Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9 (3H)-one derivatives. I.
A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives 4a--z were synthesized from 5-substituted 1,3,4-thiadiazol-2-amines 5 by the following consecutive reactions: pyrimidine ring closure with bis(2,4,6-trichlorophenyl) malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4, involving reaction of 5-substituted 2-azido-1,3,4-thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure. The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated.
Suzuki
N
N
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Miwa
T
T
Aibara
S
S
Kanno
H
H
Takamori
H
H
Tsubokawa
M
M
Ryokawa
Y
Y
Tsukada
W
W
Isoda
S
S
D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D008297:Male; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D011744:Pyrimidinones; D013189:SRS-A; D013830:Thiadiazoles; D014230:Triazoles