[3H]-17-Propylamino-17-demethoxygeldanamycin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: [3H]-17-Propylamino-17-demethoxygeldanamycin
• 英文别名: 17-Propylamino-17-demethoxygeldanamycin；17-n-propylamino-geldanamycin；[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-19-(propylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• 化学式: C₃₁H₄₅N₃O₈
• 分子量: 587.714
• InChiKey: WYFYMWZHGYHGAR-TXHRRWQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  正丙胺 、 格尔德霉素 以 N,N-二甲基甲酰胺 为溶剂， 以73%的产率得到[3H]-17-Propylamino-17-demethoxygeldanamycin
  参考文献：
  名称：

  Geldanamycin derivatives and neuroprotective effect on cultured P19-derived neurons

  摘要：

  Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a neurotrophic and neuroprotective substance against antineoplastic drugs, pactitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons from chick embryos. In this study, 1 in a large quantity, together with a known 17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N-alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the quinone ring and were evaluated for in vitro activity against P19-derived neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1 nM) enhanced survival and neurite outgrowth of P19-derived neurons and prevented neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest cytotoxicity and neurotoxicity, is serving as the most promising candidate in neurodegenerative therapy against neurotoxic anticancer drugs. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.041

文献信息

• 2-AMINO PYRIMIDINE COMPOUNDS AS POTENT HSP-90 INHIBITORS
  申请人：Kung Pei-Pei

  公开号：US20100041681A1

  公开（公告）日：2010-02-18

  The present invention is directed to compounds of formula (I), or pharmaceutically acceptable salts thereof, their synthesis, and their use as HSP-90 inhibitors.

  本发明涉及式（I）的化合物，或其药学上可接受的盐，其合成以及作为HSP-90抑制剂的用途。
• [EN] 2-AMINO PYRIMIDINE COMPOUNDS AS POTENT HSP-90 INHIBITORS<br/>[FR] COMPOSÉS 2-AMINO PYRIMIDINE COMME INHIBITEURS PUISSANTS DE L'HSP-90
  申请人：PFIZER

  公开号：WO2010018481A1

  公开（公告）日：2010-02-18

  The present invention is directed to compounds of Formula (I), or pharmaceutically acceptable salts thereof, their synthesis, and their use as HSP-90 inhibitors in the treatment of proliferative diseases, e.g. cancer.

  本发明涉及公式（I）的化合物，或其药学上可接受的盐，它们的合成以及它们在治疗增生性疾病，如癌症中作为HSP-90抑制剂的用途。
• AMIDE RESORCINOL COMPOUNDS
  申请人：Funk Lee Andrew

  公开号：US20090215742A1

  公开（公告）日：2009-08-27

  The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts and solvates thereof, their synthesis, and their use as HSP-90 inhibitors.

  本发明涉及式(I)的化合物，以及其药学上可接受的盐和溶剂化物，它们的合成，以及它们作为HSP-90抑制剂的用途。
• Synthesis and biological activities of novel 17-aminogeldanamycin derivatives
  作者：Zong-Qiang Tian、Yaoquan Liu、Dan Zhang、Zhan Wang、Steven D. Dong、Christopher W. Carreras、Yiqing Zhou、Giulio Rastelli、Daniel V. Santi、David C. Myles

  DOI：10.1016/j.bmc.2004.07.053

  日期：2004.10

  Geldanamycin interferes with the action of heat shock protein 90 (Hsp90) by binding to the N-terminal ATP binding site and inhibiting an essential ATPase activity. In a program directed toward finding potent, water soluble inhibitors of Hsp90, we prepared a library of over sixty 17-alkylamino-17-demethoxygeldanamycin analogs, and compared their affinity for Hsp90, ability to inhibit growth of SKBr3 mammalian cells, and in selected cases, water solubility. Over 20 analogs showed cell growth inhibition potencies similar to that of 17-allylamino-17-demethoxygeldanamycin (17-AAG), the front-runner geldanamycin analog that is currently in multiple clinical trials. Many of these analogs showed water solubility properties that were desirable for formulation. One of the most potent and water-soluble analogs in the series was 17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin (17-DMAG), which was independently prepared by the NCI and will soon enter clinical trials. Importantly, the binding affinity of these analogs to the molecular target Hsp90 does not correlate well with their cytotoxicity in SKBr3 cells. (C) 2004 Elsevier Ltd. All rights reserved.
• METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER
  申请人：Haggerty Timothy J.

  公开号：US20140335050A1

  公开（公告）日：2014-11-13

  The invention features methods, compositions, and kits for the administration of an HSP90 inhibitor, OBAA, flunarizine, aphidicolin, damnacanthal, dantrolene, or an analog thereof, alone, or in combination with, e.g., a TAA, an antigen-binding scaffold (e.g., an antibody, a soluble T cell receptor, or a chimeric receptor) specific for a TAA, a cell (e.g., a white blood cell that targets a cancer cell), and/or an IFN-β receptor agonist or an IFN-γ receptor agonist, for the treatment of cancer.