4-溴-2-氟-6-甲基苯甲酰胺 | 1242156-51-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-溴-2-氟-6-甲基苯甲酰胺
• 英文名称: 4-bromo-2-fluoro-6-methylbenzamide
• CAS: 1242156-51-9
• 化学式: C₈H₇BrFNO
• 分子量: 232.052
• InChiKey: IJOBPZLSYVGZPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-溴-2-氟-6-甲基苯甲酰胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 copper(l) iodide 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 三环己基膦 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 21.5h， 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-6-甲基苯甲酸 在 N,N'-羰基二咪唑 、 ammonium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以87%的产率得到4-溴-2-氟-6-甲基苯甲酰胺
  参考文献：
  名称：

  [EN] BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
  [FR] COMPOSÉS BIFONCTIONNELS POUR LA DÉGRADATION DE BTK PAR L'INTERMÉDIAIRE DE LA VOIE DE L'UBIQUITINE-PROTÉOSOME

  摘要：

  本发明涉及一种通过泛素蛋白酶途径降解BTK的化合物（I）的公式，还提供包含所述化合物的药学上可接受的组合物以及使用这些组合物治疗各种疾病、状况或障碍的方法。

  公开号：

  WO2021091575A1

文献信息

• 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。
• NOVEL TRIAZINE DERIVATIVE
  申请人：CARNA BIOSCIENCE, INC.

  公开号：US20160168122A1

  公开（公告）日：2016-06-16

  The purpose of the present invention is to provide a novel triazine derivative of the formula (I): wherein R 1 represents a substituted or unsubstituted lower alkyl group, R 2 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group, A represents a nitrogen atom or C—R 3 , R 3 represents a hydrogen atom, a cyano group, a substituted or unsubstituted acyl group, a substituted or unsubstituted sulfonyl group, or a substituted or unsubstituted carbamoyl group, and R 4 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted cycloalkyl group, or a pharmaceutically acceptable salt thereof.

  本发明的目的是提供一种新颖的三嗪衍生物，其化学式为（I）： 其中 R1代表取代或未取代的较低烷基基团， R2代表氢原子或取代或未取代的较低烷基基团， A代表氮原子或C—R3， R3代表氢原子、氰基、取代或未取代的酰基、取代或未取代的磺酰基或取代或未取代的氨基甲酰基，以及 R4代表取代或未取代的较低烷基基团， 或取代或未取代的环烷基基团， 或其药学上可接受的盐。
• NOVEL 2,6-DIAMINOPYRIMIDINE DERIVATIVE
  申请人：CARNA BIOSCIENCES, INC.

  公开号：US20160207906A1

  公开（公告）日：2016-07-21

  To provide a novel 2,6-diaminopyrimidine derivative by the following formula (I): A 2,6-diaminopyrimidine derivative is represented by the formula (I): wherein R 1 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted alkoxy group, Ar represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, Z 1 and Z 2 represent carbon atoms, or either 1 or 2 of the Z 1 and Z 2 represent nitrogen atoms, Q is selected from a structure (a) or (b) described below: R 2 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted cycloalkyl group, R 3 represents a hydrogen atom or a halogen atom, Y represents a nitrogen atom or a carbon atom, and the bond drawn with a dotted line parallel to a solid line on structure (a) represents either double bond or single bond.

  通过以下公式(I)提供一种新颖的2,6-二氨基嘧啶衍生物： 代表公式(I)的2,6-二氨基嘧啶衍生物如下： 其中 R1代表取代或未取代的较低烷基基团，或取代或未取代的烷氧基团， Ar代表取代或未取代的芳基团，或取代或未取代的杂芳基团， Z1和Z2代表碳原子，或Z1和Z2中的1个或2个代表氮原子， Q从下面描述的结构(a)或(b)中选择： R2代表取代或未取代的较低烷基基团，或取代或未取代的环烷基基团， R3代表氢原子或卤原子， Y代表氮原子或碳原子，结构(a)上与实线平行画的虚线代表双键或单键。
• [EN] BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY<br/>[FR] COMPOSÉS BIFONCTIONNELS POUR LA DÉGRADATION DE BTK PAR L'INTERMÉDIAIRE DE LA VOIE DE L'UBIQUITINE-PROTÉOSOME
  申请人：NURIX THERAPEUTICS INC

  公开号：WO2021091575A1

  公开（公告）日：2021-05-14

  The present invention relates to compounds of formula (I) useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及一种通过泛素蛋白酶途径降解BTK的化合物（I）的公式，还提供包含所述化合物的药学上可接受的组合物以及使用这些组合物治疗各种疾病、状况或障碍的方法。
• 신규 트리아진 유도체
  申请人：Carna Biosciences, Inc. 카나 바이오사이언스, 인코포레이션(520040450124)

  公开号：KR20160041946A

  公开（公告）日：2016-04-18

  본 발명의 목적은 하기 화학식 (I)로 표시되는 트리아진 유도체, 그의 약학적으로 허용되는 염을 제공하는 것이다: 상기 식에서, R은 치환되거나 비치환된 저급 알킬기를 나타내고, R는 수소 원자 또는 치환되거나 비치환된 저급 알킬기를 나타내고, A는 질소 원자 또는 C-R을 나타내고, R은 수소 원자, 시아노기, 치환되거나 비치환된 아실기, 치환되거나 비치환된 설포닐기 또는 치환되거나 비치환된 카르바모일기를 나타내고, R는 치환되거나 비치환된 저급 알킬기 또는 치환되거나 비치환된 사이클로알킬기를 나타낸다.

  The purpose of the present invention is to provide a triazine derivative represented by the following chemical formula (I) and its pharmaceutically acceptable salts: In the above formula, R represents a substituted or unsubstituted lower alkyl group, R represents a hydrogen atom or a substituted or unsubstituted lower alkyl group, A represents a nitrogen atom or C-R, R represents a hydrogen atom, cyano group, substituted or unsubstituted acyl group, substituted or unsubstituted sulfonyl group, or substituted or unsubstituted carbamoyl group, and R represents a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted cycloalkyl group.