N-phenyl-3-(3-chlorophenyl)-2-propenamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: N-phenyl-3-(3-chlorophenyl)-2-propenamide
• 英文别名: (E)-3-(3-chlorophenyl)-N-phenylacrylamide；LQM334；3-(3-Chlorophenyl)-N-phenylacrylamide；(E)-3-(3-chlorophenyl)-N-phenylprop-2-enamide
• 化学式: C₁₅H₁₂ClNO
• 分子量: 257.719
• InChiKey: FCWLPQWRAKGOGU-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-phenyl-3-(3-chlorophenyl)-2-propenamide 在 PPA 作用下， 反应 16.0h， 生成 4-(3-氯苯基)-3,4-二氢-1H-喹啉-2-酮
  参考文献：
  名称：

  法呢基蛋白转移酶抑制剂 ZARNESTRATM 的合成路线

  摘要：

  Ras 癌蛋白的翻译后法呢基化是发挥其生物学效应的重要步骤，这一发现导致了法呢基蛋白转移酶抑制剂 (FTI) 的设计，以控制带有 Ras 突变的肿瘤的生长。对小鼠模型的临床前研究证实了它们对肿瘤生长的抑制作用并促进了临床开发。R115777 (ZARNESTRATM) 目前正在进行临床评估，最近的研究证实了其抗肿瘤潜力和低毒性。我们希望在此描述我们团队开发的用于访问 ZARNESTRATM 的化学合成路线。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

  DOI：

  10.1002/ejoc.200300538
• 作为产物：
  描述：

  (E)-3-(3-chlorophenyl)-1-phenylprop-2-en-1-ol 在 copper(II) perchlorate hexahydrate 、 叠氮基三甲基硅烷 、 水 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 反应 1.25h， 生成 N-(3-chlorophenyl)-(E)-β-styrenecarboxamide 、 N-phenyl-3-(3-chlorophenyl)-2-propenamide
  参考文献：
  名称：

  铜催化仲烯丙醇和苄醇直接转化为叠氮化物和酰胺：叠氮化物作为氮源的有效用途

  摘要：

  在2,3-二氯-5存在下，以仲醇、Cu(ClO4)2·6H2O为催化剂，以叠氮化三甲基甲硅烷(TMSN3)为氮源，探索了一种温和、简便的酰胺合成方法。 ,6-二氰基对苯醌 (DDQ) 在环境温度下。该方法已成功地适用于直接从其相应的醇制备叠氮化物，并在 ω-卤代叠氮化物的形成和烯丙醇在苄醇部分存在下的叠氮化中提供出色的化学选择性。此外，该策略为合成可作为 β-氨基酸前体的叠氮化物提供了机会。

  DOI：

  10.1002/ejoc.201500010

文献信息

• 一种替吡法尼喹啉酮中间体的高效合成方法
  申请人：中国海洋大学

  公开号：CN113072490B

  公开（公告）日：2022-08-16

  本发明提供了一种替吡法尼中间体6‑(4‑氯苯甲酰基)‑4‑(3‑氯苯基)‑3,4‑二氢‑2(1H)‑喹啉酮的高效合成方法，属于有机合成技术领域。本发明所提供的方法为，在伊顿试剂存在下，(E)‑3‑(3‑氯苯基)‑N‑苯基丙烯酰胺在溶剂中发生关环反应，生成4‑(3‑氯苯基)‑3,4‑二氢‑2(1H)‑喹啉酮，再向反应体系中加入4‑氯苯甲酸和金属掺杂改性分子筛催化剂，经傅克酰基化反应，得到6‑(4‑氯苯甲酰基)‑4‑(3‑氯苯基)‑3,4‑二氢‑2(1H)‑喹啉酮，即所述的替吡法尼喹啉酮中间体。本发明的合成方法产品收率高、易纯化、后处理操作简便、催化剂可以回收套用，具有良好的应用价值。
• [EN] FARNESYL PROTEIN TRANSFERASE INHIBITING (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES<br/>[FR] DERIVES DE LA (IMIDAZOL-5-YL)METHYL-2-QUINOLEINONE COMME INHIBITEUR DE LA PROTEINE FARNESYLE-TRANSFERASE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997021701A1

  公开（公告）日：1997-06-19

  (EN) This invention comprises the novel compounds of formula (I), wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 is hydrogen, C1-12alkyl, Ar1, Ar2C1-6alkyl, quinolinylC1-6alkyl, pyridylC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, aminoC1-6alkyl, or a radical of formula -Alk1-C(=O)-R9, -Alk1-S(O)-R9 or -Alk1-S(O)2-R9; R2, R3 and R16 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyl, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; R4 and R5 each independently are hydrogen, halo, Ar1, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl; R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, 4,4-dimethyl-oxazolyl, C1-6alkyloxy or Ar2oxy; R8 is hydrogen, C1-6alkyl, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, carboxyC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, imidazolyl, haloC1-6alkyl, C1-6alkyloxyC1-6alkyl, aminocarbonylC1-6alkyl, or a radical of formula -O-R10, -S-R10, -N-R11R12; R17 is hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxycarbonyl, Ar1; R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R19 is hydrogen or C1-6alkyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.(FR) L'invention concerne de nouveaux composés de la formule générale (I). Dans cette formule, la ligne en pointillé représente une liaison facultative; X est oxygène ou soufre; R1 est un hydrogène, C1-12alkyle, Ar1, Ar2C1-6alkyle, quinoléinylC1-6alkyle, pyridiylC1-6alkyle, hydroxyC1-6alkyle, C1-6alkyloxyC1-6alkyle, mono- or di(C1-6alkyl)aminoC1-6alkyle, amino C1-6alkyle, un radical de la formule -Alk1-C(=O)-R9, Alk1-S(O)-R9 ou -Alk1-S(O)2-R9; R2, R3 et R16 sont chacun d'une manière indépendante un hydrogène, hydroxy, halo, cyano, C1-6alkyle, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- ou di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyle, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyle, C1-6alkyloxycarbonyle, trihalométhyle, trihalométhoxy, C2-6alcényle; R4 et R5 sont chacun d'une manière indépendante un hydrogène, halo, Ar1, C1-6alkyle, hydroxyC1-6alkyle, C1-6alkyloxyC1-6alkyle, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyle, C1-6alkyloxycarbonyle, C1-6alkylS(O)C1-6alkyle ou C1-6alkyl-S(O)2C1-6alkyle; R6 et R7 sont chacun d'une manière indépendante un hydrogène, halo, cyano, C1-6alkyle, 4,4-diméthyl-oxyzolyl, C1-6alkyloxy ou Ar2oxy; R8 is hydrogène, C1-6alkyle, cyano, hydroxycarbonyle, C1-6alkyloxycarbonyle, C1-6alkylcarbonylC1-6alkyle, cyanoC1-6alkyle, C1-6alkyloxycarbonylC1-6alkyle, carboxyC1-6alkyle, hydroxyC1-6alkyle, aminoC1-6alkyle, mono- ou di(C1-6alkyl)aminoC1-6alkyle, imidazolyl, haloC1-6alkyle, C1-6alkyloxyC1-6alkyle, aminocarbonylC1-6alkyle, ou un radical de la formule -O-R10, -S-R10, -N-R11R12; R17 est un hydrogène, halo, cyano, C1-6alkyle, C1-6alkyloxycarbonyle, Ar1; R18 est un hydrogène, C1-6alkyle, C1-6alkyloxy ou halo; R19 est un hydrogène ou C1-6alkyle. Ces composés sont des inhibiteurs de la protéine farnésyle transférase. L'invention concerne également la préparation de ces composés, des compositions les contenant et leur utilisation en médecine.

  该发明涉及公式（I）的新化合物，其中虚线表示可选键；X为氧或硫；R1为氢，C1-12烷基，Ar1，Ar2C1-6烷基，喹啉基C1-6烷基，吡啶基C1-6烷基，羟基C1-6烷基，C1-6烷氧基C1-6烷基，单或双（C1-6烷基）氨基C1-6烷基，氨基C1-6烷基，或公式-Alk1-C（=O）-R9，-Alk1-S（O）-R9或-Alk1-S（O）2-R9的基团；R2，R3和R16各自独立地为氢，羟基，卤素，氰基，C1-6烷基，C1-6烷氧基，羟基C1-6烷氧基，C1-6烷氧基C1-6烷氧基，氨基C1-6烷氧基，单或双（C1-6烷基）氨基C1-6烷氧基，Ar1，Ar2C1-6烷基，Ar2氧基，Ar2C1-6烷氧基，羟基羰基，C1-6烷氧羰基，三卤甲基，三卤甲氧基，C2-6烯基；R4和R5各自独立地为氢，卤素，Ar1，C1-6烷基，羟基C1-6烷基，C1-6烷氧基C1-6烷基，C1-6烷氧基，C1-6烷基硫基，氨基，羟基羰基，C1-6烷氧羰基，C1-6烷基S（O）C1-6烷基或C1-6烷基S（O）2C1-6烷基；R6和R7各自独立地为氢，卤素，氰基，C1-6烷基，4,4-二甲基噁唑基，C1-6烷氧基或Ar2氧基；R8为氢，C1-6烷基，氰基，羟基羰基，C1-6烷氧羰基，C1-6烷基羰基C1-6烷基，氰基C1-6烷基，C1-6烷氧羰基C1-6烷基，羧基C1-6烷基，羟基C1-6烷基，氨基C1-6烷基，单或双（C1-6烷基）氨基C1-6烷基，咪唑基，卤素C1-6烷基，C1-6烷氧基C1-6烷基，氨基羰基C1-6烷基，或公式-O-R10，-S-R10，-N-R11R12的基团；R17为氢，卤素，氰基，C1-6烷基，C1-6烷氧基羰基，Ar1；R18为氢，C1-6烷基，C1-6烷氧基或卤素；R19为氢或C1-6烷基；具有法尼酰转移酶抑制活性；它们的制备，含有它们的组合物以及它们作为药物的用途。
• Method of use of (imidazol-5-yl)methyl-2-quinolinone derivatives to inhibit smooth muscle cell proliferation
  申请人：——

  公开号：US20040198771A1

  公开（公告）日：2004-10-07

  This invention comprises the use of compounds of formula (I) 1 wherein the dotted line represents an optional bond; X is oxygen or sulfur; R 1 is hydrogen, C 1-12 alkyl, Ar 1 , Ar 2 C 1-6 alkyl, quinolinylC 1-6 alkyl, pyridylC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, aminoC 1-6 alkyl, or a radical of formula —Alk 1 —C(═O)—R 9 , —Alk 1 —S(O)—R 9 or —Alk 1 —S(O) 2 —R 9 ; R 2 , R 3 and R 16 each independently are hydrogen, hydroxy, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-6 alkyloxy, C 1-6 alkyloxyC 1-6 alkyloxy, aminoC 1-6 alkyloxy, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyloxy, Ar 1 , Ar 2 C 1-6 alkyl, Ar 2 oxy, Ar 2 C 1-6 alkyloxy, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2-6 alkenyl; R 4 and R 5 each independently are hydrogen, halo, Ar 1 , C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, amino, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylS(O)C 1-6 alkyl or C 1-6 alkylS(O) 2 C 1-6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1-6 alkyl, 4,4-dimethyl-oxazolyl, C 1-6 alkyloxy or Ar 2 oxy; R 8 is hydrogen, C 1-6 alkyl, cyano, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonylC 1-6 alkyl, cyanoC 1-6 alkyl, C 1-6 alkyloxycarbonylC 1-6 alkyl, carboxyC 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, imidazolyl, haloC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, aminocarbonylC 1-6 alkyl, or a radical of formula —O—R 10 , —S—R 10 , —N—R 11 R 12 ; R 17 is hydrogen, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, Ar 1 ; R 18 is hydrogen, C 1-6 alkyl, C 1-6 alkyloxy or halo; R 19 is hydrogen or C 1-6 alkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

  本发明涉及化合物的使用，其化学式为（I）1，其中虚线代表可选键；X为氧或硫；R1为氢、C1-12烷基、Ar1、Ar2C1-6烷基、喹啉基C1-6烷基、吡啶基C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、单或双（C1-6烷基）氨基C1-6烷基、氨基C1-6烷基，或式为—Alk1—C(═O)—R9、—Alk1—S(O)—R9或—Alk1—S(O)2—R9的基团；R2、R3和R16各自独立地为氢、羟基、卤、氰、C1-6烷基、C1-6烷氧基、羟基C1-6烷氧基、C1-6烷氧基C1-6烷氧基、氨基C1-6烷氧基、单或双（C1-6烷基）氨基C1-6烷氧基、Ar1、Ar2C1-6烷基、Ar2氧基、Ar2C1-6烷氧基、羟基羧基、C1-6烷氧羧基、三卤甲基、三卤甲氧基、C2-6烯基；R4和R5各自独立地为氢、卤、Ar1、C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、C1-6烷氧基、C1-6烷硫基、氨基、羟基羧基、C1-6烷氧羧基、C1-6烷基S（O）C1-6烷基或C1-6烷基S（O）2C1-6烷基；R6和R7各自独立地为氢、卤、氰、C1-6烷基、4,4-二甲基-噁唑基、C1-6烷氧基或Ar2氧基；R8为氢、C1-6烷基、氰、羟基羧基、C1-6烷氧羧基、C1-6烷基羧基C1-6烷基、氰基C1-6烷基、C1-6烷氧羧基C1-6烷基、羧基C1-6烷基、羟基C1-6烷基、氨基C1-6烷基、单或双（C1-6烷基）氨基C1-6烷基、咪唑基、卤基C1-6烷基、C1-6烷氧基C1-6烷基、氨基羧基C1-6烷基，或式为—O—R10、—S—R10、—N—R11R12的基团；R17为氢、卤、氰、C1-6烷基、C1-6烷氧羧基、Ar1；R18为氢、C1-6烷基、C1-6烷氧基或卤；R19为氢或C1-6烷基；用于制造一种抑制平滑肌细胞增殖的药物。
• TREATMENT OF MITOCHONDRIAL DISORDERS USING A FARNESYL TRANSFERASE INHIBITOR
  申请人：LANSBURY, JR. PETER T.

  公开号：US20110060005A1

  公开（公告）日：2011-03-10

  Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies and mitochondrial disorders are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject an amount of a farnesyl transferase inhibitor, wherein the amount administered is sufficient to stimulate mitophagy in said subject. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

  本发明提供了一种低剂量法尼酰转移酶抑制剂的方法和制药组合物，用于治疗蛋白质病和线粒体疾病。这些低剂量低于最初设计这些化合物用于肿瘤治疗的剂量。该治疗方法包括向受试者施用足够的法尼酰转移酶抑制剂，以刺激该受试者的线粒体自噬。根据本发明的治疗方法还可以包括乙酰胆碱酯酶抑制剂、神经营养因子受体激活剂、NMDA拮抗剂、淀粉样沉积抑制剂、抗精神病药物、抗抑郁药、抗焦虑药或抗氧化剂。
• TREATMENT OF PROTEINOPATHIES USING A FARNESYL TRANSFERASE INHIBITOR
  申请人：Lansbury, JR. Peter T.

  公开号：US20110294794A1

  公开（公告）日：2011-12-01

  Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject in need thereof a therapeutically effective amount of a farnesyl transferase inhibitor, wherein the amount is effective to inhibit the farnesylation of a non-Ras FTase substrate involved in the autophagy pathway without substantially affecting the farnesylation of Ras or other oncology related substrates. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

  本发明提供了一种低剂量法尼醇转移酶抑制剂及其制药组合物，用于治疗蛋白病。这些低剂量低于最初设计这些化合物用于肿瘤治疗所使用的剂量。治疗包括向需要治疗的受体中注射治疗有效量的法尼醇转移酶抑制剂，其中该量能够有效抑制参与自噬通路的非Ras FTase底物的法尼酰化，而不会对Ras或其他与肿瘤相关的底物的法尼酰化产生明显影响。按照本发明的治疗方法还可以包括乙酰胆碱酯酶抑制剂、神经营养因子受体激活剂、NMDA拮抗剂、淀粉样沉积抑制剂、抗精神病药物、抗抑郁药物、抗焦虑药物或抗氧化剂。