title: Synthesis of proline analogues as potent and selective cathepsin S inhibitors.
abstract: Cathepsin S is a potential target of autoimmune disease. A series of proline derived compounds were synthesized and evaluated as cathepsin S inhibitors. We discovered potent cathepsin S inhibitors through structure-activity relationship studies of proline analogues. In particular, compound 19-(S) showed promising in vitro/vivo pharmacological activities and properties as a selective cathepsin S inhibitor.
authors: Department of Drug Discovery, Hanmi Research Center, 377-1 Yeongcheon-ri, Dongtan-myeon, Hwaseong, Gyeonggi-do 445-813, Republic of Korea.
authors: Mira
authors: M
authors: Kim
authors: Jiyoung
authors: J
authors: Jeon
authors: Jiyeon
authors: J
authors: Song
authors: Kwee Hyun
authors: KH
authors: Suh
authors: Young Hoon
authors: YH
authors: Kim
authors: Kyung Hoon
authors: KH
authors: Min
authors: Kwang-Ok
authors: KO
authors: Lee
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000378:metabolism; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003094:Collagen / Q000633:toxicity; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008861:Microsomes / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D003094:Collagen; D011392:Proline; D002403:Cathepsins; D002401:Cathepsin B; C028217:cathepsin S; D056657:Cathepsin K