baccatin III 13- | 143842-96-0

• 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: baccatin III 13-
• 英文别名: N-debenzoyl-N-(4-chlorobenzoyl) taxol；baccatin III 13-[N-(p-chlorobenzoyl)-(2'R,3'S)-3'-phenylisoserinate]；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-[(4-chlorobenzoyl)amino]-2-hydroxy-3-phenylpropanoyl]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: 143842-96-0
• 化学式: C₄₇H₅₀ClNO₁₄
• 分子量: 888.365
• InChiKey: CFCVIJYLRRCBFF-MZXODVADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  63
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  221
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 咪唑 、 氢氟酸 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.83h， 生成 baccatin III 13-
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0

文献信息

• Synthesis of biologically active taxol analogs with modified phenylisoserine side chains
  作者：Gunda I. Georg、Zacharia S. Cheruvallath、Richard H. Himes、Magdalena R. Mejillano、Charles T. Burke

  DOI：10.1021/jm00100a031

  日期：1992.10

  the first synthesis and biological evaluation of taxol derivatives with substituted phenyl rings at the C-13 N-benzoyl-(2'R,3'S)-3'-phenylisoserine side chain of taxol (1). Two taxol derivatives were synthesized, one possessing a N-(p-chlorobenzoyl)-(2'R,3'S)-3'-phenylisoserine side chain (2) and the other one a N-benzoyl-(2'R,3'S)-3'-(p-chlorophenyl)isoserine side chain (3). The synthesis of the novel

  紫杉酚（1）是一种高效的抗肿瘤药，通过促进细胞中稳定的微管的组装发挥其作用机理。我们正在报道关于紫杉醇的C-13 N-苯甲酰基-（2'R，3'S）-3'-苯基异丝氨酸侧链上带有取代苯环的紫杉醇衍生物的首次合成和生物学评估（1）。合成了两种紫杉醇衍生物，一种具有N-（对氯苯甲酰基）-（2'R，3'S）-3'-苯基异丝氨酸侧链（2），另一种具有N-苯甲酰基-（2'R，3'S） -3'-（对氯苯基）异丝氨酸侧链（3）。通过酯烯酸酯-亚胺环缩合反应的不对称合成3-羟基-4-芳基-2-氮杂环丁酮衍生物，实现了新型苯基异丝氨酸侧链的合成。将2-氮杂环丁酮14和15分别用对氯苯甲酰氯和苯甲酰氯酰化，以形成N-酰基β-内酰胺16和17。随后将16和17偶联到7-（三乙基甲硅烷基）浆果赤霉素III（6）在吡啶和DMAP的存在下，在除去保护基团之后，以优异的产率提供了所需的紫杉醇类似物2和3。在微管蛋白组装测
• POLYMORPHS OF N-MALONYL-BIS(N`-METHYL-N`-THIOBENZOYLHYDRAZIDE)
  申请人：SYNTA PHARMACEUTICALS CORP.

  公开号：US20140350115A1

  公开（公告）日：2014-11-27

  At least 70% by weight of Compound 1 is the single crystalline form, Form A, Form C, or Form D, of the compound. A pharmaceutical composition comprises a pharmaceutically acceptable carrier or diluent, and compound 1, wherein at least 70% by weight of the compound is the single crystalline form, Form A, Form C, or Form D, of the compound. A method of treating a subject with cancer comprises administering to the subject an effective amount of compound 1 or the pharmaceutical composition.

  化合物1的重量至少70％是化合物的单晶形式，即A型、C型或D型。一种药物组合物包括一种药学上可接受的载体或稀释剂，以及化合物1，其中至少70％的化合物是单晶形式，即A型、C型或D型。一种治疗癌症患者的方法包括向患者投予化合物1或药物组合物的有效量。
• Paclitaxel enhancer compounds
  申请人：Koya Keizo

  公开号：US20080214655A1

  公开（公告）日：2008-09-04

  Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R 7 R 8 )—. R 1 and R 2 are independently an aryl group or a substituted aryl group, R 3 and R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 7 and R 8 are each independently —H, an aliphatic or substituted aliphatic group, or R 7 is —H and R 8 is a substituted or unsubstituted aryl group, or, R 7 and R 8 , taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

  本发明揭示了一种由结构式（I）表示的化合物： 其中，Y是共价键，苯基或取代或未取代的直链烃基团。此外，Y与其连接的两个>C=Z基团一起，是取代或未取代的芳香族基团。优选地，Y是共价键或—C（R7R8）—。R1和R2分别是芳基基团或取代芳基基团，R3和R4分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R5-R6分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R7和R8各自独立地是—H、脂肪基或取代脂肪基，或者R7是—H，R8是取代或未取代的芳基基团，或者R7和R8一起是C2-C6取代或未取代的烷基基团。Z是═O或═S。本发明还揭示了包含本发明化合物和药学可接受的载体或稀释剂的制药组合物。本发明还揭示了一种通过将Paclitaxel或Paclitaxel类似物与结构式（I）的化合物联合给予受试者治疗癌症的方法。
• Bis(thio-hydrazide amide) salts for treatment of cancers
  申请人：Synta Pharmaceuticals Corp.

  公开号：EP2305642A2

  公开（公告）日：2011-04-06

  Disclosed are bis(thio-hydrazide amide) disalts, which are represented by Structural Formula (I)          2 M+ or M2+Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group. R1-R4 are independently -H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Z is -O or -S. M+ is a pharmaceutically acceptable monovalent cation and M2+ is a pharmaceutically acceptable divalent cation. Also disclosed are pharmaceutical compositions comprising a bis(thio-hydrazide amide) disalt described above. Further disclosed are methods of treating a subject with cancer. The methods comprise the step of administering an effective amount of a bis(thio-hydrazide amide) disalt.

  所公开的是双(硫代酰肼酰胺)二盐，其结构式为 (I) 2 M+ 或 M2+Y 是共价键或取代或未取代的直链烃基。R1-R4 独立地为-H、脂肪族基团、取代的脂肪族基团、芳基或取代的芳基，或 R1 和 R3 与它们所键合的碳原子和氮原子，和/或 R2 和 R4 与它们所键合的碳原子和氮原子，形成一个可选择与芳香环融合的非芳香杂环。Z 是-O 或-S。M+ 是药学上可接受的一价阳离子，M2+ 是药学上可接受的二价阳离子。还公开了包含上述双（硫肼酰胺）二盐的药物组合物。进一步公开了治疗癌症患者的方法。这些方法包括给药有效量的双(硫代酰肼酰胺)二盐的步骤。
• Enhanced loading of intact, bacterially derived vesicles with small molecule compounds
  申请人：EnGeneIC Molecular Delivery Pty Ltd

  公开号：US11052157B2

  公开（公告）日：2021-07-06

  Enhanced loading of small molecule compounds into intact, bacterially derived vesicles provides operational and therapeutic advantages.

  将小分子化合物装载到完整的细菌衍生囊泡中，可增强操作和治疗优势。