Structure-activity relationship study on the 6-membered heteroaromatic ring system of diphenylpyrazine-type prostacyclin receptor agonists.
A series of prostacyclin receptor agonists was prepared by modifying the central heteroaromatic ring of lead compound 2, and a docking study was performed to investigate their structure-activity relationships by using a homology-modeled structure of the prostacyclin receptor. Compound 2 and its derivatives could be docked to the prostacyclin receptor in two ways depending on the position of the nitrogen atom within the heteroaromatic ring. Furthermore, hydrogen bonding between the nitrogen atom in the heteroaromatic ring and the hydroxyl group of Ser20 or Tyr75 of the receptor appears to be important for the potent expression of biological activity.
Asaki
Tetsuo
T
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, 14, Nishinosho-Monguchi-Cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. t.asaki@po.nippon-shinyaku.co.jp
Hamamoto
Taisuke
T
Sugiyama
Yukiteru
Y
Kuwano
Keiichi
K
Kuwabara
Kenji
K
Niwa
Tomoko
T
D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology*; D044006:Receptors, Epoprostenol / Q000819:agonists* / Q000502:physiology; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; D044006:Receptors, Epoprostenol