4-吡嗪-2-基苯(甲)醛 | 168266-51-1

分子结构分类

有机化合物 - 有机杂环化合物 - 哌啶类

中文名称

4-吡嗪-2-基苯(甲)醛

中文别名

N-[[2-甲氧基-5-[5-(三氟甲基)四唑-1-基]苯基]甲基]-2-苯基哌啶-3-胺二盐酸盐

英文名称

Vofopitant dihydrochloride

英文别名

(2S,3S)-N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine;dihydrochloride

CAS

168266-51-1

化学式

C21H25Cl2F3N6O

mdl

——

分子量

505.4

InChiKey

YVNRXILPJNISEM-FFUVTKDNSA-N

BEILSTEIN

——

EINECS

——

物化性质

溶解度：

溶于二甲基亚砜

计算性质

辛醇/水分配系数(LogP)：

4.12
重原子数：

33
可旋转键数：

6
环数：

4.0
sp3杂化的碳原子比例：

0.38
拓扑面积：

76.9
氢给体数：

4
氢受体数：

9

制备方法与用途

生物活性

Vofopitant dihydrochloride（GR 205171A）是一种高效、选择性的口服速激肽 NK1 受体拮抗剂。在大鼠和人类细胞膜上，它分别抑制了 [3H]SP 与 NK1 结合的 pKi 值为 9.5 和 10.6，显示出其成为广谱止吐剂的潜力。

靶点

pKi: 9.5 (NK1, 大鼠), 10.6 (NK1, 人类)

反应信息

作为反应物：

描述：

4-吡嗪-2-基苯(甲)醛、三乙胺、三溴化硼、二甲基硫、在氮、 ice 、乙酸乙酯、碳酸氢钠、 Brine 、 magnesium sulfate 、 silica 作用下，以氯仿、甲醇为溶剂，反应 144.0h，以to give the title compound as a light brown foam (672 mg), mass spectrum (thermospray +ve) m/e 419 (MH+)的产率得到[2-Hydroxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-([2S,3S]-2-phenylpiperidin-3-yl)amine

参考文献：

名称：

Piperidine derivatives having tachykinin antagonist activity

摘要：

本发明涉及式（I）的哌啶衍生物：##STR1## 其中取代基R.sup.1，R.sup.3，R.sup.4和R.sup.5如规范和权利要求中所定义，取代基R.sup.2为##STR2## 还描述了这些哌啶衍生物的药物可接受的盐和溶剂化物。本发明还涉及制备哌啶衍生物的方法，以及它们在治疗由快速激肽介导的疾病中的使用。

公开号：

US06020346A1

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文献信息

PHARMACEUTICAL COMPOSITIONS COMPRISING NK1 RECEPTOR ANTAGONISTS AND SODIUM CHANNEL BLOCKERS

申请人：Alvaro Giuseppe

公开号：US20090318530A1

公开（公告）日：2009-12-24

The present invention relates to pharmaceutical compositions comprising an NK1 receptor antagonist and a sodium channel blocker compound of formula (I) wherein R 1 and R 2 are independently hydrogen, C 1-6 alkyl or C 3-6 cycloalkylC 1-6 alkyl; or R 1 and R 2 , together with the nitrogen to which they are attached, may form an unsubstituted 3-, 4-, 5- or 6-membered saturated ring; q is 1 or 2; R 3 and R 4 are hydrogen; or when q is 1, R 3 and R 4 , together with the interconnecting atoms, may form a cyclopropane ring; X is carbon or nitrogen; n is 0, 1 or 2, wherein when present each R 5 is independently selected from the list consisting of C 1-3 alkyl, halogen, cyano, haloC 1-3 alkyl, hydroxy, C 1-3 alkoxy and C 1-3 haloalkoxy; and either R 6 or R 7 is —O—R 8 or —OCH 2 R 8 , wherein the other R 6 or R 7 is hydrogen or R 5 ; and wherein R 8 is either a phenyl ring or a 5- or 6-membered aromatic heterocyclic ring (independently containing one or more nitrogen, sulphur or oxygen atoms) wherein either the phenyl ring or the heterocyclic ring is optionally substituted by one or more groups independently selected from the list consisting of C 1-3 alkyl, halogen, cyano, haloC 1-3 alkyl, hydroxy, C 1-3 alkoxy and C 1-3 haloalkoxy; or a pharmaceutically acceptable salt or solvate thereof; as a combined preparation for simultaneous or sequential administration, and to the use of such compositions in the treatment of certain disorders, including epilepsy and mood disorders.

本发明涉及一种药物组合物，包括NK1受体拮抗剂和式(I)的钠通道阻滞剂化合物，其中R1和R2独立地为氢、C1-6烷基或C3-6环烷基C1-6烷基；或者R1和R2连同它们所连接的氮原子可以形成未取代的3、4、5或6成员饱和环；q为1或2；R3和R4为氢；或者当q为1时，R3和R4连同相互连接的原子可以形成环丙烷环；X为碳或氮；n为0、1或2，其中当存在时，每个R5独立地从C1-3烷基、卤素、氰基、卤代C1-3烷基、羟基、C1-3烷氧基和C1-3卤代烷氧基的列表中选择；且R6或R7为—O—R8或—OCH2R8，另一个R6或R7为氢或R5；其中R8为苯环或5-或6-成员芳香杂环环（独立地包含一个或多个氮、硫或氧原子），其中苯环或芳香杂环环中的任一环都可以选择一个或多个独立的基团进行取代，所述基团从C1-3烷基、卤素、氰基、卤代C1-3烷基、羟基、C1-3烷氧基和C1-3卤代烷氧基的列表中独立选择；或其药学上可接受的盐或溶剂；作为同时或顺序给药的联合制剂，并且将这种组合物用于治疗某些疾病，包括癫痫和情感障碍。
3-benzylamino-2-phenylpiperidines as neurokinin antagonists

申请人：Glaxo Group Limited

公开号：US05919803A1

公开（公告）日：1999-07-06

The invention relates to piperidine derivatives of formula (I) ##STR1## wherein R.sup.1 is a C.sub.2-4 alkoxy group; R.sup.2 is ##STR2## R.sup.3 is a hydrogen or halogen atom; R.sup.4 and R.sup.5 may each independently represent a hydrogen or halogen atom, or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trifluoromethyl group; and pharmaceutically acceptable derivatives thereof, to processes for their preparation, and their use in the treatment of conditions mediated by tachykinins.

本发明涉及式(I)的哌啶衍生物：##STR1## 其中 R.sup.1 是C.sub.2-4烷氧基；R.sup.2是 ##STR2## R.sup.3是氢原子或卤素原子；R.sup.4和R.sup.5可以各自独立地表示氢原子或卤素原子，或C.sub.1-4烷基，C.sub.1-4烷氧基或三氟甲基基团；以及其药学上可接受的衍生物，制备它们的过程，以及它们在治疗由速激肽介导的疾病中的应用。
PHARMACEUTICAL COMPOSITIONS COMPRISING 3,5-DIAMINO-6-(2,3-DICHLOPHENYL)-1,2,4-TRIAZINE OR R(-)-2,4-DIAMINO-5-(2,3-DICHLOROPHENYL)-6-FLUOROMETHYL PYRIMIDINE AND AN NK1

申请人：Alvaro Giuseppe

公开号：US20100105688A1

公开（公告）日：2010-04-29

The present invention relates to pharmaceutical compositions comprising an NK1 receptor antagonist and a sodium channel blocker, wherein at least one of them is at subtherapeutic dose, as a combined preparation for simultaneous or sequential administration, and to the use of such compositions in the treatment of certain disorders, including epilepsy, mood disorders and pain.

本发明涉及一种制药组合物，包括NK1受体拮抗剂和钠通道阻滞剂，其中至少一种剂量为亚治疗剂量，作为同时或顺序给药的联合制剂，并且本发明还涉及在治疗某些疾病，包括癫痫、情绪障碍和疼痛方面使用这种组合物的方法。
PHARMACEUTICAL COMPOSITIONS COMPRISING 2-METHOXY-5-(5-TRIFLUOROMETHYL-TETRAZOL-1-YL-BENZYL)-(2S-PHENYLPIPERIDIN-3S-YL-)

申请人：Alvaro Giuseppe

公开号：US20100113521A1

公开（公告）日：2010-05-06

The present invention relates to pharmaceutical compositions comprising the NK1 receptor antagonist [2-Methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-(2S-phenyl-piperidin-3S-yl)-amine, or a pharmaceutically acceptable salt or solvate thereof, and a sodium channel blocker, as a combined preparation for simultaneous or sequential administration and to the use of such compositions in the treatment of certain disorders, including epilepsy, mood disorders and pain.

本发明涉及制药组合物，其包括NK1受体拮抗剂[2-甲氧基-5-(5-三氟甲基-四唑-1-基)-苯基]-(2S-苯基-哌啶-3S-基)-胺，或其药学上可接受的盐或溶剂，以及钠通道阻滞剂，作为同时或顺序给药的联合制剂，并且涉及在治疗某些疾病，包括癫痫、情感障碍和疼痛中使用这种组合物的用途。
Methods and compositions for treating vasomotor symptoms

申请人：UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION

公开号：US11083726B2

公开（公告）日：2021-08-10

The present disclosure is generally directed to compositions and methods for treating or limiting development of vasomotor symptoms in a subject.

本公开总体上涉及用于治疗或限制受试者血管运动症状发展的组合物和方法。