Gao, Lanchang; Hao, Chao; Chen, Jiali; Ma, Ru; Zheng, Lu; Wu, Qingkun; Liu, Xin; Liu, Bi-Feng; Zhang, Guisen; Chen, Yin; Jin, Jian published the artcile< Discovery of a new class of multi-target heterocycle piperidine derivatives as potential antipsychotics with pro-cognitive effect>, Electric Literature of 84163-77-9, the main research area is benzoisoxazolyl piperidine synthesis antipsychotic procognitive; Atypical antipsychotics; Cognition; Dopamine; Multi-target; Serotonin.
A series of benzoisoxazolylpiperidine derivatives were synthesized by using the multi-target strategies and their potent affinities for dopamine (DA), serotonin (5-HT) and human histamine H3 receptors have been evaluated. Of these compounds, the promising candidate 4w (I) displayed high affinities for D2, D3, 5-HT1A, 5-HT2A and H3, a moderate affinity for 5-HT6, negligible effects on the human ether-a-go-go-related gene (hERG) channel, low affinities for off-target receptors (5-HT2C, adrenergic α1 and H1). In addition, the animal behavioral study revealed that, compared to risperidone, compound 4w significantly inhibited apomorphine-induced climbing and MK-801-induced movement behaviors with a high threshold for catalepsy and low liabilities for weight gain and hyperprolactinemia. Results from the conditioned avoidance response test and novel object recognition task demonstrated that 4w had pro-cognitive effects. Thus, the antipsychotic drug-like activities of 4w indicate that it may be a potential polypharmacol. antipsychotic candidate drug.
Bioorganic & Medicinal Chemistry Letters published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (receptor affinity). 84163-77-9 belongs to class benzisoxazole, and the molecular formula is C12H13FN2O, Electric Literature of 84163-77-9.
Referemce:
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics