2-chloro-6-cyclopropylbenzoyl chloride | 1561771-96-7

• 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: 2-chloro-6-cyclopropylbenzoyl chloride
• 英文别名: 2-Chloro-6-cyclopropylbenzoyl chloride
• CAS: 1561771-96-7
• 化学式: C₁₀H₈Cl₂O
• 分子量: 215.079
• InChiKey: ZKHDOWBUYPIKLV-UHFFFAOYSA-N

物化性质

• 沸点：
  283.1±33.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-6-cyclopropylbenzoyl chloride 在 4-二甲氨基吡啶 、 potassium phosphate 、 XPhos Pd G2 、 水 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (R)-4-(1-(2-chloro-6-cyclopropylbenzoyl)-6-(3-methoxyazetidine-1-carbonyl)-1H-indazol-3-yl)cyclohex-3-enecarboxylic acid
  参考文献：
  名称：

  3-CYCLOHEXENYL AND CYCLOHEXYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF

  摘要：

  本发明涉及式I化合物以及药用可接受的盐或溶剂化物。这类化合物可用于治疗RORgammaT介导的疾病或状况。

  公开号：

  US20150191434A1
• 作为产物：
  描述：

  2-氯-6-溴苯甲醛 在 sodium chlorite 、 potassium phosphate 、 sodium dihydrogenphosphate 、 四(三苯基膦)钯 、 草酰氯 、 氨基磺酸 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 15.0h， 生成 2-chloro-6-cyclopropylbenzoyl chloride
  参考文献：
  名称：

  Discovery of N-(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases

  摘要：

  The clinical success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases. The nuclear hormone receptor ROR gamma t is a master regulator of Th17 cells and affects the production of a host of cytokines, including IL-17A, IL-17F, IL -22, IL-26, and GMCSF. Substantial interest has been spurred across both academia and industry to seek small molecules suitable for ROR gamma t inhibition. A variety of ROR gamma t inhibitors have been reported in the past few years, the majority of which are orthosteric binders. Here we disclose the discovery and optimization of a class of inhibitors, which bind differently to an allosteric binding pocket. Starting from a weakly active hit 1, a tool compound 14 was quickly identified that demonstrated superior potency, selectivity, and off-target profile. Further optimization focused on improving metabolic stability. Replacing the benzoic acid moiety with piperidinyl carboxylate, modifying the 4-aza-indazole core in 14 to 4-F-indazole, and incorporating a key hydroxyl group led to the discovery of 25, which possesses exquisite potency and selectivity, as well as an improved pharmacokinetic profile suitable for oral dosing.

  DOI：

  10.1021/acsmedchemlett.9b00431

文献信息

• SUBSTITUTED BICYCLIC PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20180305320A1

  公开（公告）日：2018-10-25

  The present invention relates to compounds according to Formula I: and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.

  本发明涉及式I化合物：以及药用可接受的盐。此类化合物可用于治疗RORgammaT介导的疾病或状况。
• [EN] SUBSTITUTED DIHYDRO-BENZIMIDAZOLE COMPOUNDS AS ROR GAMMA MODULATORS<br/>[FR] UTILISATION DE COMPOSÉS SUBSTITUÉS DIHYDRO-BENZIMIDAZOLE COMME MODULATEURS DU ROR GAMMA
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2015052675A1

  公开（公告）日：2015-04-16

  The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as modulator of retinoid-related orphan receptor gamma t (RORyt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated disease, disorder, syndrome or condition such as pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, neurodegenerative diseases or cancer.

  本公开涉及式(I)的化合物及其药用盐，作为视黄醇相关孤儿受体γt（RORγt）的调节剂。这些化合物可以预防、抑制或抑制RORγt的作用，因此在治疗由RORγt介导的疾病、紊乱、综合症或病况，如疼痛、炎症、慢性阻塞性肺病（COPD）、哮喘、类风湿性关节炎、结肠炎、多发性硬化、神经退行性疾病或癌症方面具有用处。
• SUBSTITUTED PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20180016239A1

  公开（公告）日：2018-01-18

  The present invention relates to compounds according to Formula (I-1) and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.

  本发明涉及按照式(I-1)的化合物及其药用可接受的盐。这些化合物可用于治疗RORgammaT介导的疾病或症状。
• [EN] SUBSTITUTED INDAZOLE COMPOUNDS AS RORGAMMAT INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS INDAZOLE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE RORGAMMAT ET UTILISATIONS ASSOCIÉES
  申请人：MERCK SHARP & DOHME

  公开号：WO2017075182A1

  公开（公告）日：2017-05-04

  The present invention relates to compounds according to Formula (I) and pharmaceutically acceptable salts thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.

  本发明涉及式(I)化合物及其药用可接受的盐。此类化合物可用于治疗RORgammaT介导的疾病或状况。
• 4-HETEROARYL SUBSTITUTED BENZOIC ACID COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150218096A1

  公开（公告）日：2015-08-06

  The present invention relates to compounds according to Formula I (Formula I), and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.

  本发明涉及公式I（公式I）的化合物及其药学上可接受的盐或溶剂。这样的化合物可用于治疗RORgammaT介导的疾病或症状。