17-Ethyl-1,14-dihydroxy-12-[2'(3",4"-dihydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 17-Ethyl-1,14-dihydroxy-12-[2'(3",4"-dihydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone
• 英文别名: 12-[1-(3,4-dihydroxycyclohexyl)prop-1-en-2-yl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
• 化学式: C₄₂H₆₇NO₁₂
• 分子量: 778.0
• InChiKey: TXWGCZQZVCMIHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  55
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  189
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  17-Ethyl-1,14-dihydroxy-12-[2'(3",4"-dihydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone 、 三氟甲磺酸 在 碳酸氢钠 、 乙酸乙酯 、 Brine 、 magnesium sulfate 、 silica gel 作用下， 以 but-2-ynyl 2,2,2-trichloroacetimidate 为溶剂， 反应 16.08h， 生成 17-Ethyl-1,14-dihydroxy-12-[2'-(4"-(2-butynyloxy)-3"-hydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone
  参考文献：
  名称：

  Amino O-alkyl, O-alkenyl and O-alkynlmacrolides having immunosuppressive

  摘要：

  通式为I的氨基醇O-烷基、O-烯基和O-炔基大环内酯已通过在环己基环上的C-3"/C-4"处烷基化和胺化反应从适当的前体制备而成。这些大环内酯免疫抑制剂在哺乳动物宿主中用于治疗自身免疫性疾病、感染性疾病和/或预防异种器官移植的排斥。此外，这些大环内酯免疫抑制剂在治疗炎症和过度增生性皮肤病和免疫介导疾病的皮肤表现方面也很有用。此外，这些大环内酯在可逆性阻塞性气道疾病，特别是哮喘的治疗中也很有用。

  公开号：

  US05162334A1

文献信息

• Aminomacrolides and derivatives having immunosuppressive activity
  申请人：Merck & Co., Inc.

  公开号：US05208228A1

  公开（公告）日：1993-05-04

  Aminomacrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by incorporation of a nitrogen substituent at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma.

  通式I的氨基大环内酯：##STR1## 可以通过在环己基环上的C-3"和/或C-4"处引入氮取代基来从适当的前体制备而成。这些大环内酯免疫抑制剂可用于哺乳动物宿主的自身免疫性疾病、感染性疾病和/或外来器官移植的预防治疗。此外，这些大环内酯免疫抑制剂可用于治疗炎症和过度增生的皮肤疾病以及免疫介导疾病的皮肤表现。此外，这些大环内酯也可用于可逆性阻塞性气道疾病的治疗，特别是哮喘。
• Imidazolidyl macrolides having immunosuppressive activity
  申请人：Merck & Co., Inc.

  公开号：US05247076A1

  公开（公告）日：1993-09-21

  Imidazolidyl macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.

  通式I的咪唑啉基大环内酯：##STR1## 是通过在环己烷环的C-3"和/或C-4"处进行烷基化和/或芳基化反应，从适当的前体制备而成。这些大环内酯免疫抑制剂在哺乳动物宿主中用于治疗自身免疫性疾病、传染病、预防外来器官移植的排斥和/或相关疾病和疾病。
• O-aryl, O-alkyl, O-alkenyl and O-alkynylmacrolides having
  申请人：Merck & Co., Inc.

  公开号：US05250678A1

  公开（公告）日：1993-10-05

  O-Aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma; as hair revitalizing agents, especially in the treatment of male pattern alopecia or alopecia senilis; in the reversal of multidrug resistance of tumor cells; in treatment of inflammation of mucosa and blood vessels, gastric ulcers, vascular damage, ischemic bowel disease, necrotizing enterocolitis, intestinal lesions associated with thermal burns; in the treatment of cytomegalovirus infection; and in the treatment of idiopathic thrombocytopenic purpura and Basedow's disease.

  通式I的O-芳基、O-烷基、O-烯基和O-炔基大环内酯，通过在环己烷环的C-3"和/或C-4"处烷基化和/或芳基化制备而成。这些大环内酯免疫抑制剂在哺乳动物宿主中用于治疗自身免疫性疾病、传染病和/或外源性器官移植排斥的预防。此外，这些大环内酯免疫抑制剂在治疗炎症和过度增生性皮肤疾病以及免疫介导疾病的皮肤表现方面具有应用价值。此外，这些大环内酯在可逆性阻塞性呼吸道疾病，尤其是哮喘的治疗中具有应用价值；作为头发复苏剂，特别是在男性型脱发或老年性脱发的治疗中；在肿瘤细胞多药耐药性的逆转中；在黏膜和血管炎症、胃溃疡、血管损伤、缺血性肠病、坏死性肠炎、与热烧伤相关的肠道损伤的治疗中；在巨细胞病毒感染的治疗中；以及在特发性血小板减少性紫癜和Basedow病的治疗中具有应用价值。
• D-heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and
  申请人：Merck & Co., Inc.

  公开号：US05252732A1

  公开（公告）日：1993-10-12

  O-Heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroarylmacrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by alkylation and/or arylation at C-3" and/or C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases, the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.

  通式I的O-杂环芳基、O-烷基杂环芳基、O-烯基杂环芳基和O-炔基杂环芳基大环内酯，可通过在环己基环上的C-3"和/或C-4"处进行烷基化和/或芳基化反应，从适当的前体制备而成。这些大环内酯免疫抑制剂在哺乳动物宿主中用于治疗自身免疫性疾病、传染病、预防外来器官移植的排斥和/或相关的疾病、病症。
• Amino O-aryl macrolides having immunosuppressive activity
  申请人：Merck & Co., Inc.

  公开号：US05262533A1

  公开（公告）日：1993-11-16

  Amino O-aryl macrolides of the general structural Formula I: ##STR1## have been prepared from suitable precursors by arylation and amination at C-3"/C-4" of the cyclohexyl ring. These macrolide immunosuppressants are useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases and/or the prevention of rejection of foreign organ transplants. In addition, these macrolide immunosuppressants are useful in the topical treatment of inflammatory and hyperproliferative skin diseases and cutaneous manifestations of immunologically-mediated illnesses. Also, these macrolides are useful in the treatment of reversible obstructive airways disease, particularly asthma; as hair revitalizing agents, especially in the treatment of male pattern alopecia or alopecia senilis; in the reversal of multidrug resistance of tumor cells; in treatment of inflammation of mucosa and blood vessels, gastric ulcers, vascular damage, ischemic bowel disease, inflammatory bowel disease, necrotizing enterocolitis, intestinal lesions associated with thermal burns; in the treatment of cytomegalovirus infection; and in the treatment of idiopathic thrombocytopenic purpura and Basedow's disease.

  通式I的氨基酸O-芳基大环内酯（macrolides）已经通过在环己基环上的C-3"/C-4"处芳基化和胺化反应制备而成。这些大环内酯免疫抑制剂在哺乳动物宿主中用于治疗自身免疫性疾病、传染性疾病和/或预防异体器官移植的排斥。此外，这些大环内酯免疫抑制剂在治疗炎症和过度增生性皮肤疾病和免疫介导性疾病的皮肤表现方面也很有用。此外，这些大环内酯还可用于可逆性阻塞性气道疾病，特别是哮喘；作为头发复苏剂，尤其是用于男性型脱发或老年性脱发的治疗；在逆转肿瘤细胞的多药耐药性方面；在治疗粘膜和血管炎症、胃溃疡、血管损伤、缺血性肠病、炎症性肠病、坏死性肠炎、与热烧伤相关的肠道损伤方面很有用；在治疗巨细胞病毒感染、特发性血小板减少性紫癜和Basedow病方面也很有用。