(8S,13S,14S,17S)-13,17-Dimethyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol | 54690-62-9

• 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: (8S,13S,14S,17S)-13,17-Dimethyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-ol
• 英文别名: (8S,13S,14S,17S)-13,17-dimethylspiro[1,2,4,6,7,8,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-ol
• CAS: 54690-62-9
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.5
• InChiKey: JXXKWVNFMJJQTP-FYQPLNBISA-N

物化性质

• 溶解度：
  溶于二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• [EN] INHIBITORS OF GLUCOCORTICOID RECEPTOR<br/>[FR] INHIBITEURS DE RÉCEPTEURS GLUCOCORTICOÏDES
  申请人：ORIC PHARMACEUTICALS INC

  公开号：WO2017112904A1

  公开（公告）日：2017-06-29

  The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.

  本发明一般涉及治疗癌症和高皮质醇血症的组合物和方法。本文提供了替代类固醇衍生物化合物和包含该化合物的药物组合物。所述化合物和组合物对于抑制糖皮质激素受体是有用的。此外，所述化合物和组合物对于治疗癌症和高皮质醇血症是有用的。
• INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17alpha-ACETOXY-11beta-[4-(N,N-DIMETHYL-AMINO)-PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS
  申请人：Dancsi Lajosne

  公开号：US20090187032A1

  公开（公告）日：2009-07-23

  The present invention relates to a new industrial process for the synthesis of solvate-free 17α-acetoxy-11β-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB-2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method, ii) the obtained 3-(ethylene-dioxy)-17α-ethynyl-17β-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid, iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, then v) the obtained 3-(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11)-diene-20-one of formula (VI) is reacted with ethylene glycol in dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5α,10α- and 5β,10β-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran in the presence of copper(I) chloride catalyst without separation of the isomers by known method, viii) the obtained 3,3,20,20-bis(ethylene-dioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norpregn-9(11)-ene of formula (III) is reacted with potassium hydrogensulfate in water by known method, ix) the obtained 11β-[4-(N,N-dimethylamino)-phenyl]-17α-hydroxy-19-norpregn-4,9-diene-3,20-dione of formula (II) is acetylated with acetic anhydride in the presence of perchloric acid by known method, finally x) the solvate-free compound of formula (I) is liberated from the obtained solvate containing compound of formula (I) in a 1:1 mixture of ethanol and water at 70° C.

  本发明涉及一种新的工业合成过程，用于合成无溶剂17α-乙酰氧基-11β-[4-(N,N-二甲基氨基)-苯基]-19-去孕烷-4,9-二烯-3,20-二酮[CDB-2914]，其化学式为(I)，该化合物是一种强抗孕激素和抗糖皮质激素剂。本发明还涉及用作该过程中间体的化合物的化学式(VII)和(VIII)。本发明的工艺如下：i)使用已知方法，在干四氢呋喃中与现场形成的乙酰乙炔钾反应，得到化学式(X)的3-(乙二氧基)-麦角甾-5(10)，9(11)-二烯-17-酮，ii)在三乙胺和乙酸存在下，使用二氯甲烷中的苯基磺酰氯与上述得到的3-(乙二氧基)-17α-乙炔基-17β-羟基-麦角甾-5(10)，9(11)-二烯反应，得到化学式(IX)的产物，iii)使用甲醇中的甲酸钠和三甲基膦酸三甲酯，先后与上述得到的3-(乙二氧基)-21-(苯基磺酰基)-19-去孕烷-5(10)，9(11)，17(20)，20-四烯反应，得到化学式(VIII)的异构混合物，iv)使用甲醇中的氢氯酸与上述得到的3-(乙二氧基)-17α-羟基-20-甲氧基-19-去孕烷-5(10)，9(11)，20-三烯反应，得到化学式(VII)的产物，v)使用三甲基正酯和对甲苯磺酸在二氯甲烷中与上述得到的3-(乙二氧基)-17α-羟基-19-去孕烷-5(10)，9(11)-二烯-20-酮反应，得到化学式(VI)的产物，vi)使用已知方法，在吡啶和二氯甲烷的混合物中，使用六氯代丙酮，与上述得到的3,3,20,20-双(乙二氧基)-17α-羟基-19-去孕烷-5(10)，9(11)-二烯反应，得到化学式(V)的产物，vii)从溶液中分离出含有大约1:1的5α,10α-和5β,10β-环氧化物的化学式(IV)的产物，并使用已知方法，在四氢呋喃中与从4-溴-N,N-二甲基苯胺中获得的格氏试剂和氯化铜(I)催化剂反应，而不分离异构体，得到化学式(III)的产物，viii)使用已知方法，在水中使用硫酸氢钾与上述得到的3,3,20,20-双(乙二氧基)-5α,17α-二羟基-11β-[4-(N,N-二甲基氨基)-苯基]-19-去孕烷-9(11)-二烯反应，得到化学式(II)的产物，ix)使用已知方法，在高氯酸存在下，使用乙酸酐对上述得到的化学式(II)的11β-[4-(N,N-二甲基氨基)-苯基]-17α-羟基-19-去孕烷-4,9-二烯-3,20-二酮进行乙酰化，最后在70°C的乙醇和水的1:1混合物中从得到的含溶剂化合物中解放出化学式(I)的无溶剂化合物。
• INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17 ALPHA -ACETOXY-11 BETA -[4-(N,N-DIMETHYL-AMINO)- PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS
  申请人：Richter Gedeon NYRT

  公开号：EP2027140B1

  公开（公告）日：2013-03-13
• INHIBITORS OF GLUCOCORTICOID RECEPTOR
  申请人：ORIC Pharmaceuticals, Inc.

  公开号：US20210395295A1

  公开（公告）日：2021-12-23

  The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.
• US8110691B2
  申请人：——

  公开号：US8110691B2

  公开（公告）日：2012-02-07