A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity

• Published in: Bioorganic & medicinal chemistry letters 2010-10, Vol.20 (20), p.6157-6160
• Main Authors: Kang, Guifeng, Zhao, Ming, Zhang, Xiaoyi, Peng, Li, Li, Chunbo, Mao, Wei, Ye, Weidong, Peng, Shiqi
• Format: Article
• Language: English
• Subjects: 3D QSAR; Administration, Oral; Analgesia; Analgesics; Analgesics - administration & dosage; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - therapeutic use; Animals; Biological and medical sciences; Chronic Disease; Conjugate; Gly-AA-OBzl; Glycine - administration & dosage; Glycine - chemical synthesis; Glycine - chemistry; Glycine - therapeutic use; Humans; Male; Medical sciences; Mice; Neuropharmacology; Pain - drug therapy; Pharmacology. Drug treatments; Purines - administration & dosage; Purines - chemical synthesis; Purines - chemistry; Purines - therapeutic use; Quantitative Structure-Activity Relationship; Substituted purine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.05.077

Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9-(tetrahydropyran-2-yl)-9 H-purin-6-yl]- N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC 2H 5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.