(S)-3-({1-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid tert-butyl ester | 192945-03-2

• 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: (S)-3-({1-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid tert-butyl ester
• 英文别名: tert-butyl (2S)-3-[[1-[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]indazole-5-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoate
• CAS: 192945-03-2
• 化学式: C₃₁H₄₃N₇O₅S
• 分子量: 625.792
• InChiKey: QFCGQRZBQNVWQC-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  164
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 (S)-3-({1-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid tert-butyl ester 以 二氯甲烷 为溶剂， 生成 3-[1-[3-(N-3,4,5,6-Tetrahydropyrimidin-2-ylamino)-propyl]indazol-5-ylcarbonylamino]-2(S)-(2,4,6-trimethylbenzenesulfonylamino)propionic acid trifluoroacetate
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j
• 作为产物：
  描述：

  tert-butyl 3-amino-N-(2,4,6-trimethylphenyl)sulfonyl-L-alanine 在 palladium dihydroxide 吡啶 、 1,4-环己二烯 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 46.0h， 生成 (S)-3-({1-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propyl]-1H-indazole-5-carbonyl}-amino)-2-(2,4,6-trimethyl-benzenesulfonylamino)-propionic acid tert-butyl ester
  参考文献：
  名称：

  Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃

  摘要：

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.

  DOI：

  10.1021/jm990049j

文献信息

• Disubstituted Indazoles as Potent Antagonists of the Integrin α_vβ₃
  作者：Douglas G. Batt、Joseph J. Petraitis、Gregory C. Houghton、Dilip P. Modi、Gary A. Cain、Martha H. Corjay、Shaker A. Mousa、Peter J. Bouchard、Mark S. Forsythe、Patricia P. Harlow、Frank A. Barbera、Susan M. Spitz、Ruth R. Wexler、Prabhakar K. Jadhav

  DOI：10.1021/jm990049j

  日期：2000.1.1

  A new series of indazole-containing alpha(v)beta(3) integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of beta(3)-transfected 293 cells to fibrinogen and to selectivity for alpha(v)beta(3) over GPIIbIIIa, another RGD-binding integrin. Indazoles attached to a 2-aminopyridine or 2-aminoimidazole by a propylene linker at the indazole 1-position and to a diaminopropionate derivative via a 5-carboxylate amide provided the best potency with moderate selectivity. Several differences in the SAR of the diaminopropionate moiety were observed between this series and a series of isoxazoline-based selective GPIIbIIIa antagonists. Compound 34a (SM256) was a potent antagonist of alpha(v)beta(3) (IC50 2.3 nM) with 9-fold selectivity over GPIIbIIIa.