Synthesis and collateral dilator activity of nitroxyalkylamides having direct or latent sulfhydryl moieties.
To develop an orally active, long-acting nitrate that does not induce tolerance, nitroxyalkyl compounds were prepared and their activities evaluated by the use of carotid collaterals in anesthetized dogs. A compound having a favorable pharmacological profile, that is, long-lasting collateral vasodilatation and little hypotension, and lack of nitrate tolerance, was chosen for further evaluation.
Ishihara
Sadao
S
Research Laboratories, Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140, Japan. isiwar@shina.sankyo.co.jp
Saito
Fujio
F
Ohhata
Yasuo
Y
Kanai
Marie
M
Mizuno
Hiroshi
H
Fujisawa
Michio
M
Yorikane
Ryosuke
R
Koike
Hiroyuki
H
D000818:Animals; D019540:Area Under Curve; D002339:Carotid Arteries; D003097:Collateral Circulation / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D004285:Dogs; D004361:Drug Tolerance; D007275:Injections, Intravenous; D008297:Male; D009566:Nitrates / Q000138:chemical synthesis* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*
D009566:Nitrates; D020030:Nitric Oxide Donors; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D014665:Vasodilator Agents; D005996:Nitroglycerin; D003545:Cysteine