Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers.
DZ2002 and its related stereoisomers were efficiently synthesized. The optical data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In accordance with respective inhibitory potency of SAHase, the immunosuppressive potency order was demonstrated as (S)-DZ2002>(Rac)-DZ2002>(R)-DZ2002>(Keto)-DZ2002. These results indicate (S)-configuration of 2-chiral center in DZ2002 is important for binding with SAHase.
Zhang
Yang-Ming
YM
Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, 3663 North Zhong Shan Road, Shanghai 200062, China.
Ding
Yu
Y
Tang
Wei
W
Luo
Wei
W
Gu
Min
M
Lu
Wei
W
Tang
Jie
J
Zuo
Jian-Ping
JP
Nan
Fa-Jun
FJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011817:Rabbits; D013237:Stereoisomerism
D002087:Butyrates; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; C509291:methyl 4-(adenin-9-yl)-2-hydroxybutanoate; D043383:Adenosylhomocysteinase; D000225:Adenine