4-Desmethylamino-6-desmethyl-6-desoxy-tetracyclin | 15866-90-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 4-Desmethylamino-6-desmethyl-6-desoxy-tetracyclin
• 英文别名: 6-Demethyl-6-deoxy-dedimethylamino-tetracyclin
• CAS: 15866-90-7
• 化学式: C₁₉H₁₇NO₇
• 分子量: 371.346
• InChiKey: ZXFCRFYULUUSDW-UHFFFAOYSA-N

物化性质

• 熔点：
  228-231 °C
• 沸点：
  752.8±60.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO:100.0(最大浓度 mg/mL);269.29(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  0.58
• 重原子数：
  27.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  158.15
• 氢给体数：
  5.0
• 氢受体数：
  7.0

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

Incyclinide (CMT-3, COL-3) 是一种基质金属蛋白酶（MMP）抑制剂，能够诱导细胞外基质降解、抑制血管生成、肿瘤生长和侵袭以及转移。

体外研究

在体外实验中，incyclinide 已被证明能有效地抑制前列腺癌、结肠腺癌及黑色素瘤的侵袭性。当终浓度为5至20 μM时，添加 incyclinide 可抑制MT1-MMP对胶原蛋白和酪蛋白酶活性，阻止其活化前体 MMP-2，并减少HT-1080成纤维肉瘤细胞的侵袭性。此外，incyclinide 对丝状真菌的生长和存活具有特别有效的抑制作用。大多数CMT-3对抗丝状真菌的最低抑菌浓度（MIC）位于0.25至8 μg/mL之间，且由incyclinide引起的这些真菌存活率抑制通常超过90%。

体内研究

在动物实验中，incyclinide 可以抑制大鼠牙齿移动，这可能是通过减少压缩侧的破骨细胞数量实现的。这种现象可能归因于诱导活化破骨细胞凋亡或减少其迁移。此外，incyclinide 对基质金属蛋白酶活性的降低也可能直接抑制有机骨骼基质的降解。

文献信息

• [EN] TETRACYCLINES AND THEIR USE AS CALPAIN INHIBITORS<br/>[FR] TETRACYCLINES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA CALPAINE
  申请人：CA NAT RESEARCH COUNCIL

  公开号：WO2005082860A1

  公开（公告）日：2005-09-09

  Tetracyclines are useful as calpain inhibitors, particularly inhibitors of calpain I and II, as demonstrated in enzymatic assays as well as at the cellular and animal levels. Tetracyclines may be used in the treatment of a wide range of conditions implicated by or associated with calpain activity or activation, including cellular protection from apoptosis and necrosis, particularly n eu ro protection, prevention of cell motility (e.g. anti-metastasis of cancer) and treatment of certain infectious diseases (e.g. malaria and AIDS). Some tetracyclines are particularly useful as calpain inhibitors since they are also antioxidants, oxidative stress often being associated with conditions where calpain is activated.

  四环素类药物可作为卡尔佩因子的抑制剂，特别是卡尔佩因子I和II的抑制剂，在酶活性测定以及细胞和动物水平上得到证实。四环素类药物可用于治疗与卡尔佩因子活性或激活有关的或相关的一系列疾病，包括细胞保护免受凋亡和坏死的影响，特别是神经保护，防止细胞活动（例如抗癌转移）以及治疗某些传染病（例如疟疾和艾滋病）。一些四环素类药物特别适用作为卡尔佩因子的抑制剂，因为它们也是抗氧化剂，氧化应激常常与卡尔佩因子激活的疾病有关。
• Compounds and methods for the treatment of pain and other diseases
  申请人：Sucholeiki Irving

  公开号：US20110230452A1

  公开（公告）日：2011-09-22

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明通常涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，这些化合物在与目前已知的MMP-2和MMP-9抑制剂相比具有增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者施用一定量的具有减轻疼痛作用的本发明化合物。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISORDERS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE LA DOULEUR ET D'AUTRES TROUBLES
  申请人：SUCHOLEIKI IRVING

  公开号：WO2012118498A1

  公开（公告）日：2012-09-07

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明一般涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一类新的双重作用MMP-2和MMP-9抑制化合物，其在与目前已知的MMP-2和MMP-9抑制剂相比，表现出增强的效力、代谢稳定性和/或降低的毒性，用于治疗疼痛和其他疾病。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者投予一种疼痛减轻有效量的当前化合物。
• COMPOUNDS AND METHODS FOR THE TREATMENT OF PAIN AND OTHER DISEASES
  申请人：Sucholeiki Irving

  公开号：US20130338116A1

  公开（公告）日：2013-12-19

  The present invention relates generally to pharmaceutical agents, and in particular, to metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of dual acting MMP-2 and MMP-9 inhibiting compounds that exhibit increased potency, metabolic stability and/or reduced toxicity in relation to currently known MMP-2 and MMP-9 inhibitors for the treatment of pain and other diseases. Additionally, the present invention relates to methods for treating pain, addiction and/or withdrawal symptoms in a patient comprising administering to the patient a pain-reducing effective amount of a present compound.

  本发明涉及制药剂，特别是金属蛋白酶抑制剂化合物。更具体地说，本发明提供了一类新型的双重作用MMP-2和MMP-9抑制化合物，其在治疗疼痛和其他疾病方面具有增强的效力、代谢稳定性和/或降低毒性，相对于目前已知的MMP-2和MMP-9抑制剂。此外，本发明涉及一种治疗疼痛、成瘾和/或戒断症状的方法，包括向患者施用一种现有化合物的减痛有效量。
• 9-SUBSTITUTED TETRACYCLINES
  申请人：Wyeth

  公开号：EP1848686A2

  公开（公告）日：2007-10-31