N-[4-[3-(2,4-diamino-5-pyrimidinyl)propyl]benzoyl]-L-glutamic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[4-[3-(2,4-diamino-5-pyrimidinyl)propyl]benzoyl]-L-glutamic acid
• 英文别名: N-{[4-(2,6-diamino-5-pyrimidinyl)propyl]benzoyl}-L-glutamic acid；(S)-2-{(S)-4-[3-(2,4-Diamino-pyrimidin-5-yl)-propyl]-benzoylamino}-pentanedioic acid；(2S)-2-[[4-[3-(2,4-diaminopyrimidin-5-yl)propyl]benzoyl]amino]pentanedioic acid
• 化学式: C₁₉H₂₃N₅O₅
• 分子量: 401.422
• InChiKey: BGHRPMFGMOHAJK-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  182
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(3-羟基丙基)苯甲酸甲酯 在 钯 sodium hydroxide 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 氢气 、 三氟乙酸 、 2,3-二甲基苯胺 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 生成 N-[4-[3-(2,4-diamino-5-pyrimidinyl)propyl]benzoyl]-L-glutamic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of a new series of dihydrofolate reductase inhibitors based on the 4-(2,6-diamino-5-pyrimidinyl)alkyl-L-glutamic acid structure

  摘要：

  A novel series of dihydrofolate reductase inhibitors was uncovered during an expansion of the SAR of 5,10-dideazatetrahydrofolic acid, and their biological activity was evaluated. These new analogs do not possess an oxygen at the 4 position and contain a monocyclic pyrimidine ring.

  DOI：

  10.1016/0960-894x(96)00053-4

文献信息

• Pyrimidinyl-glutamic acid derivatives
  申请人：Eli Lilly and Company

  公开号：US05426110A1

  公开（公告）日：1995-06-20

  The present invention provides novel pyrimidinyl-glutamic acid derivatives and intermediates thereto. Further provided are methods for inhibiting dihydrofolate reductase in mammals and for treating susceptible neoplasms in mammals, particularly humans.

  本发明提供了新型嘧啶基谷氨酸衍生物及其中间体。进一步提供了一种在哺乳动物中抑制二氢叶酸还原酶的方法，以及用于治疗哺乳动物中易感的肿瘤，特别是人类的方法。
• MEDICINAL COMPOSITIONS CONTAINING ANTI-Fas ANTIBODY
  申请人：Sankyo Company, Limited

  公开号：EP1180369A1

  公开（公告）日：2002-02-20

  The present invention provides a novel pharmaceutical composition containing an anti-Fas antibody which is useful as an agent for prophylaxis and/or treatment of an autoimmune disease or rheumatoid arthritis. More particularly, the present invention provides a pharmaceutical composition containing an anti-human Fas antibody having apoptosis inducing activity and a compound having a folate antagonist activity or a dihydrofolate reductase inhibiting activity, as active ingredients. According to the present invention, the amount of the anti-Fas antibody to be used can be reduced in an agent for prophylaxis and/or treatment of an autoimmune disease or rheumatoid arthritis, and thereby, the possibility that the patient becomes tolerant to anti-Fas antibody as a result of the production of antibodies against the anti-Fas antibody in the patient's body or the like can be decreased, and thus there can be provided a pharmaceutical composition of the present invention useful as an excellent agent for prophylaxis and/or treatment which can be used for a long time.

  本发明提供了一种含有抗 Fas 抗体的新型药物组合物，该药物组合物可用于预防和/或治疗自身免疫性疾病或类风湿性关节炎。 更具体地说，本发明提供了一种药物组合物，它含有一种具有诱导细胞凋亡活性的抗人 Fas 抗体和一种具有叶酸拮抗剂活性或二氢叶酸还原酶抑制活性的化合物作为活性成分。 根据本发明，在预防和/或治疗自身免疫性疾病或类风湿性关节炎的药剂中，可以减少抗 Fas 抗体的用量，从而降低患者因体内产生抗 Fas 抗体的抗体等而对 Fas 抗体产生耐受性的可能性，因此可以提供本发明的药物组合物，该药物组合物可作为预防和/或治疗的优良药剂长期使用。
• Pharmaceutical compositions containing anti-fas antibody
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20020103212A1

  公开（公告）日：2002-08-01

  A pharmaceutical composition containing an anti-human Fas antibody having apoptosis inducing activity and a compound having a folate antagonist activity or a dihydrofolate reductase inhibiting activity, as active ingredients for the prophylaxis and/or treatment of an autoimmune disease or rheumatoid arthritis. According to the present invention, the amount of the anti-Fas antibody to be used can be reduced and thereby the possibility that a patient may become tolerant to anti-Fas antibody as a result of the production of antibodies against the anti-Fas antibody in the patient's body or the like can be decreased, and thus is provided a pharmaceutical composition which can be used for a long time.

  一种药物组合物，含有一种具有诱导细胞凋亡活性的抗人 Fas 抗体和一种具有叶酸拮抗剂活性或二氢叶酸还原酶抑制活性的化合物作为活性成分，用于预防和/或治疗自身免疫性疾病或类风湿性关节炎。根据本发明，可以减少抗 Fas 抗体的用量，从而降低患者因体内产生抗 Fas 抗体的抗体等而对 Fas 抗体产生耐受性的可能性，因此提供了一种可以长期使用的药物组合物。
• Combinations of antibodies selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and other therapeutic agents
  申请人：——

  公开号：US20030133932A1

  公开（公告）日：2003-07-17

  An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

  本发明的抗体与人类 DR5 或人类 DR4 相互作用，在受体下游产生激动或拮抗作用，包括抑制细胞增殖和凋亡。详细介绍了抗体的方法和用途，可选择与各种治疗剂结合使用，包括治疗细胞凋亡相关疾病和治疗细胞生长失调。
• PYRIMIDINYL-GLUTAMIC ACID DERIVATIVES
  申请人：ELI LILLY AND COMPANY

  公开号：EP0722440A1

  公开（公告）日：1996-07-24