N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]propan-2-amine | 1242134-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]propan-2-amine
• 英文别名: (2,2-dimethyl-2H-chromen-6-ylmethyl)isopropylamine；N-[(2,2-dimethylchromen-6-yl)methyl]propan-2-amine
• CAS: 1242134-84-4
• 化学式: C₁₅H₂₁NO
• 分子量: 231.338
• InChiKey: FSEWMAVQZIAANP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]propan-2-amine 在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 12.0h， 以420 mg的产率得到(2,2-dimethyl-2H-chromen-6-ylmethyl)isopropylamine hydrochloride
  参考文献：
  名称：

  New Class of Algicidal Compounds and Fungicidal Activities Derived from a Chromene Amide of Amyris texana

  摘要：

  A chromene amide, N-[2-(2,2-dimethyl-2H-1-benzopyran-6-yl)ethyl]-N,3-dimethylbutanamide, was isolated from the EtOAc extract of the leaves of Amyris texana and found to have moderate antifungal activity against Colletotrichum spp. and selective algicidal activity against Planktothrix perornata, a cyanobacterium (blue-green alga) that causes musty off-flavor in farm-raised channel catfish (Ictalurus punctatus). To improve the selective algicidal activity and provide water solubility, a series of chromene analogues were synthesized and evaluated for algicidal activity using a 96-well microplate rapid bioassay. In addition, the chromene analogues were evaluated for antifungal and phytotoxic activities. Hydrochloride salts of a chromene amine analogue showed improved water solubility and selectivity toward P. perornata with activity comparable to that of the naturally occurring chromene amide.

  DOI：

  10.1021/jf101626g
• 作为产物：
  描述：

  6-hydroxymethyl-2,2-dimethyl-2H-chromene 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]propan-2-amine
  参考文献：
  名称：

  New Class of Algicidal Compounds and Fungicidal Activities Derived from a Chromene Amide of Amyris texana

  摘要：

  A chromene amide, N-[2-(2,2-dimethyl-2H-1-benzopyran-6-yl)ethyl]-N,3-dimethylbutanamide, was isolated from the EtOAc extract of the leaves of Amyris texana and found to have moderate antifungal activity against Colletotrichum spp. and selective algicidal activity against Planktothrix perornata, a cyanobacterium (blue-green alga) that causes musty off-flavor in farm-raised channel catfish (Ictalurus punctatus). To improve the selective algicidal activity and provide water solubility, a series of chromene analogues were synthesized and evaluated for algicidal activity using a 96-well microplate rapid bioassay. In addition, the chromene analogues were evaluated for antifungal and phytotoxic activities. Hydrochloride salts of a chromene amine analogue showed improved water solubility and selectivity toward P. perornata with activity comparable to that of the naturally occurring chromene amide.

  DOI：

  10.1021/jf101626g

文献信息

• HYPOXIA INDUCIBLE FACTOR-1 PATHWAY INHIBITORS AND USES AS ANTICANCER AND IMAGING AGENTS
  申请人：EMORY UNIVERSITY

  公开号：US20130164218A1

  公开（公告）日：2013-06-27

  This disclosure relates to Hypoxia Inducible Factor-1 pathway inhibitors and uses as anticancer and imaging agents. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions disclosed herein.

  本公开涉及缺氧诱导因子-1通路抑制剂及其作为抗癌和成像剂的用途。在某些实施方式中，本公开考虑了在此披露的化合物和药物组成物。
• Structure–activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule hypoxia inducible factor-1 (HIF-1) pathway inhibitor and anti-cancer agent
  作者：Jiyoung Mun、Adnan Abdul Jabbar、Narra Sarojini Devi、Yuan Liu、Erwin G. Van Meir、Mark M. Goodman

  DOI：10.1016/j.bmc.2012.04.064

  日期：2012.7

  We have discovered that 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzene-sulfonamide, a novel small molecule HIF-1 pathway inhibitor, can antagonize tumor growth in animal models of cancer, but the treatment necessitates its delivery in a formulation, due to poor water solubility (<15 mu g/mL; pH 7.4), evidencing that the chemotype needs further exploration of its amenability to additional chemical modifications for ultimate optimization of function and pharmacology.As a first step towards this goal we investigated the structure-activity relationships of 15 lipophilic 2, 2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide to find out strategies of modification. A 3,4-dimethoxybenzenesulfonyl group in region 1 showed the strongest inhibition among five arylsulfonyl groups tested. The presence of propan-2-amine in region 2 conferred the strongest inhibitory effect of the compound on HIF-1 activated transcription in a reporter assay. These findings are important as they help define the structural motifs where the 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide can be chemically modified to improve its pharmacological properties towards development as a cancer therapeutic. (C) 2012 Elsevier Ltd. All rights reserved.
• [EN] INHIBITORS OF HIF AND ANGIOGENESIS<br/>[FR] INHIBITEURS DE HIF ET DE L'ANGIOGENÈSE
  申请人：UNIV EMORY

  公开号：WO2011133659A3

  公开（公告）日：2012-03-15
• Design and Synthesis of Novel Small-Molecule Inhibitors of the Hypoxia Inducible Factor Pathway
  作者：Suazette Reid Mooring、Hui Jin、Narra S. Devi、Adnan A. Jabbar、Stefan Kaluz、Yuan Liu、Erwin G. Van Meir、Binghe Wang

  DOI：10.1021/jm201018g

  日期：2011.12.22

  Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility, and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels but interfere with the ability of HIF-1 alpha/HIF-1 beta to interact with cofactors p300/CBP to form an active transcriptional complex.
• Design and in Vitro Activities of <i>N</i>-Alkyl-<i>N</i>-[(8-<i>R</i>-2,2-dimethyl-2<i>H</i>-chromen-6-yl)methyl]heteroarylsulfonamides, Novel, Small-Molecule Hypoxia Inducible Factor-1 Pathway Inhibitors and Anticancer Agents
  作者：Jiyoung Mun、Adnan Abdul Jabbar、Narra Sarojini Devi、Shaoman Yin、Yingzhe Wang、Chalet Tan、Deborah Culver、James P. Snyder、Erwin G. Van Meir、Mark M. Goodman

  DOI：10.1021/jm300752n

  日期：2012.8.9

  The hypoxia inducible factor (HIF) pathway is an attractive target for cancer, as it controls tumor adaptation to growth under hypoxia and mediates chemotherapy and radiation resistance. We previously discovered 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide as a novel, small-molecule HIF-1 pathway inhibitor in a high-throughput cell-based assay, but its in vivo delivery is hampered by poor aqueous solubility (0.009 mu M in water; log P-7.4 = 3.7). Here we describe the synthesis of 12 N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, which were designed to possess optimal lipophilicities and aqueous solubilities by in silico calculations. Experimental log P-7.4 values of 8 of the 12 new analogs ranged from 1.2-3.1. Aqueous solubilities of three analogs were measured, among which the most soluble N-[(8-methoxy-2,2-dimethyl-2H-chromen-6-yl)methyl]-N-(propan-2-yl)pyridine-2-sulfonamide had an aqueous solubility of 80 mu M, e.g., a solubility improvement of similar to 9000-fold. The pharmacological optimization had limited impact on drug efficacy as the compounds retained IC50 values at or below 5 mu M in our HIF-dependent reporter assay.