Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity: synthesis and evaluation of a new series of indole derivatives.
A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives were prepared and evaluated for thromboxane A2 (TXA2) synthetase-inhibitory and histaminergic H1-blocking activity. Among the compounds synthesized, indole-6-carboxylic acid derivatives showed higher activities than the other positional isomers of carboxylic acid. 1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )-1H-indole-6-carboxylic acid (12) had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8) M) and H1-blocking activity (IC50 = 8 x 10(-9) M).
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Japan.
S
S
Kamiya
H
H
Matsui
H
H
Shirahase
S
S
Nakamura
K
K
Wada
M
M
Kanda
H
H
Shimaji
N
N
Kakeya
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D007211:Indoles; D013930:Thromboxane-A Synthase