1-phenyl-N-(3,4,5-trimethoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine | 700809-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-phenyl-N-(3,4,5-trimethoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine
• 英文别名: 1-phenyl-3-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazole-3,5-diamine
• CAS: 700809-26-3
• 化学式: C₁₇H₁₉N₅O₃
• 分子量: 341.37
• InChiKey: JDDJYABYQSKLRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯胺 以 异丙醇 为溶剂， 生成 1-phenyl-N-(3,4,5-trimethoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Novel Dual Fms-Like Tyrosine Kinase 3/Stem Cell Factor Receptor (FLT3/c-KIT) Inhibitor for the Treatment of Acute Myelogenous Leukemia

  摘要：

  A high-throughput screen of our compound archive revealed a novel class of dual FMS-like tyrosine kinase 3 (FLT3)/c-KIT inhibitors. With the help of molecular modeling, this class was rapidly optimized for both potency against FLT3 and FLT3/c-KIT and excellent potency in cell-based assays, leading to dose-dependent cell death in acute myelogenous leukemia (AML) patient blast samples. Ultimately, the AML patient blast data defined the preferred target profile as we designed and evaluated a set of FLT3 selective and FLT3/c-KIT dual molecules. Further optimization for pharmacokinetic properties resulted in the selection of the dual FLT3/c-KIT inhibitor, N-3-(4-(trans-4-morpholinocyclohexyl)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5-diamine, VX-322 (compound 37), to move forward to preclinical evaluation.

  DOI：

  10.1021/jm200712h

文献信息

• Chemical compounds
  申请人：Ratcliffe James Andrew

  公开号：US20050009831A1

  公开（公告）日：2005-01-13

  The present invention concerns compounds of general formula (I): in which: R 1 represents hydrogen, R 4 , —C(═Y)—NHR 4 , —SO 2 NHR 4 , —C(=Z 1 )—R 4 , —SO 2 —R 4 or —C(=Z 1 )—OR 4 ; R 2 represents hydrogen, cyano, halogen or —C≡C—R 5 ; R 3 represents hydrogen, acyl, alkoxycarbonyl, alkyl, aroyl, aryl, aryloxycarbonyl, carboxy, cycloalkenyl, cycloalkyl, heteroaroyl, heteroaryl, heterocycloalkyl or —C(═O)—NY 1 Y 2 ; R 4 represents optionally substituted alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl or heteroaryl R 5 represents hydrogen or alkyl; R 6 represents alkyl, acyl, alkoxycarbonyl, alkylsulfonyl, aryl, arylsulfonyl, aroyl, cycloalkyl, cycloalkenyl, heteroaryl, heteroarylsulfonyl, heteroaroyl and heterocycloalkyl; R 7 represents optionally substituted alkyl, cycloalkyl or cycloalkylalkyl, R 8 represents hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; R 9 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; R 10 represents hydrogen or lower alkyl; R 11 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; or alkyl optionally substituted by —NY 1 Y 2 ; R 12 represents aryl or heteroaryl; or alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl or heterocycloalkylalkyl each optionally substituted Y represents O, S or NCN; Y 1 and Y 2 (Y 3 and Y 4 ) are independently in particular hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocycloalkyl; or the group —NY 1 Y 2 may form 5-7 membered ring or the group —NY 3 Y 4 (—NY 5 Y 6 ) may form a cyclic amine; Z (Z 1 ) represents O or S; Z 2 represents O or S(O) p ; n is zero or an integer 1 or 2; m is 1 or 2; p is 1 or 2; and their corresponding N-oxides, their prodrugs; their pharmaceutically acceptable salts and solvates (e.g. hydrates), also together with one or more pharmaceutically acceptable carriers or excipients, such novel indolizines derivatives with inhibitory effects towards kinase proteins and especially for use for preventing or treating diseases that may be modulated by the inhibition of such kinase proteins and particularly solid tumours.

  本发明涉及通式（I）的化合物： 其中： R1代表氢，R4，—C（═Y）—NHR4，—SO2NHR4，—C（=Z1）—R4，—SO2—R4或—C（=Z1）—OR4； R2代表氢，氰基，卤素或—C≡C—R5； R3代表氢，酰基，烷氧羰基，烷基，芳酰基，芳基，芳氧羰基，羧基，环烯基，环烷基，杂芳酰基，杂芳基，杂环烷基或—C（═O）—NY1Y2； R4代表可选取代的烷基，环烷基，环烯基，杂环烷基，芳基或杂芳基； R5代表氢或烷基； R6代表烷基，酰基，烷氧羰基，烷基磺酰基，芳基，芳基磺酰基，芳酰基，环烷基，环烯基，杂芳基，杂芳基磺酰基，杂芳酰基和杂环烷基； R7代表可选取代的烷基，环烷基或环烷基烷基； R8代表氢，烷基，烯基，芳基，芳基烷基，杂芳基或杂芳基烷基； R9代表烷基，芳基，芳基烷基，环烷基，环烷基烷基，杂芳基，杂芳基烷基，杂环烷基或杂环烷基烷基； R10代表氢或较低的烷基； R11代表烷基，芳基，芳基烷基，环烷基，环烷基烷基，杂芳基，杂芳基烷基，杂环烷基或杂环烷基烷基；或可选取代的烷基，被—NY1Y2取代； R12代表芳基或杂芳基；或可选取代的烷基，环烷基，环烷基烷基，杂环烷基或杂环烷基烷基； Y代表O，S或NCN； Y1和Y2（Y3和Y4）特别是独立的氢，烷基，芳基，环烷基，环烯基，杂芳基或杂环烷基；或该基团—NY1Y2可能形成5-7成员环或该基团—NY3Y4（—NY5Y6）可能形成一个环状胺； Z（Z1）代表O或S； Z2代表O或S（O）p； n为零或整数1或2； m为1或2； p为1或2； 以及它们对应的N-氧化物，它们的前药；它们的药物可接受的盐和溶剂化合物（例如水合物），还包括一个或多个药物可接受的载体或赋形剂，这种新的吲哚嗪衍生物具有对激酶蛋白的抑制作用，特别是用于预防或治疗可能通过抑制这种激酶蛋白而调节的疾病，特别是固体肿瘤。
• JNK INHIBITORS
  申请人：Nemecek Conception

  公开号：US20070238734A1

  公开（公告）日：2007-10-11

  The present invention concerns compounds of general formula (I): in which the substituents are as described herein.

  本发明涉及一般式（I）的化合物： 其中取代基如本文所述。
• DIAMINOTRIAZOLES USEFUL AS INHIBITORS OF PROTEIN KINASES
  申请人：Pierce C. Albert

  公开号：US20080014189A1

  公开（公告）日：2008-01-17

  The present invention relates to inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及蛋白激酶抑制剂。该发明还提供了包含本发明化合物的药物组合物以及使用该组合物治疗各种疾病的方法。
• INDOLIZINES AS KINASE PROTEIN INHIBITORS
  申请人：Aventis Pharma S.A.

  公开号：EP1436291B1

  公开（公告）日：2009-01-14
• US7148215B2
  申请人：——

  公开号：US7148215B2

  公开（公告）日：2006-12-12