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