His-[2-amino-iso-butyryl]-Glu-Gly-Thr-[(L)-α-methyl-(2-fluorophenyl)alanyl]-Thr-Ser-Asp-[2-amino-3-(2'-ethyl-4'-methoxy-biphenyl-4-yl)propanoyl]-[2-amino-3-(2'-methyl-biphenyl-4-yl)propanoyl]-NH2 | 516518-88-0

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: His-[2-amino-iso-butyryl]-Glu-Gly-Thr-[(L)-α-methyl-(2-fluorophenyl)alanyl]-Thr-Ser-Asp-[2-amino-3-(2'-ethyl-4'-methoxy-biphenyl-4-yl)propanoyl]-[2-amino-3-(2'-methyl-biphenyl-4-yl)propanoyl]-NH2
• 英文别名: His-Aib-Glu-Gly-Thr-[(L)-α-Me-(2-F)Phe]-Thr-Ser-Asp-(2'-Et,4'-OMe)BIP-(2'-Me)BIP-NH2；His-Aib-Glu-Gly-Thr-[α-MePhe(2-F)]-Thr-Ser-Asp-Bip(2-Et,4-OMe)-Bip(2-Me)-NH2；(4S)-4-[[2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-2-methylpropanoyl]amino]-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-[4-(2-methylphenyl)phenyl]-1-oxopropan-2-yl]amino]-3-[4-(2-ethyl-4-methoxyphenyl)phenyl]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(2-fluorophenyl)-2-methyl-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid
• CAS: 516518-88-0
• 化学式: C₇₆H₉₅FN₁₄O₁₉
• 分子量: 1527.67
• InChiKey: FQOJQWPQOOFFLK-SWNSGIGISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  110
• 可旋转键数：
  41
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  533
• 氢给体数：
  18
• 氢受体数：
  22

反应信息

• 作为产物：
  描述：

  Fmoc-O-叔丁基-L-谷氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-甘氨酸 、 N-Fmoc-N'-三苯甲基-L-组氨酸 、 Fmoc-2-氨基异丁酸 、 (S)-2-((9H-fluoren-9-yloxy)carbonylamino)-3-(2'-ethyl-4'-methoxy-biphenyl-4-yl)propanoic acid 、 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 Fmoc-O-叔丁基-L-苏氨酸 、 (S)-N-Fmoc-α-甲基-2-氟苯丙氨酸 在 N-羟基-7-氮杂苯并三氮唑 、 N,N'-二环己基碳二亚胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.35h， 生成 His-[2-amino-iso-butyryl]-Glu-Gly-Thr-[(L)-α-methyl-(2-fluorophenyl)alanyl]-Thr-Ser-Asp-[2-amino-3-(2'-ethyl-4'-methoxy-biphenyl-4-yl)propanoyl]-[2-amino-3-(2'-methyl-biphenyl-4-yl)propanoyl]-NH2
  参考文献：
  名称：

  Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity

  摘要：

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.

  DOI：

  10.1021/jm900752a

文献信息

• Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity
  作者：Claudio Mapelli、Sesha I. Natarajan、Jean-Philippe Meyer、Margarita M. Bastos、Michael S. Bernatowicz、Ving G. Lee、Jelka Pluscec、Douglas J. Riexinger、Ellen S. Sieber-McMaster、Keith L. Constantine、Constance A. Smith-Monroy、Rajasree Golla、Zhengping Ma、Daniel A. Longhi、Dan Shi、Li Xin、Joseph R. Taylor、Barry Koplowitz、Cecilia L. Chi、Ashish Khanna、Gordon W. Robinson、Ramakrishna Seethala、Ildiko A. Antal-Zimanyi、Robert H. Stoffel、Songping Han、Jean M. Whaley、Christine S. Huang、John Krupinski、William R. Ewing

  DOI：10.1021/jm900752a

  日期：2009.12.10

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.