3-溴-2-氯-5-碘吡啶 | 1211586-80-9

• 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
• 中文名称: 3-溴-2-氯-5-碘吡啶
• 英文名称: 3-bromo-2-chloro-5-iodopyridine
• CAS: 1211586-80-9
• 化学式: C₅H₂BrClIN
• 分子量: 318.339
• InChiKey: DVYGSKKFDUFJQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  3-溴-2-氯-5-碘吡啶 在 potassium phosphate 、 copper(l) iodide 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 、 乙二醇 、 异丙醇 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  新型多取代的Pyridin-3-amine衍生物作为多靶点蛋白激酶抑制剂的设计，合成和药理评价，用于治疗非小细胞肺癌

  摘要：

  设计，合成和评估了一系列新颖的吡啶-3-胺衍生物，作为多靶点蛋白激酶抑制剂用于非小细胞肺癌（NSCLC）的治疗。首先通过计算机筛选针对成纤维细胞生长因子受体（FGFR）的命中1，随后通过体外实验对其进行了验证。然后研究其类似物的结构-活性关系（SAR），以提供新型FGFR抑制剂2a - 2p和3a - 3q。其中3m对FGFR1、2和3表现出有效的抑制作用。有趣的是，化合物3m不仅抑制FGFR过度激活的癌细胞中不同致癌形​​式的各种磷酸化和下游信号传导，而且还显示出对数种其他NSCLC相关癌基因激酶（包括RET，EGFR，EGFR / T790M / L858R，DDR2和ALK）的纳摩尔水平抑制作用。最后，3m的体内药理学评估显示具有良好药代动力学特征的NCI-H1581 NSCLC异种移植物具有显着的抗肿瘤活性（TGI = 66.1％）。

  DOI：

  10.1021/acs.jmedchem.7b00076
• 作为产物：
  描述：

  3-溴-5-碘-2-吡啶胺 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 4.0h， 以63%的产率得到3-溴-2-氯-5-碘吡啶
  参考文献：
  名称：

  手性六氢杂合的4,4'-联吡啶

  摘要：

  描述了通过两种互补方法制备手性六卤代-4,4'-联吡啶的27种异构体。第一种是收敛的，基于LDA诱导的三卤代吡啶的4,4'-二聚，而第二种方法是分歧的，是通过4,4'-联吡啶-2,2'-二酮的区域选择性卤化反应实现的。通过对2，2′-二溴衍生物进行的铜催化的Finkelstein反应（Buchwald方法）引入4，4′-联吡啶的2，2′-位处的碘。通过手性固定相上的高效液相色谱对映这种新的对映异构体4,4'-联吡啶家族的选定化合物，对映体分离，并使用X射线衍射分析确定分离的对映体的绝对构型。

  DOI：

  10.1021/acs.joc.6b00413

文献信息

• Design, Synthesis, and Pharmacological Evaluation of Novel Multisubstituted Pyridin-3-amine Derivatives as Multitargeted Protein Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer
  作者：Wei Zhu、Hui Chen、Yulan Wang、Jiang Wang、Xia Peng、Xianjie Chen、Yinglei Gao、Chunpu Li、Yulong He、Jing Ai、Meiyu Geng、Mingyue Zheng、Hong Liu

  DOI：10.1021/acs.jmedchem.7b00076

  日期：2017.7.27

  derivatives were designed, synthesized, and evaluated as multitargeted protein kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC). Hit 1 was first disclosed by in silico screening against fibroblast growth factor receptors (FGFR), which was subsequently validated by in vitro experiments. The structure–activity relationship (SAR) of its analogues was then explored to afford novel FGFR

  设计，合成和评估了一系列新颖的吡啶-3-胺衍生物，作为多靶点蛋白激酶抑制剂用于非小细胞肺癌（NSCLC）的治疗。首先通过计算机筛选针对成纤维细胞生长因子受体（FGFR）的命中1，随后通过体外实验对其进行了验证。然后研究其类似物的结构-活性关系（SAR），以提供新型FGFR抑制剂2a - 2p和3a - 3q。其中3m对FGFR1、2和3表现出有效的抑制作用。有趣的是，化合物3m不仅抑制FGFR过度激活的癌细胞中不同致癌形​​式的各种磷酸化和下游信号传导，而且还显示出对数种其他NSCLC相关癌基因激酶（包括RET，EGFR，EGFR / T790M / L858R，DDR2和ALK）的纳摩尔水平抑制作用。最后，3m的体内药理学评估显示具有良好药代动力学特征的NCI-H1581 NSCLC异种移植物具有显着的抗肿瘤活性（TGI = 66.1％）。
• Heteroaryl sulfonamides and CCR2
  申请人：ChemoCentryx, Inc.

  公开号：EP2474532A1

  公开（公告）日：2012-07-11

  A compound of the formula (I), or a salt thereof: where Ar is selected from the group consisting of substituted or unsubstituted C6-10 aryl and substituted or unsubstituted 5- to 10-membered heteroaryl; R1 is selected from the group consisting of hydrogen, unsubstituted C1 alkyl, substituted or unsubstituted C3-8 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; Y1 is selected from the group consisting of -CR2a-, -N-, and -N+(O)--; Y2 is selected from the group consisting of -CR2b-, -N-, and -N+(O)--; Y3 is selected from the group consisting of -CR2c-, -N-, and -N+(O)--; R2a, R2b, and R2c are each independently selected from the group consisting of hydrogen, halogen, -CN, -C(O)R3, -CO2R3, -C(O)NR3R4, -OR3, - OC(O)R3, -OC(O)NR3R4, -SR3, -S(O)R3, -S(O)2R3, -S(O)2NR3R4, -NO2, -NR3R4, -NR3C(O)R4, -NR3C(O)OR4, -NR3S(O)2R4, -NR3C(O)NR4R5, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, and substituted or unsubstituted 5- to 10-membered heteroaryl; R3, R4, and R5 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; R3 and R4, R4 and R5 or R3 and R5 may, together with the atoms to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered ring; Y4 is selected from the group consisting of -N- and -N+(O)--; L is selected from the group consisting of a bond, -O-, -S-, -S(O)-, S(O)2-, - CR6R7-, -NR8-, -C(O)- and -NR8C(O)-; R6 and R7 are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, -CN, -OR9, -NR10R11, -S(O)R9, and -S(O)2R9; R6 and R7 may, together with the carbon atom to which they are attached, form substituted or unsubstituted C3-8 cycloalkyl or substituted or unsubstituted 3-to 10-membered heterocyclic ring; R9 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; R10 and R11 are each independently selected from the group consisting of substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted C2-8 alkenyl, and substituted or unsubstituted C2-8 alkynyl; R10 and R11 of -NR10R11 may, together with the nitrogen, form a substituted or unsubstituted C3-8 cycloalkyl or substituted or unsubstituted 3- to 10-membered heterocyclyl; R8 is selected from the group consisting of hydrogen, C(O)R12, S(O)2R12, CO2R12, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; R12 is selected from the group consisting of substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, and substituted or unsubstituted 5- to 10-membered heteroaryl; Z1 is selected from the group consisting of substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted 3- to 10-membered heterocyclyl, and -NR13R14; R13 and R14 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted (C1-4 alkyl)-(C6-10 aryl), and substituted or unsubstituted (C1-4 alkyl)-(5- to 10-membered heteroaryl); R13 and R14 may, together with the nitrogen, form a substituted or unsubstituted 4-, 5-, 6-, or 7-membered heterocyclyl with the proviso that compounds of formula CC are excluded: where X14 is selected from the group consisting of -Cl, -NO2, -OCH3, -CH3, - NHC(O)CH3, and -CH2CH2-(phenyl); R65 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-4 alkyl, and substituted or unsubstituted -SO2(phenyl); and R60 is selected from the group consisting of -NR61CH2CH2OR62, - NR61CH2CH2NR63R64, -NR61CH2CH2SR62, where R61 is selected from the group consisting of hydrogen and substituted or unsubstituted phenyl; R62 is selected from the group consisting of substituted or unsubstituted phenyl, and substituted or unsubstituted C1-4 alkyl; and R63 and R64 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted -SO2(phenyl), - C(O)CH3, -C(O)C(O)OH, and -C(O)2C(CH3)3.

  一种具有式(I)或其盐的化合物：其中，Ar选自被取代或未取代的C6-10芳基或被取代或未取代的5-至10元杂芳基；R1选自氢、未取代的C1烷基、被取代或未取代的C3-8烷基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基和被取代或未取代的3-至10元杂环基；Y1选自-CR2a-、-N-和-N+(O)-；Y2选自-CR2b-、-N-和-N+(O)-；Y3选自-CR2c-、-N-和-N+(O)-；R2a、R2b和R2c各自独立地选自氢、卤素、-CN、-C(O)R3、-CO2R3、-C(O)NR3R4、-OR3、-OC(O)R3、-OC(O)NR3R4、-SR3、-S(O)R3、-S(O)2R3、-S(O)2NR3R4、-NO2、-NR3R4、-NR3C(O)R4、-NR3C(O)OR4、-NR3S(O)2R4、-NR3C(O)NR4R5、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基和被取代或未取代的5-至10元杂芳基；R3、R4和R5各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基和被取代或未取代的3-至10元杂环基；R3和R4、R4和R5或R3和R5可与它们所连接的原子一起形成被取代或未取代的5-、6-或7元环；Y4选自-N-和-N+(O)-；L选自键、-O-、-S-、-S(O)-、S(O)2-、-CR6R7-、-NR8-、-C(O)-和-NR8C(O)-；R6和R7各自独立地选自氢、卤素、被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基、-CN、-OR9、-NR10R11、-S(O)R9和-S(O)2R9；R6和R7可与它们所连接的碳原子一起形成被取代或未取代的C3-8环烷基或被取代或未取代的3-至10元杂环基；R9选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基和被取代或未取代的3-至10元杂环基；R10和R11各自独立地选自被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的C2-8烯基和被取代或未取代的C2-8炔基；-NR10R11中的R10和R11可与氮一起形成被取代或未取代的C3-8环烷基或被取代或未取代的3-至10元杂环基；R8选自氢、C(O)R12、S(O)2R12、CO2R12、被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C2-6烯基和被取代或未取代的C2-6炔基；R12选自被取代或未取代的C1-8烷基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基和被取代或未取代的5-至10元杂芳基；Z1选自被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的3-至10元杂环基和-NR13R14；R13和R14各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的(C1-4烷基)-(C6-10芳基)和被取代或未取代的(C1-4烷基)-(5-至10元杂芳基)；R13和R14可与氮一起形成被取代或未取代的4-、5-、6-或7元杂环基；其中排除式CC的化合物：其中，X14选自-Cl、-NO2、-OCH3、-CH3、-NHC(O)CH3和-CH2CH2-(苯基)；R65选自氢、被取代或未取代的C1-4烷基和被取代或未取代的-SO2(苯基)；R60选自-NR61CH2CH2OR62、-NR61CH2CH2NR63R64和-NR61CH2CH2SR62；其中，R61选自氢和被取代或未取代的苯基；R62选自被取代或未取代的苯基和被取代或未取代的C1-4烷基；R63和R64各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的苯基、被取代或未取代的-SO2(苯基)、-C(O)CH3、-C(O)C(O)OH和-C(O)2C(CH3)3。
• [EN] TRIAZOLYL PYRIDYL BENZENESULFONAMIDES<br/>[FR] TRIAZOLYL PYRIDYL BENZÈNESULFONAMIDES
  申请人：CHEMOCENTRYX INC

  公开号：WO2008008375A2

  公开（公告）日：2008-01-17

  [EN] Compounds are provided that act as potent antagonists of the CCR2 or CCR9 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2 and CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, CCR9-mediated diseases, as controls in assays for the identification of CCR2 antagonists and as controls in assays for the identification of CCR9 antagonists.
  [FR] L'invention concerne des composés agissant comme antagonistes puissants du récepteur CCR2 ou CCR9. Une expérimentation sur des animaux démontre que ces composés sont utiles dans le traitement de l'inflammation, une maladie caractéristique pour CCR2 et CCR9. D'une manière générale, les composés sont des dérivés d'aryl sulfonamide et sont utiles dans des compositions pharmaceutiques, des procédés pour le traitement de maladies à médiation par CCR2, de maladies à médiation par CCR9, comme témoins dans des dosages permettant l'identification d'antagonistes de CCR2 et d'antagonistes de CCR9.
• Chiral Hexahalogenated 4,4′-Bipyridines
  作者：V. Mamane、P. Peluso、E. Aubert、S. Cossu、P. Pale

  DOI：10.1021/acs.joc.6b00413

  日期：2016.6.3

  Finkelstein reaction (Buchwald procedure) performed on 2,2′-dibromo derivatives. Selected compounds of this new family of atropisomeric 4,4′-bipyridines were enantioseparated by high performance liquid chromatography on chiral stationary phases, and the absolute configurations of the separated enantiomers were assigned by using X-ray diffraction analysis. The latter revealed that various halogen bond

  描述了通过两种互补方法制备手性六卤代-4,4'-联吡啶的27种异构体。第一种是收敛的，基于LDA诱导的三卤代吡啶的4,4'-二聚，而第二种方法是分歧的，是通过4,4'-联吡啶-2,2'-二酮的区域选择性卤化反应实现的。通过对2，2′-二溴衍生物进行的铜催化的Finkelstein反应（Buchwald方法）引入4，4′-联吡啶的2，2′-位处的碘。通过手性固定相上的高效液相色谱对映这种新的对映异构体4,4'-联吡啶家族的选定化合物，对映体分离，并使用X射线衍射分析确定分离的对映体的绝对构型。
• Rational Design and Development of Novel CDK9 Inhibitors for the Treatment of Acute Myeloid Leukemia
  作者：Xu Han、Ning Song、Abdusaid Saidahmatov、Peipei Wang、Yong Wang、Xiaobei Hu、Weijuan Kan、Wei Zhu、Lixin Gao、Mingjie Zeng、Yujie Wang、Chunpu Li、Jia Li、Hong Liu、Yubo Zhou、Jiang Wang

  DOI：10.1021/acs.jmedchem.1c01148

  日期：2021.10.14