89056-27-9Relevant academic research and scientific papers
Discovery of highly potent dual EP2and EP3agonists with subtype selectivity
Kinoshita, Akihiro,Higashino, Masato,Aratani, Yoshiyuki,Kakuuchi, Akito,Matsuya, Hidekazu,Ohmoto, Kazuyuki
, p. 1016 - 1019 (2016/07/26)
The cyclic carbamate derivatives, 2-{[2-((4S)-4-{(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-{[2-((4S)-4-{(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2and EP3agonists with selectivity against the EP1and EP4subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2and EP3agonist activity with EC50values of 10 nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom.
Development of a highly selective EP2-receptor agonist. Part 1: Identification of 16-hydroxy-17,17-trimethylene PGE2 derivatives
Tani, Kousuke,Naganawa, Atsushi,Ishida, Akiharu,Sagawa, Kenji,Harada, Hiroyuki,Ogawa, Mikio,Maruyama, Takayuki,Ohuchida, Shuichi,Nakai, Hisao,Kondo, Kigen,Toda, Masaaki
, p. 1093 - 1106 (2007/10/03)
Design and synthesis of an EP2-receptor selective agonist began with the chemical modification of α and ω-chains of butaprost 1a, which exhibits an affinity for the IP-receptor. Two series of prostaglandin (PG) analogues with a 16-hydroxy-17,17-trimethylene moiety as an ω-chain were identified. Among those tested, 4a,b,e,f,h and 6a,b,e,f,h were found to be highly selective EP2-receptor agonists. Structure activity relationships are discussed. Copyright
Carbacyclins, process for the preparation thereof, and use thereof as medicinal agents
-
, (2008/06/13)
The invention relates to carbacyclins of general Formula I STR1 wherein R1 is the residue CH2 OH or STR2 with R2 meaning a hydrogen atom, an alkyl, cycloalkyl, aryl residue, a STR3 or heterocyclic residue, or R1 is the residue STR4 with R3 meaning an alkanoyl or alkanesulfonyl residue of respectively 1-10 carbon atoms or the residue R2, or R1 is the residue STR5 wherein m is the number 1 or 2, X is an oxygen atom or a CH2 -group, A is a trans--CH=CH- or -- C--group, W is a free or functionally modified hydroxymethylene group wherein the OH-group can be in the α- or β- position, n is the number 1, 2, or 3, D is a straight-chain alkylene group of 1-5 carbon atoms, E is a --C C---bond or a --CR6 =CR7 --group wherein R6 and R7 are different from each other and mean a hydrogen atom or an alkyl group of 1-5 carbon atoms or a hydrogen atom or a halogen atom, preferably chlorine, R4 is an alkyl, cycloalkyl, or optionally substituted arly group, or a heterocyclic group, R5 is a free or functionally modified hydroxy group, and if R2 means a hydrogen atom, the salts thereof with physiologically compatible bases; to processes for the preparation thereof, and to the use thereof as blood-pressure-lowering agents.
