3-(Dimethylamino)-1-(2,2-dimethyl-3,4-dihydrochromen-6-yl)prop-2-en-1-one

• 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: 3-(Dimethylamino)-1-(2,2-dimethyl-3,4-dihydrochromen-6-yl)prop-2-en-1-one
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: HJFNHSQHVOPSBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(Dimethylamino)-1-(2,2-dimethyl-3,4-dihydrochromen-6-yl)prop-2-en-1-one 在 吡啶 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.75h， 生成 3-(2,2-Dimethyl-3,4-dihydrochromen-6-yl)-1-[4-(trifluoromethyl)phenyl]sulfonylpyrazole
  参考文献：
  名称：

  Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds

  摘要：

  Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI(50) at 30 nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI(50) = 296 nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various sub-stituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.05.061
• 作为产物：
  描述：

  2,2-二甲基-6-乙酰基-2H-1-苯并吡喃 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 生成 3-(Dimethylamino)-1-(2,2-dimethyl-3,4-dihydrochromen-6-yl)prop-2-en-1-one
  参考文献：
  名称：

  Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds

  摘要：

  Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI(50) at 30 nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI(50) = 296 nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various sub-stituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.05.061

文献信息

• SUBSTITUTED 2-ANILINOPYRIMIDINES USEFUL AS PROTEIN KINASE INHIBITORS
  申请人：CELLTECH THERAPEUTICS LIMITED

  公开号：EP0862560A1

  公开（公告）日：1998-09-09
• US6235746B1
  申请人：——

  公开号：US6235746B1

  公开（公告）日：2001-05-22
• [EN] SUBSTITUTED 2-ANILINOPYRIMIDINES USEFUL AS PROTEIN KINASE INHIBITORS<br/>[FR] 2-ANILINOPYRIMIDINES SUBSTITUEES UTILES EN TANT QU'INHIBITEURS DE PROTEINE KINASE
  申请人：CELLTECH THERAPEUTICS LIMITED

  公开号：WO1997019065A1

  公开（公告）日：1997-05-29

  (EN) Compounds of general formula (1) are described wherein R1 is a hydrogen or halogen atom or an optionally substitued straight or branched chain alkyl, alkenyl or alkynyl group or a group selected from hydroxyl (-OH), substituted hydroxyl, thiol (-SH), substituted thiol, amino (-NH2), or substituted amino; R2 and R3, which may be the same or different, is each an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; R4 is a hydrogen atom or a straight or branched chain alkyl group; R5 is a hydrogen atom or an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; R6 is a hydrogen or halogen atom or an amino (-NH2), substituted amino, nitro, carboxyl (-CO2H) or esterified carboxyl group or a group -X1-R6a where X1 is a direct bond or a linker atom or group and R6a is an optionally substituted straight or branched chain alkyl, alkenyl or alkynyl group; X is a direct bond or a linker atom or group; R7 is an optionally substituted aliphatic, cycloaliphatic, heteroaliphatic, heterocycloaliphatic, aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are selective protein kinase inhibitors, particularly the kinases p56lck, p59fyn, ZAP-70 and protein kinase C and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to have a role.(FR) L'invention concerne des composés représentés par la formule (1), dans laquelle R1 représente un atome d'hydrogène ou d'halogène ou un groupe alkynyle, alcényle ou alkyle à chaîne droite ou ramifiée éventuellement substitué ou un groupe sélectionné parmi hydroxyle (-OH), hydroxyle substitué, thiol (-SH), thiol substitué, amino (-NH2) ou amino substitué; R2 et R3 pouvant être semblables ou différents, représentent chacun un groupe alkynyle, alcényle ou alkyle à chaîne droite ou ramifiée éventuellement substitué; R4 représente un atome d'hydrogène ou un groupe alkyle à chaîne droite ou ramifiée; R5 représente un atome d'hydrogène ou un groupe alkynyle, alcényle ou alkyle à chaîne droite ou ramifiée éventuellement substitué; R6 représente un atome d'hydrogène ou d'halogène ou un groupe amino (-NH2), amino substitué, nitro, carboxyle (-CO2H) ou carboxyle estérifié ou un groupe -X1-R6a dans lequel X1 représente une liaison directe ou un atome de liaison ou un groupe et R6a représente un groupe alkynyle, alcényle ou alkyle à chaîne droite ou ramifiée éventuellement substitué; X représente une liaison directe ou un atome ou un groupe de liaison; R7 représente un groupe aliphatique, cycloaliphatique, hétéroaliphatique, hétérocycloaliphatique, aromatique ou hétéroaromatique; ainsi que leurs sels, solvates, hydrates et N-oxydes. Ces composés sont des inhibiteurs sélectifs de protéine kinase, en particulier, les kinases p56lck, p59fyn, ZAP-70 et la protéine kinase C, et peuvent être utilisés dans la prophylaxie et le traitement de maladies immunes, hyperprolifératives et d'autres maladies dans lesquelles on pense qu'une action inadéquate de la protéine kinase joue un rôle.
• Identification of anticancer agents based on the thieno[2,3-b]pyridine and 1H-pyrazole molecular scaffolds
  作者：Chatchakorn Eurtivong、Inga Reynisdóttir、Stephanie Kuczma、Daniel P. Furkert、Margaret A. Brimble、Jóhannes Reynisson

  DOI：10.1016/j.bmc.2016.05.061

  日期：2016.8

  Structural similarity search of commercially available analogues of thieno[2,3-b]pyridine and 1H-pyrazole derivatives, known anticancer agents, resulted in 717 hits. These were docked into the phosphoinositide specific-phospholipase C (PLC) binding pocket, the putative target of the compounds, to further focus the selection. Thirteen derivatives of the thieno[2,3-b]pyridines were identified and tested against the NCI60 panel of human tumour cell lines. The most active derivative 1 was most potent against the MDA-MB-435 melanoma cell line with GI(50) at 30 nM. Also, it was found that a piperidine moiety is tolerated on the thieno[2,3-b]pyridine scaffold with GI(50) = 296 nM (MDA-MB-435) for derivative 10 considerably expanding the structure activity relationship for the series. For the 1H-pyrazoles four derivatives were identified using the in silico approach and additionally ten were synthesised with various sub-stituents on the phenyl moiety to extend the structural activity relationship but only modest anticancer activity was found. (C) 2016 Elsevier Ltd. All rights reserved.