title: Tetrahydro-naphthols as orally available TRPV1 inhibitors.
abstract: Starting from a naphthol-based lead series with low oral bioavailability, we have identified potent TRPV1 antagonists with oral bioavailability in rats. These compounds emerged from SAR studies aimed at replacing the lead's phenol structure whilst maintaining potency. Compound rac-6a is an orally available TRPV1 antagonist with single-digit nanomolar activity. The enantiomers show a low eudismic ratio at the receptor level.
authors.affiliation: Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto, Japan. Klaus.Urbahns@merckgroup.com
authors.forename: Klaus
authors.initials: K
authors.lastname: Urbahns
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yura
authors.forename: Jang B
authors.initials: JB
authors.lastname: Gupta
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tajimi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujishima
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masuda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ikegami
authors.forename: Makiko
authors.initials: M
authors.lastname: Marumo
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasoshima
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshiya
authors.initials: T
authors.lastname: Moriwaki
authors.forename: David
authors.initials: D
authors.lastname: Madge
authors.forename: Fiona
authors.initials: F
authors.lastname: Chan
authors.forename: Muneto
authors.initials: M
authors.lastname: Mogi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D009284:Naphthols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: D009284:Naphthols; D050916:TRPV Cation Channels