[EN] PIPERIDINE DERIVATIVES USEFUL AS CCR5 ANTAGONISTS<br/>[FR] DERIVES DE PIPERIDINE FAISANT OFFICE D'ANTAGONISTES CCR5
申请人:SCHERING CORP
公开号:WO2000066559A1
公开(公告)日:2000-11-09
The use of CCR5 antagonists of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is -C(R13)2-, -C(R13)(R19)-, -C(O)-, -O-, -NH-, -N(alkyl)-, (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l), (m) or (n); R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1 is H, alkyl or alkenyl; R2 is optionally substituted phenyl, phenylalkyl, heteroaryl or heteroarylalkyl, naphthyl, fluorenyl or diphenylmethyl; R3 is optionally substituted phenyl, heteroaryl or naphthyl; R4 is H, alkyl, fluoro-alkyl, cyclopropylmethyl, -CH¿2?CH2OH, -CH2CH2-O-alkyl, -CH2C(O)-O-alkyl, -CH2C(O)NH2, -CH2C(O)-NHalkyl or -CH2C(O)-N(alkyl)2; R?19¿ is optionally substituted phenyl, heteroaryl or naphthyl, cycloalkyl, cycloalkylalkyl or alkoxyalkyl; and R?5, R13, R14, R15 and R16¿ are hydrogen or alkyl for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.
本发明涉及使用公式(I)或其药学上可接受的盐的CCR5拮抗剂,其中X为-C(R13)2-,-C(R13)(R19)-,-C(O)-,-O-,-NH-,-N(烷基)-,(a),(b),(c),(d),(e),(f),(g),(h),(i),(j),(k),(l),(m)或(n); R为可选取代苯基,吡啶基,噻吩基或萘基; R1为H,烷基或烯基; R2为可选取代苯基,苯基烷基,杂环芳基或杂环芳基烷基,萘基,芴基或二苯甲基; R3为可选取代苯基,杂环芳基或萘基; R4为H,烷基,氟代烷基,环丙基甲基,-CH¿2?CH2OH,-CH2CH2-O-烷基,-CH2C(O)-O-烷基,-CH2C(O)NH2,-CH2C(O)-NH烷基或-CH2C(O)-N(烷基)2; R19为可选取代苯基,杂环芳基或萘基,环烷基,环烷基烷基或烷氧基烷基; R5,R13,R14,R15和R16为氢或烷基,用于治疗HIV,固体器官移植排斥,移植物宿主病,关节炎,类风湿性关节炎,炎症性肠病,特应性皮炎,牛皮癣,哮喘,过敏或多发性硬化症,还公开了新化合物,包含它们的制药组合物,以及本发明CCR5拮抗剂与用于治疗HIV的抗病毒剂或用于治疗炎症性疾病的药物的组合。