5-((1,3-dihydroxypropan-2-ylamino)methyl)-6-hydroxy-4-methyl-1H-pyridin-2-one-3-carbonitrile | 1478121-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-((1,3-dihydroxypropan-2-ylamino)methyl)-6-hydroxy-4-methyl-1H-pyridin-2-one-3-carbonitrile
• 英文别名: 5-[(1,3-dihydroxypropan-2-ylamino)methyl]-6-hydroxy-4-methyl-2-oxo-1H-pyridine-3-carbonitrile
• CAS: 1478121-02-6
• 化学式: C₁₁H₁₅N₃O₄
• 分子量: 253.258
• InChiKey: GDESQZDNNPOGEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  126
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  丝氨醇 、 2,6-二羟基-3-氰基-4-甲基吡啶 在 聚合甲醛 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以44%的产率得到5-((1,3-dihydroxypropan-2-ylamino)methyl)-6-hydroxy-4-methyl-1H-pyridin-2-one-3-carbonitrile
  参考文献：
  名称：

  Design of Novel Potent Inhibitors of Human Uridine Phosphorylase-1: Synthesis, Inhibition Studies, Thermodynamics, and in Vitro Influence on 5-Fluorouracil Cytotoxicity

  摘要：

  Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors of human uridine phosphorylase (hUP) have been proposed as a strategy to increase Urd levels. We describe synthesis and characterization of a new class of ligands that inhibit hUP type 1 (hUP1). The design of ligands was based on a possible S(N)1 catalytic mechanism and as mimics of the carbocation in the transition state of hUP1. The kinetic and thermodynamic profiles showed that the ligands here presented are the most potent in vitro hUP1 inhibitors developed to date. In addition, a lead compound improved the antiproliferative effects of 5-FU on colon cancer cells, accompanied by a reduction of in vitro 5-FU cytotoxicity in aggressive SW-620 cancer cells.

  DOI：

  10.1021/jm401389u

文献信息

• USE OF 6-HYDROXY-2-PYRIDONES AND DERIVATIVES THEREOF FOR PREPARING A PHARMACEUTICAL COMPOSITION THAT ACTS BY INHIBITING THE HUMAN URIDINE PHOSPHORYLASE ENZYME
  申请人：UNIÃO BRASILEIRA DE EDUCAÇAO E ASSISTÊNCIA- MANTENEDORA DA PUCRS

  公开号：EP3042657A1

  公开（公告）日：2016-07-13

  The present invention describes the use of at least one compound of formula I or II or pharmaceutically acceptable salts thereof, for preparing a pharmaceutical composition that acts by inhibiting the phosphorylase uridine enzyme. Specifically, the present invention comprises the use of the said compounds for preparing a pharmaceutical composition that acts by inhibiting the human phosphorylase uridine enzyme, which can be optionally used in combination with at least one antineoplastic, wherein said inhibition increases the effectiveness of antineoplastic and decreases the side effects caused by the administration of antineoplastics.

  本发明描述了至少一种式 I 或式 II 化合物或其药学上可接受的盐用于制备通过抑制磷酸化酶尿苷酶发挥作用的药物组合物。具体地说，本发明包括使用上述化合物制备一种通过抑制人磷酸化酶尿苷酶而起作用的药物组合物，该组合物可选择与至少一种抗肿瘤药联合使用，其中所述抑制作用可提高抗肿瘤药的疗效并减少服用抗肿瘤药引起的副作用。
• US9700547B2
  申请人：——

  公开号：US9700547B2

  公开（公告）日：2017-07-11
• [EN] USE OF 6-HYDROXY-2-PYRIDONES AND DERIVATIVES THEREOF FOR PREPARING A PHARMACEUTICAL COMPOSITION THAT ACTS BY INHIBITING THE HUMAN URIDINE PHOSPHORYLASE ENZYME<br/>[FR] UTILISATION DE 6-HYDROXY-2-PYRIDONES ET DE SES DÉRIVÉS DANS LA PRÉPARATION D'UNE COMPOSITION PHARMACEUTIQUE AGISSANT PAR INHIBITION DE L'ENZYME URIDINE PHOSPHORYLASE HUMAINE<br/>[PT] USO DE 6-HIDROXI-2-PIRIDONAS E SEUS DERIVADOS NA PREPARAÇÃO DE UMA COMPOSIÇÃO FARMACÊUTICA QUE ATUE PELA INIBIÇÃO DA ENZIMA URIDINA FOSFORILASE HUMANA
  申请人：UNI O BRASILEIRA DE EDUCAÇ O E ASSIST NCIA MANTENEDORA DA PUCRS

  公开号：WO2015031968A1

  公开（公告）日：2015-03-12

  A presente invenção descreve o uso de pelo menos um composto de fórmula (I) ou (II) ou seus sais farmaceuticamente acetáveis na preparação de uma composição farmacêutica que atue pela inibição da enzima uridina fosforilase. Especificamente, a presente invenção compreende o uso dos referidos compostos na preparação de uma composição farmacêutica que atue pela inibição da enzima uridina fosforilase humana em combinação ou não com pelo menos um antineoplásico, em que a inibição atua no aumento da efetividade dos antineoplásicos e na diminuição dos efeitos colaterais provocados pela administração de antineoplásicos.