(2S)-2-amino-N-[4-[2-[2-[4-(2-cyanoethylamino)-1,2,5-oxadiazol-3-yl]benzimidazol-1-yl]acetyl]phenyl]propanamide | 1263384-28-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S)-2-amino-N-[4-[2-[2-[4-(2-cyanoethylamino)-1,2,5-oxadiazol-3-yl]benzimidazol-1-yl]acetyl]phenyl]propanamide
• CAS: 1263384-28-6
• 化学式: C₂₃H₂₂N₈O₃
• 分子量: 458.479
• InChiKey: HDLJXKGGVVDZFI-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  165
• 氢给体数：
  3
• 氢受体数：
  9

文献信息

• USE OF PHOSPHO-AKT AS A BIOMARKER OF DRUG RESPONSE
  申请人：Lane Heidi Alexandra

  公开号：US20140080872A1

  公开（公告）日：2014-03-20

  Use of phospho-Akt as a biomarker for predicting the response, such as resistance, to a compound, wherein phospho-Akt is Akt that has been phosphorylated on one or more residues, with the proviso that for Akt1, Akt2, and Akt3 the designation phospho-Akt is used to indicate phosphorylation at a site other than T308, T309 or T305 respectively, wherein the compound is a compound of general formula (I) wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R 1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R 2 , R 3 and R 6 represent hydrogen; R 4 and R 5 , independently of each other, represent hydrogen, lower alkyi or lower alkoxy; or R 4 and R 5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyi, halo-lower alkyi, hydroxy-lower alkyi, lower alkoxy-lower alkyi, acyloxy-lower alkyi, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R′ represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R 2 , R 3 and R 6 represent hydrogen; R 4 and R 5 , independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R 4 and R 5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.

  将磷酸化Akt作为一种生物标记物来预测对某化合物的反应，例如耐药性，其中磷酸化Akt是在一个或多个残基上磷酸化的Akt，条件是对于Akt1、Akt2和Akt3，磷酸化Akt的指定用于表示在T308、T309或T305之外的位置磷酸化，在此化合物是一般式(I)的化合物，其中R代表苯基、噻吩基或吡啶基，其中苯基可以选择性地被来自烷基、卤代较低烷基、羟基较低烷基、较低烷氧基较低烷基、酰氧较低烷基、苯基、羟基、较低烷氧基、羟基较低烷氧基、较低烷氧基较低烷氧基、苯基较低烷氧基、较低烷基羰基氧基、氨基、单烷基氨基、二烷基氨基、较低烷氧羰基氨基、较低烷基羰基氨基、取代氨基的一个或两个取代基，其中氮上的两个取代基与氮一起形成杂环烷基、较低烷基羰基、羧基、较低烷氧羰基、氰基、卤素和硝基；其中两个相邻的取代基是亚甲氧基；吡啶基可以选择性地被较低烷氧基、氨基或卤素取代；X代表基团C═Y，其中Y代表氧或氮，被羟基或较低烷氧基取代；R1代表氢、较低烷基羰基、羟基较低烷基或氰基较低烷基；R2、R3和R6代表氢；R4和R5，彼此独立地，代表氢、较低烷基或较低烷氧基；或R4和R5一起代表亚甲亚氧基；及其药用可接受的衍生物；或其中R代表苯基或吡啶基，其中苯基可以选择性地被来自烷基、卤代较低烷基、羟基较低烷基、较低烷氧基较低烷基、酰氧较低烷基、苯基、羟基、较低烷氧基、羟基较低烷氧基、较低烷氧基较低烷氧基、苯基较低烷氧基、较低烷基羰基氧基、氨基、单烷基氨基、二烷基氨基、较低烷氧羰基氨基、较低烷基羰基氨基、取代氨基的一个或两个取代基，其中氮上的两个取代基与氮一起形成杂环烷基、较低烷基羰基、羧基、较低烷氧羰基、甲酰基、氰基、卤素和硝基；其中两个相邻的取代基是亚甲亚氧基；吡啶基可以选择性地被较低烷氧基、氨基或卤素取代；X代表氧；R′代表氢、较低烷基羰基、羟基较低烷基或氰基较低烷基；R2、R3和R6代表氢；R4和R5，彼此独立地，代表氢、较低烷基或较低烷氧基；或R4和R5一起代表亚甲亚氧基；及其药用可接受的衍生物。还公开了使用这些化合物治疗肿瘤和自身免疫疾病的方法。
• FURAZANOBENZIMIDAZOLES AS PRODRUGS TO TREAT NEOPLASTIC OR AUTOIMMUNE DISEASES
  申请人：Pohlmann Jens

  公开号：US20120264792A1

  公开（公告）日：2012-10-18

  A compound of formula (II) wherein represents a divalent benzene residue which is unsubstituted or substituted by one or two additional substituents independently selected from lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, mono(lower alkyl)amino, di(lower alkyl)amino, mono(lower alkenyl)amino, di(lower alkenyl)amino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; or wherein two adjacent substituents can be methylenedioxy; or a divalent pyridine residue (Z=N) which is unsubstituted or substituted additionally by lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, amino, optionally substituted by one or two substituents selected from lower alkyl, lower alkenyl and alkylcarbonyl, halo-lower alkyl, lower alkoxy-lower alkyl, or halogen; R 1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; and R 2 represents a group selected from: or pharmaceutically acceptable salts thereof.

  化合物的式子为(II)，其中： - R表示一个双价苯基，该苯基未取代或取代一个或两个附加基团，这些基团独立地从以下基团中选择：低碳基、卤代低碳基、羟基-低碳基、低烷氧基-低碳基、酰氧基-低碳基、苯基、羟基、低烷氧基、羟基-低烷氧基、低烷氧基-低烷氧基、苯基-低烷氧基、低碳基羰基氧基、氨基、单(低碳基)氨基、二(低碳基)氨基、单(低烯基)氨基、二(低烯基)氨基、低烷氧基羰基氨基、低碳基羰基氨基、取代氨基，其中氮上的两个取代基与氮形成杂环基、低碳基羰基、羧基、低烷氧基羰基、氰基、卤素和硝基；或其中两个相邻的取代基可以是亚甲二氧基；或一个双价吡啶基(Z=N)，该基未取代或另外取代一个或多个低碳基、低烷氧基、低烷氧基-低烷氧基、氨基，可选地取代一个或两个从低碳基、低烯基和烷基羰基中选择的取代基，卤代低碳基、低烷氧基-低碳基或卤素； - R1表示氢、低碳基羰基、羟基-低碳基或氰基-低碳基； - R2表示从以下基团中选择的一个基团： 或其药学上可接受的盐。
• Use of BUBR1 as a biomarker of drug response to furazanobenzimidazoles
  申请人：Lane Heidi Alexandra

  公开号：US10222377B2

  公开（公告）日：2019-03-05

  Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a furazanobenzimidazole compound of general formula (I).

  使用 BUBR1 作为生物标记物，预测受试者对化合物的反应，最好是对癌症等疾病的抗性，其中化合物是通式（I）的呋喃苯并咪唑化合物。
• Use of glu-tubulin as a biomarker of drug response to furazanobenzimidazoles
  申请人：Basilea Pharmaceutica AG

  公开号：US10656162B2

  公开（公告）日：2020-05-19

  Use of glu-tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).

  使用谷粒-微管蛋白作为生物标志物，预测受试者对化合物的反应，最好是对癌症等疾病的抗药性，其中所述化合物是通式（I）的呋喃苯并咪唑化合物。
• Use of phospho-Akt as a biomarker of drug response
  申请人：Basilea Pharmaceutica AG

  公开号：US10724072B2

  公开（公告）日：2020-07-28

  Use of phospho-Akt as a biomarker for predicting the response, such as resistance, to a compound, wherein phospho-Akt is Akt that has been phosphorylated on one or more residues, with the proviso that fir Akt1, Akt2, and Akt3 the designation phospho-Akt is used to indicate phosphorylation at a site other than T308, T309 or T305 respectively, wherein the compound is a compound of general formula (I) wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy, and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkoxycarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds we also disclosed.

  使用磷酸化-Akt 作为预测对化合物的反应（如抗性）的生物标志物，其中磷酸化-Akt 是指在一个或多个残基上被磷酸化的 Akt，但条件是 Akt1、Akt2 和 Akt3 的磷酸化-Akt 这一名称用于表示在 T308、T309 或 T305 以外的位点上的磷酸化、其中 R 代表苯基、噻吩基或吡啶基，其中苯基可任选被一个或两个独立选自烷基、卤代低级烷基、羟基或烷基的取代基取代、卤代-低级烷基、羟基-低级烷基、低级烷氧基-低级烷基、酰氧基-低级烷基、苯基、羟基、低级烷氧基、羟基-低级烷氧基、低级烷氧基-低级烷氧基、苯基-低级烷氧基、低级烷基羰氧基、氨基、单烷基氨基、二烷基氨基、低级烷氧基羰基氨基、低级烷基羰基氨基、取代氨基（其中氮上的两个取代基与氮一起形成杂环基）、低级烷基羰基、羧基、低级烷氧基羰基、氰基、卤素和硝基；其中相邻的两个取代基为亚甲基二氧基；吡啶基可选择被低级烷氧基、氨基或卤素取代；X 代表基团 C═Y，其中 Y 代表被羟基或低级烷氧基取代的氧或氮；R1 代表氢、低级烷基羰基、羟基-低级烷基或氰基-低级烷基；R2、R3 和 R6 代表氢；R4 和 R5 各自代表氢、低级烷基或低级烷氧基，或 R4 和 R5 共同代表亚甲基二氧基，以及它们的药学上可接受的衍生物；或其中 R 代表苯基或吡啶基，其中苯基任选被一个或两个取代基取代，这些取代基独立选自烷基、卤代低级烷基、羟基低级烷基、低级烷氧基低级烷基、酰氧基低级烷基、苯基、羟基、低级烷氧基、羟基低级烷氧基、低级烷氧基低级烷氧基、苯基-低级烷氧基、低级烷基羰氧基、氨基、单烷基氨基、二烷基氨基、低级烷氧基羰基氨基、低级烷氧基羰基氨基、取代氨基，其中氮上的两个取代基与氮一起形成杂环基、低级烷基羰基、羧基、低级烷氧基羰基、甲酰基、氰基、卤素和硝基；X代表氧；R1代表氢、低级烷基羰基、羟基-低级烷基或氰基-低级烷基；R2、R3和R6代表氢；R4和R5相互独立地代表氢、低级烷基或低级烷氧基，或R4和R5一起代表亚甲二氧基；及其药学上可接受的衍生物。我们还公开了用这些化合物治疗肿瘤性和自身免疫性疾病的方法。