3-(5-aminomethyltetrazol-1-yl)propionitrile | 479646-00-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(5-aminomethyltetrazol-1-yl)propionitrile
• 英文别名: 3-[5-(Aminomethyl)tetrazol-1-yl]propanenitrile
• CAS: 479646-00-9
• 化学式: C₅H₈N₆
• 分子量: 152.159
• InChiKey: KVAGCSCXPMMQCM-UHFFFAOYSA-N

物化性质

• 沸点：
  456.2±38.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(5-aminomethyltetrazol-1-yl)propionitrile 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (S)-4-((R)-2-(Acetylamino-methylsulfanyl)-1-{[1-(2-cyano-ethyl)-1H-tetrazol-5-ylmethyl]-carbamoyl}-ethylcarbamoyl)-2-tert-butoxycarbonylamino-butyric acid tert-butyl ester
  参考文献：
  名称：

  Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl–GSH analogue

  摘要：

  Glutathione (GSH) conjugates inhibit enzymes that are involved in drug metabolism and drug resistance, but their cellular uptake is very low. To improve membrane-permeability, we synthesized a novel GSH-conjugate analogue with a tetrazole carboxylate isostere at the glycine position. Introduction of the tetrazole decreases inhibitory potency towards CDNB conjugation by glutathione S-transferase. However, the tetrazole derivative inhibited 2-bromoisovalerylurea conjugation in rat liver cytosol, as well as in hepatocytes. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00247-0
• 作为产物：
  描述：

  [1-(2-Cyano-ethyl)-1H-tetrazol-5-ylmethyl]-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到3-(5-aminomethyltetrazol-1-yl)propionitrile
  参考文献：
  名称：

  Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl–GSH analogue

  摘要：

  Glutathione (GSH) conjugates inhibit enzymes that are involved in drug metabolism and drug resistance, but their cellular uptake is very low. To improve membrane-permeability, we synthesized a novel GSH-conjugate analogue with a tetrazole carboxylate isostere at the glycine position. Introduction of the tetrazole decreases inhibitory potency towards CDNB conjugation by glutathione S-transferase. However, the tetrazole derivative inhibited 2-bromoisovalerylurea conjugation in rat liver cytosol, as well as in hepatocytes. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00247-0

文献信息

• Potent and Selective Non-Peptidic Inhibitors of Endothelin-Converting Enzyme-1 with Sustained Duration of Action
  作者：Stéphane De Lombaert、Louis Blanchard、Lisa B. Stamford、Jenny Tan、Eli M. Wallace、Yoshitaka Satoh、John Fitt、Denton Hoyer、David Simonsbergen、John Moliterni、Nicholas Marcopoulos、Paula Savage、Mary Chou、Angelo J. Trapani、Arco Y. Jeng

  DOI：10.1021/jm990507o

  日期：2000.2.1

  Functionally, 27and 29 were the two most efficacious compounds from this study, producing sustained inhibition of ECE-1 activity in rats, as measured by their ability to block the hypertensive effects induced by big ET-1. This profile was similar to that of a potent ET(A)/ET(B) dual receptor antagonist, SB 209670. Due to their favorable in vitro and in vivo profiles, 27 (CGS 34043) and 29 (CGS 35066) constitute

  人类内皮素转化酶-1（ECE-1）的有效和选择性非肽类抑制剂已被设计为体内内皮素（ET-1）生产的潜在调节剂。由于其独特的结构特征和在体内的长效作用，双重ECE-1和中性肽链内切酶24.11（NEP）抑制剂CGS 26303被选为进一步优化效能和选择性的诱人先导。用构象受限的3-二苯并呋喃基取代CGS 26303的P（1）'联苯取代基导致更有效和更具选择性的ECE-1抑制剂，如四唑27。这种P（1）'修饰的显着效果首次允许膦酰基甲基羧酸（如29）显示出强效（IC（50）= 22 nM）和选择性（相对NEP的104倍）ECE-1抑制作用。开发了新的α-氨基酸（S）-3-二苯并呋喃-3-基丙氨酸中间体的化学合成方法，并设计了改进的程序来生成取代的α-氨基烷基膦酸以支持各种类似物的生产。尽管通过添加P（1）侧链偶尔可以实现内在ECE-1抑制能力的额外提高，但这些化合物（例如43a）在大ET-1加
• Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl–GSH analogue
  作者：Danny Burg、Liesbeth Hameetman、Dmitri V Filippov、Gijs A van der Marel、Gerard J Mulder

  DOI：10.1016/s0960-894x(02)00247-0

  日期：2002.6

  Glutathione (GSH) conjugates inhibit enzymes that are involved in drug metabolism and drug resistance, but their cellular uptake is very low. To improve membrane-permeability, we synthesized a novel GSH-conjugate analogue with a tetrazole carboxylate isostere at the glycine position. Introduction of the tetrazole decreases inhibitory potency towards CDNB conjugation by glutathione S-transferase. However, the tetrazole derivative inhibited 2-bromoisovalerylurea conjugation in rat liver cytosol, as well as in hepatocytes. (C) 2002 Elsevier Science Ltd. All rights reserved.