(6-氨基甲基-1H-吲唑-3-基)胺 | 368426-75-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: (6-氨基甲基-1H-吲唑-3-基)胺
• 中文别名: (6-氨甲基-1H-吲唑-3-基)胺
• 英文名称: 6-(aminomethyl)-1H-indazol-3-amine
• 英文别名: 6-aminomethyl-1H-indazol-3-ylamine
• CAS: 368426-75-9
• 化学式: C₈H₁₀N₄
• 分子量: 162.194
• InChiKey: WVCSMKWWSLUJBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6-氨基甲基-1H-吲唑-3-基)胺 在 三异丙基硅烷 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 6-氯-1-羟基苯并三氮唑 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 2.0h， 生成
  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
• 作为产物：
  描述：

  2-氟对苯二腈 在 一水合肼 、 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 正丁醇 、 四氢呋喃 为溶剂， 反应 24.0h， 以0.58 g的产率得到(6-氨基甲基-1H-吲唑-3-基)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

• 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。
• N-(4-CARBAMIMIDOYL-BENZYL)-2-ALKOXY-2-HETEROCYCLYL ACETAMIDES AS INHIBITORS OF THE FORMATION OF COAGULATION FACTORS XA, IXA AND THROMBIN INDUCED BY FACTOR VIIA
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1706396A1

  公开（公告）日：2006-10-04
• US7056932B2
  申请人：——

  公开号：US7056932B2

  公开（公告）日：2006-06-06
• US7265220B2
  申请人：——

  公开号：US7265220B2

  公开（公告）日：2007-09-04