title: Novel synthetic route for antimalarial benzo[a]phenoxazine derivative SSJ-183 and two active metabolites.
abstract: A productive synthesis of benzo[a]phenoxazine derivative SSJ-183 (1), a promising lead for antimalarial agents, was developed using a one pot procedure. Furthermore, N-deethylated metabolite 3 and bis-N,N-deethylated metabolite 4 were synthesized by the application of the method. The metabolites 3 and 4 showed comparable and ∼2-fold increased activities against drug-sensitive and drug-resistant Plasmodium falciparum parasites.
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan; Synstar Japan Co., Ltd, Orbic Bldg 3F, 2-9-46 Sakaecho, Odawara 250-0011, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mizukawa
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan; College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215006, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Ge
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan; Center for Advanced Research in Sciences, University of Dhaka, Bangladesh.
authors.forename: Abu
authors.initials: A
authors.lastname: Bakar Md
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan; Synstar Japan Co., Ltd, Orbic Bldg 3F, 2-9-46 Sakaecho, Odawara 250-0011, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Itoh
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, CH-4003 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Scheurer
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, CH-4003 Basel, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, CH-4003 Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: School of Medicine, Department of Infection and Immunity, Division of Medical Zoology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi 329-0498, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. Electronic address: m-ihara@hoshi.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D010078:Oxazines; D011725:Pyridines; C561763:SSJ 183
keywords: Antimalarial; Benzo[a]phenoxazine; Drug-sensitive and drug-resistant; Metabolites; Plasmodium falciparum