(Z)-5-(3-(dimethylamino)propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-3-carboxylic acid. | 109293-34-7

• 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: (Z)-5-(3-(dimethylamino)propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-3-carboxylic acid.
• 英文别名: (Z)-5-(3-(Dimethylamino)propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-3-carboxylic acid；(2Z)-2-[3-(dimethylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaene-5-carboxylic acid
• CAS: 109293-34-7
• 化学式: C₂₁H₂₃NO₂
• 分子量: 321.419
• InChiKey: YQRKYUIQPJNNPY-UWVJOHFNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(3-bromo-10,11-dihydrodibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropylamine 在 正丁基锂 、 二氧化碳 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 生成 (Z)-5-(3-(dimethylamino)propylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-3-carboxylic acid.
  参考文献：
  名称：

  Tricyclic aromatic compounds

  摘要：

  本发明涉及以下式I的化合物##STR1##或其盐、酯或酰胺；其中R.sup.1为--CH.sub.2 --CH.sub.2 --，CH.sub.2 --O--或--O--CH.sub.2 --；R.sup.2和R.sup.3相同或不同，分别为氢、C.sub.1-4烷基或与氮一起构成含有四至六个环成员的含氮杂环环；R.sup.4为单键或C.sub.1-7双价脂肪烃基，可以连接到芳香环系统的2,3,8或9位置；n为0至3，并且它们作为抗组胺和抗哮喘剂的用途。

  公开号：

  US04871865A1

文献信息

• An Integrated Approach toward NanoBRET Tracers for Analysis of GPCR Ligand Engagement
  作者：Michael P. Killoran、Sergiy Levin、Michelle E. Boursier、Kristopher Zimmerman、Robin Hurst、Mary P. Hall、Thomas Machleidt、Thomas A. Kirkland、Rachel Friedman Ohana

  DOI：10.3390/molecules26102857

  日期：——

  Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) monitoring competitive binding between fluorescent tracers and unmodified test compounds has emerged as a robust and sensitive method to quantify ligand engagement with specific GPCRs genetically fused to NanoLuc luciferase or the luminogenic HiBiT peptide. However, development of fluorescent tracers is often challenging and remains the principal bottleneck for this approach. One way to alleviate the burden of developing a specific tracer for each receptor is using promiscuous tracers, which is made possible by the intrinsic specificity of BRET. Here, we devised an integrated tracer discovery workflow that couples machine learning-guided in silico screening for scaffolds displaying promiscuous binding to GPCRs with a blend of synthetic strategies to rapidly generate multiple tracer candidates. Subsequently, these candidates were evaluated for binding in a NanoBRET ligand-engagement screen across a library of HiBiT-tagged GPCRs. Employing this workflow, we generated several promiscuous fluorescent tracers that can effectively engage multiple GPCRs, demonstrating the efficiency of this approach. We believe that this workflow has the potential to accelerate discovery of NanoBRET fluorescent tracers for GPCRs and other target classes.

  获取有关配体在生物相关条件下与G蛋白偶联受体（GPCRs）相互作用的药理学见解对于药物发现和基础研究至关重要。基于NanoLuc的生物发光共振能量转移（NanoBRET）监测荧光示踪剂与未修改的测试化合物之间的竞争结合已经成为一种强大而敏感的方法，用于量化与特定GPCRs遗传融合到NanoLuc荧光酶或发光HiBiT肽的配体相互作用。然而，开发荧光示踪剂通常具有挑战性，并且仍然是该方法的主要瓶颈。减轻为每个受体开发特定示踪剂的负担的一种方法是使用多功能示踪剂，这是由BRET的固有特异性所实现的。在这里，我们设计了一种集成示踪剂发现工作流程，将机器学习引导的体外筛选具有对GPCRs显示多功能结合的支架与合成策略的混合相结合，以快速生成多个示踪剂候选物。随后，这些候选物在HiBiT标记的GPCRs库中进行了NanoBRET配体结合筛选的结合评估。利用这种工作流程，我们生成了几种可以有效与多个GPCRs相互作用的多功能荧光示踪剂，展示了这种方法的效率。我们相信这种工作流程有潜力加速发现用于GPCRs和其他靶标类别的NanoBRET荧光示踪剂。
• Tricyclic compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0214779A1

  公开（公告）日：1987-03-18

  The present invention provides a compound of formula (I) or a salt, ester or amide thereof: wherein R1 is -CH2-CH2-, CH2-O- or -O-CH2-: R2 and R3 are the same or different and are each hydrogen, C1-4 alkyl or taken together with the nitrogen comprise a nitrogen-containing heterocyclic ring having four to six ring members; R4 is a single bond or a C1-7 bivalent aliphatic hydrocarbon group may be joined to the aromatic ring system at the 2, 3. 8 or 9 positions; n is 0 to 3. processes for its preparation and intermediates therefor, pharmaceutical compositions containing it and its use in medicine.

  本发明提供了式(I)化合物 或其盐、酯或酰胺： 其中 R1 是 -CH2-CH2-、CH2-O- 或 -O-CH2-：R2 和 R3 相同或不同，各自为氢、C1-4 烷基或与氮一起组成具有四至六个环成员的含氮杂环；R4 为单键或 C1-7 二价脂肪族烃基，可在 2、3.其制备过程及其中间体、含有该物质的药物组合物及其在医学中的用途。
• Carboxylic acid derivatives of doxepin formulations preserved with low-irritation preservative
  申请人：Smith D. Glenn

  公开号：US20050209312A1

  公开（公告）日：2005-09-22

  The present invention relates to topical formulations used for treating allergic and inflammatory diseases. More particularly, the present invention relates to formulations of carboxylic acid derivatives of doxepin preserved with gentle preservative formulations and their use for treating and/or preventing allergic or inflammatory disorders of the eye and nose.

  本发明涉及用于治疗过敏性和炎症性疾病的外用制剂。更具体地说，本发明涉及用温和的防腐剂配方保存的多塞平羧酸衍生物制剂及其用于治疗和/或预防眼鼻过敏性或炎症性疾病的用途。
• USE OF CONNECTIVE TISSUE MAST CELL STABILIZERS TO FACILITATE OCULAR SURFACE RE-EPITHELIZATION AND WOUND REPAIR
  申请人：Yanni John M.

  公开号：US20080139531A1

  公开（公告）日：2008-06-12

  Disclosed are methods of treating a wound in a subject that involve administering to the subject a pharmaceutically effective amount of a composition that includes one or more human connective tissue mast cell stabilizers, wherein administration of the composition results in treatment of the wound. In particular embodiments, the wound is an ophthalmic or dermal wound, such as a corneal epithelial defect, a conjunctival wound, or dermal abrasion. Administration, for example, may be by topical application of the composition to the ocular surface or skin. Exemplary mast cell stabilizers include olopatadine, variants of olopatadine, alcaftidine, derivatives of alcaftidine, dihydropyridines, and spleen tyrosine kinase inhibitors.
• US4871865A
  申请人：——

  公开号：US4871865A

  公开（公告）日：1989-10-03