title: Synthetic studies on selective adenosine A2A receptor antagonists: synthesis and structure-activity relationships of novel benzofuran derivatives.
abstract: A series of benzofuran derivatives were prepared to study their antagonistic activities to the A(2A) receptor. Replacement of the ester group of the lead compound 1 with phenyl ring improved the PK profile, while modifications of the amide moiety showed enhanced antagonistic activity. From these studies, compounds 13c, 13f, and 24a showed good potency in vitro and were identified as novel A(2A) receptor antagonists suitable for oral activity evaluation in animal models of catalepsy.
authors.affiliation: Fuji Research Park, Kyowa Hakko Kirin Co, Ltd, 1188 Shimotogari, Nagaizumi-cho, Suntou-gun, Shizuoka 411-8731, Japan. osamu.saku@kyowa-kirin.co.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Saku
authors.forename: Mayumi
authors.initials: M
authors.lastname: Saki
authors.forename: Masako
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Ken
authors.initials: K
authors.lastname: Ikeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Takizawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Uesaka
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D001572:Benzofurans; D043705:Receptor, Adenosine A2A