methyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-phenoxy-phosphoryl]amino]propanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-phenoxy-phosphoryl]amino]propanoate
• 英文别名: methyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-phenoxyphosphoryl]amino]propanoate
• 化学式: C₁₈H₂₃N₆O₅P
• 分子量: 434.392
• InChiKey: JIQWPHCYEYORRP-LGHQJEIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  阿德福韦 在 吡啶 、 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 32.5h， 生成 methyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-phenoxy-phosphoryl]amino]propanoate
  参考文献：
  名称：

  Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA

  摘要：

  Some novel amidate prodrugs of PMEA and PMPA have been synthesised and tested in vitro for their biological activity. Compound 5 in particular showed greatly enhanced antiviral potency compared with the parent nucleotide analogue. In vitro enzymatic studies and structure-activity relationships indicate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00128-7

文献信息

• ANTI-PROLIFERATIVE COMPOUNDS, COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：Cheng Xiaoqin

  公开号：US20090291922A1

  公开（公告）日：2009-11-26

  Compounds and compositions of Formula I are described, useful as anti-proliferative agents, and in particular anti-HPV, wherein: Y 1A and Y 1B are independently Y 1 ; R X1 and R X2 are independently R X ; Y 1 is ═O, —O(R X ), ═S, —N(R X ), —N(O)(R X ), —N(OR X ), —N(O)(OR X ), or —N(N(R X )(R X )); R X is independently R 1 , R 2 , R 4 , W 3 , or a protecting group; R 1 is independently —H or alkyl of 1 to 18 carbon atoms; R 2 is independently R 3 or R 4 wherein each R 4 is independently substituted with 0 to 3 R 3 groups or taken together at a carbon atom, two R 2 groups form a ring of 3 to 8 carbons and the ring may be substituted with 0 to 3 R 3 groups; R 3 is R 3a , R 3b , R 3c or R 3d , provided that when R 3 is bound to a heteroatom, then R 3 is R 3c or R 3d ; R 3a is —H, —F, —Cl, —Br, —I, —CF 3 , —CN, N 3 , —NO 2 , or —OR 4 ; R 3b is ═O, —O(R 4 ), ═S, —N(R 4 ), —N(O)(R 4 ), —N(OR 4 ), —N(O)(OR 4 ), or —N(N(R 4 )(R 4 )); R 3c is —R 4 , —N(R 4 )(R 4 ), —SR 4 , —S(O)R 4 , —S(O) 2 R 4 , —S(O)(OR 4 ), —S(O) 2 (OR 4 ), —OC(R 3b )R 4 , —OC(R 3b )OR 4 , —OC(R 3b )(N(R 4 )(R 4 )), —SC(R 3b )R 4 , —SC(R 3b )OR 4 , —SC(R 3b )(N(R 4 )(R 4 )), —N(R 4 )C(R 3b )R 4 , —N(R 4 )C(R 3b )OR 4 , —N(R 4 )C(R 3b ) (N(R 4 )(R 4 )), W 3 or —R 5 W 3 ; R 3d is —C(R 3b )R 4 , —C(R 3b )OR 4 , —C(R 3b )W 3 , —C(R 3b )OW 3 or —C(R 3b )(N(R 4 )(R 4 )); R 4 is —H, or an alkyl of 1 to 18 carbon atoms, alkenyl of 2 to 18 carbon atoms, or alkynyl of 2 to 18 carbon atoms; R 5 is alkylene of 1 to 18 carbon atoms, alkenylene of 2 to 18 carbon atoms, or alkynylene of 2 to 18 carbon atoms; W 3 is W 4 or W 5 ; W 4 is R 6 , —C(R 3b )R 6 , —C(R 3b )W 5 , —SO M2 R 6 , or —SO M2 W 5 , wherein R 6 is R 4 wherein each R 4 is substituted with 0 to 3 R 3 groups; W 5 is carbocycle or heterocycle wherein W 5 is independently substituted with 0 to 3 R 2 groups; and M2 is 0, 1 or 2; and pharmaceutically acceptable salts thereof.

  本发明涉及一种公式I的化合物和组合物，用作抗增殖剂，特别是抗HPV，其中：Y1A和Y1B独立地为Y1;RX1和RX2独立地为RX；Y1为═O，—O（RX），═S，—N（RX），—N（O）（RX），—N（ORX），—N（O）（ORX）或—N（N（RX）（RX））；RX独立地为R1，R2，R4，W3或保护基；R1独立地为—H或1至18个碳原子的烷基；R2独立地为R3或R4，其中每个R4独立地用0至3个R3基替代或在一个碳原子上结合，两个R2基形成3至8个碳原子的环，并且该环可以用0至3个R3基替代；R3为R3a，R3b，R3c或R3d，但当R3与杂原子结合时，则R3为R3c或R3d；R3a为—H，—F，—Cl，—Br，—I，—CF3，—CN，N3，—NO2或—OR4；R3b为═O，—O（R4），═S，—N（R4），—N（O）（R4），—N（OR4），—N（O）（OR4）或—N（N（R4）（R4））；R3c为—R4，—N（R4）（R4），—SR4，—S（O）R4，—S（O）2R4，—S（O）（OR4），—S（O）2（OR4），—OC（R3b）R4，—OC（R3b）OR4，—OC（R3b）（N（R4）（R4）），—SC（R3b）R4，—SC（R3b）OR4，—SC（R3b）（N（R4）（R4）），—N（R4）C（R3b）R4，—N（R4）C（R3b）OR4，—N（R4）C（R3b）（N（R4）（R4）），W3或—R5W3；R3d为—C（R3b）R4，—C（R3b）OR4，—C（R3b）W3，—C（R3b）OW3或—C（R3b）（N（R4）（R4））；R4为—H，或1至18个碳原子的烷基，2至18个碳原子的烯基或2至18个碳原子的炔基；R5为1至18个碳原子的亚烷基，2至18个碳原子的烯亚烷基或2至18个碳原子的炔亚烷基；W3为W4或W5；W4为R6，—C（R3b）R6，—C（R3b）W5，—SOM2R6或—SOM2W5，其中R6为R4，其中每个R4用0至3个R3基替代；W5为碳环或杂环，其中W5独立地用0至3个R2基替代；M2为0、1或2；以及其药学上可接受的盐。
• US7553825B2
  申请人：——

  公开号：US7553825B2

  公开（公告）日：2009-06-30
• US8088754B2
  申请人：——

  公开号：US8088754B2

  公开（公告）日：2012-01-03
• US8268802B2
  申请人：——

  公开号：US8268802B2

  公开（公告）日：2012-09-18
• Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA
  作者：Carlo Ballatore、Christopher McGuigan、Erik De Clercq、Jan Balzarini

  DOI：10.1016/s0960-894x(01)00128-7

  日期：2001.4

  Some novel amidate prodrugs of PMEA and PMPA have been synthesised and tested in vitro for their biological activity. Compound 5 in particular showed greatly enhanced antiviral potency compared with the parent nucleotide analogue. In vitro enzymatic studies and structure-activity relationships indicate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues. (C) 2001 Elsevier Science Ltd. All rights reserved.