound I-6 was higher than those of I-2, I-3, I-7 and I-8, which was further elucidated by TD-DFT.