Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidine-2,4-dione derivatives as potent GnRH receptor antagonists

The synthesis and SAR studies of thieno[2,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists to treat reproductive diseases are discussed. It was found that the 2-(2-pyridyl)ethyl group on the 5-aminomethyl functionality of the core structure was a key feature for good receptor binding act...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2003-10, Vol.13 (20), p.3617-3622
Main Authors: ZHIQIANG GUO, YONGSHENG CHEN, DONGPEI WU, ZHU, Yun-Fei, STRUTHERS, R. Scott, SAUNDERS, John, QIU XIE, CHEN CHEN
Format: Article
Language:English
Subjects:
Biological and medical sciences
Hormones. Endocrine system
Medical sciences
Pharmacology. Drug treatments
Pyrimidinones - chemical synthesis
Pyrimidinones - chemistry
Pyrimidinones - pharmacology
Receptors, LHRH - antagonists & inhibitors
Structure-Activity Relationship
Thiophenes - chemical synthesis
Thiophenes - chemistry
Thiophenes - pharmacology
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Summary:The synthesis and SAR studies of thieno[2,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists to treat reproductive diseases are discussed. It was found that the 2-(2-pyridyl)ethyl group on the 5-aminomethyl functionality of the core structure was a key feature for good receptor binding activity. SAR study of the 6-(4-aminophenyl) group suggests that hydrophobic substituents were preferred. The best compound from this series had binding affinity (K(i)) of 0.4 nM to the human GnRH receptor.
ISSN:0960-894X
1464-3405
DOI:10.1016/s0960-894x(03)00746-7