6-(o-nitrophenyl)-5-hexenic acid | 108807-12-1

• 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: 6-(o-nitrophenyl)-5-hexenic acid
• 英文别名: 6-(2-nitrophenyl)hex-5-enoic acid
• CAS: 108807-12-1
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: GQLXKNKNOXKCJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(o-nitrophenyl)-5-hexenic acid 在 platinum(IV) oxide potassium dihydrogenphosphate 、 N-溴代丁二酰亚胺(NBS) 、 氢气 、 sodium methylate 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 39.09h， 生成 Methyl 3-cyano-3-hydroxy-4-[6-(2-nitrophenyl)hexylsulfanyl]butanoate
  参考文献：
  名称：

  ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. Design and Synthesis of 2-Substituted Butanedioic Acids as Novel, Potent Inhibitors of the Enzyme

  摘要：

  ATP-citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. A series of a-substituted butanedioic acids have been designed and synthesized as inhibitors of the enzyme, The best compounds, 58, 68, 71, 74 have reversible K-i's in the 1-3 mu M range against the isolated rat enzyme, As representative of this compound class, 58, has been shown to exert its inhibitory action through a mainly competitive mechanism with respect to citrate and a noncompetitive one with respect to CoA. None of the inhibitors were able to inhibit cholesterol and/or fatty acid synthesis in HepG2 cells. This has been attributed to the adverse physicochemical properties of the molecules leading to a lack of cell penetration. Despite this, a lead structural class of compound has been identified with the potential for modification into potent, cell-penetrant, and efficacious inhibitors of ATP-citrate lyase.

  DOI：

  10.1021/jm960167w
• 作为产物：
  描述：

  4-羧丁基三苯基溴化膦 、 邻硝基苯甲醛 在 dimsyl sodium 作用下， 生成 6-(o-nitrophenyl)-5-hexenic acid
  参考文献：
  名称：

  ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. Design and Synthesis of 2-Substituted Butanedioic Acids as Novel, Potent Inhibitors of the Enzyme

  摘要：

  ATP-citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. A series of a-substituted butanedioic acids have been designed and synthesized as inhibitors of the enzyme, The best compounds, 58, 68, 71, 74 have reversible K-i's in the 1-3 mu M range against the isolated rat enzyme, As representative of this compound class, 58, has been shown to exert its inhibitory action through a mainly competitive mechanism with respect to citrate and a noncompetitive one with respect to CoA. None of the inhibitors were able to inhibit cholesterol and/or fatty acid synthesis in HepG2 cells. This has been attributed to the adverse physicochemical properties of the molecules leading to a lack of cell penetration. Despite this, a lead structural class of compound has been identified with the potential for modification into potent, cell-penetrant, and efficacious inhibitors of ATP-citrate lyase.

  DOI：

  10.1021/jm960167w

文献信息

• Phenylene derivatives and anti-allergic use thereof
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US04994479A1

  公开（公告）日：1991-02-19

  Novel phenylene derivatives shown by the general formula ##STR1## wherein A represents a hydrogen atom, a phenyl group or a phenoxy group, n represents an integer of 3 to 10, R.sub.1 represents a hydrogen atom or a lower alkoxy group, X.sub.1 represents --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CONH--, .circle.B represents ##STR2## (wherein R.sub.2 represents a hydrogen atom, a halogen atom, a nitro group, etc.), ##STR3## (wherein R.sub.3 represents a hydrogen atom, a hydroxyl group or a lower alkoxy group), X.sub.2 represents --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --, etc. and D represents a carboxy group, a lower alkoxycarbonyl group or ##STR4## which are useful as drugs, particularly SRS-A (slow reacting substance of anaphylaxis) antagonist, i.e. they are useful as prophylaxis and treatment for various allergic diseases (e.g. bronchial asthma, allergic rhinitis, urticaria) or, ischemic heart diseases, inflammation, etc. induced by SRS-A.

  一种新型苯基衍生物，其通式为##STR1##其中A代表氢原子、苯基或苯氧基，n代表3至10的整数，R.sub.1代表氢原子或低碳基氧基，X.sub.1代表-CH.sub.2 CH.sub.2-, -CH.dbd.CH-, -CONH-, .circle.B代表##STR2##（其中R.sub.2代表氢原子、卤素原子、硝基等），##STR3##（其中R.sub.3代表氢原子、羟基或低碳基氧基），X.sub.2代表-CH.dbd.CH-, -CH.sub.2 CH.sub.2 -等，D代表羧基、低碳基氧羧基或##STR4##，这些衍生物可用作药物，特别是SRS-A（慢反应性过敏反应物质）拮抗剂，即它们可用于各种过敏性疾病（如支气管哮喘、过敏性鼻炎、荨麻疹）或SRS-A引起的缺血性心脏病、炎症等的预防和治疗。
• Phenylene derivatives
  申请人：——

  公开号：US05116853A1

  公开（公告）日：1992-05-26

  Novel phenylene derivatives shown by the general formula ##STR1## wherein A represents a hydrogen atom, a phenyl group or a phenoxy group, n represents an integer of 3 to 10, R.sub.1 represents a hydrogen atom or a lower alkoxy group, X.sub.1 represents --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CONH--, B represents ##STR2## (wherein R.sub.2 represents a hydrogen atom, a halogen, atom, a nitro group, etc.), ##STR3## (wherein R.sub.3 represents a hydrogen atom, a hydroxyl group or a lower alkoxy group), X.sub.2 represents --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --, etc. and D represents a carboxy group, a lower alkoxycarbonyl group or ##STR4## which are useful as drugs, particularly SRS-A (slow reacting substance of anaphylaxis) antagonist, i.e. they are useful as prophylaxis and treatment for various allergic diseases (e.g. bronchial asthma, allergic rhinitis, urticaria) or, ischemic heart diseases, inflammation, etc. induced by SRS-A.

  一种通式为 ##STR1## 的新型苯基衍生物，其中A代表氢原子、苯基或苯氧基，n代表3至10的整数，R.sub.1代表氢原子或低级烷氧基，X.sub.1代表--CH.sub.2 CH.sub.2 --、--CH.dbd.CH--、--CONH--，B代表 ##STR2## （其中R.sub.2代表氢原子、卤素原子、硝基等）， ##STR3## （其中R.sub.3代表氢原子、羟基或低级烷氧基），X.sub.2代表--CH.dbd.CH--、--CH.sub.2 CH.sub.2 --等，D代表羧基、低级烷氧羰基基或 ##STR4## 的新型苯基衍生物，其作为药物具有广泛应用，特别是作为SRS-A（过敏反应缓慢反应物质）拮抗剂，可用于预防和治疗各种过敏性疾病（如支气管哮喘、过敏性鼻炎、荨麻疹）或SRS-A引起的缺血性心脏病、炎症等。
• Phenylene derivatives, compositions and use
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05140046A1

  公开（公告）日：1992-08-18

  Novel phenylene derivatives shown by the general formula ##STR1## where A represents a hydrogen atom, a phenyl group or a phenoxy group, n represents an integer of 3 to 10, R.sub.1 represents a hydrogen atom or a lower alkoxy group, X.sub.1 represents --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CONH--, B represents ##STR2## wherein R.sub.2 represents a hydrogen atom, a halogen atom, a nitro group, etc.), ##STR3## (wherein R.sub.3 represents a hydrogen atom, a hydroxyl group or a lower alkoxy group), X.sub.2 represents --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --, etc. and D represents a carboxy group, a lower alkoxycarbonyl group or ##STR4## which are useful as drugs, particularly SRS-A(slow reacting substance of anaphylaxis) antagonist, i.e. they are useful as prophylaxis and treatment for various allergic diseases (e.g. bronchial asthma, allergic rhinitis, urticaria) or, ischemic heart diseases, inflammation, etc. induced by SRS-A.

  一般式为##STR1##的新型苯基衍生物，其中A代表氢原子、苯基或苯氧基，n代表3到10的整数，R.sub.1代表氢原子或低级烷氧基，X.sub.1代表--CH.sub.2 CH.sub.2 --、--CH.dbd.CH--、--CONH--，B代表##STR2##其中R.sub.2代表氢原子、卤素原子、硝基等，##STR3##（其中R.sub.3代表氢原子、羟基或低级烷氧基），X.sub.2代表--CH.dbd.CH--、--CH.sub.2 CH.sub.2 --等，D代表羧基、低级烷氧羰基基或##STR4##，它们可用作药物，特别是SRS-A（慢性过敏反应物质）拮抗剂，即它们可用于预防和治疗各种过敏性疾病（如支气管哮喘、过敏性鼻炎、荨麻疹）或由SRS-A引起的缺血性心脏病、炎症等。
• ATP-Citrate Lyase as a Target for Hypolipidemic Intervention. Design and Synthesis of 2-Substituted Butanedioic Acids as Novel, Potent Inhibitors of the Enzyme
  作者：Andrew D. Gribble、Roland E. Dolle、Antony Shaw、David McNair、Riccardo Novelli、Christine E. Novelli、Brian P. Slingsby、Virendra P. Shah、David Tew、Barbara A. Saxty、Mark Allen、Pieter H. Groot、Nigel Pearce、John Yates

  DOI：10.1021/jm960167w

  日期：1996.1.1

  ATP-citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agent, which are anticipated to have combined hypocholesterolemic and hypotriglyceridemic properties. A series of a-substituted butanedioic acids have been designed and synthesized as inhibitors of the enzyme, The best compounds, 58, 68, 71, 74 have reversible K-i's in the 1-3 mu M range against the isolated rat enzyme, As representative of this compound class, 58, has been shown to exert its inhibitory action through a mainly competitive mechanism with respect to citrate and a noncompetitive one with respect to CoA. None of the inhibitors were able to inhibit cholesterol and/or fatty acid synthesis in HepG2 cells. This has been attributed to the adverse physicochemical properties of the molecules leading to a lack of cell penetration. Despite this, a lead structural class of compound has been identified with the potential for modification into potent, cell-penetrant, and efficacious inhibitors of ATP-citrate lyase.