A class of novel conjugates of substituted purine and Gly-AA-OBzl: synthesis and evaluation of orally analgesic activity.
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)-9H-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(2)H(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.
Kang
Guifeng
G
College of Pharmaceutical Sciences, Peking University, Beijing, PR China.
Zhao
Ming
M
Zhang
Xiaoyi
X
Peng
Li
L
Li
Chunbo
C
Mao
Wei
W
Ye
Weidong
W
Peng
Shiqi
S
D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D005998:Glycine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy*; D011687:Purines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D021281:Quantitative Structure-Activity Relationship
D000700:Analgesics; D011687:Purines; D005998:Glycine