5-(2-((6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethoxy)-5-oxopentanoic acid | 409094-09-3

• 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: 5-(2-((6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethoxy)-5-oxopentanoic acid
• 英文别名: Pentanedioic acid mono-[2-((4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS)-4b-fluoro-5-hydroxy-4a,6a,8,8-tetramethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-7,9-dioxa-pentaleno[2,1-a]phenanthren-6b-yl)-2-oxo-ethyl] ester；5-[2-[(1S,2S,4R,8S,9S,11S,12R,13S)-12-fluoro-11-hydroxy-6,6,9,13-tetramethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-8-yl]-2-oxoethoxy]-5-oxopentanoic acid
• CAS: 409094-09-3
• 化学式: C₂₉H₃₇FO₉
• 分子量: 548.606
• InChiKey: VIMSELZDLPHJRC-PSNXDGKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5-(2-((6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethoxy)-5-oxopentanoic acid 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 4-((S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl (2-((6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethyl) glutarate dihydrochloride
  参考文献：
  名称：

  [EN] STABLE ISOQUINOLINE-CORTICOSTEROID CONJUGATES AND USES THEREOF
  [FR] CONJUGUÉS D'ISOQUINOLÉINE-CORTICOSTÉROÏDES STABLES ET LEURS UTILISATIONS

  摘要：

  Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. These compounds are conjugates of glucocorticoids with rho-kinase inhibitors. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.

  公开号：

  WO2022232602A1
• 作为产物：
  描述：

  曲安西龙 在 吡啶 、 盐酸 作用下， 反应 19.0h， 生成 5-(2-((6aS,6bR,7S,8aS,8bS,11aR,12aS,12bS)-6b-fluoro-7-hydroxy-6a,8a,10,10-tetramethyl-4-oxo-1,2,4,6a,6b,7,8,8a,11a,12,12a,12b-dodecahydro-8bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-8b-yl)-2-oxoethoxy)-5-oxopentanoic acid
  参考文献：
  名称：

  Synthesis, Pharmacokinetics, Efficacy, and Rat Retinal Toxicity of a Novel Mitomycin C-Triamcinolone Acetonide Conjugate

  摘要：

  A novel conjugate of mitomycin C (MMC) and triamcinolone acetonide (TA) was synthesized using glutaric acid as a linker molecule. To determine the rate of hydrolysis, the conjugate was dissolved in aqueous solution and the rate of appearance of free MMC and TA was determined by high-performance liquid chromatography analysis. Antiproliferative activity of the MMC-TA conjugate and parent compounds was assessed using an NIH 3T3 fibroblast cell line. Cell growth was quantified using the MTT assay. Kinetic analysis of the hydrolysis rate demonstrated that the conjugate had a half-life of 23.6 h in aqueous solutions. The antiproliferative activities of the MMC-TA conjugate and MMC were both concentration dependent, with similar IC50 values of 2.4 and 1.7 muM, respectively. However, individual responses at concentrations above 3 muM showed that the conjugate was less active than MMC alone. TA alone showed only limited inhibition of cell growth. Studies evaluating intravitreal injection of the conjugate demonstrate that this agent produced no measurable toxicity. Our data provide evidence that the MMC-TA conjugate could be used as a slow-release drug delivery system. This could in turn be used to modulate a posttreatment wound healing process or to treat various proliferative diseases.

  DOI：

  10.1021/jm010511b

文献信息

• WO2019209662A5
  申请人：——

  公开号：WO2019209662A5

  公开（公告）日：2022-04-14
• CONJUGATES OF CARTILAGE-HOMING PEPTIDES
  申请人：FRED HUTCHINSON CANCER RESEARCH CENTER

  公开号：US20210252159A1

  公开（公告）日：2021-08-19

  Compositions such as pharmaceutical compositions and uses for peptide-drug conjugates are disclosed. Such compositions can deliver a drug, a peptide, or a conjugate thereof to a target region, tissue, structure or cell in cartilage.