5-(溴甲基)-1H-吲唑-1-羧酸,1,1-二甲基乙酯 | 209804-25-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 5-(溴甲基)-1H-吲唑-1-羧酸,1,1-二甲基乙酯
• 中文别名: 1-BOC-5-溴甲基吲唑；N-Boc-5-溴甲基吲唑
• 英文名称: 2-methyl-2-propanyl 5-(bromomethyl)-1H-indazole-1-carboxylate
• 英文别名: tert-butyl 5-(bromomethyl)indazole-1-carboxylate；tert-butyl 5-(bromomethyl)-1H-indazole-1-carboxylate
• CAS: 209804-25-1
• 化学式: C₁₃H₁₅BrN₂O₂
• 分子量: 311.178
• InChiKey: LKQALJCINTYLIY-UHFFFAOYSA-N

物化性质

• 沸点：
  400.3±37.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(溴甲基)-1H-吲唑-1-羧酸,1,1-二甲基乙酯 在 盐酸 、 甲醇 、 sodium hydride 作用下， 反应 1.5h， 生成 (4R,5S,6S,7R)-4,7-Dibenzyl-5,6-dihydroxy-1-(1H-indazol-5-ylmethyl)-[1,3]diazepan-2-one
  参考文献：
  名称：

  Nonsymmetric P2/P2‘ Cyclic Urea HIV Protease Inhibitors. Structure−Activity Relationship, Bioavailability, and Resistance Profile of Monoindazole-Substituted P2 Analogues

  摘要：

  Using the structural information gathered from the X-ray structures of various cyclic urea/ HIVPR complexes, we designed and synthesized many nonsymmetrical P2/P2'-substituted cyclic urea analogues. Our efforts concentrated on using an indazole as one of the P2 substituents since this group imparted enzyme (K-i) potency as well as translation into excellent antiviral (IC90) potency. The second P2 substituent was used to adjust the physical and chemical properties in order to maximize oral bioavailability. Using this approach several very potent (IC90 11 nM) and orally bioavailable (F% 93-100%) compounds were discovered (21, 22). However, the resistance profiles of these compounds were inadequate, especially against the double (I84V/V82F) and ritonavir-selected mutant viruses. Further modification of the second P2 substituent in order to increase H-bonding interactions with the backbone atoms of residues Asp 29, Asp 30, and Gly 48 led to analogues with much better resistance profiles. However, these larger analogues were incompatible with the apparent molecular weight requirements for good oral bioavailability of the cyclic urea class of HIVPR inhibitors (MW < 610).

  DOI：

  10.1021/jm980103g
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 三乙胺 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 5-(溴甲基)-1H-吲唑-1-羧酸,1,1-二甲基乙酯
  参考文献：
  名称：

  KIT INHIBITORS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

  摘要：

  Provided herein are compounds and compositions useful in inhibiting a receptor tyrosine kinase, KIT.　The compounds and compositions provided herein are useful for the prevention or treatment of one or more KIT mediated diseases or conditions (e.g., cancers, autoimmune diseases, allergic diseases, inflammatory diseases, fibrosis, metabolic disorders, and neurodegenerative diseases).

  公开号：

  WO2024117179A1

文献信息

• [EN] COMPOUNDS AND METHODS FOR MODULATING SPLICING<br/>[FR] COMPOSÉS ET PROCÉDÉS DE MODULATION DE L'ÉPISSAGE
  申请人：[en]REMIX THERAPEUTICS INC.

  公开号：WO2023034812A1

  公开（公告）日：2023-03-09

  The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.
• Nonsymmetric P2/P2‘ Cyclic Urea HIV Protease Inhibitors. Structure−Activity Relationship, Bioavailability, and Resistance Profile of Monoindazole-Substituted P2 Analogues
  作者：George V. De Lucca、Ui T. Kim、Jing Liang、Beverly Cordova、Ronald M. Klabe、Sena Garber、Lee T. Bacheler、Gilbert N. Lam、Matthew R. Wright、Kelly A. Logue、Susan Erickson-Viitanen、Soo S. Ko、George L. Trainor

  DOI：10.1021/jm980103g

  日期：1998.6.1

  Using the structural information gathered from the X-ray structures of various cyclic urea/ HIVPR complexes, we designed and synthesized many nonsymmetrical P2/P2'-substituted cyclic urea analogues. Our efforts concentrated on using an indazole as one of the P2 substituents since this group imparted enzyme (K-i) potency as well as translation into excellent antiviral (IC90) potency. The second P2 substituent was used to adjust the physical and chemical properties in order to maximize oral bioavailability. Using this approach several very potent (IC90 11 nM) and orally bioavailable (F% 93-100%) compounds were discovered (21, 22). However, the resistance profiles of these compounds were inadequate, especially against the double (I84V/V82F) and ritonavir-selected mutant viruses. Further modification of the second P2 substituent in order to increase H-bonding interactions with the backbone atoms of residues Asp 29, Asp 30, and Gly 48 led to analogues with much better resistance profiles. However, these larger analogues were incompatible with the apparent molecular weight requirements for good oral bioavailability of the cyclic urea class of HIVPR inhibitors (MW < 610).
• KIT INHIBITORS, COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：[en]ALIVEXIS, INC.

  公开号：WO2024117179A1

  公开（公告）日：2024-06-06

  Provided herein are compounds and compositions useful in inhibiting a receptor tyrosine kinase, KIT.　The compounds and compositions provided herein are useful for the prevention or treatment of one or more KIT mediated diseases or conditions (e.g., cancers, autoimmune diseases, allergic diseases, inflammatory diseases, fibrosis, metabolic disorders, and neurodegenerative diseases).