2-methoxy-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate | 185910-34-3

• 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: 2-methoxy-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate
• 英文别名: 3-sulfamate-2-methoxyestra-1,3,5(10)-trien-17-one；2-methoxyoestrone-3-O-sulphamate；2-MeOEMATE；[(8R,9S,13S,14S)-2-methoxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate
• CAS: 185910-34-3
• 化学式: C₁₉H₂₅NO₅S
• 分子量: 379.477
• InChiKey: BTQHAWWINOTNQQ-QPWUGHHJSA-N

物化性质

• 熔点：
  183-185 °C
• 沸点：
  560.8±60.0 °C(Predicted)
• 密度：
  1.308±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 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：

  2-methoxy-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以73%的产率得到2-methoxy-(E)-17-(oximino)estra-1,3,5(10)-trien-3-yl sulfamate
  参考文献：
  名称：

  [DE] ANTITUMOR WIRKSAME 2-SUBSTITUIERTE ESTRA-1,3,5(10)-TRIEN-3-YL SULFAMATE
  [EN] 2-SUBSTITUTED ESTRA-1,3,5(10)-TRIENE-3-YL SULFAMATE WITH AN ANTI-TUMOUR ACTION
  [FR] SULFAMATE ESTRA-1,3,5(10)-TRIENE-3-YLE 2-SUBSTITUE A EFFET ANTITUMEUR

  摘要：

  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。

  公开号：

  WO2004074307A1
• 作为产物：
  描述：

  2-formyl-3-O-methoxymethyl-17,17-ethylenedioxyestrone 在 盐酸 、 sodium hydroxide 、 disodium hydrogenphosphate 、 2,6-二叔丁基-4-甲基吡啶 、 氨基磺酰氯 、 四丁基碘化铵 、 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 76.0h， 生成 2-methoxy-17-oxoestra-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

文献信息

• [EN] OESTROGEN DERIVATIVES AS INHIBITORS OF STEROID SULPHATASE<br/>[FR] DERIVES ESTROGENES UTILISES EN TANT QU'INHIBITEURS DE STEROIDE SULFATASE
  申请人：STERIX LTD

  公开号：WO2004085459A1

  公开（公告）日：2004-10-07

  The present invention provides a compound comprising a steroidal ring system and an optional group R1 selected from any one of -OH, a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; wherein the D ring of the steroidal ring system is substituted by a group R2 of the formula -L-R3, wherein L is an optional linker group and R3 is selected from groups which are or which comprise one of a nitrite group, an alcohol, an ester, an ether, an amine and an alkene, provided that when R3 is or comprises an alcohol, L is present; and wherein the A ring of the steroidal ring system is substituted at position 2 or 4 with a group R4, wherein R4 is a hydrocarbyl group.

  本发明提供一种化合物，包括一种甾体环系统和一个可选的基团R1，所述基团R1从以下任一基团中选择：-OH、磺酸酯基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团；其中所述甾体环系统的D环通过一个公式-L-R3的基团R2取代，其中L是一个可选的连接基团，R3选择自一个亚硝酸盐基团、醇基团、酯基团、醚基团、胺基团和烯烃基团中的一个或组成一个，条件是当R3是或包含一个醇基团时，L存在；以及所述甾体环系统的A环在位置2或4处被一个基团R4取代，其中R4是一个烃基团。
• Compound
  申请人：——

  公开号：US20040019016A1

  公开（公告）日：2004-01-29

  There is provided a compound of Formula I 1 wherein each T is independently selected from H, hydrocarbyl, —F—R, and a bond with one of D, E, P or Q, or together with one of P and Q forms a ring; Z is a suitable atom the valency of which is m; D, E and F are each independently of each other an optional linker group, wherein when Z is nitrogen E is other than CH 2 and C═O; P, Q and R are independently of each other a ring system; and at least Q comprises a sulphamate group.

  提供了一个式I1的化合物，其中每个T分别选自H、烃基、—F—R和与D、E、P或Q中的一个之一形成键，或者与P和Q中的一个一起形成环；Z是一个适当的原子，其价数为m；D、E和F分别独立于彼此，是可选的连接基团，其中当Z是氮时，E不是CH2和C═O；P、Q和R独立于彼此，是一个环系统；至少Q包含一个磺酰胺基团。
• [EN] PHENYL-SULFAMATES AS AROMATASE INHIBITORS<br/>[FR] PHENYL-SULFAMATES EN TANT QU'INHIBITEURS DE L'AROMATASE
  申请人：STERIX LTD

  公开号：WO2005118560A1

  公开（公告）日：2005-12-15

  There is provided a compound of Formula (I) wherein X, Y and Z are each independently of each other an optional linker group; R, is a ring system; R2 is selected from hydrocarbyl groups, oxyhydrocarbyl groups, cyano (CN), nitro (-NO2) and halogens; R3 and R4 are independently selected from H and hydrocarbyl, ring A and B are independently optionally further substituted.

  提供了一个化合物的结构式（I），其中X、Y和Z分别独立地是一个可选的连接基团；R是一个环系统；R2从烃基团、氧烃基团、氰基（CN）、硝基（-NO2）和卤素中选择；R3和R4分别独立地从氢和烃基团中选择，环A和B分别独立地可进一步取代。
• [EN] SULFAMIC ACID ESTER COMPOUNDS USEFUL IN THE INHIBITION OF SEROID SULPHATASE ACTIVITY AND AROMATASE ACTIVITY<br/>[FR] COMPOSES D'ESTER D'ACIDE SULFAMIQUE UTILISES POUR INHIBER L'ACTIVITE DE LA STEROIDE SULFATASE ET L'ACTIVITE DE L'AROMATASE
  申请人：STERIX LTD

  公开号：WO2005115996A1

  公开（公告）日：2005-12-08

  There is provided a compound of Formula (III) or Formula (IV), wherein A is selected from H, OH, halogen and hydrocarbyl D, E and F are each independently of each other an optional linker group; P, Q and R are independently of each other a ring system, wherein R4 and R5 are independently selected from H, alkyl, cycloalkyl, alkenyl, acyl and aryl, or combinations thereof, or together represent alkylene, wherein the or each alkyl or cycloalkyl or alkenyl or optionally contain one or more hetero atoms or groups.

  提供一种化合物，其化学式为（III）或（IV），其中A从H、OH、卤素和烃基中选择，D、E和F分别是可选的连接基团；P、Q和R分别是独立的环系统，其中R4和R5从H、烷基、环烷基、烯烃基、酰基和芳基中独立选择，或者它们的组合，或者一起代表烷基，其中每个烷基或环烷基或烯烃基或可选地含有一个或多个杂原子或基团。
• Composition
  申请人：——

  公开号：US20010021707A1

  公开（公告）日：2001-09-13

  There is provided a pharmaceutical composition comprising (i) a compound of the formula 1 wherein: X is a hydrocarbyl ring having at least 4 atoms in the ring; K is a hydrocarbyl group; Rs is a sulphamate group; (ii) optionally admixed with a pharmaceutically acceptable carrier, diluent, excipient or adjuvant, wherein the compound is present in an amount to provide a dosage of no greater than 200 &mgr;g/day.

  提供一种制药组合物，包括（i）化合物的化学式1，其中：X是具有至少4个原子的烃基环；K是烃基团；Rs是磺酰基团；（ii）可选地与药用可接受的载体、稀释剂、赋形剂或辅助剂混合，其中该化合物的含量使得每日剂量不超过200微克。