4-N,N-dimethylamino-3-nitrophenylguanidine nitrate | 674333-66-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-N,N-dimethylamino-3-nitrophenylguanidine nitrate
• 英文别名: N-(4-dimethylamino-3-nitro-phenyl)-guanidine nitrate；2-[4-(dimethylamino)-3-nitrophenyl]guanidine;nitric acid
• CAS: 674333-66-5
• 化学式: C₉H₁₃N₅O₂*HNO₃
• 分子量: 286.247
• InChiKey: JVJRDTLFASQOPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.22
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  180
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-3-(dimethylamino)-1-(2,4-dimethylthiazol-5-yl)prop-2-en-1-one 、 4-N,N-dimethylamino-3-nitrophenylguanidine nitrate 在 potassium carbonate 作用下， 以 乙二醇甲醚 为溶剂， 反应 18.0h， 以43%的产率得到N⁴-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N¹,N¹-dimethyl-2-nitro-benzene-1,4-diamine
  参考文献：
  名称：

  2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity

  摘要：

  Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.

  DOI：

  10.1021/jm0309957
• 作为产物：
  描述：

  4-氟-3-硝基苯胺 在 硝酸 作用下， 以 乙醇 为溶剂， 反应 36.0h， 生成 4-N,N-dimethylamino-3-nitrophenylguanidine nitrate
  参考文献：
  名称：

  2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity

  摘要：

  Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.

  DOI：

  10.1021/jm0309957

文献信息

• Therapeutic applications of 2-substituted 4-heteroarylpyrimidines
  申请人：Wang Shudong

  公开号：US20050282843A1

  公开（公告）日：2005-12-22

  The present invention relates to the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein (A) one of X and Y is S, and the other is N; or one of X and Y is NH or N—R 5 , and the other is C—R 6 ; “a” is a single bond; “b”, “c”, “d”, “e” and “f” are single or double bonds so as to form a heteroaryl ring; R 1 is is R 7 with the proviso that R 1 is other than H or Me; or (B) one of X and Y is S, and the other is NH or N—R 5 ; “a” and “d” are each double bonds; “b”, “c”, “e” and “f” are each single bonds; R 1 is oxo; and R 2 , R 3 , R 4 , R 5 , and R 6 are each independently H or R 7 ; R 7 is a group (CH 2 ) n —R 8 , wherein n is 0, 1, 2, 3 or 4 and wherein R 8 is selected from alkyl, aryl, heteroaryl, heterocycloalkyl, F, Cl, Br, I, CF 3 , NO 2 , CN, OH, O-alkyl, O-aryl, O-heteroaryl, O-heterocycloalkyl, CO-alkyl, CO-aryl, CO-heteroaryl, CO-heterocycloalkyl, COO-alkyl, NH 2 , NH-alkyl, NH-aryl, N(alkyl) 2 , NH-heteroaryl, NH-heterocycloalkyl, COOH, CONH 2 , CONH-alkyl, CON(alkyl) 2 , CONH-aryl, CONH-heteroaryl, CONH-heterocycloalkyl, SO 3 H, SO 2 -alkyl, SO 2 -aryl, SO 2 -heteroaryl, SO 2 -heterocycloalkyl, SO 2 NH 2 , SO 2 NH-alkyl, SO 2 N(alkyl) 2 , SO 2 NH-aryl, SO 2 NH-heteroaryl, or SO 2 NH-heterocycloalkyl, wherein said alkyl, aryl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or more groups selected from halogeno, NO 2 , OH, O-methyl, NH 2 , COOH, CONH 2 and CF 3 ; in the preparation of a medicament for treating diabetes. The compounds of the invention also have applications in the treatment of CNS disorders, alopecia, cardiovascular disorders and stroke.

  本发明涉及使用公式I的化合物或其药学上可接受的盐，其中(A) X和Y中的一个是S，另一个是N；或者X和Y中的一个是NH或N-R5，另一个是C-R6；“a”是单键；“b”，“c”，“d”，“e”和“f”是单键或双键，以形成杂环芳基环；R1是R7，但R1不是H或Me；或(B) X和Y中的一个是S，另一个是NH或N-R5；“a”和“d”均为双键；“b”，“c”，“e”和“f”均为单键；R1是氧代；R2，R3，R4，R5和R6均独立地为H或R7；R7是(CH2)n-R8基团，其中n为0、1、2、3或4，而R8是选自烷基、芳基、杂芳基、杂环烷基、F、Cl、Br、I、CF3、NO2、CN、OH、O-烷基、O-芳基、O-杂芳基、O-杂环烷基、CO-烷基、CO-芳基、CO-杂芳基、CO-杂环烷基、COO-烷基、NH2、NH-烷基、NH-芳基、N(烷基)2、NH-杂芳基、NH-杂环烷基、COOH、CONH2、CONH-烷基、CON(烷基)2、CONH-芳基、CONH-杂芳基、CONH-杂环烷基、SO3H、SO2-烷基、SO2-芳基、SO2-杂芳基、SO2-杂环烷基、SO2NH2、SO2NH-烷基、SO2N(烷基)2、SO2NH-芳基、SO2NH-杂芳基或SO2NH-杂环烷基的基团，其中所述的烷基、芳基、杂芳基和杂环烷基基团可以选择地用一种或多种从卤代、 、OH、O-甲基、NH2、COOH、CONH2和 中选择的基团进行取代；用于制备治疗糖尿病的药物。本发明的化合物还可用于治疗中枢神经系统疾病、脱发、心血管疾病和中风。
• THERAPEUTIC APPLICATIONS OF 2-SUBSTITUTED 4-HETEROARYLPYRIMIDINES
  申请人：Cyclacel Limited

  公开号：EP1572211A1

  公开（公告）日：2005-09-14
• [EN] THERAPEUTIC APPLICATIONS OF 2-SUBSTITUTED 4-HETEROARYLRYRIMIDINES<br/>[FR] APPLICATIONS THERAPEUTIQUES DES 4-HETEROARYLRYRIMIDINES 2-SUBSTITUEES
  申请人：CYCLACEL LTD

  公开号：WO2004056368A1

  公开（公告）日：2004-07-08

  The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein (A) one of X and Y is S, and the other is N; or one of X and Y is NH or N-R5, and the other is C-R6; 'a' is a single bond; 'b', 'c', 'd', 'e' and 'f' are single or double bonds so as to form a heteroaryl ring; R1 is is R7 with the proviso that R1 is other than H or Me; or (B) one of X and Y is S, and the other is NH or N-R5; 'a' and 'd' are each double bonds; 'b', 'c', 'e' and 'f' are each single bonds; R1 is oxo; and R2, R3, R4, R5, and R6 are each independently H or R7; R7 is a group (CH2)n-R8, wherein n is 0, 1, 2, 3 or 4 and wherein R8 is selected from alkyl, aryl, heteroaryl, heterocycloalkyl, F, Cl, Br, I, CF3, NO2, CN, OH, O-alkyl, O-aryl, 0­- heteroaryl, 0-heterocycloalkyl, CO-alkyl, CO-aryl, CO-heteroaryl, CO-heterocycloalkyl, COO-alkyl, NH2, NH-alkyl, NH-aryl, N(alkyl)2, NH-heteroaryl, NH-heterocycloalkyl, COOH, CONH2, CONH-alkyl, CON(alkyl)2, CONH-aryl, CONH-heteroaryl, CONH­heterocycloalkyl, SO3H, S02-alkyl, SO2-aryl, S02-heteroaryl, SO2-heterocycloalkyl, SO2NH2, SO2NH-alkyl, SO2N(alkyl)2, SO2NH-aryl, SO2NH-heteroaryl, or SO2NH­heterocycloalkyl, wherein said alkyl, aryl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or more groups selected from halogeno, NO2, OH, 0­methyl, NH2, COOH, CONH2 and CF3; in the preparation of a medicament for treating diabetes. The compounds of the invention also have applications in the treatment of CNS disorders, alopecia, cardiovascular disorders and stroke.