(1,2-cis-2,3-cis-3,4-cis)-1,3-bis[4-{[(tbutoxy)carbonyl]amino}benzamido]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)phenyl]cyclobutane-1,3-dicarboxylic acid | 1245286-74-1

• 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: (1,2-cis-2,3-cis-3,4-cis)-1,3-bis[4-{[(tbutoxy)carbonyl]amino}benzamido]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)phenyl]cyclobutane-1,3-dicarboxylic acid
• CAS: 1245286-74-1
• 化学式: C₅₄H₅₂N₄O₁₆S₂
• 分子量: 1077.16
• InChiKey: JSLFGFBQFKCNSQ-NHONBVHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.35
• 重原子数：
  76.0
• 可旋转键数：
  16.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  280.52
• 氢给体数：
  6.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (1,2-cis-2,3-cis-3,4-cis)-1,3-bis[4-{[(tbutoxy)carbonyl]amino}benzamido]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)phenyl]cyclobutane-1,3-dicarboxylic acid 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 (1,2-cis-2,3-cis-3,4-cis)-1,3-bis[4-(3-naphthalen-1-yl)thioureidobenzamido]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)phenyl]cyclobutane-1,3-dicarboxylic acid
  参考文献：
  名称：

  Cyclobutane Derivatives As Novel Nonpeptidic Small Molecule Agonists of Glucagon-Like Peptide-1 Receptor

  摘要：

  A novel cyclobutane class of nonpeptidic glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by 3, was identified using receptor binding and multiple response element/cAMP response element (MRE/CRE)-driven reporter gene assays. The structures of 3 and its three isomers were elucidated by NMR, HRESIMS, and X-ray crystallography. A series of structural modifications were also made based on the core structure of 3 with different substitution groups at the west and east ends. Among these analogues, compound 16 was found to be 4- to 5-fold more potent than 3 both in vitro and in vivo.

  DOI：

  10.1021/jm201150j
• 作为产物：
  描述：

  (Z)-4-((2-[4-{[(t-butoxy)carbonyl]amino}phenyl]-5-oxooxazol-4(5H)-ylidene)methyl)-2-methoxyphenyl thiophene-2-carboxylate 以 二甲基亚砜 为溶剂， 反应 72.0h， 以10.6%的产率得到(1,2-cis-2,3-cis-3,4-cis)-1,3-bis[4-{[(tbutoxy)carbonyl]amino}benzamido]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)phenyl]cyclobutane-1,3-dicarboxylic acid
  参考文献：
  名称：

  Cyclobutane Derivatives As Novel Nonpeptidic Small Molecule Agonists of Glucagon-Like Peptide-1 Receptor

  摘要：

  A novel cyclobutane class of nonpeptidic glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by 3, was identified using receptor binding and multiple response element/cAMP response element (MRE/CRE)-driven reporter gene assays. The structures of 3 and its three isomers were elucidated by NMR, HRESIMS, and X-ray crystallography. A series of structural modifications were also made based on the core structure of 3 with different substitution groups at the west and east ends. Among these analogues, compound 16 was found to be 4- to 5-fold more potent than 3 both in vitro and in vivo.

  DOI：

  10.1021/jm201150j

文献信息

• Cyclobutane Derivatives As Novel Nonpeptidic Small Molecule Agonists of Glucagon-Like Peptide-1 Receptor
  作者：Qing Liu、Na Li、Yunyun Yuan、Huili Lu、Xiaoyan Wu、Caihong Zhou、Min He、Haoran Su、Meng Zhang、Jia Wang、Bao Wang、You Wang、Dawei Ma、Yang Ye、Hans-Christoph Weiss、Ernst R. F. Gesing、Jiayu Liao、Ming-Wei Wang

  DOI：10.1021/jm201150j

  日期：2012.1.12

  A novel cyclobutane class of nonpeptidic glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by 3, was identified using receptor binding and multiple response element/cAMP response element (MRE/CRE)-driven reporter gene assays. The structures of 3 and its three isomers were elucidated by NMR, HRESIMS, and X-ray crystallography. A series of structural modifications were also made based on the core structure of 3 with different substitution groups at the west and east ends. Among these analogues, compound 16 was found to be 4- to 5-fold more potent than 3 both in vitro and in vivo.