11,17,21-三羟基-3,20-二氧代孕甾烷-1,4-二烯-16-羧酸甲酯 | 111802-47-2

• 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
• 中文名称: 11,17,21-三羟基-3,20-二氧代孕甾烷-1,4-二烯-16-羧酸甲酯
• 英文名称: P16CM
• 英文别名: methyl 11β,17α,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16α-carboxylate；methyl 11β,17α,21-trihydroxy-3,20-dioxo-1,4-pregnadiene 16α-carboxylate；16α-methoxycarbonyl prednisolone；11β,17α,21-trihydroxy-16α-methoxy-carbonyl-3,20-dioxo-1,4-pregnadiene；Methyl prednisolone-16alpha-carboxylate；methyl (8S,9S,10R,11S,13S,14S,16R,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-16-carboxylate
• CAS: 111802-47-2
• 化学式: C₂₃H₃₀O₇
• 分子量: 418.487
• InChiKey: SNIXVWCOGOOOGH-UAHQIDPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  11,17,21-三羟基-3,20-二氧代孕甾烷-1,4-二烯-16-羧酸甲酯 在 吡啶 、 4-甲基苯磺酸吡啶 、 三氟乙酸酐 作用下， 反应 7.5h， 生成 methyl 17α,21-diacetoxy-11β-hydroxy-3,20-dioxo-pregna-1,4-diene-16α-carboxylate
  参考文献：
  名称：

  具有降低的副作用的新型有效的局部抗炎类固醇：类固醇16-羧基酯的衍生物。

  摘要：

  由于消炎类固醇对垂体-肾上腺功能和免疫系统有潜在的抑制作用，因此其治疗用途受到限制。基于前药概念，通过在C-16处引入代谢不稳定的甲氧羰基取代基，由泼尼松龙合成了一类新型的具有降低副作用风险的有效局部活性化合物。铅化合物局部使用的结果11甲基11β，17α，21-三羟基-3,20-二氧代-孕烷-1,4-二烯-16α-羧酸盐（P16CM; 1）显示为14倍比强的松龙更有效，并且它大大降低了引起全身性副作用的趋势。在目前的研究中，我们已经证明了化学修饰，例如17-和/或21-酯化以及17，1的21-乙酰胺化进一步增强了巴豆油耳水肿模型的局部活性。在1或其衍生物多次ID50局部应用后，未观察到胸腺溶解。在急性炎症的角叉菜胶浸泡的海绵模型中，所有衍生物都是白细胞迁移，PGE2生成和弹性蛋白酶释放的有效抑制剂。总之，这些结果表明，在17和/或21位上的羟基的酯化或乙酰化与不稳定的C-16甲氧基羰基结

  DOI：

  10.1002/jps.2600790716
• 作为产物：
  描述：

  21-acetoxy-16α-cyano-11β,21-dihydroxy-3,20-dioxo-1,4-pregna-diene 在 盐酸 、 过氧乙酸 、 sodium hydroxide 、 高氯酸 、 硫酸 、 4-甲基苯磺酸吡啶 、 乙酸酐 作用下， 以 乙醚 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 14.5h， 生成 11,17,21-三羟基-3,20-二氧代孕甾烷-1,4-二烯-16-羧酸甲酯
  参考文献：
  名称：

  Taraporewala; Kim; Heiman, Arzneimittel-Forschung/Drug Research, 1989, vol. 39, # 1, p. 21 - 25

  摘要：

  DOI：

文献信息

• Suppression of the Mattox rearrangement of 16α-cyanoprednisolones in acid: Synthesis of methyl 16α-prednisolonecarboxylates
  作者：Zhengqing You、Mounir A. Khalil、Dong-Hoon Ko、Henry J. Lee

  DOI：10.1016/0040-4039(95)00526-i

  日期：1995.5

  addition of fulminic acid to 21-acetyloxy-11β-hydroxy-3,20-dioxo-1,4,16-pregnatriene, followed by base-catalyzed ring opening of the resulting isoxazoline to yield a 16α-cyanoprednisolone derivative and treatment of the nitrile with methanolic HCl. Conversion of the cyanosteroids in the acid to the corresponding methyl carboxylates was achieved with or without the Mattox rearrangement by controlling reaction

  通过将新的1,3-偶极海藻酸加至21-乙酰氧基-11β-羟基-3,20-dioxo-1,4,16-孕三烯的新方法合成具有16α-羧酸甲酯基的泼尼松龙衍生物，然后所得异恶唑啉的碱催化的开环，得到16α-氰基间苯二酚衍生物，并用甲醇的HCl处理腈。通过控制21-OH的反应温度和保护基团，在有或没有Mattox重排的情况下，将酸中的氰基类固醇转化为相应的羧酸甲酯。
• New steroidal anti-inflammatory antedrugs: methyl 21-desoxy-21-chloro-11β,17α-dihydroxy-3,20-dioxo-1,4-pregnadiene-16α-carboxylate, methyl 21-desoxy-21-chloro-11β-hydroxy-3,20-dioxo-1,4-pregnadiene-16α-carboxylate, and their 9α-fluoro derivatives⋆
  作者：D Ko

  DOI：10.1016/s0039-128x(99)00103-8

  日期：2000.4

  To a series of 21-desoxy-21-chloro-corticosteroids, a metabolically labile methoxycarbonyl group at C-16 has been incorporated The approach is to synthesize locally active compounds that are hydrolyzed to inactive and readily excretable acid metabolites upon entry into the systemic circulation. Novel antedrugs were evaluated for anti-inflammatory activity and their adverse effects in an acute and semichronic croton oil-induced ear edema bioassay. Binding affinity to glucocorticoid receptors and induction of L-tyrosine-2-oxoglutarate aminotransferase were studied in hepatoma tissue culture cells. After a single topical application in the croton oil-induced ear edema bioassay, treatment with all the compounds resulted in dose-dependent inhibition of edema. From these dose-response profiles, the following ID50 values (nmol/year resulting in a 50% reduction of edema) were calculated: 540, 618, 454, and 346 nmol for prednisolone (P), methyl 21-desoxy-21-chloro-11 beta,17 alpha-dihydroxy-3,20-dioxo-1,4-pregnadien-16 alpha-carboxylate (PClCM), methyl 21-desoxy-21-chloro-11 beta, 17 alpha-dihydroxy-9 alpha-fluoro-3,20-dioxo-1,4-pregnadien-16 alpha-carboxylate (FPClCM), and methyl 21-desoxy-21-chloro-9 alpha-fluoro-11 beta-hydroxy-3,20-dioxo-1,4-pregnadien-16 alpha-carboxylate (FDPClCM), respectively. Results of the 5-day rat croton oil ear edema bioassay indicated that, in contrast with the parent compound P, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, or plasma corticosterone levels. The binding affinities for cytosolic hepatoma tissue culture glucocorticoid receptors were 33, 201, 471, 5304, and 3765 nM for P, PClCM, FPClCM, methyl 21-desoxy-21-chloro-11 beta-hydroxy-3,20-dioxo-1,4-pregnadien-16 alpha-carboxylate (DPClCM), and FDPClCM, respectively. Collectively, results of these investigations suggest that modifications of P, which included replacement of 21-hydroxyl group with chlorine and addition of 16-methoxycarbonyl group with or without 17-hydroxyl moiety, retained the topical anti-inflammatory activity of the parent compound P without significant adverse systemic effects. (C) 2000 Elsevier Science Inc. All rights reserved.
• HEIMAN, ANN S.;TARAPOREWALA, IRACH B.;MCLEAN, HUGH M.;HONG, DEASIK;LEE, H+, J. PHARM. SCI., 79,(1990) N, C. 617-621
  作者：HEIMAN, ANN S.、TARAPOREWALA, IRACH B.、MCLEAN, HUGH M.、HONG, DEASIK、LEE, H+

  DOI：——

  日期：——
• US4762919A
  申请人：——

  公开号：US4762919A

  公开（公告）日：1988-08-09