Synthesis and structure-activity relationships of antiallergic N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamides possessing both antihistaminic and anti slow-reacting substance (SRS) activities.
A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2- thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti slow-reacting substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2- thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED50 = 0.92 mg/kg p.o.; anti-SRS activity, IC50 = 0.89 microgram/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
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S
Shigenaga
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T
Manabe
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H
Matsuda
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T
Fujii
M
M
Matsuo
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D006967:Hypersensitivity / Q000188:drug therapy*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
D000577:Amides; D006633:Histamine Antagonists; D007211:Indoles; D013189:SRS-A; D013844:Thiazoles