(3S,6S,9R,1'R)-3-[9'-fluorenylmethyloxycarbonyl]-9-[(1'-carbamoyl-2'-phenyl)ethyl]carbamoyl-2-oxo-7-thio-1-azabicyclo[4.3.0]nonane | 872035-23-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,6S,9R,1'R)-3-[9'-fluorenylmethyloxycarbonyl]-9-[(1'-carbamoyl-2'-phenyl)ethyl]carbamoyl-2-oxo-7-thio-1-azabicyclo[4.3.0]nonane
• 英文别名: 9H-fluoren-9-ylmethyl N-[(3R,6S,8aS)-3-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-5-oxo-2,3,6,7,8,8a-hexahydro-[1,3]thiazolo[3,2-a]pyridin-6-yl]carbamate
• CAS: 872035-23-9
• 化学式: C₃₂H₃₂N₄O₅S
• 分子量: 584.696
• InChiKey: CZTKLWOATUEGEO-PUHABZHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,6S,9R,1'R)-3-[9'-fluorenylmethyloxycarbonyl]-9-[(1'-carbamoyl-2'-phenyl)ethyl]carbamoyl-2-oxo-7-thio-1-azabicyclo[4.3.0]nonane 在 哌啶 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 tert-butyl N-[(2S)-1-[[(3R,6S,8aS)-3-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-5-oxo-2,3,6,7,8,8a-hexahydro-[1,3]thiazolo[3,2-a]pyridin-6-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  Conformationally Constrained CCK4 Analogues Incorporating IBTM and BTD β-Turn Mimetics

  摘要：

  To test whether a turnlike arrangement is involved in the bioactive conformation of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been replaced by recognized beta-turn mimetics (2S,5S,11bR)- and (2R,5R,11bS)-2-amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred over its type II' counterpart for efficient CCK1 receptor recognition, while BTD derivatives were completely inactive. The structure-conformation-activity relationship study in the IBTM series has shown some essential requirement of these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the adoption of turnlike conformations, (b) the presence of an 1-Phe residue and a C-terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton. Moreover, the existence of pi-pi interactions between the phenyl ring of D-Phe residues and the indole ring of IBTM framework is detrimental for binding affinity. A series of potent and selective CCK1 receptor antagonists, exemplified by compounds 8a and 8b, emerges among these IBTM-containing derivatives.

  DOI：

  10.1021/jm050689o
• 作为产物：
  描述：

  D-苯丙氨酰胺 、 Fmoc-β-turn-dipeptide 在 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到(3S,6S,9R,1'R)-3-[9'-fluorenylmethyloxycarbonyl]-9-[(1'-carbamoyl-2'-phenyl)ethyl]carbamoyl-2-oxo-7-thio-1-azabicyclo[4.3.0]nonane
  参考文献：
  名称：

  Conformationally Constrained CCK4 Analogues Incorporating IBTM and BTD β-Turn Mimetics

  摘要：

  To test whether a turnlike arrangement is involved in the bioactive conformation of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been replaced by recognized beta-turn mimetics (2S,5S,11bR)- and (2R,5R,11bS)-2-amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred over its type II' counterpart for efficient CCK1 receptor recognition, while BTD derivatives were completely inactive. The structure-conformation-activity relationship study in the IBTM series has shown some essential requirement of these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the adoption of turnlike conformations, (b) the presence of an 1-Phe residue and a C-terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton. Moreover, the existence of pi-pi interactions between the phenyl ring of D-Phe residues and the indole ring of IBTM framework is detrimental for binding affinity. A series of potent and selective CCK1 receptor antagonists, exemplified by compounds 8a and 8b, emerges among these IBTM-containing derivatives.

  DOI：

  10.1021/jm050689o

文献信息

• Conformationally Constrained CCK4 Analogues Incorporating IBTM and BTD β-Turn Mimetics
  作者：Mercedes Martín-Martínez、Natalia De la Figuera、Miriam LaTorre、M. Teresa García-López、Edurne Cenarruzabeitia、Joaquín Del Río、Rosario González-Muñiz

  DOI：10.1021/jm050689o

  日期：2005.12.1

  To test whether a turnlike arrangement is involved in the bioactive conformation of CCK4 analogues upon CCK1 receptor recognition, we describe the preparation of two series of CCK4 derivatives, in which the central dipeptide Met-Asp has been replaced by recognized beta-turn mimetics (2S,5S,11bR)- and (2R,5R,11bS)-2-amino-5-carboxy-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole (IBTM) and beta-turn dipeptide, 2-oxo-7-thio-1-azabicyclo[4.3.0]nonane (BTD)}. The incorporation of the indolizinoindole IBTM type II beta-turn mimetic is preferred over its type II' counterpart for efficient CCK1 receptor recognition, while BTD derivatives were completely inactive. The structure-conformation-activity relationship study in the IBTM series has shown some essential requirement of these CCK4 derivatives to favorably interact with CCK1 receptors: (a) the adoption of turnlike conformations, (b) the presence of an 1-Phe residue and a C-terminal carboxamide moiety, and (c) the indole ring of the IBTM skeleton. Moreover, the existence of pi-pi interactions between the phenyl ring of D-Phe residues and the indole ring of IBTM framework is detrimental for binding affinity. A series of potent and selective CCK1 receptor antagonists, exemplified by compounds 8a and 8b, emerges among these IBTM-containing derivatives.