3-methyl-5,5-diphenyl-2-iminohydantoin | 26975-80-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-methyl-5,5-diphenyl-2-iminohydantoin
• 英文别名: 2-amino-3-methyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one；(2e)-2-Imino-3-Methyl-5,5-Diphenylimidazolidin-4-One；2-amino-3-methyl-5,5-diphenylimidazol-4-one
• CAS: 26975-80-4
• 化学式: C₁₆H₁₅N₃O
• 分子量: 265.315
• InChiKey: RNWLAFWLSSMCLN-UHFFFAOYSA-N

物化性质

• 沸点：
  417.6±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-methyl-2-methylsulfanyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one 在 碘化铵 、 乙醇 、 氨 作用下， 生成 3-methyl-5,5-diphenyl-2-iminohydantoin
  参考文献：
  名称：

  Lempert; Breuer, Chemische Berichte, 1959, vol. 92, p. 1710

  摘要：

  DOI：

文献信息

• Design, synthesis and evaluation of 2-amino-imidazol-4-one derivatives as potent β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) inhibitors
  作者：Tian-Yuan Fan、Wen-Yu Wu、Shao-Peng Yu、Yue Zhong、Chao Zhao、Min Chen、He-Min Li、Nian-Guang Li、Zhi Chen、Sai Chen、Zhi-Hui Sun、Jin-Ao Duan、Zhi-Hao Shi

  DOI：10.1016/j.bmcl.2019.126772

  日期：2019.12

  protein cleaving enzyme 1 (BACE1) to prevent brain β-amyloid (Aβ) peptide’s formation is a potential effective approach to treat Alzheimer’s disease. In this report we described a structure-based optimization of a series of BACE1 inhibitors derived from an iminopyrimidinone scaffold W-41 (IC50 = 7.1 μM) by Wyeth, which had good selectivity and brain permeability but low activity. The results showed that

  抑制β-位淀粉样蛋白前体蛋白裂解酶1（BACE1）以防止脑β-淀粉样蛋白（Aβ）肽的形成是治疗阿尔茨海默氏病的潜在有效方法。在本报告中，我们描述了一系列由Wyeth衍生自亚氨基嘧啶酮支架W-41（IC 50 = 7.1μM）的BACE1抑制剂的结构优化，该抑制剂具有良好的选择性和脑通透性，但活性较低。结果表明，占领BACE1酶的S 3腔可能是提高生物学活性的有效策略，其中5种化合物对L-5的抑制活性和脂溶性均高于W-41。是最有效的BACE1抑制剂（IC 50 = 0.12μM，logP = 2.49）。
• Heterocyclic aspartyl protease inhibitors
  申请人：Zhu Zhaoning

  公开号：US20080200445A1

  公开（公告）日：2008-08-21

  Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula 1. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m 1 agonist or m 2 antagonist.

  本发明涉及公式I的化合物或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中W是键，—C(═S)—，—S(O)—，—S(O)2—，—C(═O)—，—O—，—C(R6)(R7)—，—N(R5)—或—C(═N(R5))—；X是—O—，—N(R5)—或—C(R6)(R7)—；但当X为—O—时，U不是—O—，—S(O)—，—S(O)2—，—C(═O)—或—C(═NR5)—；U是键，—S(O)—，—S(O)2—，—C(O)—，—O—，—P(O)(OR15)—，—C(═NR5)—，—(C(R6)(R7))b—或—N(R5)—；其中b为1或2；但当W为—S(O)—，—S(O)2—，—O—或—N(R5)—时，U不是—S(O)—，—S(O)2—，—O—或—N(R5)—；当X为—N(R5)—且W为—S(O)—，—S(O)2—，—O—或—N(R5)—时，U不是键；R1、R2、R3、R4、R5、R6和R7如规范中所定义；以及包括公式1的化合物的药物组合物。本发明还涉及抑制天冬氨酸蛋白酶的方法，特别是治疗心血管疾病、认知和神经退行性疾病的方法，以及抑制人类免疫缺陷病毒、贫血原虫、D蛋白酶和原虫酶的方法。本发明还涉及使用公式I的化合物与胆碱酯酶抑制剂或肌动蛋白m1受体激动剂或m2受体拮抗剂相结合治疗认知或神经退行性疾病的方法。
• HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS
  申请人：Zhu Zhaoning

  公开号：US20090258868A1

  公开（公告）日：2009-10-15

  Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m 1 agonist or m 2 antagonist.

  本发明涉及公式I的化合物或其立体异构体，互变异构体，或其药学上可接受的盐或溶剂，其中W是键，—C(═S)—，—S(O)—，—S(O)2—，—C(═O)—，—O—，—C(R6)(R7)—，—N(R5)—或—C(═N(R5))—；X是—O—，—N(R5)—或—C(R6)(R7)—；前提是当X为—O—时，U不是—O—，—S(O)—，—S(O)2—，—C(═O)—或—C(═NR5)—；U是键，—S(O)—，—S(O)2—，—C(O)—，—O—，—P(O)(OR15)—，—C(═NR5)—，—(C(R6)(R7))b—或—N(R5)—；其中b为1或2；前提是当W为—S(O)—，—S(O)2—，—O—或—N(R5)—时，U不是—S(O)—，—S(O)2—，—O—或—N(R5)—；前提是当X为—N(R5)—，W为—S(O)—，—S(O)2—，—O—或—N(R5)—时，U不是键；以及R1，R2，R3，R4，R5，R6和R7如规范中所定义的；以及包括公式I的化合物的药物组合物。本发明还涉及抑制天冬氨酸蛋白酶的方法，特别是治疗心血管疾病、认知和神经退行性疾病的方法，以及抑制人类免疫缺陷病毒、质膜蛋白酶、D蛋白酶和原虫酶的方法。本发明还涉及使用公式I的化合物与胆碱酯酶抑制剂或肌动蛋白m1激动剂或m2拮抗剂相结合治疗认知或神经退行性疾病的方法。
• Novel 2-Amino-Imidazole-4-One Compounds And Their Use In The Manufacture Of A Medicament To Be Used In The Treatment Of Cognitive Impairment, Alzheimer's Disease, Neurodegeneration And Dementia
  申请人：Albert Jeffrey

  公开号：US20090176850A1

  公开（公告）日：2009-07-09

  This invention relates to novel compounds having the structural formula I below and to their pharmaceutically acceptable salts, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

  本发明涉及具有下面的结构式I的新化合物及其药学上可接受的盐、组合物和使用方法。这些新化合物可用于治疗或预防认知障碍、阿尔茨海默病、神经退行性疾病和痴呆症。
• 10.1002/rcm.9853
  作者：Bai, Yunpeng、Zou, Yuming、Zeng, Yingjia、Hu, Linhui、Huang, Sumei、Wu, Kunyong、Yi, Qingxia、Chen, Jingchun、Liang, Guowu、Li, Yingbang、Huang, Wendong、Chen, Chunbo

  DOI：10.1002/rcm.9853

  日期：——

  patients with CSA‐AKI at different time points.ResultsMS/MS analysis in positive ion mode showed that benzylic GCs/UCs exhibited similar fragmentation processes, which could produce the characteristic ion (C13H12N+) at m/z 182.0. Furthermore, an obviously different fragmentation pattern of benzylic UCs in the positive ion mode might be due to the neutral loss of the H2CO2 group under low collision energy

  理由：由于急性肾损伤（AKI）与危重患者的不良预后密切相关，因此开发用于其预测和早期诊断的生物标志物显得尤为重要。内源性胍基化合物（GC）和脲基化合物（UC）因其重要的生理活性而可以参与各种生化过程。本研究的目的是探讨尿液 GCs/UCs 的变化特征，作为心脏手术相关急性肾损伤 (CSA-AKI) 患者不同阶段的潜在生物标志物。它们的衍生物用于使用正离子模式下的串联质谱 (MS/MS) 研究碎片机制。此外，还开发了高效液相色谱（HPLC）-MS/MS 方法来测量 CSA-AKI 患者不同时间点尿液样本中 GCs/UCs 的浓度。结果正离子模式下的 MS/MS 分析显示苄基 GCs/UCs 表现出相似的裂解过程，可以产生特征离子（C 13 H 12氮+ ） 在质量分数182.0。此外，在正离子模式下，苄基UCs的碎片模式明显不同，这可能是由于H的中性损失造成的。 2一氧化碳2低碰撞能量下的基团。在八个选定的