6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one | 1242157-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one
• 英文别名: 6-cyclopropyl-8-fluoro-3,4-dihydro-2H-isoquinolin-1-one
• CAS: 1242157-16-9
• 化学式: C₁₂H₁₂FNO
• 分子量: 205.232
• InChiKey: WLRAGDCTPXHVFU-UHFFFAOYSA-N

物化性质

• 沸点：
  442.1±45.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one 在 copper(l) iodide 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 三环己基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 39.5h， 生成 RN486抑制剂
  参考文献：
  名称：

  Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis

  摘要：

  Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.

  DOI：

  10.1021/jm500305p
• 作为产物：
  描述：

  4-溴-2-氟苯甲酰氯 在 aluminum (III) chloride 、 potassium phosphate 、 sodium azide 、 甲烷磺酸 、 palladium diacetate 、 sodium chloride 、 三环己基膦 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 12.0h， 生成 6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one
  参考文献：
  名称：

  Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis

  摘要：

  Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.

  DOI：

  10.1021/jm500305p

文献信息

• NOVEL TRIAZINE DERIVATIVE
  申请人：Carna Biosciences, Inc.

  公开号：EP2824099A1

  公开（公告）日：2015-01-14

  To provide a novel triazine derivative represented by the following formula (I): A triazine derivative represented by the following formula (I) : wherein R1 represents a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic ring, a substituted or unsubstituted heterocyclic fused ring, or a substituted or unsubstituted alkynyl group, R2 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted alkoxy group, R3 represents a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic ring, or a substituted or unsubstituted heterocyclic fused ring, R4 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted amino group, or a halogen atom, and R5 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, or R1 and R5 may be combined to form a saturated or unsaturated 5- to 6-membered ring, thereby forming a multiply fused ring, or a pharmaceutically acceptable salt thereof.

  提供以下式(I)所代表的一种新型三嗪衍生物： 由以下式(I)表示的三嗪衍生物： 其中 R1代表取代或未取代的芳基、取代或未取代的杂环基、取代或未取代的杂环融合环或取代或未取代的炔基， R2代表氢原子、卤原子、取代或未取代的较低烷基或取代或未取代的烷氧基， R3代表取代或未取代的芳基、取代或未取代的杂环基或取代或未取代的杂环融合环， R4代表氢原子、取代或未取代的较低烷基、取代或未取代的烷氧基、取代或未取代的氨基或卤原子，以及 R5代表氢原子、取代或未取代的较低烷基，或R1和R5可结合形成饱和或不饱和的5-至6元环，从而形成多重融合环， 或其药学上可接受的盐。
• Inhibitors of Bruton's Tyrosine Kinase
  申请人：Berthel Steven

  公开号：US20100222325A1

  公开（公告）日：2010-09-02

  This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y 1 , Y 2 , Y 2′ , Y 3 , Y 4 , Y 5 , m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.

  该应用程序根据通用公式I-III披露了5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡啶-3-酮和5-苯基-1H-吡嗪-2-酮衍生物： 其中，变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些化合物抑制Btk。本文披露的化合物对调节Btk的活性并治疗与过度Btk活性相关的疾病有用。这些化合物进一步有助于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还披露了含有公式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。
• Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton’s Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis
  作者：Wataru Kawahata、Tokiko Asami、Takao Kiyoi、Takayuki Irie、Haruka Taniguchi、Yuko Asamitsu、Tomoko Inoue、Takahiro Miyake、Masaaki Sawa

  DOI：10.1021/acs.jmedchem.8b01147

  日期：2018.10.11

  the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective

  Bruton的酪氨酸激酶（BTK）是用于治疗多种疾病（如B细胞恶性肿瘤，哮喘和类风湿关节炎）的有希望的药物靶标。通过脚手架跳跃方法，一系列新型氨基三嗪被确定为BTK的高选择性抑制剂。随后使用两种构象不同的BTK蛋白（一种活化形式的BTK和一种未活化形式的BTK）对该系列进行SAR研究，导致发现了高度选择性的BTK抑制剂4b。4b在体内模型中具有显着的疗效，并具有良好的ADME和安全性，已被推进临床前研究。
• Inhibitors of Bruton's tyrosine kinase
  申请人：Roche Palo Alto LLC

  公开号：US08299077B2

  公开（公告）日：2012-10-30

  This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formula I-III: wherein, variables Q, R, X, X′, Y1, Y2, Y2′, Y3, Y4, Y5, m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formula I-III and at least one carrier, diluent or excipient.

  本申请披露了根据通式I-III制备的5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡嗪-3-酮和5-苯基-1H-吡嗪-2-酮衍生物，其中变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些衍生物可以抑制Btk。本文所披露的化合物可用于调节Btk的活性和治疗与Btk过度活性相关的疾病。这些化合物还可用于治疗与异常B细胞增殖相关的炎症和自身免疫性疾病，如类风湿性关节炎。本申请还披露了包含通式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。
• US8299077B2
  申请人：——

  公开号：US8299077B2

  公开（公告）日：2012-10-30