Synthesis and biological evaluation of antiplatelet 2-aminochromones.
The synthesis and biological evaluation of a series of antiplatelet 2-morpholinylchromones has been described. Modification of the C-7 phenylmethoxy group of 8-methyl-7-(phenylmethoxy)-2-(4-morpholinyl)-4H-1-benzopyran-4-one (2) has led to the discovery of a series of 7-[(amino-ethyl)oxy]-8-methyl derivatives which are potent inhibitors of ADP-induced platelet aggregation. Several members of this class proved active in preventing platelet-dependent thrombus formation in the dog, including 8-methyl-7-[2-(4-methyl-1-piperazinyl)ethoxy]-2-(4- morpholinyl)-4H-1-benzopyran-4-one (39) which was devoid of hemodynamic effects at the effective antithrombotic dose.
Morris
J
J
Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan 49001.
Wishka
D G
DG
Lin
A H
AH
Humphrey
W R
WR
Wiltse
A L
AL
Gammill
R B
RB
Judge
T M
TM
Bisaha
S N
SN
Olds
N L
NL
Jacob
C S
CS
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D002867:Chromones; D009025:Morpholines; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; C082308:8-methyl-7-(2-(4-methyl-1-piperazinyl)ethoxy)-2-(4-morpholinyl)-4H-1-benzopyran-4-one; D000244:Adenosine Diphosphate