3-(3-methoxycarbonylbenzenesulfonyl)-1-phenyl-imidazolidin-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-(3-methoxycarbonylbenzenesulfonyl)-1-phenyl-imidazolidin-2,4-dione
• 英文别名: 3-(3-Methoxycarbonylbenzensulfonyl)-1-phenylimidazolidine-2,4-dione；3-(3-Methoxycarbonylbenzenesulfonyl)-1-phenylimidazolidine-2,4-dione；3-(2,5-Dioxo-3-phenyl-imidazolidine-1-sulfonyl)-benzoic acid methyl ester；methyl 3-(2,5-dioxo-3-phenylimidazolidin-1-yl)sulfonylbenzoate
• 化学式: C₁₇H₁₄N₂O₆S
• 分子量: 374.374
• InChiKey: PNEMWQVQIVXXIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-苯基甘氨酸 在 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 3-(3-methoxycarbonylbenzenesulfonyl)-1-phenyl-imidazolidin-2,4-dione
  参考文献：
  名称：

  Substituted 3-(Phenylsulfonyl)-1-phenylimidazolidine-2,4-dione Derivatives as Novel Nonpeptide Inhibitors of Human Heart Chymase

  摘要：

  A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond accepters such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P-1 pocket, the 3-phenylsulfonyl moiety resides in the S-1'-S-2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.

  DOI：

  10.1021/jm960793t

文献信息

• Imidazolidine derivative and use thereof
  申请人：Suntory Limited

  公开号：US05691335A1

  公开（公告）日：1997-11-25

  The invention relates to an imidazolidine derivative represented by the following general formula (1): ##STR1## wherein A and B mean individually an aromatic hydrocarbon group which may be substituted by 1-3 substituents selected from halogen atoms, C.sub.1-4 alkyl groups, C.sub.1-4 alkoxy groups, C.sub.1-4 alkylenedioxy groups, a phenoxy group, a nitro group, a cyano group, a phenyl group, C.sub.2-5 alkanoylamino groups, a carboxyl group which may be esterified with a C.sub.1-4 alkyl or alkenyl group, carboxyalkyl groups which may be esterified with a C.sub.1-4 alkyl or alkenyl group, carboxyalkyloxy groups which may be esterified with a C.sub.1-4 alkyl or alkenyl group, N-alkylpiperazinylcarbonyl groups, N-alkylpiperazinylcarbonylalkyl groups, N-alkylpiperazinylcarbonylalkyloxy groups, and a morpholinocarbonyl group; X denotes a sulfonyl or carbonyl group; and Y stands for an oxygen or sulfur atom, a chymase inhibitor comprising the same as an active ingredient, and a medicine comprising the same as an active ingredient, typified by a prophylactic and therapeutic agent for a disease of the heart or circulatory system, which is caused by the abnormal acceleration of production of angiotensin II.

  该发明涉及一种由以下一般式（1）表示的咪唑啉衍生物：##STR1##其中A和B分别表示芳香烃基，该基可能被1-3个卤原子、C.sub.1-4烷基、C.sub.1-4烷氧基、C.sub.1-4烷二氧基、苯氧基、硝基、氰基、苯基、C.sub.2-5烷酰氨基、可能与C.sub.1-4烷基或烯基酯化的羧基、可能与C.sub.1-4烷基或烯基酯化的羧基烷基、可能与C.sub.1-4烷基或烯基酯化的羧基烷氧基、N-烷基哌嗪甲酰基、N-烷基哌嗪甲酰基烷基、N-烷基哌嗪甲酰基烷氧基和吗啉甲酰基；X表示磺酰基或羰基；Y代表氧原子或硫原子，包括作为活性成分的Ⅰ型肽酶抑制剂、以及作为活性成分的药物，其为一种心脏或循环系统疾病的预防和治疗剂，该疾病是由于抑制Ⅱ型肽酶的异常加速产生而引起的。
• PREVENTIVES OR REMEDIES FOR EYE CIRCULATORY FAILURE
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1112749A2

  公开（公告）日：2001-07-04

  The conventional pharmaootherapy for diseases caused by a disturbance of ocular circulation, inclusive of glaucoma, comprises oral administration of steroids and other drugs and/or topical administration of β -adrenergic antagonists but these therapeutic regimens are invariably not effective enough but rather entail adverse reactions characteristic of the respective drugs used. This invention is characterized in that a chymase inhibitor is used for the prevention or treatment of diseases caused by a disturbance of ocular circulation and enables positive prophylaxis or therapy with reduced risks for side effects.

  传统的药物疗法用于治疗眼循环障碍引起的疾病，包括青光眼，包括口服类固醇和其他药物和/或局部使用β-肾上腺素能拮抗剂，但这些治疗方案总是不够有效，反而会引起所用药物特有的不良反应。 本发明的特点在于，糜蛋白酶抑制剂可用于预防或治疗由眼部循环障碍引起的疾病，并能在降低副作用风险的同时进行积极的预防或治疗。
• TENSION-RELIEVING AGENTS FOR CILIARY MUSCLE
  申请人：Senju Pharmaceutical Co., Ltd.

  公开号：EP1224945A1

  公开（公告）日：2002-07-24

  Use of a chymase inhibitor in preventing and treating nearsightedness caused by the continuous tension of ciliary muscles makes it possible to achieve exact preventive and therapeutic effects with little side effects.

  使用糜蛋白酶抑制剂来预防和治疗因睫状肌持续紧张而引起的近视，可以达到确切的预防和治疗效果，而且副作用很小。
• Prophylactic or threapeutic composition for ocular circulation disorders
  申请人：——

  公开号：US20040086537A1

  公开（公告）日：2004-05-06

  The conventional pharmacotherapy for diseases caused by a disturbance of ocular circulation, inclusive of glaucoma, comprises oral administration of steroids and other drugs and/or topical administration of &bgr;-adrenergic antagonists but these therapeutic regimens are invariably not effective enough but rather entail adverse reactions characteristic of the respective drugs used. This invention is characterized in that a chymase inhibitor is used for the prevention or treatment of diseases caused by a disturbance of ocular circulation and enables positive prophylaxis or therapy with reduced risks for side effects.

  对眼部循环障碍引起的疾病（包括青光眼）的传统药物治疗包括口服类固醇和其他药物和/或局部使用肾上腺素能拮抗剂，但这些治疗方案总是不够有效，反而会引起所用药物特有的不良反应。 本发明的特点在于，糜蛋白酶抑制剂可用于预防或治疗由眼部循环障碍引起的疾病，并能在降低副作用风险的情况下进行积极的预防或治疗。
• IMIDAZOLIDINE DERIVATIVE AND USE THEREOF
  申请人：SUNTORY LIMITED

  公开号：EP0721944B1

  公开（公告）日：2001-01-17