(+)-dehydroabietylamine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-dehydroabietylamine
• 英文别名: [(1R,4aS,10aS)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine
• 化学式: C₂₀H₃₁N
• 分子量: 285.473
• InChiKey: JVVXZOOGOGPDRZ-HSALFYBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+)-dehydroabietylamine 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 N-((1S)-cyano((1R,4aS)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)methyl)-4-methylbenzenesulfonamide
  参考文献：
  名称：

  通过碱介导的CH氰化直接从磺酰胺合成α-氨基腈

  摘要：

  在这里，我们公开了一种无过渡金属的反应体系，该体系可使磺酰胺通过C–H键断裂进行α-氰化，以制备α-氨基腈，包括难以接近的全烷基α-叔骨架。超过50个底物实例证明了广泛的官能团耐受性。另外，其合成实用性通过克可缩放性和天然化合物的后期修饰得到突出。机理实验表明，该过程涉及通过碱促进的HF的消除而原位形成亚胺中间体。

  DOI：

  10.1021/acs.orglett.1c01232

文献信息

• N-SUBSTITUTED-DIOXOCYCLOBUTENYLAMINO-3-HYDROXY-PICOLINAMIDES USEFUL AS CCR6 INHIBITORS
  申请人：Pfizer Inc.

  公开号：US20200095239A1

  公开（公告）日：2020-03-26

  The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

  本发明涉及式(IA和1B)所示的N-取代-二氧环丁烯基氨基-3-羟基-吡咯烷酰胺化合物或其药用可接受盐或水合物，这些化合物抑制CC趋化因子受体6 (CCR6)，包含这些化合物的药物组合物，以及使用这些化合物来治疗或预防通过抑制CCR6而改善的疾病、状况或失调。
• Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo
  作者：Fengyi Zhao、Wen Lu、Yuanyuan Xu、Li Xu、Jingjing Zhang、Xu Sun、Shilong Yang、Mengyi Zhou、Fan Su、Feng Lin、Fuliang Cao

  DOI：10.1042/bcj20200337

  日期：2020.6.26

  Several bioactive dehydroabietylamine Schiff-bases (L1−L4), amides (L5−L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.

  成功合成了几种具有生物活性的脱氢二乙胺希夫碱（L1-L4）、酰胺（L5-L11）和络合物 CuL3(NO3)2、Cu(L5)3、Co(L6)2CL2，用于开发更高效但毒性更低的抗增殖化合物。体外研究了这些化合物对 Hela（宫颈）、HepG2（肝）、MCF-7（乳腺）、A549（肺）和 HUVEC（脐静脉正常细胞）的抗增殖活性。所有化合物的毒性都低于脱氢阿糖胞苷胺（L0）。对于 HepG2 细胞，L1、L2 和 L3 具有较高的抗 HepG2 活性，尤其是 L1（0.52 µM）的抗 HepG2 活性最高，但毒性较低。对于 MCF-7 细胞，L1、L2、L3 和 L4 具有较高的抗 MCF-7 活性，尤其是 L3（0.49 µM）的抗 MCF-7 活性最高，但毒性较低。对于 A549 细胞，L2 和 L3 具有更高的抗 A549 活性。此外，L1和L3在体内的抗HepG2和抗MCF-7抑制率很高，分别为65%和61%，因此可能是很有希望的无毒副作用的抗增殖药物。L1、L2 和 L3 可通过插入 DNA 诱导细胞凋亡。
• CYCLOPROPANAMINE COMPOUND AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150291577A1

  公开（公告）日：2015-10-15

  The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  本发明提供了一种具有赖氨酸特异性去甲基化酶-1抑制作用的化合物，可用作药物，例如预防或治疗精神分裂症、发育障碍，特别是智力障碍性疾病（例如自闭症谱系障碍、雷特综合征、唐氏综合征、歌舞伎综合征、脆性X综合征、Kleefstra综合征、神经纤维瘤病1型、Noonan综合征、结节性硬化）和神经退行性疾病（例如阿尔茨海默病、帕金森病、小脑萎缩性疾病（例如小脑纹状体苍白球变性症）和亨廷顿病）、癫痫（例如Dravet综合征）或药物依赖等。其中每个符号如本说明书中所定义的，或其盐的化合物。
• Cyclopropanamine compound and use thereof
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10053456B2

  公开（公告）日：2018-08-21

  The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  本发明提供了一种具有赖氨酸特异性去甲基化酶-1 抑制作用的化合物，该化合物可用作药物，如精神分裂症、发育障碍，尤其是智力障碍疾病（如自闭症谱系障碍、雷特综合征、唐氏综合征、卡布基综合征、脆性 X 综合征、克莱夫斯特拉综合征、神经纤维瘤病 1 型、努南综合征、结节性硬化症）的预防或治疗药物、自闭症谱系障碍、雷特综合征、唐氏综合征、歌舞伎综合征、脆性 X 综合征、克莱夫斯特拉综合征、神经纤维瘤病 1 型、努南综合征、结节性硬化症）、神经退行性疾病（如阿尔茨海默病、帕金森病、脊髓小脑变性（如齿状突眼苍白肌萎缩症）和亨廷顿病）、癫痫（如德拉韦特综合征）或药物依赖等。由式（其中各符号如本说明书所定义）代表的化合物或其盐。
• N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as CCR6 inhibitors
  申请人：Pfizer Inc.

  公开号：US10975065B2

  公开（公告）日：2021-04-13

  The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

  本发明涉及式（IA 和 1B）的 N-取代-二氧代环丁烯基氨基-3-羟基吡啶酰胺化合物 或其药学上可接受的盐或水合物、抑制 CC 趋化因子受体 6 (CCR6)的化合物、含有这些化合物的药物组合物，以及这些化合物用于治疗或预防通过抑制 CCR6 而改善的疾病、病症或紊乱的用途。