A prodrug approach to COX-2 inhibitors with methylsulfone.
2,2-dimethyl-4-phenyl-5-[4-(methylsulfinyl)phenyl]-3(2H)furanone derivatives, 3 and 6, were shown to be effectively transformed in vivo into the corresponding methylsulfone derivatives 1 and 4, when orally administered to rats. Pharmacological implications for use of sulfoxide analogues 3 and 6 are discussed as prodrugs to potent selective COX-2 inhibitors 1 and 4.
Moh
Joo Hyun
JH
Drug Discovery, AmorePacific R&D Center, 314-1 Bora-ri, Giheung-eup, Yongin, Gyeonggi-do 449-729, Republic of Korea.
Choi
Young Hoon
YH
Lim
Kyoung Min
KM
Lee
Ki-Wha
KW
Shin
Song Seok
SS
Choi
Jin Kyu
JK
Koh
Hyun Joo
HJ
Chung
Shin
S
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D004121:Dimethyl Sulfoxide; D004305:Dose-Response Relationship, Drug; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000008:administration & dosage* / Q000737:chemistry
D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D013450:Sulfones; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide