28-O-甲基-雷帕霉素 | 159351-88-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 中文名称: 28-O-甲基-雷帕霉素
• 英文名称: 28-methoxyrapamycin
• 英文别名: (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-27-hydroxy-3-((R)-1-((1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl)propan-2-yl)-9,10,21-trimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1]oxa[4]azacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentaone；(23E,25E,27E,28E,30R,31S,32R,33R,35S,37S,39S,40S,41R,42R,51R)-51-hydroxy-40-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-39,41,42-trimethoxy-30,31,32,33,43,44-hexamethyl-60,61-dioxa-52-azatricyclohexatriaconta-23,25,27(43),28(44)-tetraene-45,46,47,48,49-pentone；28-O-Methyl-rapamycin；(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1-hydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-18,19,30-trimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
• CAS: 159351-88-9
• 化学式: C₅₂H₈₁NO₁₃
• 分子量: 928.214
• InChiKey: TXZXMCLTSBPVQD-JQEUAWNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  66
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  184
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  28-O-甲基-雷帕霉素 在 2,6-二叔丁基-4-甲基吡啶 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.17h， 生成 (1R,2R,4S)-4-((2R)-2-((3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,23S,26R,27R,34aS)-27-hydroxy-9,10-dimethoxy-6,8,12,14,20,26-hexamethyl-21-(2-(oxetan-3-yloxy)ethoxy)-l,5,ll,28,29-pentaoxo-1,4,5,6,9,10,11 ,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1]oxa[4]azacyclohentriacontin-3-yl)propyl)-2-methoxycyclohexyl dimethylphosphinate
  参考文献：
  名称：

  [EN] RAPAMYCIN ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE LA RAPAMYCINE ET LEURS UTILISATIONS

  摘要：

  本发明提供了化合物、其组合物以及使用它们的方法。

  公开号：

  WO2022159976A1
• 作为产物：
  描述：

  雷帕霉素 在 咪唑 、 pyridine hydrofluoride 、 1,8-双二甲氨基萘 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 28-O-甲基-雷帕霉素
  参考文献：
  名称：

  [EN] RAPAMYCIN ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE LA RAPAMYCINE ET LEURS UTILISATIONS

  摘要：

  本发明提供了化合物、其组合物以及使用它们的方法。

  公开号：

  WO2022159976A1

文献信息

• [EN] METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS<br/>[FR] MÉTHODES DE RETARDEMENT, DE PRÉVENTION ET DE TRAITEMENT DE LA RÉSISTANCE ACQUISE AUX INHIBITEURS DE RAS
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2021257736A1

  公开（公告）日：2021-12-23

  The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.

  本公开涉及使用双-立体异构体mTOR抑制剂与RAS抑制剂联合治疗疾病或病状（例如，癌症）的配方和方法。具体而言，在某些实施方式中，本公开包括用于诱导肿瘤细胞凋亡和/或用于延迟、预防或治疗对RAS抑制剂获得性耐药性的双-立体异构体mTOR抑制剂的配方和方法。
• X-ray Crystal Structure of 28-<i>O</i>-Methylrapamycin complexed with FKBP12:  Is the Cyclohexyl Moiety Part of the Effector Domain of Rapamycin?
  作者：Joerg A. Kallen、Richard Sedrani、Sylvain Cottens

  DOI：10.1021/ja954328h

  日期：1996.1.1

  The X-ray crystal structure of 28-O-methylrapamycin 2 bound to FKBP12 is described. This rapamycin analogue binds to FKBP12 with an affinity comparable to that of rapamycin, but its immunosupressive activity is reduced by a factor of 1000. The atomic structure of the complex formed by FKBP12 and 28-O-methylrapamycin is compared with those of the FKBP12-rapamycin and FKBP12-FK506 complexes. The steric 28-O-methyl group induces a dramatic shift in the orientation of the cyclohexyl moiety, which is now in a position similar to the one observed for the cyclohexyl subunit in the FKBP12-FK506 complex. The conformation of the macrocyclic part of the molecule remains unchanged. As a consequence of 28-O-methylation and the resulting modified orientation taken by the cyclohexyl subunit, two intermolecular hydrogen bonds between the ligand and the binding protein are lost in comparison to the FKBP12-rapamycin complex. The affinity for FKBP12 is not significantly affected by these structural changes, but the immunosuppressive activity is greatly reduced, suggesting a critical role for the cyclohexyl ring in the interaction of the FKBP12-rapamycin complex with its molecular target.
• RAPAMYCIN ANALOGS AND USES THEREOF
  申请人：Navitor Pharmaceuticals, Inc.

  公开号：US20210186935A1

  公开（公告）日：2021-06-24

  The present invention provides compounds, compositions thereof, and methods of using the same.
• [EN] RAPAMYCIN ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE LA RAPAMYCINE ET LEURS UTILISATIONS
  申请人：ANAKURIA THERAPEUTICS INC

  公开号：WO2022159976A1

  公开（公告）日：2022-07-28

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。