tert-butyl ((8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)methyl)carbamate | 1332700-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑四嗪类
• 英文名称: tert-butyl ((8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)methyl)carbamate
• 英文别名: tert-butyl N-[(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3-yl)methyl]carbamate
• CAS: 1332700-58-9
• 化学式: C₁₁H₁₅N₇O₄
• 分子量: 309.285
• InChiKey: NJBYAIOUESQTRK-UHFFFAOYSA-N

物化性质

• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl ((8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)methyl)carbamate 在 盐酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 替莫唑胺
  参考文献：
  名称：

  An Efficient and Practical Radiosynthesis of [¹¹C]Temozolomide

  摘要：

  Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [C-11]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [C-11]TMZ synthesis and reformulation make it difficult for routine production. A highly reproducible one-pot radiosynthesis of [C-11]TMZ with a radiochemical yield of 17 +/- 5% and >= 97% radiochemical purity is reported.

  DOI：

  10.1021/ol302791x
• 作为产物：
  描述：

  Boc-Gly-OCOOEt 在 sodium azide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 3.17h， 生成 tert-butyl ((8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)methyl)carbamate
  参考文献：
  名称：

  An Efficient and Practical Radiosynthesis of [¹¹C]Temozolomide

  摘要：

  Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [C-11]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [C-11]TMZ synthesis and reformulation make it difficult for routine production. A highly reproducible one-pot radiosynthesis of [C-11]TMZ with a radiochemical yield of 17 +/- 5% and >= 97% radiochemical purity is reported.

  DOI：

  10.1021/ol302791x

文献信息

• [EN] METHODS AND INTERMEDIATES FOR THE SYNTHESIS OF 4-OXO-3,4-DIHYDRO-IMIDAZO[5,1-D][1,2,3,5]TETRAZINES<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES POUR EFFECTUER LA SYNTHÈSE DE 4-OXO-3,4-DIHYDRO-IMIDAZO[5,1-D][1,2,3,5]TÉTRAZINES
  申请人：PHARMINOX LTD

  公开号：WO2011107726A1

  公开（公告）日：2011-09-09

  The present invention provides a compound of general formula (II), or a salt or solvate thereof wherein A is independently -A1, -A2, -A3, -A4, -A5, -A6, or -A7, wherein: -A1 is independently C5-12heteroaryl, and is optionally substituted; -A2 is independently thioamido or substituted thioamido; -A3 is independently imidamido, substituted imidamido, N-hydroxyimidamido, or substituted N-hydroxyimidamido; -A4 is independently hydroxamic acid or hydroxamate; -A5 is independently carboxamide or substituted carboxamide; -A6 is independently aliphatic C2-6alkenyl, and is optionally substituted; and -A7 is independently carboxy or C1-4alkyl-carboxylate; and its use in the synthesis of temozolomide and analogues thereof.

  本发明提供了通式（II）的化合物，或其盐或溶剂化合物，其中A独立地为-A1、-A2、-A3、-A4、-A5、-A6或-A7，其中：-A1独立地为C5-12杂环芳基，并且可以被取代；-A2独立地为硫代酰胺或取代硫代酰胺；-A3独立地为咪唑酰胺、取代咪唑酰胺、N-羟基咪唑酰胺或取代N-羟基咪唑酰胺；-A4独立地为羟肟酸或羟肟酸酯；-A5独立地为羧酰胺或取代羧酰胺；-A6独立地为脂肪族C2-6烯基，并且可以被取代；-A7独立地为羧基或C1-4烷基羧酸酯；以及其在替莫唑胺及其类似物的合成中的用途。
• Methods and Intermediates for the Synthesis of 4-oxo-3,4-dihydro-imidazo[5,1-d][1,2,3,5]tetrazines
  申请人：Hummersone Marc Geoffery

  公开号：US20130012706A1

  公开（公告）日：2013-01-10

  The present invention provides a compound of general formula (II), or a salt or solvate thereof: wherein A is independently -A 1 , -A 2 , -A 3 , -A 4 , -A 5 , -A 6 , or -A 7 , wherein: -A 1 is independently C 5-12 heteroaryl, and is optionally substituted; -A 2 is independently thioamido or substituted thioamido; -A 3 is independently imidamido, substituted imidamido, N-hydroxyimidamido, or substituted N-hydroxyimidamido; -A 4 is independently hydroxamic acid or hydroxamate; -A 5 is independently carboxamide or substituted carboxamide; -A 6 is independently aliphatic C 2-6 alkenyl, and is optionally substituted; and -A 7 is independently carboxy or C 1-4 alkyl-carboxylate; and its use in the synthesis of temozolomide and analogues thereof.

  本发明提供一种通式（II）的化合物或其盐或溶剂化物：其中A独立地为-A1，-A2，-A3，-A4，-A5，-A6或-A7，其中：-A1独立地为C5-12杂环芳基，并且可以被取代；-A2独立地为硫酰胺基或取代硫酰胺基；-A3独立地为咪唑酰胺基，取代咪唑酰胺基，N-羟基咪唑酰胺基或取代N-羟基咪唑酰胺基；-A4独立地为羟肟酸或羟肟酸盐；-A5独立地为羧酰胺或取代羧酰胺；-A6独立地为脂肪族C2-6烯基，并且可以被取代；-A7独立地为羧基或C1-4烷基羧酸盐；以及其在替莫唑胺及其类似物的合成中的用途。
• Med. Chem. Commun. 2012, 11, 1419-1422
  作者：

  DOI：——

  日期：——
• [EN] IMIDAZOTETRAZINE COMPOUNDS AND TREATMENT OF TMZ-RESISTANT CANCERS<br/>[FR] COMPOSÉS D'IMIDAZOTÉTRAZINE ET TRAITEMENT DE CANCERS RÉSISTANTS AU TMZ
  申请人：[en]THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：WO2023150569A1

  公开（公告）日：2023-08-10

  Imidazotetrazines were designed to evade resistance byO6-methylguanine DNA methyltransferase (MGMT) while retaining suitable hydrolytic stability, allowing for effective prodrug activation and biodistribution. One compound, called TABZ, exhibits activity against cancer cells irrespective of MGMT expression and MMR status. TABZ has comparable blood-brain barrier penetrance and comparable hematological toxicity relative to TMZ, while also matching its maximum tolerated dose (MTD) in mice when dosed once-per-day over five days. The activity of TABZ is independent of the two principal mechanisms suppressing the effectiveness of TMZ, making it a promising new candidate for the treatment of GBM, especially those that are TMZ resistant.
• An Efficient and Practical Radiosynthesis of [¹¹C]Temozolomide
  作者：Christian K. Moseley、Stephen M. Carlin、Ramesh Neelamegam、Jacob M. Hooker

  DOI：10.1021/ol302791x

  日期：2012.12.7

  Temozolomide (TMZ) is a prodrug for an alkylating agent used for the treatment of malignant brain tumors. A positron emitting version, [C-11]TMZ, has been utilized to help elucidate the mechanism and biodistribution of TMZ. Challenges in [C-11]TMZ synthesis and reformulation make it difficult for routine production. A highly reproducible one-pot radiosynthesis of [C-11]TMZ with a radiochemical yield of 17 +/- 5% and >= 97% radiochemical purity is reported.