ethyl 5-amino-1,2-dihydro-3-<(N-methyl-N-phenylamino)methyl>pyrido<3,4-b>pyrazine-7-carbamate | 80434-77-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: ethyl 5-amino-1,2-dihydro-3-<(N-methyl-N-phenylamino)methyl>pyrido<3,4-b>pyrazine-7-carbamate
• 英文别名: Ethyl 5-amino-1,2-dihydro-3-[(N-methyl-N-phenyl)aminomethyl]pyrido[3,4-b]pyrazine-7-carbamate；ethyl 5-amino-1,2-dihydro-3-[(N-methyl-N-phenylamino)methyl]pyrido[3,4-b]pyrazine-7-carbamate；Carbamic acid, (5-amino-1,2-dihydro-3-((methylphenylamino)methyl)pyrido(3,4-b)pyrazin-7-yl)-, ethyl ester；ethyl N-[5-amino-3-[(N-methylanilino)methyl]-1,2-dihydropyrido[3,4-b]pyrazin-7-yl]carbamate
• CAS: 80434-77-1
• 化学式: C₁₈H₂₂N₆O₂
• 分子量: 354.412
• InChiKey: KNHPZFQUZAMWBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 5-amino-1,2-dihydro-3-<(N-methyl-N-phenylamino)methyl>pyrido<3,4-b>pyrazine-7-carbamate 以12%的产率得到
  参考文献：
  名称：

  TEMPLE, C. ,, JR;WHEELER, G. P.;ELLIOTT, R. D.;ROSE, J. D.;COMBER, R. N.;+, J. MED. CHEM., 1983, 26, N 1, 91-95

  摘要：

  DOI：
• 作为产物：
  描述：

  1-Amino-3--2-propanol 在 镍 磷酸 、 氢气 、 二甲基亚砜 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 25.0~60.0 ℃ 、101.33 kPa 条件下， 反应 62.5h， 生成 ethyl 5-amino-1,2-dihydro-3-<(N-methyl-N-phenylamino)methyl>pyrido<3,4-b>pyrazine-7-carbamate
  参考文献：
  名称：

  New anticancer agents: synthesis of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines)

  摘要：

  Reaction of alpha-aminoacetophenone oximes (2) with ethyl 6-amino-4-chloro-5-nitropyridine-2-carbamate (1) gave ethyl 6-amino-5-nitro-4-[(2-oxo-2-phenylethyl)amino]pyridine-2-carbamate oximes (3), which were hydrolyzed under acidic conditions to give the corresponding ketones (4). Related pyridines substituted with a keto side chain were prepared from 1 and 1,3-diaminopropanone oximes and by oxidation of the side-chain hydroxy group of ethyl 6-amino-4- [[3-(N-methyl-N-phenylamino)-2-hydroxypropyl]amino]-5-nitropyridine-7- carbamates (6). Catalytic hydrogenation of the nitro group of 4 over Raney nickel in a large volume of ethanol gave the 1-deaza-7,8-dihydropteridines (7). Several of the oximes 3 were successfully hydrogenated to give 7 directly. The resulting 1-deaza-7,8-dihydropteridines showed potent cytotoxicity against cultured L1210 cells and significant anticancer activity against lymphocytic leukemia P-388 in mice. These biological activities are attributed to the accumulation of cells at mitosis.

  DOI：

  10.1021/jm00351a008

文献信息

• 1,2-Dihydropyrido[3,4-b]pyrazines: structure-activity relationships
  作者：Carroll Temple、Glynn P. Wheeler、Robert D. Elliott、Jerry D. Rose、Robert N. Comber、John A. Montgomery

  DOI：10.1021/jm00355a018

  日期：1983.1

  Certain derivatives containing the 1,2-dihydropyrido[3,4-b]pyrazine (1-deaza-7,8-dihydropteridine) ring system are active against experimental neoplasms in mice. The mechanism of action of these agents has been attributed to the accumulation of cells at mitosis. Identification of the structural features that are necessary for activity was accomplished by evaluation of modified 1-deazapteridines and

  某些含有1,2-二氢吡啶并[3,4-b]吡嗪（1-deaza-7,8-dihydropteridine）环系统的衍生物具有抗小鼠实验肿瘤的活性。这些试剂的作用机理已归因于有丝分裂时细胞的积累。活性必需的结构特征的鉴定是通过评估修饰的1-脱氮哌啶以及开环和开环的类似物来完成的。相对于4-氨基-1-脱氮基-7，8-二氢-6-[（（N-甲基苯胺基）甲基]蝶啶-2-氨基甲酸酯（11）和相应的6-苯基化合物（12），没有抗肿瘤活性用7,8-二氢蝶啶，3-deaza-7,8-二氢蝶啶和相应的杂芳族化合物观察到。而且，当1-deaza-7,8-dihydropteridines氧化为1-deazapteridines或还原为1-deaza-5时，活性会降低或破坏。6,7,8-四氢蝶啶。另外，用其他取代基取代4-氨基会破坏活性。似乎需要具有芳基的6位取代基，这对于活性是必要的，当在7位上取代甲基时，活性会增加。
• Novel 1,2-dihydropyrido-(3,4-b)pyrazines
  申请人：Southern Research Institute

  公开号：EP0090681A2

  公开（公告）日：1983-10-05

  1,2-Dihydropyrido[3,4-b]pyrazines are provided which possess anticancer activity. The compounds have the structure: wherein x has a value of 1, 2 or 3; Y is CH2 or N(CH3); R1is a lower alkyl group; e.g., an alkyl group containing up to six carbon atoms such as methyl, ethyl, propyl, butyl, etc.; R2 is a member selected from the group consisting of hydrogen, alkyl radicals having from about one to about 12 carbon atoms, preferably from about one to about 6 carbon atoms; alkenyl radicals having from about two to about 15 carbon atoms, preferably from about two to about 10 carbon atoms; cycloalkyl radi- cads having from about three to about 20 carbon atoms, preferably from about three to about 15 carbon atoms; aralkyl and alkaryl radicals having from about six to about 20 carbon atoms, preferably from about six to about 15 carbon atoms; a halogen radical, e.g., chlorine, fluorine, bromine and iodine; a hydroxyl group; an amino group; an alkoxy or aryloxy group; an alkylthio group or an arylthio group having from about one to about 20 carbon atoms, preferably from about one to about 15 carbon atoms; a sulfonic acid group or alkyl- or arylsulfonyl group having from about one to about 20 carbon atoms, preferably from about one to about 15 carbon atoms; an alkyl- or arylsulfinyl group having from about one to about 20 carbon atoms, preferably from about one to about 15 carbon atoms; an alkyl- or aryl mono- or diamino group having from about one to about 20 carbon atoms, preferably from about one to about 15 carbon atoms; a hydrocarbyl group, such as defined above, carrying halogen, hydroxyl; amino, alkoxy or aryloxy; and, when taken together with the aromatic ring to which it is attached , a fused ring structure such as naphthyl; and R3 and R4 are either both hydrogen or one is hydrogen and the other is a lower alkyl group; provided that when each of R2, R3 and R4 are hydrogen, Y is CH2.

  本研究提供了具有抗癌活性的 1,2-二氢吡啶并[3,4-b]吡嗪类化合物。这些化合物具有如下结构 其中 x 的值为 1、2 或 3；Y 为 CH2 或 N(CH3)；R1 为低级烷基；例如R1 是低级烷基；例如，含有多达六个碳原子的烷基，如甲基、乙基、丙基、丁基等； R2 是选自下列化合物的成员R2 是选自以下组别的成员：氢、具有约 1 至约 12 个碳原子，最好是约 1 至约 6 个碳原子的烷基；具有约 2 至约 15 个碳原子，最好是约 2 至约 10 个碳原子的烯基；具有约 3 至约 20 个碳原子，最好是约 3 至约 15 个碳原子的环烷基；具有约 6 至约 20 个碳原子，最好是约 6 至约 15 个碳原子的芳烷基和烷芳基；卤素基，例如：氯、氟、溴、烷基、烯烷基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、炔烃基、羟基；氨基；烷氧基或芳氧基；烷硫基或芳硫基，具有约 1 至约 20 个碳原子，最好是约 1 至约 15 个碳原子；磺酸基或烷基或芳基磺酰基，具有约 1 至约 20 个碳原子，最好是约 1 至约 15 个碳原子；烷基或芳基亚磺酰基，具有约 1 至约 20 个碳原子，最好是约 1 至约 15 个碳原子；具有约 1 至约 20 个碳原子，最好是约 1 至约 15 个碳原子的烷基或芳基一元或二元基团； 如上定义的烃基，带有卤素、羟基、氨基、烷氧基或芳氧基；当与所连接的芳环一起时，为融合环结构，如萘基；以及 R3 和 R4 要么都是氢，要么一个是氢，另一个是低级烷基；条件是当 R2、R3 和 R4 都是氢时，Y 为 CH2。
• Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders
  申请人：——

  公开号：US20020165261A1

  公开（公告）日：2002-11-07

  The invention features a method for treating a patient having a cancer or other neoplasm, by administering to the patient (i) a benzimidazole or a metabolite or analog thereof; and (ii) pentamidine or a metabolite or analog thereof simultaneously or within 14 days of each other in amounts sufficient to inhibit the growth of the neoplasm.

  本发明的特点是一种治疗癌症或其他肿瘤患者的方法，其方法是同时或在 14 天内向患者施用(i) 苯并咪唑或其代谢物或类似物；(ii) 戊脒或其代谢物或类似物，其用量足以抑制肿瘤的生长。
• ——
  作者：TEMPLE C. G.、 MONTGOMERY J. A.、 ELLIOTT R. D.、 WHEELER G. P.

  DOI：——

  日期：——
• Soft tissue implants and drug combination compositions, and use thereof
  申请人：Hunter L. William

  公开号：US20070196421A1

  公开（公告）日：2007-08-23

  Soft tissue implants (e.g., breast, pectoral, chin, facial, lip, and nasal implants) are used in combination with an anti-scarring drug combination in order to inhibit scarring that may otherwise occur when the implant is placed within an animal.