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

被引：16

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.

引用

页数：17

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