N1-(4-氯苯基)-6-甲基-N5-[3-(9H-嘌呤-6-基)-2-吡啶]-1,5-异喹啉二胺 | 1093100-40-3

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: N1-(4-氯苯基)-6-甲基-N5-[3-(9H-嘌呤-6-基)-2-吡啶]-1,5-异喹啉二胺
• 英文名称: N5-(3-(9H-purin-6-yl)pyridin-2-yl)-N1-(4-chlorophenyl)-6-methylisoquinoline-1,5-diamine
• 英文别名: N1-(4-chlorophenyl)-6-methyl-N5-(3-(9H-purin-6-yl)-2-pyridinyl)-1,5-isoquinolinediamine；B-Raf inhibitor 1；1-N-(4-chlorophenyl)-6-methyl-5-N-[3-(7H-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine
• CAS: 1093100-40-3
• 化学式: C₂₆H₁₉ClN₈
• 分子量: 478.943
• InChiKey: KKVYYGGCHJGEFJ-UHFFFAOYSA-N

物化性质

• 沸点：
  735.4±60.0 °C(Predicted)
• 密度：
  1.461±0.06 g/cm3(Predicted)
• 溶解度：
  ≥ 47.9mg/mL，溶于 DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

Raf inhibitor 1是一种有效的 Raf 激酶抑制剂，作用于 B-RafWT, B-RafV600E, 和 C-Raf, Ki 分别为 1 nM, 1 nM, 和 0.3 nM。

靶点

B-Raf 1 nM (Ki)

B-Raf V600E 1 nM (Ki)

c-Raf 0.3 nM (Ki)

体外研究

Raf inhibitor 1 (Compound 13) inhibits A375 and HCT-116 proliferation with IC ₅₀ s of 0.31 and 0.72 μM, respectively. Raf inhibitor 1 (Compound 13) binds to and stabilizes B-Raf in a DFG-out, inactive conformation in which the ATP pocket is partially filled by Phe595 and Gly596 from the DFG motif. Raf inhibitor 1 (Compound 13) additionally exhibits low micromolar inhibition against wild type B-Raf cell lines, which may be due to off-target kinase activities or alternatively to pan-Raf inhibition, including Raf dimers.

文献信息

• CELL DEATH INDUCING AGENT FOR CELLS HAVING BRAF GENE MUTATION, AGENT FOR INHIBITING PROLIFERATION OF SAID CELLS AND PHARMACEUTICAL COMPOSITION FOR TREATING PATIENT SUFFERING FROM EFFECTS OF ABNORMAL PROLIFERATION OF SAID CELLS
  申请人：Nitto Denko Corporation

  公开号：EP3284481A1

  公开（公告）日：2018-02-21

  Cell death is induced and/or cell growth is suppressed for a cell having a mutation in the BRAF gene. A drug suppressing GST-π is comprised as an active ingredient.

  对于 BRAF 基因突变的细胞，可诱导细胞死亡和/或抑制细胞生长。一种抑制 GST-π 的药物作为活性成分。
• Use of BRaf inhibitors for treating cutaneous reactions
  申请人：Lutris Pharma Ltd.

  公开号：US10632123B2

  公开（公告）日：2020-04-28

  The invention discloses compositions comprising BRaf inhibitors and uses thereof for treating and/or preventing by topical or systemic administration cutaneous conditions caused by treatment with EGFR inhibitors and/or PI3K inhibitors.

  本发明公开了包含 BRaf 抑制剂的组合物及其用途，可通过局部或全身给药治疗和/或预防表皮生长因子受体抑制剂和/或 PI3K 抑制剂治疗引起的皮肤病。
• BRaf inhibitors and use thereof for treatment of cutaneous reactions
  申请人：LUTRIS PHARMA LTD.

  公开号：US10927112B2

  公开（公告）日：2021-02-23

  The present invention discloses novel BRaf inhibitors of formula (I), (II) or (III), wherein R is defined as set forth in the specification, compositions comprising these BRaf inhibitors and uses thereof for the treatment, amelioration and/or prevention of cutaneous reactions.

  本发明公开了式(I)、(II)或(III)（其中R的定义如说明书所述）的新型BRaf抑制剂、包含这些BRaf抑制剂的组合物及其用于治疗、改善和/或预防皮肤反应的用途。
• Methods of screening BRaf inhibitors for treating cutaneous reactions
  申请人：Lutris Pharma Ltd.

  公开号：US11197861B2

  公开（公告）日：2021-12-14

  The invention discloses methods for screening out of a BRaf inhibitor population, suitable BRaf inhibitors as candidates for clinical development of drugs for treating and/or preventing cutaneous reaction caused by treatment with EGFR inhibitor and/or PI3K inhibitors.

  本发明公开了从BRaf抑制剂群体中筛选出合适的BRaf抑制剂作为临床开发候选药物的方法，这些候选药物可用于治疗和/或预防表皮生长因子受体抑制剂和/或PI3K抑制剂治疗引起的皮肤反应。
• THERAPEUTIC AGENT FOR TUMOR
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP2700403B1

  公开（公告）日：2015-11-25