SDM25N | 342884-62-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: SDM25N
• 英文别名: (1S,2S,13R,21R)-22-(2-methylprop-2-enyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaene-2,16-diol
• CAS: 342884-62-2
• 化学式: C₂₆H₂₆N₂O₃
• 分子量: 414.504
• InChiKey: ZFMVWAWSKLAVOE-IFKAHUTRSA-N

物化性质

• 沸点：
  630.5±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  SDM25N 、 三甲基硅烷化重氮甲烷 在 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 (1S,2S,13R,21R)-16-methoxy-22-(2-methylprop-2-enyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaen-2-ol
  参考文献：
  名称：

  Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor

  摘要：

  In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00580-7
• 作为产物：
  描述：

  14-羟基二氢降吗啡酮盐酸盐 在 盐酸 、 碳酸氢钠 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 SDM25N
  参考文献：
  名称：

  Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor

  摘要：

  In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00580-7

文献信息

• Conjugates for immunotherapy
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10449227B2

  公开（公告）日：2019-10-22

  The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.

  本发明涉及一种分子共轭物，包括一种靶细胞特异性细胞表面受体的拮抗剂和一种与拮抗剂共轭的免疫效应物，如 T 细胞调节剂。靶细胞可以是导致受试者发病的细胞，例如癌细胞。在某些实施方案中，免疫效应物是免疫效应蛋白或其免疫效应物片段。本发明还涉及一种治疗受试者疾病的方法，该方法包括向受试者施用药学上有效量的本发明分子共轭物。本发明的方法可用于治疗癌症，如乳腺癌、卵巢癌、前列腺癌、肺癌、胰腺癌或黑色素瘤。
• Effect of <i>N</i>-Alkyl and <i>N</i>-Alkenyl Substituents in Noroxymorphindole, 17-Substituted-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7:2‘,3‘-indolomorphinans, on Opioid Receptor Affinity, Selectivity, and Efficacy
  作者：Sherita McLamore、Thomas Ullrich、Richard B. Rothman、Heng Xu、Christina Dersch、Andrew Coop、Peg Davis、Frank Porreca、Arthur E. Jacobson、Kenner C. Rice

  DOI：10.1021/jm000511w

  日期：2001.4.1

  The N-alkyl analogues (N-ethyl through N-heptyl), branched N-alkyl chain analogues (N-isopropyl, N-2-methylpropyl, and N-3-methylbutyl), and N-alkenyl analogues ((E)-N-3-methylallyl (crotyl), N-2-methylallyl, and N-3,3-dimethylallyl) were prepared in the noroxymorphindole series (17-substituted-6,7-dehydro-4,5 alpha -epoxy-3,12-dihydroxy-6,7:2 ' ,3 ' -indolomorphinans), and the effect of the N-substituent on opioid receptor affinity, selectivity, and efficacy was examined using receptor binding assays, [S-35]GTP gammaS efficacy determinations, and smooth muscle functional assays (electrically stimulated mouse vas deferens and guinea pig ileum). All of the compounds acted as opioid antagonists, including those with N-substituents which usually confer either weak agonist-antagonist behavior (N-ethyl) or potent opioid agonist activity (N-pentyl) in morphinan-like ligands which interact with the mu -receptor. Several N-substituted noroxymorphindoles were found to be more mu/delta -selective than naltrindole (NTI). The N-2-methylallylnoroxymorphindole, in particular, was found to be more selective than NTI in receptor binding assays (mu/delta = 1700 vs 120; kappa/delta = 810 vs 140), as an antagonist in the GTP gammaS assay (mu/delta = 170 vs 140; kappa/delta = 620 vs 160), and considerably more selective than NTI in the functional assays (mu/delta > 2200 vs 90), It also had high affinity for the delta -opioid receptor (K-i = 4.7 nM in the binding assay) and high antagonist potency (1.2 nM in the GTP gammaS assay; 8.9 nM in the MVD assay).
• CONJUGATES FOR IMMUNOTHERAPY
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20170202902A1

  公开（公告）日：2017-07-20

  The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.
• [EN] DELTA OPIOID RECEPTOR ANTAGONISTS REPROGRAM IMMUNOSUPPRESSIVE MICROENVIRONMENT TO BOOST IMMUNOTHERAPY<br/>[FR] ANTAGONISTES DU RÉCEPTEUR OPIOÏDE DELTA REPROGRAMMANT LE MICRO-ENVIRONNEMENT IMMUNOSUPPRESSEUR POUR AMPLIFIER L'IMMUNOTHÉRAPIE
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2021188473A1

  公开（公告）日：2021-09-23

  Disclosed are compositions and methods for mediating immunosuppressive myelopoiesis. Additionally, disclosed herein are combination therapies for treating cancers and methods of using the same.
• Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor
  作者：Thomas Ullrich、Christina M Dersch、Richard B Rothman、Arthur E Jacobson、Kenner C Rice

  DOI：10.1016/s0960-894x(01)00580-7

  日期：2001.11

  In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd.