3-((13S,15R)-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide

• 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-((13S,15R)-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide
• 英文别名: 3-[(13S,15R)-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-15-yl]-N-(5-methyl-1,3-thiazol-2-yl)propanamide
• 化学式: C₂₅H₂₉FN₂O₃S
• 分子量: 456.581
• InChiKey: IUHPXNRLEMCZKK-IGGGATHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-((13S,15R)-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide 在 硫酸 、 palladium on activated charcoal 、 氢气 、 silica gel 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 3-((13S,15R)-2-amino-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide
  参考文献：
  名称：

  [EN] PRODRUGS OF 17.BETA.-HSD1 -INHIBITORS
  [FR] PROMÉDICAMENTS D'INHIBITEURS DE LA 17Β-HSD1

  摘要：

  本发明涉及式(I)化合物及其药用可接受的盐，其中R1至R4如权利要求中定义。本发明进一步涉及它们作为17β-HSD1抑制剂的用途，以及在治疗或预防甾体激素依赖性疾病或失调症，如需要抑制17β-HSD1酶和/或需要降低内源性雌二醇浓度的甾体激素依赖性疾病或失调症中的应用。本发明还涉及前述化合物的制备，以及包含一个或多个前述化合物或其药用可接受盐作为活性成分的药物组合物。

  公开号：

  WO2016102776A1
• 作为产物：
  描述：

  3-((13S,15R)-4-amino-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide 在 tetrafluoroboric acid 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以22 mg的产率得到3-((13S,15R)-4-fluoro-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-15-yl)-N-(5-methylthiazol-2-yl)propanamide
  参考文献：
  名称：

  [EN] PRODRUGS OF 17.BETA.-HSD1 -INHIBITORS
  [FR] PROMÉDICAMENTS D'INHIBITEURS DE LA 17Β-HSD1

  摘要：

  本发明涉及式(I)化合物及其药用可接受的盐，其中R1至R4如权利要求中定义。本发明进一步涉及它们作为17β-HSD1抑制剂的用途，以及在治疗或预防甾体激素依赖性疾病或失调症，如需要抑制17β-HSD1酶和/或需要降低内源性雌二醇浓度的甾体激素依赖性疾病或失调症中的应用。本发明还涉及前述化合物的制备，以及包含一个或多个前述化合物或其药用可接受盐作为活性成分的药物组合物。

  公开号：

  WO2016102776A1

文献信息

• [EN] THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17 B-HYDROXYSTEROID DEHYDROGENASE, TYPE 1<br/>[FR] DÉRIVÉS D'ESTRATRIÉNTHIAZOLE THÉRAPEUTIQUEMENT ACTIFS UTILISÉS COMME INHIBITEURS DE LA 17&Bgr;-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：FORENDO PHARMA LTD

  公开号：WO2014207309A1

  公开（公告）日：2014-12-31

  The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R6 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de- pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

  本发明涉及式(I)化合物及其药用可接受的盐，其中R1至R6如权利要求中定义。本发明进一步涉及它们作为17β-HSD抑制剂的应用，以及在治疗或预防甾体激素依赖性疾病或失调症，例如需要抑制17β-HSD1酶和/或需要降低内源性雌二醇浓度的甾体激素依赖性疾病或失调症中的应用。本发明还涉及前述化合物的制备，以及包含一个或多个前述化合物或其药用可接受盐作为活性成分的药物组合物。
• [EN] THERAPEUTICALLY ACTIVE 17-NITROGEN SUBSTITUTED ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA.-HYDROXYSTEROID DEHYDROGENASE<br/>[FR] DÉRIVÉS THÉRAPEUTIQUEMENT ACTIFS D'ESTRATRIÈNE-THIAZOLE À SUBSTITUTION AZOTE EN POSITION 17 EN TANT QU'INHIBITEURS DE LA 17BÊTA.-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE
  申请人：FORENDO PHARMA LTD

  公开号：WO2014207310A1

  公开（公告）日：2014-12-31

  The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2to R7are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de- pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the afore- mentioned compounds or pharmaceutically acceptable salts thereof.

  该发明涉及公式（I）的化合物及其药学上可接受的盐，其中R2至R7如权利要求中定义的。该发明还涉及它们作为17β-HSD抑制剂的用途，并用于治疗或预防类固醇激素依赖性疾病或紊乱，例如需要抑制17β-HSD1酶或需要降低内源性雌二醇浓度的类固醇激素依赖性疾病或紊乱。本发明还涉及上述化合物的制备以及包含作为活性成分的药物组合物，其中活性成分为上述化合物之一或更多个或其药学上可接受的盐。
• Therapeutically active estratrienthiazole derivatives as inhibitors of 17 B-hydroxysteroid dehydrogenase, type 1
  申请人：FORENDO PHARMA LTD

  公开号：US10377791B2

  公开（公告）日：2019-08-13

  The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R6 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

  本发明涉及式（I）化合物及其药学上可接受的盐，其中 R1 至 R6 如权利要求中定义。本发明进一步涉及其作为 17β-HSD 抑制剂的用途，以及在治疗或预防类固醇激素依赖性疾病或紊乱中的用途，例如需要抑制 17β-HSD1 酶和/或需要降低内源性雌二醇浓度的类固醇激素依赖性疾病或紊乱。本发明还涉及上述化合物的制备，以及包含一种或多种上述化合物或其药学上可接受的盐作为活性成分的药物组合物。
• Prodrugs of 17.BETA.-HSD1-inhibitors
  申请人：FORENDO PHARMA LTD

  公开号：US10413557B2

  公开（公告）日：2019-09-17

  The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

  本发明涉及式（I）化合物及其药学上可接受的盐，其中 R1 至 R4 如权利要求中定义。本发明还涉及它们作为 17β-HSD1 抑制剂和在治疗或预防类固醇激素依赖性疾病或紊乱中的用途，例如需要抑制 17β-HSD1 酶和/或需要降低内源性雌二醇浓度的类固醇激素依赖性疾病或紊乱。本发明还涉及上述化合物的制备，以及包含一种或多种上述化合物或其药学上可接受的盐作为活性成分的药物组合物。
• THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17B-HYDROXYSTEROID DEHYDROGENASE, TYPE 1
  申请人：Forendo Pharma Ltd

  公开号：EP3013845B1

  公开（公告）日：2020-03-18