Development of selective heterocyclic PDE4 inhibitors for treatment of psoriasis.
Autor: | Li G; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., He D; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Qian X; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Liu Y; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Ou Y; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Li M; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Song L; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Xu Z; Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou, 510632, China., Zhang G; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Wang J; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Pan W; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Chen J; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Zhang Y; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Wu JQ; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Chen D; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Chen C; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China., Peng S; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China., Yao H; Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China. Electronic address: yaohl@giz.gd.cn., Ke H; Department of Biochemistry and Biophysics, The University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC, 27599, USA. Electronic address: hke@med.unc.edu. |
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Jazyk: | angličtina |
Zdroj: | European journal of medicinal chemistry [Eur J Med Chem] 2024 Dec 15; Vol. 280, pp. 116930. Date of Electronic Publication: 2024 Oct 09. |
DOI: | 10.1016/j.ejmech.2024.116930 |
Abstrakt: | Psoriasis is a chronic autoimmune disease that badly affects the life quality of patients and their families. Inadequate efficacy, safety risks, high cost and low compliance of current psoriasis drugs urge development of novel small molecular drugs. In this study, two series of 37 novel compounds were designed and synthesized as inhibitors of phosphodiesterase 4 (PDE4) that specifically hydrolyzes second messenger cAMP and is an effective target for treatment of inflammatory diseases. Comprehensive structural-activity optimization led to finding of inhibitor 2e with IC Competing Interests: Declaration of competing interest Authors declare no conflict interests. (Copyright © 2024. Published by Elsevier Masson SAS.) |
Databáze: | MEDLINE |
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