title: C-H activation enables a rapid structure-activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors.
abstract: We describe the structure-activity relationship of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38.
authors.affiliation: Institute of Transformative Bio-Molecules (WPI-ITbM) and Graduate School of Science, Nagoya University, Chikusa, Nagoya, 464-8602, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Miyamura
authors.forename: Misaho
authors.initials: M
authors.lastname: Araki
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ota
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yasuda
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Masuda
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Itami
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamaguchi
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D056466:Histone Demethylases; C495195:KDM1A protein, human