chloromethyl 11β-hydroxy-17α-methoxycarbonyloxy-3-oxo-androst-4-ene-17β-carboxylate

• 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: chloromethyl 11β-hydroxy-17α-methoxycarbonyloxy-3-oxo-androst-4-ene-17β-carboxylate
• 英文别名: chloromethyl 11β-hydroxy-17α-methoxycarbonyloxyandrost-4-en-3-one-17β-carboxylate；chloromethyl (8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-methoxycarbonyloxy-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate
• 化学式: C₂₃H₃₁ClO₇
• 分子量: 454.948
• InChiKey: AYHGVKILAOLGHV-NGVSTBRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氢化可的松 在 氢氧化钾 、 sodium periodate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 0.5h， 生成 chloromethyl 11β-hydroxy-17α-methoxycarbonyloxy-3-oxo-androst-4-ene-17β-carboxylate
  参考文献：
  名称：

  摘要：

  Purpose. The soft drug approach was applied to the design of analogs of highly potent synthetic steroids but with a metabolically labile ester group which at the same time served as an activating group.Methods. Several structural modifications of soft antiinflammatory steroids were synthesized and tested in several assays of biological activity. The hydrolytic stability of the compounds was also determined.Results. One of the compounds synthesized was determined to be a very potent steroid and had a highly significant separation of topical from systemic activity. However, the compound demonstrated greater than expected stability in the hydrolysis studies.Conclusions. The goal of the soft drug approach has been achieved with the development of a highly potent drug which displays little or no systemic activity as measured in the tests presented here. The anticipated hydrolytic instability of the compounds was not corroborated, however, in view of other results, the interpretation is allowed that the rapid hydrolysis of the unbound fraction of the drug is an important factor in its lack of systemic effects.

  DOI：

  10.1023/a:1018907026460

文献信息

• ENHANCEMENT OF ACTIVITY AND/OR DURATION OF ACTION OF SOFT ANTI-INFLAMMATORY STEROIDS FOR TOPICAL OR OTHER LOCAL APPLICATION
  申请人：BODOR, Nicholas S.

  公开号：EP1653974B1

  公开（公告）日：2010-01-06
• COMBINATION OF STEROIDS HAVING TRANSPORTER-ENHANCED CORTICOSTEROID ACTIVITY
  申请人：Bodor, Nicholas S.

  公开号：EP2026818B1

  公开（公告）日：2010-12-22
• Enhancement of activity and/or duration of action of soft anti-inflammatory steroids for topical or other local application
  申请人：Bodor S. Nicholas

  公开号：US20050026892A1

  公开（公告）日：2005-02-03

  Methods and compositions for enhancing the activity and/or duration of action of loteprednol etabonate and other soft anti-inflammatory steroids of the haloalkyl 17α-alkoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylate type and the corresponding Δ 1,4 -compounds are described. The enhancing agents have the formula: wherein R is H or C 1 -C 4 alkyl; Z 1 is carbonyl or β-hydroxymethylene; X 1 is —O— or —S—; R 5 is —OH, —OR 6 , —OCOOR 6 or —OCOR 7 wherein R 6 is C 1 -C 4 alkyl and R 7 is C 1 -C 4 alkyl, fluoromethyl or chloromethyl; and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated; with the proviso that when R is C 1 -C 4 alkyl, then R 5 is —OH.
• Transporter enhanced corticosteroid activity
  申请人：Bodor S. Nicholas

  公开号：US20080004246A1

  公开（公告）日：2008-01-03

  Methods and compositions for enhancing the activity and/or duration of action of loteprednol etabonate and other soft anti-inflammatory steroids of the haloalkyl 17α-alkoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylate type and the corresponding Δ 1,4 -compounds are described. The enhancing agents have the formula: wherein Z 1 is carbonyl, β-hydroxymethylene or methylene; R 2 is H, —OH or —OCOR 3 wherein R 3 is C 1 -C 5 alkyl; Y is —OH, —SH or —OCOR 4 wherein R 4 is C 1 -C 5 alkyl, cyclopentylethyl or diethylaminoethyl; and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated.
• TRANSPORTER-ENHANCED CORTICOSTEROID ACTIVITY AND METHODS AND COMPOSITIONS FOR TREATING DRY EYE
  申请人：Bodor Nicholas S.

  公开号：US20080194468A1

  公开（公告）日：2008-08-14

  Methods and compositions for enhancing the activity and/or duration of action of loteprednol etabonate and other soft anti-inflammatory steroids of the haloalkyl 17α-alkoxycarbonyloxy-11β-hydroxyandrost-4-cn-3-one-17β-carboxylate type and the corresponding Δ 1,4 -compounds are described. The enhancing agents have the formula: wherein Z 1 is carbonyl, β-hydroxymethylene or methylene; R 2 is H, —OH or —OCOR 3 wherein R 3 is C 1-5 alkyl; Y is —OH, —SH or —OCOR 4 wherein R 4 is C 1-5 alkyl, cyclopentylethyl or diethylaminoethyl; and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated. Ophthalmic administration in the treatment of dry eye is specifically targeted.