Design and synthesis of novel annulated thienopyrimidines as phosphodiesterase 5 (PDE5) inhibitors

被引：15
作者：
El-Sharkawy, Lina Y. [1 ]
El-Sakhawy, Rowaida A. [1 ]
Abdel-Halim, Mohammad [1 ]
Lee, Kevin [2 ]
Piazza, Gary A. [2 ]
Ducho, Christian [3 ]
Hartmann, Rolf W. [4 ]
Abadi, Ashraf H. [1 ]
机构：
[1] German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmaceut Chem, Cairo 11835, Egypt
[2] Univ S Alabama, Drug Discovery Res Ctr, Mitchell Canc Inst, Mobile, AL USA
[3] Saarland Univ, Dept Pharm Pharmaceut & Med Chem, Saarbrucken, Germany
[4] Helmholtz Inst Pharmaceut Res Saarland HIPS, Dept Drug Design & Optimizat, Saarbrucken, Germany
来源：
ARCHIV DER PHARMAZIE | 2018年 / 351卷 / 05期
关键词：
annulated thienopyrimidines; cycloalkene-fused thienopyrimidines; phosphodiesterase inhibitor; planarity; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; DRUG DEVELOPMENT; DERIVATIVES; DISCOVERY; AGENTS;
D O I：
10.1002/ardp.201800018
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Novel cycloalkene-fused thienopyrimidine analogues with enhanced phosphodiesterase 5 (PDE5) inhibitory properties are presented. The structure of the reported scaffold was modulated through variation of the terminal cycloalkene ring size, as well as by varying the substituents at position 4 through the attachment of different groups including aniline, benzylamine, cyclohexylethylamine, methyl/acetyl/aryl piperazines, and aryl hydrazones. Compound 15Y with a benzylamine substituent and cycloheptene as terminal ring showed the highest PDE5 inhibitory activity with an IC50 value as low as 190 nM and with good selectivity versus PDE7 and PDE9.
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收藏
页数：17
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