2,3-二氢-1H-吡啶并[2,3-b][1,4]噁嗪 | 1112193-37-9

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2,3-二氢-1H-吡啶并[2,3-b][1,4]噁嗪
• 中文别名: 2,3-二氢-1H-吡啶并[2,3-B][1,4]恶嗪
• 英文名称: 2,3-Dihydro-1H-4-oxa-1,5-diaza-naphthalene
• 英文别名: 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine
• CAS: 1112193-37-9
• 化学式: C₇H₈N₂O
• mdl: MFCD08692103
• 分子量: 136.153
• InChiKey: LTWFBZQFHPDLNU-UHFFFAOYSA-N

物化性质

• 沸点：
  285.7±29.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• WGK Germany：
  3
• 危险标志：
  GHS07
• 危险性描述：
  H319
• 危险性防范说明：
  P305 + P351 + P338
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2,3-二氢-1H-吡啶并[2,3-b][1,4]噁嗪 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-[3-chloro-4-(2,3-dihydropyrido[2,3-b][1,4]oxazin-1-yl)phenyl]-3-methylfuran-2-carboxamide
  参考文献：
  名称：

  Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs

  摘要：

  This Letter describes the further lead optimization of the VU0486321 series of mGlu(1) positive allosteric modulators (PAMs), focused on addressing the recurrent issue of plasma instability of the phthalimide moiety. Here, we evaluated a number of phthalimide bioisosteres, and ultimately identified isoindolinones as the ideal replacement that effectively address plasma instability, while maintaining acceptable mGlu(1) PAM potency, DMPK profile, CNS penetration and mGluR selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.031
• 作为产物：
  描述：

  1H-吡啶并[2,3-b][1,4]噁嗪-2(3h)-酮 在 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以88%的产率得到2,3-二氢-1H-吡啶并[2,3-b][1,4]噁嗪
  参考文献：
  名称：

  HETEROCYCLIC DERIVATIVES

  摘要：

  本发明涉及杂环衍生物，更具体地，涉及用于制备治疗与尿酸相关疾病的药物的新颖杂环衍生物。

  公开号：

  US20110028467A1

文献信息

• [EN] AZADECALIN DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] DÉRIVÉS D'AZADÉCALINE EN TANT QU'INHIBITEURS DE LA RÉPLICATION DU VIRUS DE L'IMMUNODÉFICIENCE HUMAINE
  申请人：VIIV HEALTHCARE UK (NO 5) LTD

  公开号：WO2018002848A1

  公开（公告）日：2018-01-04

  Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, azadecaline derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.

  具有药物和生物影响特性的化合物，其药物组合物和使用方法已列出。具体来说，提供了具有独特抗病毒活性的阿扎德卡林衍生物，作为HIV成熟抑制剂，如化合物(I)的公式所代表的那样。这些化合物对于治疗HIV和艾滋病是有用的。
• 8-AMINOISOQUINOLINE COMPOUNDS AND USES THEREOF
  申请人：Genentech, Inc.

  公开号：US20200108075A1

  公开（公告）日：2020-04-09

  3-Carbonylamino-8-aminoisoquinoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline compounds.

  公式（I）的3-羰基氨基异喹啉化合物及其变体，以及它们作为HPK1（造血激酶1）抑制剂的用途被描述。这些化合物在治疗HPK1依赖性疾病和增强免疫应答方面是有用的。还描述了抑制HPK1的方法，治疗HPK1依赖性疾病的方法，增强免疫应答的方法，以及制备3-羰基氨基异喹啉化合物的方法。
• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：SENEXIS LTD

  公开号：WO2011144578A1

  公开（公告）日：2011-11-24

  A compound of formula (I) or a pharmaceutically acceptable salt or prodrug thereof wherein X is N or CH; Q is NR6 or O; A1 and A2 are independently hydrogen or C1-6 alkyl or may together form a carbonyl group; R1 and R2 are independently hydrogen, halogen, CF3, CN, OR7, OR8, NR8R9, NR8COR10, NR8S02R10, S02NR8R9, SO2R10 or C1-6 alkyl optionally and independently substituted by one or more of hydroxyl, C1-6 alkoxy, halogen or NR8 R9; R 3 is hydrogen, halogen, CF3 or OR 7; R4 is hydrogen, halogen, CF3, OR8, NR8R9, NR8COR10, NR8S02R10 or C1-6 alkyl optionally substituted by hydroxyl, C1-6 alkoxy or NR 8 R 9; or when R3 and R4 are positioned ortho and taken together form -0(CH2)mO-, where m is 1-3; R5 is hydrogen or C1-6 alkyl optionally substituted by hydroxyl, C1-6 alkoxy or NR8 R9; R6 is hydrogen or C1-6 alkyl; R7 is hydrogen or C1-6 alkyl optionally substituted by OR8 or NR8R9; R8 is hydrogen, C1-6 alkyl, optionally substituted by hydroxyl or C1-6 alkoxy or C1-3 alkylphenyl wherein said phenyl group is optionally substituted by one or more substituents selected from halogen, C1-6 alkyl, CF3, OR7, NR8R9 or OCF3; or the groups R8 and R9 when they are attached to a nitrogen atom may together form a 5- or 6-membered ring which optionally contains one further heteroatom selected from NR7, S and O said 5 or 6 membered ring being optionally substituted by hydroxyl or C1-6 alkoxy; or the groups R8 and R9 when they are attached to a nitrogen atom may together form an azetidinyl ring optionally substituted by hydroxyl or C1-6 alkoxy; and R10 is C1-6 alkyl or a phenyl group optionally substituted by one or more substituents selected from halogen, C1-6 alkyl, CF3, OCF3 or OR7; and n is 1 or 2. The use of the compounds in treating amyloid disease is also disclosed.

  式（I）的化合物或其药学上可接受的盐或前药，其中X为N或CH；Q为NR6或O；A1和A2独立地为氢或C1-6烷基，或者可共同形成一个羰基团；R1和R2独立地为氢、卤素、CF3、CN、OR7、OR8、NR8R9、NR8COR10、NR8S02R10、S02NR8R9、SO2R10或C1-6烷基，可选地并独立地被一个或多个羟基、C1-6烷氧基、卤素或NR8R9取代；R3为氢、卤素、CF3或OR7；R4为氢、卤素、CF3、OR8、NR8R9、NR8COR10、NR8S02R10或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；或者当R3和R4位于邻位并共同形成-0(CH2)mO-时，其中m为1-3；R5为氢或C1-6烷基，可选地被羟基、C1-6烷氧基或NR8R9取代；R6为氢或C1-6烷基；R7为氢或C1-6烷基，可选地被OR8或NR8R9取代；R8为氢、C1-6烷基，可选地被羟基或C1-6烷氧基或C1-3烷基苯基取代，其中所述苯基可选地被一个或多个卤素、C1-6烷基、CF3、OR7、NR8R9或OCF3中的一种或多种取代基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个含有一个进一步异原子（选自NR7、S和O）的5-或6-成员环，所述5-或6-成员环可选地被羟基或C1-6烷氧基取代；或者当R8和R9连接到一个氮原子时，它们可共同形成一个可选地被羟基或C1-6烷氧基取代的氮杂环戊烷环；R10为C1-6烷基或一个苯基，可选地被一个或多个卤素、C1-6烷基、CF3、OCF3或OR7中的一种或多种取代基取代；n为1或2。还公开了这些化合物在治疗淀粉样蛋白病中的用途。
• [EN] INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] INHIBITEURS DE LA RÉPLICATION DU VIRUS DE L'IMMUNODÉFICIENCE HUMAINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2016172424A1

  公开（公告）日：2016-10-27

  Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth: (I)

  公式I的化合物，包括其药用可接受的盐，以及用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法被描述如下：（I）
• [EN] AMINOPYRAZINE COMPOUNDS AS HPK1 INHIBITOR AND THE USE THEREOF<br/>[FR] COMPOSÉS D'AMINOPYRAZINE UTILISÉS EN TANT QU'INHIBITEURS DE HPK1 ET LEUR UTILISATION
  申请人：BEIGENE LTD

  公开号：WO2021032148A1

  公开（公告）日：2021-02-25

  Disclosed herein is an aminopyrazine compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.

  本文揭示了一种式(I)的氨基吡嗪化合物，或其立体异构体，或其药学上可接受的盐，以及包含它们的药物组合物。还公开了利用本文所披露的化合物治疗HPK1相关疾病或疾病的方法。