9-butyl-8-(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine | 352519-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-butyl-8-(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine
• 英文别名: 9-Butyl-8-(3,4,5-trimethoxybenzyl)-9H-purin-6-amine；9-butyl-8-[(3,4,5-trimethoxyphenyl)methyl]purin-6-amine
• CAS: 352519-21-2
• 化学式: C₁₉H₂₅N₅O₃
• 分子量: 371.439
• InChiKey: TUOSCZDRWRYPRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  97.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-butyl-8-(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine 在 盐酸 、 叔丁基过氧化氢 作用下， 以 甲醇 、 水 为溶剂， 以72%的产率得到PU3PhCl
  参考文献：
  名称：

  Development of a Purine-Scaffold Novel Class of Hsp90 Binders that Inhibit the Proliferation of Cancer Cells and Induce the Degradation of Her2 Tyrosine Kinase

  摘要：

  The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71) exhibits binding to hsp90 comparable to the natural product derivative 17AAG that is now in Phase I clinical trial as a cancer therapeutic. 71 Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50 = 2 muM). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00253-5
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 sodium methylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.08h， 生成 9-butyl-8-(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine
  参考文献：
  名称：

  Adenine derived inhibitors of the molecular chaperone HSP90—SAR explained through multiple X-ray structures

  摘要：

  Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.011

文献信息

• HSP90 INHIBITING INDAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SAME AND USE THEREOF
  申请人：Bertin Luc

  公开号：US20120010241A1

  公开（公告）日：2012-01-12

  The invention relates to novel products having formula (I), wherein: R4 represents H, CH3, CH2CH3, CF3, F, Cl, Br, I; Het represents a heterocycle optionally substituted by one or more R1 or R′1 radicals selected from H, halogen, CF3, nitro, cyano, alkyl, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, phenylalkoxy, alkylthio, carboxy that is free or sterified with an alkyl radical, carboxamide, CO—NH(alkyl), CON(alkyl)2, NH—CO-alkyl, sulfonamide, NH—SO2-alkyl, S(O)2-NHalkyl, S(O2)-N(alkyl)2, all of the alkyl, alkoxy and alkylthio radicals being optionally substituted; R being selected from the group comprising (A′), (B), (C), (D) and (F), wherein W1, W2, W3 represent independently CH or N, X represents O, S, NR2, C(O), S(O) or S(O)2; V represents H, Hal, —O—R2 or —NH—R2 with R2 representing H, alkyl, cycloalkyl or heterocycloalkyl, optionally substituted; said products being in all isomer forms, as well as the salts and intended for use as drugs.

  本发明涉及具有公式(I)的新产品，其中：R4代表H，CH3，CH2CH3，CF3，F，Cl，Br，I；Het代表一个杂环，可选地由一个或多个R1或R'1自由基取代，这些自由基选自H，卤素，CF3，硝基，腈基，烷基，羟基，巯基，氨基，烷基氨基，二烷基氨基，烷氧基，苯基烷氧基，烷基硫醚，游离或与烷基自由基酯化的羧基，羧酰胺，CO—NH(烷基)，CON(烷基)2，NH—CO-烷基，磺酰胺，NH—SO2-烷基，S(O)2-NH烷基，S(O2)-N(烷基)2，所有烷基，烷氧基和烷基硫醚自由基都是可选取代的；R选自包括(A′)，(B)，(C)，(D)和(F)的组，其中W1，W2，W3独立代表CH或N，X代表O，S，NR2，C(O)，S(O)或S(O)2；V代表H，Hal，—O—R2或—NH—R2，R2代表H，烷基，环烷基或杂环烷基，可选取代；所述产品为所有异构体形式，以及盐，用于作为药物使用。
• Compounds Useful for Promoting Protein Degradation and Methods Using Same
  申请人：Yale University

  公开号：US20160022642A1

  公开（公告）日：2016-01-28

  The present description includes compounds that act as degraders of a target protein, wherein degradation is independent of the class of the target protein or its localization. In certain embodiments, the description includes a compound comprising a protein degradation moiety covalently bound to a linker, wherein the ClogP of the compound is equal to or higher than 1.5. The target protein contemplated within the description comprises an androgen receptor. Compounds of the present description may be used to treat disease states wherein protein degradation is a viable therapeutic approach, such as cancer or any sort of oxidative stress disease state.

  本描述包括作为目标蛋白质降解剂的化合物，其中降解与目标蛋白质的类别或其定位无关。在某些实施例中，描述包括一种化合物，其中蛋白质降解基团与连接剂共价结合，该化合物的ClogP等于或高于1.5。描述中考虑的目标蛋白质包括雄激素受体。本描述的化合物可用于治疗蛋白质降解是可行治疗方法的疾病状态，如癌症或任何一种氧化应激疾病状态。
• NOVEL HSP90 INHIBITORY CARBAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SAME AND USE THEREOF
  申请人：RUXER Jean-Marie

  公开号：US20110166169A1

  公开（公告）日：2011-07-07

  The invention relates to the novel substances in Formula (I): wherein Het is a heterocycle optionally substituted by one or a plurality of radicals R1 or R′1; R is selected from the group comprising Formula (A′), (B), (C), (D), or (E), with R1 and/or R′1 selected from H, halogen, CF3, nitro, cyano, alkyl, hydroxyl, mercapto, amino, alkylamino, dialkylamino, alkoxy, phenylalcoxy, alkylhio, or carboxy that is free or esterified by an alkyl, carboxamide, CO—NH(alkyl), CON(alkyl)2, NH—CO-alkyl, sulfonamide, NH—S02-alkyl, S(0)2-NHalkyl, or S(02)-N(alkyl)2 radical; all these radicals are optionally substituted; W1, W2, and W3 independently are CH or N; X is 0, S, NR2, C(O), S(O), or S(0)2; Z is optionally substituted H, Hal, -0-R2 or —NH—R2 with R2 being H, alkyl, cycloalkyl, or heterocycloalkyl; and these substances are all isomeric forms and salts thereof, used as drugs.

  该发明涉及式（I）中的新物质：其中Het是一种杂环，可选择地由一个或多个基团R1或R′1取代；R从包括式（A′）、（B）、（C）、（D）或（E）的基团中选择，其中R1和/或R′1从H、卤素、CF3、硝基、氰基、烷基、羟基、巯基、氨基、烷基氨基、二烷基氨基、烷氧基、苯基氧基、烷硫基或自由或被烷基、羧酰胺、CO—NH（烷基）、CON（烷基）2、NH—CO-烷基、磺酰胺、NH—S02-烷基、S(0)2-NH烷基或S(02)-N(烷基)2基团中选择；所有这些基团可选择地被取代；W1、W2和W3独立地是CH或N；X是0、S、NR2、C(O)、S(O)或S(0)2；Z是可选择地取代的H、卤素、-0-R2或—NH—R2，其中R2是H、烷基、环烷基或杂环烷基；这些物质都是同分异构体和其盐，用作药物。
• CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
  申请人：Arvinas, Inc.

  公开号：US20180215731A1

  公开（公告）日：2018-08-02

  The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。
• COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF
  申请人：BioTheryX, Inc.

  公开号：US20180170948A1

  公开（公告）日：2018-06-21

  The present invention provides compounds that modulate protein function, to restore protein homeostasis, including cytokine, CK1α, GSPT1, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of diseases, disorders, or conditions associated with a protein, such as diseases, disorders, and conditions associated with cytokines, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.

  本发明提供了调节蛋白功能的化合物，以恢复蛋白稳态，包括细胞因子、CK1α、GSPT1、艾奥洛斯和/或伊卡洛斯活性和细胞间粘附。该发明提供了一种调节蛋白介导的疾病的方法，如细胞因子介导的疾病、障碍、状况或反应。提供了包括与其他细胞因子和炎症介质结合的组合物。提供了治疗、改善或预防与蛋白相关的疾病、障碍或状况的方法，包括与细胞因子相关的疾病、障碍和状况，包括炎症、纤维肌痛、类风湿性关节炎、骨关节炎、强直性脊柱炎、银屑病、银屑病关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、葡萄膜炎、炎症性肺病、慢性阻塞性肺病、阿尔茨海默病和癌症。