4-morpholine-N,N'-dicyclohexylcarboxamidinium guanosine-5'-monophosphomorpholidate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-morpholine-N,N'-dicyclohexylcarboxamidinium guanosine-5'-monophosphomorpholidate
• 英文别名: 4-morpholino-N-N'-dicyclohexylcarboxamidinium guanosine 5'-monophosphomorpholidate；guanosine 5'-monophosphomorpholidate 4-morpholine-N,N'-dicyclohexylcarboxamidine salt；[(2R,3S,4R,5R)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-morpholin-4-ylphosphinate;N,N'-dicyclohexyl-1-morpholin-4-ium-4-ylidenemethanediamine
• 化学式: C₁₄H₂₁N₆O₈P*C₁₇H₃₁N₃O
• 分子量: 725.783
• InChiKey: CFNWUGDJWKRMBL-VAMAKUSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.63
• 重原子数：
  50
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  231
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  4-morpholine-N,N'-dicyclohexylcarboxamidinium guanosine-5'-monophosphomorpholidate 在 吡啶 、 水 、 5-(乙硫基)-1H-四唑 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2S)-2-propylpentyl 2-(((((((2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryl)oxy)(2-aminoethoxy)phosphoryl)amino)propanoate
  参考文献：
  名称：

  [EN] RAS INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE RAS ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2014160200A9

文献信息

• [EN] USE OF FUCOSYLATION INHIBITOR FOR PRODUCING AFUCOSYLATED ANTIBODY<br/>[FR] UTILISATION D'UN INHIBITEUR DE FUCOSYLATION POUR PRODUIRE UN ANTICORPS AFUCOSYLÉ
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2021127414A1

  公开（公告）日：2021-06-24

  The present invention provides inhibitors of fucosylation during protein expression from mammalian cells. The inhibitors are derived from rhamnose and act by inhibition of GDP-mannose 4,6-dehydratase (GMD). The invention further provides methods of making proteins with reduced level of fucosylation, such as antibodies and antibodies made by the methods of the present invention. Such hypofucosylated or nonfucosylated antibodies may find use, for example, in treatment of human disease in which is it therapeutically beneficial to direct antibody dependent cellular cytotoxicity (ADCC) mediated killing of cells expressing the antibody target on their surface, for example in depletion of Tregs in cancer patients using a hypofucosylated or nonfucosylated anti-CTLA-4 antibody.

  本发明提供了在哺乳动物细胞中蛋白质表达过程中抑制富糖基化的抑制剂。这些抑制剂源自鼠李糖，并通过抑制 GDP-甘露糖4,6-脱水酶（GMD）来发挥作用。该发明还提供了制备具有降低富糖基化水平的蛋白质的方法，例如通过本发明的方法制备的抗体和抗体。这种低富糖化或无富糖化的抗体可以在治疗人类疾病中发挥作用，例如在治疗中对表达抗体靶点的细胞进行抗体依赖性细胞毒作用（ADCC）介导的杀伤，例如在癌症患者中使用低富糖化或无富糖化的抗CTLA-4抗体去除Treg细胞。
• Process for preparing nucleotide inhibitors of glycosyltransferases
  申请人：The Scripps Research Institute

  公开号：US05770407A1

  公开（公告）日：1998-06-23

  Nucleotide linked 2-deoxy-2-fluoroglycosides are employed as potent competitive inhibitors of glycosyltransferases. More particularly, uridine-5'-diphospho-2-deoxy-2-fluoro-galactose (UDP-2F-Gal), guanidine-5'-diphospho-2-deoxy-2-fluoro-L-fucose (GDP-2F-Fuc), uridine-51-diphospho-2-deoxy-2-fluoro-D-glucose (UDP-2F-Glu), guanosine-5'-diphospho-2-deoxy-2-fluoro-D-mannose (GDP-2F-Man), cytosine-5'-monophospho-2-deoxy-2-fluoro-D-sialic acid, and cytosine-5'-monophospho-2-deoxy-2-KDO may be employed as inhibitors of .beta.-1,4-galactosyltransferase, .alpha.-1,3-fucosyltransferase, glucosyltransferases, N-acetylglucosaminyltransferases, (.alpha.-mannosyltransferases, .alpha.-sialyltransferases, and KDO-transferases, respectively. Synthesis of nucleotide-linked-2-deoxy-2-fluoroglycosides is achieved using either chemoenzymatic or chemical methodologies.

  核苷酸连接的2-脱氧-2-氟糖苷被用作糖基转移酶的有效竞争性抑制剂。更具体地说，尿苷-5'-二磷酸-2-脱氧-2-氟半乳糖（UDP-2F-Gal）、鸟苷-5'-二磷酸-2-脱氧-2-氟-L-岩藻糖（GDP-2F-Fuc）、尿苷-51-二磷酸-2-脱氧-2-氟-D-葡萄糖（UDP-2F-Glu）、鸟苷-5'-二磷酸-2-脱氧-2-氟-D-甘露糖（GDP-2F-Man）、胞嘧啶-5'-单磷酸-2-脱氧-2-氟-D-唾液酸酸和胞嘧啶-5'-单磷酸-2-脱氧-2-KDO可以作为β-1,4-半乳糖转移酶、α-1,3-岩藻糖转移酶、葡糖转移酶、N-乙酰氨基葡萄糖转移酶、α-甘露糖转移酶、α-唾液酸转移酶和KDO转移酶的抑制剂。核苷酸连接的2-脱氧-2-氟糖苷的合成可使用化学酶法或化学方法实现。
• RAS INHIBITORS AND USES THEREOF
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160046661A1

  公开（公告）日：2016-02-18

  Described herein are compounds of Formulae (I)-(II), and pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases such as cancers (e.g., lung cancer, large bowel cancer, pancreas cancer, biliary tract cancer, or endometrial cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases in a subject.

  本文描述了式（I）-（II）的化合物，以及其药学上可接受的盐和制药组合物。还提供了涉及创新化合物或组合物的方法和工具包，用于治疗或预防受试者的增殖性疾病，如癌症（例如肺癌，大肠癌，胰腺癌，胆道癌或子宫内膜癌），良性肿瘤，血管生成，炎症性疾病，自身炎症性疾病和自身免疫性疾病。
• Chemo-enzymatic synthesis of fluorinated sugar nucleotide: useful mechanistic Probes for glycosyltransferases
  作者：Michael D Burkart、Stéphane P Vincent、Arno Düffels、Brion W Murray、Steven V Ley、Chi-Huey Wong

  DOI：10.1016/s0968-0896(00)00139-5

  日期：2000.8

  An effective procedure for the synthesis of 2-deoxy-2-fluoro-sugar nucleotides via Selectfluor-mediated electrophilic fluorination of glycals with concurrent nucleophilic addition or chemo-enzymatic transformation has been developed. and the fluorinated sugar nucleotides have been used as probes For glycosyltransferases, including fucosyltransferase III, V, VI, and VII, and sialyl transferases. In general, these fluorinated sugar nuclceotides act as competitive inhibitors versus sugar nucleotide substrates and form a tight complex with the glycosyltransferase. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis of Guanosine 5′-(β-L-Fucopyranosyl)-Diphosphate Revisited
  作者：B. M. Heskamp、H. J.G. Broxterman、G. A. van der Marel、J. H. van Boom

  DOI：10.1080/07328309608005678

  日期：1996.7

  It will be demonstrated that a successful synthesis of beta-L-fucopyranose-1-phosphate (2), a key intermediate in the preparation of guanosine 5'-(beta-L-fucopyranose)-diphosphate (1), strongly depends on the nature of the acyl protecting groups for the non-anomeric hydroxyl functions. Thus, the perbenzoylated, instead of peracetylated, alpha-L-fucopyranosyl trichloroacetimidate (11) or the corresponding ethyl beta-thiofucopyranoside proved to be a convenient starting compound for the preparation of 2. Further, condensation of N,N'-dicyclohexyl-4-morpholinecarboxamidinium guanosine 5'-morpholidophosphate with excess 2 gave the title compound without concomitant formation of bisguanosine-5'-diphosphate (16).