title: Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers.
abstract: 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.
authors.affiliation: Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University, 3663 North Zhong Shan Road, Shanghai 200062, China.
authors.forename: Yang-Ming
authors.initials: YM
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
authors.forename: Fa-Jun
authors.initials: FJ
authors.lastname: Nan
mesh_terms: 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
chemical_list: D002087:Butyrates; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; C509291:methyl 4-(adenin-9-yl)-2-hydroxybutanoate; D043383:Adenosylhomocysteinase; D000225:Adenine