8-(N-allyl-carbamoyl)-3-(2-chloroethyl)-[3H]-imidazo[5,1-d]-1,2,3,5-tetrazin-4-one | 85622-92-0

• 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: 8-(N-allyl-carbamoyl)-3-(2-chloroethyl)-[3H]-imidazo[5,1-d]-1,2,3,5-tetrazin-4-one
• 英文别名: 3-(2-chloroethyl)-4-oxo-N-prop-2-enylimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
• CAS: 85622-92-0
• 化学式: C₁₀H₁₁ClN₆O₂
• 分子量: 282.689
• InChiKey: MXMYVOXORZOUFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  米托唑胺 在 氯化亚砜 、 硫酸 、 N,N-二甲基甲酰胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.5h， 生成 8-(N-allyl-carbamoyl)-3-(2-chloroethyl)-[3H]-imidazo[5,1-d]-1,2,3,5-tetrazin-4-one
  参考文献：
  名称：

  Antitumor imidazotetrazines. 20. Preparation of the 8-acid derivative of mitozolomide and its utility in the preparation of active antitumor agents

  摘要：

  The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8-carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines.

  DOI：

  10.1021/jm00167a018

文献信息

• Tetrazine derivatives
  申请人：Cancer Research Campaign Technology Limited

  公开号：US05260291A1

  公开（公告）日：1993-11-09

  [ 3H]-Imidazo[ 5,1-d] -1,2,3,5-tetrazin-4-one derivatives of the formula: ##STR1## wherein R.sup.1 represents hydrogen, or an alkyl, alkenyl or alkynyl group containing up to 6 carbon atoms, each such group being unsubstituted or substituted by from one to three substituents selected from halogen atoms, alkoxy, alkylthio, alkylsulphinyl and alkylsulphonyl groups containing up to 4 carbon atoms, and optionally substituted phenyl groups, or R.sup.1 represents a cycloalkyl group containing from 3 to 8 carbon atoms, and R.sup.2 represents a carbamoyl group optionally N-substituted by one or two groups selected ftom alkyl and alkenyl groups containing up to 4 carbon atoms, and cycloalkyl groups containing 3 to 8 carbon atoms, are new therapeutically useful compounds possessing antineoplastic and immunomodulatory activity.

  [3H]-Imidazo[5,1-d]-1,2,3,5-四氮唑-4-酮衍生物的化学式为：##STR1##其中R.sup.1代表氢，或者一个含有最多6个碳原子的烷基，烯基或炔基基团，每个这样的基团未被取代或者被一个到三个取代基所取代，这些取代基选择自含有最多4个碳原子的卤素原子，烷氧基，烷硫基，烷磺基和可选择被取代的苯基团，或者R.sup.1代表含有3到8个碳原子的环烷基基团，R.sup.2代表一个氨基甲酰基团，该氨基甲酰基团可选择通过一个或两个来自含有最多4个碳原子的烷基和烯基基团以及含有3到8个碳原子的环烷基团的基团N-取代，这些化合物是新的具有抗肿瘤和免疫调节活性的治疗用化合物。
• Tetrazines
  申请人：MAY & BAKER LIMITED

  公开号：EP0252682A2

  公开（公告）日：1988-01-13

  Tetrazines of the formula: wherein R¹ represents cycloalkyl, optionally substituted alkyl, alkenyl or alkynyl, A¹ represents nitrogen or -CR³= wherein R³ represents hydrogen or a substituent, A² represents nitrogen or, when A¹ represents nitrogen, A² represents nitrogen or a group -CR³= as hereinbefore defined, Z¹ represents oxygen or sulphur, and R² represents a cyano or azidocarbonyl group or a group of the formula -COZ²R⁹, -CONHOR⁹, -CONHNR⁹R¹⁰, -CONHNHCOOR⁹, -CONHNHCONHR⁹ -COCR¹¹=N₂, -CONHR¹² or -CON=S(O)R¹³R¹⁴ wherein Z² is oxygen or sulphur and R⁹ and R¹⁰ each represents hydrogen, alkyl which may carry an optionally substituted phenyl substituent, or represents optionally substituted phenyl, R¹¹ represents hydrogen or alkyl, and R¹² represents optionally substituted alkyl and R¹³ and R¹⁴ each represent alkyl, and when R¹, R², or R³ represents or contains an acidic group, salts thereof are useful as pharmaceuticals; processes for their preparation and new intermediates are described.

  式中的四嗪： 其中 R¹ 代表环烷基、任选取代的烷基、烯基或炔基，A¹ 代表氮或-CR³= 其中 R³ 代表氢或取代基，A² 代表氮或当 A¹ 代表氮时、Z¹ 代表氧或硫，R² 代表氰基或叠氮羰基或式-COZ²R⁹、-CONHOR⁹、-CONHNR⁹R¹⁰、-CONHNHCOOR⁹、-CONHNHCONHR⁹ -COR¹=N₂的基团、-CONHR¹²或-CON=S(O)R¹³R¹⁴，其中 Z² 是氧或硫，R⁹和 R¹⁰ 各自代表氢、可带有任选取代的苯基取代基的烷基或代表任选取代的苯基、 R¹¹代表氢或烷基，R¹²代表任选取代的烷基，R¹³和R¹⁴各自代表烷基，当R¹、R²或R³代表或含有酸性基团时，其盐可用作药物；描述了其制备工艺和新的中间体。
• Methods and Means for the Treatment of Cancer
  申请人：Van Tellingen Olaf

  公开号：US20090170880A1

  公开（公告）日：2009-07-02

  Provided are Breast Cancer Resistance Protein (BCRP) inhibitors, P-glycoprotein (P-gp) inhibitors and chemotherapeutic agents for use in the treatment of cancer by combination therapy of the BCRP inhibitor and/or P-gp inhibitor with the chemotherapeutic agent. The chemotherapeutic agent is an imidazotetrazine, e.g. temozolomide.
• US5260291A
  申请人：——

  公开号：US5260291A

  公开（公告）日：1993-11-09
• Antitumor imidazotetrazines. 20. Preparation of the 8-acid derivative of mitozolomide and its utility in the preparation of active antitumor agents
  作者：K. R. Horspool、M. F. G. Stevens、Christopher G. Newton、E. Lunt、R. J. A. Walsh、B. L. Pedgrift、G. U. Baig、F. Lavelle、C. Fizames

  DOI：10.1021/jm00167a018

  日期：1990.5

  The preparation of 3-(2-chlorethyl)-4-oxo-3H-imidazo[5,1-d]-1,2,3,5- tetrazine-8-carboxylic acid, a key derivative of mitozolomide in our exploration of the structure-activity relationships of this class of antitumor agents, is described. The facile conversion to the 8-carbonyl chloride gave a derivative that reacted preferentially with nucleophiles at the 8-position rather than at the reactive 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide (including an amide derived from an amino acid), hydroxamic acid, hydrazide and sulfoximide, azide and diazoacetyl derivatives. The in vivo activity is presented of a range of these compounds against TLX5 lymphoma and L1210 leukemia cell lines.