2. Academic Validation
  3. Design, synthesis and biological activity of a novel ethylenediamine derivatives as H1 receptor antagonists

Design, synthesis and biological activity of a novel ethylenediamine derivatives as H1 receptor antagonists

  • Bioorg Med Chem. 2019 Dec 15;27(24):115127. doi: 10.1016/j.bmc.2019.115127.
Shiyang Zhou 1,  Gangliang Huang 2,  Guangying Chen 3
Affiliations

Affiliations

  • 1 Active Carbohydrate Research Institute, Chongqing Key Laboratory of Inorganic Functional Materials, College of Chemistry, Chongqing Normal University, Chongqing 401331, China; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China.
  • 2 Active Carbohydrate Research Institute, Chongqing Key Laboratory of Inorganic Functional Materials, College of Chemistry, Chongqing Normal University, Chongqing 401331, China. Electronic address: [email protected].
  • 3 Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China.
PMID: 31703894 DOI: 10.1016/j.bmc.2019.115127
Abstract

In this study, a series of novel ethylenediamine compounds were obtained by structural modification of the lead compounds with thonzylamine, and using the principle of modifying by bioisostere formation and modification with alkyl groups. In vitro assay, the biological activities showed that the target compounds have good properties in inhibiting mast cell degranulation and releasing histamine and β-aminohexidase, such as the compounds 5c, 5g, 5k, 5l and 5o, especially of compound 5k to mast cell degranulation is IC50 = 0.0106 ± 0.001 μmol⋅L-1, histamine release was IC50 = 0.0192 ± 0.005 μmol⋅L-1 and β-hexosaminidase release was IC50 = 0.0455 ± 0.002 μmol⋅L-1in vitro. At the same time, in vivo biological activities assay results showed that have a good Histamie induce bronchospasm effect with relatively long duration and good protective effect in vivo, among which the protective effect of compound 5k was 79.74 ± 0.30%, compounds 5c, 5g, 5k, 5l and 5o could inhibit the capillary permeability of increasing which were caused by histamine.

Keywords

Biological activity; Design; H(1) receptor; Synthesis.

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