Synthetic studies on selective adenosine A2A receptor antagonists. Part II: synthesis and structure-activity relationships of novel benzofuran derivatives.
Based on the previously reported lead compound, a series of benzofuran derivatives were prepared to study their antagonistic activities to A(2A) receptor. The replacement of the phenyl group at the 4-position with a heterocyclic ring improved the PK profile and aqueous solubility. From these studies, we discovered a potent new A(2A) antagonist, 12a, which has both a good oral bioavailability and in vivo efficacy on motor disability in MPTP-treated common marmosets.
Saku
Osamu
O
Fuji Research Park, Kyowa Hakko Kirin Co., Ltd, Suntou-gun, Shizuoka, Japan. osamu.saku@kyowa-kirin.co.jp
Saki
Mayumi
M
Kurokawa
Masako
M
Ikeda
Ken
K
Uchida
Shin-ichi
S
Takizawa
Takuya
T
Uesaka
Noriaki
N
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D002144:Callithrix; D019957:Motor Skills Disorders / Q000188:drug therapy; D012995:Solubility; D013329:Structure-Activity Relationship
D058917:Adenosine A2 Receptor Antagonists; D001572:Benzofurans