D-369 | 1253693-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: D-369
• 英文别名: 4-(4-(2-((5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol；4-[4-[2-[(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-propylamino]ethyl]piperazin-1-yl]quinolin-8-ol
• CAS: 1253693-65-0
• 化学式: C₂₈H₃₆N₄O₂
• 分子量: 460.619
• InChiKey: SWEZRIWMOXWKPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  63.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  D-369 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 生成 D-340 hydrochloride
  参考文献：
  名称：

  Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol and Its Analogues as Highly Potent Dopamine D2/D3 Agonists and as Iron Chelator: In Vivo Activity Indicates Potential Application in Symptomatic and Neuroprotective Therapy for Parkinson’s Disease

  摘要：

  The role of iron in the pathogenesis of Parkinson's disease (PD) has been implicated strongly because of generation of oxidative stress leading to dopamine cell death. In our overall goal to develop bifunctional/multifunctional drugs, we designed dopamine D2/D3 agonist molecules with a capacity to bind to iron. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptor with tritiated spiperone to evaluate inhibition constants (K-i). Functional activity of selected compounds was carried out with GTP gamma S binding assay. SAR results identified compounds (+)-19a and (-)-19b as two Potent agonists for both D2 and D3 receptors (EC50 (GTP gamma S); D2 = 4.51 and 1.69 nM and D3 = 1.58 and 0.74 nM for (-)-19b and (+)-19a, respectively). In vitro complexation Studies with 19b demonstrated efficient chelation with iron. Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant activity. In PD animal model study, (-)-19b exhibited potent in vivo activity in reversing locomotor activity in reserpinized rats and also in producing potent rotational activity in 6-OHDA lesioned rats. This reports initial development of unique lead molecules that might find potential use in Symptomatic and neuroprotective treatment of PD.

  DOI：

  10.1021/jm901618d
• 作为产物：
  描述：

  6-((2-(4-(8-methoxyquinolin-4-yl)piperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol 在 氢溴酸 、 碳酸氢钠 作用下， 以 水 为溶剂， 生成 D-369
  参考文献：
  名称：

  Discovery of 4-(4-(2-((5-Hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)ethyl)piperazin-1-yl)quinolin-8-ol and Its Analogues as Highly Potent Dopamine D2/D3 Agonists and as Iron Chelator: In Vivo Activity Indicates Potential Application in Symptomatic and Neuroprotective Therapy for Parkinson’s Disease

  摘要：

  The role of iron in the pathogenesis of Parkinson's disease (PD) has been implicated strongly because of generation of oxidative stress leading to dopamine cell death. In our overall goal to develop bifunctional/multifunctional drugs, we designed dopamine D2/D3 agonist molecules with a capacity to bind to iron. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptor with tritiated spiperone to evaluate inhibition constants (K-i). Functional activity of selected compounds was carried out with GTP gamma S binding assay. SAR results identified compounds (+)-19a and (-)-19b as two Potent agonists for both D2 and D3 receptors (EC50 (GTP gamma S); D2 = 4.51 and 1.69 nM and D3 = 1.58 and 0.74 nM for (-)-19b and (+)-19a, respectively). In vitro complexation Studies with 19b demonstrated efficient chelation with iron. Furthermore, the deoxyribose assay with 19b demonstrated potent antioxidant activity. In PD animal model study, (-)-19b exhibited potent in vivo activity in reversing locomotor activity in reserpinized rats and also in producing potent rotational activity in 6-OHDA lesioned rats. This reports initial development of unique lead molecules that might find potential use in Symptomatic and neuroprotective treatment of PD.

  DOI：

  10.1021/jm901618d

文献信息

• INHIBITORS FOR THE TREATMENT OF CANCER AND RELATED METHODS
  申请人：UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.

  公开号：US20190127329A1

  公开（公告）日：2019-05-02

  Some embodiments of the invention include inventive compounds. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Other embodiments include PFKFB4 inhibitors and methods of using the same that can target neoplastic cells, including, such as, mechanisms within those cells that relate to the use of the glycolytic pathway. In other embodiments, small molecule PFKFB4 inhibitors are used to disrupt the kinase domain of PFKFB4 and, in some instances, decrease the glucose metabolism and growth of human cancers. Additional embodiments of the invention are also discussed herein.

  一些实施例涉及创新化合物。其他实施例包括包含该创新化合物的组合物（例如，药物组合物）。发明的另一些实施例涉及使用这些化合物治疗特定疾病的组合物（例如，药物组合物）。一些实施例包括使用这些创新化合物的方法（例如，在组合物或药物组合物中）进行给药和治疗（例如，癌症等疾病）。进一步的实施例包括制备这些创新化合物的方法。其他实施例包括PFKFB4抑制剂及其使用方法，可以针对肿瘤细胞，包括与糖酵解途径有关的这些细胞内的机制。在其他实施例中，小分子PFKFB4抑制剂被用于破坏PFKFB4的激酶结构域，并且在某些情况下，降低人类癌症的葡萄糖代谢和生长。此外，还讨论了本发明的其他实施例。
• [EN] SELECTIVE PFKFB4 INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] INHIBITEURS SÉLECTIFS DE PFKFB4 POUR LE TRAITEMENT DU CANCER
  申请人：UNIV LOUISVILLE RES FOUND INC

  公开号：WO2016172499A1

  公开（公告）日：2016-10-27

  Methods and pharmaceutical compositions for inhibiting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4) and the treatment of cancer are described.

  描述了用于抑制6-磷酸果糖激酶/果糖-2,6-二磷酸酶4（PFKFB4）并治疗癌症的方法和药物组合物。
• [EN] QUINOLINE DERIVATIVE, COMPOSITIONS COMPRISING THIS COMPOUND AND USES THEREOF IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉ DE QUINOLINE, COMPOSITIONS COMPRENANT CE COMPOSÉ ET UTILISATIONS ASSOCIÉES DANS LE TRAITEMENT DU CANCER
  申请人：UNIV LOUISVILLE RES FOUND INC

  公开号：WO2019046497A1

  公开（公告）日：2019-03-07

  Some embodiments of the invention include inventive compounds (e.g., compounds of Formula (I)). Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as cancer). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.

  该发明的一些实施例包括创新化合物（例如，符合式（I）的化合物）。其他实施例包括包括该创新化合物的组合物（例如，药物组合物）。该发明的另一些实施例包括使用该创新化合物的组合物（例如，药物组合物）来治疗，例如使用该创新化合物治疗某些疾病。一些实施例包括使用该创新化合物的方法（例如，在组合物或药物组合物中）进行给药和治疗（例如，癌症等疾病）。进一步的实施例包括制备该创新化合物的方法。此外，本文还讨论了该发明的其他实施例。
• [EN] BIFUNCTIONAL/POLYFUNCTIONAL DOPAMINE D2/D3 AGONIST AS NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] AGONISTE BIFONCTIONNEL/POLYFONCTIONNEL DE DOPAMINE D2/D3 EN TANT QU'AGENTS NEUROPROTECTEURS POUR UN TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：UNIV WAYNE STATE

  公开号：WO2010123995A1

  公开（公告）日：2010-10-28

  Compounds having a piperazinyl group for treating a neurodegenerative disease such as Parkinsons Disease are provided. The compounds are described by general formulae I and Vl: Synthetic scheme for preparing the compounds are also provided.

  提供了一种具有哌嗪基团的化合物，用于治疗神经退行性疾病，如帕金森病。这些化合物由一般式I和Vl描述：还提供了制备这些化合物的合成方案。
• BIFUNCTIONAL/POLYFUNCTIONAL DOPAMINE D2/D3 AGONIST AS NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Dutta Aloke K.

  公开号：US20120108815A1

  公开（公告）日：2012-05-03

  A precursor for the deposition of a thin film by atomic layer deposition is provided. The compound has the formula M x L y where M is a metal and L is an amidrazone-derived ligand or an amidate-derived ligand. A process of forming a thin film using the precursors is also provided.

  提供了一种用于原子层沉积薄膜的前体。该化合物具有MxLy的公式，其中M是金属，L是来自酰胺肼衍生的配体或酰胺酸衍生的配体。还提供了使用前体形成薄膜的过程。