2-(benzylthio)pyrimidine-4,5,6-triamine | 95493-97-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(benzylthio)pyrimidine-4,5,6-triamine
• 英文别名: 2-butylthio-4,5,6-triaminopyrimidine；2-benzylsulfanyl-pyrimidine-4,5,6-triamine；2-(benzylthio)-pyrimidine-4,5,6-triamine；2-benzylthio-4,5,6-triaminopyrimidine；4,5,6-Triamino-2-benzylmercapto-pyrimidin；2-benzylsulfanylpyrimidine-4,5,6-triamine
• CAS: 95493-97-3
• 化学式: C₁₁H₁₃N₅S
• 分子量: 247.324
• InChiKey: TXUMUGFOEVKZPM-UHFFFAOYSA-N

物化性质

• 沸点：
  528.5±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(benzylthio)pyrimidine-4,5,6-triamine 在 盐酸 、 H₄N⁽¹⁺⁾*O₄S^(2-) 、 六甲基二硅氮烷 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 18.0h， 生成 (2R,3R,4S,5R)-2-(7-amino-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors

  摘要：

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant

  DOI：

  10.1021/jm101286g
• 作为产物：
  描述：

  2-苄硫基-4,6-二氨基嘧啶 在 platinum(IV) oxide 、 氢气 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 6.5h， 生成 2-(benzylthio)pyrimidine-4,5,6-triamine
  参考文献：
  名称：

  Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors

  摘要：

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant

  DOI：

  10.1021/jm101286g

文献信息

• [EN] NEW 2-SUBSTITUTED, 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES, USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS, ESP. CX3CR1<br/>[FR] NOUVELLES 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES SUBSTITUEES EN 2, UTILES COMME ANTAGONISTES DU RECEPTEUR CHIMIOKINE, NOTAMMENT CX3CR1
  申请人：ASTRAZENECA AB

  公开号：WO2005033115A1

  公开（公告）日：2005-04-14

  There are disclosed novel compounds of formula (I) wherein A, R1, R2, R3 and X are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX3CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, atherosclerosis and pain.

  已披露了化合物的新型结构，其化学式为(I)，其中A、R1、R2、R3和X如规范中所定义，以及其药用盐，以及它们的制备方法、包含它们的药物组合物以及它们在治疗中的应用。化合物的化学式(I)是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病、动脉粥样硬化和疼痛的治疗或预防中特别有用。
• New 2-substituted, 4-amino-thiazolo[4,5-d] pyrimidines, useful as chemokine receptor antagonists, esp. cx3cr1
  申请人：Nordvall Gunnar

  公开号：US20070142386A1

  公开（公告）日：2007-06-21

  There are disclosed novel compounds of formula (I) wherein A, R 1 , R 2 , R 3 and X are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX 3 CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, atherosclerosis and pain.

  本发明公开了化合物(I)的新型化合物，其中A，R1，R2，R3和X如规范中所定义，并且其药学上可接受的盐，以及其制备方法，包括它们的制药组合物和它们在治疗中的应用。化合物(I)是CX3CR1受体拮抗剂，因此在神经退行性疾病，脱髓鞘性疾病，动脉粥样硬化和疼痛的治疗或预防中特别有用。
• Exploring 8-benzyl pteridine-6,7-diones as inhibitors of glutamate racemase (MurI) in Gram-positive bacteria
  作者：Gloria A. Breault、Janelle Comita-Prevoir、Charles J. Eyermann、Bolin Geng、Randy Petrichko、Peter Doig、Elise Gorseth、Brian Noonan

  DOI：10.1016/j.bmcl.2008.10.022

  日期：2008.12

  A successful scaffold-hopping approach gave a novel series of inhibitors of bacterial glutamate racemase (MurI). Early SAR studies of the 8-benzyl pteridine-6,7-diones led to compounds with micromolar enzyme potency and antibacterial activity. (C) 2008 Elsevier Ltd. All rights reserved.
• NEW 2-SUBSTITUTED, 4-AMINO-THIAZOLO 4,5-D PYRIMIDINES, USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS, ESP. CX3CR1
  申请人：AstraZeneca AB

  公开号：EP1675862A1

  公开（公告）日：2006-07-05
• Investigations into the Origin of the Molecular Recognition of Several Adenosine Deaminase Inhibitors
  作者：Irina Gillerman、Bilha Fischer

  DOI：10.1021/jm101286g

  日期：2011.1.13

  Inhibitors of adenosine deaminase (ADA, EC 3 5 4 4) are potential therapeutic agents for the treatment of various health disorders Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA However several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K-i values of 25, 22, 6, and 3 mu M, respectively We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant