3-(3-phthalimidobutyl)-5-<2-(ethylamino)-4-pyridyl>-1,2,4-triazole | 86649-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-(3-phthalimidobutyl)-5-<2-(ethylamino)-4-pyridyl>-1,2,4-triazole
• 英文别名: 2-[4-[3-[2-(ethylamino)pyridin-4-yl]-1H-1,2,4-triazol-5-yl]butyl]isoindole-1,3-dione
• CAS: 86649-66-3
• 化学式: C₂₁H₂₂N₆O₂
• 分子量: 390.445
• InChiKey: WZPFOKVGZBXCKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(3-phthalimidobutyl)-5-<2-(ethylamino)-4-pyridyl>-1,2,4-triazole 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 54.33h， 生成 1-cyano-3-[4-[3-[2-(ethylamino)pyridin-4-yl]-1H-1,2,4-triazol-5-yl]butyl]-2-methylguanidine
  参考文献：
  名称：

  Bioisosteric prototype design of biaryl imidazolyl and triazolyl competitive histamine H2-receptor antagonists

  摘要：

  The structural relationship of the competitive histamine H2-receptor antagonist 3-amino-5-(2-amino-4-pyridyl)-1,2,4-triazole (1) to the agonist histamine and to antagonists of the cimetidine type was explored by the design and synthesis of four series of bioisosterically designed prototypes. Biological data from these series was best interpreted as indicating a similarity between the imidazole moiety of histamine and cimetidine and the 2-amino-4-pyridyl moiety of 1. On the basis of this data, sequential replacement of 2-amino-4-pyridyl by 2-[(dimethylamino)methyl]-5-furyl and 2-guanidino-4-triazolyl moieties led to a structurally more potent series of biaryl histamine H2-receptor antagonists. The best of these, 2-methyl-4-(2-guanidino-4-thiazolyl)imidazole (29, CP-57,361-1) was 120 times more potent as a histamine H2-receptor antagonist than 1.

  DOI：

  10.1021/jm00161a005
• 作为产物：
  描述：

  2-(乙基氨基)异烟酰肼 、 ethyl 5-phthalimidopentimidate hydrochloride 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 3-(3-phthalimidobutyl)-5-<2-(ethylamino)-4-pyridyl>-1,2,4-triazole
  参考文献：
  名称：

  Bioisosteric prototype design of biaryl imidazolyl and triazolyl competitive histamine H2-receptor antagonists

  摘要：

  The structural relationship of the competitive histamine H2-receptor antagonist 3-amino-5-(2-amino-4-pyridyl)-1,2,4-triazole (1) to the agonist histamine and to antagonists of the cimetidine type was explored by the design and synthesis of four series of bioisosterically designed prototypes. Biological data from these series was best interpreted as indicating a similarity between the imidazole moiety of histamine and cimetidine and the 2-amino-4-pyridyl moiety of 1. On the basis of this data, sequential replacement of 2-amino-4-pyridyl by 2-[(dimethylamino)methyl]-5-furyl and 2-guanidino-4-triazolyl moieties led to a structurally more potent series of biaryl histamine H2-receptor antagonists. The best of these, 2-methyl-4-(2-guanidino-4-thiazolyl)imidazole (29, CP-57,361-1) was 120 times more potent as a histamine H2-receptor antagonist than 1.

  DOI：

  10.1021/jm00161a005

文献信息

• Triazole gastric anti-secretory agents
  申请人：PFIZER INC.

  公开号：EP0074229A1

  公开（公告）日：1983-03-16

  Gastric anti-secretory agents of the formula or pharmaceutically acceptable salts thereof, wherein R is alkyl and R' is hydrogen, methyl or ethyl; and Y is hydrogen, hydroxymethyl, alkyl or -(CH2)nNHC(Z)Q wherein n is an integer from 1 to 4; and Z and Q, when taken together, form a 4-pyrimidinone group; or when taken separately, Z is oxygen, sulfur, =N-C-N, or =(CH)N02; and Q is -CH=CHR" wherein R" is 2-methyl-5-thiazolyl, 4-pyridyl or 4-imidazolyl; or Q is -(CH2)mR"', wherein R" is hydrogen, alkyl, thioalkoxy, alkoxy, amino, N-monoalkylamino, N,N-dialkylamino, 2-guanidino-4-thiazolyl, 5-dimethylaminomethyl-2-furyl, 2-pyrazinyl, 4-imidazolyl, 5-methyl-4-imidazolyl, phenyl, mono-substituted phenyl, 3-pyridyl, mono-substituted 3-pyridyl, 4-pyridyl, or mono-substituted 4-pyridyl, wherein said substituents are halo, alkoxy, hydroxy or alkylamino; and m is 0 or an integer from 1 to 3; provided that when R'" is hydrogen, alkoxy, phenoxy or pyridoxy, m is other than 0; said alkyl, alkoxy, and thioalkoxy groups having from 1 to 4 carbon atoms.

  式中的抗胃分泌剂 或其药学上可接受的盐，其中 R 是烷基，R' 是氢、甲基或乙基；以及 Y 是氢、羟甲基、烷基或-(CH2)nNHC(Z)Q 其中 n 是 1 到 4 的整数；以及 Z 和 Q 合在一起时形成 4-嘧啶酮基团；或分开时，Z 是氧、硫、=N-C-N 或 =(CH)N02；Q 是-CH=CHR"，其中 R "是 2-甲基-5-噻唑基、4-吡啶基或 4-咪唑基；或 Q是-(CH2)mR"'，其中R "是氢、烷基、硫代烷氧基、烷氧基、氨基、N-单烷基氨基、N,N-二烷基氨基、2-胍基-4-噻唑基、5-二甲基氨基甲基-2-呋喃基、2-吡嗪基、4-咪唑基、5-甲基-4-咪唑基、苯基、单取代苯基、3-吡啶基、单取代 3-吡啶基、4-吡啶基或单取代 4-吡啶基，其中所述取代基为卤代、烷氧基、羟基或烷基氨基；和 m 为 0 或 1 至 3 的整数； 但当 R'"为氢、烷氧基、苯氧基或吡啶氧基时，m 不为 0；所述烷基、烷氧基和硫代烷氧基具有 1 至 4 个碳原子。
• LIPINSKI C. A.; LAMATTINA J. L.; OATES P. J., J. MED. CHEM., 29,(1986) N 11, 2154-2163
  作者：LIPINSKI C. A.、 LAMATTINA J. L.、 OATES P. J.

  DOI：——

  日期：——
• Bioisosteric prototype design of biaryl imidazolyl and triazolyl competitive histamine H2-receptor antagonists
  作者：Christopher A. Lipinski、John L. LaMattina、P. J. Oates

  DOI：10.1021/jm00161a005

  日期：1986.11

  The structural relationship of the competitive histamine H2-receptor antagonist 3-amino-5-(2-amino-4-pyridyl)-1,2,4-triazole (1) to the agonist histamine and to antagonists of the cimetidine type was explored by the design and synthesis of four series of bioisosterically designed prototypes. Biological data from these series was best interpreted as indicating a similarity between the imidazole moiety of histamine and cimetidine and the 2-amino-4-pyridyl moiety of 1. On the basis of this data, sequential replacement of 2-amino-4-pyridyl by 2-[(dimethylamino)methyl]-5-furyl and 2-guanidino-4-triazolyl moieties led to a structurally more potent series of biaryl histamine H2-receptor antagonists. The best of these, 2-methyl-4-(2-guanidino-4-thiazolyl)imidazole (29, CP-57,361-1) was 120 times more potent as a histamine H2-receptor antagonist than 1.