[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-15-[(2R,3S)-2-[2-[2-[[5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 1613697-49-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-15-[(2R,3S)-2-[2-[2-[[5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 1613697-49-6
• 化学式: C₆₂H₇₆N₂O₂₀S₂
• 分子量: 1233.42
• InChiKey: NTXZCSQXGYIHFV-VAVBHSHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  86
• 可旋转键数：
  28
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  351
• 氢给体数：
  3
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-15-[(2R,3S)-2-[2-[2-[[5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 、 1-氨基-11-叠氮-3,6,9-三氧杂十一烷 以 二氯甲烷 为溶剂， 反应 17.0h， 以85%的产率得到
  参考文献：
  名称：

  [EN] SYNTHESIS OF NOVEL ASYMMETRIC BOW-TIE PAMAM DENDRIMER-BASED CONJUGATES FOR TUMOR-TARGETING DRUG DELIVERY
  [FR] SYNTHÈSE DE NOUVEAUX CONJUGUÉS ASYMÉTRIQUES À BASE D'UN DENDRIMÈRE PAMAM EN NŒUD PAPILLON POUR ADMINISTRATION DE MÉDICAMENTS CIBLÉE VERS UNE TUMEUR

  摘要：

  本公开涉及一种公式为Vm-D-C-D'-(T-F)n的基于树状聚合物的结合物，该结合物对于肿瘤靶向药物传递很有用。不对称树状聚合物的使用可以实现特定的靶向以及合成的可重复性。

  公开号：

  WO2015038493A1
• 作为产物：
  描述：

  4-(2-pyridyldithio)-pentanoic acid 在 4-二甲氨基吡啶 、 氟化氢吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 乙腈 为溶剂， 反应 103.0h， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-12-(cyclopropanecarbonyloxy)-15-[(2R,3S)-2-[2-[2-[[5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  [EN] THERAPEUTIC AGENT FOR TREATING TUMORS
  [FR] AGENT THÉRAPEUTIQUE POUR LE TRAITEMENT DE TUMEURS

  摘要：

  本公开涉及一种治疗剂，其化学式为：Z-C(=O)-(CH2)n-ϕ-S-S-(CRR')m-(CH2)p-C(=O)- NH-(CH2)q-NH-Y[NH-(CH2)r-X-T-W][NH-(CH2-CH-O)t (CH2)s-NH-V] 化学式I或其药学上可接受的盐，用于治疗肿瘤，包括癌症。化合物I的化学式还包含放射性核素或成像剂或两者的情况下，化合物I是一种治疗和诊断肿瘤，包括癌症的治疗剂。

  公开号：

  WO2015143092A1

文献信息

• Therapeutic agent for treating tumors
  申请人：THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK

  公开号：US10280183B2

  公开（公告）日：2019-05-07

  The present disclosure relates to a therapeutic agent of the formula: Z—C(═O)—(CH2)n-Φ-S—S—(CRR′)m-(CH2)p-C(═O)—NH—(CH2)q-NH—Y[NH—(CH2)r-X-T-W][NH—(CH2—CH—O)t(CH2)s-NH—V]  Formula I or a pharmaceutically acceptable salt thereof, useful for treating tumors, including cancers. Where the compound of Formula I also contains a radionuclide or an imaging agent or both, the compound of formula I is a theranostic agent useful for treating and diagnosing tumors, including cancers.

  本公开涉及一种式的治疗剂： Z-C(═O)-(CH2)n-Φ-S-S-(CRR′)m-( )p-C(═O)-NH-( )q-NH-Y[NH-( )r-X-T-W][NH-( -CH-O)t( )s-NH-V] 式 I 或其药学上可接受的盐，可用于治疗肿瘤，包括癌症。如果式 I 的化合物还含有放射性核素或成像剂或两者兼有，则式 I 的化合物是一种治疗和诊断肿瘤（包括癌症）的治疗剂。
• Design, Synthesis, and Biological Evaluations of Tumor-Targeting Dual-Warhead Conjugates for a Taxoid–Camptothecin Combination Chemotherapy
  作者：Jacob G. Vineberg、Edison S. Zuniga、Anushree Kamath、Ying-Jen Chen、Joshua D. Seitz、Iwao Ojima

  DOI：10.1021/jm500631u

  日期：2014.7.10

  Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two warheads, self-immolative disulfide linkers for drug release, biotin as the tumor-targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR (BR+, biotin receptor overexpressed) and WI38 (BR-, normal) cell lines in the absence and presence of glutathione (GSH), which is an endogenous thiol that triggers drug release inside the cancer cells. With the GSH and resuspension protocol, 2 exhibited IC50 values of 3.22-9.80 nM against all BR+ cancer cell lines, and 705 nM against WI38. Thus, there was a two orders of magnitude higher selectivity to cancer cells. Also, a clear cooperative effect was observed for the taxoid-camptothecin combination when two drugs were delivered to the cancer cells specifically in the form of a dual-warhead conjugate.
• Design, Synthesis, and Biological Evaluation of Theranostic Vitamin–Linker–Taxoid Conjugates
  作者：Jacob G. Vineberg、Tao Wang、Edison S. Zuniga、Iwao Ojima

  DOI：10.1021/jm5019115

  日期：2015.3.12

  Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential F-18-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) cancer cells via receptor-mediated endocytosis (RME) based on flow cytometry and confocal fluorescence microscopy (CFM) analyses, which exhibited very high specificity to BR+ cancer cells. The potency and cancer-cell selectivity of 1 were evaluated against MX-1, L1210FR and ID8 cancer cells (BR+) as well as L1210 cells and WI38 normal human lung fibroblast cells (biotin-receptor negative: BR-). In particular, we designed and performed an assay in the presence of glutathione ethyl ester (GSH-OEt) wherein only 1 molecules internalized into cells via RME in the first 24 h period exert cytotoxic effect. The observed selectivity of 1 was remarkable, with 2 orders of magnitude difference in IC50 values between BR+ cancer cells and WI38 cells, demonstrating a salient feature of this tumor-targeted drug delivery system.
• THERAPEUTIC AGENT FOR TREATING TUMORS
  申请人：THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK

  公开号：US20170166591A1

  公开（公告）日：2017-06-15

  The present disclosure relates to a therapeutic agent of the formula: Z—C(═O)—(CH 2 ) n -Φ-S—S—(CRR′) m -(CH 2 ) p —C(═O)—NH—(CH 2 ) q —NH—Y[NH—(CH 2 ) r —X-T-W][NH—(CH 2 —CH—O) t (CH 2 ) s —NH—V]  Formula I or a pharmaceutically acceptable salt thereof, useful for treating tumors, including cancers. Where the compound of Formula I also contains a radionuclide or an imaging agent or both, the compound of formula I is a theranostic agent useful for treating and diagnosing tumors, including cancers.