3-sulfamate-2-ethoxyestra-1,3,5(10)-trien-17-one | 824946-42-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-sulfamate-2-ethoxyestra-1,3,5(10)-trien-17-one
• 英文别名: (8R,9S,13S,14S)-2-Ethoxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-sulfonic acid amide；[(8R,9S,13S,14S)-2-ethoxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate
• CAS: 824946-42-1
• 化学式: C₂₀H₂₇NO₅S
• 分子量: 393.504
• InChiKey: KLUBMCIEPHWLGE-IDLUEMFASA-N

物化性质

• 熔点：
  179-181 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  569.1±60.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-sulfamate-2-ethoxyestra-1,3,5(10)-trien-17-one 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 3.0h， 以85%的产率得到2-ethoxy-17β-hydroxy-estra-1,3,5(10)-trien-3-yl sulfamate
  参考文献：
  名称：

  A-Ring-Substituted Estrogen-3-O-sulfamates:  Potent Multitargeted Anticancer Agents

  摘要：

  Efficient and flexible syntheses of 2-substituted estrone, estradiol and their 3-O-sulfamate (EMATE) derivatives have been developed using directed ortho-lithiation methodology. 2-Substituted EMATEs display a similar antiproliferative activity profile to the corresponding estradiols against a range of human cancer cell lines. 2-Methoxy (3, 4), 2-methylsulfanyl (20, 21) and 2-ethyl EMATEs (32, 33) proved the most active compounds with 2-ethylestradiol-3-O-sulfamate (33), displaying a mean activity over the NCI 55 cell line panel 80-fold greater than the established anticancer agent 2-methoxyestradiol (2). 2-Ethylestradiol-3-O-sulfamate (33) was also an effective inhibitor of angiogenesis using three in vitro markers, and various 2-substituted EMATEs also proved to be inhibitors of steroid sulfatase (STS), a therapeutic target for the treatment of hormone-dependent breast cancer. The potential of this novel class of multimechanism anticancer agents was confirmed in vivo with good activity observed in the NCI hollow fiber assay and in a MDA-MB-435 xenograft mouse model.

  DOI：

  10.1021/jm050066a
• 作为产物：
  描述：

  雌酮17-乙烯缩酮 在 盐酸 、 sodium hydroxide 、 disodium hydrogenphosphate 、 2,6-二叔丁基-4-甲基吡啶 、 氨基磺酰氯 、 仲丁基锂 、 四丁基碘化铵 、 sodium hydride 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 59.0h， 生成 3-sulfamate-2-ethoxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  A-Ring-Substituted Estrogen-3-O-sulfamates:  Potent Multitargeted Anticancer Agents

  摘要：

  Efficient and flexible syntheses of 2-substituted estrone, estradiol and their 3-O-sulfamate (EMATE) derivatives have been developed using directed ortho-lithiation methodology. 2-Substituted EMATEs display a similar antiproliferative activity profile to the corresponding estradiols against a range of human cancer cell lines. 2-Methoxy (3, 4), 2-methylsulfanyl (20, 21) and 2-ethyl EMATEs (32, 33) proved the most active compounds with 2-ethylestradiol-3-O-sulfamate (33), displaying a mean activity over the NCI 55 cell line panel 80-fold greater than the established anticancer agent 2-methoxyestradiol (2). 2-Ethylestradiol-3-O-sulfamate (33) was also an effective inhibitor of angiogenesis using three in vitro markers, and various 2-substituted EMATEs also proved to be inhibitors of steroid sulfatase (STS), a therapeutic target for the treatment of hormone-dependent breast cancer. The potential of this novel class of multimechanism anticancer agents was confirmed in vivo with good activity observed in the NCI hollow fiber assay and in a MDA-MB-435 xenograft mouse model.

  DOI：

  10.1021/jm050066a

文献信息

• [DE] ANTITUMOR WIRKSAME 2-SUBSTITUIERTE ESTRA-1,3,5(10)-TRIEN-3-YL SULFAMATE<br/>[EN] 2-SUBSTITUTED ESTRA-1,3,5(10)-TRIENE-3-YL SULFAMATE WITH AN ANTI-TUMOUR ACTION<br/>[FR] SULFAMATE ESTRA-1,3,5(10)-TRIENE-3-YLE 2-SUBSTITUE A EFFET ANTITUMEUR
  申请人：SCHERING AG

  公开号：WO2004074307A1

  公开（公告）日：2004-09-02

  Die Erfindung betrifft die Verwendung von 2-substituierten Estra-1,3,5(10)-trien-3-yl sulfamaten der allgemeinen Formel I sowie ihrer pharmazeutisch annehmbaren Salze zur Herstellung eines Arzneimittels. Die Verbindungen sind Antitumor wirksam.

  这项发明涉及使用一般式I的2-取代基Estra-1,3,5(10)-三烯-3-基磺酸酯及其药学上可接受的盐来制备药物。这些化合物具有抗肿瘤活性。
• Antiangiogenic agents
  申请人：Agoston E. Gregory

  公开号：US20050014737A1

  公开（公告）日：2005-01-20

  Compositions and methods for treating mammalian disease characterized by undesirable angiogenesis by administering compounds of the general formula: wherein the variables are defined in the specification.

  通过给予一般公式中的化合物治疗具有不良血管生成特征的哺乳动物疾病的方法和组合物。其中，变量在规范中有定义。
• 2-Substituted estra-1,3,5(10)-triene-3-yl sulfamate with an anti-tumour action
  申请人：Hillisch Alexander

  公开号：US20060160782A1

  公开（公告）日：2006-07-20

  The invention relates to the use of 2-substituted estra-1,3,5(10)-triene-3-yl sulfamates of general formula I, in addition to their pharmaceutically acceptable salts for producing a medicament Said compounds have an anti-tumour action.

  本发明涉及使用一般式I的2-取代的Estra-1,3,5（10）-三烯-3-基磺酸盐，以及其药学上可接受的盐，用于制备药物。所述化合物具有抗肿瘤作用。
• 2-SUBSTITUTED ESTRA-1,3,5(10)-TRIENE-3-YL SULFAMATE WITH AN ANTI-TUMOUR ACTION
  申请人：HILLISCH Alexander

  公开号：US20090221841A1

  公开（公告）日：2009-09-03

  The invention relates to the use of 2-substituted estra-1,3,5(10)-triene-3-yl sulfamates of general formula I, in addition to their pharmaceutically acceptable salts for producing a medicament. Said compounds have an anti-tumour action.

  该发明涉及使用一般式I中的2-取代的estra-1,3,5（10）-三烯-3-基磺酸盐，以及其药学上可接受的盐来制备药物。这些化合物具有抗肿瘤作用。
• Antitumor wirksame 2-alkoxyestradiolsulfamate
  申请人：Schering AG

  公开号：US20030100544A1

  公开（公告）日：2003-05-29

  The present invention relates to the use of 2-alkoxyestrogen sulfamates of general formula I 1 wherein R 1 and R 2 independently represent H, methyl, C 1 -C 4 acyl, benzoyl R 3 represents C 1 -C 4 alkyl or a group of formula C n F m H o , wherein n=1, 2, 3, 4, 5 or 6, m>1, and m+o=2n+1, R 4 and R 5 in each case represent H or, together, a methylene group or an additional double bond, R 6 represents H. R 7 represents OH, OC 1 -C 4 -alkyl, OC 1 -C 11 -acyl or OSO 2 NR 1 R 2 , the dashed lines in the B and C rings of the steroid skeleton additionally representing up to two double bonds, for the production of a medical drug for the treatment of tumor diseases which can be affected positively by inhibiting the tubulin polymerization. The inventive compounds are distinguished by the 2-alkoxy substitution in conjunction with the 17-hydroxy substitution. They have a special effect with regard to inhibiting tubulin polymerization and can be used, for example, for the treatment of prostate cancers.

  本发明涉及使用一般式I1中的2-烷氧基雌激素磺酸酯，其中R1和R2独立地表示H、甲基、C1-C4酰基、苯甲酰基，R3表示C1-C4烷基或公式CnFmHo的基团，其中n=1、2、3、4、5或6，m>1，且m+o=2n+1，R4和R5分别表示H或一起表示亚甲基基团或额外的双键，R6表示H，R7表示OH、OC1-C4烷基、OC1-C11酰基或OSO2NR1R2，类固醇骨架的B和C环中的虚线还可以表示多达两个双键，用于制备治疗肿瘤疾病的药物，该药物可以通过抑制微管聚合而产生积极影响。本发明的化合物具有2-烷氧基取代与17-羟基取代的特殊效果，可以用于治疗前列腺癌等疾病。