2-chloroestrone 3-O-sulfamate | 344565-79-3

• 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-chloroestrone 3-O-sulfamate
• 英文别名: 2-chloroestrone 3-sulfamate；2-Chloroestrone 3-O-sulphamate；2-ChloroEMATE；[(8R,9S,13S,14S)-2-chloro-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-yl] sulfamate
• CAS: 344565-79-3
• 化学式: C₁₈H₂₂ClNO₄S
• 分子量: 383.896
• InChiKey: OCMPCNKBNUQUCT-JPVZDGGYSA-N

物化性质

• 熔点：
  212-215 °C(Solv: acetone (67-64-1))
• 沸点：
  545.4±60.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 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：
  5

反应信息

• 作为反应物：
  描述：

  2-chloroestrone 3-O-sulfamate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以81%的产率得到Sulfamic acid (8R,9S,13S,14S,17S)-2-chloro-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：

  3-羟基-2-碘-雌-1,3,5(10)-三烯-17-酮 以68%的产率得到2-chloroestrone 3-O-sulfamate
  参考文献：
  名称：

  Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonate- and sulphonamide- compounds as inhibitors of steroid sulphatase

  摘要：

  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。

  公开号：

  US20030134829A1

文献信息

• 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
• 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。
• 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.