3-氨基-1,2-苯并异恶唑-6-甲胺 | 368426-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 中文名称: 3-氨基-1,2-苯并异恶唑-6-甲胺
• 中文别名: 3-氨基-1,2-苯异噁唑-6-甲胺
• 英文名称: 6-(aminomethyl)benzo[d]isoxazol-3-amine
• 英文别名: 3-Amino-1,2-benzisoxazole-6-methanamine；6-(aminomethyl)-1,2-benzoxazol-3-amine
• CAS: 368426-78-2
• 化学式: C₈H₉N₃O
• mdl: MFCD09907913
• 分子量: 163.179
• InChiKey: GHYKJSGZYRADNG-UHFFFAOYSA-N

物化性质

• 沸点：
  388.3±27.0 °C(Predicted)
• 密度：
  1.339±0.06 g/cm3(Predicted)
• 溶解度：
  甲醇（少量溶解）、水（少量溶解）

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-1,2-苯并异恶唑-6-甲胺 在 palladium on activated charcoal 盐酸 、 PS-DCC 、 氢气 、 1-羟基苯并三唑 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-[6-(3-aminophenyl)-5-chloro-3-(cyclobutylamino)-2-oxo-1,2-dihydropyrazin-1-yl]-N-[(4-carbamimidoyl-3-hydroxyphenyl)methyl]acetamide
  参考文献：
  名称：

  含新型P1针作为TF / VIIa抑制剂的吡嗪酮的设计，合成和生物学评估。

  摘要：

  本文描述了一系列取代的吡嗪酮作为TF / VIIa复合物抑制剂的设计，合成和酶促活性。设计这些抑制剂以探索先前描述的P1 idine的置换和变异[J. 中 Chem.2003，46，4050]。根据与母体苯基am（pKa约为12）相比降低的碱性，选择P1针头替代品。影响化合物口服生物利用度的一个因素是该化合物在肠道中的电离状态。该研究的理想结果是确定一种口服生物利用的TF-VIIa抑制剂。

  DOI：

  10.1016/j.bmcl.2007.05.090
• 作为产物：
  描述：

  2-氟对苯二腈 在 乙酰氧肟酸 、 potassium carbonate 、 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 水 、 N,N-二甲基甲酰胺 、 四氢呋喃 为溶剂， 反应 20.0h， 以73%的产率得到3-氨基-1,2-苯并异恶唑-6-甲胺
  参考文献：
  名称：

  Improving the Selectivity of PACE4 Inhibitors through Modifications of the P1 Residue

  摘要：

  Paired basic amino acid cleaving enzyme 4 (PACE4), a serine endoprotease of the proprotein convertases family, has been recognized as a promising target for prostate cancer. We previously reported a selective and potent peptide based inhibitor for PACE4, named the multi-Leu peptide (Ac-LLLLRVKR-NH2 sequence), which was then modified into a more potent and stable compound named C23 with the following structure: Ac-DLeu-LLLRVK-Amba (Amba: 4-amidinobenzylamide). Despite improvements in both in vitro and in vivo profiles of C23, its selectivity for PACE4 over furin was significantly reduced. We examined other Argmimetics instead of Amba to regain the lost selectivity. Our results indicated that the replacement of Amba with 5-(aminomethyl)picolinimidamide increased affinity for PACE4 and restored selectivity. Our results also provide a better insight on how structural differences between 51 pockets of PACE4 and furin could be employed in the rational design of selective inhibitors.

  DOI：

  10.1021/acs.jmedchem.8b01381

文献信息

• Substituted phenyl acetamides and their use as protease inhibitors
  申请人：——

  公开号：US20040254166A1

  公开（公告）日：2004-12-16

  Phenyl acetamide compounds are described, including compounds of Formula I: 1 or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R 3 -R 6 , R 11 , B, Y and W are set forth in the specification. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as thrombin and factor Xa. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi.

  苯乙酰胺化合物的描述，包括式I的化合物： 或其溶剂化合物、水合物或药用可接受盐；其中R 3 -R 6 ，R 11 ，B，Y和W在说明书中列出。本发明的化合物是蛋白酶的强效抑制剂，特别是胰蛋白酶样丝氨酸蛋白酶，如凝血酶和Xa因子。描述了用于抑制血小板丢失、抑制血小板聚集物形成、抑制纤维蛋白形成、抑制血栓形成和抑制栓塞形成的组合物。本发明化合物的其他用途是作为抗凝剂，嵌入或物理连接到用于制造用于血液采集、血液循环和血液储存的设备中的材料中，如导管、血液透析机、血液采集器和管、血管和支架。此外，这些化合物可以被检测标记并用于体内血栓的成像。
• Heterocyclyl substituted 1-alkoxy acetic acid amides
  申请人：Gobbi Claudio Luca

  公开号：US20050137168A1

  公开（公告）日：2005-06-23

  The invention is concerned with novel heterocyclyl substituted 1-alkoxy acetic acid derivatives of formula (I) wherein R 1 to R 6 and A are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the formation of coagulation factors Xa, IXa and thrombin induced by factor VIIa and tissue factor and can be used as medicaments.

  这项发明涉及一种新颖的杂环烷基取代的1-烷氧基乙酸衍生物，其化学式为（I），其中R1至R6和A的定义如描述和索赔中所述，以及其生理上可接受的盐。这些化合物抑制由VIIa因子和组织因子诱导的凝血因子Xa、IXa和凝血酶的形成，并可用作药物。
• Novel amino acid derivatives, method for production thereof and pharmaceutical compositions comprising said derivative
  申请人：De Nanteuil Guillaume

  公开号：US20050085517A1

  公开（公告）日：2005-04-21

  Compound of formula (I): wherein: R 1 represents aryl, heteroaryl or alkyl which is optionally substituted, or a group of formula —(CO)—CR 6 R 7 NR 8 R 9 wherein R 6 , R 7 , R 8 and R 9 are as defined in the description, R 2 represents hydrogen or alkyl, R 3 represents hydrogen or optionally substituted alkyl, R 4 represents a saturated or unsaturated, 7- to 15-membered bicyclic system or optionally substituted alkyl, or R 3 and R 4 , together with the carbon atom carrying them, form a saturated or unsaturated, 3- to 18-membered, mono-, bi- or tri-cyclic system optionally containing one or more hetero atoms selected from O, S and N and optionally substituted, n represents zero, 1 or 2, Ar represents aryl or heteroaryl, R 5 represents amino, guanidino, cyano or amidino which is optionally substituted, its optical isomers, and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in pathological conditions involving activated protein C.

  化合物的分子式（I）如下所示：其中：R1代表芳基、杂环芳基或烷基，可以选择性地被取代，或者是下述分子式的基团—(CO)—CR6R7NR8R9，其中R6、R7、R8和R9如描述中定义，R2代表氢或烷基，R3代表氢或可选择性取代的烷基，R4代表饱和或不饱和的7至15环双环系统或可选择性取代的烷基，或者R3和R4与携带它们的碳原子一起形成饱和或不饱和的3至18环的单环、双环或三环系统，该系统可以选择性地含有一个或多个来自O、S和N的杂原子，并且可以被取代，n代表零、1或2，Ar代表芳基或杂环芳基，R5代表氨基、胍基、氰基或酰胺基，可以选择性地被取代，其光学异构体，以及与药学上可接受的酸形成的相应的盐。含有这些化合物的药物制剂在涉及活化蛋白C的病理状况中是有用的。
• Thrombin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06376499B1

  公开（公告）日：2002-04-23

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is N Y1 or O; c is CY2 or N; d is CY2; e is CY1 or N; f is CY1 or N; g is CY1 or N; Y1 is hydrogen, C1-4 alkyl, or halogen; Y2 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, halogen, NH2, OH or C1-4 alkoxy; A is  and W, X, Z, R3, R4 and R5 are defined in the specification.

  本发明的化合物在抑制凝血酶和相关的血栓闭塞方面具有以下结构：或其药用盐，其中b为N、Y1或O；c为CY2或N；d为CY2；e为CY1或N；f为CY1或N；g为CY1或N；Y1为氢、C1-4烷基或卤素；Y2为氢、C1-4烷基、C3-7环烷基、卤素、NH2、OH或C1-4烷氧基；A为，W、X、Z、R3、R4和R5在说明书中有定义。
• [EN] FACTOR XIIa INHIBITORS<br/>[FR] INHIBITEURS DU FACTEUR XIIA
  申请人：UNIV LEEDS INNOVATIONS LTD

  公开号：WO2019211585A1

  公开（公告）日：2019-11-07

  This invention relates to compounds of formula (I). The compounds of formula (I) are modulators of Factor XII, specifically Factor XIIa. The compounds are inhibitors of Factor XIIa and may be useful as anticoagulants. The compounds of formula (I) may be used in methods of treatment (or prevention) of blood disorders related to bleeding or coagulation.

  本发明涉及式(I)的化合物。式(I)的化合物是凝血因子XII的调节剂，具体来说是凝血因子XIIa的调节剂。这些化合物是凝血因子XIIa的抑制剂，可能作为抗凝剂有用。式(I)的化合物可以用于治疗（或预防）与出血或凝血相关的血液疾病的方法中。