699016-00-7Relevant academic research and scientific papers
Discovery of a novel series of biphenyl benzoic acid derivatives as highly potent and selective human β3 adrenergic receptor agonists with good oral bioavailability. Part II
Imanishi, Masashi,Itou, Shinji,Washizuka, Kenichi,Hamashima, Hitoshi,Nakajima, Yutaka,Araki, Takanobu,Tomishima, Yasuyo,Sakurai, Minoru,Matsui, Shigeo,Imamura, Emiko,Ueshima, Koji,Yamamoto, Takao,Yamamoto, Nobuhiro,Ishikawa, Hirofumi,Nakano, Keiko,Unami, Naoko,Hamada, Kaori,Matsumura, Yasuhiro,Takamura, Fujiko,Hattori, Kouji
experimental part, p. 4002 - 4020 (2009/05/07)
The left-hand side (LHS) and central part of our first generation biphenyl (FGB) series was modified to improve in vitro and in vivo β3-AR potency without loss of oral bioavailability. First, in this study, we focused our efforts on replacement of the 3-chlorophenyl moiety in the LHS of FGB analogues with 3-pyridyl ring analogues to adjust the lipophilicity. Second, we investigated the replacement of the central part of this series and discovered that introduction of a methyl group into the α-position of the phenethylamine moiety greatly enhanced potency keeping good oral availability. Finally, the replacement of the two carbon linker of the central part with an ethoxy-based linker provided improved potency and PK profiles. As a result of these studies, several analogues (i.e., 9h, 9k, 91, 10g, 10m, 10p, 10r, 11b, and 11l) were identified that displayed an excellent balance of very higher human β3-AR potency compared to the FGB compounds, high selectivity, and good pharmacokinetic profiles. Furthermore, these several compounds showed high in vivo efficacy in an overactive bladder (OAB) model. These findings suggest that our selected second generation biphenyl (SGB) series compounds may be attractive new successful therapeutic candidates for the treatment of OAB.
Aminoalcohol derivatives
-
Page/Page column 40, (2010/02/07)
The present invention relates to a compound formula [I]: wherein R1 is hydrogen or halogen, R2 is hydrogen or an amino protective group, R3 is hydrogen or lower alkyl, X is bond, —CH2— or —O—, and Y is ?in which R4 is lower alkoxycarbonyl, ?in which R5 is carboxy(lower)alkyl, etc., ?in which R6 is hydroxy, etc., and so on, or a salt thereof. The compound [I] of the present invention and pharmaceutically acceptable salts thereof are useful for the prophylactic and/or the therapeutic treatment of pollakiurea or urinary incontinence.
