Substituted N-arylsulfonylheterocyclic amines as gamma-secretase inhibitors
    5.
    发明申请
    Substituted N-arylsulfonylheterocyclic amines as gamma-secretase inhibitors 失效
    取代的N-芳基磺酰基杂环胺作为γ-分泌酶抑制剂

    公开(公告)号:US20060040936A1

    公开(公告)日:2006-02-23

    申请号:US11168797

    申请日:2005-06-28

    摘要: This invention discloses novel gamma secretase inhibitors of the formula: wherein: L is —O—, —N(R6)—, —S—, —S(O)—, or —S(O2)—; R1 is selected from the group consisting of aryl and heteroaryl; R2 is selected from the group consisting of alkyl, —C(O)—Y, —X—C(O)—Y, -alkylene-X—C(O)—Y, -alkylene-C(O)—Y, -alkylene-cycloalkylene-X—C(O)—Y, -alkylene-cycloalkylene-C(O)—Y, -cycloalkylene-alkylene-X—C(O)—Y, -cycloalkylene-alkylene-C(O)—Y, -cycloalkylene-X—C(O)—Y, -cycloalkylene-C(O)—Y, -alkylene-cycloalkylene-alkylene-X—C(O)—Y, -alkylene-cycloalkylene-alkylene-C(O)—Y, aryl, and heteroaryl; R3 is selected from the group consisting of aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, and alkoxyalkyl; each R4 and R5 is independently selected from the group consisting of H and alkyl; and Y is selected from the group consisting of —NR8R9, —N(R6)—(CH2)b—NR8R9, aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, and arylheterocycloalkyl; or Y is selected from the group consisting of: One or more compounds of formula I, or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

    摘要翻译: 本发明公开了下式的新型γ分泌酶抑制剂:其中:L是-O-,-N(R 6) - , - S - , - S(O) - 或-S(O - ; R 1选自芳基和杂芳基; R 2选自烷基,-C(O)-Y,-XC(O)-Y, - 亚烷基-XC(O)-Y, - 亚烷基-C(O )-Y-亚烷基 - 亚环烷基-OC(O)-Y-亚烷基 - 亚环烷基-C(O)-Y-亚烷基 - 亚烷基-OC(O)-Y-亚烷基 - 亚烷基-C(O) Y( - )亚环烷基-C(O)-Y-亚烷基-C(O)-Y-亚烷基 - 亚环烷基亚烷基-XC(O)-Y-亚烷基 - 亚环烷基 - 亚烷基-C(O)-Y, 芳基和杂芳基; R 3选自芳基,杂芳基,烷基,环烷基,芳基烷基,芳基环烷基,杂芳基烷基,杂芳基环烷基,芳基杂环烷基和烷氧基烷基; 每个R 4和R 5独立地选自H和烷基; 并且Y选自-NR 8 R 9,-N(R 6) - (CH 2) 芳基,杂芳基,烷基,环烷基,芳基烷基,芳基环烷基,杂芳基烷基,杂芳基环烷基和芳基杂环烷基 ; 或Y选自:一种或多种式I化合物或包含该化合物的制剂可用于,例如, 治疗阿尔茨海默病。

    Novel gamma secretase inhibitors
    6.
    发明申请
    Novel gamma secretase inhibitors 审中-公开
    新型γ分泌酶抑制剂

    公开(公告)号:US20060004004A1

    公开(公告)日:2006-01-05

    申请号:US11098745

    申请日:2005-04-04

    摘要: Gamma-secretase inhibitors of the formula: are useful in treating various neurodegenerative diseases, wherein, for example: R1 includes unsubstituted or substituted aryl or heteroaryl groups; R2 includes —C(O)—Y, -alkylene-C(O)—Y, -alkylene-cycloalkylene-C(O)—Y, -cycloalkylene-alkylene-C(O)—Y, -alkylene-cycloalkylene-alkylene-C(O)—Y, -cycloalkylene-C(O)—Y, —S(O)—Y, -alkylene-S(O)—Y, -alkylene-cycloalkylene-S(O)—Y, -cycloalkylene-alkylene-S(O)—Y, -alkylene-cycloalkylene-alkylene-S(O)—Y, -cycloalkylene-S(O)—Y, —S(O2)—Y, -alkylene-S(O2)—Y, -alkylene-cycloalkylene-S(O2)—Y, -cycloalkylene-alkylene-S(O2)—Y, -alkylene-cycloalkylene-alkylene-S(O2)—Y, and -cycloalkylene-S(O2)—Y, wherein Y is as defined herein, and each of said alkylene or cycloalkylene may be unsubstituted or substituted as provided herein; each R3 is independently includes H, alkyl, —O-alkyl, —OH, —N(R9)2, acyl, and aroyl; or the moiety (R3)2, together with the ring carbon atom to which it is shown attached in formula I, defines a carbonyl group, —C(O)—; each R3A and R3B independently includes H, or alkyl; R11 includes aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, or alkoxyalkyl. One or more of the compounds of formula I, or pharmaceutically acceptable salts, solvates, and/or esters, or compositions comprised thereof, may be used to treat, e.g., Alzheimer's Disease.

    摘要翻译: 下式的γ-分泌酶抑制剂:可用于治疗各种神经变性疾病,其中例如:R 1包括未取代或取代的芳基或杂芳基; R 2包括-C(O)-Y, - 亚烷基-C(O)-Y-亚烷基 - 亚环烷基-C(O)-Y-亚烷基 - 亚烷基-C(O) - Y, - 亚烷基 - 亚环烷基 - 亚烷基-C(O)-Y-环亚烷基-C(O)-Y,-S(O)-Y-亚烷基-S(O)-Y-亚烷基 - 亚环烷基-S (O)-Y-亚烷基 - 亚烷基-S(O)-Y-亚烷基 - 亚环烷基 - 亚烷基-S(O)-Y-亚烷基-S(O)-Y,-S(O) - 亚烷基-S(O)2 - 亚烷基 - 亚环烷基-S(O)2 - 亚烷基-S(O 2) -S(O)2 - 亚烷基 - 亚环烷基 - 亚烷基-S(O)2 - 和 - 亚环烷基-S(O 2) / Y,其中Y如本文所定义,并且所述亚烷基或亚环烷基中的每一个可以是未经取代的或如本文所提供的取代的; 每个R 3独立地包括H,烷基,-O-烷基,-OH,-N(R 9)2,酰基和 芳酰基 或其部分(R 3)2和连接在式I中的环碳原子一起定义为羰基,-C(O) - ; 每个R 3A和R 3B独立地包括H或烷基; R 11包括芳基,杂芳基,烷基,环烷基,芳基烷基,芳基环烷基,杂芳基烷基,杂芳基环烷基,芳基杂环烷基或烷氧基烷基。 一种或多种式I化合物或其药学上可接受的盐,溶剂化物和/或酯或其组合物可用于治疗,例如阿尔茨海默氏病。

    Gamma secretase modulators
    7.
    发明授权
    Gamma secretase modulators 有权
    伽玛分泌酶调节剂

    公开(公告)号:US09096582B2

    公开(公告)日:2015-08-04

    申请号:US14354992

    申请日:2012-10-26

    IPC分类号: C07D413/10

    CPC分类号: C07D413/10 C07D413/14

    摘要: Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and use of the compounds in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.

    摘要翻译: 本文公开了式(I)的化合物及其药学上可接受的盐,其中每个取代基被给出如说明书和权利要求书中所阐述的定义。 还公开了含有式(I)化合物的药物组合物和该化合物在治疗神经变性疾病或病症如阿尔茨海默病中的用途。