1,2,3,4-tetrahydro-2-ethyl-6,7-dimethoxyisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1,2,3,4-tetrahydro-2-ethyl-6,7-dimethoxyisoquinoline
• 英文别名: 2-ethyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；2-ethyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline；2-Aethyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin；2-ethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: KGMSKRGSHTVCKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-2-ethyl-6,7-dimethoxyisoquinoline 、 苯基溴化镁 在 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 以68%的产率得到1-Phenyl-2-ethyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin
  参考文献：
  名称：

  N-烷基-四氢异喹啉在氧化条件下无过渡金属的芳基化：C1-丙烯酸化的四氢异喹啉生物碱的便捷合成

  摘要：

  摘要 已经开发了一种在无金属条件下通过偶氮二羧酸二乙酯（DEAD）介导的氧化CH活化四氢异喹啉与芳基格氏试剂进行C1芳基化的简单协议。以中等至良好的产率获得了目标化合物，包括一些天然存在的生物碱。 已经开发了一种在无金属条件下通过偶氮二羧酸二乙酯（DEAD）介导的氧化CH活化四氢异喹啉与芳基格氏试剂进行C1芳基化的简单协议。以中等至良好的产率获得了目标化合物，包括一些天然存在的生物碱。

  DOI：

  10.1055/s-0034-1378337
• 作为产物：
  描述：

  6,7-二甲氧基-3,4-二氢异喹啉 在 硫酸 、 水 、 锌 、 苯 作用下， 生成 1,2,3,4-tetrahydro-2-ethyl-6,7-dimethoxyisoquinoline
  参考文献：
  名称：

  2-Alkyl-1,2,3,4-tetrahydroisoquinoline Hydrochlorides¹

  摘要：

  DOI：

  10.1021/ja01276a023

文献信息

• Dioxanes and uses thereof
  申请人：——

  公开号：US20040072849A1

  公开（公告）日：2004-04-15

  In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel compounds of general formula (I): 1 and pharmaceutically acceptable derivatives thereof, wherein R 1 , R 2 , R 3 , n, X and Y are as defined herein. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The present invention further provides compounds capable of inhibiting histone deacetylatase activity and methods for treating disorders regulated by histone deacetylase activity (e.g., cancer and protozoal infections) comprising administering a therapeutically effective amount of a compound of formula (I) to a subject in need thereof. The present invention additionally provides methods for modulating the glucose-sensitive subset of genes downstream of Ure2p. The present invention also provides methods for preparing compounds of the invention.

  鉴于需要开发新型治疗剂和有效的合成方法，本发明提供了一般式(I)的新化合物： 1 及其药学上可接受的衍生物，其中R 1 ，R 2 ，R 3 ，n，X和Y如本文所定义。本发明还提供了包含一种式(I)化合物和药学上可接受的载体的药物组合物。本发明还提供了能够抑制组蛋白去乙酰化酶活性的化合物以及治疗由组蛋白去乙酰化酶活性调节的疾病的方法（例如，癌症和原虫感染），包括向需要的受体施用一种式(I)化合物的治疗有效量。本发明还提供了调节Ure2p下游葡萄糖敏感基因子集的方法。本发明还提供了制备本发明化合物的方法。
• Cephem Compounds with Latent Reactive Groups
  申请人：Gladius Pharmaceuticals, Inc.

  公开号：US20190100534A1

  公开（公告）日：2019-04-04

  Cephem and penem compounds having a styrylmethylene moiety at the 3-position in the cephem or penem ring to which a positively charged leaving group is bonded and wherein the leaving group contains a vicinal diol or is bonded to a unsubstituted or substituted catechol. The leaving group can be a positively charge nitrogen leaving group. Cephems include cephalosporins, cephamycins, carbacephems, and oxacephems. Penems include penems, carbapenems and oxapenems. Preferred cephems are cephalosporins. Preferred penems are carbapenems. Compounds exhibit antibiotic activity against Gram-negative bacteria and/or Gram-positive bacteria. Compounds exhibit antibiotic activity against bacteria which exhibit multi-drug resistance. Compounds of the invention exhibit antibiotic activity against bacterial strains which produce extended spectrum beta-lactamases (ESBL), which produce AmpC beta-lactamases or which produce a carbapenemase. Pharmaceutical compositions comprising one or more cephems or penems or methods of treatment of bacterial infections with such compounds and compositions.

  具有在头孢菌素或青霉烷素环中3位处具有苯乙烯亚甲基基团的头孢菌素和青霉烷素化合物，其中正电离子离去基团与离去基团中含有邻二醇或连接到未取代或取代过的邻苯二酚。离去基团可以是正电离子离去基团。头孢菌素包括头孢菌素、头孢菌烷、卡巴头孢菌素和氧头孢菌素。青霉烷素包括青霉烷素、碳青霉烷素和氧青霉烷素。首选头孢菌素是头孢菌素。首选青霉烷素是碳青霉烷素。化合物对革兰氏阴性细菌和/或革兰氏阳性细菌表现出抗生素活性。化合物对表现出多重耐药性的细菌表现出抗生素活性。本发明的化合物表现出抗生素活性，对产生扩展谱β-内酰胺酶（ESBL）、产生AmpCβ-内酰胺酶或产生碳青霉烷酶的细菌菌株表现出抗生素活性。包括一种或多种头孢菌素或青霉烷素的制药组合物或使用这些化合物和组合物治疗细菌感染的方法。
• ARYLPIPERIDINYL AND ARYLPYRROLIDINYL MACROCYCLIC HEPATITIS C SERINE PROTEASE INHIBITORS
  申请人：Niu Deqiang

  公开号：US20080279821A1

  公开（公告）日：2008-11-13

  The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明涉及具有以下结构的化合物I，或其药用可接受的盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰乙型肝炎病毒的生命周期，并且还可用作抗病毒剂。本发明还涉及含有上述化合物的制药组合物，用于治疗患有HCV感染的受试者。该发明还涉及通过给受试者施用含有本发明化合物的制药组合物来治疗受试者的HCV感染的方法。
• An Improved Synthesis of 1,2,3,4-Tetrahydroisoquinolines via Intramolecular Cyclization of N-Acyl-N-(aryl)methyl-2-(phenylsulfinyl)ethylamine by Pummerer Reaction.
  作者：Tatsumi SHINOHARA、Jun TODA、Takehiro SANO

  DOI：10.1248/cpb.45.813

  日期：——

  Pummerer reaction of the sulfoxides 5 of N-acyl-N-(aryl)methyl-2-(phenylthio)ethylamines (4) on treatment with trifluoroacetic anhydride (TFAA) effectively caused intramolecular cyclization under a mild condition to give N-acyl-4-phenylthio-1, 2, 3, 4-tetrahydroisoquinolines (TIQs) (7). The reaction of the N-formyl sulfoxide 5c without a methoxy group in the benzene ring using a formyl group for N-protection is particularly efficient. Treatment of the N-formyl sulfoxide 5f with TFAA did not give any TIQ, but a sequential treatment using TFAA and BF3·Et2O afforded N-formyl-4-phenylthio-TIQ (7f) in quantitative yield. The efficiency of this method of preparing TIQs was demonstrated in the synthesis of 1, 4-dideuterio-TIQ (10D) and its N-methyl derivative (11D).

  N-酰基-N-(芳基)甲基-2-(硫苯基)乙胺（4）中的亚砜化合物5与三氟醋酸酐（TFAA）反应后，能有效引发分子内环化，生成N-酰基-4-硫苯基-1, 2, 3, 4-四氢异喹啉（TIQs）(7)，该反应在温和条件下进行。对于没有甲氧基的N-甲酰亚砜5c，使用甲酰基进行N-保护特别高效。N-甲酰亚砜5f与TFAA反应时未能生成任何TIQ，但使用TFAA和BF3·Et2O进行顺序处理则定量产出N-甲酰基-4-硫苯基-TIQ（7f）。这种制备TIQs的方法在合成1, 4-二氘-TIQ（10D）及其N-甲基衍生物（11D）中展示了其高效性。
• HISTONE DEACETYLASE INHIBITORS
  申请人：Bradner James Elliot

  公开号：US20100056588A1

  公开（公告）日：2010-03-04

  In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.

  为了开发新型治疗剂，本发明提供了新型组蛋白去乙酰化酶抑制剂。这些化合物包括酯键，使它们对酯酶的失活敏感。因此，这些化合物在治疗皮肤疾病方面特别有用。当这些化合物进入血液循环时，酯酶或具有酯酶活性的酶将其裂解成生物学上不活性的碎片或具有大大降低活性的碎片。理想情况下，这些降解产物表现出短的血清和/或系统半衰期，并迅速被排出体外。这些化合物及其制剂在治疗切除性T细胞淋巴瘤、神经纤维瘤、银屑病、脱发、皮肤色素沉着和皮炎等方面特别有用。本发明还提供了制备本发明化合物及其中间体的方法。