3-methoxy-16-methylene-13β-ethyl-gona-3,5-dien-17-one | 192721-91-8

• 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-methoxy-16-methylene-13β-ethyl-gona-3,5-dien-17-one
• 英文别名: (8R,9S,10R,13S,14S)-13-ethyl-3-methoxy-16-methylidene-1,2,7,8,9,10,11,12,14,15-decahydrocyclopenta[a]phenanthren-17-one
• CAS: 192721-91-8
• 化学式: C₂₁H₂₈O₂
• 分子量: 312.452
• InChiKey: GEJQAYYRQYKMLP-KKKDIUQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methoxy-16-methylene-13β-ethyl-gona-3,5-dien-17-one 在 正丁基锂 、 TEA 、 硫酸 、 三乙胺 、 mercury(II) oxide 、 三甲氧基磷 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 丙酮 为溶剂， 反应 11.67h， 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：

  13-ethyl-3-methoxy-gona-3,5-diene-17-one 在 sodium methylate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.5h， 生成 3-methoxy-16-methylene-13β-ethyl-gona-3,5-dien-17-one
  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

• 17Beta-CYANO-18A-HOMO-19-NOR-ANDROST-4-ENE DERIVATIVE, ITS USE AND MEDICAMENTS COMPRISING THE DERIVATIVE
  申请人：KUHNKE JOACHIM

  公开号：US20090048218A1

  公开（公告）日：2009-02-19

  The 17β-cyano-18a-homo-19-nor-androst-4-ene derivatives of the present invention possess gestagenic activity. They have the general chemical formula 1, in which Z is selected from the group comprising O, two hydrogen atoms, NOR and NNHSO 2 R, in which R is hydrogen or C 1 -C 4 -alkyl, R 4 is hydrogen or halogen, furthermore either: R 6a , R 6b together form methylene or 1,2-ethanediyl or R 6a is hydrogen and R 6b is selected from the group comprising hydrogen, methyl and hydroxymethylene, and R 7 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl, C 2 -C 3 -alkenyl and cyclopropyl, or: R 6a is hydrogen and R 6b and R 7 either together form methylene or are omitted with formation of a double bond between C 6 and C 7 , R 9 , R 10 are hydrogen or are omitted with formation of a double bond between C 9 and C 10 , R 15 , R 16 are hydrogen or together form methylene, R 17 is selected from the group comprising hydrogen, C 1 -C 4 -alkyl and allyl, at least one of the substituents R 4 , R 6a , R 6b , R 7 , R 15 , R 16 and R 17 not being hydrogen or R 6b and R 7 being omitted with formation of a double bond between C 6 and C 7 or being omitted with formation of a double bond between C 1 and C 2 , and moreover comprise their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts.

  本发明的17β-氰基-18a-同型-19-去氢雄烯-4-烯衍生物具有孕激素活性。它们具有一般化学式1，其中Z选自包括O、两个氢原子、NOR和NNHSO2R的基团，其中R为氢或C1-C4-烷基，R4为氢或卤素，此外还有：R6a、R6b共同形成亚甲基或1,2-乙二基或R6a为氢且R6b选自包括氢、甲基和羟甲基的基团，R7选自包括氢、C1-C4-烷基、C2-C3-烯基和环丙基的基团，或：R6a为氢且R6b和R7共同形成亚甲基或省略，形成C6和C7之间的双键，R9、R10为氢或省略，形成C9和C10之间的双键，R15、R16为氢或共同形成亚甲基，R17选自包括氢、C1-C4-烷基和烯丙基的基团，其中至少有一个取代基R4、R6a、R6b、R7、R15、R16和R17不是氢或R6b和R7省略，形成C6和C7之间的双键或省略，形成C1和C2之间的双键，此外还包括它们的溶剂化合物、水合物、立体异构体、对映异构体、对映体和盐。
• [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.
• Synthesis and biological activity of a new progestogen, 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate
  作者：Zoltán Tuba、C.Wayne Bardin、Anna Dancsi、Erzsébet Francsics–Czinege、Csaba Molnár、János Csörgei、George Falkay、Samuel S Koide、Narender Kumar、Kalyan Sundaram、Vilma Dukát–Abrók、Gábor Balogh

  DOI：10.1016/s0039-128x(99)00109-9

  日期：2000.5

  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.