(1S,3R)-1-chloro-3-triphenylmethoxy-4-cyclopentene | 426226-18-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1S,3R)-1-chloro-3-triphenylmethoxy-4-cyclopentene
• 英文别名: [[(1R,4S)-4-chlorocyclopent-2-en-1-yl]oxy-diphenylmethyl]benzene
• CAS: 426226-18-8
• 化学式: C₂₄H₂₁ClO
• 分子量: 360.883
• InChiKey: APNVLYNEEJLKIG-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1S,3R)-1-chloro-3-triphenylmethoxy-4-cyclopentene 在 sodium hydride 、 对甲苯磺酸 、 lithium iodide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.25h， 生成 (1R,3S)-1-hydroxy-3-(methyl-carboxymethyl)-4-cyclopentene
  参考文献：
  名称：

  Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists

  摘要：

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.

  DOI：

  10.1021/jm0205604
• 作为产物：
  描述：

  2-环戊烯-1-醇,4-[[(1,1-二甲基乙基)二甲基甲硅烷基]氧代]-,(1R,4S)- 在 甲醇 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 sodium methylate 、 甲基磺酰氯 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.0h， 生成 (1S,3R)-1-chloro-3-triphenylmethoxy-4-cyclopentene
  参考文献：
  名称：

  Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists

  摘要：

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.

  DOI：

  10.1021/jm0205604

文献信息

• Regulation of type 5 adenylyl cyclase for treatment of neurodegenerative and cardiac diseases
  申请人：Vatner F. Stephen

  公开号：US20060252774A1

  公开（公告）日：2006-11-09

  The invention concerns pharmaceutical compositions that contain a compound or compounds that can effectively regulate the activity of Type 5 Adenylyl Cyclase and methods for treatment of neurological diseases and disorders, as well as motor function loss therefrom, as well as treatment for cardiac conditions and diseases including conditions characterized by abnormal heart rate.

  这项发明涉及含有一种或多种能够有效调节第5型腺苷酸环化酶活性的化合物的药物组合物，以及治疗神经系统疾病和障碍、以及由此引起的运动功能丧失的方法，以及用于治疗心脏疾病和疾病的方法，包括以异常心率为特征的情况。
• Adenine based inhibitors of adenylyl cyclase, pharmaceutical compositions, and method of use thereof
  申请人：——

  公开号：US20020068745A1

  公开（公告）日：2002-06-06

  The present invention relates to derivatives and analogues of adenine, which inhibit adenylyl cyclase activity. The present invention also relates to a method of preventing and inhibiting a patient's fibroproliferative vasculopathy following vascular injury or a vascular surgical operation which includes administering to the patient, an effective amount of a compound according to the invention subsequent to a vascular injury, or subsequent to a vascular surgical operation, for one to two weeks after the injury or surgical operation, effective to treat or prevent a patient's fibroproliferative vasculopathy such as chronic allograft rejection or vascular restenosis following vascular trauma. The present invention also relates to a method for measuring the inhibition of adenylyl cyclase activity and a method for treating congestive heart failure.

  本发明涉及腺嘌呤的衍生物和类似物，其抑制腺苷酸环化酶活性。本发明还涉及一种预防和抑制患者血管损伤后纤维增殖性血管病的方法，或血管手术后的方法，包括向患者施用根据本发明的化合物的有效量，即在血管损伤后或血管手术后的一到两周内，有效地治疗或预防患者的纤维增殖性血管病，如慢性移植物排斥或血管创伤后的血管再狭窄。本发明还涉及一种测量腺苷酸环化酶活性抑制的方法和一种治疗充血性心力衰竭的方法。
• Metal Coordination-Based Inhibitors of Adenylyl Cyclase:  Novel Potent P-Site Antagonists
  作者：Daniel E. Levy、Ming Bao、Diana B. Cherbavaz、James E. Tomlinson、David M. Sedlock、Charles J. Homcy、Robert M. Scarborough

  DOI：10.1021/jm0205604

  日期：2003.5.1

  The adenylyl cyclases (ACS) are a family of intracellular enzymes associated with signal transduction by virtue of their ability to convert ATP to cAMP. The catalytic mechanism of this transformation proceeds through initial binding of ATP to the so-called purine binding site (P-site) of the enzyme followed by metal-mediated cyclization with loss of pyrophosphate. Crystallographic analysis of ACs with known inhibitors reveals the presence of two metals in the active site. Presently, nine isoforms of adenylyl cyclase are known, and unique isoform combinations are expressed in a tissue-specific manner. The development of isoform-specific inhibitors of adenylyl cyclase may prove to be a useful strategy toward the design of unique signal transduction inhibitors. To develop novel AC inhibitors, we have chosen an approach to inhibitor design utilizing an adenine ring system joined to a metal-coordinating hydroxamic acid via various linkers. Previous work in our group has validated this approach and identified novel inhibitors that possess an adenine ring joined to a metal-coordinating hydroxamic acid through flexible acyclic linkers (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 30853088). Subsequent studies have focused on the introduction of conformational restrictions into the tether of the inhibitors with the goal of increasing potency (Levy, D. E., et al. Bioorg. Med. Chem. Lett. 2002, 12, 3089-3092). Building upon the favorable spatial positioning of the adenine and hydroxamate groups coupled with potentially favorable entropic factors, the unit joining the carbocycle to the hydroxamate was explored further and a stereochemical-based SAR was elucidated, leading to a new series of highly potent AC inhibitors.