1-benzhydryl-3-(3-fluorophenoxy)azetidine

• 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-benzhydryl-3-(3-fluorophenoxy)azetidine
• 英文别名: 1-(diphenylmethyl)-3-[3-(fluoro)phenoxy]azetidine；3-(3-fluorophenoxy)-1-(diphenylmethyl)azetidine
• 化学式: C₂₂H₂₀FNO
• 分子量: 333.405
• InChiKey: BHELLAOXDCZWRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzhydryl-3-(3-fluorophenoxy)azetidine 在 palladium 10% on activated carbon 甲酸铵 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 3-(3-fluorophenoxy)azetidine hydrochloride
  参考文献：
  名称：

  AMINO-HETEROCYCLIC COMPOUNDS

  摘要：

  这项发明提供了式（I）中的PDE9抑制化合物，以及其药学上可接受的盐，其中R1、R2、R3、A和n的定义如本文所述。还提供了含有式I中化合物的药物组合物，并且提供了在治疗神经退行性和认知障碍疾病，如阿尔茨海默病和精神分裂症中的用途。

  公开号：

  US20100190771A1
• 作为产物：
  描述：

  1-(diphenylmethyl)-3-methane sulfonyl azetidine 、 3-氟苯酚 在 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 生成 1-benzhydryl-3-(3-fluorophenoxy)azetidine
  参考文献：
  名称：

  [(Indol-3-yl)-cycloalkyl]-3-substituted azetidines for the treatment of central nervous system disorders

  摘要：

  这项发明提供了新型化合物、药物组合物和使用这些化合物治疗中枢神经系统疾病（如焦虑和抑郁症）的方法，其中所述化合物具有如下结构式I：其中：X为N—R、O、S(O)m；m为0至2；n为0至4；Ar为含有6至12个碳原子的芳基基团，可选择地取代1至3个R3基团，或含有4至10个碳原子的杂环基团，可选择地取代1至3个R3基团；R和R2独立地为H、1至6个碳原子的直链烷基、3至6个碳原子的支链烷基、3至6个碳原子的环烷基、1至6个碳原子的烷氧羰基、1至6个碳原子的烷基羰基、氨基羰基或1至4个碳原子的烷基氨基羰基；R1和R3独立地为H、1至4个碳原子的直链烷基、3至6个碳原子的支链烷基、3至8个碳原子的环烷基、卤素、1至4个碳原子的烷氧基、1至4个碳原子的卤代烷基、OH、硝基、氨基、磺酰基、CN、羧基、1至4个碳原子的烷氧羰基、1至4个碳原子的烷基羰基、氨基羰基或1至4个碳原子的烷基氨基羰基；或其药学上可接受的盐。

  公开号：

  US06245799B1

文献信息

• PYRIDINE AMIDE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS
  申请人：Borriello Manuela

  公开号：US20130261100A1

  公开（公告）日：2013-10-03

  The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is —O—, —O(C1-C3 alkyl)-; —(C1-C3 alkyl)O—; —C(O)—; —C(═N—O(C1-C3 alkyl))-; —NH— or —NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, —NH(C1-C3alkyl)-; —N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is covalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, endometriosis and migraine.

  该发明涉及式(I)的吡啶酰胺衍生物或其药学上可接受的盐，其中R1和R2独立地为氢、直链或支链(C1-C3)烷基，或者它们结合在一起形成环丙基环；R独立地选自卤素和三氟甲基的群，p为1、2或3；A为C或N；E为式(B)或(C)的基团，其中B为C(O)OH、C(O)O(C1-C3)烷基，C选自式(I)的群，m为1、2或3，n为0或1，W为—O—、—O(C1-C3烷基)-、—(C1-C3烷基)O—、—C(O)—、—C(═N—O(C1-C3烷基))-、—NH—或—NH(C1-C3烷基)-；Ar为苯基，可选地取代一个或多个取代基，选自卤素、三氟甲基、三氟甲氧基、甲基、—NH(C1-C3烷基)-、—N(C1-C3烷基)(C1-C3烷基)-，a为含有一个氮原子的5至7元杂环，与Ar共价键合，可选地含有一个或两个来自N、O和S的杂原子；以及含有1至3个来自S、O和N的杂原子的5-或6元杂芳环，该杂芳环被选自(C1-C3)烷基、(C3-C5)环烷氧基、(C1-C3)烷基羰基的一或两个取代基取代。该发明的化合物可用于制造用于治疗需要使用EP4受体拮抗剂的病理病变的药物，例如治疗急性和慢性疼痛、炎症性疼痛、骨关节炎、与炎症相关的疾病如关节炎、类风湿性关节炎、癌症、子宫内膜异位症和偏头痛。
• [EN] PYRIDINE AMIDE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE PYRIDINAMIDE EN TANT QU'ANTAGONISTES DE RÉCEPTEUR EP4
  申请人：ROTTAPHARM SPA

  公开号：WO2012076063A1

  公开（公告）日：2012-06-14

  The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is -O-, -O(C1-C3 alkyl)-; -(C1-C3 alkyl)O-; -C(O)-; -C(=N-O(C1-C3 alkyl))-; -NH- or -NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, -NH(C1-C3alkyl)-; -N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is convalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid artrhritis, cancer, endometriosis and migraine.

  该发明涉及式(I)的吡啶酰胺衍生物或其药学上可接受的盐，其中R1和R2独立地为氢、直链或支链(C1-C3)烷基，或者它们结合在一起形成环丙基环；R独立地选自卤素和三氟甲基的群，p为1、2或3；A为C或N；E为式(B)或(C)的基团，其中B为C(O)OH、C(O)O(C1-C3)烷基，C选自式(I)的群，m为1、2或3，n为0或1，W为-O-、-O(C1-C3烷基)-、-(C1-C3烷基)O-、-C(O)-、-C(=N-O(C1-C3烷基))-、-NH-或-NH(C1-C3烷基)-；Ar为苯基，可选择地取代一个或多个取代基，选自卤素、三氟甲基、三氟甲氧基、甲基、-NH(C1-C3烷基)-、-N(C1-C3烷基)(C1-C3烷基)-，a为含有一个氮原子的5至7元杂环环，与Ar共价键合，可选择地含有一个或两个来自N、O和S的杂原子；以及含有1至3个来自S、O和N的杂原子的5-或6元杂芳环，该杂芳环被选自(C1-C3)烷基、(C3-C5)环烷氧基、(C1-C3)烷基羰基的一或两个取代基取代。该发明的化合物可用于制造用于治疗需要使用EP4受体拮抗剂的病理的药物，例如治疗急性和慢性疼痛、炎症性疼痛、骨关节炎、关节炎、类风湿性关节炎、癌症、子宫内膜异位症和偏头痛。
• Amino-Heterocyclic Compounds
  申请人：Claffey Michelle Marie

  公开号：US20120329777A1

  公开（公告）日：2012-12-27

  The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , A, and n are as defined herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in treating neurodegenerative and cognitive disorders, such as Alzheimer's disease and schizophrenia, are also provided.

  本发明提供了PDE9抑制化合物(I)及其药学上可接受的盐，其中R1、R2、R3、A和n如本文所定义。还提供了含有化合物I的药物组合物，并将其用于治疗神经退行性和认知障碍，如阿尔茨海默病和精神分裂症。
• Pyridine amide derivatives as EP4 receptor antagonists
  申请人：Borriello Manuela

  公开号：US08828987B2

  公开（公告）日：2014-09-09

  The invention relates pyridine amide derivative of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are independently hydrogen, linear o branched (C1-C3)alkyl or joined together they form a cyclopropyl ring; R is independently selected from the group consisting of halogens and trifluoromethyl and p is 1, 2 or 3; A is C or N; E is a group of formula (B) or (C), wherein B is C(O)OH, C(O)O(C1-C3)alkyl, and C is selected from the group consisting of formula (I) m is 1,2 or 3, n is 0 or 1, W is —O—, —O(C1-C3 alkyl)-; —(C1-C3 alkyl)O—; —C(O)—; —C(═N—O(C1-C3 alkyl))-; —NH— or —NH(C1-C3alkyl)-; Ar is phenyl, optionally substituted with one or more substituents selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, methyl, —NH(C1-C3alkyl)-; —N(C1-C3alkyl)(C1-C3alkyl)-, a from 5 to 7 membered heterocyclic ring containing one nitrogen atom which is covalently bonded to Ar and optionally containing one or two heteroatoms selected from N, O and S; and a 5- or 6-membered heteroaromatic ring containing 1 to 3 heteroatoms selected from S, O e N, such heteroaromatic ring being substituted with one or two substituents selected from the group consisting of (C1-C3)alkyl, (C3-C5)cycloalkyloxy, (C1-C3)alkylcarbonyl. The compounds of the invention could be used for manufacturing a medicament for the treatment of pathologies which require the use of an antagonist of the EP4 receptor, such as the treatment of acute and chronic pain, inflammatory pain, osteoarthritis, inflammation-associated disorder as arthritis, rheumatoid arthritis, cancer, endometriosis and migraine.

  本发明涉及式（I）的吡啶酰胺衍生物或其药学上可接受的盐，其中R1和R2分别独立地为氢、线性或支链（C1-C3）烷基或结合在一起形成环丙基环；R独立地选自卤素和三氟甲基，p为1、2或3；A为C或N；E为式（B）或（C）的基团，其中B为C（O）OH、C（O）O（C1-C3）烷基，C选自式（I），m为1、2或3，n为0或1，W为—O—、—O（C1-C3烷基）-、—（C1-C3烷基）O—、—C（O）—、—C（═N—O（C1-C3烷基））-、—NH—或—NH（C1-C3烷基）-；Ar为苯基，可选地取代一个或多个取代基，所述取代基选自卤素、三氟甲基、三氟甲氧基、甲基、—NH（C1-C3烷基）-、—N（C1-C3烷基）（C1-C3烷基）-、含有一个氮原子的5至7元杂环，该氮原子与Ar共价键合，并可选地含有一或两个选自N、O和S的杂原子；以及含有1至3个选自S、O和N的杂环芳烃环，该杂环芳烃环被一个或两个选自（C1-C3）烷基、（C3-C5）环烷氧基、（C1-C3）烷基羰基的取代基取代。本发明的化合物可用于制造治疗需要使用EP4受体拮抗剂的病理学的药物，例如治疗急性和慢性疼痛、炎症性疼痛、骨关节炎、关节炎、类风湿性关节炎、癌症、子宫内膜异位症和偏头痛等炎症相关疾病。
• Process for preparing 3-phenoxy-1-azetidines and carboxamide derivatives
  申请人：A.H. ROBINS COMPANY, INCORPORATED

  公开号：EP0131435A1

  公开（公告）日：1985-01-16

  A process for preparing 3-phenoxyazetidines uses a phase transfer catalyst to add the phenoxy group to azetidine blocked in the 1-position by a diphenylmethane group and uses a stabilizing tertiary amine base to prevent dimerization during hydrogenolysis to remove the blocking group. The crude product containing diphenylmethane may be used without purification to prepare 3-phenoxy-1-azetidine carboxamides.

  一种制备 3-苯氧基氮杂环丁烷的工艺使用相转移催化剂将苯氧基加到被二苯基甲烷基团封堵在 1 位的氮杂环丁烷上，并使用稳定叔胺碱防止在氢解过程中发生二聚反应以去除封堵基团。含有二苯基甲烷的粗产品无需纯化即可用于制备 3-苯氧基-1-氮杂环丁烷羧酰胺。