4-chloro-2-[5-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[1,3,4]oxadiazol-2-ylmethoxymethyl]-phenylamine | 748805-77-8

• 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: 4-chloro-2-[5-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[1,3,4]oxadiazol-2-ylmethoxymethyl]-phenylamine
• 英文别名: 4-Chloro-2-[[5-(1-pyridin-2-ylpiperidin-4-yl)-1,3,4-oxadiazol-2-yl]methoxymethyl]aniline
• CAS: 748805-77-8
• 化学式: C₂₀H₂₂ClN₅O₂
• 分子量: 399.88
• InChiKey: RNNMAQNMWRZRFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  90.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-chloro-2-[5-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[1,3,4]oxadiazol-2-ylmethoxymethyl]-phenylamine 在 对甲苯磺酸 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 18.0h， 生成 8-chloro-1-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl)-4H,6H-5-oxa-2,3,10b-triazabenzo[e]azulene
  参考文献：
  名称：

  Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability

  摘要：

  The V1a receptor has emerged as an attractive target for a range of indications including Raynaud's disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.038
• 作为产物：
  描述：

  1-(pyridin-2-yl)piperidine-4-carbohydrazide 在 N-甲基吗啉 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 4-chloro-2-[5-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[1,3,4]oxadiazol-2-ylmethoxymethyl]-phenylamine
  参考文献：
  名称：

  Preparation of triazolobenzodiazepine derivatives as Vasopressin V1a antagonists

  摘要：

  This Letter describes the synthesis of a number of fused tricyclic and bicyclic triazolobenzodiazepines for the Vasopressin Via antagonist programme. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.08.011

文献信息

• [EN] TRIAZOLE COMPOUNDS USEFUL IN THERAPY<br/>[FR] COMPOSES DE TRIAZOLE UTILISES EN THERAPIE
  申请人：PFIZER LTD

  公开号：WO2004074291A1

  公开（公告）日：2004-09-02

  A compound of formula (I), or a pharmaceutically acceptable derivative thereof, wherein V represents -(CH2)d(O)e-, -CO-, or -CH(C1-6 alkyl)-; W is -0-, -S(O)a , or -N(R1')-R1 represents H, C 1-6 alkyl, (CH2)bCOR2, CO(CH2)bNR2R3, S02R2, (CH2 )cOR2, (CH2)c,NR2R3, or (CH2)bhet1; het1 represents a saturated or unsaturated heterocycle of from 3 to 8 atoms containing one or more heteroatoms selected from O, N, or S, optionally substituted with C 1-6 alkyl; X and Y independently represent H, C 1-6 alkyl, halogen, OH, CF3, OCF3, OR4; Z represents -(CH2)f(O)g , -CO- or -CH(C 1-6 alkyl)-; Ring A represents a 4-7 membered, saturated N-containing heterocycle, optionally substituted with OH, and in which optionally at least one ring N is substituted with O;Ring B represents phenyl or a 4-7 membered unsaturated N-containing heterocycle, optionally substituted with OH, halogen, CN, CONH2, CF3, OCF3, and in which optionally at least one ring N is substituted with O; R2 and R3 independently represent H, C 1-6 alkyl [optionally substituted with OH, halogen,N(C 1.6 alkyl)2, or C 1.6 alkyloxy], C 1.6 alkyloxy, N(C 1-6 alkyl)2, or [C 3-8 cycloalkyl]; or R2 and R3, together with the nitrogen atom to which they are attached independently represent a heterocycle of from 3 to 8 atoms, optionally substituted with C 1-6 alkyl;R4 represents straight or branched C 1-6 alkyl, a and c independently represent 0, 1, or 2; b, e and g independently represent 0 or 1; d and f independently represent 1 or 2;are useful in the treatment of dysmenorrhoea.

  式(I)的化合物，或其药学上可接受的衍生物，其中V代表-(CH2)d(O)e-, -CO-,或-CH(C1-6烷基)-；W为-0-, -S(O)a,或-N(R1')-R1代表H，C1-6烷基，(CH2)bCOR2，CO(CH2)bNR2R3，S02R2，(CH2)cOR2，(CH2)c,NR2R3，或(CH2)bhet1；het1代表一个饱和或不饱和的含有3至8个原子的杂环，其中含有一个或多个从O、N或S中选择的杂原子，可选择地用C1-6烷基取代；X和Y独立地代表H，C1-6烷基，卤素，OH，CF3，OCF3，或OR4；Z代表-(CH2)f(O)g，-CO-或-CH(C1-6烷基)-；环A代表一个4-7成员的饱和N-含杂环，可选择地用OH取代，并且其中可选择地至少一个环N用O取代；环B代表苯或一个4-7成员的不饱和N-含杂环，可选择地用OH，卤素，CN，CONH2，CF3，OCF3取代，并且其中可选择地至少一个环N用O取代；R2和R3独立地代表H，C1-6烷基[可选择地用OH，卤素，N(C1-6烷基)2，或C1-6烷氧基取代]，C1-6烷氧基，N(C1-6烷基)2，或[C3-8环烷基]；或R2和R3，连同它们附着的氮原子，独立地代表一个含有3至8个原子的杂环，可选择地用C1-6烷基取代；R4代表直链或支链C1-6烷基，a和c独立地代表0，1，或2；b，e和g独立地代表0或1；d和f独立地代表1或2；在痛经的治疗中是有用的。
• Triazole compounds useful in therapy
  申请人：Bryans Stephen Justin

  公开号：US20060194794A1

  公开（公告）日：2006-08-31

  A compound of formula (I), or a pharmaceutically acceptable derivative, wherein A, B, V, W, X, Y, and Z are as defined herein; pharmaceutical compositions thereof; and uses thereof.

  一种化合物的公式（I），或其药学上可接受的衍生物，其中A、B、V、W、X、Y和Z的定义如本文所述；其制药组合物；以及其用途。
• Discovery of PF-184563, a potent and selective V1a antagonist for the treatment of dysmenorrhoea. The influence of compound flexibility on microsomal stability
  作者：Patrick S. Johnson、Thomas Ryckmans、Justin Bryans、Dave M. Beal、Kevin N. Dack、Neil Feeder、Anthony Harrison、Mark Lewis、Helen J. Mason、James Mills、Julie Newman、Christelle Pasquinet、Dave J. Rawson、Lee R. Roberts、Rachel Russell、Deborah Spark、Alan Stobie、Toby J. Underwood、Robin Ward、Simon Wheeler

  DOI：10.1016/j.bmcl.2011.08.038

  日期：2011.10

  The V1a receptor has emerged as an attractive target for a range of indications including Raynaud's disease and dysmenorrhoea. As part of an effort to discover a new class of orally active V1a antagonist, we optimised a highly lipophilic, metabolically unstable lead into a range of potent, selective and metabolically stable V1a antagonists. In this communication, we demonstrate the series-dependent effect of limiting the number of rotatable bonds in order to decrease Cytochrome P450-mediated metabolism. This effort culminated in the discovery of PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo properties. (C) 2011 Elsevier Ltd. All rights reserved.
• TRIAZOLE COMPOUNDS USEFUL IN THERAPY
  申请人：Pfizer Limited

  公开号：EP1597260A1

  公开（公告）日：2005-11-23
• US7119088B2
  申请人：——

  公开号：US7119088B2

  公开（公告）日：2006-10-10