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Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (8): 540-552.DOI: 10.5246/jcps.2018.08.055

• Original articles • Previous Articles     Next Articles

The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives

Zongze Huang1, Xintong Wang2, Ying Meng1, Xin Li1, Haoran Xiao1, Xiling Bian2, KeWei Wang2,3*, Qi Sun1*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. Department of Molecular and cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    3. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China
  • Received:2018-04-23 Revised:2018-05-28 Online:2018-09-04 Published:2018-06-13
  • Contact: Tel.: +86-532-82991070; +86-010-82801504, E-mail: wangkw@qdu.edu.cn; sunqi@bjmu.edu.cn
  • Supported by:

    National Natural Science Foundation of China (NSFC, Grant No. 21572011) and Ministry of Science and Technology of China (Grant No. 2013CB531302).

Abstract:

A series of new 6-substituted 3H-quinazolin-4-ones (3a3d) were designed, synthesized and evaluated as the type I positive allosteric modulators (PAMs) of human α7 nAChR expressed in Xenopus ooctyes by two-electrode voltage clamp. However, no compound showed a better efficacious PAM than lead compound 2 in the presence of acetylcholine (100 μM). The structure-activity relationship (SAR) analysis suggested that thiazolo[4,5-d]pyrimidin-7(6H)-one was the key biological skeleton. 

Key words: 3H-Quinazolin-4-ones, α7 nAChR, Positive allosteric modulators, Structure-activity relationship, Schizophrenia disease

CLC Number: 

Supporting: