2-[4-(三氟甲基)苯基]胍硝酸盐 | 674333-63-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[4-(三氟甲基)苯基]胍硝酸盐
• 英文名称: N-(4-trifluoromethylphenyl)guanidine nitrate
• 英文别名: N-(4-trifluoromethyl-phenyl)-guanidine nitrate；nitric acid;2-[4-(trifluoromethyl)phenyl]guanidine
• CAS: 674333-63-2
• 化学式: C₈H₈F₃N₃*HNO₃
• 分子量: 266.18
• InChiKey: ODMFOCBPZGXXKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[4-(三氟甲基)苯基]胍硝酸盐 在 sodium hydroxide 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 {4-[4-(Piperazine-1-sulfonyl)-phenyl]-pyrimidin-2-yl}-(4-trifluoromethyl-phenyl)-amine
  参考文献：
  名称：

  A novel series of potent and selective IKK2 inhibitors

  摘要：

  A novel series of ammopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.047
• 作为产物：
  描述：

  对三氟甲基苯胺 、 氰胺 在 硝酸 作用下， 生成 2-[4-(三氟甲基)苯基]胍硝酸盐
  参考文献：
  名称：

  A novel series of potent and selective IKK2 inhibitors

  摘要：

  A novel series of ammopyrimidine IKK2 inhibitors have been developed which show excellent in vitro inhibition of this enzyme and good selectivity over the IKK1 isoform. The relative potency and selectivity of these compounds has been rationalized using QSAR and structure-based modelling. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.047

文献信息

• [EN] THIAZOLO-, OXAZALO AND IMIDAZOLO-QUINAZOLINE COMPOUNDS CAPABLE OF INHIBITING PROT EIN KINASES<br/>[FR] COMPOSES A BASE DE THIAZOLO-, OXAZALO ET IMIDAZOLO-QUINAZOLINE CAPABLES D'INHIBITION DE PROTEINE-KINASES
  申请人：CYCLACEL LTD

  公开号：WO2005005438A1

  公开（公告）日：2005-01-20

  compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein: X is S, 0, or NH; 'a' is a single bond; or 'a' is a double bond and one of R3 and R4 and one of R5 and R6 are absent; R1 is H; or is selected from an alkyl group, a cycloalkyl group, a heteroaryl group, an aralkyl group, CO-alkyl, S02-alkyl, C02R13 and an aryl group, each of which optionally contains one or more heteroatoms, and is optionally substituted with one or more groups selected from R8 and R9; R2 is H, R8 , or an alkyl group optionally substituted with one or more R8 groups; R3 , R4, R5, and R6 are each independently selected from H, R8 , an alkyl group and an alkenyl group, wherein said alkyl and alkenyl groups are optionally substituted with one or more R8 groups; or R3 and R4, and/or R5 and R6 together represent =0; R7 is H, R8, NH(CH2)nR9, CO(CH2)nR9, NHCO(CH2)nR9, O(CH2)nR9, or an alkyl or phenyl group, each of which is optionally substituted with one or more groups selected from R8 and R9; R8 is OR10, NR10R11, halogen, CF3, N02, COR10, CN, COOR10, CONR10R11, S02R10 or S02NR10R11; R9 is a saturated or unsaturated 5- or 6-membered cyclic group optionally containing one or more heteroatoms selected from N, 0 and S, and optionally substituted with one or more R8 groups; R10, R11, R12 and R13 are each independently H or a hydrocarbyl group; and n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising compounds of formula (1), and the therapeutic use thereof in the treatment of proliferative disorders, viral disorders, CNS disorders, diabetes, stroke and cardiovascular disorders.

  化合物的公式（1）或其药学上可接受的盐，其中：X为S、O或NH；'a'为单键；或'a'为双键，且R3和R4中的一个以及R5和R6中的一个不存在；R1为H；或从烷基、环烷基、杂环烷基、芳基、CO-烷基、SO2-烷基、CO2R13和芳基中选择，每种基可选地含有一个或多个杂原子，并可选地用R8和R9中的一个或多个基替代；R2为H、R8或烷基，烷基可选地用一个或多个R8基替代；R3、R4、R5和R6各自独立地选自H、R8、烷基和烯基，其中所述烷基和烯基可选地用一个或多个R8基替代；或R3和R4，和/或R5和R6一起代表=O；R7为H、R8、NH(CH2)nR9、CO(CH2)nR9、NHCO(CH2)nR9、O(CH2)nR9或烷基或苯基，每种基可选地用一个或多个R8和R9中的一个或多个基替代；R8为OR10、NR10R11、卤素、CF3、NO2、COR10、CN、COOR10、CONR10R11、SO2R10或SO2NR10R11；R9为饱和或不饱和的含有一个或多个来自N、O和S的杂原子的5-或6-成员环基，并可选地用一个或多个R8基替代；R10、R11、R12和R13各自独立地为H或烃基；n为0、1、2或3。该发明的进一步方面涉及包含化合物的公式（1）的药物组合物，以及其在治疗增殖性疾病、病毒性疾病、中枢神经系统疾病、糖尿病、中风和心血管疾病中的治疗用途。
• Thiazolo-, oxazalo and imidazolo-quinazoline compounds capable of inhibiting protein kinases
  申请人：McInnes Campbell

  公开号：US20060264628A1

  公开（公告）日：2006-11-23

  A compound of formula 1, or a pharmaceutically acceptable salt thereof, wherein: X is S, O, or NH; “a” is a single bond; or “a” is a double bond and one of R 3 and R 4 , and one of R 5 and R 6 are absent; R 1 is H; or is selected from an alkyl group, a cycloalkyl group, a heteroaryl group, an aralkyl group, CO-alkyl, SO 2 -alkyl, CO 2 R 13 and an aryl group, each of which optionally contains one or more heteroatoms, and is optionally substituted with one or more groups selected from R 8 and R 9 ; R 2 is H, R 8 , or an alkyl group optionally substituted with one or more R 8 groups; R 3 , R 4 , R 5 , and R 6 are each independently selected from H, R 8 , an alkyl group and an alkenyl group, wherein said alkyl and alkenyl groups are optionally substituted with one or more R 8 groups; or R 3 and R 4 , and/or R 5 and R 6 together represent ═O; R 7 is H, R 8 , NH(CH 2 ) n R 9 , CO(CH 2 ) n R 9 , NHCO(CH 2 ) n R 9 , O(CH 2 ) n R 9 , or an alkyl or phenyl group, each of which is optionally substituted with one or more groups selected from R 8 and R 9 ; R 8 is OR 10 , NR 10 R 11 , halogen, CF 3 , NO 2 , COR 10 , CN, COOR 10 , CONR 10 R 11 , SO 2 R 10 or SO 2 NR 10 R 11 ; R 9 is a saturated or unsaturated 5- or 6-membered cyclic group optionally containing one or more heteroatoms selected from N, O and S, and optionally substituted with one or more R 8 groups; R 10 , R 11 , R 12 and R 13 are each independently H or a hydrocarbyl group; and n is 0, 1, 2 or 3. Further aspects of the invention relate to pharmaceutical compositions comprising compounds of formula 1, and the therapeutic use thereof in the treatment of proliferative disorders, viral disorders, CNS disorders, diabetes, stroke and cardiovascular disorders.

  化合物1的公式，或其药学上可接受的盐，其中：X为S，O或NH；"a"为单键；或"a"为双键，其中R3和R4中的一个，以及R5和R6中的一个缺失；R1为H；或从烷基，环烷基，杂环烷基，芳基烷基，CO-烷基，SO2-烷基，CO2R13和芳基中选择，每个都可以选择性地包含一个或多个杂原子，并且可以选择性地用一个或多个从R8和R9中选择的基团取代；R2为H，R8或烷基，可选择性地用一个或多个R8基团取代；R3、R4、R5和R6各自独立地选择自H、R8、烷基和烯基中的一个，其中所述的烷基和烯基可以选择性地用一个或多个R8基团取代；或者R3和R4，和/或R5和R6一起代表═O；R7为H、R8、NH(CH2)nR9、CO(CH2)nR9、NHCO(CH2)nR9、O(CH2)nR9或烷基或苯基，每个都可以选择性地用一个或多个从R8和R9中选择的基团取代；R8为OR10、NR10R11、卤素、CF3、NO2、COR10、CN、COOR10、CONR10R11、SO2R10或SO2NR10R11；R9为选择性地含有一个或多个R8基团的饱和或不饱和的5或6元环状基团，其中可以选择性地含有一个或多个来自R8的基团；R10、R11、R12和R13各自独立地为H或烃基；n为0、1、2或3。发明的另一方面涉及包括化合物1的制药组合物以及其在治疗增殖性疾病、病毒性疾病、中枢神经系统疾病、糖尿病、中风和心血管疾病中的治疗用途。
• 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity
  作者：Shudong Wang、Christopher Meades、Gavin Wood、Andrew Osnowski、Sian Anderson、Rhoda Yuill、Mark Thomas、Mokdad Mezna、Wayne Jackson、Carol Midgley、Gary Griffiths、Ian Fleming、Simon Green、Iain McNae、Su-Ying Wu、Campbell McInnes、Daniella Zheleva、Malcolm D. Walkinshaw、Peter M. Fischer

  DOI：10.1021/jm0309957

  日期：2004.3.1

  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.
• THIAZOLO-, OXAZALO AND IMIDAZOLO-QUINAZOLINE COMPOUNDS CAPABLE OF INHIBITING PROTEIN KINASES
  申请人：Cyclacel Limited

  公开号：EP1641805A1

  公开（公告）日：2006-04-05
• US7576091B2
  申请人：——

  公开号：US7576091B2

  公开（公告）日：2009-08-18