2H-1-Benzopyran-4-acetamide, 7-amino-2-oxo- | 296236-23-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2H-1-Benzopyran-4-acetamide, 7-amino-2-oxo-
• 英文别名: 2-(7-amino-2-oxochromen-4-yl)acetamide
• CAS: 296236-23-2
• 化学式: C₁₁H₁₀N₂O₃
• 分子量: 218.21
• InChiKey: NTQCWVJNMKBKFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  95.4
• 氢给体数：
  2
• 氢受体数：
  4

文献信息

• [EN] SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS<br/>[FR] HYDANTOÏNAMIDES SUBSTITUÉS UTILISÉS EN TANT QU'ANTAGONISTES D'ADAMTS7
  申请人：BAYER AG

  公开号：WO2021094436A1

  公开（公告）日：2021-05-20

  The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, heteroaryl or phenyl; R2 is hydrogen, cyano, halogen, alkylsulfonyl, alkyl, cycloalkyl or alkoxy; R3, R4, R5, R6, R7 and R8 are independently hydrogen, halogen, alkyl or alkoxy; most groups being optionally substituted; with the proviso that at least one of R2, R3, R4 is H; X1, X2, X3, X4, X5 and X6 are independently N or C; with the proviso that in each ring maximal one X is N.

  本申请涉及式(I)所示的取代脒酰胺作为ADAMTS7拮抗剂，涉及它们的制备过程，以及它们单独或组合用于治疗或预防疾病，特别是心血管疾病，包括动脉粥样硬化、冠心病(CAD)、外周血管病(PAD)、动脉闭塞性疾病或血管成形术后的再狭窄。R1是氢、烷基、环烷基、杂环烷基、杂芳基或苯基；R2是氢、氰基、卤素、烷基亚磺酰基、烷基、环烷基或烷氧基；R3、R4、R5、R6、R7和R8独立的是氢、卤素、烷基或烷氧基；大多数基团可被选择性地取代；条件是至少R2、R3、R4中的一个为H；X1、X2、X3、X4、X5和X6独立的是N或C；条件是每个环中最多只有一个X是N。
• [EN] SUBSTITUTED HYDANTOINAMIDES AS ADAMTS7 ANTAGONISTS<br/>[FR] HYDANTOINAMIDES SUBSTITUÉS EN TANT QU'ANTAGONISTES D'ADAMTS7
  申请人：BAYER AG

  公开号：WO2021094434A1

  公开（公告）日：2021-05-20

  The application relates to substituted hydantoinamides of formula (I) as ADAMTS7 antagonists, to processes for their preparation, their use alone or in combination for the treatment or prophylaxis of diseases, in particular of cardiovascular diseases, including atherosclerosis, coronary artery disease (CAD), peripheral vascular disease (PAD), arterial occlusive disease or restenosis after angioplasty. R1 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, 5- to 6-membered heteroaryl or phenyl; R2 is hydrogen or alkyl; A is 5-membered heteroaryl; Z is 6- to 10-membered aryl or 5- to 10-membered heteroaryl; all groups being optionally substituted.

  该申请涉及公式（I）的替代咪唑酰脲作为ADAMTS7拮抗剂，以及它们的制备方法，它们单独或与其他药物联合用于治疗或预防疾病，特别是心血管疾病，包括动脉粥样硬化、冠状动脉疾病（CAD）、外周血管疾病（PAD）、动脉闭塞病或血管成形术后再狭窄。R1为氢、烷基、环烷基、杂环烷基、5-至6-成员杂芳基或苯基；R2为氢或烷基；A为5-成员杂芳基；Z为6-至10-成员芳基或5-至10-成员杂芳基；所有基团均可选择性地被取代。
• Profiling of protease specificity using combinatorial fluorogenic substrate libraries
  申请人：——

  公开号：US20020022243A1

  公开（公告）日：2002-02-21

  A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques. The approximately 3-fold increased quantum yield of ACC over AMC permits reduction in enzyme and substrate concentrations. As a consequence, a greater number of substrates can be tolerated in a single assay, thus enabling an increase in the diversity space of the library. Soluble positional protease substrate libraries of 137,180 and 6,859 members, possessing amino acid diversity at the P4-P3-P2-P1 and P4-P3-P2 positions, respectively, were constructed. Employing this screening method the substrate specificities of a diverse array of proteases were profiled, including the serine proteases thrombin, plasmin, factor Xa, uPA, tPA, granzyme B, trypsin, chymotrypsin, human neutrophil elastase, and the cysteine proteases papain and cruzain. The resulting profiles create a pharmacophoric portrayal of the proteases allowing for the design of selective substrates and potent inhibitors.

  本文介绍了一种制备和使用荧光肽底物的方法，可以配置通用底物库，快速确定酶（如蛋白酶）的主要和扩展特异性。底物含有荧光离开基，如7-氨基-4-羧甲基香豆素（ACC）。含有ACC离开基的底物显示出与传统使用的7-氨基-4-甲基香豆素（AMC）离开基相似的动力学特性。ACC的双功能性允许使用固相合成技术高效地生产单个底物和底物库。 ACC比AMC的量子产率约高3倍，可以减少酶和底物浓度。因此，单个试验中可以容纳更多的底物，从而增加库的多样性空间。构建了137,180和6,859个可溶性定位蛋白酶底物库，分别在P4-P3-P2-P1和P4-P3-P2位置具有氨基酸多样性。利用这种筛选方法，对多种蛋白酶的底物特异性进行了分析，包括丝氨酸蛋白酶凝血酶、纤溶酶、Xa因子、uPA、tPA、颗粒酶B、胰蛋白酶、胰凝乳蛋白酶、人类中性粒细胞弹性蛋白酶和半胱氨酸蛋白酶木瓜蛋白酶和克鲁赛因。所得到的特异性分析结果描绘了蛋白酶的药效学特征，可以设计选择性底物和有效的抑制剂。
• CONTROLLED DRUG RELEASE FROM DENDRIMERS
  申请人：Ashley Gary

  公开号：US20130123461A1

  公开（公告）日：2013-05-16

  The invention relates to compositions that comprise dendrimers useful in medical and veterinary applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the dendrimer through a linkage that releases the drug or a prodrug through controlled beta elimination.

  本发明涉及一种包含树状分子的组合物，该组合物在医疗和兽医应用中有用，能够提供药物的控制释放，例如肽，核酸和小分子。药物通过一个连接与树状分子共价耦合，该连接通过控制的β消除释放药物或前药。
• Methods and kits to detect Hereditary angioedema type III
  申请人：Dewald, Georg

  公开号：EP1598428A1

  公开（公告）日：2005-11-23

  The present invention relates to a method of diagnosing hereditary angioedema type III (HAE III) or a predisposition thereto in a subject being suspected of having developed or of having a predisposition to develop a hereditary angioedema type III or in a subject being suspected of being a carrier for hereditary angioedema type III, the method comprising determining in vitro from a biological sample of said subject the presence or absence of a disease-associated mutation in a nucleic acid molecule regulating the expression of or encoding coagulation factor XII; wherein the presence of such a mutation is indicative of a hereditary angioedema type III or a predisposition thereto. The present invention also relates to a method of diagnosing hereditary angioedema type III (HAE III) or a predisposition thereto in a subject being suspected of having developed or of having a predisposition to develop a hereditary angioedema type III or in a subject being suspected of being a carrier for hereditary angioedema type III, the method comprising assessing the presence, amount and/or activity of coagulation factor XII in said subject and including the steps of: (a) determining from a biological sample of said subject in vitro, the presence, amount and /or activity of: (i) a (poly)peptide encoded by the coagulation factor XII gene; (ii) a substrate of the (poly)peptide of (i); or (iii) a (poly)peptide processed by the substrate mentioned in (ii); (b) comparing said presence, amount and/or activity with that determined from a reference sample; and (c) diagnosing, based on the difference between the samples compared in step (b), the pathological condition of a hereditary angioedema type III or a predisposition thereto. The present invention also relates to a method of identifying a compound modulating coagulation factor XII activity which is suitable as a medicament or a lead compound for a medicament for the treatment and/or prevention of hereditary angioedema type III, the method comprising the steps of: (a) in vitro contacting a coagulation factor XII (poly)peptide or a functionally related (poly)peptide with the potential modulator; and (b) testing for modulation of coagulation factor XII activity, wherein modulation of coagulation factor XII activity is indicative of a compound's suitability as a medicament for the treatment and/or prevention of hereditary angioedema type III. Furthermore, the present invention relates to gene therapy methods and to a kit for diagnosing hereditary angioedema type III.

  本发明涉及一种诊断遗传性血管性水肿 III 型（HAE III）或其易感性的方法，该受试者疑似已患或有患遗传性血管性水肿 III 型的易感性，或受试者疑似遗传性血管性水肿 III 型的携带者、该方法包括从所述受试者的生物样本中体外测定调节凝血因子 XII 表达或编码凝血因子 XII 的核酸分子中是否存在与疾病相关的突变；其中，这种突变的存在表明存在遗传性血管性水肿 III 型或其易感性。本发明还涉及一种诊断遗传性血管性水肿 III 型（HAE III）或遗传性血管性水肿 III 型易感性的方法，该方法用于诊断疑似患遗传性血管性水肿 III 型或有患遗传性血管性水肿 III 型易感性的受试者或疑似遗传性血管性水肿 III 型携带者，该方法包括评估所述受试者体内凝血因子 XII 的存在、数量和/或活性，并包括以下步骤：(a) 从所述受试者的体外生物样本中确定以下物质的存在、数量和/或活性：(i)由凝血因子 XII 基因编码的（多）肽；(ii)(i)的（多）肽的底物；或(iii)由(ii)中提及的底物加工的（多）肽；(b)将所述存在、量和/或活性与从参考样本中确定的存在、量和/或活性进行比较；以及(c)根据步骤(b)中比较的样本之间的差异，诊断遗传性血管性水肿 III 型的病理状况或其易患性。本发明还涉及一种鉴定调节凝血因子 XII 活性的化合物的方法，该化合物适合作为治疗和/或预防遗传性血管性水肿 III 型的药物或药物的先导化合物，该方法包括以下步骤：(a) 在体外将凝血因子 XII（多）肽或功能相关的（多）肽与潜在的调节剂接触；以及 (b) 测试凝血因子 XII 活性的调节，其中凝血因子 XII 活性的调节表明化合物适合作为治疗和/或预防遗传性血管性水肿 III 型的药物。此外，本发明还涉及基因治疗方法和诊断遗传性血管性水肿 III 型的试剂盒。