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Efflux-pump inhibitors and therapeutic uses thereof
专利权人:
Basilea Pharmaceutica International AG;MME Muller-Regush
发明人:
Jürg Dreier,Berangere Gaucher,Eric Desarbre,Marc Muller
申请号:
US15580008
公开号:
US10464896B2
申请日:
2016.06.13
申请国别(地区):
US
年份:
2019
代理人:
摘要:
The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein ASC is —;N(R8)(R9)ASC-1 ASC-1 is Ring A represents a 4- to 6-membered saturated ring containing carbon atoms as ring members in addition to the nitrogen atom and wherein one CH2 moiety in ring A is optionally replaced by CH(R21) and wherein one carbon atom in ring A that is not adjacent to the nitrogen atom is optionally replaced by O, and wherein ring A is connected to X via a carbon atom; X represents a bond, —;CH2- or —;C(═;O)—;; AR1, AR2 represent independently phenyl or a 5- to 6-membered heteroaryl ring containing one to three heteroatoms selected from O, S and N, wherein AR1 is connected to L1 via a carbon atom, and wherein AR2 is connected to L1 and L2 via a carbon atom; R1, R2, R3 represent independently hydrogen, halogen, cyano, hydroxyl, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, —;C1-C6alkylene-N(R12)R13, —;N(R12)R13, —;C(O)OR111, —;C(O)N(R12)R13, —;S(O)OR11 or phenyl; R4 represents hydroxyl, hydrogen, halogen, nitro, cyano, amino, C1-C6alkyl optionally substituted by 1 to 5 R14, C2-C6alkenyl optionally substituted by 1 to 5 R14, C2-C6alkynyl optionally substituted by 1 to 5 R14, C1-C6alkoxy optionally substituted by 1 to 5 R14, C2-C6alkenyloxy optionally substituted by 1 to 5 R14, C2-C6alkynyloxy optionally substituted by 1 to 5 R14, —;C(O)OR15, —;CHO, —;C(O)N(R16)R17, —;C1-C6alkylene-N(R9)(R16)R17, —;O-Cycle-P or —;O-Cycle-Q; R5, R6, R7 represent independently hydrogen, halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy or C1-C6haloalkoxy; R8 represents hydrogen, methyl or ASC-1; R9 is methyl or absent, and wherein when R9 is present the respective nitrogen atom carries a positive charge; R10 represents hydrogen or methyl; R11 represents independently at each occurrence hydrogen or C1-C6alkyl; R
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