DL-methyl folate (γ)

• 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: DL-methyl folate (γ)
• 英文别名: (DL)-methyl folate；Methylfolate；2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic acid
• 化学式: C₂₀H₂₁N₇O₆
• 分子量: 455.43
• InChiKey: BNZPKFAGFVCCMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  198
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  L-谷氨酸 在 1,1,2,3-四甲基胍 、 caesium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 DL-methyl folate (γ)
  参考文献：
  名称：

  Efficient Syntheses of Pyrofolic Acid and Pteroyl Azide, Reagents for the Production of Carboxyl-Differentiated Derivatives of Folic Acid

  摘要：

  Reaction of folic acid (1) with excess trifluoroacetic anhydride provides access to both the previously unknown N-10-(trifluoroacetyl)pyrofolic acid (8) and pyrofolic acid (9). Reaction of either of these materials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall from 1 without the need for chromatography). Treatment of 27 with differentially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.

  DOI：

  10.1021/ja971568j

文献信息

• Folate-modified cholesterol-bearing pullulan as a drug carrier
  申请人：Sunamoto Junzo

  公开号：US20070042970A1

  公开（公告）日：2007-02-22

  Folate modified cholesterol-bearing pullulan (FA-CHP) was synthesized by the reaction of folic acid γ-2-aminoethylamide and 4-nitorophenyl chloroformate-activated cholesterol-bearing pullulan, wherein folate and pullulan are connected through a NH—CH 2 —CH 2 —NH group. Approximately 0.5-1 folates are connected per about 100 glycoside units of pullulan. Then, several combinations of FA-CHP, cholesterol-bearing pullulan (CHP) and doxorubicin (DOX) mixture were tested for cancer selective cytotoxicity. A mixture of FA-CHP, CHP and DOX of 1:4:0.02 (weight ratio) gave sharp and selective damage to cells of a human epidermoid cancer KB known as expressing a high level of folate receptor. The same mixture inhibited the growth of HuH7 cells, which is a human hepatocellular carcinoma and is unknown as a folate receptor.

  叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）是通过叶酸γ-2-氨基乙酰胺和4-硝基苯基氯甲酸酯活化的胆固醇载体泊洛聚糖反应合成的，其中叶酸和泊洛聚糖通过一个NH—CH2— —NH基团连接。每约100个葡糖苷单元中连接了大约0.5-1个叶酸。然后，对叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）、胆固醇载体泊洛聚糖（CHP）和阿霉素（DOX）混合物进行了多种组合的癌症选择性细胞毒性测试。FA-CHP、CHP和DOX的混合物比例为1:4:0.02（重量比）对人表皮癌KB细胞具有高叶酸受体表达水平的细胞造成了明显和选择性的损伤。同样的混合物抑制了HuH7细胞的生长，这是一种人类肝细胞癌，并且未知是否具有叶酸受体。
• INACTIVATORS OF O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE
  申请人：Moschel Robert C.

  公开号：US20100204172A1

  公开（公告）日：2010-08-12

  Disclosed are compounds that are AGT inactivators that include a folate residue, e.g., a compound of formula (I), wherein X 1 , X 2 , R 1 , and R 2 are as described herein. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed are methods of enhancing the chemotherapeutic treatment of tumor cells and inactivating AGT in a tumor cell. The methods comprise, inter alia, administering a compound or pharmaceutically acceptable salt of formula (I).

  本发明涉及一种包括叶酸残基的AGT失活剂化合物，例如式(I)的化合物，其中X1、X2、R1和R2如本文所述。本发明还涉及一种包括本发明化合物和药学上可接受的载体的制药组合物。本发明还涉及增强肿瘤细胞化疗治疗和失活肿瘤细胞中AGT的方法。该方法包括，除其他外，给予式(I)的化合物或药学上可接受的盐。
• Derivatized oligonucleotides having improved uptake and other properties
  申请人：ISIS Pharmaceutical, Inc.

  公开号：US20020177150A1

  公开（公告）日：2002-11-28

  Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

  具有至少一个功能化核苷的连接核苷，其具有一种取代基，例如类固醇分子、报告分子、非芳香族亲脂分子、报告酶、肽、蛋白质、水溶性维生素、脂溶性维生素、RNA裂解复合物、金属螯合剂、卟啉、烷基化剂、芘、混合光核酶/插入剂或芳基叠氮化合物光交联剂，表现出增加的细胞摄取和其他特性。取代基可以通过连接基连接到功能化核苷的2'-位。如果其余连接的核苷至少部分为2'-脱氧-2'-氟、2'-O-甲氧基、2'-O-乙氧基、2'-O-丙氧基、2'-O-氨基烷氧基或2'-O-烯丙氧基核苷，则取代基可以通过连接基连接到核苷的3'或5'位置，或连接核苷的杂环碱基上，或连接相邻核苷的核苷酸间连接上。
• Arzneimittel zur Prophylaxe und Therapie von neurologischen und psychiatrischen Schäden durch Alkoholmissbrauch, enthaltend Thiamin, Folsäure und Cobalamin
  申请人：WÖRWAG PHARMA GmbH

  公开号：EP0558960A1

  公开（公告）日：1993-09-08

  Ein Arzneimittel zur Prophylaxe und Therapie von neurologischen und psychiatrischen Schäden durch Alkoholmißbrauch weist als Wirkstoffe Thiamin, Folsäure und eine deren biologische Verwertbarkeit ermöglichende Menge an Cobalaminen und/oder pharmakologisch gleichwirkende Analoge der vorgenannten Stoffe in einem pharmazeutisch verträglichen Träger auf.

  一种用于预防和治疗酗酒引起的神经和精神损伤的药物，其有效成分包括硫胺素、叶酸和一定量的钴胺素和/或上述物质的药理等效类似物，并以药学上可接受的载体保存，使其能够被生物利用。
• Treatment of neurodegenerative disorders
  申请人：Wageningen Centre for Food Sciences

  公开号：EP1645276A1

  公开（公告）日：2006-04-12

  The present invention is dedicated to the treatment of neurodegenerative disorders, in particular age related cognitive decline and age related hearing loss. These disorders can be alleviated by increasing 10-formyltetrahydrofolate or increasing thymidylate synthesis. The invention is of particular benefit to subjects that are MTHFR 677CT heterozygote and MTHFR 677CC homozygote. The substance that increases 10-formyltetrahydrofolate or increases thymidylate synthesis is selected from 10-formyltetrahydrofolate, 5-formyltetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-methylentetrahydrofolate, methionine, S-adenosylmethionine and poly-glutamate forms of 10-formyltetrahydrofolate, 5-formyltetrahydrofolate, 5,10-methenyltetrahydrofolate and 5,10-methylentetrahydrofolate and the substance may be in an acid or salt or ester form.

  本发明致力于治疗神经退行性疾病，特别是与年龄相关的认知能力下降和与年龄相关的听力损失。这些疾病可以通过增加 10-甲酰四氢叶酸或增加胸苷酸合成来缓解。本发明对 MTHFR 677CT 杂合子和 MTHFR 677CC 同合子的受试者特别有益。 增加10-甲酰基四氢叶酸或增加胸苷酸合成的物质选自10-甲酰基四氢叶酸、5-甲酰基四氢叶酸、5,10-亚甲基四氢叶酸、5,10-亚甲基五氢叶酸、蛋氨酸、10-甲酰基四氢叶酸、5-甲酰基四氢叶酸、5,10-亚甲基四氢叶酸、5,10-甲基五氢叶酸、蛋氨酸、S-腺苷蛋氨酸和多谷氨酸的形式，该物质可以是酸或盐或酯的形式。