Synthesis and biological activities of new 1,4-benzothiazine derivatives.
New 2H-1,4-benzothiazin-3(4H)-one derivatives possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position were synthesized and tested for calcium antagonistic and calmodulin antagonistic activities. Antihypertensive effects in spontaneously hypertensive rats were also evaluated. In general, these compounds were rather weak calcium channel blockers, although, in contrast, many of them had moderate to potent calmodulin antagonistic activity, and 2-[3-(4-(4-fluorophenyl)-1-piperazinyl]propyl]-2H-1,4-benzothiazin -3 (4H)-one derivatives 45, 74 and 75 showed potent antihypertensive effects.
Kajino
M
M
Chemistry Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Mizuno
K
K
Tawada
H
H
Shibouta
Y
Y
Nishikawa
K
K
Meguro
K
K
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000138:chemical synthesis*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002147:Calmodulin; D010879:Piperazines; D013843:Thiazines