N-Phenyl-N-cyclopentylchloracetamid | 67091-03-6

• 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: N-Phenyl-N-cyclopentylchloracetamid
• 英文别名: 2-chloro-N-cyclopentyl-N-phenylacetamide
• CAS: 67091-03-6
• 化学式: C₁₃H₁₆ClNO
• 分子量: 237.729
• InChiKey: KNCQCVVIGWFLFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-Phenyl-N-cyclopentylchloracetamid 在 potassium carbonate 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Higher-Affinity Agonists of 5-HT_1AR Discovered through Tuning the Binding-Site Flexibility

  摘要：

  Discovery of high-affinity and high-selectivity agonists of 5-HT1AR. has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR-related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (K-i = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agornst-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with,similar to 50-fold increase in receptor-binding affinity and similar to 25-fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D-1, D-2, and D-3).

  DOI：

  10.1021/acs.jcim.5b00164
• 作为产物：
  描述：

  苯胺 在 水 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 为溶剂， 生成 N-Phenyl-N-cyclopentylchloracetamid
  参考文献：
  名称：

  Higher-Affinity Agonists of 5-HT_1AR Discovered through Tuning the Binding-Site Flexibility

  摘要：

  Discovery of high-affinity and high-selectivity agonists of 5-HT1AR. has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR-related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (K-i = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agornst-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with,similar to 50-fold increase in receptor-binding affinity and similar to 25-fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D-1, D-2, and D-3).

  DOI：

  10.1021/acs.jcim.5b00164

文献信息

• [EN] COMPOUNDS OF THE FORMU;A R1-X-Y-Z-NR2R3 AS ABCA-1 ELEVATING AGENTS AGAINST CAD OR ATHEROSCLEROSIS<br/>[FR] COMPOSES DE FORMULE R1-X-Y-Z-NR2R3 UTILISES EN TANT QU'AGENTS PERMETTANT D'AUGMENTER LE NIVEAU D'EXPRESSION DU GENE ABCA-1 CONTRE LES CORONAROPATHIES (CAD) ET L'ARTHERIOSCLEROSE
  申请人：CV THERAPEUTICS INC

  公开号：WO2003103651A1

  公开（公告）日：2003-12-18

  The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

  本发明提供了一种能够提高细胞中ABCA-1基因表达的化合物，促进胆固醇从细胞中外流，并增加哺乳动物，特别是人类体内高密度脂蛋白水平的化合物。这些化合物对治疗冠状动脉疾病很有用。
• ABCA-1 ELEVATING COMPOUNDS
  申请人：Ibrahim N. Prabha

  公开号：US20050267215A1

  公开（公告）日：2005-12-01

  The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

  本发明提供了一种能够提升细胞中ABCA-1基因表达的化合物，促进胆固醇从细胞中流出，并增加哺乳动物（特别是人类）血浆中的HDL水平。这些化合物可用于治疗冠状动脉疾病。
• ABCA-1 Elevating compounds
  申请人：——

  公开号：US20020082257A1

  公开（公告）日：2002-06-27

  The present invention provides compounds that elevate cellular expression of the ABCA-1 gene, promoting cholesterol efflux from cells and increasing HDL levels in the plasma of a mammal, in particular humans. The compounds are useful for treating coronary artery disease.

  本发明提供了一种能够提高ABCA-1基因在细胞中表达的化合物，促进胆固醇从细胞中流出，并增加哺乳动物（特别是人类）血浆中的HDL水平。这些化合物可用于治疗冠状动脉疾病。
• COMPOUNDS OF THE FORMULA R1-X-Y-Z-NR2R3 AS ABCA-1 ELEVATING AGENTS AGAINST CORONARY ARTERY DISEASE OR ATHEROSCLEROSIS
  申请人：CV THERAPEUTICS, INC.

  公开号：EP1377283A2

  公开（公告）日：2004-01-07
• JPS5318540A
  申请人：——

  公开号：JPS5318540A

  公开（公告）日：1978-02-20