2-fluoroestrone 3-sulfamate

• 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-fluoroestrone 3-sulfamate
• 英文别名: 2-fluoroestrone-3-O-sulfamate；2-fluorooestrone-3-O-sulphamate；2-fluoroEMATE；[(8R,9S,13S,14S)-2-fluoro-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate
• 化学式: C₁₈H₂₂FNO₄S
• 分子量: 367.441
• InChiKey: HRICESCEKKGRKZ-JPVZDGGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-fluoroestrone 3-sulfamate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以50.5%的产率得到Sulfamic acid (8R,9S,13S,14S,17S)-2-fluoro-17-hydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl ester
  参考文献：
  名称：

  Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates

  摘要：

  our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6 beta-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with K-i's ranging between 4.0 and 11.3 nM (K-i for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2005.12.004
• 作为产物：
  描述：

  2-fluoroestrone 在 2,6-二叔丁基-4-甲基吡啶 、 氨基磺酰氯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以57%的产率得到2-fluoroestrone 3-sulfamate
  参考文献：
  名称：

  雌激素-3-邻氨基磺酸雌酮类似物作为强效类固醇硫酸酯酶抑制剂的合成与评价

  摘要：

  氨基磺酸雌酮（EMATE）是一种强力不可逆的甾族硫酸酯酶（STS）抑制剂。为了进一步扩大SAR，将该化合物在2-和/或4-位取代，并且还除去其17-羰基。对于两个衍生物，在两个体外系统中观察到针对STS的以下一般效力顺序：4-NO 2  > 2-卤素，2-氰基> EMATE（未取代）> 17-脱氧EMATE> 2-NO 2  > 4-溴> 2-（2-丙烯基），2-正丙基> 4-（2-丙烯基），4-正丙基> 2,4-（2-丙烯基）= 2,4-二-n-丙基。将吸电子取代基放置在A环上具有明显的优势，而卤素优选在2位上，而硝基在4位上。在EMATE的2-和/或4-位上用2-丙烯基或正丙基取代，以及除去17-羰基对效能是有害的。设计的三种环状氨基磺酸盐不是STS抑制剂。这进一步证实，如EMATE和Irosustat抑制剂所示，游离或N-未取代的氨基磺酸酯基团（H 2 NSO 2 O–）是有效和不可

  DOI：

  10.1016/j.bmc.2012.03.007

文献信息

• Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonate- and sulphonamide- compounds as inhibitors of steroid sulphatase
  申请人：——

  公开号：US20030134829A1

  公开（公告）日：2003-07-17

  A compound is described. The compound has the formula (Ia) as presented in the FIG. 1; wherein: X is a ring having at least 4 atoms in the ring; K is hydrocarbyl group; Rh1 is an optional halo group; Rh2 is an optional halo group; at least one of Rh1 and Rh2 is present; Rs is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group. The compound is capable of inhibiting steroid sulphatase (STS) activity.

  描述了一种化合物。该化合物的化学式如图1所示；其中：X是具有至少4个原子的环；K是烃基团；Rh1是可选的卤素基团；Rh2是可选的卤素基团；Rh1和Rh2中至少有一个存在；Rs是磺酸酯基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团中的任意一个。该化合物能够抑制类固醇硫酸酶（STS）活性。
• HALOGENATED SULPHAMATE-, PHOSPHONATE-, THIOPHOSPHONATE-, SULPHONATE- AND SULPHONAMIDE- COMPOUNDS AS INHIBITORS OF STEROID SULPHATASE
  申请人：Sterix Limited

  公开号：EP1237902B1

  公开（公告）日：2005-11-02
• US6858597B2
  申请人：——

  公开号：US6858597B2

  公开（公告）日：2005-02-22
• Synthesis and evaluation of analogues of estrone-3-O-sulfamate as potent steroid sulfatase inhibitors
  作者：L.W. Lawrence Woo、Bertrand Leblond、Atul Purohit、Barry V.L. Potter

  DOI：10.1016/j.bmc.2012.03.007

  日期：2012.4

  Estrone sulfamate (EMATE) is a potent irreversible inhibitor of steroid sulfatase (STS). In order to further expand SAR, the compound was substituted at the 2- and/or 4-positions and its 17-carbonyl group was also removed. The following general order of potency against STS in two in vitro systems is observed for the derivatives: The 4-NO2 > 2-halogens, 2-cyano > EMATE (unsubstituted) > 17-deoxyEMA

  氨基磺酸雌酮（EMATE）是一种强力不可逆的甾族硫酸酯酶（STS）抑制剂。为了进一步扩大SAR，将该化合物在2-和/或4-位取代，并且还除去其17-羰基。对于两个衍生物，在两个体外系统中观察到针对STS的以下一般效力顺序：4-NO 2  > 2-卤素，2-氰基> EMATE（未取代）> 17-脱氧EMATE> 2-NO 2  > 4-溴> 2-（2-丙烯基），2-正丙基> 4-（2-丙烯基），4-正丙基> 2,4-（2-丙烯基）= 2,4-二-n-丙基。将吸电子取代基放置在A环上具有明显的优势，而卤素优选在2位上，而硝基在4位上。在EMATE的2-和/或4-位上用2-丙烯基或正丙基取代，以及除去17-羰基对效能是有害的。设计的三种环状氨基磺酸盐不是STS抑制剂。这进一步证实，如EMATE和Irosustat抑制剂所示，游离或N-未取代的氨基磺酸酯基团（H 2 NSO 2 O–）是有效和不可
• Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates
  作者：Mitsuteru Numazawa、Takako Tominaga、Yoko Watari、Yasue Tada

  DOI：10.1016/j.steroids.2005.12.004

  日期：2006.5

  our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6 beta-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with K-i's ranging between 4.0 and 11.3 nM (K-i for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer. (c) 2006 Elsevier Inc. All rights reserved.