Patent RU-2693459-C2 (RU)
Title: 5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as adamts inhibitors for treating osteoarthritis
Inventor: BREBION FRANCK LAURENT
IPC: A61P19/02
Filed: 2015-12-18
Granted: 2019-07-03
Abstract: FIELD: chemistry. 
     SUBSTANCE: in general formula I R 1  is H, C 1-4  alkyl, optionally substituted with one group R 4 ; C 3-7  monocyclic cycloalkyl optionally substituted with one group R 4 ; 4-7 membered monocyclic heterocycloalkyl containing 1 to 2 heteroatoms N, optionally substituted with one -C(=O)C 1-4  alkyl or -C(=O)OC 1-4  alkyl; phenyl, optionally substituted with one or two independently selected groups R 5 ; phenyl condensed with 5-membered monocyclic heterocycloalkyl containing 1 heteroatom N, wherein said heterocycloalkyl is optionally substituted with one =O; 5-6 membered monocyclic heteroaryl containing 1 or 2 heteroatoms independently selected from N and O, optionally substituted with one or two independently selected groups R 5 ; R 2  is independently selected from H, C 1-4  alkoxy and C 1-4  alkyl, optionally substituted with one group of OH, CN, C 1-4  alkoxy optionally substituted with one phenyl group, or 5-6 membered monocyclic heteroaryl, including 2 heteroatoms independently selected from N, optionally substituted with one or two independently selected C 1-4  alkyl groups; each R 3a  and R 3b  is independently selected from H and C 1-4  alkyl; Cy is 6-10-member monocyclic or condensed bicyclic aryl, optionally substituted with one to three independently selected groups R 6 ; 5-10-member monocyclic or condensed bicyclic heteroaryl, including 1, 2 or 3 heteroatoms independently selected from N, O and S, optionally substituted with one or two independently selected groups R 6 ; R 4  is OH, C 1-4  alkoxy, optionally substituted C 1-4  alkoxy or phenyl; C 1-4  thioalkoxy, 4-6-membered monocyclic heterocycloalkyl, including one or more heteroatoms independently selected from N and O, optionally substituted with one or two independently selected halogen groups or -C(=O)OC 1-4  alkyl; -C(=O)OR 7a , -C(=O)NR 7b R 7c , -NHC(=O)OR 7d , -NHC(=O)R 7e  or -NR 8a R 8b ; each R 5  is halogen, CN, C 1-4  alkyl optionally substituted with one or three independently selected halogen groups or -NR 9a R 9b ; C 1-4  alkoxy optionally substituted with -NR 9e R 9f , or -S(=O) 2 C 1-4  alkyl; each R 6  is a halogen, -CN, -NO 2 , -CH 3 , 5-6 membered monocyclic heteroaryl containing 1 or 2 heteroatoms of N, optionally substituted with one independently selected group of halogen or C 1-4  alkyl, or -NR 9g R 9h ; each R 7a , R 7b , R 7c , R 7d  or R 7e  is H or C 1-4  alkyl, optionally substituted with OH or C 1-4  alkoxy group; each R 8a  or R 8b  is independently selected from H and C 1-4  alkyl, optionally substituted with phenyl; each R 9a , R 9b , R 9c , R 9d , R 9e , R 9f , R 9g  and R 9h  is independently selected from H and C 1-4  alkyl. 
     EFFECT: disclosed is a compound of formula I, having the properties of an ADAMTS inhibitor, and a pharmaceutical composition based thereon for preventing and / or treating inflammatory conditions and / or diseases associated with cartilage degradation and / or cartilage tissue homeostasis associated with ADAMTS activity. 
     16 cl, 14 tbl, 5 ex