phosphoric acid diethyl ester 4-{2-[6-fluoro-3-(4-methanesulfinyl-benzylidene)-2-methyl-3H-inden-1-yl]-acetylamino}-butyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: phosphoric acid diethyl ester 4-{2-[6-fluoro-3-(4-methanesulfinyl-benzylidene)-2-methyl-3H-inden-1-yl]-acetylamino}-butyl ester
• 英文别名: diethyl 4-[[2-[(3Z)-6-fluoro-2-methyl-3-[(4-methylsulfinylphenyl)methylidene]inden-1-yl]acetyl]amino]butyl phosphate
• 化学式: C₂₈H₃₅FNO₆PS
• 分子量: 563.627
• InChiKey: DUIFTVBDSZZHDU-UQQQWYQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  phosphoric acid diethyl ester 4-{2-[6-fluoro-3-(4-methanesulfinyl-benzylidene)-2-methyl-3H-inden-1-yl]-acetylamino}-butyl ester 在 glucose-6-phosphate dehydrogenase 、 glucose-6-phosphate 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 magnesium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 3.0h， 生成 Sulindac
  参考文献：
  名称：

  The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent

  摘要：

  Phospho-sulindac amide (PSA) is a novel potential anti-cancer and anti-inflammatory agent. Here we report the metabolism of PSA in vitro. PSA was rapidly hydroxylated at its butane-phosphate moiety to form two di-hydroxyl-PSA and four mono-hydroxyl-PSA metabolites in mouse and human liver microsomes. PSA also can be oxidized or reduced at its sulindac moiety to form PSA sulfone and PSA sulfide, respectively. PSA was mono-hydroxylated and cleared more rapidly in mouse liver microsomes than in human liver microsomes. Of eight major human cytochrome P450s (CYPs), CYP3A4 and CYP2D6 exclusively catalyzed the hydroxylation and sulfoxidation reactions of PSA, respectively. We also examined the metabolism of PSA by three major human flavin monooxygenases (FMOs). FMO1, FMO3 and FMO5 were all capable of catalyzing the sulfoxidation (but not hydroxylation) of PSA, with FMO1 being by far the most active isoform. PSA was predominantly sulfoxidized in human kidney microsomes because FMO1 is the dominant isoform in human kidney. PSA (versus sulindac) is a preferred substrate of both CYPs and FMOs, likely because of its greater lipophilicity and masked-COOH group. Ketoconazole (a CYP3A4 inhibitor) and alkaline pH strongly inhibited the hydroxylation of PSA, but moderately suppressed its sulfoxidation in liver microsomes. Together, our results establish the metabolic pathways of PSA, identify the major enzymes mediating its biotransformations and reveal significant inter-species and inter-tissue differences in its metabolism. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2014.07.007
• 作为产物：
  描述：

  Sulindac 在 4-二甲氨基吡啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 phosphoric acid diethyl ester 4-{2-[6-fluoro-3-(4-methanesulfinyl-benzylidene)-2-methyl-3H-inden-1-yl]-acetylamino}-butyl ester
  参考文献：
  名称：

  PHOSPHO-ESTER DERIVATIVES AND USES THEREOF

  摘要：

  磷酸酯化合物及其制剂可通过呼吸道及其他途径用于预防和/或治疗肺癌和脑癌及其癌前病变条件，用于疼痛治疗，用于皮肤疾病治疗，用于治疗和/或预防与炎症相关的疾病，以及用于癌症的治疗和预防。

  公开号：

  US20130225529A1

文献信息

• COMPOUNDS AND COMPOSITIONS FOR USE IN THE TREATMENT AND PREVENTION OF LUNG AND BRAIN CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Medicon Pharmaceuticals, Inc.

  公开号：US20140178461A1

  公开（公告）日：2014-06-26

  Novel compounds and pharmaceutical compositions thereof administered by the respiratory route for prevention and/or treatment of lung and brain cancer and precancerous conditions thereof.

  通过呼吸道给予的新化合物和其制药组合物，用于预防和/或治疗肺癌、脑癌及其癌前状态。
• Product Comprising a Nicotine-Containing Material and an Anti-Cancer Agent
  申请人：Rigas, Basil

  公开号：EP2711006A1

  公开（公告）日：2014-03-26

  The invention is directed to a product comprising a nicotine-containing material and an anti-cancer agent. The product is applicable in the treatment and/or prevention of cancer and precancerous conditions as well as for preventing cancer recurrence.

  本发明涉及一种由含尼古丁材料和抗癌剂组成的产品。该产品适用于治疗和/或预防癌症和癌前病变，以及预防癌症复发。
• COMPOUNDS AND COMPOSITIONS FOR USE IN THE PREVENTION AND TREATMENT OF INFLAMMATION-RELATED DISORDERS, PAIN AND FEVER, SKIN DISORDERS, CANCER AND PRECANCEROUS CONDITIONS THEREOF
  申请人：Rigas, Basil

  公开号：EP2897621A2

  公开（公告）日：2015-07-29
• PRODUCT COMPRISING A NICOTINE-CONTAINING MATERIAL AND AN ANTI-CANCER AGENT
  申请人：Rigas Basil

  公开号：US20140088044A1

  公开（公告）日：2014-03-27

  The invention is directed to a product comprising a nicotine-containing material and an anti-cancer agent. The product is applicable in the treatment and/or prevention of cancer and precancerous conditions as well as for preventing cancer recurrence.
• [EN] PHOSPHO-ESTER DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHOSPHO-ESTER ET LEURS UTILISATIONS
  申请人：RIGAS BASIL

  公开号：WO2013130625A1

  公开（公告）日：2013-09-06

  Phospho-ester compounds and pharmaceutical compositions thereof administered by the respiratory and other routes for the prevention and/or treatment of lung and brain cancer and precancerous conditions thereof, for the treatment of pain, for the treatment of skin disorders, for treating and/or preventing inflammation-related diseases, and for the treatment and prevention of cancer.