Novel amides and esters prodrugs of olmesartan: Synthesis, bioconversion, and pharmacokinetic evaluation.
Synthesis of novel amides and esters prodrugs of olmesartan is described. Their in vitro stability in rat plasma was tested. The results showed that the ester derivative IIa with n-octyl substituted dioxolone moiety was rapidly converted into olmesartan within 30 min. The pharmacokinetic parameters of IIa were studied and compared with those of olmesartan medoxomil. Compound IIa is proposed to be a promising prodrug of olmesartan.
Park
Jin-Hun
JH
Biomaterials Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Chang
Jeong-Soo
JS
El-Gamal
Mohammed I
MI
Choi
Won-Kyoung
WK
Lee
Woong San
WS
Chung
Hye Jin
HJ
Kim
Hyun-Il
HI
Cho
Young-Jin
YJ
Lee
Bong Sang
BS
Jeon
Hong-Ryeol
HR
Lee
Yong Sup
YS
Choi
Young Wook
YW
Lee
Jaehwi
J
Oh
Chang-Hyun
CH
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000818:Animals; D004952:Esters; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D000068557:Olmesartan Medoxomil; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
D000577:Amides; D004952:Esters; D007093:Imidazoles; D011355:Prodrugs; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; C437965:olmesartan