(2-methoxy-10,11-dihydro-5H-dibenzocyclohepten-5-yl)methylamine | 141528-88-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: (2-methoxy-10,11-dihydro-5H-dibenzocyclohepten-5-yl)methylamine
• 英文别名: C-(2-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl)-methylamine；(6-methoxy-2-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaenyl)methanamine
• CAS: 141528-88-3
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: BRCXFMUPKJNQFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2-methoxy-10,11-dihydro-5H-dibenzocyclohepten-5-yl)methylamine 、 1-<4,6-bis(allylamino)-1,3,5-triazin-2-yl>-4-piperidone hydrochloride 在 盐酸 、 3 A molecular sieve 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 N,N'-Diallyl-6-{4-[(2-methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylmethyl)-amino]-piperidin-1-yl}-[1,3,5]triazine-2,4-diamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017
• 作为产物：
  描述：

  2-甲氧基二苯并软木酮 在 盐酸 、 sodium tetrahydroborate 、 氨 、 氢气 、 镍 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 60.0~80.0 ℃ 、6.08 MPa 条件下， 反应 6.5h， 生成 (2-methoxy-10,11-dihydro-5H-dibenzocyclohepten-5-yl)methylamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017

文献信息

• New Purines and Purine Analogs as Modulators of Multidrug Resistance
  作者：Alain Dhainaut、Gilbert Regnier、Andre Tizot、Alain Pierre、Stephane Leonce、Nicolas Guilbaud、Laurence Kraus-Berthier、Ghanem Atassi

  DOI：10.1021/jm960361i

  日期：1996.1.1

  A series of 36 purine and purine analog derivatives have been synthesized and tested for their ability to modulate multidrug resistance in vitro (P388/VCR-20 and KB-A1 cells) and in vivo (P388/VCR leukemia). Compounds were compared to S9788, a triazine derivative which has already shown some activity during phase 1 clinical trials and also a limiting cardiovascular side effect possibly linked to its calcium channel affinity. The fact that active compounds increase adriamycin accumulation in the resistant KB-A1 cells, and not in the sensitive KB-3-1 cells, suggests they act predominantly by inhibiting the P-glycoprotein-catalyzed efflux of cytotoxic agents. No direct relation was found between the affinity for the phenylalkylamine binding site of the calcium channel and in vitro sensitization of resistant cells. In vivo, when administered po in association with vincristine (0.25 mg/kg), five compounds (3, 4, 9, 25, and 26), of very differing calcium channel affinities (K-i from 5 to 560 nM), fully restored (T/V greater than or equal to 1.4) the sensitivity of P388/VCR leukemia to vincristine.
• New triazine derivatives as potent modulators of multidrug resistance
  作者：Alain Dhainaut、Gilbert Regnier、Ghanem Atassi、Alain Pierre、Stephane Leonce、Laurence Kraus-Berthier、Jean Francois Prost

  DOI：10.1021/jm00091a017

  日期：1992.6

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.
• Ring substituted analogues of 5-aminomethyl-10,11-dihydro-dibenzo[a,d]cycloheptene (AMDH): potential modes of binding to the 5-HT2A receptor
  作者：Srinivas Peddi、Bryan L. Roth、Richard A. Glennon、Richard B. Westkaemper

  DOI：10.1016/s0960-894x(03)00504-3

  日期：2003.8

  The synthesis and 5-HT2A receptor affinities of 2-substituted-5-aminomethyl-10,11-dihydrodibenzo[a,d]cycloheptene (AMDH) derivatives are described. Comparison of the effects of substitution on affinities allowed assignment of potential binding modes in comparison with DOB-like agonists/antagonists and 3-substituted 1-(aminomethyl)-9,10-dihydroanthracene structures. (C) 2003 Elsevier Ltd. All rights reserved.