(+/-)-tert-butyl {6-{[1'-(2''-tert-butoxycarbonylamino-ethyl)-4'-oxo-pyrrolidin-3'-yl]methyl}-pyridin-2-yl}carbamate | 848472-69-5

• 分子结构分类: 有机化合物
• 英文名称: (+/-)-tert-butyl {6-{[1'-(2''-tert-butoxycarbonylamino-ethyl)-4'-oxo-pyrrolidin-3'-yl]methyl}-pyridin-2-yl}carbamate
• 英文别名: {6-[1-(2-tert-butoxycarbonylamino-ethyl)-4-oxo-pyrrolidin-3-ylmethyl]-pyridin-2-yl}-carbamic acid tert-butyl ester；tert-butyl N-[6-[[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-4-oxopyrrolidin-3-yl]methyl]pyridin-2-yl]carbamate
• CAS: 848472-69-5
• 化学式: C₂₂H₃₄N₄O₅
• 分子量: 434.536
• InChiKey: RSQUOBUVYLUJFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+/-)-tert-butyl {6-{[1'-(2''-tert-butoxycarbonylamino-ethyl)-4'-oxo-pyrrolidin-3'-yl]methyl}-pyridin-2-yl}carbamate 、 3-氨基-1-丙醇 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 36.0h， 生成 (+/-)-tert-butyl {6-{[trans-1'-(2''-tert-butoxycarbonylaminoethyl)-4'-(3''-hydroxypropylamino)-pyrrolidin-3'-yl]methyl}pyridin-2-yl}-carbamate 、 (+/-)-tert-butyl {6-{[cis-1'-(2''-tert-butoxycarbonylaminoethyl)-4'-(3''-hydroxypropylamino)-pyrrolidin-3'-yl]methyl}pyridin-2-yl}-carbamate
  参考文献：
  名称：

  Exploration of the Active Site of Neuronal Nitric Oxide Synthase by the Design and Synthesis of Pyrrolidinomethyl 2-Aminopyridine Derivatives

  摘要：

  Neuronal nitric oxide synthase (nNOS) represents an important therapeutic target for the prevention of brain injury and the treatment of various neurodegenerative disorders. A series of trans-substituted amino pyrrolidinomethyl 2-aminopyridine derivatives (8-34) was designed and synthesized. A structure activity relationship analysis led to the discovery of low nanomolar nNOS inhibitors ((+/-)-32 and (+/-)-34) with more than 1000-fold selectivity for nNOS over eNOS. Four enantiomerically pure isomers of 3'-[2 ''-(3 ''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine (4) also were synthesized. It was found that (3'R,4'R)-4 can induce enzyme elasticity to generate a new "hot spot" for ligand binding. The inhibitor adopts a unique binding mode, the same as that observed for (3'R,4'R)-3'-[2 ''-(3'''-fluorophenethylamino)ethylamino]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine ((3'R,4'R)-3) (J. Am. Chem. Soc. 2010, 132 (15), 5437-5442). On the basis of structure-activity relationships of 8-34 and different binding conformations of the cis and trans isomers of 3 and 4, critical structural requirements of the NOS active site for ligand binding are revealed.

  DOI：

  10.1021/jm100947x
• 作为产物：
  描述：

  (+/-)-tert-butyl {6-[trans-1'-(2''-tert-butoxycarbonylamino-ethyl)-4'-hydroxy-pyrrolidin-3'-ylmethyl]-pyridin-2-yl}carbamate 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以85%的产率得到(+/-)-tert-butyl {6-{[1'-(2''-tert-butoxycarbonylamino-ethyl)-4'-oxo-pyrrolidin-3'-yl]methyl}-pyridin-2-yl}carbamate
  参考文献：
  名称：

  Exploration of the Active Site of Neuronal Nitric Oxide Synthase by the Design and Synthesis of Pyrrolidinomethyl 2-Aminopyridine Derivatives

  摘要：

  Neuronal nitric oxide synthase (nNOS) represents an important therapeutic target for the prevention of brain injury and the treatment of various neurodegenerative disorders. A series of trans-substituted amino pyrrolidinomethyl 2-aminopyridine derivatives (8-34) was designed and synthesized. A structure activity relationship analysis led to the discovery of low nanomolar nNOS inhibitors ((+/-)-32 and (+/-)-34) with more than 1000-fold selectivity for nNOS over eNOS. Four enantiomerically pure isomers of 3'-[2 ''-(3 ''-fluorophenethylamino)ethoxy]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine (4) also were synthesized. It was found that (3'R,4'R)-4 can induce enzyme elasticity to generate a new "hot spot" for ligand binding. The inhibitor adopts a unique binding mode, the same as that observed for (3'R,4'R)-3'-[2 ''-(3'''-fluorophenethylamino)ethylamino]pyrrolidin-4'-yl}methyl}-4-methylpyridin-2-amine ((3'R,4'R)-3) (J. Am. Chem. Soc. 2010, 132 (15), 5437-5442). On the basis of structure-activity relationships of 8-34 and different binding conformations of the cis and trans isomers of 3 and 4, critical structural requirements of the NOS active site for ligand binding are revealed.

  DOI：

  10.1021/jm100947x

文献信息

• Heteroaromatic selective inhibitors of neuronal nitric oxide synthase
  申请人：Silverman B. Richard

  公开号：US20050107369A1

  公开（公告）日：2005-05-19

  Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.

  抑制神经元一氧化氮合酶(nNOS)的化合物，用于潜在的神经退行性疾病治疗，如中风、阿尔茨海默病、帕金森病、亨廷顿病等，该化合物的公式为：
• Potent and highly selective heteroaromatic inhibitors of neuronal nitric oxide synthase
  申请人：Silverman B. Richard

  公开号：US20080108814A1

  公开（公告）日：2008-05-08

  Peptidomimetic compounds as can inhibit neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as but not limited to stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease.

  肽类类似物化合物可抑制神经元一氧化氮合酶(nNOS)，用于潜在的治疗神经退行性疾病，如中风、阿尔茨海默病、帕金森病、亨廷顿病等。
• Heteroaromatic Selective Inhibitors of Neuronal Nitric Oxide Synthase
  申请人：Silverman Richard B.

  公开号：US20090104677A1

  公开（公告）日：2009-04-23

  Compounds inhibiting neuronal nitric oxide synthase (nNOS) for potential treatment in neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, Huntington's disease, such compounds of a formula.

  抑制神经元一氧化氮合酶(nNOS)的化合物，用于潜在治疗神经退行性疾病，如中风、阿尔茨海默病、帕金森病、亨廷顿病等，这些化合物的公式为：
• US7470790B2
  申请人：——

  公开号：US7470790B2

  公开（公告）日：2008-12-30
• US7994326B2
  申请人：——

  公开号：US7994326B2

  公开（公告）日：2011-08-09