[2-(cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-yl]-acetonitrile | 925418-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [2-(cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-yl]-acetonitrile
• 英文别名: 2-[2-(Cyclohexyl-hydroxy-phenylmethyl)-1,3-oxazol-5-yl]acetonitrile
• CAS: 925418-89-9
• 化学式: C₁₈H₂₀N₂O₂
• 分子量: 296.369
• InChiKey: LOOQCAWZYRLGOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  490.6±45.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [2-(cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-yl]-acetonitrile 在 dimethyl sulfide borane 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以67%的产率得到[5-(2-amino-ethyl)-oxazol-2-yl]-cyclohexyl-phenyl-methanol
  参考文献：
  名称：

  WO2008/96128

  摘要：

  公开号：
• 作为产物：
  描述：

  (5-bromomethyl-oxazol-2-yl)-cyclohexyl-phenyl-methanol 、 氰化钠 以 industrial methylated spirit (IMS) 为溶剂， 反应 1.0h， 以79%的产率得到[2-(cyclohexyl-hydroxy-phenyl-methyl)-oxazol-5-yl]-acetonitrile
  参考文献：
  名称：

  WO2008/96093

  摘要：

  公开号：

文献信息

• 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 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。
• WO2007/17669
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] AZOLE AND THIAZOLE DERIVATIVES AND THEIR USE<br/>[FR] DERIVES D'AZOLE ET DE THIAZOLE ET UTILISATION DE CEUX-CI
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2007017669A1

  公开（公告）日：2007-02-15

  [EN] 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-_[AE11]C(O)O-R⁷, or -Z-C(O)-R⁷; and R³ is a lone pair, or C₁C₆-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-_[AE12]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-_[AE13]C(O)O-R⁷; or; -Z-C(O)-R⁷; and R³ is a lone pair, or C₁-C₆-aIkyl; R⁴ and R⁵ are independently selected from the group consisting of aryl, arytfused-heterocycloalkyl, heteroaryl, C₁-C₆-alkyl, cycloalkyl; R⁶ is -OH, C₁-C₆-alkyl, C₁-C₆-alkoxy, hydroxy-C₁-C₆-alkyl, nitrile, a group CONR⁸
  [FR] L'invention concerne des composés représentés par la formule (I), qui sont utiles pour traiter des maladies comportant une activation accrue des récepteurs M3, telles que les maladies des voies respiratoires. Dans la formule, (1) R¹ représente alkyle en C₁-C₆ ou hydrogène; et R² représente hydrogène ou un groupe -R⁷, -Z-Y-R⁷, -Z-NR⁹R¹⁰; -Z-CO-NR⁹R¹⁰, -Z-NR⁹-_[AE11]C(O)O-R⁷ ou -Z-C(O)-R⁷; et R³ représente un doublet libre ou alkyle en C₁-C₆; ou (2) R¹ et R³ forment ensemble un cycle hétérocycloalkyle avec l'atome d'azote auquel ils sont liés, et R² représente un doublet libre ou un groupe -R⁷, -Z-Y-R⁷, -Z-NR⁹R¹⁰, -Z-CO-NR⁹R¹⁰, -Z-NR⁹-_[AE12]C(O)O-R⁷ ou -Z-C(O)-R⁷; ou (3) R¹ et R² forment ensemble un cycle hétérocycloalkyle avec l'atome d'azote auquel ils sont liés, ledit cycle étant substitué par un groupe -Y-R⁷, -Z-Y-R⁷, -Z-NR⁹R¹⁰; -Z-CO-NR⁹R¹⁰; -Z-NR⁹-_[AE13]C(O)O-R⁷ ou -Z-C(O)-R⁷; et R³ représente un doublet libre ou aIkyle en C₁-C₆; R⁴ et R⁵ sont sélectionnés indépendamment dans le groupe constitué par aryle, aryle condensé-hétérocycloalkyle, hétéroaryle, alkyle en C₁-C₆, cycloalkyle; R⁶ représente -OH, alkyle en C₁-C₆, alcoxy en C₁-C₆, hydroxy-C₁-C₆-alkyle, nitrile, un groupe CONR⁸