N-[[5-[2-[(6R)-2-Amino-3,4,5,6,7,8-hexahydro-4-oxopyrido-(2,3-d)-pyrimidin-6-yl]ethyl]-2-thienyl]carbonyl]-L-glutamic Acid | 127228-54-0

• 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-[[5-[2-[(6R)-2-Amino-3,4,5,6,7,8-hexahydro-4-oxopyrido-(2,3-d)-pyrimidin-6-yl]ethyl]-2-thienyl]carbonyl]-L-glutamic Acid
• 英文别名: N-[(5-{2-[(6R)-2-Amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-D]pyrimidin-6-YL]ethyl}-2-thienyl)carbonyl]-L-glutamic acid；(2S)-2-[[5-[2-[(6R)-2-amino-4-oxo-5,6,7,8-tetrahydro-3H-pyrido[2,3-d]pyrimidin-6-yl]ethyl]thiophene-2-carbonyl]amino]pentanedioic acid
• CAS: 127228-54-0
• 化学式: C₁₉H₂₃N₅O₆S
• 分子量: 449.488
• InChiKey: GQCXGHHHNACOGE-SKDRFNHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  211
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  谷氨酸二乙酯 在 盐酸 、 sodium hydroxide 、 2-chloro-2,4-dimethoxy-1,3,5-triazine 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[[5-[2-[(6R)-2-Amino-3,4,5,6,7,8-hexahydro-4-oxopyrido-(2,3-d)-pyrimidin-6-yl]ethyl]-2-thienyl]carbonyl]-L-glutamic Acid
  参考文献：
  名称：

  Asymmetric synthesis of dideazafolate antitumor agents via amidomethylation of nonracemic oxazolidinone imidates. Synthesis of LY309887, a cytotoxic dideazafolate analog related to lometrexol

  摘要：

  The asymmetric synthesis of LY309887, a cytotoxic dideazatetrahydrofolate analog related to lometrexol, has been accomplished via an application of diastereoselective amidomethylation of a chiral titanium (TV) acyloxazolidinone enolate. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(96)02418-5

文献信息

• N-(5,6,7,8-tetrahydropyrido(2,3-D)pyrimidin-6-yl-alkanoyl)-glutamic acid derivatives
  申请人：THE TRUSTEES OF PRINCETON UNIVERSITY

  公开号：EP0343801A2

  公开（公告）日：1989-11-29

  A compound selected from the group consisting of a glutamic acid derivative of the formula: in which: R¹ is -OH or -NH₂; R² is hydrogen or a carboxy protecting group; R³ is a carbon-carbon bond, alkylene of 1 to 4 car­bon atoms, cyclohexylene, or R⁴ is hydrogen or an amino protecting group; Q is -S- or -O-; R⁵ is hydrogen, chloro or fluoro; and the configuration about the carbon atom designated * is S; and the pharmaceutically acceptable salts thereof. Also disclosed is a method of combatting neoplastic growth in a mammal and a pharmaceutical composition for combatting neoplastic growth in a mammal making use of the above compound.

  本发明涉及一种从以下组合中选择的化合物：其中：R¹为-OH或-NH₂；R²为氢或羧基保护基；R³为碳-碳键，1到4个碳原子的烷基，环己烷基，或R⁴为氢或氨基保护基；Q为-S-或-O-；R⁵为氢，氯或氟；并且指定的碳原子*的构型为S；以及其药学上可接受的盐。本发明还公开了一种在哺乳动物中对抗肿瘤生长的方法和一种制备上述化合物的药物组合物，用于对抗哺乳动物中的肿瘤生长。
• Substituted Pyrimidine Compounds and Methods of Use and Manufacture
  申请人：Duquesne University of the Holy Spirit

  公开号：US20160039830A1

  公开（公告）日：2016-02-11

  This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH 2 , S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

  本发明提供了具有以下式子的取代嘧啶化合物：其中X为不存在，CH2，S或O，而R是具有从一到十个碳原子的烷基，以及其可选的盐、水合物或溶剂化物，这些化合物在治疗患有疾病或癌症的患者方面是有用的。本发明的化合物可用作多酶抗叶酸剂，有选择性地靶向叶酸受体（FR）。此外，本发明还提供了一种制备5-和6-取代环戊[d]嘧啶用于非经典和经典抗叶酸剂作为TS和DHFR抑制剂的方法。
• Substituted pyrimidine compounds and methods of use and manufacture
  申请人：Duquesne University of the Holy Spirit

  公开号：US10167287B2

  公开（公告）日：2019-01-01

  This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

  本发明提供了具有以下式子的取代嘧啶化合物： 其中，X 为无、CH2、S 或 O，R 为具有一至十个碳原子的烷基，以及可选的盐类、水合物或溶液，这些化合物可用于治疗疾病或癌症患者。本发明的化合物作为选择性靶向叶酸受体（FR）的多酶抗叶酸盐是有用的。此外，本发明还提供了一种制造 5-和 6-取代环戊并[d]嘧啶的方法，用于作为 TS 和 DHFR 抑制剂的非经典和经典抗叶酸盐。
• Modulatable switch for selection of donor modified cells
  申请人：Calimmune, Inc.

  公开号：US10426798B2

  公开（公告）日：2019-10-01

  The disclosed methods are generally directed to preventing, treating, suppressing, controlling or otherwise mitigating side effects of T-cell therapy, the T-cell therapy designed to accelerate immune reconstitution, induce a GVM effect, and/or target tumor cells.

  所公开的方法一般用于预防、治疗、抑制、控制或以其他方式减轻 T 细胞疗法的副作用，T 细胞疗法旨在加速免疫重建、诱导龙胆紫效应和/或靶向肿瘤细胞。
• 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。