4-chloro-1-nitro-2-(propan-2-yloxy)benzene | 40422-90-0

• 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-1-nitro-2-(propan-2-yloxy)benzene
• 英文别名: 4-chloro-1-nitro-2-propan-2-yloxybenzene
• CAS: 40422-90-0
• 化学式: C₉H₁₀ClNO₃
• 分子量: 215.636
• InChiKey: HCIBCEGQISKOTI-UHFFFAOYSA-N

物化性质

• 沸点：
  308.7±22.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chloro-1-nitro-2-(propan-2-yloxy)benzene 在 2-双环己基膦-2',6'-二甲氧基联苯 、 platinum(IV) oxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 氢气 、 palladium diacetate 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0~150.0 ℃ 、101.33 kPa 条件下， 生成 5-氯-N2-(2-异丙氧基-4-(哌啶-4-基)苯基)-N4-(2-(异丙基磺酰基)苯基)嘧啶-2,4-二胺
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

  摘要：

  The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.

  DOI：

  10.1021/jm400402q
• 作为产物：
  描述：

  3-氯氟苯 在 硫酸 、 caesium carbonate 、 potassium nitrate 作用下， 生成 4-chloro-1-nitro-2-(propan-2-yloxy)benzene
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

  摘要：

  The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.

  DOI：

  10.1021/jm400402q

文献信息

• [EN] NOVEL THIENOPYRIMIDINE DERIVATIVES, PROCESSES FOR THE PREPARATION THEREOF AND THERAPEUTIC USES THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS DE THIÉNOPYRIMIDINE, LEURS PROCÉDÉS DE PRÉPARATION ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：SANOFI SA

  公开号：WO2013150036A1

  公开（公告）日：2013-10-10

  The present invention relates to compounds of formula (I): wherein R6 is -CONH2 or a -C(Rα)(Rβ)(OH) group; R is a substituted phenyl or heteroaryl group; R7 is an optionally substituted aryl or heteroaryl group. Process for the preparation thereof and therapeutic use thereof.

  本发明涉及式(I)化合物的制备过程及其治疗用途：其中R6是-CONH2或一个-C(Rα)(Rβ)(OH)基团；R是一个取代的苯基或杂芳基团；R7是一个可选地取代的芳基或杂芳基团。
• NOVEL THIENOPYRIMIDINE DERIVATIVES, PROCESSES FOR THE PREPARATION THEREOF AND THERAPEUTIC USES THEREOF
  申请人：CARRY Jean-Christophe

  公开号：US20130261106A1

  公开（公告）日：2013-10-03

  The present invention relates to compounds of formula (I): wherein R6 is —CONH 2 or a —C(R α )(R β )(OH) group; R is a substituted phenyl or heteroaryl group; R7 is an optionally substituted aryl or heteroaryl group. Process for the preparation thereof and therapeutic use thereof.

  本发明涉及具有公式(I)的化合物： 其中R6是—CONH2或—C(Rα)(Rβ)(OH)基团；R是取代的苯基或杂芳基团；R7是可选地取代的芳基或杂芳基团。 其制备过程及其治疗用途。
• [EN] PYRROPYRIMIDINE COMPOUNDS AS MNKS INHIBITORS<br/>[FR] COMPOSÉS DE PYRROPYRIMIDINE EN TANT QU'INHIBITEURS DE MNKS
  申请人：MEDICAL RES COUNCIL TECH

  公开号：WO2017085483A1

  公开（公告）日：2017-05-26

  The present invention relates to compounds of formulae I, or pharmaceutically acceptable salts or esters thereof, wherein: R1 is selected from H and CO-NR8R9, wherein R8 and R9 are each independently selected from H, alkyl, cycloalkyl and mono or bicyclic heterocycloalkyl, wherein said alkyl group is optionally substituted by one or more R12 groups, and said heterocycloalkyl is optionally substituted by R10 or R12; or R8 and R9 are linked, together with the nitrogen to which they are attached, to form a heterocycloalkyl group optionally containing one or more additional heteroatoms, and optionally substituted by one or more groups select from R10 and (CH2)mR12; R2 is selected from H and alkyl, wherein said alkyl group is optionally substituted by one or more R12 groups; R3 is selected from alkyl, cycloalkyl and heterocycloalkyl, each of which may be optionally substituted by halo, OH or alkoxy; Z1, Z2, Z3 and Z4 are all C; R4, R5, R6 and R7 are each independently selected from H, alkyl, CN, NO2,OH, alkoxy, NHCO-alkyl, halo and haloalkyl; or Ζ1, Z3 and Z4 are ail C, Z2 is N, R5 is absent and R4, R6 and R7 are as defined above; or Z1, Z3 and Z4 are all C, Z1 is N, R4 is absent and R5, R6 and R7 are as defined above; each R10 and R11 is independently alkyl; each R12 is independently selected from CO2R10, COOH, OH, alkoxy, haloalkyl, NH2, NHR10, NR10R11, heteroaryl and heterocycloalkyl; R13 is H or halo. Further aspects relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.

  本发明涉及以下式I的化合物，或其药学上可接受的盐或酯，其中：R1从H和CO-NR8R9中选择，其中R8和R9各自独立地从H、烷基、环烷基和单环或双环杂环烷基中选择，其中所述烷基基团可以选择性地被一个或多个R12基团取代，所述杂环烷基可以选择性地被R10或R12取代；或R8和R9与它们连接，连同它们附着的氮一起形成一个可能含有一个或多个额外杂原子的杂环烷基基团，并且可以选择性地被一个或多个基团选择自R10和(CH2)mR12；R2从H和烷基中选择，其中所述烷基基团可以选择性地被一个或多个R12基团取代；R3从烷基、环烷基和杂环烷基中选择，每个都可以选择性地被卤、OH或烷氧基取代；Z1、Z2、Z3和Z4都是C；R4、R5、R6和R7各自独立地从H、烷基、CN、NO2、OH、烷氧基、NHCO-烷基、卤和卤代烷基中选择；或Ζ1、Z3和Z4都是C，Z2是N，R5不存在，R4、R6和R7如上所定义；或Z1、Z3和Z4都是C，Z1是N，R4不存在，R5、R6和R7如上所定义；每个R10和R11独立地是烷基；每个R12独立地从CO2R10、COOH、OH、烷氧基、卤代烷基、NH2、NHR10、NR10R11、杂芳基和杂环烷基中选择；R13是H或卤。进一步方面涉及所述化合物在治疗细胞生长、增殖和/或存活失控的疾病、不当的细胞免疫反应、不当的细胞炎症反应或神经退行性疾病，优选是tau病变，甚至更优选是阿尔茨海默病中的药物组合物和治疗用途。
• Isoxazolecarboxamide derivatives
  申请人：RECORDATI, S.A., CHEMICAL AND PHARMACEUTICAL COMPANY

  公开号：US20020161012A1

  公开（公告）日：2002-10-31

  The invention relates to novel N-(substituted phenyl)-N′-[(&ohgr;-(3-substituted phenyl-4-isoxazolecarbonylamino)alkyl]piperazines, their N-oxides, and pharmaceutically acceptable salts thereof. The compounds are endowed with enhanced selectivity for alpha1-adrenergic receptors and a low activity in lowering blood pressure. The compounds are useful in the treatment of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and in the treatment of lower urinary tract symptoms (LUTS) and neurogenic lower urinary tract dysfunction (NLUTD), and other conditions. The compounds may be administered alone or in combination with an anticholinergic compound.

  该发明涉及一种新型N-（取代苯基）-N' - [[（&ohgr; -（3-取代苯基-4-异噁唑-4-羧酰胺基）烷基]哌嗪，其N-氧化物和其药学上可接受的盐。这些化合物具有增强的α1-肾上腺素受体选择性和降低血压的低活性。这些化合物可以用于治疗下尿路阻塞性综合症，包括良性前列腺增生（BPH），以及下尿路症状（LUTS）和神经源性下尿路功能障碍（NLUTD）和其他疾病。这些化合物可以单独或与抗胆碱化合物联合使用。
• Thienopyrimidine derivatives, processes for the preparation thereof and therapeutic uses thereof
  申请人：SANOFI

  公开号：US09115140B2

  公开（公告）日：2015-08-25

  The present invention relates to compounds of formula (I): wherein R6 is —CONH2 or a —C(Rα)(Rβ)(OH) group; R is a substituted phenyl or heteroaryl group; R7 is an optionally substituted aryl or heteroaryl group. Process for the preparation thereof and therapeutic use thereof.

  本发明涉及式(I)的化合物：其中R6是—CONH2或—C(Rα)(Rβ)(OH)基团；R是取代苯基或杂环基团；R7是可选取代的芳基或杂环基团。本发明还涉及制备这些化合物的方法和治疗应用。