1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,4-dihydro-1H-1,3-diazepin-2(7H)-one | 75421-11-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,4-dihydro-1H-1,3-diazepin-2(7H)-one
• 英文别名: 1-(β-D-Ribofuranosyl)1,3,4,7-tetrahydro-2H-1,3-diazepin-2-one；Diazepinone riboside；3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,7-dihydro-1H-1,3-diazepin-2-one
• CAS: 75421-11-3
• 化学式: C₁₀H₁₆N₂O₅
• 分子量: 244.247
• InChiKey: HBBIVXDEBCKFIZ-FNCVBFRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide 在 氨 、 N,O-双(三甲基硅烷基)三氟乙酰胺 、 mercury dibromide 、 mercury(II) oxide 作用下， 以 甲醇 为溶剂， 生成 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3,4-dihydro-1H-1,3-diazepin-2(7H)-one
  参考文献：
  名称：

  Synthesis of 1,3-diazepin-2-one nucleosides as transition-state inhibitors of cytidine deaminase. 2

  摘要：

  DOI：

  10.1021/jo01313a049

文献信息

• [EN] (2 ' -DEOXY-RIBOFURANOSYL) -1,3,4, 7-TETRAHYDRO- (1,3) IAZEPIN-2-0NE DERIVATIVES FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE (2 ' -DÉSOXY-RIBOFURANOSYL) -1,3,4, 7-TÉTRAHYDRO- (1,3) IAZÉPINE-2-0NE POUR LE TRAITEMENT DU CANCER
  申请人：EISAI INC

  公开号：WO2010118006A1

  公开（公告）日：2010-10-14

  Provided herein are compounds used to inhibit the deamination enzyme responsible for the inactivation of therapeutic compounds, and methods of using them.

  本文提供了用于抑制脱氨酶的化合物，该脱氨酶负责使治疗化合物失活，并提供了使用它们的方法。
• Cyclic urea nucleosides. Cytidine deaminase activity as a function of aglycon ring size
  作者：Paul S. Liu、Victor E. Marquez、John S. Driscoll、Richard W. Fuller、John J. McCormack

  DOI：10.1021/jm00138a003

  日期：1981.6

  by the mercury-catalyzed condensation procedure. CDA activity varies significantly with the ring size of the urea aglycon the reaches its maximum level for the seven-membered analogues 16 and 17. The unexpected high potency of nucleoside 17 (Ki = 2.5 X 10(-8) M, human liver enzyme) is reported. This compound represents the most potent inhibitor of human liver CDA yet discovered.

  合成了五种β-D-呋喃呋喃糖基环状脲核苷（14-18），其环大小为五至八元，并被评估为胞苷脱氨酶（CDA）抑制剂。在含有仅提供β-端基异构体的HgO / HgBr2混合物的比催化活性下，通过缩合反应利用前体保护的核苷（9-13），该缩合反应是利用硅烷化的脲与卤代糖。已知的1-（2,3,5-三-O-苯甲酰基-β-呋喃呋喃糖基）-1,2-二氢嘧啶-2-酮（19）的催化加氢提供与通过汞催化的缩合步骤获得的核苷10相同。CDA活性随尿素糖苷配基的环大小变化而显着变化，达到七元类似物16和17的最大水平。核苷17的意想不到的高效能（Ki = 2.5 X 10（-8）M，人肝酶）的报道。该化合物代表尚未发现的最有效的人类肝脏CDA抑制剂。
• A facile synthetic route to diazepinone derivatives via ring closing metathesis and its application for human cytidine deaminase inhibitors
  作者：Minkyoung Kim、Kondaji Gajulapati、Chorong Kim、Hwa Young Jung、Jail Goo、Kyeong Lee、Navneet Kaur、Hyo Jin Kang、Sang J. Chung、Yongseok Choi

  DOI：10.1039/c2cc35484e

  日期：——

  A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3,4-dihydro-1H-1,3-diazepin-2(7H)-one (3) showed a potent inhibitory effect (Ki = 145.97 ± 4.87 nM) against human cytidine deaminase.

  通过一种基于环闭合互变的新的合成方法，从α-氨基酸和氨基醇中制备了多种二氮杂庚烯酮衍生物。这些二氮杂庚烯酮与核糖衍生物偶联，生成新型二氮杂庚烯酮核苷。其中，(4R)-1-核糖基-4-甲基-3,4-二氢-1H-1,3-二氮杂庚烯-2(7H)-酮（3）对人细胞胞苷脱氨酶表现出显著的抑制作用（Ki = 145.97 ± 4.87 nM）。
• Seven-membered ring compounds as inhibitors of cytidine deaminase
  申请人：THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce

  公开号：EP0034424A2

  公开（公告）日：1981-08-26

  Seven-membered heterocyclic nucleosides used to inhibit the deamination enzyme responsible for the inactivation of arabinosylcytosine (ara-C). Preferred nucleosides containing a seven-member aglycone are as follows: R = H, benzoyl, para-nitrobenzoyl X = H, OR A = R, mono-, di- and tri-phosphates (P03E2, P206E3, P3O9E4) E =H, Na Preferred aglyconies are as follows: 1a: X = OCH2CH20 1b: X = SCH2CH2S 1c: X = O 1d: X = H, OH 1e: X = 2H Active components utilized against pyrimidine deaminases from mammalian tissues (mouse kidney and human liver) showed optimum advantage when compared with tetrahydrouridine (THU).

  七元杂环核苷用于抑制负责使阿拉伯核糖基胞嘧啶（ara-C）失活的脱氨酶。含有七元苷元的首选核苷如下： R = H、苯甲酰基、对硝基苯甲酰基 X = H、OR A = R、一磷酸盐、二磷酸盐和三磷酸盐（P03E2、P206E3、P3O9E4） E =H、Na 首选苷元如下： 1a: X = OCH2CH20 1b: X = SCH2CH2S 1c: X = O 1d:X = H, OH 1e:X = 2H 与四氢尿苷 (THU) 相比，针对哺乳动物组织（小鼠肾脏和人类肝脏）嘧啶脱氨酶的活性成分显示出最佳优势。
• 1,3-Diazepine compounds
  申请人：THE UNITED STATES OF AMERICA as represented by the Secretary United States Department of Commerce

  公开号：EP0065324A1

  公开（公告）日：1982-11-24

  Aglycone intermediate: 15 1a: X = OCH2CH2O 1b: X = SCH2CH2S 1c: X = O 1d: X = H, OH 1e: X = 2H

  苷元中间体： 15 1a: X = OCH2CH2O 1b: X = SCH2CH2S 1c: X = O 1d: X = H, OH 1e: X = 2H