4-甲氧基-1,2-苯并异噻唑 | 35272-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 4-甲氧基-1,2-苯并异噻唑
• 英文名称: 4-Methoxy-1,2-benzisothiazol
• 英文别名: 4-methoxybenzo[d]isothiazole；4-Methoxy-benzisothiazol；4-methoxy-1,2-benzisothiazole；4-methoxy-1,2-benzoisothiazole；4-methoxy-1,2-benzothiazole
• CAS: 35272-30-1
• 化学式: C₈H₇NOS
• 分子量: 165.216
• InChiKey: WILUPWLPVVSGHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  50.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲氧基-1,2-苯并异噻唑 在 盐酸 、 水 、 吡啶盐酸盐 、 铁粉 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 61.0h， 生成 N-[2-(4-{[4-(1,2-benzisothiazol-4-yloxy)-3-chlorophenyl]amino}-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl]acetamide
  参考文献：
  名称：

  Design and Synthesis of Pyrrolo[3,2-d]pyrimidine Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors: Exploration of Novel Back-Pocket Binders

  摘要：

  To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC50, 0.98/2.5 nM; and GI activity BT-474 cells, GI(50), 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg.

  DOI：

  10.1021/jm300185p
• 作为产物：
  描述：

  4-chloro-7-nitro-benzo[d]isothiazole 在 氢氧化钾 、 铁粉 作用下， 以 溶剂黄146 为溶剂， 生成 4-甲氧基-1,2-苯并异噻唑
  参考文献：
  名称：

  1,2,3-苯并噻二唑。第五部分：衍生自7-氨基苯并噻唑的重氮盐的重排

  摘要：

  苯并异噻唑-7-重氮盐重排成7-酰基苯并噻二唑的标准反应优于通过某些金属盐的存在消除氮的标准反应。这两个竞争反应的程度取决于金属的氧化电势。

  DOI：

  10.1039/j39710003994

文献信息

• [EN] 3-ARYLOXY/ THIO-2, 3-SUBSTITUTED PROPANAMINES AND THEIR USE IN INHIBITING SEROTONIN AND NOREPINEPHRINE REUPTAKE<br/>[FR] 3-ARYLOXY/THIO-2, 3-SUBSTITUE PROPANAMINES ET LEUR UTILISATION POUR INHIBER LE RECAPTAGE DE LA SEROTONINE ET DE LA NOREPINEPHRINE
  申请人：LILLY CO ELI

  公开号：WO2004043903A1

  公开（公告）日：2004-05-27

  There is provided a compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereofwith the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is OR3 and X is optionally substituted phenyl then A is -S-.

  提供一种化合物，其化学式为（I），其中A从-O-和-S-中选择；X从苯基选项地取代，每个取代基可独立地从卤素、C1-C4烷基和C1-C4烷氧基中选择最多5个取代基，噻吩基选项地取代，每个取代基可独立地从卤素和C1-C4烷基中选择最多3个取代基，以及C2-C8烷基、C2-C8烯基、C3-C8环烷基和C4-C8环烷基烷基，每个基可选地取代，每个取代基可独立地从卤素、C1-C4烷基、C1-C4烷氧基、C1-C4烷基-S(O)n-（其中n为0、1或2）、-CF3、-CN和-CONH2中选择；Y从苯基、萘基、二氢苯并噻吩基、苯并噻唑基、苯并异噻唑基、喹啉基、异喹啉基、萘啉基、噻吩吡啉基、茚基、1,3-苯并二氧杂环戊基、苯并噻吩基、吲哚基和苯并呋喃基中选择，每个基可选地取代，最多可独立地从卤素、C1-C4烷基、C1-C4烷氧基、C1-C4烷基-S(O)n-（其中n为0、1或2）、硝基、乙酰基、-CF3、-SCF3和氰基中选择最多4个或在可能的情况下最多5个取代基；当Y为吲哚基时，它可以被取代或进一步被N-取代基取代，N-取代基从C1-C4烷基中选择；Z从OR3或F中选择，其中R3从H、C1-C6烷基和苯基C1-C6烷基中选择；R1和R2各自独立地为H或C1-C4烷基；以及其药学上可接受的盐，但有一个条件，即当Y为可选地取代的苯基或可选地取代的1,3-苯并二氧杂环戊基，Z为OR3且X为可选地取代的苯基时，A为-S-。
• [EN] 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS<br/>[FR] DÉRIVÉS D'AZÉTIDINE OU DE CYCLOBUTANE 1,3-DISUBSTITUÉS UTILISÉS COMME INHIBITEURS DE LA PROSTAGLANDINE D SYNTHASE HÉMATOPOÏÉTIQUE (H-PGDS)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018069863A1

  公开（公告）日：2018-04-19

  A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  式（I）的化合物，其中R、R1、R2、R3、Y、Y1、a、X和Z的定义如本文所述。本发明的化合物是造血前列腺素D合成酶（H-PGDS）的抑制剂，可用于治疗杜兴氏肌肉萎缩症。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物来抑制H-PGDS活性和治疗相关疾病的方法。
• FUSED HETEROCYCLIC COMPOUND
  申请人：ISHIKAWA Tomoyasu

  公开号：US20090233937A1

  公开（公告）日：2009-09-17

  The present invention provides a fused heterocyclic compound having a tyrosine kinase inhibitory action, which is represented by the formula: wherein ring A is an optionally substituted benzene ring; ring B is an optionally substituted benzoisothiazole ring; R 1 is a hydrogen atom, a halogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom or an oxygen atom; R 2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom; R 3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group; or R 1 and R 2 , or R 2 and R 3 are optionally bonded to each other to form an optionally substituted ring structure; or R 3 is optionally bonded to the carbon atom on ring A to form an optionally substituted ring structure; or a salt thereof.

  本发明提供了一种具有酪氨酸激酶抑制作用的融合杂环化合物，其由以下式表示： 其中 环A是一个可选择取代的苯环； 环B是一个可选择取代的苯并异噻唑环； R1是氢原子、卤素原子或通过碳原子、氮原子或氧原子键合的可选择取代基团； R2是氢原子，或通过碳原子或硫原子键合的可选择取代基团； R3是氢原子或可选择取代的脂肪烃基团； 或 R1和R2，或R2和R3可选择键合在一起形成一个可选择取代的环结构； 或 R3可选择键合到环A上的碳原子上形成一个可选择取代的环结构； 或其盐。
• [EN] 3-ARYLOXY/THIO-3-SUBSTITUTED PROPANAMINES AND THEIR USE IN INHIBITING SEROTONIN AND NOREPHINEPHRINE REUPTAKE<br/>[FR] COMPOSES PHARMACEUTIQUES
  申请人：LILLY CO ELI

  公开号：WO2004043904A1

  公开（公告）日：2004-05-27

  There is provided a compound of formula (I) wherein A is selected from -O- and -S-; X is selected from C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from H, OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; with the proviso that, when Z is H, then Y may not be optionally substituted phenyl or optionally substituted naphthyl.

  提供一种具有以下结构的化合物（I）：其中A从-O-和-S-中选择；X从C2-C8烷基，C2-C8烯基，C3-C8环烷基和C4-C8环烷基烷基中选择，每种基团可能分别被选自卤素，C1-C4烷基，C1-C4烷氧基，C1-C4烷基-S(O)n-（其中n为0，1或2），-CF3，-CN和-CONH2的最多3个取代基所取代；Y从苯基，萘基，二氢苯并噻吩基，苯并噻唑基，苯并异噻唑基，喹啉基，异喹啉基，萘啉基，噻吩吡啉基，茚基，1,3-苯并二氧杂环戊基，苯并噻吩基，吲哚基和苯并呋喃基中选择，每种基团可能分别被选自卤素，C1-C4烷基，C1-C4烷氧基，C1-C4烷基-S(O)n-（其中n为0，1或2），硝基，乙酰基，-CF3，-SCF3和氰基的最多4个或在可能的情况下5个取代基所取代；当Y为吲哚基时，它可以被选自C1-C4烷基的N-取代基取代或进一步取代；Z从H，OR3或F中选择，其中R3从H，C1-C6烷基和苯基C1-C6烷基中选择；R1和R2分别独立地为H或C1-C4烷基；但是，当Z为H时，Y可能不是可选择地取代的苯基或可选择地取代的萘基。
• 4-Hydroxy-1,2-benzisothiazoles and their manufacture
  申请人：BASF Aktiengesellschaft

  公开号：US04189433A1

  公开（公告）日：1980-02-19

  The new compound 4-hydroxy-1,2-benzisothiazole and its derivatives, and their manufacture. The products are intermediates for new drugs which are useful in cardiac and circulatory disorders.

  新化合物4-羟基-1,2-苯并异噻唑及其衍生物及其制造方法。这些产品是用作新的心脏病和循环系统疾病药物的中间体。