2-amino-5-(3-bromophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one | 856875-46-2

• 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: 2-amino-5-(3-bromophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
• 英文别名: 2-amino-5-(3-bromophenyl)-3-methyl-5-phenyl-3,5-dihydro-imidazol-4-one；2-amino-5(3-bromo-phenyl)-3-methyl-5-phenyl-3, 5-4H-dihydro-imidazol-4-one；2-amino-5-(3-bromophenyl)-3-methyl-5-phenylimidazol-4-one
• CAS: 856875-46-2
• 化学式: C₁₆H₁₄BrN₃O
• 分子量: 344.211
• InChiKey: JJAICPQAWSIWNG-UHFFFAOYSA-N

物化性质

• 沸点：
  463.8±55.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 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

• 作为反应物：
  描述：

  2-amino-5-(3-bromophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 正己烷 、 异丙醇 、 甲苯 为溶剂， 反应 1.16h， 生成 (2e,5r)-2-Imino-5-(3'-Methoxybiphenyl-3-Yl)-3-Methyl-5-Phenylimidazolidin-4-One
  参考文献：
  名称：

  发现一种可有效减少 CNS Aβ 的口服、脑渗透 BACE1 抑制剂

  摘要：

  抑制 BACE1 以防止脑 Aβ 肽形成是治疗阿尔茨海默病的潜在疾病修饰方法。尽管进行了十多年的药物发现工作，但在全身给药后能显着降低 CNS Aβ 水平的脑渗透性 BACE1 抑制剂的鉴定仍然具有挑战性。在本报告中，我们描述了一系列源自亚氨基嘧啶酮支架的脑渗透 BACE1 抑制剂的基于结构的优化。将基于结构的设计与物理化学性质的控制相结合，最终发现了化合物16，当对大鼠口服给药时，该化合物有效地降低了皮质和脑脊液 Aβ40 的水平。

  DOI：

  10.1021/ml3001165
• 作为产物：
  描述：

  1-溴-3-(苯基乙炔基)苯 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 22.0h， 生成 2-amino-5-(3-bromophenyl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one
  参考文献：
  名称：

  设计，合成和评估2-氨基-咪唑-4-酮衍生物作为有效的β位淀粉样蛋白前体蛋白裂解酶1（BACE-1）抑制剂。

  摘要：

  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）。

  DOI：

  10.1016/j.bmcl.2019.126772

文献信息

• NEW COMPOUNDS 835
  申请人：Burrows Jeremy Nicholas

  公开号：US20080287460A1

  公开（公告）日：2008-11-20

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

  这项发明涉及具有以下结构式I的新化合物，以及它们的药用盐、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。
• 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。
• 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：Berg Stefan

  公开号：US20090233930A9

  公开（公告）日：2009-09-17

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

  本发明涉及具有以下结构式I的新化合物，以及它们的药学上可接受的盐、组合物和使用方法。这些新化合物提供了治疗或预防认知障碍、阿尔茨海默病、神经退行性和痴呆症的方法。
• 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。
• AMINO-5,5-DIPHENYLIMIDAZOLONE DERIVATIVES FOR THE INHIBITION OF BETA-SECRETASE
  申请人：Malamas Michael S.

  公开号：US20090093498A1

  公开（公告）日：2009-04-09

  The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.

  本发明提供了一种I式化合物及其用于治疗、预防或改善患有β-淀粉样蛋白沉积或β-淀粉样蛋白水平升高的疾病或疾病状态的患者的用途。