N-des-methyl-clarithromycin | 118058-75-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-des-methyl-clarithromycin
• 英文别名: 3'-N,N-didemethyl-6-O-methylerythromycin A；5-O-(3'-N-bis-demethyl)-6-O-methyl-erythromycin A；3'-N-didemethyl-6-O-methylerythromycin A；N,N-Didemethyl-6-O-methylerythromycin；(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-amino-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-12,13-dihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-7-methoxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione
• CAS: 118058-75-6
• 化学式: C₃₆H₆₅NO₁₃
• 分子量: 719.911
• InChiKey: JWCOYCBCUODHBU-QNPWSHAKSA-N

物化性质

• 沸点：
  800.2±65.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  50
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  206
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-des-methyl-clarithromycin 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 3'-N,N-didemethyl-2'-O,3'-N-carbonyl-3'-N-ethyl-6-O-methylerythromycin A
  参考文献：
  名称：

  Novel desosamine-modified 14- and 15-membered macrolides without antibacterial activity

  摘要：

  Novel modifications of the desosamine sugar of 14- and 15-membered antibacterial macrolides, in which the desosamine was fused with N-substituted-1,3-oxazolidin-2-ones, were developed in order to completely suppress antibacterial activity and make them promising agents for other biological targets. The synthesis of such bicyclic desosamine derivatives, especially 1,3-oxazolidin-2-one formation, was optimized and conducted under mild conditions without a need for protection/deprotection steps for other functional groups. A focused series of novel desosamine-modified macrolide derivatives was prepared and their antibacterial activities tested. It was shown that these macrolide derivatives do not possess any residual antibacterial activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.076
• 作为产物：
  描述：

  克拉霉素 在 碘 、 sodium acetate 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以99%的产率得到N-des-methyl-clarithromycin
  参考文献：
  名称：

  Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production

  摘要：

  Macrolide antibiotics have immunomodulatory activities, including suppression of cytokine production, cell adhesion molecule expression, and mucin production. These immunomodulatory activities improve the symptoms of respiratory diseases associated with chronic inflammation. However, the underlying molecular mechanism(s) is not well understood yet. To address this, we prepared clarithromycin (CAM)-conjugated Sepharose and examined bound cellular proteins by proteome analysis. We identified mitochondrial proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25-like protein homolog (NIP-SNAP)-1 and -2 and very long-chain acyl-CoA dehydrogenase (VLCAD) as CAM-binding proteins. Production of proinflammatory cytokines (IL-8 and IL-6) induced by lipopolysaccharides (LPSs) and Pam(3)-CSK4 in human epithelial cell lines BEAS-2B and T24 were suppressed by knockdown of NIP-SNAP -1 or -2, and partly by knockdown of VLCAD. Also, knockdown of NIP SNAP-1 or -2 in various cell lines suppressed LPS-induced expression of IL-8 and IL-6 mRNA and NF-kappa B activity. Thus, CAM suppresses NF-kappa B-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2. (C) 2016 The Authors. Published by Elsevier Inc.

  DOI：

  10.1016/j.bbrc.2016.12.100

文献信息

• MACROLIDE DERIVATIVES
  申请人：Kashimura Masato

  公开号：US20090076253A1

  公开（公告）日：2009-03-19

  Compounds represented by formula (I) and the formula (IV) have an inhibitory activity of MMP-9 production, therefore, are useful as a medicine agent with fewer side effects than conventional MMP enzyme activity inhibitors, as a prophylactic and therapeutic drug for oncogenic angiogenesis, chronic rheumatoid arthritis, vascular intimal thickening after a percutaneous coronary transluminal angioplasty, vascular atherosclerosis, hemorrhagic apoplexy, acute myocardial infarction, chronic heart failure, aneurysm, lung cancer metastasis, adult respiratory distress syndrome, asthma, interstitial pulmonary fibrosis, chronic rhinosinusitis, bronchitis or chronic obstructive pulmonary disease (COPD).

  由公式（I）和公式（IV）表示的化合物具有抑制MMP-9产生的活性，因此，它们可用作药物代理，其副作用比传统的MMP酶活性抑制剂少，作为预防和治疗肿瘤血管生成、慢性类风湿关节炎、经皮冠状动脉病变介入治疗后的血管内膜增厚、血管动脉粥样硬化、出血性中风、急性心肌梗死、慢性心力衰竭、动脉瘤、肺癌转移、成人呼吸窘迫综合征、哮喘、间质性肺纤维化、慢性鼻窦炎、支气管炎或慢性阻塞性肺疾病（COPD）的药物。
• [EN] NEW MACROLIDES AND THEIR USE<br/>[FR] NOUVEAUX MACROLIDES ET LEUR UTILISATION
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2009106419A1

  公开（公告）日：2009-09-03

  The invention relates to macrolide compounds of formula (I),the use of said compounds as medicaments, in particular for the treatment or prevention of inflammatory and allergic diseases, pharmaceutical compositions containing said compounds and to processes for their preparation. The invention relates in particular to macrolide compounds with anti-inflammatory activity mediated primarily through inhibition of phosphodiesterase 4 (PDE4) which makes them useful for the treatment and/or prevention of inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, atopic dermatitis or inflammatory bowel disease or proliferative diseases such as cancer.

  本发明涉及公式(I)的大环内酯化合物，以及所述化合物作为药物的应用，特别是用于治疗或预防炎性和过敏性疾病，包含所述化合物的药物组合物，以及它们的制备过程。本发明特别涉及主要通过抑制磷酸二酯酶4（PDE4）介导抗炎活性的大环内酯化合物，这使得它们可用于治疗和/或预防诸如慢性阻塞性肺病（COPD）、哮喘、类风湿性关节炎、特应性皮炎、炎症性肠病或增殖性疾病，例如癌症等炎性和过敏性疾病。
• WO2008/99368
  申请人：——

  公开号：——

  公开（公告）日：——
• MACROLIDES AND THEIR USE
  申请人：Kellenberger Johannes Laurenz

  公开号：US20110053876A1

  公开（公告）日：2011-03-03

  The invention relates to macrolide compounds of formula (I), the use of said compounds as medicaments, in particular for the treatment or prevention of inflammatory and allergic diseases, pharmaceutical compositions containing said compounds and to processes for their preparation. The invention relates in particular to macrolide compounds with anti-inflammatory activity mediated primarily through inhibition of phosphodiesterase 4 (PDE4) which makes them useful for the treatment and/or prevention of inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, atopic dermatitis or inflammatory bowel disease or proliferative diseases such as cancer.
• US8410065B2
  申请人：——

  公开号：US8410065B2

  公开（公告）日：2013-04-02