3-((naphthalen-2-ylmethyl)amino)propan-1-ol | 163083-82-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-((naphthalen-2-ylmethyl)amino)propan-1-ol
• 英文别名: 3-(Naphthalen-2-ylmethylamino)propan-1-ol
• CAS: 163083-82-7
• 化学式: C₁₄H₁₇NO
• mdl: MFCD11162898
• 分子量: 215.295
• InChiKey: JBMODXGSXLPSMS-UHFFFAOYSA-N

物化性质

• 沸点：
  392.7±25.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-((naphthalen-2-ylmethyl)amino)propan-1-ol 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 20.5h， 生成 methyl 11-cyano-8-(2-naphthylmethyl)-3-phenyl-4,8-diazaundecanoate
  参考文献：
  名称：

  三氨基和四氨基酯的金属模板化大环内酰胺化。大环亚精胺和精胺生物碱、(S)-(+)-Dihydroperiphylline、(±)-Buchnerine、(±)-Verbacine、(±)-Verbaskine 和 (±)-Verbascenine 的简便合成

  摘要：

  亚精胺和精胺生物碱、(S)-(+)-dihydroperiphylline (1)、(±)-buchnerine (2)、(±)-verbacine (3)、(±)-verbaskine (4) 和(±)-verbascenine (5)，描述。大环内酰胺的构建已通过三氨基酯和四氨基酯的金属模板环化有效完成。还发现乙氧基锑(III)可用作分子间酰胺化催化剂。

  DOI：

  10.1246/bcsj.71.1221
• 作为产物：
  描述：

  3-{[1-Naphthalen-2-yl-meth-(E)-ylidene]-amino}-propan-1-ol 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以5.15 g的产率得到3-((naphthalen-2-ylmethyl)amino)propan-1-ol
  参考文献：
  名称：

  Synthesis of 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones: selective antagonists of muscarinic (M3) receptors

  摘要：

  针对四氢-[1H]-2-苯并氮杂环-4-酮作为潜在选择性毒蕈碱（M3）受体拮抗剂，已开发出两种合成途径。通过碱促反应，将2-(叔丁氧羰基氨基)甲基-1,3-二硫杂环烷-5与2-(叔丁基二甲基硅氧基甲基)苯甲基氯化物-14反应，得到了相应的2,2-二烷基化的1,3-二硫杂环烷-15，然后通过去硅化、氧化和还原胺化反应合成了母体2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮的二硫杂环烷衍生物-19。在转化为N-叔丁氧羰基、N-甲苯p-磺酰基和N-苄基衍生物-20至-22后，二硫杂环烷的水解得到了N保护的四氢-[1H]-2-苯并氮杂环-4-酮-23至-25。然而，初步尝试将这些化合物转化为5-环烷基-5-羟基衍生物未成功。在第二种方法中，采用环闭合钠发生反应制备了2,3-二氢-[1H]-2-苯并氮杂环，并对其进行羟基化和氧化，得到所需的5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮。经过初步研究，dienyl N-(2-硝基苯基)磺酰胺-48的环闭合钠发生反应生成了二氢苯并氮杂环-50，随后通过羟基化和去保护N基，再通过还原胺化进行N-烷基化和氧化，得到了2-丁基-5-环丁基-5-羟基四氢苯并氮杂环-4-酮-55。该化学反应进一步用于合成2-[(N-芳基甲基)氨基烷基]类似物-69、72、76和78。采用N-酰化，然后使用硼烷–四氢呋喃络合物进行酰胺还原，也用于实现二氢苯并氮杂环的N-烷基化，此方法可合成5-环戟基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-103和5-环丁基-8-氟-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-126。2-叔丁氧羰基-4,4-丙烯二硫-2,3,4,5-四氢-[1H]-2-苯并氮杂环-20和(4RS,5SR)-2-丁基-5-环丁基-4,5-二羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-53的结构通过X射线衍射得到确认。对外消旋的5-环烷基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮进行了毒蕈碱受体拮抗活性筛选。在来自豚鼠回肠的M3受体实验中，这些化合物的log10KB值最高可达7.2，对来自豚鼠左心房的M2受体的选择性约为40。

  DOI：

  10.1039/b801206g

文献信息

• Chemokine receptor binding heterocyclic compounds
  申请人：AnorMED, Inc.

  公开号：US06750348B1

  公开（公告）日：2004-06-15

  This invention relates to a novel class of heterocyclic compounds that bind chemokine receptors, inhibiting the binding of their natural ligands thereby. These compounds result in protective effects against infection by HIV through binding to chemokine receptors, including CXCR4 and CCR5, thus inhibiting the subsequent binding by these chemokines. The present invention provides a compound of Formula I wherein, W is a nitrogen atom and Y is absent or, W is a carbon atom and Y═H; R1 to R7 may be the same or different and are independently selected from hydrogen or straight, branched or cyclic C1-6 alkyl; R8 is a substituted heterocyclic group or a substituted aromatic group Ar is an aromatic or heteroaromatic ring each optionally substituted at single or multiple, non-linking positions with electron-donating or withdrawing groups; n and n′ are independently, 0-2; X is a group of the formula: Wherein, Ring A is an optionally substituted, saturated or unsaturated 5 or 6-membered ring, and P is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur or oxygen atom. Ring B is an optionally substituted 5 to 7-membered ring. Ring A and Ring B in the above formula can be connected to the group W from any position via the group V, wherein V is a chemical bond, a (CH2)n″ group (where n″=0-2) or a C═O group. Z is, (1) a hydrogen atom, (2) an optionally substituted C1-6 alkyl group, (3) a C0-6 alkyl group substituted with an optionally substituted aromatic or heterocyclic group, (4) an optionally substituted C0-6 alkylamino or C3-7 cycloalkylamino group, (5) an optionally substituted carbonyl group or sulfonyl. These compounds further include any pharmaceutically acceptable acid addition salts and metal complexes thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof.

  这项发明涉及一类新型的杂环化合物，它们结合趋化因子受体，抑制其天然配体的结合。这些化合物通过结合趋化因子受体，包括CXCR4和CCR5，从而抑制这些趋化因子的后续结合，产生对HIV感染的保护效果。本发明提供了一个式I的化合物 其中，W是氮原子，Y不存在，或者W是碳原子，Y═H； R1至R7可以相同也可以不同，并且独立地选择自氢或直链、支链或环状的C1-6烷基； R8是一个取代的杂环基或取代的芳香基 Ar是一个芳香或杂芳环，每个环在单个或多个非连接位置可选择地取代有电子给体或吸引体基团； n和n′独立地为0-2； X是下式的一个基团： 其中，环A是一个可选择地取代的饱和或不饱和的5或6元环，P是一个可选择地取代的碳原子、一个可选择地取代的氮原子、硫或氧原子。环B是一个可选择地取代的5到7元环。上述式中的环A和环B可以通过基团V从任何位置连接到基团W，其中V是一个化学键，一个(CH2)n″基团（其中n″=0-2）或一个C═O基团。Z是(1)一个氢原子，(2)一个可选择地取代的C1-6烷基基团，(3)一个用可选择地取代的芳香或杂环基团取代的C0-6烷基基团，(4)一个可选择地取代的C0-6烷基氨基或C3-7环烷氨基基团，(5)一个可选择地取代的羰基或磺酰基。这些化合物还包括任何药学上可接受的酸盐和金属络合物，以及它们的任何立体异构体形式和立体异构体形式的混合物。
• [EN] NOVEL HISTONE METHYLTRANSFERASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASES
  申请人：UNIV FREIBURG ALBERT LUDWIGS

  公开号：WO2021053158A1

  公开（公告）日：2021-03-25

  The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.

  本发明涉及式(I)定义的新的化合物。这些化合物是七-β-链家族组蛋白甲基转移酶的抑制剂，特别是KMT9的抑制剂。
• Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties
  作者：Jui-Yin Yu、Hsiu-Jung Cheng、Huei-Ru Wu、Wei-Shen Wu、Jui-Wen Lu、Ting-Jen Cheng、Ying-Ta Wu、Jim-Min Fang

  DOI：10.1016/j.ejmech.2018.03.034

  日期：2018.4

  Transglycosylase (TGase) is essential to biosynthesis of peptidoglycan for formation of bacterial cell wall. Moenomycin is a potent TGase inhibitor, but not used in clinic treatment due to its poor pharmacokinetics. The E−F disaccharide, phosphoglycerate and lipid tail in moenomycin are crucial elements for TGase inhibition and antibacterial activity. Based on this scaffold, a series of truncated mimics

  转糖基化酶（TGase）对肽聚糖生物合成以形成细菌细胞壁至关重要。Moenomycin是一种有效的TGase抑制剂，但由于其药代动力学较差，因此未用于临床治疗。Moenomycin中的E-F二糖，磷酸甘油酸酯和脂质尾巴是TGase抑制和抗菌活性的关键元素。基于此支架，设计了一系列包含联苯，胺连接基和2-烷氧基-3-磷酸基丙酸酯的截短模拟物，以测试其TGase抑制活性。在该设计中，磷酸酰基丙酸酯基团是磷酸甘油酸酯的替代物，具有改善的稳定性。可以使用Cu（I）催化的（3 + 2）环加成反应通过直接方法构建脂质尾巴库，合成的三唑环可以在TGase活性位点提供额外的氢键。我们的分子对接实验表明，联苯基团提供π–π和π–阳离子相互作用，可以作为莫诺霉素中C–E二糖的简化替代品。为了在氧化糖基化中发挥氧鎓过渡态的作用，胺接头在生理条件下以带正电荷的形式存在，以实现与酸性残基的静电相互作用。在这项研究中
• [EN] SPECIFIC SMALL MOLECULE INHIBITORS THAT BLOCK KMT9 METHYLTRANSFERASE ACTIVITY AND FUNCTION<br/>[FR] INHIBITEURS À PETITES MOLÉCULES SPÉCIFIQUES QUI BLOQUENT L'ACTIVITÉ ET LA FONCTION DE LA MÉTHYLTRANSFÉRASE KMT9
  申请人：[en]ALBERT-LUDWIGS-UNIVERSITÄT FREIBURG

  公开号：WO2023017152A1

  公开（公告）日：2023-02-16

  The present invention relates to novel specific small molecule inhibitors that block KMT9 methyltransferase activity. In particular, the present invention is concerned with a compound of formula (I) wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein. Further, the present invention is concerned with a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I). The present invention also relates to a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use in medicine. Yet further, the present invention is concerned with a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use as inhibitor of KMT9. Finally, the present invention is concerned with a compound of formula (I), wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein, for use in the treatment of cancer selected from the group as defined herein.
• Synthesis of 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones: selective antagonists of muscarinic (M3) receptors
  作者：Benjamin Bradshaw、Paul Evans、Jane Fletcher、Alan T. L. Lee、Paul G. Mwashimba、Daniel Oehlrich、Eric J. Thomas、Robin H. Davies、Benjamin C. P. Allen、Kenneth J. Broadley、Amar Hamrouni、Christine Escargueil

  DOI：10.1039/b801206g

  日期：——

  Two approaches to tetrahydro-[1H]-2-benzazepin-4-ones of interest as potentially selective, muscarinic (M3) receptor antagonists have been developed. Base promoted addition of 2-(tert-butoxycarbonylamino)methyl-1,3-dithiane 5 with 2-(tert-butyldimethylsiloxymethyl)benzyl chloride 14 gave the corresponding 2,2-dialkylated 1,3-dithiane 15 which was taken through to the dithiane derivative 19 of the parent 2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one by desilylation, oxidation and cyclisation via a reductive amination. After conversion into the N-tert-butyloxycarbonyl, N-toluene p-sulfonyl and N-benzyl derivatives 20–22, hydrolysis of the dithiane gave the N-protected tetrahydro-[1H]-2-benzazepin-4-ones 23–25. However, preliminary attempts to convert these into 5-cycloalkyl-5-hydroxy derivatives were not successful. In the second approach, ring-closing metathesis was used to prepare 2,3-dihydro-[1H]-2-benzazepines which were hydroxylated and oxidized to give the required 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones. Following preliminary studies, ring-closing metathesis of the dienyl N-(2-nitrophenyl)sulfonamide 48 gave the dihydrobenzazepine 50 which was converted into the 2-butyl-5-cyclobutyl-5-hydroxytetrahydrobenzazepin-4-one 55 by hydroxylation and N-deprotection followed by N-alkylation via reductive amination, and oxidation. This chemistry was then used to prepare the 2-[(N-arylmethyl)aminoalkyl analogues 69, 72, 76 and 78. N-Acylation followed by amide reduction using the borane–tetrahydrofuran complex was also used to achieve N-alkylation of dihydrobenzazepines and this approach was used to prepare the 5-cyclopentyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one 103 and the 5-cyclobutyl-8-fluoro-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one 126. The structures of 2-tert-butyloxycarbonyl-4,4-propylenedithio-2,3,4,5-tetrahydro-[1H]-2-benzazepine 20 and (4RS,5SR)-2-butyl-5-cyclobutyl-4,5-dihydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepine 53 were confirmed by X-ray diffraction. The racemic 5-cycloalkyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones were screened for muscarinic receptor antagonism. For M3 receptors from guinea pig ileum, these compounds had log10KB values of up to 7.2 with selectivities over M2 receptors from guinea pig left atria of approximately 40.

  针对四氢-[1H]-2-苯并氮杂环-4-酮作为潜在选择性毒蕈碱（M3）受体拮抗剂，已开发出两种合成途径。通过碱促反应，将2-(叔丁氧羰基氨基)甲基-1,3-二硫杂环烷-5与2-(叔丁基二甲基硅氧基甲基)苯甲基氯化物-14反应，得到了相应的2,2-二烷基化的1,3-二硫杂环烷-15，然后通过去硅化、氧化和还原胺化反应合成了母体2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮的二硫杂环烷衍生物-19。在转化为N-叔丁氧羰基、N-甲苯p-磺酰基和N-苄基衍生物-20至-22后，二硫杂环烷的水解得到了N保护的四氢-[1H]-2-苯并氮杂环-4-酮-23至-25。然而，初步尝试将这些化合物转化为5-环烷基-5-羟基衍生物未成功。在第二种方法中，采用环闭合钠发生反应制备了2,3-二氢-[1H]-2-苯并氮杂环，并对其进行羟基化和氧化，得到所需的5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮。经过初步研究，dienyl N-(2-硝基苯基)磺酰胺-48的环闭合钠发生反应生成了二氢苯并氮杂环-50，随后通过羟基化和去保护N基，再通过还原胺化进行N-烷基化和氧化，得到了2-丁基-5-环丁基-5-羟基四氢苯并氮杂环-4-酮-55。该化学反应进一步用于合成2-[(N-芳基甲基)氨基烷基]类似物-69、72、76和78。采用N-酰化，然后使用硼烷–四氢呋喃络合物进行酰胺还原，也用于实现二氢苯并氮杂环的N-烷基化，此方法可合成5-环戟基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-103和5-环丁基-8-氟-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-126。2-叔丁氧羰基-4,4-丙烯二硫-2,3,4,5-四氢-[1H]-2-苯并氮杂环-20和(4RS,5SR)-2-丁基-5-环丁基-4,5-二羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-53的结构通过X射线衍射得到确认。对外消旋的5-环烷基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮进行了毒蕈碱受体拮抗活性筛选。在来自豚鼠回肠的M3受体实验中，这些化合物的log10KB值最高可达7.2，对来自豚鼠左心房的M2受体的选择性约为40。