Citation: Zhao Dongsheng, Wan Jinyu, Gao Yinyi, Guo Youhong. Quantitative Structure-Activity Relationship and Molecular Docking of Phosphodiesterase 4b Inhibitors[J]. Chemistry, ;2020, 83(10): 940-945. shu

Quantitative Structure-Activity Relationship and Molecular Docking of Phosphodiesterase 4b Inhibitors

1.
College of Pharmacy, Quanzhou Medical College, Quanzhou, 362100
2.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080

Corresponding author: Guo Youhong, guo_youhong@163.com
Received Date: 13 March 2020
Accepted Date: 12 June 2020

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Phosphodiesterase 4b plays a key role in catalyzing the hydrolysis of the secondary signal messenger cyclic adenosine monophosphate (cAMP), which is able to regulate the function of airway smooth muscle, inflammatory cells and immune cells. Selective phosphodiesterase 4b (PDE4b) inhibitors received great attentions because they do not cause nausea and vomit while being used as anti-inflammatory drugs for asthma and chronic obstructive pulmonary disease (COPD). In this paper, a comparative molecular field (CoMFA) method was used to construct a reasonable three-dimensional quantitative structure-activity relationship (3D-QSAR) model for a series of pyrimidine derivatives PDE4b inhibitors. The molecular docking method was used to study the interactions between inhibitors and PDE4b. The results showed that the introduction of a five-membered cyclic hydrocarbon group with an electronegative group at the 2 position of the pyrimidine can increase the activity. Small substituent group at the 4 and 5 positions of the pyrimidine ring is suitable. The introduction of an aromatic hydrocarbon group with a hydrogen bond donor or hydrogen bond acceptor at the 6-position of pyrimidine helps to improve the activity of the compounds. This study provides theoretical guidance for the rational design of efficient PDE4b inhibitors.
- Phosphodiesterase 4b (PDE4b),
- Inhibitors,
- 3D-QSAR,
- CoMFA,
- Molecular docking
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