2-chloro-11-cyclopropyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one | 135575-99-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-11-cyclopropyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one
• 英文别名: 7-chloro-5-cyclopropyl-9-methyl-5,10-dihydro-4,5,6,10-tetraaza-dibenzo[a,d]cyclohepten-11-one；2-chloro-11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one；Dipyridodiazepinone deriv. 14；5-chloro-2-cyclopropyl-7-methyl-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 135575-99-4
• 化学式: C₁₅H₁₃ClN₄O
• 分子量: 300.747
• InChiKey: QAVCQCQQTYJKSO-UHFFFAOYSA-N

物化性质

• 沸点：
  453.3±45.0 °C(Predicted)
• 密度：
  1.439±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-11-cyclopropyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one 在 palladium on activated charcoal 氢气 作用下， 以 二乙二醇二甲醚 为溶剂， 100.0 ℃ 、344.73 kPa 条件下， 反应 12.0h， 生成 萘维拉平
  参考文献：
  名称：

  奈韦拉平及其主要代谢产物的合成

  摘要：

  在工艺优化过程中开发了几种合成方法，用于大规模合成奈韦拉平（1），这是一种HIV-1逆转录酶的非核苷抑制剂。推定的主要代谢物11-环丙基-5,11-二氢-4-羟甲基-6 H- [3,2- b：2'，3'- e ] [1,4]二氮杂6-1-6（2）和氧化2成相应的醛3，中有描述。

  DOI：

  10.1002/jhet.5570320144
• 作为产物：
  描述：

  2,6-二氯-4-甲基-3-氨基吡啶 在 sodium hydride 作用下， 以 various solvent(s) 为溶剂， 生成 2-chloro-11-cyclopropyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepine-6-one
  参考文献：
  名称：

  Novel Non-nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase. 4. 2-Substituted Dipyridodiazepinones as Potent Inhibitors of Both Wild-Type and Cysteine-181 HIV-1 Reverse Transcriptase Enzymes

  摘要：

  The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT), An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wildtype and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. The more potent 8-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also.

  DOI：

  10.1021/jm00024a010

文献信息

• 5,11-dihydro-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepines and their use in
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05366972A1

  公开（公告）日：1994-11-22

  Disclosed are novel 5,11-dihydro-6H-dipyrido[3,2-b; 2',3'-e][1,4]diazepines. These are useful in the prevention or treatment of HIV infection.

  本文披露了新型的5,11-二氢-6H-二吡啶并[3,2-b; 2',3'-e][1,4]二氮杂环。这些化合物在预防或治疗HIV感染方面具有用处。
• Synthesis of five nevirapine metabolites
  作者：Karl G. Grozinger、Denis P. Byrne、Laurence J. Nummy、Michael D. Ridges、Annette Salvagno

  DOI：10.1002/jhet.5570370203

  日期：2000.3

  Nevirapine (1) is a non-nucleoside reverse transcriptase inhibitor marketed for HIV treatment by Boehringer Ingelheim as Viramune® since 1996. In vitro studies of nevirapine biotransformation using human liver microsomes demonstrated the formation of five major metabolites. This paper describes the syntheses of these metabolites.

  奈韦拉平（1）是一种非核苷类逆转录酶抑制剂，自1996年起由勃林格殷格翰（Boehringer Ingelheim）以Viramune®的形式出售给HIV治疗。使用人肝微粒体对奈韦拉平进行生物转化的体外研究表明，五种主要代谢物的形成。本文描述了这些代谢产物的合成。
• Synthesis and Crystal Structure Studies of Novel Bioactive Heterocycle: 7-Chloro-5-Cyclopropyl-9-Methyl-10-(2-Piperidin-1-yl-Ethyl)-5,10-Dihydro-4,5,6,10-Tetraaza-Dibenzo[a, d] Cyclohepten-11-One
  作者：N. R. Thimmegowda、G. Sarala、C. S. Ananda Kumar、S. Chandrappa、S. B. Benaka Prasad、Sridhar M. Anandalwar、J. Shashidhara Prasad、K. S. Rangappa

  DOI：10.1007/s10870-008-9508-6

  日期：2009.7

  The compound, 7-chloro-5-cyclopropyl-9-methyl-10-(2-piperidin-1-yl-ethyl)-5,10-dihydro-4,5,6,10-tetraaza-dibenzo[a, d] cyclohepten-11-one, C22H26N5ClO, crystallizes in the triclinic space group Pī with cell parameters a = 8.918(7) Å, b = 9.297(7) Å, c = 14.184(8) Å, V = 1095.98(1) Å3 and Z = 2. The final residual factor R 1 = 0.0451. The structure exhibits intermolecular hydrogen bonds. The 2-piperidin-1-yl-ethyl ring adopts a chair conformation. The starting material used to synthesize the title compound is the intermediate compound of well known anti-HIV drug Nevirapine hence the title compound is having biological importance and hence this crystal structure will helps to structural characterization of the molecule and also for the molecular modeling it will helps for biological study. The title compound 7-chloro-5-cyclopropyl-9-methyl-10-(2-piperidin-1-yl-ethyl)-5,10-dihydro-4,5,6,10-tetraaza-dibenzo[a, d] cyclohepten-11-one was synthesized by condensation of 7-chloro-5-cyclopropyl-9-methyl-5,10-dihydro-4,5,6,10-tetraaza-dibenzo[a, d] cyclohepten-11-one with 1-(2-chloro-ethyl)-piperidine hydrochloride in presence of anhydrous powdered potassium carbonate as base using N,N-dimethyl formamide as solvent and its crystal structure determined. The title compound derived from bioactive molecule and it is also having biological importance hence this crystal structure will helps for the structural characterization and the biological study of the novel molecule.

  7-氯-5-环丙基-9-甲基-10-(2-哌啶-1-基-乙基)-5,10-二氢-4,5,6,10-四氮杂-二苯并[a,d]环庚烯-11-酮，C22H26N5ClO，在三linic空间群Pī中结晶，晶胞参数a = 8.最终残差因子 R 1 = 0.0451。该结构显示出分子间氢键。2-piperidin-1-yl-ethyl 环呈椅状构象。用于合成标题化合物的起始原料是众所周知的抗艾滋病毒药物奈韦拉平（Nevirapine）的中间化合物，因此标题化合物具有重要的生物学意义。标题化合物 7-氯-5-环丙基-9-甲基-10-(2-哌啶-1-基-乙基)-5,10-二氢-4,5,6,10-四氮杂-二苯并[a,d] 环庚烯-11-酮是通过缩合 7-氯-5-环丙基-9-甲基-5,10-二氢-4,5,6,10-四氮杂-二苯并[a,d] 环庚烯-11-酮而合成的、10-tetraaza-dibenzo[a, d] cyclohepten-11-one 与 1-(2-氯乙基)-哌啶盐酸盐在无水碳酸钾粉末作为碱存在下，以 N,N-二甲基甲酰胺为溶剂进行缩合，并测定了其晶体结构。标题化合物来源于生物活性分子，具有重要的生物学意义，因此该晶体结构将有助于对该新型分子进行结构表征和生物学研究。
• 5,11-dihyro-6H-dipyrido[3,2-B:2',3'-e][1,3]diazepines and their use in
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05620974A1

  公开（公告）日：1997-04-15

  Disclosed are novel 5,11-dihydro-6H-dipyrido[3,2-b; 2',3'-e][1,4]diazepines. These are useful in the prevention or treatment of HIV infection.

  本发明涉及一种新型的5,11-二氢-6H-二吡啶[3,2-b; 2',3'-e][1,4]二氮杂环。该化合物可用于预防或治疗HIV感染。
• Crystal and Molecular Structure Analysis of Novel Bioactive Heterocyclic Compound: 7-Chloro-5-cyclopropyl-9-methyl-10-(4-nitro-benzyl)-5,10-Dihydro-4,5,6,10-Tetraaza-dibenzo [a,d] Cyclohepten-11-one
  作者：N. R. Thimmegowda、G. Sarala、C. S. Ananda Kumar、D. S. Prasanna、S. Chandrappa、H. Raju、M. A. Sridhar、J. Shashidhara Prasad、K. S. Rangappa

  DOI：10.1080/15421400802406406

  日期：2008.10.27

  The title compound 7-chloro-5-cyclopropyl-9-methyl-10-(4-nitro-benzyl)-5,10-dihydro-4,5,6,10-tetraaza-dibenzo [a,d] cyclohepten-11-one was synthesized and characterized spectroscopically and finally confirmed by X-ray diffraction study. The title compound crystallizes in the monoclinic space group P21/c with cell parameters a=11.644(8) , b=14.826(1) , c=15.919(8) , =90, =130.377(4),=90, V=2093.5(2) 3, and Z=4. The NO2 group in the ring is almost in the same plane of the nitrobenzyl ring. The structure exhibits neither inter nor intra molecular hydrogen bonding.