N-((phenylamino)carbonyl)leucine | 92033-74-4

• 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: N-((phenylamino)carbonyl)leucine
• 英文别名: (N-phenylcarbamoyl)leucine；N-phenylcarbamoyl-L-leucine；N-Phenylcarbamoyl-L-leucin；L-N-(N-phenylaminocarbonyl)leucine；(2S)-4-methyl-2-(phenylcarbamoylamino)pentanoic acid
• CAS: 92033-74-4
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: OHTKVDOCUSBJJA-NSHDSACASA-N

物化性质

• 熔点：
  119-120 °C(Solv: ethanol (64-17-5))
• 沸点：
  399.9±34.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-((phenylamino)carbonyl)leucine 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-Methyl-2-{(R)-2-(1-methyl-1H-indol-3-yl)-1-[(S)-4-methyl-2-(3-phenyl-ureido)-pentanoylamino]-ethyl}-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Azole Endothelin Antagonists. 2. Structure−Activity Studies

  摘要：

  Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or arylureas led to substantial improvements in activity. Conformational restriction of these groups provides an additional benefit. N-Methylation of the indole moiety which is part of the heterocyclic dipeptide surrogate also improves potency. The effects of these two modifications appear to be synergistic, with the best of the resultant doubly modified analogs (e.g. 14q, 15y, and 15ff) exhibiting an 80-200-fold improvement over the original leads.

  DOI：

  10.1021/jm950592+
• 作为产物：
  描述：

  (S)-benzyl 4-methyl-2-(3-phenylureido)pentanoate 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 14.0h， 生成 N-((phenylamino)carbonyl)leucine
  参考文献：
  名称：

  Azole Endothelin Antagonists. 2. Structure−Activity Studies

  摘要：

  Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or arylureas led to substantial improvements in activity. Conformational restriction of these groups provides an additional benefit. N-Methylation of the indole moiety which is part of the heterocyclic dipeptide surrogate also improves potency. The effects of these two modifications appear to be synergistic, with the best of the resultant doubly modified analogs (e.g. 14q, 15y, and 15ff) exhibiting an 80-200-fold improvement over the original leads.

  DOI：

  10.1021/jm950592+

文献信息

• Protease inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US20030144175A1

  公开（公告）日：2003-07-31

  The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.

  本发明提供了4-氨基-氮杂七环-3-酮蛋白酶抑制剂及其药用可接受的盐、水合物和溶剂化物，其抑制蛋白酶，包括卡特普辛K，这些化合物的药物组合物，这些化合物的新中间体，以及治疗骨骼过度流失或软骨或基质降解疾病的方法，包括骨质疏松症；牙龈疾病，包括牙龈炎和牙周炎；关节炎，更具体地说，是骨关节炎和类风湿关节炎；帕吉特病；恶性高钙血症；和代谢性骨病，包括通过向需要的患者施用本发明化合物来抑制骨质流失或过度软骨或基质降解。
• One-pot preparation of carbamoyl benzotriazoles and their applications in the preparation of ureas, hydrazinecarboxamides and carbamic esters
  作者：Hui Mao、Huili Liu、Yawei Tu、Zhiyun Zhong、Xin Lv、Xiaoxia Wang

  DOI：10.2298/jsc150126069m

  日期：——

  synthesized in one-pot from carboxylic acids, diphenylphosphorazidate (DPPA) and benzotriazole (BtH). The reactivity and applications of carbamoyl benzotriazoles were also explored. Carbamoyl benzotriazoles react smoothly with amino acids, hydrazines and alcohols respectively, thus providing facile access to the corresponding ureas, hydrazinecarboxamides and carbamic esters in good to excellent yields

  氨基甲酰基苯并三唑可方便地由羧酸，叠氮磷酸二苯酯（DPPA）和苯并三唑（BtH）一锅合成。还探讨了氨基甲酰基苯并三唑的反应性和应用。氨基甲酰基苯并三唑分别与氨基酸，肼和醇平稳反应，因此可以轻松获得相应的脲，肼甲酰胺和氨基甲酸酯，收率高至优异。
• [EN] PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE PROTEASES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2000038687A1

  公开（公告）日：2000-07-06

  The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.

  本发明提供了4-氨基-氮杂丙烷-3-酮蛋白酶抑制剂及其药学上可接受的盐、水合物和溶剂化物，其能够抑制蛋白酶，包括卡他普西蛋白酶K，还提供了这些化合物的制药组合物、这些化合物的新中间体以及用于治疗过度骨质流失或软骨或基质降解等疾病的方法，包括骨质疏松症；牙龈疾病，包括牙龈炎和牙周炎；关节炎，更具体地说是骨关节炎和类风湿性关节炎；帕吉特病；恶性高钙血症；以及代谢性骨病，通过向需要的患者施用本发明化合物来抑制骨质流失或过度软骨或基质降解。
• Aldehyde derivatives and their use as calpain inhibitors
  申请人：FUJIREBIO Inc.

  公开号：EP0520336A2

  公开（公告）日：1992-12-30

  Aldehyde derivatives with a specific calpain inhibiting activity and a platelet-aggregation inhibiting effect with formula (I) or formula (II): wherein R1 represents an aromatic hydrocarbon group, a heterocyclic group, or a group of -X-R3 in which X represents O, -S(O)m- (m = 0, 1, or 2), and R3 represents an aromatic hydrocarbon group, a heterocyclic group, or an alkyl group; Z represents R4-Y- or R60-CH(R5)- in which Y represents a 3- to 7-membered nitrogen-containing saturated heterocyclic group, or a single cyclic saturated hydrocarbon group, R4 represents an alkyl group, an alkenyl group, an alkynyl group, an acyl group, a sulfonyl group, an alkoxycarbonyl group, a carbamoyl group, or a thiocarbamoyl group, R5 represents hydrogen, an alkyl group, or an aromatic hydrocarbon group, and R6 represents an acyl group, a carbamoyl group, a thiocarbamoyl group, or an alkyl group; and n is an integer of 1 to 5. wherein R7, R8, R9, and R10 are defined in the specification.

  具有特异性钙蛋白酶抑制活性和血小板聚集抑制作用的式 (I) 或式 (II) 醛衍生物： 其中 R1 代表芳香烃基团、杂环基团或-X-R3 的基团，其中 X 代表 O、-S(O)m- (m = 0、1 或 2)，R3 代表芳香烃基团、杂环基团或烷基；Z 代表 R4-Y- 或 R60-CH(R5)-，其中 Y 代表 3 至 7 元含氮饱和杂环基团，或单环饱和烃基团，R4 代表烷基、烯基、炔基、酰基、磺酰基、烷基、炔基或烷基R5 代表氢、烷基或芳香烃基，R6 代表酰基、氨基甲酰基、硫代氨基甲酰基或烷基；n 是 1 至 5 的整数。 其中 R7、R8、R9 和 R10 的定义见说明书。
• 4-amino-azepan-3-one derivatives as protease inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：EP1384713A1

  公开（公告）日：2004-01-28

  Compounds of formula I are useful as protease inhibitors.

  式 I 的化合物 可用作蛋白酶抑制剂。