2-Heteroaryl 2-substituted phenylketone derivatives and their inhibitory activity on platelet aggregation.
R 68070 and CV-4151 are two compounds possessing both thromboxane synthetase inhibitory activity and thromboxane receptor antagonist properties. 2-Heteroaryl 2-substituted phenylketone derivatives with a partial structural similarity to R 68070 and CV-4151, i.e. possessing a phenyl and a heteroaryl moiety, have been prepared and found to have antiplatelet activity. The compound 2-thienyl 2'-hydroxyphenyl ketone (4) was shown to completely inhibit platelet aggregation induced by arachidonic acid at a concentration of 5.0 microM. Structure-activity analysis indicated that the presence of a ketone group is an important requirement for this inhibitory activity. An o-hydroxyl substitution on the phenyl ring, and a 2-thienyl of heteroaryl ring might increase inhibitory activity.
Hsu
L Y
LY
School of Pharmacy, National Defense Medical Center, Taipei, Republic of China.
Lee
C F
CF
Chou
T C
TC
Ding
Y A
YA
D000818:Animals; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010421:Pentanoic Acids / Q000737:chemistry / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000737:chemistry / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D005229:Fatty Acids, Monounsaturated; D005343:Fibrinolytic Agents; D010421:Pentanoic Acids; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C045446:isbogrel; C060219:ridogrel