(S)-1-((3aS,6R,7aR)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-3-(2,6-dimethylphenyl)-2-((diphenylmethylene)amino)propan-1-one | 187829-92-1

• 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: (S)-1-((3aS,6R,7aR)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-3-(2,6-dimethylphenyl)-2-((diphenylmethylene)amino)propan-1-one
• CAS: 187829-92-1
• 化学式: C₃₄H₃₈N₂O₃S
• 分子量: 554.753
• InChiKey: CELRVXYPCWNDDH-LFLQOBSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  40.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.81
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-1-((3aS,6R,7aR)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-3-(2,6-dimethylphenyl)-2-((diphenylmethylene)amino)propan-1-one 在 盐酸 、 lithium hydroxide 、 四丁基溴化铵 、 lithium bromide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.0h， 生成 L-2',6'-dimethylphenylalanine
  参考文献：
  名称：

  Tachykinin NK-1 receptor probed with constrained analogues of substance P

  摘要：

  The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid (Tie), L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of L-1-indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (Delta(Z)Phe, Delta(E)Phe, Delta(Z)Nal, Delta(E)Nal) and L-o,o'-dimethylphenylalanine (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S-7 and S-8 subsites, corresponding to residues Phe(7) and Phe(8) of substance P. According to the binding potencies of these substituted-SP analogues, the S-7 binding subsite is smaller than the S-8 subsite: the S-7 subsite accepts only one aromatic nucleus, while the S-8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S, binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu(6), Pro(9)]SP(6-11), discrepancies are observed between affinity (K-i) and activity (EC(50)) values for IPs production. While a weak correlation between K-i and EC(50) values for IPs production could be found (r=0.70), an excellent correlation could be demonstrated between their affinities (K-i) and their potencies (EC(50)) for cAMP production (r=0.97). The high potency (EC(50)) observed for 'septide-like' molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC(50) values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r=0.94). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0968-0896(96)00230-1
• 作为产物：
  描述：

  2,6-二甲基苄醇 在 正丁基锂 、 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 反应 18.33h， 生成 (S)-1-((3aS,6R,7aR)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-3-(2,6-dimethylphenyl)-2-((diphenylmethylene)amino)propan-1-one
  参考文献：
  名称：

  Tachykinin NK-1 receptor probed with constrained analogues of substance P

  摘要：

  The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid (Tie), L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of L-1-indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylalanine (Delta(Z)Phe, Delta(E)Phe, Delta(Z)Nal, Delta(E)Nal) and L-o,o'-dimethylphenylalanine (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S-7 and S-8 subsites, corresponding to residues Phe(7) and Phe(8) of substance P. According to the binding potencies of these substituted-SP analogues, the S-7 binding subsite is smaller than the S-8 subsite: the S-7 subsite accepts only one aromatic nucleus, while the S-8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S, binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu(6), Pro(9)]SP(6-11), discrepancies are observed between affinity (K-i) and activity (EC(50)) values for IPs production. While a weak correlation between K-i and EC(50) values for IPs production could be found (r=0.70), an excellent correlation could be demonstrated between their affinities (K-i) and their potencies (EC(50)) for cAMP production (r=0.97). The high potency (EC(50)) observed for 'septide-like' molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC(50) values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r=0.94). Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0968-0896(96)00230-1