Ro 09-4889 | 216449-60-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: Ro 09-4889
• 英文别名: 4-amino-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-5-vinyl-1H-pyrimidin-2-one；2',3'-di-O-acetyl-5'-deoxy-5-vinylcytidine；[(2R,3R,4R,5R)-4-acetyloxy-5-(4-amino-5-ethenyl-2-oxopyrimidin-1-yl)-2-methyloxolan-3-yl] acetate
• CAS: 216449-60-4
• 化学式: C₁₅H₁₉N₃O₆
• 分子量: 337.332
• InChiKey: NELWQUQCCZMRPB-UBPLGANQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ro 09-4889 在 吡啶 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 RO0094226
  参考文献：
  名称：

  Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine

  摘要：

  A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues by sequential conversion of 11c by three enzymes: esterase, cytidine deaminase and thymidine phosphorylase, the latter two of which are known to be highly expressed in various tumor tissues. When capecitabine (1), a tumor-activated prodrug of 5-FU, was co-administered orally with 11c, 5-FU in tumor tissues was significantly increased with only a slight increase of 5-FU in plasma as compared with oral capecitabine alone. (C) 2003 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(02)01082-x
• 作为产物：
  描述：

  2',3'-di-O-acetyl-5'-deoxy-5-iodocytidine 以92的产率得到Ro 09-4889
  参考文献：
  名称：

  5’－脱氧胞苷衍生物

  摘要：

  用于医疗，尤其是肿瘤治疗的通式I所示的新的5′-脱氧-胞苷衍生物，其中的R 1 是氢原子或易于在生理条件下水解的基团；R 2 是氢原子，或-CO-OR 4 基[其中的R 4 是由1-15个碳原子的饱和或不饱和的、直链或支链的烃基，或通式-(CH 2 )n-Y的基团(其中的Y是环己基或苯基；n是从0到4的整数)]；R 3 是氢原子、溴基、碘基、氰基、C 1-4 烷基[其可用卤素原子取代]、乙烯基或乙炔基[其可用卤素原子、C 1-4 烷基、环烷基、芳烷基、或可带有一个或多个杂原子的芳环取代]，或是可被取代的芳烷基。

  公开号：

  CN1197871C

文献信息

• 5'-deoxy-cytidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06114520A1

  公开（公告）日：2000-09-05

  Novel 5'-deoxy-cytidine derivatives represented by the general formula (I) ##STR1## wherein R.sup.1 is a hydrogen atom or a group easily hydrolyzable under physiological conditions; R.sup.2 is a hydrogen atom, or --CO--OR.sup.4 group [wherein R.sup.4 is a saturated or unsaturated, straight or branched hydrocarbon group consisting of one to fifteen carbon atoms, or a group of the formula --(CH.sub.2).sub.n --Y (in which Y is cyclohexyl or phenyl; n is an integer from 0 to 4)]; R.sup.3 is a hydrogen atom, bromo, iodo, cyano, a C.sub.1-4 alkyl group [which may be substituted with halogen atom(s)], a vinyl or ethynyl group [which may be substituted with halogen atom(s), C.sub.1-4 alkyl, cycloalkyl, aralkyl, or aromatic ring which may have one or more hetero atom(s)], or an aralkyl group which may be substituted for use in medical therapy, especially tumor therapy.

  一种以通式（I）表示的新型5'-去氧胞苷衍生物，其中R1是氢原子或在生理条件下易水解的基团；R2是氢原子，或--CO--OR4基团[其中R4是由1至15个碳原子组成的饱和或不饱和的直链或支链碳氢基团，或者是公式--（CH2）n--Y（其中Y是环己基或苯基；n是0至4的整数）]；R3是氢原子、溴、碘、氰基、C1-4烷基[可以被卤素原子取代]、乙烯基或乙炔基[可以被卤素原子、C1-4烷基、环烷基、芳基或含有一个或多个杂原子的芳环取代]，或者是可以用于医疗治疗的取代的芳基烷基。该化合物特别适用于肿瘤治疗。
• Vinylating of pyrimidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06437118B1

  公开（公告）日：2002-08-20

  The invention relates to a process for the preparation of vinyl pyrimidines of the formula I wherein R1 is hydrogen or a carboxylic ester group, and R2 is hydrogen or a group of the formula (a) wherein Ra is hydrogen, a protecting group or a group easily hydrolyzable under physiological conditions, by reacting a compound of the formula II wherein R21 is hydrogen or a group (a) wherein hydroxy groups are optionally protected, R3 is bromo, chloro or iodo, and R1 is as above, with a vinyl borane compound in the presence of a Pd complex and a base, and optionally, further reacting a product of formula I wherein R2 is hydrogen with a compound of the formula IV wherein Rb is a hydroxy protecting group and Z is a leaving group, in the presence of a Lewis acid catalyst.

  本发明涉及制备式I的乙烯基嘧啶的过程，其中R1为氢或羧酸酯基团，R2为氢或式（a）的基团，其中Ra为氢，保护基或在生理条件下容易水解的基团。该过程通过将式II的化合物与乙烯基硼烷化合物在Pd配合物和碱的存在下反应，其中R21为氢或式（a）的羟基可选择保护，R3为溴、氯或碘，R1如上所述，并且在路易斯酸催化剂的存在下，如果需要，可以进一步将式I的产物（其中R2为氢）与式IV的化合物（其中Rb为羟基保护基，Z为离去基团）反应。
• 5’－脱氧胞苷衍生物
  申请人：霍夫曼-拉罗奇有限公司

  公开号：CN1197871C

  公开（公告）日：2005-04-20

  用于医疗，尤其是肿瘤治疗的通式I所示的新的5′-脱氧-胞苷衍生物，其中的R 1 是氢原子或易于在生理条件下水解的基团；R 2 是氢原子，或-CO-OR 4 基[其中的R 4 是由1-15个碳原子的饱和或不饱和的、直链或支链的烃基，或通式-(CH 2 )n-Y的基团(其中的Y是环己基或苯基；n是从0到4的整数)]；R 3 是氢原子、溴基、碘基、氰基、C 1-4 烷基[其可用卤素原子取代]、乙烯基或乙炔基[其可用卤素原子、C 1-4 烷基、环烷基、芳烷基、或可带有一个或多个杂原子的芳环取代]，或是可被取代的芳烷基。
• 5'deoxycytidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06005098A1

  公开（公告）日：1999-12-21

  Compounds of the formula (I) ##STR1## wherein R.sup.1 is each independently hydrogen or a group easily hydrolyzable under physiological conditions; R.sup.2 is --(CH.sub.2).sub.n -cycloalkyl wherein cycloalkyl contains 3 to 5 carbon atoms and n is an integer from 0 to 4, heteroaryl-(lower-alkyl), (lower-alkoxy)-(lower-alkyl), aryloxy-(lower-alkyl), aralkyloxy-(lower-alkyl), (lower-alkylthio)-(lower-alkyl), arylthio-(lower-alkyl), aralkylthio-(lower-alkyl), oxo-(lower-alkyl), acylamino-(lower-alkyl), cyclic amino-(lower-alkyl), (2-oxocyclic amino)-(lower-alkyl) wherein the alkylene chain is unsubstituted or substituted with one or two lower-alkyl group(s); and R.sup.3 is iodo, or a vinyl or ethynyl group which group is unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, C.sub.1-4 alkyl, cycloalkyl, aralkyl, carbocyclic aromatic ring and heteorcyclic aromatic ring. The compounds of formula I are useful in the treatment of malignant diseases and can also be administered together with 5-fluorouracil or derivatives thereof to enhance the antitumour activity of the latter.

  化合物的化学式（I）如下：##STR1## 其中，R.sup.1 独立地为氢或在生理条件下容易水解的基团；R.sup.2 为 --(CH.sub.2).sub.n -环烷基，其中环烷基含有3到5个碳原子，n为0到4的整数，杂环芳基-(较低烷基)，(较低烷氧基)-(较低烷基)，芳氧基-(较低烷基)，芳基烷氧基-(较低烷基)，(较低烷硫基)-(较低烷基)，芳硫基-(较低烷基)，芳基烷硫基-(较低烷基)，氧代-(较低烷基)，酰胺基-(较低烷基)，环状氨基-(较低烷基)，(2-氧代环状氨基)-(较低烷基)，其中烷基链未取代或取代有一个或两个较低烷基；R.sup.3 为碘，或者为乙烯基或乙炔基，该基团未取代或取代有一个或多个卤素、C.sub.1-4 烷基、环烷基、芳基烷基、碳环芳香环和杂环芳香环中的一种或多种取代基。式（I）化合物在恶性疾病的治疗中有用，并且还可以与5-氟尿嘧啶或其衍生物一起给予，以增强后者的抗肿瘤活性。
• 5′-deoxy-cytidine derivative administration to treat solid tumors
  申请人：Hoffman-La Roche Inc.

  公开号：US06211166B1

  公开（公告）日：2001-04-03

  Novel 5′-deoxy-cytidine derivatives represented by the general formula (I) wherein R1 is a hydrogen atom or a group easily hydrolyzable under physiological conditions; R2 is a hydrogen atom, or —CO—OR4 group [wherein R4 is a saturated or unsaturated, straight or branched hydrocarbon group consisting of one to fifteen carbon atoms, or a group of the formula —(CH2)n—Y (in which Y is cyclohexyl or phenyl; n is an integer from 0 to 4)]; R3 is a hydrogen atom, bromo, iodo, cyano, a C1-4 alkyl group [which may be substituted with halogen atom(s)], a vinyl or ethynyl group [which may be substituted with halogen atom(s), C1-4 alkyl, cycloalkyl, aralkyl, or aromatic ring which may have one or more hetero atom(s)], or an aralkyl group which may be substituted for use in medical therapy, especially tumor therapy.

  化合物的通式为(I)，其中R1是氢原子或在生理条件下易水解的基团；R2是氢原子或—CO—OR4基团[其中R4是由1至15个碳原子组成的饱和或不饱和的直链或支链烃基，或者是由(CH2)n—Y式组成的基团(其中Y是环己基或苯基; n是0至4的整数)]; R3是氢原子、溴、碘、氰基、C1-4烷基[可以被卤原子取代]、乙烯基或乙炔基[可以被卤原子、C1-4烷基、环烷基、芳基或含有一个或多个杂原子的芳环取代]或者是可以被用于医疗治疗，特别是肿瘤治疗的取代的芳基烷基。