Synthesis of a novel human PPARδ selective agonist and its stimulatory effect on oligodendrocyte differentiation.
We successfully synthesized a novel peroxisome proliferator-activated receptor (PPAR)δ selective agonist, namely, compound 20, with a characteristic benzisoxazole ring. Compound 20 exhibited potent human PPARδ transactivation activity and high δ selectivity. Further, it stimulated differentiation of primary oligodendrocyte precursor cells in vitro, indicating that it may be an effective drug in the treatment of demyelinating disorders such as multiple sclerosis.
Discovery Research Laboratories, Nippon Chemiphar Co Ltd, 1-22, Hikokawado, Misato, Saitama 341-0005, Japan. s-sakuma@chemiphar.co.jp
Shogo
S
Sakuma
Tsuyoshi
T
Endo
Takashi
T
Kanda
Hideki
H
Nakamura
Satomi
S
Yamasaki
Tomio
T
Yamakawa
D000818:Animals; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy; D009836:Oligodendroglia / Q000166:cytology*; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D047494:PPAR delta / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D015533:Transcriptional Activation
D007555:Isoxazoles; D010080:Oxazoles; D047494:PPAR delta