title: Synthesis of PDE IV inhibitors. First asymmetric synthesis of two of GlaxoSmithKline's highly potent Rolipram analogues.
abstract: Asymmetric syntheses of two of GlaxoSmithKline’s highly potent phosphodiesterase IV inhibitors CMPI 1 and CMPO 2 have been accomplished from nitroethane and simple precursors in 8 and 7 steps, respectively. The suggested synthetic strategy involves as a key stage the silylation of enantiopure six-membered cyclic nitronates. In vitro studies of PDE IVB1 inhibition revealed a significant difference in the activity of CMPI 1 and CMPO 2 enantiomers.
authors.affiliation: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Leninsky prospect, 47, Moscow, Russian Federation. sukhorukov@ioc.ac.ru.
authors.forename: Petr A
authors.initials: PA
authors.lastname: Zhmurov
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Sukhorukov
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Chupakhin
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Khomutova
authors.forename: Sema L
authors.initials: SL
authors.lastname: Ioffe
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Tartakovsky
mesh_terms: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008968:Molecular Conformation; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D020889:Rolipram / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011994:Recombinant Proteins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human; D020889:Rolipram