4-溴-1,5-萘啶 | 90001-34-6

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-溴-1,5-萘啶
• 英文名称: 4-bromo-1,5-naphthyridine
• CAS: 90001-34-6
• 化学式: C₈H₅BrN₂
• 分子量: 209.045
• InChiKey: RUZMWDKSPLIZSY-UHFFFAOYSA-N

物化性质

• 沸点：
  311 °C
• 密度：
  1.656
• 闪点：
  142 °C

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-溴-1,5-萘啶 在 吡啶 、 盐酸丙胺 作用下， 反应 3.0h， 以97%的产率得到1,5-萘啶-4-胺
  参考文献：
  名称：

  Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: Possible confounding effects on in vivo and in vitro studies

  摘要：

  SB-334867 has been an important ligand for the study of the orexin 1 (OX1) receptor due to its high OX1/OX2 selectivity and bioavailability. This ligand however, contains a 2-methylbenzoxazole ring system which is known to undergo hydrolysis, particularly under acidic or basic conditions. The possibility that SB-334867 would be susceptible to significant hydrolysis was evaluated in various formulations and in the solid state. SB-334867 was found to be unstable under conditions commonly employed to prepare stock solutions for in vitro and in vivo studies. In addition, and most alarmingly, the hydrochloride salt of SB-334867 was found to quantitatively decompose to an OX1-inactive product even in the solid state. These findings combine to suggest that studies using SB-334867 (and any other 2-methylbenzoxazole-containing compound) should be performed with great care to avoid the confounding effects of the rapid hydrolytic decomposition of this susceptible structure. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.08.109
• 作为产物：
  描述：

  4-羟基-1,5-萘啶 在 三溴化磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 以94%的产率得到4-溴-1,5-萘啶
  参考文献：
  名称：

  Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: Possible confounding effects on in vivo and in vitro studies

  摘要：

  SB-334867 has been an important ligand for the study of the orexin 1 (OX1) receptor due to its high OX1/OX2 selectivity and bioavailability. This ligand however, contains a 2-methylbenzoxazole ring system which is known to undergo hydrolysis, particularly under acidic or basic conditions. The possibility that SB-334867 would be susceptible to significant hydrolysis was evaluated in various formulations and in the solid state. SB-334867 was found to be unstable under conditions commonly employed to prepare stock solutions for in vitro and in vivo studies. In addition, and most alarmingly, the hydrochloride salt of SB-334867 was found to quantitatively decompose to an OX1-inactive product even in the solid state. These findings combine to suggest that studies using SB-334867 (and any other 2-methylbenzoxazole-containing compound) should be performed with great care to avoid the confounding effects of the rapid hydrolytic decomposition of this susceptible structure. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.08.109

文献信息

• Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme
  作者：Matthew M. Hamilton、Faika Mseeh、Timothy J. McAfoos、Paul G. Leonard、Naphtali J. Reyna、Angela L. Harris、Alan Xu、Michelle Han、Michael J. Soth、Barbara Czako、Jay P. Theroff、Pijus K. Mandal、Jason P. Burke、Brett Virgin-Downey、Alessia Petrocchi、Dana Pfaffinger、Norma E. Rogers、Connor A. Parker、Simon S. Yu、Yongying Jiang、Stephan Krapp、Alfred Lammens、Graham Trevitt、Martin R. Tremblay、Keith Mikule、Keith Wilcoxen、Jason B. Cross、Philip Jones、Joseph R. Marszalek、Richard T. Lewis

  DOI：10.1021/acs.jmedchem.1c00679

  日期：2021.8.12

  Indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme that mediates the rate-limiting step in the metabolism of l-tryptophan to kynurenine, has been widely explored as a potential immunotherapeutic target in oncology. We developed a class of inhibitors with a conformationally constrained bicyclo[3.1.0]hexane core. These potently inhibited IDO1 in a cellular context by binding to the apoenzyme

  吲哚胺 2,3-双加氧酶 1 (IDO1) 是一种含血红素的酶，可介导l-色氨酸代谢为犬尿氨酸的限速步骤，已被广泛探索为肿瘤学中潜在的免疫治疗靶点。我们开发了一类具有构象受限的双环 [3.1.0] 己烷核心的抑制剂。这些通过与脱辅基酶结合在细胞环境中有效抑制 IDO1，如生化表征和 X 射线晶体学所阐明的那样。SKOV3 肿瘤模型有助于区分化合物，从而鉴定出 IACS-9779 ( 62 ) 和 IACS-70465 ( 71）。IACS-70465 具有出色的细胞效力、强大的药效学反应，并且在人体全血测定中比 linrodostat (BMS-986205) 更有效。IACS-9779 预测人类每日有效剂量低于 1 mg/kg 以维持对 IDO1 的抑制 > 90%，在啮齿动物毒理学和狗心血管研究中显示出可接受的安全范围，以支持推进人类发育的临床前安全性评估。
• Zn-, Mg-, and Li-TMP Bases for the Successive Regioselective Metalations of the 1,5-Naphthyridine Scaffold (TMP=2,2,6,6-Tetramethylpiperidyl)
  作者：Moritz Balkenhohl、Robert Greiner、Ilya S. Makarov、Benjamin Heinz、Konstantin Karaghiosoff、Hendrik Zipse、Paul Knochel

  DOI：10.1002/chem.201703638

  日期：2017.9.21

  A set of successive regioselective metalations and functionalizations of the 1,5‐naphthyridine scaffold are described. A combination of Zn‐, Mg‐, and Li‐TMP (TMP=2,2,6,6‐tetramethylpiperidyl) bases and the presence or absence of a Lewis acid (BF3⋅OEt2) allows the introduction of up to three substituents to the 1,5‐naphthyridine core. Also, a novel “halogen dance” reaction was discovered upon metalation

  描述了1,5-萘啶骨架的一系列连续的区域选择性金属化和功能化。含有Zn，Mg的和Li-TMP（TMP = 2,2,6,6-四甲基）碱基的组合和路易斯酸（BF的存在或不存在3 ⋅OEt 2）允许引入向上的三个1,5-萘啶核的取代基。同样，在8-碘-2,4-三官能化的1,5-萘啶金属化后发现了一种新颖的“卤素舞”反应，可进行第四次区域选择性官能化。此外，还进行了导致制备OLED材料的关键1,5-萘啶和潜在的抗菌剂的反应。
• ORGANIC LIGHT-EMITTING DIODE MATERIALS
  申请人：President and Fellows of Harvard College

  公开号：US20180212158A1

  公开（公告）日：2018-07-26

  Described herin are molecules for use in organic light emitting diodes. Example molecules comprise at least one acceptor moiety A, at least one donor moiety D, and optionally one or more bridge moieties B. Each moiety A is covalently attached to either the moiety B or the moeity D, each moiety D is covalently attached to either the moeity B or the moeity A, and each B is covalently attached to at least one moiety A and at least one moiety D. Values and preferred values of moieties A, D and B are defined herein.

  本文描述了用于有机发光二极管的分子。示例分子包括至少一个受体基团A，至少一个给体基团D，以及可选地一个或多个桥接基团B。每个基团A与基团B或基团D中的任一基团共价连接，每个基团D与基团B或基团A中的任一基团共价连接，每个基团B与至少一个基团A和至少一个基团D共价连接。这里定义了基团A、D和B的值和首选值。
• SPIRODIAMINE-DIARYL KETOXIME DERIVATIVE
  申请人：Ando Makoto

  公开号：US20110071129A1

  公开（公告）日：2011-03-24

  [Problem] To provide a melanin concentrating hormone receptor antagonist useful as medicines for central system disorders, cardiovascular disorders, metabolic disorders. [Means for Resolution] Provided are compound of a formula (I): [wherein R 1 a and R 1 b each are a hydrogen atom, etc.; R 2 is a hydrogen atom, a C 1-6 alkyl, etc.; Ar 1 is a 6-membered aromatic carbocyclic group or a 6-membered aromatic nitrogen-containing heterocyclic group; Ar 2 is a group to be formed by removing two hydrogen atoms from a 6-membered aromatic carbon ring, a 6-membered aromatic nitrogen-containing hetero ring, etc.; Ar 3 is a mono- or bi-cyclic aromatic carbon ring or aromatic hetero ring; m 1 , m 2 , m 3 and m 4 each are independently 0, 1, 2, 3 or 4, provided that the total of m 1 and m 2 is from 2 to 6, the total of m 3 and m 4 is from 2 to 6]. The compounds are useful as medicines for central system disorders, cardiovascular disorders, metabolic disorders.

  [问题] 提供一种黑色素浓集激素受体拮抗剂，可用作中枢系统疾病、心血管疾病和代谢性疾病的药物。[解决方案] 提供了一种公式（I）的化合物：[其中R1a和R1b分别是氢原子等；R2是氢原子、C1-6烷基等；Ar1是6元芳香碳环基或6元芳香氮杂环基；Ar2是从6元芳香碳环、6元芳香氮杂环等中去除两个氢原子形成的基团；Ar3是单环或双环芳香碳环或芳香杂环；m1、m2、m3和m4各自独立地为0、1、2、3或4，前提是m1和m2的总和为2到6，m3和m4的总和为2到6]。这些化合物可用作中枢系统疾病、心血管疾病和代谢性疾病的药物。
• Therapeutic Compounds
  申请人：Katz Jason

  公开号：US20110207711A1

  公开（公告）日：2011-08-25

  The present invention relates to pyrazolopyridines and imidazopyridines which are inhibitors of the kinase PDK1 and are thus useful for the treatment of myeloproliferative disorders or cancer. The compounds are also useful as inhibitors of other kinases such as FGFR3, NTRK3, RP-S6K and WEE1. Furthermore, the present compounds also selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease.

  本发明涉及一种抑制激酶PDK1的吡唑吡啶和咪唑吡啶化合物，因此可用于治疗骨髓增生性疾病或癌症。这些化合物也可用作其他激酶的抑制剂，例如FGFR3、NTRK3、RP-S6K和WEE1。此外，本化合物还具有选择性抑制微管亲和力调节激酶（MARK）的作用，因此可用于治疗或预防阿尔茨海默病。