8-chloro-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one | 114368-11-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 8-chloro-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one
• 英文别名: 8-chloro-5,11-dihydro-6H-benzo[e]pyrido[3,2-b][1,4]diazepin-6-one；8-Chloro-5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-one
• CAS: 114368-11-5
• 化学式: C₁₂H₈ClN₃O
• 分子量: 245.668
• InChiKey: IHORFTBDOGAILO-UHFFFAOYSA-N

物化性质

• 熔点：
  307-309 °C
• 沸点：
  374.4±42.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-chloro-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one 在 sodium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 10.0h， 生成 8-chloro-11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one
  参考文献：
  名称：

  Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics

  摘要：

  On the basis of the cardioselective muscarinic receptor antagonist AF-DX 116 (2), a series of 11-substituted pyridobenzodiazepinones (9-35) was prepared and screened for their binding affinity to muscarinic receptors located in cardiac (M2) and glandular (M3) tissue. The ratio of IC50 values of the test compounds in the two different tissues was taken as a measure of cardiac (M2) receptor selectivity. Qualitative structure-selectivity relationships point to the fact that it is the spatial orientation of the protonated side-chain nitrogen atom in relation to the tricycle that is the main determinant for receptor subtype recognition and hence is important for the achievement of cardiac (M2) selectivity.

  DOI：

  10.1021/jm00128a008
• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 吡啶 、 盐酸 、 氯化亚砜 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 8-chloro-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one
  参考文献：
  名称：

  作为潜在抗精神病药的新吡啶并二氮杂卓衍生物：合成和神经化学研究。

  摘要：

  发现一种新的，安全的，非典型的抗精神病药仍然是一项重要的挑战。为实现此目标，需要一系列N-甲基哌嗪子并吡啶并[2,3-b] [1,4]-和-[1,5]-和-pyrido [4,3-b] [1,4]-和-合成了[1,5]-苯并二氮杂s。多巴胺能（D1，D2），血清素能（5-HT2）和胆碱能（M）亲和力（通常在抗精神病药物的作用机理中得到体现）是使用它们各自的体外受体结合测定法确定的。每种化合物的所有亲和力均降低。发现最佳取代基在2或8位上以保持亲和力，而在5位上被酰基或烷基取代显着降低结合亲和力。吡啶并二氮杂卓衍生物，例如氯氮平，被发现对阿扑吗啡介导的刻板印象无活性或仅弱效。8-氯-6-（4-甲基-1-哌嗪基）-11H-吡啶酮在狗身上建立的原始且复杂的行为模型已成功用于区分不同种类的精神药物并区分典型和非典型的精神安定药[ 2,3-b] [1,4]苯二氮卓（9），8-甲基-6-（4-甲基-1-哌嗪基）-11H-吡啶基[2

  DOI：

  10.1021/jm00067a009

文献信息

• Synthesis of some substituted dibenzodiazepinones and pyridobenzodiazepinones
  作者：Victor I. Cohen、Biyun Jin、Emil I. Cohen、Barry R. Zeeberg、Richard C. Reba

  DOI：10.1002/jhet.5570350329

  日期：1998.5

  Some fluoro- and iodo-derivative of 5-[[4-[(4-diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-1l-one and 11-[[4-[(dialkylamino)butyl]-1-phenyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-ones 6 (Scheme 1) and their analogues were synthesized. The synthesis of dibenzodiazepinones 1 (Scheme 1) is based on the reaction between 1,4-phenylenediamine and substituted

  5-[[4-[（4-二异丁基氨基）丁基] -1-苯基]乙酰基] -10,11-二氢-5 H-二苯并[ b，e ] [1,4]的某些氟代和碘代衍生物diazepin-1l-one和11-[[[4-[（（二烷基氨基）丁基] -1-苯基]乙酰基] -5,11-二氢-6 H-吡啶基[2,3- b ] [1,4]苯并二氮杂-合成了6-ones 6（方案1）及其类似物。二苯并二氮杂醌1的合成（方案1）是基于1，4-苯二胺和取代的苯甲酸之间的反应。中间体吡啶基苯二酮3（方案1）通过使2-氯-3-氨基吡啶与邻氨基苯甲酸甲酯及其氯衍生物缩合而制备。4-[（卤代）烷基]苯乙酰氯与二苯并二氮杂酮和吡啶基苯并二氮杂酮的缩合，然后单或二烷基或二烯基胺的反应提供了6（方案1）。
• New pyridobenzodiazepine derivatives as potential antipsychotics: synthesis and neurochemical study
  作者：Jean Francois F. Liegeois、Jacques Bruhwyler、Jacques Damas、Thuy Phuong Nguyen、Eric M. G. Chleide、Michel G. A. Mercier、Francoise A. Rogister、Jacques E. Delarge

  DOI：10.1021/jm00067a009

  日期：1993.7

  The discovery of a new, safe, atypical antipsychotic remains an important challenge. To achieve this goal, a series of N-methylpiperazinopyrido[2,3-b] [1,4]- and -[1,5]- and -pyrido[4,3-b][1,4]- and -[1,5]- benzodiazepines were synthesized. The dopaminergic (D1, D2), serotonergic (5-HT2), and cholinergic (M) affinities, frequently remarked in the action mechanisms of antipsychotic drugs, were determined

  发现一种新的，安全的，非典型的抗精神病药仍然是一项重要的挑战。为实现此目标，需要一系列N-甲基哌嗪子并吡啶并[2,3-b] [1,4]-和-[1,5]-和-pyrido [4,3-b] [1,4]-和-合成了[1,5]-苯并二氮杂s。多巴胺能（D1，D2），血清素能（5-HT2）和胆碱能（M）亲和力（通常在抗精神病药物的作用机理中得到体现）是使用它们各自的体外受体结合测定法确定的。每种化合物的所有亲和力均降低。发现最佳取代基在2或8位上以保持亲和力，而在5位上被酰基或烷基取代显着降低结合亲和力。吡啶并二氮杂卓衍生物，例如氯氮平，被发现对阿扑吗啡介导的刻板印象无活性或仅弱效。8-氯-6-（4-甲基-1-哌嗪基）-11H-吡啶酮在狗身上建立的原始且复杂的行为模型已成功用于区分不同种类的精神药物并区分典型和非典型的精神安定药[ 2,3-b] [1,4]苯二氮卓（9），8-甲基-6-（4-甲基-1-哌嗪基）-11H-吡啶基[2
• New Pyridobenzodiazepine Derivatives:  Modifications of the Basic Side Chain Differentially Modulate Binding to Dopamine (D_4.2, D_2L) and Serotonin (5-HT_2A) Receptors
  作者：Jean-François Liégeois、Laurence Eyrolles、Bart A. Ellenbroek、Christel Lejeune、Pascal Carato、Jacques Bruhwyler、Joseph Géczy、Jacques Damas、Jacques Delarge

  DOI：10.1021/jm0104825

  日期：2002.11.1

  A series of new pyridobenzodiazepines with variation of the basic side chain were synthesized and evaluated for their binding to D-4.2, D-2L, and 5-HT2A receptors in comparison with clozapine, haloperidol, and two parent compounds previously described, 8-chloro-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,4]benzodiazepine (8) and 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1,4]benzodiazepine (9). In the piperazine series, replacing the N-methyl group by a N-phenyl moiety (15-17, 30-32) provided a dramatic decrease of affinity for all receptors (K-i > 1000 nM). A N-cyclohexyl group (20, 35) restored some affinity. Compounds with a N-benzyl (18, 33) or N-phenethyl side chain (19, 34) had significant affinities at D-4.2 and 5-HT2A receptors. Homologation of the piperazine nucleus (29, 44) led to a significant decrease of the affinity at all receptors investigated. In the 4-aminopiperidine series, N-methyl derivatives (21, 36) possessed less affinity in comparison with the N-metbylpiperazine analogues (8, 9) while the N-benzyl congeners (22, 37) showed similar affinities. The rigidification of piperidine nucleus as obtained in azabicyclo [3.2.1] octane derivatives (23, 38) involved a slight reduction of the affinity at D-4.2 and 5-HT2A receptors while the affinity at D-2L receptors was dramatically increased. The introduction of N-substituted aminoalkylamines to replace N-methylpiperazine generally led to a significant decrease in the affinity for D-4.2 receptors but some of these molecules (24, 25, 41) presented a significant 5-HT2A binding affinity. The presence of a more flexible side chain induced an increased conformational freedom. Consequently, the preferential position of the distal nitrogen or its basicity in piperazine derivatives was greatly modified. 19 with a high D-4.2 and 5-HT2A affinity (K-i = 40 and 103 nM, respectively) did not induce cataleptic phenomenon in the paw test in rats but significantly reduced the immobility time in Porsolt's test in mice suggesting antidepressant properties.
• ENGEL, WOLFHARD W.;EBERLEIN, WOLFGANG G.;MIHM, GERHARD;HAMMER, RUDOLF;TRU+, J. MED. CHEM., 32,(1989) N, C. 1718-1724
  作者：ENGEL, WOLFHARD W.、EBERLEIN, WOLFGANG G.、MIHM, GERHARD、HAMMER, RUDOLF、TRU+

  DOI：——

  日期：——
• ENGEL, WOLFHARD;EBERLEIN, WOLFGANG;TRUMMLITZ, GUNTER;MIHM, GERHARD;MAYER,+
  作者：ENGEL, WOLFHARD、EBERLEIN, WOLFGANG、TRUMMLITZ, GUNTER、MIHM, GERHARD、MAYER,+

  DOI：——

  日期：——