methyl 3-(4-fluoro-3-nitrophenyl)propanoate | 907602-44-2

• 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: methyl 3-(4-fluoro-3-nitrophenyl)propanoate
• 英文别名: 3-(4-Fluoro-3-nitro-phenyl)-propionic acid methyl ester
• CAS: 907602-44-2
• 化学式: C₁₀H₁₀FNO₄
• 分子量: 227.192
• InChiKey: BBYSSQZSIUKMFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-fluoro-3-nitrophenyl)propanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以86%的产率得到3-(4-fluoro-3-nitrophenyl)propionic acid
  参考文献：
  名称：

  Simplified Cyclic Analogues of Bastadin-5. Structure−Activity Relationships for Modulation of the RyR1/FKBP12 Ca²⁺ Channel Complex

  摘要：

  Bastadin-5, a brominated macro-dilactam from the marine sponge Ianthella basta, enhances release of Ca2+ from stores within the sarcoplasmic reticulum (SR) of muscle and nonmuscle cells by modulating RyR1/FKBP12 complex. Analogues of bastadin-5 present desirable targets for SAR studies to shed light on the gating mechanism and locus of bastadin-5 binding on these heteromeric channels that mediate essential steps in early coupling of membrane excitation to Ca2+ signaling cascades. Simple, ring-constrained analogues of bastadin-5 were synthesized from substituted benzaldehydes in a convergent manner, featuring an efficient SNAr macroetherification, and evaluated in an assay that measures [H-3]-ryanodine that is known to correlate with the functional open state of the Ca2+ channel. The simplified 14-membered ring, atropisomeric analogue (+/-)-7, like bastadin-5, enhanced ryanodine binding to the RyR1/FKBP12 complex (EC50 11 mu M), however, unexpectedly, the corresponding achiral 18-membered ring analogue 14 potently inhibited binding (IC50 6 mu M) under the same conditions. Structure-activity relationships of both families of cyclic analogues showed activity in a ryanodine binding assay that varied with substitutions of the Br atom on the trisubstituted aryl ring by various functional groups. The most active analogues were those that conserved the dibromocatechol ether moiety that corresponds to the 'western edge' of the bastadin-5 structure. These data suggest that cyclic analogues of bastadin-5 interact with the channel complex in a complex manner that can either enhance or inhibit channel activity.

  DOI：

  10.1021/jm050708u
• 作为产物：
  描述：

  methyl 4-fluoro-3-nitrocinnamate 在 Wilkinson's catalyst 、 氢气 作用下， 以 甲苯 为溶剂， 60.0 ℃ 、303.97 kPa 条件下， 反应 8.0h， 以95%的产率得到methyl 3-(4-fluoro-3-nitrophenyl)propanoate
  参考文献：
  名称：

  Simplified Cyclic Analogues of Bastadin-5. Structure−Activity Relationships for Modulation of the RyR1/FKBP12 Ca²⁺ Channel Complex

  摘要：

  Bastadin-5, a brominated macro-dilactam from the marine sponge Ianthella basta, enhances release of Ca2+ from stores within the sarcoplasmic reticulum (SR) of muscle and nonmuscle cells by modulating RyR1/FKBP12 complex. Analogues of bastadin-5 present desirable targets for SAR studies to shed light on the gating mechanism and locus of bastadin-5 binding on these heteromeric channels that mediate essential steps in early coupling of membrane excitation to Ca2+ signaling cascades. Simple, ring-constrained analogues of bastadin-5 were synthesized from substituted benzaldehydes in a convergent manner, featuring an efficient SNAr macroetherification, and evaluated in an assay that measures [H-3]-ryanodine that is known to correlate with the functional open state of the Ca2+ channel. The simplified 14-membered ring, atropisomeric analogue (+/-)-7, like bastadin-5, enhanced ryanodine binding to the RyR1/FKBP12 complex (EC50 11 mu M), however, unexpectedly, the corresponding achiral 18-membered ring analogue 14 potently inhibited binding (IC50 6 mu M) under the same conditions. Structure-activity relationships of both families of cyclic analogues showed activity in a ryanodine binding assay that varied with substitutions of the Br atom on the trisubstituted aryl ring by various functional groups. The most active analogues were those that conserved the dibromocatechol ether moiety that corresponds to the 'western edge' of the bastadin-5 structure. These data suggest that cyclic analogues of bastadin-5 interact with the channel complex in a complex manner that can either enhance or inhibit channel activity.

  DOI：

  10.1021/jm050708u

文献信息

• Benzylbenzimidazolyl derivatives
  申请人：Stahle Wolfgang

  公开号：US20070066606A1

  公开（公告）日：2007-03-22

  Novel benzyl-benzimidazolyl derivatives as inhibitors of tyrosine kinases, particularly TIE-2, VEGFR, PDGFR, FGFR and/or FLT/KDR, for the treatment of tumors, according to formula (I), wherein the radicals R 1 , R 2 , r and s are defined according to Claim ( 1 ).

  新型苄基-苄并咪唑衍生物作为酪氨酸激酶抑制剂，特别是TIE-2、VEGFR、PDGFR、FGFR和/或FLT/KDR，用于肿瘤治疗，根据式(I)，其中基团R1、R2、r和s的定义如权利要求（1）所述。
• [EN] BENZIMIDAZOL-2-AMINES AS MIDH1 INHIBITORS<br/>[FR] BENZIMIDAZOL-2-AMINES EN TANT QU'INHIBITEURS MIDH1
  申请人：BAYER PHARMA AG

  公开号：WO2015121210A1

  公开（公告）日：2015-08-20

  The present invention relates to benzimidazol-2-amines of general formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的苯并咪唑-2-胺化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和R12如本文所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分组合使用。
• [EN] N-MENTHYLBENZIMIDAZOLES AS MIDH1 INHIBITORS<br/>[FR] N-MENTHYLBENZIMIDAZOLES À TITRE D'INHIBITEURS DE MIDH1
  申请人：BAYER PHARMA AG

  公开号：WO2016198322A1

  公开（公告）日：2016-12-15

  The present invention relates to benzimidazol-2-amines of general formula (I), in which R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的苯并咪唑-2-胺化合物，其中R1、R2、R3、R4、R5、R6、R7和R8如本文所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分结合使用。
• [EN] 5-HYDROXYALKYLBENZIMIDAZOLES AS MIDH1 INHIBITORS<br/>[FR] 5-HYDROXYALKYLBENZIMIDAZOLES EN TANT QU'INHIBITEURS DE MIDH1
  申请人：BAYER PHARMA AG

  公开号：WO2017009325A1

  公开（公告）日：2017-01-19

  The present invention relates to benzimidazol-2-amines of general formula (I) in which R1, R2, R3, R4, R5, R6 and R7 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及通式(I)中R1、R2、R3、R4、R5、R6和R7如所定义的苯并咪唑-2-胺，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分组合使用。
• [EN] INHIBITOR OF THE MUTATED ISOCITRATE DEHYDROGENASE IDH1 R132H<br/>[FR] INHIBITEUR D'ISOCITRATE DÉSHYDROGÉNASE MUTÉE IDH1 R132H
  申请人：BAYER PHARMA AG

  公开号：WO2017016992A1

  公开（公告）日：2017-02-02

  The present invention relates to the adduct (2E)-but-2-enedioic acid - 3-(2-[4- (trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol- -yl)propanoic acid (1:4), methods for preparing this adduct, pharmaceutical compositions comprising this adduct and also the use of this adduct for preparing a medicament for the treatment of a disease.

  本发明涉及加合物(2E)-丁-2-烯二酸 - 3-(2-[4-三氟甲氧基)苯基]氨基}-1-[(1R,5R)-3,3,5-三甲基环己基]-1H-苯并咪唑- -基)丙酸(1:4)，制备该加合物的方法，包含该加合物的药物组合物，以及利用该加合物制备治疗疾病的药物的用途。