dimethyl (2-cyano-1-phenylethyl)phosphonate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: dimethyl (2-cyano-1-phenylethyl)phosphonate
• 英文别名: 3-Dimethoxyphosphoryl-3-phenylpropanenitrile；3-dimethoxyphosphoryl-3-phenylpropanenitrile
• 化学式: C₁₁H₁₄NO₃P
• 分子量: 239.211
• InChiKey: QKQXREMPTBQFCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  肉桂腈 、 亚磷酸二甲酯 在 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine supported on polystyrene 作用下， 反应 24.0h， 以76%的产率得到dimethyl (2-cyano-1-phenylethyl)phosphonate
  参考文献：
  名称：

  PS-BEMP作为弱电子烯烃中磷-迈克尔加成反应的基本催化剂†

  摘要：

  PS-BEMP用作非均相催化剂，用于将磷亲核体的磷-迈克尔加成到各种电子贫乏的烯烃中。加成反应通常在无溶剂条件下用等摩尔量的试剂进行。事实证明，该方案对于添加芳族，非芳族和环状酮非常有效，在所有情况下均具有良好的收率（78-85％）。该方案还扩展到了α，β-不饱和酯和腈，并获得了良好的结果。这表明PS-BEMP是将磷-迈克尔加成至电子贫乏烯烃的良好催化剂。

  DOI：

  10.1039/c6ob00242k

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：US20110218194A1

  公开（公告）日：2011-09-08

  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.

  本发明揭示了公式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为键，—C(═S)—，—S(O)—，—S(O)2—，—C(═O)—，—O—，—C(R6)(R7)—，—N(R5)—或—C(═N(R5))—；X为—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为键，—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；以及规范中定义的R1、R2、R3、R4、R5、R6和R7；以及包含公式I化合物的药物组成物。本发明还揭示了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、贫血原虫酶、天冬氨酸蛋白酶和原虫酶的方法。本发明还揭示了使用公式I化合物与胆碱酯酶抑制剂或肌动蛋白m1激动剂或m2拮抗剂联合治疗认知或神经退行性疾病的方法。
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