16-methylene-17β-hydroxy-18-methyl-19-nor-17α-pregn-4-en-3,20-dione | 192721-93-0

• 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: 16-methylene-17β-hydroxy-18-methyl-19-nor-17α-pregn-4-en-3,20-dione
• 英文别名: (8R,9S,10R,13S,14S,17S)-17-acetyl-13-ethyl-17-hydroxy-16-methylidene-2,6,7,8,9,10,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-one
• CAS: 192721-93-0
• 化学式: C₂₂H₃₀O₃
• 分子量: 342.478
• InChiKey: BZLUPEQWHVJLKH-REGVOWLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  16-methylene-17β-hydroxy-18-methyl-19-nor-17α-pregn-4-en-3,20-dione 在 TEA 、 三乙胺 、 三甲氧基磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.17h， 生成 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione
  参考文献：
  名称：

  Synthesis and biological activity of a new progestogen, 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate

  摘要：

  The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17 alpha-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel. and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit. and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-merhyl group to Nestorone markedly increased its potency as noted above. but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00109-9
• 作为产物：
  描述：

  (8R,9S,10R,13S,14S,17S)-17-(1-Ethoxy-vinyl)-13-ethyl-3-methoxy-16-methylene-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-ol 在 盐酸 作用下， 反应 8.0h， 以31.6 g的产率得到16-methylene-17β-hydroxy-18-methyl-19-nor-17α-pregn-4-en-3,20-dione
  参考文献：
  名称：

  Synthesis and biological activity of a new progestogen, 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate

  摘要：

  The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17 alpha-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel. and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit. and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-merhyl group to Nestorone markedly increased its potency as noted above. but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(99)00109-9

文献信息

• [EN] PROCESS FOR ALKYNYLATING 16-SUBSTITUTED-17-KETO STEROIDS<br/>[FR] PROCÉDÉ POUR ALCYNYLER DES 17-CÉTO-STÉROÏDES 16-SUBSTITUÉS
  申请人：CRYSTAL PHARMA SAU

  公开号：WO2013092668A1

  公开（公告）日：2013-06-27

  The invention relates to a process for ethynylating 16-methylene-17-keto steroids to the corresponding 16-methylene-17α-ethynyl-17β-hydroxy steroids by treatment with silyl-protected lithium acetylides followed by further desilylation. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as e.g. Nestorone® or melengestrol acetate.

  该发明涉及一种将16-亚甲基-17-酮类固醇乙炔化为相应的16-亚甲基-17α-乙炔基-17β-羟基类固醇的方法，方法是通过与硅保护的锂乙炔基作用，然后进行进一步的去硅化处理。所得产物是制备几种药用活性剂的有用中间体，例如Nestorone®或乙烯孕酮醋酸酯。
• PROCESS FOR ALKYNYLATING 16-SUBSTITUTED-17-KETO STEROIDS
  申请人：Crystal Pharma S.A.U

  公开号：EP2794632A1

  公开（公告）日：2014-10-29
• EP2794632B1
  申请人：——

  公开号：EP2794632B1

  公开（公告）日：2016-03-16
• US9296780B2
  申请人：——

  公开号：US9296780B2

  公开（公告）日：2016-03-29
• [EN] 18-METHYL 16-METHYLENE 19-NOR PREGNANE DERIVATIVES AS PROGESTINS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] DERIVES DE 18-METHYL-16-METHYLENE-19-NOR PREGNANE UTILISES EN TANT QUE PROGESTINES, COMPOSITIONS PHARMACEUTIQUES CONTENANT CES DERIVES ET PROCEDE DE PREPARATION CORRESPONDANTS
  申请人：RICHTER GEDEON VEGYÉSZETI GYÁR RT.

  公开号：WO1997023498A1

  公开（公告）日：1997-07-03

  (EN) The invention relates to novel 16-methylene-17$g(a)-acyloxy-18-methyl-19-norpregn-4-ene-3,20-dione derivatives to pharmaceutical compositions containing these compounds; to the intermediates useful for the preparation of these compounds as well as a process for the preparation of these compounds and compositions. The compounds exert a progestogenic effect.(FR) L'invention se rapporte à de nouveaux dérivés de 16-méthylène-17$g(a)-acyloxy-18-méthyl-19-norpregn-4-ène-3,20-dione, à des compositions pharmaceutiques contenant ces composés, à des intermédiaires utiles à la préparation de ces composés ainsi qu'à un procédé de préparation de ces composés et compositions. Lesdits composés ont un effet progestatif.