1-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol | 1229024-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol
• 英文别名: 1-(4-amino-2-butylimidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol
• CAS: 1229024-78-5
• 化学式: C₁₈H₂₄N₄O
• 分子量: 312.415
• InChiKey: GITVQUOQRHRGQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  552.9±40.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 5-[[2-[2-[1-(4-amino-2-butylimidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yl]oxycarbonyloxyethyldisulfanyl]-1-carboxyethyl]amino]-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  [EN] METHOD OF TREATING CANCER BY TARGETING MYELOID-DERIVED SUPPRESSOR CELLS
  [FR] PROCÉDÉ DE TRAITEMENT DU CANCER PAR CIBLAGE DE CELLULES SUPPRESSIVES D'ORIGINE MYÉLOÏDE

  摘要：

  本发明涉及使用一种或多种包含通过连接剂连接的叶酸受体结合配体的药物来治疗癌症的方法。更具体地说，本发明涉及使用一种或多种包含通过连接剂连接的叶酸受体结合配体的药物来治疗癌症，以靶向骨髓源性抑制细胞。

  公开号：

  WO2017205661A1
• 作为产物：
  描述：

  1-[(3-氨基-2-氯-4-喹啉)氨基]-2-甲基-2-丙醇 在 氨 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 11.0h， 生成 1-(4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol
  参考文献：
  名称：

  [EN] LOCALLY ACTING TOLL-LIKE RECEPTOR 7 (TLR7) AND/OR TLR8 AGONIST IMMUNOTHERAPY COMPOUNDS AND THEIR USES
  [FR] COMPOSÉS D'IMMUNOTHÉRAPIE AGONISTES DU RÉCEPTEUR 7 DE TYPE TOLL (TLR7) ET/OU TLR8 À ACTION LOCALE ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2020205996A3

文献信息

• [EN] IMIDAZOQUINOLINE-TYPE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DU TYPE IMIDAZOQUINOLINE ET LEURS UTILISATIONS
  申请人：ALTIMMUNE UK LTD

  公开号：WO2021202921A1

  公开（公告）日：2021-10-07

  Provided in the present disclosure are imidazoquinoline-type compounds, methods for their preparation, pharmaceutical compositions thereof and their use, wherein the imidazoquinoline-type compounds, upon local administration, form depots inducing cell mediated immune response while mitigating a systemic proinflammatory immune response.

  本公开提供了咪唑喹啉类化合物，其制备方法，其制药组合物及其用途，其中咪唑喹啉类化合物在局部给药时形成沉积物，诱导细胞介导的免疫反应，同时减轻全身的促炎免疫反应。
• [EN] METHOD OF TREATING CANCER BY TARGETING MYELOID-DERIVED SUPPRESSOR CELLS<br/>[FR] PROCÉDÉ DE TRAITEMENT DU CANCER PAR CIBLAGE DE CELLULES SUPPRESSIVES D'ORIGINE MYÉLOÏDE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2017205661A1

  公开（公告）日：2017-11-30

  The invention described herein relates to methods for treating a cancer using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker. More particularly, the invention described herein relates to methods for treating a cancer using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker to target myeloid-derived suppressor cells.

  本发明涉及使用一种或多种包含通过连接剂连接的叶酸受体结合配体的药物来治疗癌症的方法。更具体地说，本发明涉及使用一种或多种包含通过连接剂连接的叶酸受体结合配体的药物来治疗癌症，以靶向骨髓源性抑制细胞。
• Process for preparing tetrahdroimidazoquinolinamines
  申请人：Minnesota Mining and Manufacturing Company

  公开号：US05693811A1

  公开（公告）日：1997-12-02

  A process for preparing 6, 7, 8, 9-tetrahydro-1H-imidazo\x9b4,5-c!quinolin-4-amines is disclosed. The process involves the reduction of a 1H-imidazo\x9b4,5-c!quinolin-4-amine or of a 6H-imidazo\x9b4,5-c!tetrazolo\x9b1,5-a!quinoline.

  揭示了一种制备6,7,8,9-四氢-1H-咪唑[4,5-c]喹啉-4-胺的过程。该过程涉及将1H-咪唑[4,5-c]喹啉-4-胺或6H-咪唑[4,5-c]四唑[1,5-a]喹啉还原。
• [EN] METHODS FOR ENHANCEMENT OF ENGINEERED CELL THERAPIES IN CANCER TREATMENT<br/>[FR] PROCÉDÉS D'AMÉLIORATION DE THÉRAPIES CELLULAIRES MODIFIÉES DANS LE TRAITEMENT DU CANCER
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2022147576A1

  公开（公告）日：2022-07-07

  Methods are provided for reprogramming M2 -like macrophages to Ml -like macrophages, which reverses the proinflammatory to anti-inflammatory shift observed during the course of certain cancers, co-administered with one or more types of engineered cells such as, without limitation, CAR T-cells, engineered natural killer cells, engineered stem cells or the like. The compounds comprise an immune modulator that targets a pattern recognition receptor of a cell and are specific to the cells of interest through the incorporation of a targeting moiety (e.g., folate or a functional fragment or analog thereof). Releasable and/or non-releasable linkers can be included and engineered to facilitate the optimal delivery of the immune modulator. The compounds and compositions can be employed in one or more methods of treatment for cancers.

  提供了一种将M2型巨噬细胞重新编程为M1型巨噬细胞的方法，这可以逆转某些癌症过程中观察到的促炎症到抗炎症的转变，与一种或多种工程细胞（例如CAR T细胞，工程自然杀伤细胞，工程干细胞等）共同使用。这些化合物包括一个免疫调节剂，其靶向细胞的模式识别受体，并通过纳入靶向基团（例如叶酸或其功能性片段或类似物）特异性地作用于感兴趣的细胞。可以包括可释放和/或不可释放的连接剂，并设计为促进免疫调节剂的最佳输送。这些化合物和组合物可以用于一个或多个癌症治疗方法。
• Structure−Activity Relationships in Human Toll-Like Receptor 7-Active Imidazoquinoline Analogues
  作者：Nikunj M. Shukla、Subbalakshmi S. Malladi、Cole A. Mutz、Rajalakshmi Balakrishna、Sunil A. David

  DOI：10.1021/jm100358c

  日期：2010.6.10

  Engagement of toll-like receptors serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. A structure activity study was conducted on the TLR7-agonistic imidazoquinolines, starting with 1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as a lead. Modifications of the secondary amine of the C2 ethylaminomethylene side chain are poorly tolerated. The 4-amino group must be retained for activity. Replacement of the imidazole ring of the scaffold with triazole or cyclic urea led to complete loss of activity. A systematic exploration of N-1-benzyl-C2-alkyl substituents showed a very distinct relationship between alkyl length and TLR7-agonistic potency with the optimal compound bearing a C2-n-butyl group. Transposition of the N-1 and C2 substituents led to the identification of an extremely active TLR7-agonistic compound with an EC50 value of 8.6 nM. The relative potencies in human TLR7-based primary reporter gene assays were paralleled by interferon-alpha induction activities in whole human blood models.