N-(4-carboxybenzyl)-4-phenylbutyramide | 112916-56-0

• 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: N-(4-carboxybenzyl)-4-phenylbutyramide
• 英文别名: 4-[(4-phenylbutanoylamino)methyl]benzoic acid
• CAS: 112916-56-0
• 化学式: C₁₈H₁₉NO₃
• 分子量: 297.354
• InChiKey: JDLDTNJGBSFKII-UHFFFAOYSA-N

物化性质

• 熔点：
  178-179 °C
• 沸点：
  567.3±50.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-carboxybenzyl)-4-phenylbutyramide 在 palladium on activated charcoal TEA 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 N-hydroxy-4-[(4-phenylbutyrylamino)methyl]benzamide
  参考文献：
  名称：

  Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors

  摘要：

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.

  DOI：

  10.1021/jm0303655
• 作为产物：
  描述：

  4-氨甲基苯甲酸甲酯 在 氢氧化钾 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 N-(4-carboxybenzyl)-4-phenylbutyramide
  参考文献：
  名称：

  Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors

  摘要：

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.

  DOI：

  10.1021/jm0303655
• 作为试剂：
  描述：

  己酸 、 N-甲基吗啉 、 氯甲酸乙酯 、 4-氨甲基苯甲酸 、 三甲基氯硅烷 在 二氯甲烷 、 盐酸 、 Brine 、 magnesium sulfate 作用下， 以 乙腈 、 N-(4-carboxybenzyl)-4-phenylbutyramide 、 三乙胺 为溶剂， 反应 20.67h， 以leaving N-(4-carboxybenzyl)hexanamide as an off-white solid的产率得到N-(4-carboxybenzyl)hexanamide
  参考文献：
  名称：

  Benzoic acid and benzoic acid ester derivatives having anti-inflammatory

  摘要：

  该发明涉及新型苯甲酸或苯甲酸酯衍生物、制药组合物及其使用方法。其用途是治疗关节炎、哮喘、雷诺氏病、炎症性肠病、三叉神经或疱疹性神经痛、炎症性眼部疾病、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、群集头痛、混合性血管综合症，以及非血管性张力性头痛。

  公开号：

  US04990533A1

文献信息

• Benzoic acid and benzoic acid ester derivatives to treat headaches
  申请人：Warner-Lambert Company

  公开号：US04719232A1

  公开（公告）日：1988-01-12

  Novel benzoic acid or benzoic acid ester derivatives, pharmaceutical compositions and methods of use thereof are the present invention. Utility is for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, dental pain, and headaches, particularly vascular headache, such as migraine, cluster, mixed vascular syndromes, as well as nonvascular, tension headaches.

  本发明涉及新型苯甲酸或苯甲酸酯衍生物、药物组合物及其使用方法。其用途是治疗关节炎、哮喘、雷诺氏病、炎症性肠病、三叉或疱疹性神经痛、炎症性眼部疾病、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、群集性头痛、混合性血管综合症，以及非血管性紧张性头痛。
• Imidazolyl or tetrazolyl substituted benzoic acid derivatives and
  申请人：Warner-Lambert Company

  公开号：US04755518A1

  公开（公告）日：1988-07-05

  Novel benzoic acid or benzoic acid ester derivatives, pharmaceutical compositions and methods of use thereof are the present invention. Utility is for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, dental pain, and headaches, particularly vascular headaches, such as migraine, cluster, mixed vascular syndromes, as well as nonvascular, tension headaches.

  本发明涉及苯甲酸或苯甲酸酯衍生物的新型，药物组合物及其使用方法。其用途是治疗关节炎、哮喘、雷诺氏病、炎症性肠病、三叉或疱疹性神经痛、炎症性眼疾、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、群集性头痛、混合性血管综合症，以及非血管性紧张性头痛。
• Benzoic acid and benzoic acid ester derivatives to treat pain
  申请人：Warner-Lambert Company

  公开号：US04719233A1

  公开（公告）日：1988-01-12

  Novel benzoic acid or benzoic acid ester derivatives, pharmaceutical compositions and methods of use thereof are the present invention. Utility is for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, dental pain, and headaches, particularly vascular headache, such as migraine, cluster, mixed vascular syndromes, as well as nonvascular, tension headaches.

  本发明涉及新型苯甲酸或苯甲酸酯衍生物、制药组合物及其使用方法。其应用于治疗关节炎、哮喘、雷诺氏病、炎症性肠病、三叉或疱疹性神经痛、炎症性眼部疾病、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、集群头痛、混合性血管综合症，以及非血管性张力性头痛。
• Benzoic acid and benzoic acid ester derivatives to treat inflammation
  申请人：Warner-Lambert Company

  公开号：US04719234A1

  公开（公告）日：1988-01-12

  Novel benzoic acid or benzoic acid ester derivatives, pharmaceutical compositions and methods of use thereof are the present invention. Utility is for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, dental pain, and headaches, particularly vascular headache, such as a migraine, cluster, mixed vascular syndromes, as well as nonvascular, tension headaches.

  本发明涉及新型苯甲酸或苯甲酸酯衍生物、制药组合物及其使用方法。其用途是治疗关节炎、哮喘、雷诺氏病、炎性肠病、三叉或带状疱疹性神经痛、炎性眼病、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、集群性头痛、混合性血管综合症，以及非血管性紧张性头痛。
• Sodium salt of N-C4-carboxybenzyl nonanamide
  申请人：Warner-Lambert Company

  公开号：US04980095A1

  公开（公告）日：1990-12-25

  Novel benzoic acid or benzoic acid ester derivatives, pharmaceutical compositions and methods of use thereof are the present invention. Utility is for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, dental pain, and headaches, particularly vascular headache, such as migraine, cluster, mixed vascular syndromes, as well as nonvascular, tension headaches.

  本发明涉及新型苯甲酸或苯甲酸酯衍生物、制药组合物及其使用方法。其用途在于治疗关节炎、哮喘、雷诺病、炎症性肠病、三叉或疱疹性神经痛、炎症性眼部疾病、牛皮癣、牙痛和头痛，特别是血管性头痛，如偏头痛、集群头痛、混合性血管综合症，以及非血管性张力性头痛。