85554-68-3Relevant articles and documents
Synthesis and evaluation of a potent, well-balanced EP2/EP3 dual agonist
Kinoshita, Akihiro,Higashino, Masato,Yoshida, Koji,Aratani, Yoshiyuki,Kakuuchi, Akito,Hanada, Keisuke,Takeda, Hiroyuki,Naganawa, Atsushi,Matsuya, Hidekazu,Ohmoto, Kazuyuki
, p. 200 - 214 (2017/12/06)
A highly potent and well-balanced dual agonist for the EP2 and EP3 receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC50 EP2 = 1.1 nM, EP3 = 1.0 nM) with acceptable selectivity over the EP1 and EP4 subtypes (>2000-fold). Further fine-tuning of compound 10 led to identification of ONO-8055 as a clinical candidate. ONO-8055 was effective at an extremely low dose (0.01 mg/kg, po, bid) in rats, and dose-dependently improved voiding dysfunction in a monkey model of underactive bladder (UAB). ONO-8055 is expected to be a novel and highly promising drug for UAB.
A new method for the catalytic aldol reaction to ketones
Oisaki, Kounosuke,Suto, Yutaka,Kanai, Motomu,Shibasaki, Masakatsu
, p. 5644 - 5645 (2007/10/03)
A new method for the catalytic aldol reaction to ketones, using CuF·3PPh3·2EtOH complex as the catalyst and (EtO)3SiF as the additive, is described. The reaction can be applied to a wide range of ketones and trimethylsilyl enolates. On the basis of mechanistic studies, a working hypothesis for the catalytic cycle is proposed, in which the dynamic ligand exchange mediated by copper silicates produces the active copper enolate. Moreover, the present reaction can be extended to the catalytic enantioselective reaction using tol-BINAP as a chiral ligand. Copyright
