7-氨基-1,3-二甲基-2,4-二羰基-1,2,3,4-四氢吡啶并[2,3-d]嘧啶-6-甲腈 | 17789-33-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 7-氨基-1,3-二甲基-2,4-二羰基-1,2,3,4-四氢吡啶并[2,3-d]嘧啶-6-甲腈
• 英文名称: 1,3-Dimethyl-2,4-dioxo-6-cyano-7-amino-1,2,3,4,-tetrahydropyrido<2,3-d>-pyrimidine
• 英文别名: 7-amino-6-cyano-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido<2,3-d>pyrimidine；7-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile；7-amino-6-cyano-1,3-dimethylpyrido<2,3-d>pyrimidine-2,4(1H,3H)-dione；7-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carbonitrile；7-Amino-2,4-dioxo-1,3-dimethyl-6-cyan-1,2,3,4-tetrahydro-pyrido<2,3-d>pyrimidin；7-amino-1,3-dimethyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carbonitrile
• CAS: 17789-33-2
• 化学式: C₁₀H₉N₅O₂
• mdl: MFCD01114843
• 分子量: 231.214
• InChiKey: AGTYJDRLIOPVMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-氨基-1,3-二甲基-2,4-二羰基-1,2,3,4-四氢吡啶并[2,3-d]嘧啶-6-甲腈 在 sodium nitrite 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 0.5h， 以80 mg的产率得到6-cyano-1,3-dimethylpyrido<2,3-d>pyrimidine-2,4,7-(1H,3H,8H)-trione
  参考文献：
  名称：

  Hirota, Kosaku; Kitade, Yukio; Senda, Shigeo, Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 345 - 347

  摘要：

  DOI：
• 作为产物：
  描述：

  6-氨基-1,3-二甲基-2,4-二氧代-1,2,3,4-四氢嘧啶-5-甲醛 在 sodium ethanolate 作用下， 生成 7-氨基-1,3-二甲基-2,4-二羰基-1,2,3,4-四氢吡啶并[2,3-d]嘧啶-6-甲腈
  参考文献：
  名称：

  Synthesis and pharmacology of pyrido[2,3-d]pyrimidinediones bearing polar substituents as adenosine receptor antagonists

  摘要：

  Amino-substituted pyrido[2,3-d]pyrimidinediones have previously been found to bind to adenosine A(1) and A(2A) receptors in micromolar concentrations. The present study was aimed at studying the structure-activity relationships of this class of compounds in more detail. Most of the investigated compounds were provided with polar substituents. such as ethoxycarbonyl groups and basic amino functions, in order to improve their water-solubility. The compounds were synthesized starting from 6-amino-1,3-dimethyfuracil via different reaction sequences involving (cyano)acetylation, Vilsmeier formylation, or reaction with diethyl ethoxymethylemalonate (EMME). The most potent and selective compound of the present series was 6-carbethoxy-1,2,3,4-tetrahydro-1.3-dimethyl-5-(2-naphthylmethyl) aminopyrido[2,3-d]pyrimidine-2,4-dione (11c) with a K-i value of 5 nM at rat and 25 nM at human A, receptors. The compound was more than 60-fold selective versus A(3) and more than 300-fold selective versus A2A receptors. It showed all over 300-fold improvement with respect to the lead compound. In GTP gamma S binding studies at membranes of Chinese hamster ovary cells recombinantly expressing the human adenosine A, receptor, 11c behaved as an antagonist with inverse agonistic activity. A regioisomer of 11c, 6-carbethoxy-1,2,3,4-tetrahydro-1,3-dimethyl-7-(2-naphthylmethyl)aminopyrido[2,3-d]pyrimidine-2,4-dione (7a) in which the 2-naphthylmethylamino substituent at position 5 of 11c was moved to the 7-position, was a relatively potent (K-i = 226 nM) and selective (> 20-fold) A(3) ligand. In the series of compounds lacking an electron-withdrawing ethoxycarbonyl or cyano substituent in the 6-position, compounds with high affinity for adenosine A(2A) receptors were identified. Such as 1,2,3,4-tetrahydro-1,3-dimethyl-5-(1-naphthyl)aminopyrido[2,3-d]pyrimidine-2,4-dioile 16b (K-i human A(2A) = 81.3 nM, K-i human A(1) = 153 nM, and K-i human A(3) > 10,000 nM). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.12.008

文献信息

• Pyrido[2,3-<i>d</i>]pyrimidines and pyrido[2,3-<i>d</i>; 5-<i>d</i>′]dipyrimidines as potential chemotherapeutic agents.<b>VIII</b>
  作者：Vishnu J. Ram、D. A. Vanden Berghe、A. J. Vlietinck

  DOI：10.1002/jhet.5570250133

  日期：1988.1

  ne-6-imino-1,3-dimethyluracil hydrochloride (1) with active methylene compounds 2 and 4 yielded bi- and tricyclic heterocyclic compounds 3 and 5. All the prepared compounds were screened for chemotherapeutical activities but none were active.

  5-二甲基氨基亚甲基-6-亚氨基-1,3-二甲基尿嘧啶盐酸盐（1）与活性亚甲基化合物2和4的反应生成双环和三环杂环化合物3和5。筛选所有制备的化合物的化学治疗活性，但没有活性。
• A Novel Microwave-assisted One-pot Synthesis of Pyrano[2,3-<i>d</i>]pyrimidines and Pyrido[2,3-<i>d</i>]pyrimidines via a Three Component Reaction in Solvent-Free Condition
  作者：Pulak J. Bhuyan、Ipsita Devi

  DOI：10.1055/s-2003-43367

  日期：——

  nitriles 3 in presence of acetic anhydride proceeds under microwave-assisted conditions to give pyrano[2,3-d]pyrimidines 4 in excellent yields. 6-Aminouracils 5 or 6-hydroxy-aminouracils 7 react with 2 and 3 under identical conditions to yield pyrido[2,3-d]pyrimidines 6 or pyrido[2,3-d]pyrimidine oxides 8 in high yields.

  在乙酸酐存在下，巴比妥酸 1、原甲酸三乙酯 2 和烷基腈 3 的三组分环缩合反应在微波辅助条件下进行，以优异的收率得到吡喃并 [2,3-d] 嘧啶 4。6-氨基尿嘧啶5或6-羟基-氨基尿嘧啶7在相同条件下与2和3反应以高产率产生吡啶并[2,3-d]嘧啶6或吡啶并[2,3-d]嘧啶氧化物8。
• Reactivities of 6-Amino-1,3-dimethyl-5-thioformyluracil toward Nucleophiles and Its Application to Synthesis of Pyrido(2,3-d)pyrimidines.
  作者：Kosaku HIROTA、Keiko KUBO、Hironao SAJIKI

  DOI：10.1248/cpb.45.542

  日期：——

  The reaction of the 5-thioformyluracil 1 with phenylhydrazine and various amines readily afforded the hydrazone 3a and Schiff bases 3b-d, respectively. Further, carbanions and Wittig reagents reacted with 1 to give pyrido[2, 3-d]pyrimidines 4 and 9. The corresponding 5-formyluracil 2 possessed much lower reactivities toward these nucleophiles than did 1.

  5-硫代甲酰尿嘧啶1与苯肼和各种胺的反应容易地分别得到腙3a和希夫碱3b-d。此外，碳负离子和维蒂希试剂与1反应得到吡啶并[2, 3-d]嘧啶4和9。相应的5-甲酰尿嘧啶2对这些亲核试剂的反应活性比1低得多。
• Pyrimidines. 21. Novel reactions of 5-cyano-1,3-dimethyluracil with carbon nucleophiles. A facile preparation of certain pyrido[2,3-<i>d</i>]pyrimidines
  作者：Tsann-Long Su、Kyoichi A. Watanabe

  DOI：10.1002/jhet.5570210560

  日期：1984.9

  respectively) in high yields. On the other hand, reaction of 8 with acetonitrile in base gave the Michael adduct, 5-cyano-6-cyanomethyl-5,6-dihydrouracil (15, R = H), and the hydrated product, 1,3-dimethyluracil-5-carboxamide (9) as the major products, and 7-amino-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (18a) in only very low yield. Similar reaction with butanone gave 7-ethyl-1,3-dimethyl- and

  在碱中用活化的乙腈如丙二腈，氰基乙酸乙酯或氰基乙酰胺处理5-氰基-1,3-二甲基尿嘧啶（8），得到7-氨基-6-氰基-，7-氨基-6-乙氧基羰基-和7-氨基-6-氨基羰基-1,3-二甲基吡啶并[2,3- d ]嘧啶-2,4（1 H，3 H）-二酮（分别为18b，18c和18d）。另一方面，8与碱中的乙腈反应生成迈克尔加合物5-氰基-6-氰甲基-5,6-二氢尿嘧啶（15，R = H）和水合产物1,3-二甲基尿嘧啶-5 -羧酰胺（9）为主要产物，7-氨基-1,3-二甲基吡啶[2,3- d] pyrimidine-2,4（1 H，3 H）-dione（18a）的收率非常低。与丁酮类似的反应得到7-乙基-1,3-二甲基-和1,3,6,7-四甲基吡啶并[2,3 - d ]嘧啶-2,4（1 H，3 H）-二酮（10b和10c），产量低。
• Synthesis of pyrido [2,3-d]pyrimidines on the basis of 5-formyl-6-aminouracils
  作者：N. M. Cherdantseva、V. M. Nesterov、T. S. Safonova

  DOI：10.1007/bf00523084

  日期：1983.6