{1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-iodo-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester | 216449-58-0

• 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: {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-iodo-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester
• 英文别名: 2',3'-Bis-o-(tert-butyldimethylsilyl)-5'-deoxy-5-iodo-n4-(n-pentyloxycarbonyl)cytidine；pentyl N-[1-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyloxolan-2-yl]-5-iodo-2-oxopyrimidin-4-yl]carbamate
• CAS: 216449-58-0
• 化学式: C₂₇H₅₀IN₃O₆Si₂
• 分子量: 695.786
• InChiKey: ILLCRJYQHXHKEB-KTDPBYDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.28
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-iodo-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 5'-deoxy-5-iodo-N4-(n-pentyloxycarbonyl)cytidine
  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：

  5'-deoxy-5-iodocytidine 在 吡啶 、 咪唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 {1-[(2R,3R,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-methyl-tetrahydro-furan-2-yl]-5-iodo-2-oxo-1,2-dihydro-pyrimidin-4-yl}-carbamic acid pentyl ester
  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

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.

  化合物的通用式为(I)，其中R1是氢原子或在生理条件下容易水解的基团；R2是氢原子或--CO--OR4基团[其中R4是由一到十五个碳原子组成的饱和或不饱和、直链或支链的碳氢基团，或者是公式--(CH2)n--Y的基团（其中Y是环己基或苯基；n是0到4的整数）]；R3是氢原子、溴、碘、氰基、C1-4烷基[可以用卤原子替代]、乙烯基或乙炔基[可以用卤原子、C1-4烷基、环烷基、芳基烷基或含有一个或多个杂原子的芳环替代]、或者是可替代的芳基烷基用于医学治疗，特别是肿瘤治疗。
• 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。