4-((1,3-二氧代异吲哚啉-2-基)甲基)-2-氟苯甲腈 | 368426-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 4-((1,3-二氧代异吲哚啉-2-基)甲基)-2-氟苯甲腈
• 英文名称: 4-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-2-fluoro-benzonitrile
• 英文别名: 4-((1,3-Dioxoisoindolin-2-yl)methyl)-2-fluorobenzonitrile；4-[(1,3-dioxoisoindol-2-yl)methyl]-2-fluorobenzonitrile
• CAS: 368426-72-6
• 化学式: C₁₆H₉FN₂O₂
• 分子量: 280.258
• InChiKey: ZHETYOCOSCHYLL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((1,3-二氧代异吲哚啉-2-基)甲基)-2-氟苯甲腈 在 肼 作用下， 以 正丁醇 为溶剂， 反应 0.08h， 生成 4-(氨基乙基)-2-氟苯腈
  参考文献：
  名称：

  Non-covalent thrombin inhibitors featuring P3-Heterocycles with P1-Bicyclic arginine surrogates

  摘要：

  Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P-4-aromatics and P-2-P-3-heterocyclic dipeptide surrogates with weakly basic (calcd pK(a) similar tonon-basic-8.6) bicyclic P-1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P-1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00585-1
• 作为产物：
  描述：

  2-氟-4-甲基苯腈 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 caesium carbonate 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 4-((1,3-二氧代异吲哚啉-2-基)甲基)-2-氟苯甲腈
  参考文献：
  名称：

  Optimization of Novel 1-Methyl-1H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber’s Pole Worm

  摘要：

  A phenotypic screen of a diverse library of small molecules for inhibition of the development of larvae of the parasitic nematode Haemonchus contortus led to the identification of a 1-methyl-1H-pyrazole-5-carboxamide derivative with an IC50 of 0.29 mu M. Medicinal chemistry optimization targeted modifications on the left-hand side (LHS), middle section, and right-hand side (RHS) of the scaffold in order to elucidate the structure-activity relationship (SAR). Strong SAR allowed for the iterative and directed assembly of a focus set of 64 analogues, from which compound 60 was identified as the most potent compound, inhibiting the development of the fourth larval (L4) stage with an IC50 of 0.01 mu M. In contrast, only 18% inhibition of the mammary epithelial cell line MCF10A viability was observed, even at concentrations as high as 50 mu M.

  DOI：

  10.1021/acs.jmedchem.8b01544

文献信息

• NITROGEN-CONTAINING HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE
  申请人：Livo (Shanghai) Pharmaceutical Co., Ltd

  公开号：EP3539963A1

  公开（公告）日：2019-09-18

  Disclosed are a nitrogen-containing heterocyclic compound, preparation method, intermediate, pharmaceutical composition and use. The nitrogen-containing heterocyclic compound of the present invention has a novel structure, relatively high TLR7 agonist activity, high selectivity and good safety.

  本发明公开了一种含氮杂环化合物、制备方法、中间体、药物组合物及用途。本发明的含氮杂环化合物结构新颖，具有较高的 TLR7 激动剂活性、高选择性和良好的安全性。
• Nitrogen-containing heterocyclic compound, preparation method, intermediate, pharmaceutical composition and use
  申请人：HEPO PHARMACEUTICAL CO., LTD.

  公开号：US11084818B2

  公开（公告）日：2021-08-10

  Disclosed are a nitrogen-containing heterocyclic compound, a preparation method thereof, an intermediate thereof, a pharmaceutical composition thereof and a use thereof. The nitrogen-containing heterocyclic compound is a compound of formula I or formula II, a tautomer thereof, an optical isomer thereof, a deuterated compound thereof, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, which can be used for treating a disease associated with TLR7 activity. The nitrogen-containing heterocyclic compound has a relatively high TLR7 agonist activity, high selectivity and good safety.

  本发明公开了一种含氮杂环化合物、其制备方法、中间体、药物组合物及其用途。该含氮杂环化合物是式 I 或式 II 的化合物、其同分异构体、其光学异构体、其氘代化合物、其水合物、其溶液或其药学上可接受的盐，可用于治疗与 TLR7 活性相关的疾病。含氮杂环化合物具有相对较高的TLR7激动剂活性、高选择性和良好的安全性。
• [EN] NITROGEN-CONTAINING HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE CONTENANT DE L'AZOTE, PROCÉDÉ DE PRÉPARATION, INTERMÉDIAIRE, COMPOSITION PHARMACEUTIQUE ET UTILISATION<br/>[ZH] 含氮杂环化合物、制备方法、中间体、药物组合物和应用
  申请人：LIVO SHANGHAI PHARMACEUTICAL CO LTD

  公开号：WO2018086593A1

  公开（公告）日：2018-05-17

  本发明公开了一种含氮杂环化合物、制备方法、中间体、药物组合物和应用。本发明中的含氮杂环化合物结构新颖、具有较高的TLR7激动活性，且选择性高，安全性好。
• Non-covalent thrombin inhibitors featuring P3-Heterocycles with P1-Bicyclic arginine surrogates
  作者：Jingrong Jean Cui、Gian-Luca Araldi、John E Reiner、Komandla Malla Reddy、Scott J Kemp、Jonathan Z Ho、Daniel V Siev、Lala Mamedova、Tony S Gibson、John A Gaudette、Nathaniel K Minami、Susanne M Anderson、Annette E Bradbury、Thomas G Nolan、J.Edward Semple

  DOI：10.1016/s0960-894x(02)00585-1

  日期：2002.10

  Novel, potent, and highly selective classes of thrombin inhibitors were identified, which resulted from judicious combination of P-4-aromatics and P-2-P-3-heterocyclic dipeptide surrogates with weakly basic (calcd pK(a) similar tonon-basic-8.6) bicyclic P-1-arginine mimics. The design, synthesis, and biological activity of achiral, non-covalent, orally bioavailable inhibitors NC1-NC44 featuring P-1-indazoles, benzimidazoles, indoles, benzotriazoles, and aminobenzisoxazoles is disclosed. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Nitrogen-Containing Heterocyclic Compound, Preparation Method, Intermediate, Pharmaceutical Composition and use
  申请人：HEPO PHARMACEUTICAL CO., LTD

  公开号：US20200062758A1

  公开（公告）日：2020-02-27

  Disclosed are a nitrogen-containing heterocyclic compound, preparation method, intermediate, pharmaceutical composition and use. The nitrogen-containing heterocyclic compound of the present invention has a novel structure, relatively high TLR7 agonist activity, high selectivity and good safety.