5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one | 183549-97-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one
• 英文别名: 7-phenyl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocine-6-one；5-[3,5-bis(trifluoromethyl)benzyl]-2,3,4,5-tetrahydro-6-oxo-7-phenyl-6H-pyrido[2,3-b] [1,5]oxazocine；5-[3,5-Bis(trifluoromethyl)benzyl]-2,3,4,5-tetrahydro-6-oxo-7-phenyl-6H-pyrido[2,3-b][1,5]oxazocine；5-[3,5-bis(trifluoromethyl)benzyl]-6-oxo-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine；4-Phenyl-6-[3,5-bis(trifluoromethyl)benzyl]-8,9-dihydro-7H-10-oxa-1,6-diazabenzocyclooctene-5(6H)-one；5-[[3,5-bis(trifluoromethyl)phenyl]methyl]-7-phenyl-3,4-dihydro-2H-pyrido[2,3-b][1,5]oxazocin-6-one
• CAS: 183549-97-5
• 化学式: C₂₄H₁₈F₆N₂O₂
• 分子量: 480.41
• InChiKey: CARZFIAHOCLKTQ-UHFFFAOYSA-N

物化性质

• 熔点：
  188-189 °C(Solv: ethyl acetate (141-78-6); isopropyl ether (108-20-3))
• 沸点：
  543.1±50.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one 在 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 生成 5-[3,5-bis(trifluoromethyl)benzyl]-9-chloro-7-phenyl-3,4,5,6-tetrahydro-2H-pyrido[2,3-b]-1,5-oxazocin-6-one
  参考文献：
  名称：

  设计，合成和评估新型2-取代-4-芳基-6,7,8,9-四氢-5H-嘧啶[4,5-b] [1,5]恶唑啉-5-酮类药物作为NK1拮抗剂。

  摘要：

  制备了一系列新颖的双环嘧啶衍生物，作为寻找旨在治疗尿失禁的NK1拮抗剂的一部分。其中3g，带有4-乙酰基哌嗪基和2-甲基苯基的嘧啶并[4,5-b] [1,5]恶唑啉衍生物，显示出有效的NK1拮抗剂活性，其K（B）值​​为为0.105 nM，显着增加了豚鼠的有效膀胱容量（0.3 mg / kg iv时为59.4％，id 3 mg / kg时为62.8％）。此外，使用尿烷麻醉的豚鼠模型，通过扩张诱导的节律性膀胱收缩试验确定了3g对膀胱功能的影响似乎与另一种经典的抗尿蛋白尿症托特罗定不同。化合物3g有望成为治疗尿失禁的有前途的药物。

  DOI：

  10.1016/j.bmc.2005.06.015
• 作为产物：
  描述：

  3,5-双三氟甲基苄醇 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one
  参考文献：
  名称：

  Amide-based atropisomers in tachykinin NK1-receptor antagonists: synthesis and antagonistic activity of axially chiral N-benzylcarboxamide derivatives of 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one

  摘要：

  A series of novel N-benzylcarboxamide derivatives of bicyclic compounds, 3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one and 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one, were synthesized by cyclization of N-benzyl-2-chloro-N-(2-hydroxyethyl)-and -(3-hydroxypropyl)-nicotinamides, respectively. Atropisomerism was observed in 5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-ones due to steric hindrance of the carboxamide moiety and restriction of its rotation. Cyclization of N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-[(2S)-3-hydroxy-2-methylpropyl]-5-methyl-4-phenylnicotinamide gave (3S)5-[3,5-bis(trifluoromethyl)benzyl]-3,8-dimethyl-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3b][1,5]oxazocin-6-one, which exists predominantly in the thermodynamically stable aR-conformer in CDCl3. This compound showed excellent NK1-antagonistic activity with IC50 value (in vitro inhibition of [I-125]-Bolton-Hunter-substance P binding in human IM-9 cells) of 0.47 nM, which is ca. 200-fold more potent than that of its enantiomer, indicating that the atropisomer chirality affects NK1-receptor recognition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.01.097

文献信息

• Heterocyclic compounds, their production and use
  申请人：——

  公开号：US20020132817A1

  公开（公告）日：2002-09-19

  A compound represented by the formula: 1 wherein ring M is a heterocyclic ring wherein —X═Y< is one of —N═C<, —CO—N< or —CS—N<; R a and R b are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, with the proviso that at least one of them is an optionally substituted heterocyclic ring; Ring C is an optionally substituted homocyclic or heterocyclic ring; Ring Z is an optionally substituted nitrogen-containing heterocyclic ring; and n is an integer from 1 to 6, or a salt thereof has a tachykinin receptor antagonistic activity in vitro, and is useful for preventing or treating depression, anxiety, manic-depressive illness or psychopathy.

  一种由以下通式表示的化合物：1，其中环M为杂环环，其中—X═Y<为—N═C<、—CO—N<或—CS—N<之一；Ra和Rb彼此连接形成环A，或者它们相同或不同，独立地表示氢原子或环M上的取代基；环A和环B独立地表示可任选取代的碳环或杂环环，条件是至少一个为可任选取代的杂环环；环C为可任选取代的碳环或杂环环；环Z为可任选取代的含氮杂环环；n为1至6的整数，或其盐在体外具有速激肽受体拮抗活性，并可用于预防或治疗抑郁症、焦虑症、双相情感障碍或精神病。
• Fused bicyclic pyridine derivative as tachykinin receptor antagonist
  申请人：Seto Shigeki

  公开号：US20050101591A1

  公开（公告）日：2005-05-12

  A fused bicyclic pyridine derivative represented by the following general formula (1), or a salt thereof: wherein the rings A and B are each a benzene ring, which may have 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring) that are each independently selected from the group consisting of a halogen atom, a substituted or unsubstituted C 1 to C 6 alkyl group, and a substituted or unsubstituted C 1 to C 6 alkoxyl group; R is a C 1 to C 6 alkylsulfonyl group, a C 1 to C 6 alkylcarbonyl group, a C 1 to C 6 alkoxycarbonyl group, or a formyl group; m is 1 or 2; n is 2 or 3; and q is 1 or 2.

  以下是一种由以下通式（1）表示的融合双环吡啶衍生物，或其盐： 其中，环A和环B均为苯环，可以具有1至3个取代基（任意相邻两个取代基可以相互结合形成环），每个取代基独立地选自由卤素原子，取代或未取代的C1至C6烷基基团，以及取代或未取代的C1至C6烷氧基基团；R为C1至C6烷基磺酰基、C1至C6烷基羰基基团、C1至C6烷氧基羰基基团或甲酰基；m为1或2；n为2或3；q为1或2。
• Fused bicyclic pyridine derivatives as tachykinin receptor antagonists
  申请人：Seto Shigeki

  公开号：US20050107375A1

  公开（公告）日：2005-05-19

  A novel fused bicyclic pyridine derivative or a salt thereof that acts as a tachykinin receptor antagonist, in particular as an NK1 receptor antagonist, is represented by the following general formula (1): wherein the rings A and B are each a benzene ring which may have 1 to 3 substituents (any adjacent two of which may be bound to one another to form a ring); the ring C is a nitrogen-containing ring having a hydrogen atom substituted with a nitrogen atom; R 1 and R 2 are each independently a hydrogen atom, a C 1 to C 6 alkyl group, a C 1 to C 6 alkylsulfonyl group, a C 1 to C 6 alkylcarbonyl group, or a C 1 to C 6 alkoxycarbonyl group, or R 1 and R 2 are bound to one another to form the ring D; m is 1 or 2; n is 2 or 3; and q is an integer from 1 to 4.

  下列一种新型的融合双环吡啶衍生物或其盐，作为一种速激肽受体拮抗剂，特别是NK1受体拮抗剂，其通式如下（1）：其中，环A和环B分别为苯环，可以有1-3个取代基（任意相邻两个可以结合形成环）；环C为含氮环，氢原子被氮原子取代；R1和R2分别为氢原子、C1-C6烷基、C1-C6烷基磺酰基、C1-C6烷基羰基或C1-C6烷氧羰基，或R1和R2结合形成环D；m为1或2；n为2或3；q为1-4的整数。
• Cyclic compounds, their production and use as tachykinin receptor antagonists
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0733632A1

  公开（公告）日：1996-09-25

  Novel compounds of the following general formula or salts thereof. wherein Ring M is a heterocyclic ring having -N=C<, -CO-N< or -CS-N< as the partial structure -X Y<; Ra and Rb are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, and at least one of them is optionally substituted heterocyclic ring; Ring C is optionally substituted homocyclic or heterocyclic ring; Rng Z is an optionally substituted ring; and n represents an integer of from 1 to 6, or a salt thereof, which has an excellent tachykinin receptor antagonistic effect, and their production, and pharmaceutical compositions.

  以下通式的新型化合物或其盐。 其中，环 M 是具有-N=C<、-CO-N<或-CS-N<作为部分结构-X Y<的杂环；Ra 和 Rb 相互键合形成环 A，或者它们相同或不同，并独立地代表环 M 上的氢原子或取代基；环 A 和环 B 独立地代表任选取代的同环或杂环，其中至少一个是任选取代的杂环；环 C 是任选取代的同环或杂环； Rng Z 是任选取代的环； n 代表 1 至 6 的整数，或其盐，具有优异的速激肽受体拮抗作用，及其生产和药物组合物。
• Heterocyclic compounds, their production and use as tachykinin receptor antagonists
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1184036A2

  公开（公告）日：2002-03-06

  A compound represented by the formula: wherein ring M is a heterocyclic ring wherein is one of -N=C<, -CO-N< or -CS-N<; Ra and Rb are bonded to each other to form Ring A, or they are the same or different and represent, independently, a hydrogen atom or a substituent on the Ring M; Ring A and Ring B represent, independently, an optionally substituted homocyclic or heterocyclic ring, with the proviso that at least one of them is an optionally substituted heterocyclic ring; Ring C is an optionally substituted homocyclic or heterocyclic ring; Ring Z is an optionally substituted nitrogen-containing heterocyclic ring; and n is an integer from 1 to 6, or a salt thereof has a tachykinin receptor antagonistic activity in vitro, and is useful for preventing or treating depression, anxiety, manic-depressive illness or psychopathy.

  式所代表的化合物： 其中环 M 是杂环，其中 是-N=C<、-CO-N<或-CS-N<中的一种； Ra 和 Rb 相互结合形成环 A，或者它们相同或不同，并独立地代表氢原子或环 M 上的取代基； 环 A 和环 B 独立地代表任选取代的同环或杂环，但其中至少有一个是任选取代的杂环； 环 C 是任选取代的均环或杂环； 环 Z 是任选取代的含氮杂环；以及 n 是 1 至 6 的整数，或其盐在体外具有速激肽受体拮抗活性，可用于预防或治疗抑郁症、焦虑症、躁狂抑郁症或精神病。