Watanabe, Hitoshi’s team published research in Bioorganic & Medicinal Chemistry Letters in 2020-11-01 | 112-63-0

Bioorganic & Medicinal Chemistry Letters published new progress about Agranulocytosis. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Quality Control of 112-63-0.

Watanabe, Hitoshi; Ishida, Kyoji; Yamamoto, Masanori; Horiguchi, Masakuni; Isobe, Yoshiaki published the artcile< 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>, Quality Control of 112-63-0, the main research area is dibenzo diazepine preparation dopamine schizophrenia agranulocytosis antipsychotic; Agranulocytosis; Antipsychotics; Clozapine; Dopamine; Reactive metabolites; Treatment resistant schizophrenia.

Clozapine-like compound without agranulocytosis risk is need to cure the treatment resistant schizophrenia (TRS). We discovered I 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 I gave compound II to be best compound (approx. 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 II was considered to be lower than Clozapine. The pharmacol. detail of compound II is being investigated to develop it for TRS treatment.

Bioorganic & Medicinal Chemistry Letters published new progress about Agranulocytosis. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Quality Control of 112-63-0.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics