4-amino-4-deoxy-5,8,10-trideazapteroic acid | 227016-65-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4-amino-4-deoxy-5,8,10-trideazapteroic acid
• 英文别名: 4-[2-(2,4-diamino-quinazolin-6-yl)-ethyl]-benzoic acid；4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoic acid
• CAS: 227016-65-1
• 化学式: C₁₇H₁₆N₄O₂
• 分子量: 308.34
• InChiKey: AWRNCYYACMZJOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  620.9±65.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-amino-4-deoxy-5,8,10-trideazapteroic acid 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.25h， 生成 diethyl-4-methylene-5,8,10-trideazaaminopterin
  参考文献：
  名称：

  Nair, M. Gopal; Fayard, Melanie L.; Lariccia, Joanna M., Medicinal Chemistry Research, 1999, vol. 9, # 3, p. 176 - 185

  摘要：

  DOI：
• 作为产物：
  描述：

  5-甲基-2-硝基苯甲腈 在 palladium on activated charcoal sodium hydroxide 、 sodium dithionite 、 氢气 、 sodium methylate 、 sodium 作用下， 以 甲醇 、 乙二醇乙醚 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 60.0~210.0 ℃ 、137.9 kPa 条件下， 反应 141.08h， 生成 4-amino-4-deoxy-5,8,10-trideazapteroic acid
  参考文献：
  名称：

  Nair, M. Gopal; Fayard, Melanie L.; Lariccia, Joanna M., Medicinal Chemistry Research, 1999, vol. 9, # 3, p. 176 - 185

  摘要：

  DOI：

文献信息

• Process for synthesizing antifolates
  申请人：Wu Ye

  公开号：US20050020833A1

  公开（公告）日：2005-01-27

  A process for synthesizing antifolate compounds is disclosed. The process includes cyclization of a readily available starting reagent, followed by one or more coupling steps to produce compounds that mimic folic acid. The compounds synthesized have commercial use as drugs in oncology, inflammatory disease, and other medical fields.

  公开了一种合成抗叶酸化合物的过程。该过程包括将易得的起始试剂环化，然后经过一个或多个偶联步骤，以产生模拟叶酸的化合物。合成的化合物在肿瘤学、炎症性疾病和其他医学领域具有商业用途。
• CRYSTALLINE SALT FORMS OF ANTIFOLATE COMPOUNDS AND METHODS OF MANUFACTURING THEREOF
  申请人：Pimplaskar Harish K.

  公开号：US20090253719A1

  公开（公告）日：2009-10-08

  The present invention provides methods of preparing antifolate compounds. The inventive methods can particularly be use for preparing compounds exhibiting improved bioavailability, making the compound particularly useful in pharmaceutical compositions. The compounds prepared according to the inventive methods are useful in the treatment of multiple conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.

  本发明提供了制备抗叶酸化合物的方法。本发明的方法特别适用于制备具有改善生物利用度的化合物，使该化合物特别适用于制药组合物。根据本发明方法制备的化合物在治疗多种疾病方面有用，包括异常细胞增殖、炎症性疾病、哮喘和关节炎。
• Antifolates for the treatment of cardiovascular, inflammatory, neoplastic, autoimmune and related diseases in sublingual dosage units, film strips, or skin patches
  申请人：Nair Madhavan G.

  公开号：US20100260825A1

  公开（公告）日：2010-10-14

  New metabolism blocked antifolates and their salts are provided along with new indications (coronary heart disease, cardiovascular diseases, stroke and termination of tubal or ectopic pregnancy) and methods (sublingual dosage forms, filmstrips or patches) for their use and delivery. Sublingual dosage forms or trans-dermal patches of metabolically blocked entities of this invention offer superior alternatives to traditional oral dosage forms to achieve greater and predictable therapeutic efficacy, lower toxicity and to overcome drug resistance by virtue of elimination of oxidative deactivation and production of toxic metabolites. Metabolism blocked antifolates bearing a fluorinated benzene ring, a thiophene ring, a pyrrole ring, a furan ring or a 8-deazapteridine ring that are provided in this invention are not previously described. The use of metabolism blocked antifolates to terminate medically complicated pregnancies that are taught herein are new inventions targeted to eliminate drug related toxicity to the host and to enhance therapeutic efficacy.

  本发明提供了新的代谢阻断型抗叶酸剂及其盐，并提供了新的适应症（冠心病、心血管疾病、中风以及输卵管或异位妊娠的终止）和使用方法（舌下剂型、薄膜或贴片）以及其输送方式。本发明中代谢阻断型实体的舌下剂型或经皮贴片，相对于传统的口服剂型，提供了更优越的选择，以实现更大且可预测的治疗效果、更低的毒性，并通过消除氧化失活和产生有毒代谢物来克服药物抵抗。本发明提供的带有氟苯环、噻吩环、吡咯环、呋喃环或8-脱氨嘌呤环的代谢阻断型抗叶酸剂在先前并未描述。本发明中教授的使用代谢阻断型抗叶酸剂来终止医疗复杂的妊娠是新的发明，旨在消除药物相关的对宿主的毒性，并增强治疗效果。
• ENZYME INHIBITING COMPOUNDS
  申请人：Roberts Michael J.

  公开号：US20110112126A1

  公开（公告）日：2011-05-12

  The present invention is directed to compounds that are specifically structured to provide enzyme inhibition. In specific embodiments, the enzyme inhibiting compounds exhibit antifolate activity. Particularly, the inventive compounds are formed of an antifolate residue that is active in inhibiting one or more of TS, DHFR, GAR, FPGS, and AICAR Tfase. The enzyme inhibiting compounds are useful in a variety of methods of treatment, including treating abnormal cell proliferation and treating inflammation.

  本发明涉及一种具有特定结构以提供酶抑制作用的化合物。在具体实施例中，这些酶抑制化合物表现出抗叶酸活性。特别地，本发明的化合物由一个抗叶酸残基形成，该残基在抑制TS、DHFR、GAR、FPGS和AICAR Tfase中的一个或多个方面具有活性。这些酶抑制化合物在多种治疗方法中有用，包括治疗异常细胞增殖和治疗炎症。
• [EN] QUINAZOLINE DERIVATIVES AS METABOLICALLY INERT ANTIFOLATE COMPOUNDS.<br/>[FR] ANTIFOLIQUES METABOLIQUEMENT INERTES UTILES DANS LE TRAITEMENT DES MALADIES LIEES A LA PROLIFERATION CELLULAIRE ANORMALE ET A UNE INFLAMMATION
  申请人：CHELSEA THERAPEUTICS INC

  公开号：WO2006029385A3

  公开（公告）日：2006-05-11