Recent findings leading to the discovery of selective dopamine D4 receptor ligands for the treatment of widespread diseases

被引：14

作者：

Giorgioni, Gianfabio ^{[1
]}

Del Bello, Fabio ^{[1
]}

Pavletic, Pegi ^{[1
]}

Quaglia, Wilma ^{[1
]}

Botticelli, Luca ^{[2
]}

Cifani, Carlo ^{[2
]}

Di Bonaventura, Emanuela Micioni ^{[2
]}

Di Bonaventura, Maria Vittoria Micioni ^{[2
]}

Piergentili, Alessandro ^{[1
]}

机构：

[1] Univ Camerino, Sch Pharm, Med Chem Unit, Via S Agostino 1, I-62032 Camerino, Italy

[2] Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna Carceri 9, I-62032 Camerino, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2021年 / 212卷

关键词：

Dopamine D-4 receptor; D-4 receptor agonists and antagonists; Crystal structures; Structure-activity relationships; Chemotypes; Therapeutic potential of D-4 receptor ligands; PRELIMINARY PHARMACOLOGICAL EVALUATION; SUBSTITUTED PIPERIDINE NAPHTHAMIDES; IMPROVES COGNITIVE PERFORMANCE; INDUCED PENILE ERECTION; D4; DRD4; GENE; HIGH-AFFINITY; PARAVENTRICULAR NUCLEUS; INDUCED DYSKINESIA; MESSENGER-RNA; MALE RATS;

D O I：

10.1016/j.ejmech.2020.113141

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Since its discovery, the dopamine D-4 receptor (D4R) has been suggested to be an attractive target for the treatment of neuropsychiatric diseases. Novel findings have renewed the interest in such a receptor as an emerging target for the management of different diseases, including cancer, Parkinson's disease, alcohol or substance use disorders, eating disorders, erectile dysfunction and cognitive deficits. The recently resolved crystal structures of D4R in complexes with the potent ligands nemonapride and L-745870 strongly improved the knowledge on the molecular mechanisms involving the D4R functions and may help medicinal chemists in drug design. This review is focused on the recent development of the subtype selective D4R ligands belonging to classical or new chemotypes. Moreover, ligands showing functional selectivity toward G protein activation or beta-arrestin recruitment and the effects of selective D4R ligands on the above-mentioned diseases are discussed. (C) 2020 Elsevier Masson SAS. All rights reserved.

引用

页数：19

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