cis-4-nitrobenzoic acid 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyl ester | 478832-23-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-4-nitrobenzoic acid 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyl ester
• 英文别名: cis-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)cyclohexyl 4-nitrobenzoate
• CAS: 478832-23-4
• 化学式: C₂₁H₁₈N₂O₆
• 分子量: 394.384
• InChiKey: SIFPNWFAWFKFSG-FZNQNYSPSA-N

物化性质

• 沸点：
  576.9±45.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.36
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  106.82
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  cis-4-nitrobenzoic acid 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyl ester 在 sodium hydroxide 、 偶氮二甲酸二异丙酯 、 一水合肼 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 trans-4-{4-[3-(4-trifluoromethoxyphenyl)ureido]cyclohexyloxy}benzoic acid ethyl ester
  参考文献：
  名称：

  Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

  摘要：

  A series of N,N'-disubstituted ureas having a conformationally restricted cis- or traiis-1,4-cyclohexane alpha to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 +/- 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models.

  DOI：

  10.1021/jm070270t
• 作为产物：
  描述：

  trans-4-aminocyclohexanol hydrochloride 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.5h， 生成 cis-4-nitrobenzoic acid 4-(1,3-dioxo-1,3-dihydroisoindol-2-yl)cyclohexyl ester
  参考文献：
  名称：

  Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors

  摘要：

  A series of N,N'-disubstituted ureas having a conformationally restricted cis- or traiis-1,4-cyclohexane alpha to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 +/- 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models.

  DOI：

  10.1021/jm070270t

文献信息

• [EN] SORAFENIB DERIVATIVES AS sEH INHIBITORS<br/>[FR] DÉRIVÉS DE SORAFÉNIB UTILISÉS EN TANT QU'INHIBITEURS DE LA SEH
  申请人：UNIV CALIFORNIA

  公开号：WO2012112570A1

  公开（公告）日：2012-08-23

  The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

  本发明提供了用于抑制可溶性环氧化物水解酶及相关疾病状况的化合物。
• Rho kinase inhibitors
  申请人：——

  公开号：US20040138286A1

  公开（公告）日：2004-07-15

  A compound represented by the formula (1): 1 wherein R 1 —X— indicates that 1 to 4 R 1 —X— groups are present which may be the same or different, the ring A is a saturated or unsaturated 5-membered heterocyclic ring, X is a single bond, a group represented by the formula: —N(R 3 )—, —O— or —S—, or the like. R 1 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, R 2 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, and R 3 is a hydrogen atom, a substituted or unsubstituted alkyl group, or the like; a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug is a useful compound as a therapeutic agent for diseases for which Rho kinase is responsible.

  化合物的化学式为（1）：1，其中R1—X—表示存在1到4个R1—X—基团，可以相同也可以不同，环A是饱和或不饱和的5元杂环，X是单键，一个由式子表示的基团：—N（R3）—，—O—或—S—等。R1是氢原子，卤素原子，硝基，羧基，取代或未取代的烷基或类似物，R2是氢原子，卤素原子，硝基，羧基，取代或未取代的烷基或类似物，R3是氢原子，取代或未取代的烷基或类似物；该化合物的前药或药物可接受的盐是治疗Rho激酶相关疾病的有用化合物。
• SORAFENIB DERIVATIVES AS SEH INHIBITORS
  申请人：Hammock Bruce D.

  公开号：US20140088156A1

  公开（公告）日：2014-03-27

  The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

  本发明提供了用于抑制可溶性环氧酰胺酶及相关疾病状况的化合物。
• Sorafenib derivatives as sEH inhibitors
  申请人：Hammock Bruce D.

  公开号：US09029401B2

  公开（公告）日：2015-05-12

  The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

  本发明提供了用于抑制可溶性环氧酰基酶和相关疾病条件的化合物。
• Rho KINASE INHIBITORS
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1403255A1

  公开（公告）日：2004-03-31

  A compound represented by the formula (1): wherein R1-X- indicates that 1 to 4 R1-X- groups are present which may be the same or different,    the ring A is a saturated or unsaturated 5-membered heterocyclic ring,    X is a single bond, a group represented by the formula: -N(R3)-, -O- or -S-, or the like.    R1 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like,    R2 is a hydrogen atom, a halogen atom, a nitro group, a carboxyl group, a substituted or unsubstituted alkyl group, or the like, and    R3 is a hydrogen atom, a substituted or unsubstituted alkyl group, or the like; a prodrug of said compound, or a pharmaceutically acceptable salt of said compound or prodrug is a useful compound as a therapeutic agent for diseases for which Rho kinase is responsible.

  由式（1）代表的化合物： 其中 R1-X- 表示存在 1 至 4 个 R1-X- 基团，这些基团可以相同或不同、 环 A 是饱和或不饱和的五元杂环、 X 是单键、由式子表示的基团：-N(R3)-、-O- 或 -S- 或类似的基团。 R1 是氢原子、卤素原子、硝基、羧基、取代或未取代的烷基或类似基团、 R2 是氢原子、卤素原子、硝基、羧基、取代或未取代的烷基或类似物，以及 R3 是氢原子、取代或未取代的烷基或类似物； 所述化合物的原药或所述化合物或原药的药学上可接受的盐是一种有用的化合物，可作为治疗 Rho 激酶引起的疾病的药物。