2-amino-4,5,6,7-tetrahydro-8H-cyclohepta[d]thiazol-8-one | 883195-38-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-4,5,6,7-tetrahydro-8H-cyclohepta[d]thiazol-8-one
• 英文别名: 2-amino-6,7-dihydro-4H-cyclohepta[d]thiazol-8(5H)-one；2-amino-4,5,6,7-tetrahydrocycloheptathiazol-8-one；2-amino-4,5,6,7-tetrahydrocyclohepta[d][1,3]thiazol-8-one
• CAS: 883195-38-8
• 化学式: C₈H₁₀N₂OS
• 分子量: 182.246
• InChiKey: NFAOGEPIABIIAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-4,5,6,7-tetrahydro-8H-cyclohepta[d]thiazol-8-one 在 溴 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 N-(8-((5-chloro-2-methoxyphenyl)amino)-5,6-dihydro-4Hcyclohepta[1,2-d:3,4-d′]bis(thiazole)-2-yl)-2-methylpentanamide
  参考文献：
  名称：

  Constrained Bithiazoles: Small Molecule Correctors of Defective ΔF508–CFTR Protein Trafficking

  摘要：

  Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the ΔF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were designed, synthesized, and tested in vitro using ΔF508-CFTR expressing epithelial cells. The SAR data demonstrated that modulating the constraining ring size between 7- versus 8-membered in these constrained bithiazole correctors did not significantly enhance their potency (IC50), but strongly affected maximum efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5-fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8-membered constrained ring bithiazoles are similar in their ability to accommodate the requisite geometric constraints during protein binding.

  DOI：

  10.1021/jm5007885
• 作为产物：
  描述：

  1-(三甲基硅氧基)环戊烯 在 palladium 10% on activated carbon 、 溴 、 sodium formate 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 正己烷 、 氯仿 、 水 、 异丙醇 为溶剂， 反应 1.0h， 生成 2-amino-4,5,6,7-tetrahydro-8H-cyclohepta[d]thiazol-8-one
  参考文献：
  名称：

  Constrained Bithiazoles: Small Molecule Correctors of Defective ΔF508–CFTR Protein Trafficking

  摘要：

  Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the ΔF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were designed, synthesized, and tested in vitro using ΔF508-CFTR expressing epithelial cells. The SAR data demonstrated that modulating the constraining ring size between 7- versus 8-membered in these constrained bithiazole correctors did not significantly enhance their potency (IC50), but strongly affected maximum efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5-fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8-membered constrained ring bithiazoles are similar in their ability to accommodate the requisite geometric constraints during protein binding.

  DOI：

  10.1021/jm5007885

文献信息

• [DE] PI3-KINASEN<br/>[EN] PI3 KINASES<br/>[FR] PI3-KINASES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006040279A1

  公开（公告）日：2006-04-20

  Es werden neue Verbindungen der Formel (1) bereitgestellt, die aufgrund ihrer pharmazeutischen Wirksamkeit als PI3-Kinase Modulator zur Anwendung auf therapeutischem Gebiet zur Behandlung von entzündlichen oder allergischen Erkrankungen gelangen können. Beispielhaft seien hier entzündliche und allergische Atemwegserkrankungen, entzündliche Erkrankungen des Magen-Darm-Traktes und des Bewegungsapparates, entzündliche und allergische Hauterkrankungen, entzündliche Augenerkrankungen, Erkrankungen der Nasenschleimhaut, entzündliche oder allergische Krankheitszustände, bei denen Autoimmun-Reaktionen beteiligt sind oder Nierenentzündungen genannt.

  提供公式（1）的新颖化合物，由于其药理活性可作为PI3激酶调节剂应用于治疗领域，用于治疗炎性疾病或过敏性疾病。例如，这里可以列举的包括炎性和过敏性呼吸道疾病、炎性疾病、胃肠道的运动系统、炎性和过敏性皮肤病、炎性疾病、鼻粘膜疾病、炎症或过敏性疾病，其中涉及自身免疫反应或肾盂肾炎。
• [EN] THIA-TRIAZA-CYCLOPENTAZULENES AS PI3-KINASES INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] THIATRIAZACYCLOPENTAZULÈNES COMME INHIBITEURS DES PI3-KINASES POUR LE TRAITEMENT D'UN CANCER
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010122071A1

  公开（公告）日：2010-10-28

  The present invention encompasses compounds of general formula (1) wherein 5 R1 to R3 and X are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式（1）中的化合物，其中R1至R3和X的定义如权利要求书中所述，适用于治疗以细胞过度或异常增殖为特征的疾病，并用于制备具有上述特性的药物。
• FUSED RING COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES
  申请人：Che Quinglin

  公开号：US20080132513A1

  公开（公告）日：2008-06-05

  The invention relates to certain fused ring compounds, or pharmaceutically acceptable salts, solvates, clathrates, or prodrugs thereof, that are useful as immunosuppressive agents and for treating and preventing inflammatory conditions, allergic disorders, and immune disorders.

  本发明涉及某些融合环化合物，或其药学上可接受的盐，溶剂合物，笼合物或前药，它们可用作免疫抑制剂，用于治疗和预防炎症状况，过敏性疾病和免疫障碍。
• Thia-triaza-cyclopentazulenes
  申请人：Boehringer Ingelheim International GmbH

  公开号：US08288379B2

  公开（公告）日：2012-10-16

  The present invention encompasses compounds of general formula (1) wherein R1 to R3 and X are defined as in claim 1, which are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式（1）的化合物，其中R1至R3和X的定义如权利要求书中所述，适用于治疗由过度或异常细胞增殖所表征的疾病，并且其用于制备具有上述特性的药物。
• Compounds Having Activity in Correcting Mutant-CFTR Processing and Uses Thereof
  申请人：Kurth Mark J.

  公开号：US20100273839A1

  公开（公告）日：2010-10-28

  The invention provides compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The compositions pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The compositions and pharmaceutical preparations of the invention may comprise one or more bithiazole-containing compounds of the invention, or an analog or derivative thereof.

  本发明提供了用于增加突变囊性纤维化跨膜传导调节因子蛋白（突变CFTR）活性的组合物、制药制剂和方法。该组合物、制药制剂和方法可用于突变CFTR相关的疾病的研究和治疗，如囊性纤维化。本发明的组合物和制药制剂可以包含本发明的一种或多种双噻唑含有化合物，或其类似物或衍生物。