当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia.

Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia.

Abstract：

:Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Helal CJ,Kang Z,Hou X,Pandit J,Chappie TA,Humphrey JM,Marr ES,Fennell KF,Chenard LK,Fox C,Schmidt CJ,Williams RD,Chapin DS,Siuciak J,Lebel L,Menniti F,Cianfrogna J,Fonseca KR,Nelson FR,O'Connor R,MacDougall M,Mc

doi

10.1021/jm2001508

subject

Has Abstract

pub_date

2011-07-14 00:00:00

pages

4536-47

issue

13

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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