人参皂苷CK | 160729-91-9

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 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
• 中文名称: 人参皂苷CK
• 英文名称: L 754394
• 英文别名: 1-Piperazinepentanamide, N-((1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl)-2-(((1,1-dimethylethyl)amino)carbonyl)-4-(furo(2,3-b)pyridin-5-ylmethyl)-gamma-hydroxy-alpha-(phenylmethyl)-, (alphaR,gammaS,2S)-；(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl]-N-tert-butyl-4-(furo[2,3-b]pyridin-5-ylmethyl)piperazine-2-carboxamide
• CAS: 160729-91-9
• 化学式: C₃₈H₄₇N₅O₅
• 分子量: 653.822
• InChiKey: UBUFVRJUGFJQSI-PPJSLLJVSA-N

物化性质

• 熔点：
  184-185 °C
• 沸点：
  903.1±65.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  人参皂苷CK 在 palladium on activated charcoal ammonium formate 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以46%的产率得到N-(2(R)-hydroxy-1(S)-indanyl)-2(R)-phenylmethyl-4(S)-hydroxy-5-(1-(4-(5-(2,3-dihydrofuro[2,3-b]pyridyl)methyl)-2(S)-N'-(tert-butylcarboxamido)piperazinyl))pentanamide
  参考文献：
  名称：

  Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors

  摘要：

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

  DOI：

  10.1021/jm9903848
• 作为产物：
  描述：

  [1(1S,2R),5(S)]-2,3,5-三脱氧-N-(2,3-二氢-2-羟基-1H-茚-1-基)-5-[2-[(叔丁基氨基)甲酰]-1-哌嗪基]-2-(苯基甲基)-D-赤式-戊酰胺 、 5-(chloromethyl)furo[2,3-b]pyridine 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以84%的产率得到人参皂苷CK
  参考文献：
  名称：

  Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors

  摘要：

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.

  DOI：

  10.1021/jm9903848

文献信息

• Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors
  作者：Bruce D. Dorsey、Colleen McDonough、Stacey L. McDaniel、Rhonda B. Levin、Christina L. Newton、Jacob M. Hoffman、Paul L. Darke、Joan A. Zugay-Murphy、Emilio A. Emini、William A. Schleif、David B. Olsen、Mark W. Stahlhut、Carrie A. Rutkowski、Lawrence C. Kuo、Jiunn H. Lin、I-W. Chen、Stuart R. Michelson、M. Katharine Holloway、Joel R. Huff、Joseph P. Vacca

  DOI：10.1021/jm9903848

  日期：2000.9.1

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.