[2-((S)-cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]-dimethyl-(3-phenoxy-propyl)-ammonium bromide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [2-((S)-cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]-dimethyl-(3-phenoxy-propyl)-ammonium bromide
• 英文别名: [2-((R)-cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]-dimethyl-(3-phenoxy-propyl)-ammonium bromide；[2-[(R)-cyclohexyl-hydroxy-phenylmethyl]-1,3-oxazol-5-yl]methyl-dimethyl-(3-phenoxypropyl)azanium;bromide
• 化学式: Br*C₂₈H₃₇N₂O₃
• 分子量: 529.517
• InChiKey: APJGCTYGKOXHNB-JCOPYZAKSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.54
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2-((S)-cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]-dimethyl-(3-phenoxy-propyl)-ammonium bromide 在 水 、 silver(l) oxide 作用下， 反应 5.0h， 生成
  参考文献：
  名称：

  WO2007/17669

  摘要：

  公开号：
• 作为产物：
  描述：

  (R)-cyclohexyl-(5-dimethylaminomethyl-oxazol-2-yl)-phenyl-methanol 、 3-苯氧基溴丙烷 在 乙醚 、 methanol-dichloromethane 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 22.0h， 生成 [2-((S)-cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-ylmethyl]-dimethyl-(3-phenoxy-propyl)-ammonium bromide
  参考文献：
  名称：

  COMBINATION OF A MUSCARINIC RECEPTOR ANTAGONIST AND A BETA-2-ADRENOCEPTOR AGONIST

  摘要：

  该发明提供了一种药品、试剂盒或组合物，包括第一活性成分，该成分为选择的肌动蛋白受体拮抗剂，以及第二活性成分，该成分为β2-肾上腺素能受体激动剂，用于治疗慢性阻塞性肺疾病和哮喘等呼吸系统疾病。

  公开号：

  US20110046191A1

文献信息

• Pharmaceutical Product Comprising a P38 Kinase Inhibitor and a Second Active Ingredient
  申请人：Cooper Anne Elizabeth

  公开号：US20120028941A1

  公开（公告）日：2012-02-02

  The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclopropyl-3-fluoro-4-methyl-5[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a β2 adrenoceptor agonist; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DPI antagonist; an Histone Deacetylase activator; an IKK2 kinase inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; a MABA compound; an MPO inhibitor; a muscarinic antagonist; a PDE4 inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

  该发明提供了一种制药产品、套装或组合物，包括第一活性成分N-环丙基-3-氟-4-甲基-5-[3-[[1-[2-[2-(甲氨基)乙氧基]苯基]环丙基]氨基]-2-氧代-1(2H)-吡嗪基]-苯甲酰胺或其盐，以及从以下选取的第二活性成分：非类固醇糖皮质激素受体（GR受体）激动剂；抗氧化剂；β2肾上腺素受体激动剂；CCR1拮抗剂；趋化因子拮抗剂（非CCR1）；皮质类固醇；CRTh2拮抗剂；DPI拮抗剂；组蛋白去乙酰化酶激活剂；IKK2激酶抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MABA化合物；MPO抑制剂；毛细血管抗药性剂；PDE4抑制剂；PPARγ激动剂；蛋白酶抑制剂；他汀类药物；前列腺素拮抗剂；扩血管剂；或者ENAC拮抗剂（上皮钠通道拮抗剂）；以及其在呼吸系统疾病治疗中的用途。
• Azole and Thiazole Derivatives and Their Use
  申请人：Ray Nicholas Charles

  公开号：US20100113540A1

  公开（公告）日：2010-05-06

  Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiratory tract diseases: wherein (i) R 1 is C 1 -C 6 -alkyl or hydrogen; and R 2 is hydrogen or a group —R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 ; —Z—CO—NR 9 R 10 , —Z—NR 9 — [AE11] C(O)O—R 7 , or —Z—C(O)—R 7 ; and R 3 is a lone pair, or C 1 C 6 -alkyl; or (ii) R 1 and R 3 together with the nitrogen to which they are attached form a heterocycloalkyl ring and R 2 is a lone pair or a group —R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 , —Z—CO—NR 9 R 10 , —Z—NR 9 — [AE12] C(O)O—R 7 ; or; —Z—C(O)—R 7 ; or (iii) R 1 and R 2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group —Y—R 7 , —Z—Y—R 7 , —Z—NR 9 R 10 ; —Z—CO—NR 9 R 10 ; —Z—NR 9 — [AE13] C(O)O—R 7 ; or; —Z—C(O)—R 7 ; and R 3 is a lone pair, or C 1 -C 6 -alkyl; R 4 and R 5 are independently selected from the group consisting of aryl, ary-tfused-heterocycloalkyl, heteroaryl, C 1 -C 6 -alkyl, cycloalkyl; R 6 is —OH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy-C 1 -C 6 -alkyl, nitrile, a group CONR 8 2 or a hydrogen atom; A is an oxygen or a sulfur atom; X is an alkylene, alkenylene or alkynylene group; R 7 is an C 1 -C 6 -alkyl, aryl, aryl-fused-cycloalkyl, aryl-fused-heterocycloalkyl, heteroaryl, aryl(C 1 -C 8 -alkyl)-, heteroaryl(C 1 -C 8 -alkyl)-, cycloalkyl or heterocycloalkyl group; R 8 is C 1 -C 6 -alkyl or a hydrogen atom; Z is a C 1 -C 16 -alkylene, C 2 -C 16 -alkenylene or C 2 -C 16 -alkynylene group; Y is a bond or oxygen atom; R 9 and R 10 are independently a hydrogen atom, C 1 -C 6 -alkyl, aryl, aryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl, heteroaryl, aryl(C 1 -C 6 -alkyl)-, or heteroaryl(C 1 -C 6 -alkyl)- group; or R 9 and R 10 together with the nitrogen atom to which they are attached form a heterocyclic ring of 48 atoms, optionally containing a further nitrogen or oxygen atom.

  式（I）的化合物在治疗呼吸道疾病等需要增强M3受体激活的疾病中有用，其中（i）R1为C1-C6烷基或氢，R2为氢或基团-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE11]C（O）O-R7或-Z-C（O）-R7，R3为孤对电子或C1-C6烷基；或（ii）R1和R3与它们连接的氮一起形成杂环烷基环，R2为孤对电子或基团-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE12]C（O）O-R7或-Z-C（O）-R7；或（iii）R1和R2与它们连接的氮一起形成杂环烷基环，该环被基团-Y-R7、-Z-Y-R7、-Z-NR9R10、-Z-CO-NR9R10、-Z-NR9-[AE13]C（O）O-R7或-Z-C（O）-R7取代，R3为孤对电子或C1-C6烷基；R4和R5独立地选自芳基、芳基融合的杂环烷基、杂芳基、C1-C6烷基、环烷基；R6为-OH、C1-C6烷基、C1-C6-烷氧基、羟基-C1-C6烷基、腈基、基团CONR82或氢原子；A为氧原子或硫原子；X为烷基、烯基或炔基；R7为C1-C6烷基、芳基、芳基融合的环烷基、芳基融合的杂环烷基、杂芳基、芳基（C1-C8烷基）-、杂芳基（C1-C8烷基）-、环烷基或杂环烷基；R8为C1-C6烷基或氢原子；Z为C1-C16烷基、C2-C16烯基或C2-C16炔基；Y为键或氧原子；R9和R10独立地为氢原子、C1-C6烷基、芳基、芳基融合的杂环烷基、芳基融合的环烷基、杂芳基、芳基（C1-C6烷基）-或杂芳基（C1-C6烷基）-基团；或R9和R10与它们连接的氮原子一起形成48个原子的杂环，可选地含有进一步的氮或氧原子。
• AZOLE AND THIAZOLE DERIVATIVES AND THEIR USE
  申请人：Ray Nicholas Charles

  公开号：US20120277275A1

  公开（公告）日：2012-11-01

  Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiratory tract diseases:

  式(I)的化合物在治疗呼吸道疾病等需要增强M3受体激活的疾病中很有用。
• PHARMACEUTICAL PRODUCT COMPRISING A P38 KINASE INHIBITOR AND A SECOND ACTIVE INGREDIENT
  申请人：AstraZeneca AB

  公开号：US20150141387A1

  公开（公告）日：2015-05-21

  The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a β2 adrenoceptor agonist; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DPI antagonist; an Histone Deacetylase activator; an IKK2 kinase inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; a MABA compound; an MPO inhibitor; a muscarinic antagonist; a PDE4 inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

  本发明提供一种药物产品、试剂盒或组合物，包括第一种活性成分 N-环丙基-3-氟-4-甲基-5-[3-[[1-[2-[2-(甲基氨基)乙氧]苯基]环丙基]氨基]-2-氧代-1(2H)-吡嗪基]-苯甲酰胺或其盐，以及从以下选择的第二种活性成分：非类固醇糖皮质激素受体（GR受体）激动剂；抗氧化剂；β2肾上腺素受体激动剂；CCR1拮抗剂；趋化因子拮抗剂（不包括CCR1）；类固醇激素；CRTh2拮抗剂；DPI拮抗剂；组蛋白去乙酰化酶激活剂；IKK2激酶抑制剂；COX抑制剂；脂氧合酶抑制剂；白三烯受体拮抗剂；MABA化合物；MPO抑制剂；毒蕈碱受体拮抗剂；PDE4抑制剂；PPARγ激动剂；蛋白酶抑制剂；他汀类药物；血栓素拮抗剂；扩血管剂；或EPIthelial Sodium-channel拮抗剂（ENAC拮抗剂）；以及其在呼吸系统疾病治疗中的用途。
• PHARMACEUTICAL COMPOSITION FOR INHALATION COMPRISING AN OXAZOLE OR THIAZOLE M3 MUSCARINIC RECEPTOR ANTAGONIST
  申请人：Pulmagen Therapeutics (Synergy) Limited

  公开号：EP2280006A1

  公开（公告）日：2011-02-02

  Pharmaceutical compositions for inhalation comprising compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiritory tract diseases: wherein (i) R1 is C1-C6-alkyl or hydrogen; and R2 is hydrogen or a group -R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10, -Z-NR9-C(O)O-R7, or -Z-C(O)-R7; and R3 is a lone pair, or C1-C6-alkyl; or (ii) R1 and R3 together with the nitrogen to which they are attached form a heterocycloalkyl ring, and R2 is a lone pair or a group -R7, -Z-Y-R7, -Z-NR9R10, -Z-CO-NR9R10, -Z-NR9-C(O)O-R7; or; -Z-C(O)-R7; or (iii) R1 and R2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group -Y-R7, -Z-Y-R7, -Z-NR9R10; -Z-CO-NR9R10; -Z-NR9-C(O)OR7; or; -Z-C(O)-R7; and R3 is a lone pair, or C1-C6-alkyl; R4 and R5 are independently selected from the group consisting of aryl, aryl-fused-heterocycloalkyl, heteroaryl, C1-C6-alkyl, cycloalkyl; R6 is -OH, C1-C6-alkyl, C1-C6-alkoxy, hydroxy-C1-C6-alkyl, nitrile, a group CONR82 or a hydrogen atom; A is an oxygen or a sulfur atom; X is an alkylene, alkenylene or alkynylene group; R7 is an C1-C6-alkyl, aryl, aryl-fused-cycloalkyl, aryl-fused-heterocycloalkyl, heteroaryl, aryl(C1-C8-alkyl)-, heteroaryl(C1-C8-alkyl)-, cycloalkyl or heterocycloalkyl group; R8 is C1-C6-alkyl or a hydrogen atom; Z is a C1-C16-alkylene, C2-C16-alkenylene or C2-C16-alkynylene group; Y is a bond or oxygen atom; R9 and R10 are independently a hydrogen atom, C1-C6-alkyl, aryl, aryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl, heteroaryl, aryl(C1-C6-alkyl)-, or heteroaryl(C1-C6-alkyl)- group; or R9 and R10 together with the nitrogen atom to which they are attached form a heterocyclic ring of 4-8 atoms, optionally containing a further nitrogen or oxygen atom.

  由式（I）化合物组成的吸入用药物组合物可用于治疗与 M3 受体激活增强有关的疾病，如呼吸道疾病： 其中 (i) R1 是 C1-C6- 烷基或氢；R2 是氢或基团 -R7、-Z-Y-R7、 -Z-CO-NR9R10，-Z-NR9-C(O)O-R7，或-Z-C(O)-R7；R3 是孤对或 C1-C6-烷基；或 (ii) R1 和 R3 与它们所连接的氮一起形成杂环烷基环，R2 是孤对或基团 -R7，-Z-Y-R7，-Z-NR9R10、 -Z-CO-NR9R10、-Z-NR9-C(O)O-R7；或；-Z-C(O)-R7；或 (iii) R1 和 R2 与它们所连接的氮一起形成杂环烷基环，所述环被基团 -Y-R7、-Z-Y-R7、-Z-NR9R10 取代；-Z-CO-NR9R10；-Z-NR9-C(O)OR7；或；-Z-C(O)-R7；R4 和 R5 独立地选自由芳基、芳基-融合-杂环烷基、杂芳基、C1-C6-烷基、环烷基组成的组；R6 是-OH、C1-C6-烷基、C1-C6-烷氧基、羟基-C1-C6-烷基、腈、基团 CONR82 或氢原子；A 是氧原子或硫原子；X 是亚烷基、烯基或炔基；R7 是 C1-C6 烷基、芳基、芳基-融合环烷基、芳基-融合杂环烷基、杂芳基、芳基（C1-C8-烷基）-、杂芳基（C1-C8-烷基）-、环烷基或杂环烷基；R8 是 C1-C6 烷基或氢原子；Z 是 C1-C16 烯基、C2-C16 烯基或 C2-C16 烯炔基；Y 是键或氧原子；R9 和 R10 独立地为氢原子、C1-C6-烷基、芳基、芳基-熔合杂环烷基、芳基-熔合环烷基、杂芳基、芳基（C1-C6-烷基）- 或杂芳基（C1-C6-烷基）- 基团；或 R9 和 R10 与它们所连接的氮原子一起形成一个 4-8 个原子的杂环，可选地含有另一个氮原子或氧原子。