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

共 50 条

[11] PDE5 inhibitors as therapeutics for heart disease, diabetes and cancer [J].

Das, Anindita ;

Durrant, David ;

Salloum, Fadi N. ;

Xi, Lei ;

Kukreja, Rakesh C. .

PHARMACOLOGY & THERAPEUTICS, 2015, 147 :12-21

[12] PDE5 inhibitors as potential tools in the treatment of cystic fibrosis [J].

Noel, Sabrina ;

Dhooghe, Barbara ;

Leal, Teresinha .

FRONTIERS IN PHARMACOLOGY, 2012, 3

[13] On the Viability of Tadalafil-Based 18F-Radiotracers for In Vivo Phosphodiesterase 5 (PDE5) PET Imaging [J].

Bailey, Justin J. ;

Wuest, Melinda ;

Bojovic, Tamara ;

Kronemann, Travis ;

Waengler, Carmen ;

Waengler, Bjoern ;

Wuest, Frank ;

Schirrmacher, Ralf .

ACS OMEGA, 2021, 6 (33) :21741-21754

[14] Phenotypical Effect of Phosphodiesterase 5 (PDE5) Inhibitor on Behavioral Activities of Fruit Fly Drosophila melanogaster [J].

Jaya, Azan ;

Wahyudin, Elly ;

Djabir, Yulia Yusrini ;

Roska, Tri Puspita ;

Arfiansyah, Rudi ;

Dirpan, Andi ;

Nainu, Firzan .

BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY, 2022, 12 (01) :222-229

[15] Pyrazolopyrimidinone Based Selective Inhibitors of PDE5 for the Treatment of Erectile Dysfunction [J].

Hudwekar, Abhinandan D. ;

Kotwal, Pankul ;

Dar, Mohd. Ishaq ;

Balgotra, Shilpi ;

Dogra, Ashish ;

Kour, Jaspreet ;

Chobe, Santosh S. ;

Nandi, Utpal ;

Hussain Syed, Sajad ;

Sawant, Sanghapal D. .

CHEMISTRY & BIODIVERSITY, 2023, 20 (04)

[16] Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries [J].

Wareing, M ;

Myers, JE ;

O'Hara, M ;

Kenny, LC ;

Warren, AY ;

Taggart, MJ ;

Skillern, L ;

Machin, I ;

Baker, PN .

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2004, 190 (05) :1283-1290

[17] Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetyicholinesterase (AChE) and Phosphodiesterase 5 (PDE5) [J].

Ni, Wei ;

Wang, Huan ;

Li, Xiaokang ;

Zheng, Xinyu ;

Wang, Manjiong ;

Zhang, Jian ;

Gong, Qi ;

Ling, Dazheng ;

Mao, Fei ;

Zhang, Haiyan ;

Li, Jian .

ACS CHEMICAL NEUROSCIENCE, 2018, 9 (07) :1625-1636

[18] Enantioselective total synthesis of pyrroloquinolone as a potent PDE5 inhibitor [J].

Shankaraiah, Nagula ;

Silva Santos, Leonardo .

TETRAHEDRON LETTERS, 2009, 50 (05) :520-523

[19] Design and synthesis of furyl/thineyl pyrroloquinolones based on natural alkaloid perlolyrine, lead to the discovery of potent and selective PDE5 inhibitors [J].

Zheng, Hongbo ;

Li, Lin ;

Sun, Bin ;

Gao, Yun ;

Song, Wei ;

Zhao, Xiaoyu ;

Gao, Yanhui ;

Xie, Zhiyu ;

Zhang, Nianzhao ;

Ji, Jianbo ;

Yuan, Huiqing ;

Lou, Hongxiang .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 150 :30-38

[20] Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5 [J].

Gong, Xudong ;

Wang, Guan ;

Ren, Jing ;

Liu, Zheng ;

Wang, Zhen ;

Chen, Tiantian ;

Yang, Xiaojun ;

Jiang, Xiangrui ;

Shen, Jingshan ;

Jiang, Hualiang ;

Aisa, Haji Akber ;

Xu, Yechun ;

Li, Jianfeng .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (17) :4944-4947

← 1 2 3 4 5 →