1-(4-氰基苯基)环戊烷-1-羧酸 | 135569-29-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-氰基苯基)环戊烷-1-羧酸
• 英文名称: 1-(4-cyanophenyl)cyclopentanecarboxylic acid
• 英文别名: 1-(p-cyanophenyl)cyclopentanecarboxylic acid；1-(4-cyanophenyl)cyclopentane-1-carboxylic acid
• CAS: 135569-29-8
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: PMILUQHECXXKGR-UHFFFAOYSA-N

物化性质

• 沸点：
  409.4±38.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  1-(4-氰基苯基)环戊烷-1-羧酸 在 氯化亚砜 作用下， 以 苯 为溶剂， 反应 8.0h， 生成 2-(diethylamino)ethyl 1-(p-cyanophenyl)cyclopentanecarboxylate
  参考文献：
  名称：

  Muscarinic receptor binding profile of para-substituted caramiphen analogs

  摘要：

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).

  DOI：

  10.1021/jm00114a005
• 作为产物：
  描述：

  1-(对氨基苯基)环戊烷羧酸 、 氰化钾 在 盐酸 、 sodium carbonate 、 sodium nitrite 作用下， 生成 1-(4-氰基苯基)环戊烷-1-羧酸
  参考文献：
  名称：

  Muscarinic receptor binding profile of para-substituted caramiphen analogs

  摘要：

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).

  DOI：

  10.1021/jm00114a005

文献信息

• Novel (4-Phenylpiperidinyl)- and (4-Phenylpiperazinyl)alkyl-Spaced Esters of 1-Phenylcyclopentanecarboxylic Acids as Potent .sigma.-Selective Compounds
  作者：Robert L. Hudkins、Richard B. Mailman、Diane L. DeHaven-Hudkins

  DOI：10.1021/jm00039a008

  日期：1994.6

  A series of novel 4-phenylpiperidinyl and (4-phenylpiperazinyl) alkyl 1-phenylcyclopentanecarboxylates was synthesized and evaluated for affinity at sigma(1) and sigma(2) sites by inhibition of [H-3]-(+)-pentazocine (PENT) and [H-3]-1,3-di(2-tolyl)guanidine (DTG) binding in guinea pig brain. The phenylpiperidines were more potent sigma ligands than the corresponding piperazines. Structural modifications varying the optimal spatial distance between the piperidine nitrogen and ester functions led to the identification of the propyl compound 24 ([H-3]PENT K-i = 0.50 nM; [H-3]DTG K-i = 1.17 nM) and the butyl derivative 32 ([H-3]PENT K-i = 0.51 nM; [H-3]DTG K-i = 0.69 nM) as novel high-affinity sigma-selective agents. An ethylene spacer was optimum with para-substituted analogs. A notable finding was the discovery of 2-(4-phenylpiperidinyl) ethyl 1-(4-nitrophenyl)cyclopentanecarboxylate hydrochloride (15) (RLH-033), which demonstrated potent affinity for the [H-3]PENT-defined sigma site with a K-i of 50 pM, selectivity for sigma(1) over muscarinic M(1) (> 17600-fold), M(2) (> 34200-fold), dopamine D-1 (> 58000-fold), and D-2 (> 7000-fold) receptors, and inactivity at phencyclidine, NMDA, and opioid receptors. RLH-033 is a valuable tool which will aid further in understanding the biology of the sigma recognition site. Information from this research has further defined the topography of the sigma recognition site, which may provide an explanation for the diverse structures which bind with relatively high affinity.
• Hudkins Robert L., Mailman Richard B., DeHaven-Hudkins Diane L., J. Med. Chem, 37 (1994) N 13, S 1964- 1970
  作者：Hudkins Robert L., Mailman Richard B., DeHaven-Hudkins Diane L.

  DOI：——

  日期：——
• Muscarinic receptor binding profile of para-substituted caramiphen analogs
  作者：Robert L. Hudkins、Diane L. DeHaven-Hudkins、James F. Stubbins

  DOI：10.1021/jm00114a005

  日期：1991.10

  Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's-sigma or Hansch's pi-values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl (-sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (K(i) = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron-donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The +sigma derivatives showed a decrease in M2 affinity while the p-nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, K(i) = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, K(i) = 5.21 nM).