3,5,6,7-四氢-4H-苯并[D]咪唑-4-酮 | 70500-91-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3,5,6,7-四氢-4H-苯并[D]咪唑-4-酮
• 英文名称: 1,5,6,7-tetrahydro-4H-benzimidazol-4-one
• 英文别名: 1,5,6,7-tetrahydrobenzimidazol-4-one
• CAS: 70500-91-3
• 化学式: C₇H₈N₂O
• mdl: MFCD20617825
• 分子量: 136.153
• InChiKey: RBTNKOKYJAHDSF-UHFFFAOYSA-N

物化性质

• 熔点：
  221-222 °C(Solv: ethanol (64-17-5))
• 沸点：
  405.1±14.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,5,6,7-四氢-4H-苯并[D]咪唑-4-酮 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 144.0h， 生成 3-(1,2,3,4-tetrahydroquinolin-6-yl)-3,5,6,7-tetrahydrobenzoimidazol-4-one
  参考文献：
  名称：

  [EN] BICYCLIC IMIDAZOLE DERIVATIES USEFUL FOR THE TREATMENT OF RENAL DISEASE, CARDIOVASCULAR DISEASES AND FIBROTIC DISORDERS
  [FR] DÉRIVÉS D'IMIDAZOLE BICYCLIQUES UTILISÉES POUR LE TRAITEMENT DE MALADIES RÉNALES, CARDIOVASCULAIRES ET DE TROUBLES FIBROTIQUES

  摘要：

  本发明涉及以下化合物的公式I：及其药用盐，其中R1、R2、R3、R4、R5和n的定义如本文所述。该发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和障碍的方法，制备这些化合物的过程以及在这些过程中有用的中间体。

  公开号：

  WO2018005177A1
• 作为产物：
  描述：

  1,2,3-环己烷三酮-1,3-二肟 在 盐酸 、 ammonium acetate 、 三乙胺 、 一氯丙酮 、 sodium nitrite 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 27.5h， 生成 3,5,6,7-四氢-4H-苯并[D]咪唑-4-酮
  参考文献：
  名称：

  由2,6-双（羟基亚氨基）环己基-1-酮合成1,5,6,7-四氢-4 H-苯并咪唑-4-酮衍生物

  摘要：

  2，6-双（羟基亚氨基）环己酮-1-酮与醛和氨的反应得到2-取代的4-羟基亚氨基-4,5,6,7-四氢-1 H-苯并咪唑-1-醇，其被水解为1-羟基-2-R-1,5,6,7-四氢-4 H-苯并咪唑-4-酮。后者中的N-羟基可通过在碱（碳酸钾或三乙胺）存在下，通过氯丙酮的作用而容易地除去；结果，获得2-取代的1,5,6,7-四氢-4 H-苯并咪唑-4-酮。

  DOI：

  10.1134/s1070428017010122

文献信息

• Regioselective Alkylation of 2-Alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-ones and 2-Alkyl-3H-cycloheptimidazol-4-ones
  作者：Motoharu Sonegawa、Masayuki Yokota、Hiroshi Tomiyama、Tsuyoshi Tomiyama

  DOI：10.1248/cpb.54.706

  日期：——

  Regioselective alkylation of 2-alkyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (1) and 2-alkyl-3H-cycloheptimidazol-4-one (2) was investigated. 3-[2′-(1-tert-Butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-1H-cycloheptimidazol-4-one (6) was preferentially obtained under the conditions by using NaH in DMF or THF. On the other hand, 3-[2′-(1-tert-butyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-2-propyl-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (5), the synthetic intermediate compound of Pratosartan, was obtained selectively in the presence of n-Bu4NBr in toluene by using aqueous sodium hydroxide as a base. In this reaction, it was found that the concentration of the alkaline solution influences its regioselectivity. This selectivity was observed even for aldehyde and ester derivatives.

  研究了2-烷基-5,6,7,8-四氢-3H-环庚咪唑-4-酮（1）和2-烷基-3H-环庚咪唑-4-酮（2）的区域选择性烷基化反应。在DMF或THF中使用NaH的条件下，优先得到3-[2′-(1-叔丁基-1H-四唑-5-基)联苯-4-基甲基]-2-丙基-5,6,7,8-四氢-1H-环庚咪唑-4-酮（6）。另一方面，在甲苯中使用水合氢氧化钠作为碱和n-Bu4NBr存在下，选择性得到3-[2′-(1-叔丁基-1H-四唑-5-基)联苯-4-基甲基]-2-丙基-5,6,7,8-四氢-3H-环庚咪唑-4-酮（5），即普拉托沙坦的合成中间体化合物。在这项反应中，发现碱性溶液的浓度影响其区域选择性。这种选择性甚至在醛和酯衍生物中也观察到。
• [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。
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS WITH ENHANCED EFFICACY
  申请人：BRIDGER Gary

  公开号：US20080167341A1

  公开（公告）日：2008-07-10

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及由一个核心氮原子和三个侧链基团组成的杂环化合物，其中三个侧链基团中有两个是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可以含有额外的环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护效果。
• Chemokine Receptor Binding Heterocyclic Compounds With Enhanced Efficacy
  申请人：Genzyme Corporation

  公开号：US20150038509A1

  公开（公告）日：2015-02-05

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及杂环化合物，其由一个核心氮原子和三个下垂基团组成，其中三个下垂基团中的两个优选为苯并咪唑甲基和四氢喹啉基，第三个下垂基团含有N，并且可以包含其他环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且对人类免疫缺陷病毒（HIV）感染目标细胞具有保护作用。