发明名称 Substituted [1,4]diazepino[6,7,1-ij]quinolines as serotonin 5-HT2C receptor modulators
摘要 The present invention relates to compound of formula (I) as tricyclic hexahydrodiazepinoquinolines carrying a cyclic substituent, useful for modulating the 5-HT2C receptor and preventing and/or treating conditions and disorders that respond to the modulation of the 5-HT2C receptor. The present invention also relates to methods for producing compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for preventing or treating conditions and disorders that respond to the modulation of the 5-HT2C receptor by administering compounds of formula (1) or pharmaceutical compositions thereof.
申请公布号 US9573950(B2) 申请公布日期 2017.02.21
申请号 US201514657840 申请日期 2015.03.13
申请人 AbbVie Deutschland GmbH & Co KG 发明人 Backfisch Gisela;Bakker Margaretha Henrica Maria;Blaich Günter;Braje Wilfried;Drescher Karla;Erhard Thomas;Haupt Andreas;Koolman Hannes;Lakics Viktor;Linsenmeier Anna;Mack Helmut;Peter Raimund;Relo Ana Lucia;Zhao Xiaona;Wang Jincheng
分类号 A61K31/551;C07D487/16;C07D471/06;C07D471/04 主分类号 A61K31/551
代理机构 Neal Gerber & Eisenberg LLP 代理人 Neal Gerber & Eisenberg LLP
主权项 1. A compound of the formula (I) wherein R1 is selected from the group consisting of hydrogen, cyano, C1-C6-alkyl, fluorinated C1-C6-alkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, —C(═O)R9, phenyl, phenyl-C1-C2-alkyl and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO2 and optionally also 1 or 2 C═O and/or C═S groups as ring members, where the cyclic moieties in the three last-mentioned radicals may be substituted with one or more substituents R10; each R2 is independently selected from the group consisting of cyano, nitro, C1-C6-alkyl, fluorinated C1-C6alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, —CH2NR11aR11b, —C(═O)R9, phenyl, phenyl-C1-C2-alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R10; R3a and R3b, independently of each other, are selected from the group consisting of hydrogen, cyano, nitro, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, —CH2NR11aR11b, —C(═O)R9, phenyl, phenyl-C1-C2-alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R10; R4a and R4b, independently of each other, are selected from the group consisting of hydrogen, cyano, nitro, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, —CH2NR11aR11b, —C(═O)R9, phenyl, phenyl-C1-C2-alkyl, and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R10; or R4a and R4b form together a group ═O or ═S; R5a and R5b, independently of each other, are selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxy, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, C1-C6-alkylthio, fluorinated C1-C6-alkylthio, C1-C6-alkylsulfinyl, fluorinated C1-C6-alkylsulfonyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfonyl, —NR11a -R11b, —CH2NR11aR11b, —NR11aC(O)R9, —C(═O)R9, SO2NR11aR11b, C1-C6-alkylcarbonyloxy, fluorinated C1-C6-alkylcarbonyloxy, phenyl, phenyl-C1-C2-alkyl, phenoxy, phenylsulfonyl, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals may be substituted with one or more substituents R10; where R5a and R5b are not simultaneously hydroxy; R6 is a cyclic radica selected from the group consisting of C3-C6-cycloalkyl which may carry one or more radicals R8; and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO and SO2, and optionally also 1 or 2 groups C═O and/or C═S, as ring members, where the heterocyclic ring may be substituted with one or more substituents R10; each R7 is independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6-alkyl, fluorinated C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C3-C8-cycloalkenyl, fluorinated C3-C8-cycloalkenyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, C1-C6-alkylthio, fluorinated C1-C6-alkylthio, C1-C6-alkylsulfinyl, fluorinated C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsulfonyl, —NR11aR11b, —CH2NR11aR11b, —NR11aC(O)R9, —C(═O)R9, SO2NR11aR11b, C1-C6-alkylcarbonyloxy, fluorinated C1-C6-alkylcarbonyloxy, phenyl, phenyl-C1-C2-alkyl, phenoxy, phenylsulfonyl, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the six last-mentioned radicals my be substituted with one or more substituents R10; each R8 is independently selected from the group consisting of halogen, cyano, hydroxy, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2,-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6 -alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, —NR11aR11b, —CH2NR11aR11b, phenyl, phenyl-C1-C2-alkyl, phenoxy, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the five last-mentioned radicals may be substituted with one or more substituents R10; or two radicals R8 bound to the same carbon atom may form together a group ═O or ═S; each R9 is independently selected from the group consisting of hydrogen, cyano, hydroxy, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, —NR11aR11b, —CH2NR11aR11b, phenyl, phenyl-C1-C2-alkyl, phenoxy, benzyloxy and a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated ring containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members, where the cyclic moieties in the five last-mentioned radicals may be substituted with one or more substituents R10; each R10 is independently selected from the group consisting of halogen, cyano, nitro, hydroxy, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6-alkoxy-C1-C4-alkyl, fluorinated C1-C6-alkoxy-C1-C4-alkyl, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, C1-C6-alkylthio, fluorinated C1-C6-alkylthio, C1-C6-alkylsulfinyl, fluorinated C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, fluorinated C1-C6-alkylsuifonyl, —COOH, —NR11aR11b, —CH2NR11aR11b, C1-C6-alkylcarbonyl, fluorinated C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, fluorinated C1-C6-alkoxycarbonyl, SO2NR11aR11b, C1-C6-alkylcarbonyloxy and fluorinated C1-C6-alkylcarbonyloxy; or two radicals R10, together with the atom(s) they are bound to, form a saturated, partially unsaturated or maximally unsaturated 3-, 4-, 5-, 6- or 7-membered carbocyclic or heterocyclic ring, where the heterocyclic ring contains 1, 2 or 3 heteroatoms or heteroatom groups independently selected from N, O, S, NO, SO, SO2, C═O and C═S as ring members; R11a and R11b, independently of each other and independently of each occurrence, are selected from the group consisting of hydrogen, cyano, C1-C6-alkyl, fluorinated C1-C6-alkyl, C2-C6-alkenyl, fluorinated C2-C6-alkenyl, C2-C6-alkynyl, fluorinated C2-C6-alkynyl, C3-C8-cycloalkyl, fluorinated C3-C8-cycloalkyl, C1-C6-alkoxy, fluorinated C1-C6-alkoxy, C1-C6-alkylcarbonyl, fluorinated C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, fluorinated C1-C6-alkoxycarbonyl, phenyl and benzyl, where the phenyl moieties in the two last-mentioned radicals may carry 1, 2 or 3 substituents selected from halogen, cyano nitro, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-alkoxy and fluorinated C1-C6-alkoxy; or, if R11a and R11b are hound to the same nitrogen atom, together with this nitrogen atom may form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or maximally unsaturated heterocyclic ring, where the ring may further contain 1, 2, 3 or 4 heteroatoms or heteroatom-containing groups selected from O, S, N, SO, SO2, C═O and C═S as ring members, and where the ring may be substituted with one or more substituents selected from halogen, cyano nitro, C1-C6-alkyl, fluorinated C1-C6-alkyl, C1-C6-alkoxy and fluorinated C1-C6-alkoxy; a is 0, 1 or 2; and b is 0, 1, 2 or 3; or an N-oxide, a tautorneric form, a stereoisomer or a pharmaceutically acceptable salt thereof.
地址 Wiesbaden DE