(3,4-diaminophenyl) (3-fluorophenyl) methanone | 115577-03-2

• 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: (3,4-diaminophenyl) (3-fluorophenyl) methanone
• 英文别名: 3,4-diaminophenyl-(3-fluorophenyl)methanone；(3,4-diaminophenyl)-(3-fluorophenyl)methanone
• CAS: 115577-03-2
• 化学式: C₁₃H₁₁FN₂O
• 分子量: 230.242
• InChiKey: OENYVXQFYOZWRA-UHFFFAOYSA-N

物化性质

• 沸点：
  451.6±45.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3,4-diaminophenyl) (3-fluorophenyl) methanone 在 吡啶 、 sodium hydroxide 作用下， 以 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 5.0h， 生成 2-amino-6-(3-fluorobenzoyl)-N,N-dimethylbenzimidazole-1-sulfonamide
  参考文献：
  名称：

  Antirhino/Enteroviral Vinylacetylene Benzimidazoles:  A Study of Their Activity and Oral Plasma Levels in Mice

  摘要：

  In an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a-o, 12, and 18a was made. Initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. To ascertain the generality of this finding and to broaden the scope of the structure-activity relationship (SAR), the present study concentrated on fluoro substitution of this class of molecules. The initial antiviral activity for each analogue was measured using human rhinovirus 14 (HRV-14). This served as an indicator of general antiviral activity for SAR purposes. Subsequently, the spectrum of antirhino/enteroviral activity of the more interesting analogues was evaluated through testing against a panel of seven additional rhino/enteroviruses. Broad-spectrum activity was present and consistent for all analogues tested, and it tracked closely with the antiviral activity observed against HRV-14. A simple screening protocol for oral bioavailability was established whereby compounds were administered orally to mice and plasma levels were measured. This procedure facilitated the evaluation of numerous analogues in a rapid manner. The C-max was used as a measure of oral bioavailability to allow relative ranking of compounds. In general, fluorine substitution directly on the left-hand aromatic ring does give good oral blood levels. However, fluorine incorporation at other positions in the molecule was not as effective at maintaining either the activity or the oral plasma levels. The constructive combination of activity and oral plasma levels was maximized in three derivatives: 11a,e,g.

  DOI：

  10.1021/jm970423k
• 作为产物：
  描述：

  3-氟苯乙腈 在 镍 potassium tert-butylate 、 氢气 、 双氧水 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、413.69 kPa 条件下， 反应 16.0h， 生成 (3,4-diaminophenyl) (3-fluorophenyl) methanone
  参考文献：
  名称：

  Antirhino/Enteroviral Vinylacetylene Benzimidazoles:  A Study of Their Activity and Oral Plasma Levels in Mice

  摘要：

  In an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a-o, 12, and 18a was made. Initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. To ascertain the generality of this finding and to broaden the scope of the structure-activity relationship (SAR), the present study concentrated on fluoro substitution of this class of molecules. The initial antiviral activity for each analogue was measured using human rhinovirus 14 (HRV-14). This served as an indicator of general antiviral activity for SAR purposes. Subsequently, the spectrum of antirhino/enteroviral activity of the more interesting analogues was evaluated through testing against a panel of seven additional rhino/enteroviruses. Broad-spectrum activity was present and consistent for all analogues tested, and it tracked closely with the antiviral activity observed against HRV-14. A simple screening protocol for oral bioavailability was established whereby compounds were administered orally to mice and plasma levels were measured. This procedure facilitated the evaluation of numerous analogues in a rapid manner. The C-max was used as a measure of oral bioavailability to allow relative ranking of compounds. In general, fluorine substitution directly on the left-hand aromatic ring does give good oral blood levels. However, fluorine incorporation at other positions in the molecule was not as effective at maintaining either the activity or the oral plasma levels. The constructive combination of activity and oral plasma levels was maximized in three derivatives: 11a,e,g.

  DOI：

  10.1021/jm970423k

文献信息

• Respiratory syncytial virus replication inhibitors
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1418175A1

  公开（公告）日：2004-05-12

  This invention concerns compounds of formula    prodrugs, N-oxides, addition salts, quaternary amines, metal complexes or stereochemically isomeric forms thereof wherein -a1=a2-a3=a4- is a radical of formula - CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, -CH=CH-CH=N- wherein each hydrogen atom may optionally be substituted; Q is a radical of formula wherein Alk is C1-6alkanediyl; Y1 is a bivalent radical of formula -NR2- or -CH(NR2R4)-; X1 is NR4, S, S(=O), S(=O)2, O, CH2, C(=O), CH(=CH2), CH(OH), CH(CH3), CH(OCH3), CH(SCH3), CH(NR5aR5b), CH2-NR4 or NR4-CH2; X2 is a direct bond, CH2, C(=O), NR4, C1-4alkyl-NR4, NR4-C1-4alkyl; t is 2 to 5; u is 1 to 5; v is 2 or 3; and whereby each hydrogen in Alk and in (b-3), (b-4), (b-5), (b-6), (b-7) and (b-8), may optionally be replaced by R3; provided that when R3 is hydroxy or C1-6alkyloxy, then R3 can not replace a hydrogen atom in the α position relative to a nitrogen atom; G is a direct bond or C1-10alkanediyl; R1 is an optionally substituted monocyclic heterocycle; R2 is hydrogen, formyl, pyrrolidinyl, piperidinyl, homoiperidinyl, C3- 7cycloalkyl or C1-10alkyl substituted with N(R6)2 and optionally with another substituent; R3 is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, arylC1-6alkyl or arylC1- 6alkyloxy; R4 is hydrogen, C1-6alkyl or arylC1-6alkyl; R5a, R5b, R5c and R5d each independently are hydrogen or C1-6alkyl; or R5a and R5b, or R5c and R5d taken together from a bivalent radical of formula -(CH2)s- wherein s is 4 or 5; R6 is hydrogen, C1- 4alkyl, formyl, hydroxyC1-6alkyl, C1-6alkylcarbonyl or C1-alkyloxyarbonyl; aryl is optionally substituted phenyl; and their use for the manufacture of a medicament for the treatment of viral infections, in particular RSV infections.

  这项发明涉及以下化合物：前药、N-氧化物、加合盐、季铵盐、金属配合物或其立体化学异构体，其中-a1=a2-a3=a4-是一个具有以下结构的基团：-CH=CH-CH=CH-、-N=CH-CH=CH-、-CH=N-CH=CH-、-CH=CH-N=CH-、-CH=CH-CH=N-，其中每个氢原子可能被取代；Q是一个具有以下结构的基团：其中Alk是C1-6烷二基；Y1是一个具有以下结构的二价基团：-NR2-或-CH(NR2R4)-；X1是NR4、S、S(=O)、S(=O)2、O、CH2、C(=O)、CH(=CH2)、CH(OH)、CH(CH3)、CH(OCH3)、CH(SCH3)、CH(NR5aR5b)、CH2-NR4或NR4-CH2；X2是一个直接键、CH2、C(=O)、NR4、C1-4烷基-NR4、NR4-C1-4烷基；t为2至5；u为1至5；v为2或3；其中Alk和(b-3)、(b-4)、(b-5)、(b-6)、(b-7)和(b-8)中的每个氢原子可以选择地被R3取代；但是当R3为羟基或C1-6烷氧基时，R3不能取代相对于氮原子的α位上的氢原子；G是一个直接键或C1-10烷二基；R1是一个可选择地取代的单环杂环；R2是氢、甲酰、吡咯啉基、哌啶基、环戊基或C1-10烷基，其中烷基被N(R6)2取代并可选择地带有另一个取代基；R3是氢、羟基、C1-6烷基、C1-6烷氧基、芳基C1-6烷基或芳基C1-6烷氧基；R4是氢、C1-6烷基或芳基C1-6烷基；R5a、R5b、R5c和R5d各自独立地是氢或C1-6烷基；或者R5a和R5b，或者R5c和R5d共同形成一个具有以下结构的二价基团：-(CH2)s-，其中s为4或5；R6是氢、C1-4烷基、甲酰、羟基C1-6烷基、C1-6烷基羰基或C1-烷氧基羰基；芳基是可选择地取代的苯基；以及它们用于制造用于治疗病毒感染的药物，特别是RSV感染。
• [EN] RESPIRATORY SYNCYTIAL VIRUS REPLICATION INHIBITORS<br/>[FR] INHIBITEURS DE REPLICATION DE VIRUS SYNCYTIAUX RESPIRATOIRES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2001000611A1

  公开（公告）日：2001-01-04

  This invention concerns the use of compounds of formula (I) wherein -a?1=a2-a3=a4¿- is a radical of formula -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH-, -CH=CH-CH=N- wherein each hydrogen atom may optionally be substituted; Q is a radical of formulas (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7), (b-8), G is a direct bond or C¿1-10?alkanediyl; R?1¿ is an optionally substituted monocyclic heterocycle; for the manufacture of a medicament for the treatment of viral infections, in particular RSV infections. Certain compounds of formula (I) are new.

  本发明涉及使用公式(I)中的化合物，其中-a?1=a2-a3=a4¿-是公式-CH=CH-CH=CH-，-N=CH-CH=CH-，-CH=N-CH=CH-，-CH=CH-N=CH-，-CH=CH-CH=N= N-的基团，其中每个氢原子可以选择被取代; Q是公式(b-1)，(b-2)，(b-3)，(b-4)，(b-5)，(b-6)，(b-7)，(b-8)的基团; G是直接键或C¿1-10?烷二基; R?1¿是可选择被取代的单环杂环；用于制造治疗病毒感染的药物，特别是RSV感染。公式(I)的某些化合物是新的。
• (1H-imidazol-1-ylmethyl) substituted benzimidazole derivatives and use
  申请人：Janssen Pharmaceutica N.V.

  公开号：US04859684A1

  公开（公告）日：1989-08-22

  Novel (1H-imidazol-1-ylmethyl) substituted benzimidazole derivatives, compositions containing the same, and methods of treating androgen dependent disorders in mammals.

  小说(1H-咪唑-1-基甲基)取代苯并咪唑衍生物，含有相同成分的组合物，以及治疗哺乳动物雄激素依赖性疾病的方法。
• Design and synthesis of a novel candidate compound NTI-007 targeting sodium taurocholate cotransporting polypeptide [NTCP]–APOA1–HBx–Beclin1-mediated autophagic pathway in HBV therapy
  作者：Jin Zhang、Lei-lei Fu、Mao Tian、Hao-qiu Liu、Jing-jing Li、Yan Li、Jun He、Jian Huang、Liang Ouyang、Hui-yuan Gao、Jin-hui Wang

  DOI：10.1016/j.bmc.2015.01.020

  日期：2015.3

  Sodium taurocholate cotransporting polypeptide (NTCP) is a multiple transmembrane transporter predominantly expressed in the liver, functioning as a functional receptor for HBV. Through our continuous efforts to identify NTCP as a novel HBV target, we designed and synthesized a series of new compounds based on the structure of our previous compound NT-5. Molecular docking and MD simulation validated that a new compound named NTI-007 can tightly bind to NTCP, whose efficacy was also measured in vitro virological examination and cytotoxicity studies. Furthermore, autophagy was observed in NTI-007 incubated HepG2.2.15 cells, and results of q-PCR and Western blotting revealed that NTI-007 induced autophagy through NTCP-APOA1-HBx-Beclin1-mediated pathway. Taken together, considering crucial role of NTCP in HBV infection, NTCP-mediated autophagic pathway may provide a promising strategy of HBV therapy and given efficacy of NTI-007 triggering autophagy. Our study suggests pre-clinical potential of this compound as a novel anti-HBV drug candidate. (C) 2015 Elsevier Ltd. All rights reserved.
• RESPIRATORY SYNCYTIAL VIRUS REPLICATION INHIBITORS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP1196408B1

  公开（公告）日：2004-09-15