2-amino-4-(4-methoxyphenyl)-1-methyl-4-phenyl-1H-imidazol-5(4H)-one | 856875-41-7

• 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-4-(4-methoxyphenyl)-1-methyl-4-phenyl-1H-imidazol-5(4H)-one
• 英文别名: 2-amino-5-(4-methoxyphenyl)-3-methyl-5-phenylimidazol-4-one
• CAS: 856875-41-7
• 化学式: C₁₇H₁₇N₃O₂
• 分子量: 295.341
• InChiKey: VJOYOUKJSHACSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-甲基胍盐酸盐 、 4-甲氧基苯偶酰 在 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以80%的产率得到2-amino-4-(4-methoxyphenyl)-1-methyl-4-phenyl-1H-imidazol-5(4H)-one
  参考文献：
  名称：

  5,5'-双取代氨基乙内酰脲作为强效和选择性人β-分泌酶（BACE1）抑制剂的设计与合成

  摘要：

  报道了鉴定小分子氨基乙内酰脲作为有效的和选择性的人β-分泌酶抑制剂。这些类似物对BACE1表现出低的纳米摩尔效价，在基于细胞的（ELISA）分析中显示出可比的活性，并且对其他结构相关的天冬氨酰蛋白酶BACE2，组织蛋白酶D，肾素和胃蛋白酶显示出大于100倍的选择性。基于BACE1活性位点中HTS-hit 2的共晶体结构，并使用基于结构的药物设计方法，我们系统地探索了BACE1酶的较大结合口袋，并确定了配体与有助于亲和力的蛋白质。一种更有效的化合物（S）-55的IC 50的BACE1值为10 nM，在ELISA分析中显示出可比的细胞活性（EC 50 = 20 nM）。急性口服100 mg / kg的（S）-55导致Tg2576小鼠在8 h时血浆Aβ40降低69％（p <0.001）。

  DOI：

  10.1021/jm901414e

文献信息

• 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。
• 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：Astra Zeneca AB

  公开号：EP1954682A1

  公开（公告）日：2008-08-13
• US7592348B2
  申请人：——

  公开号：US7592348B2

  公开（公告）日：2009-09-22