92022-83-8Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of 11-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-5H-dibenzo[b,e][1,4]diazepines with clozapine-like receptor occupancy at dopamine D1/D2 receptor
Watanabe, Hitoshi,Ishida, Kyoji,Yamamoto, Masanori,Horiguchi, Masakuni,Isobe, Yoshiaki
, (2020/10/02)
Clozapine-like compound without agranulocytosis risk is need to cure the treatment resistant schizophrenia (TRS). We discovered (S)-3 as Clozapine-like dopamine D2/D1 receptor selectivity and improved reactive metabolites formation profile by the modification of piperazine moiety in Clozapine. The optimization of (S)-3 gave compound 5 to be best compound (approximately 10-fold stronger affinity for D2/D1 receptor and similar D2/D1 selectivity ratio with Clozapine). Clozapine-like D2/D1 receptor occupancy profile was proved by in vivo evaluation. In addition, the reactive metabolites derived agranulocytosis risk of compound 5 was considered to be lower than Clozapine. The pharmacology detail of compound 5 is being investigated to develop it for TRS treatment.
Modification of the clozapine structure by parallel synthesis
Su, Jing,Tang, Haiqun,McKittrick, Brian A.,Burnett, Duane A.,Zhang, Hongtao,Smith-Torhan, April,Fawzi, Ahmad,Lachowicz, Jean
, p. 4548 - 4553 (2007/10/03)
A structure-activity study based on the core structure of clozapine 1b was accomplished by utilizing high-throughput synthesis. Several focused libraries were designed and synthesized to quickly develop SAR. The results indicate that by varying different regions of clozapine, both D1-selective and D2-selective compounds can be obtained.
