1-{4-[(4-methylbenzyl)oxy]phenyl}-N-(piperidin-4-ylmethyl)methanamine | 924855-67-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-{4-[(4-methylbenzyl)oxy]phenyl}-N-(piperidin-4-ylmethyl)methanamine
• 英文别名: N-[[4-[(4-methylphenyl)methoxy]phenyl]methyl]-1-piperidin-4-ylmethanamine
• CAS: 924855-67-4
• 化学式: C₂₁H₂₈N₂O
• 分子量: 324.466
• InChiKey: WBNXAOHQUDYELA-UHFFFAOYSA-N

物化性质

• 沸点：
  473.0±30.0 °C(Predicted)
• 密度：
  1.044±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  33.3
• 氢给体数：
  2
• 氢受体数：
  3

文献信息

• Efflux-pump inhibitors and therapeutic uses thereof
  申请人：Basilea Pharmaceutica International AG

  公开号：US10464896B2

  公开（公告）日：2019-11-05

  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; R12, R13 represent independently at each occurrence hydrogen or C1-C6alkyl; R14 represents independently at each occurrence halogen, cyano, hydroxyl, C1-C6alkoxy, C1-C6haloalkoxy, C3-C8cycloalkyl, —C(O)OR11, —CHO, —C(O)N(R12)R13, —C1-C6alkylene-N(R12)R13, Cycle-P, O-Cycle-P, Cycle-Q or O-Cycle-Q; Cycle-P represents independently at each occurrence a saturated or partially unsaturated C3-C8 carbocyclic ring optionally substituted by 1 to 3 R18, or a saturated or partially unsaturated C3-C8 heterocyclic ring optionally substituted by 1 to 3 R18 containing carbon atoms as ring members and one or two ring members independently selected from N(R9)(R12), N(R9) and O; Cycle-Q represents independently at each occurrence phenyl optionally substituted by 1 to 3 R19 or a 5- to 6-membered heteroaryl ring containing one to four heteroatoms selected from O, S and N, optionally substituted by 1 to 3 R19; R15 represents independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R16 and R17 represent independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R18 and R19 represent independently at each occurrence halogen, cyano, hydroxyl, oxo, amino, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy or —CO(O)R11; R20 represents independently at each occurrence hydrogen or methyl; R21 represents N(R20)2 or CH2-N(R20)2; LI represents —CH═CH—, —CH2-O—, —O—CH2-, —CH2-O—CH2-, —CH2-S—, —S—CH2-, —CH2-S(O)—, —CH2-S(O2)-, —S(O)—CH2-; —S(O2)-CH2-, —C(CH3)(CH3)-, —C(═O)—NH—, —NH—C(═O)—, —CH2-CH2-, —CH═CH—CH2-, —CH2-NH—C(═O)—, —C(═O)—NH—CH2, —C≡C—, —S(O2)-NH—CH2-, —S(O2)-NH, —O—CH2-CH2-O—, —O—, —NH— CH2-, —CH2-NH—, —CH2-CH2-O—, or —NH—C(═O)—CH2-O—, or a bond; L2 represents C1-C7alkylene, wherein one or more CH2 moieties in the alkylene are optionally replaced independently by —N(R9)(R20)-, —CH(N(R9)(R20)(R20))-, or —C(═O)—, wherein within L2 there are no adjacent C(═O) moieties or adjacent —N(R9)(R20)— moieties, and wherein the terminal moiety of L2 is not —N(R9) (R20)-, or L2 represents —O—C1-C6alkylene-, or L2 represents a bond, providing that X represents —CH2- when L2 is a bond; as well as methods of using the compounds of formula I for treating or preventing bacterial infections.

  本发明涉及式I化合物或其药学上可接受的盐、溶液或水合物，其中ASC为-N(R8)(R9)ASC-1 ASC-1为 环A代表除氮原子外含有碳原子作为环成员的4至6元饱和环，其中环A中的一个CH2分子任选被CH(R21)取代，环A中不与氮原子相邻的一个碳原子任选被O取代，其中环A通过一个碳原子与X连接；X代表键、- -或-C(═O)-； AR1、AR2 独立地代表苯基或含有一至三个选自 O、S 和 N 的杂原子的 5 至 6 元杂芳基环，其中 AR1 通过一个碳原子与 L1 连接，AR2 通过一个碳原子与 L1 和 L2 连接；R1、R2、R3 独立地代表氢、卤素、氰基、羟基、C1-C6 烷基、C1-C6 卤代烷基、C3-C8 环烷基、C1-C6 烷氧基、C1-C6 卤代烷氧基、-C1-C6 亚烷基-N(R12)R13、-N(R12)R13、-C(O)OR111、-C(O)N(R12)R13、-S(O)OR11 或苯基；R4 代表羟基、氢、卤素、硝基、氰基、氨基、被 1 至 5 个 R14 任选取代的 C1-C6 烷基、被 1 至 5 个 R14 任选取代的 C2-C6 烯基、被 1 至 5 个 R14 任选取代的 C2-C6 烷炔基、被 1 至 5 个 R14 任选取代的 C1-C6 烷氧基、被 1 至 5 个 R14 任选取代的 C2-C6 烷氧基、被 1 至 5 个 R14 任选取代的 C2-C6 烷炔氧基、-C(O)OR15、-CHO、-C(O)N(R16)R17、-C1-C6 亚烷基-N(R9)(R16)R17、-O-Cycle-P 或 -O-Cycle-Q；R5、R6、R7 独立地代表氢、卤素、氰基、C1-C6烷基、C1-C6 卤代烷基、C1-C6 烷氧基或 C1-C6 卤代烷氧基；R8 代表氢、甲基或 ASC-1；R9 代表甲基或不存在，其中当 R9 存在时，相应的氮原子带有正电荷；R10 代表氢或甲基；R11 在每次出现时独立地代表氢或 C1-C6 烷基；R12、R13在每次出现时独立地代表氢或C1-C6烷基；R14在每次出现时独立地代表卤素、氰基、羟基、C1-C6烷氧基、C1-C6卤代烷氧基、C3-C8环烷基、-C(O)OR11、-CHO、-C(O)N(R12)R13、-C1-C6亚烷基-N(R12)R13、Cycle-P、O-Cycle-P、Cycle-Q或O-Cycle-Q；Cycle-P 在每次出现时独立地代表被 1 至 3 个 R18 任选取代的饱和或部分不饱和 C3-C8 碳环，或被 1 至 3 个 R18 任选取代的饱和或部分不饱和 C3-C8 杂环，该杂环含有作为环成员的碳原子和一个或两个独立选自 N(R9)(R12)、N(R9) 和 O 的环成员；Cycle-Q 在每次出现时均独立地代表被 1 至 3 个 R19 任选取代的苯基或含有 1 至 4 个选自 O、S 和 N 的杂原子的 5 至 6 元杂芳基环；R15 独立地在每次出现时代表氢或被 1 至 5 个 R14 任选取代的 C1-C6 烷基；R16 和 R17 独立地在每次出现时代表氢或被 1 至 5 个 R14 任选取代的 C1-C6 烷基；R18 和 R19 独立地在每次出现时代表卤素、氰基、羟基、氧代、氨基、C1-C4 烷基、C1-C4 卤代烷基、C1-C4 烷氧基、C1-C4 卤代烷氧基或-CO(O)R11；R20 独立地在每次出现时代表氢或甲基；R21 代表 N(R20)2 或 -N(R20)2； LI 代表 -CH═CH-、- -O-、-O- -、- -O- -、- -S-、-S- -、- -S(O)-、- -S(O2)-、-S(O)- -；-S(O2)- -，-C(CH3)( )-，-C(═O)-NH-，-NH-C(═O)-，- - -，-CH═ -，- -NH-C(═O)-，-C(═O)-NH- ，-C≡C-、-S(O2)-NH- -，-S(O2)-NH，-O- - -O-，-O-，-NH- -，- -NH-，- - -O-，或-NH-C(═O)- -O-，或键；L2 代表 C1-C7 亚烷基，其中亚烷基中的一个或多个 基团可选择地独立地被 -N(R9)(R20)-、-CH(N(R9)(R20)(R20))- 或 -C(═O)-取代，其中在 L2 内没有相邻的 C(═O) 基团或相邻的 -N(R9)(R20)- 基团、其中 L2 的末端分子不是-N(R9) (R20)-，或者 L2 代表-O-C1-C6 亚烷基-，或者 L2 代表键，条件是当 L2 为键时 X 代表- -；以及使用式 I 化合物治疗或预防细菌感染的方法。
• EFFLUX-PUMP INHIBITORS AND THERAPEUTIC USES THEREOF
  申请人：Basilea Pharmaceutica International AG

  公开号：US20180179158A1

  公开（公告）日：2018-06-28

  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; R12, R13 represent independently at each occurrence hydrogen or C1-C6alkyl; R14 represents independently at each occurrence halogen, cyano, hydroxyl, C1-C6alkoxy, C1-C6haloalkoxy, C3-C8cycloalkyl, —C(O)OR11, —CHO, —C(O)N(R12)R13, —C1-C6alkylene-N(R12)R13, partially unsaturated C3-C8 carbocyclic ring optionally substituted by 1 to 3 R18, or a saturated or partially unsaturated C3-C8 heterocyclic ring optionally substituted by 1 to 3 R18 containing carbon atoms as ring members and one or two ring members independently selected from N(R9)(R12), N(R9) and O; Cycle-Q represents independently at each occurrence phenyl optionally substituted by 1 to 3 R19 or a 5- to 6-membered heteroaryl ring containing one to four heteroatoms selected from O, S and N, optionally substituted by 1 to 3 R19; R15 represents independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R16 and R17 represent independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R18 and R19 represent independently at each occurrence halogen, cyano, hydroxyl, oxo, amino, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy or —CO(O)R11; R20 represents independently at each occurrence hydrogen or methyl; R21 represents N(R20)2 or CH2-N(R20)2; LI represents —CH═CH—, —CH2-O—, —O—CH2-, —CH2-O—CH2-, —CH2-S—, —S—CH2-, —CH2-S(O)—, —CH2-S(O2)-, —S(O)—CH2-; —S(O2)-CH2-, —C(CH3)(CH3)-, —C(═O)—NH—, —NH—C(═O)—, —CH2-CH2-, —CH═CH—CH2-, —CH2-NH—C(═O)—, —C(═O)—NH—CH2, —C═C—, —S(O2)-NH—CH2-, —S(O2)-NH, —O—CH2-CH2-O—, —O—, —NH— CH2-, —CH2-NH—, —CH2-CH2-O—, or —NH—C(═O)—CH2-O—, or a bond; L2 represents C1-C7alkylene, wherein one or more CH2 moieties in the alkylene are optionally replaced independently by —N(R9)(R20)-, —CH(N(R9)(R20)(R20))-, or —C(═O)—, wherein within L2 there are no adjacent C(═O) moieties or adjacent —N(R9)(R20)— moieties, and wherein the terminal moiety of L2 is not —N(R9) (R20)-, or L2 represents —O—C1-C6alkylene-, or L2 represents a bond, providing that X represents —CH2- when L2 is a bond; as well as methods of using the compounds of formula I for treating or preventing bacterial infections.