(12bS)-12b-甲基-1H-四苯o[5,4-Bc]呋喃-3,6,8,11(2H,12bH)-四酮 | 86690-14-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: (12bS)-12b-甲基-1H-四苯o[5,4-Bc]呋喃-3,6,8,11(2H,12bH)-四酮
• 英文名称: (+)-halenaquinone
• 英文别名: Halenaquinone；(1S)-1-methyl-14-oxapentacyclo[11.6.1.02,11.04,9.016,20]icosa-2(11),3,6,9,13(20),15-hexaene-5,8,12,17-tetrone
• CAS: 86690-14-4
• 化学式: C₂₀H₁₂O₅
• 分子量: 332.312
• InChiKey: SMGBXXZKAPMTBB-FQEVSTJZSA-N

物化性质

• 沸点：
  601.2±55.0 °C(Predicted)
• 密度：
  1.501±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (12bS)-12b-甲基-1H-四苯o[5,4-Bc]呋喃-3,6,8,11(2H,12bH)-四酮 在 sodium dithionite 作用下， 以 水 、 丙酮 为溶剂， 以100%的产率得到halenaquinol
  参考文献：
  名称：

  Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquinol

  摘要：

  DOI：

  10.1021/jo960773z
• 作为产物：
  描述：

  (1S,2S,4aS,8aR)-(-)-1,2,3,4,4a,7,8,8a-octahydro-1-(hydroxymethyl)-4a-methyl-2-naphthalenol 在 吡啶 、 3,5-二甲基吡唑 、 chromium(VI) oxide 、 ammonium cerium(IV) nitrate 、 potassium tert-butylate 、 氧气 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 叔丁醇 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 苯 为溶剂， 反应 57.5h， 生成 (12bS)-12b-甲基-1H-四苯o[5,4-Bc]呋喃-3,6,8,11(2H,12bH)-四酮
  参考文献：
  名称：

  Total synthesis of (+)-halenaquinol and (+)-halenaquinone. Experimental proof of their absolute stereostructures theoretically determined

  摘要：

  DOI：

  10.1021/ja00233a026

文献信息

• Treatment of high Trop-2 expressing triple negative breast cancer (TNBC) with sacituzumab govitecan (IMMU-132) overcomes homologous recombination repair (HRR) rescue mediated by Rad51
  申请人：Immunomedics, Inc.

  公开号：US10918734B2

  公开（公告）日：2021-02-16

  The present invention relates to treatment of Trop-2 positive cancers with the combination of anti-Trop-2 ADC and a Rad51 inhibitor. Preferably the drug conjugated to the antibody is SN-38, and the ADC is sacituzumab govitecan. The ADC may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg. When administered at specified dosages and schedules, the combination of ADC and Rad51 inhibitor can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the combination is effective to treat cancers that are refractory to or relapsed from irinotecan or topotecan.

  本发明涉及用抗Trop-2 ADC和Rad51抑制剂联合治疗Trop-2阳性癌症。与抗体结合的药物最好是 SN-38，ADC 最好是 sacituzumab govitecan。ADC的给药剂量可在4毫克/千克到16毫克/千克之间，最好是4、6、8、9、10、12或16毫克/千克。按规定的剂量和时间给药时，ADC 和 Rad51 抑制剂的组合可缩小实体瘤的大小，减少或消除转移，并能有效治疗对标准疗法（如放疗、化疗或免疫疗法）耐药的癌症。令人惊奇的是，这种组合还能有效治疗对伊立替康或托泊替康难治或复发的癌症。
• Chemical and biological explorations of the electrophilic reactivity of the bioactive marine natural product halenaquinone with biomimetic nucleophiles
  作者：Jiayi Wang、Marie-Lise Bourguet-Kondracki、Arlette Longeon、Joëlle Dubois、Alexis Valentin、Brent R. Copp

  DOI：10.1016/j.bmcl.2010.12.056

  日期：2011.2

  The electrophilic reactivity of the bioactive marine sponge natural product halenaquinone has been investigated by reaction with the biomimetic nucleophiles N-acetyl-L-cysteine and N-alpha-acetyl-L-lysine. While cysteine reacted at the vacant quinone positions C-14 and C-15, lysine was found to react preferentially at the keto-furan position C-1. A small library of analogues was prepared by reaction of halenaquinone with primary amines, and evaluated against a range of biological targets including phospholipase A(2), farnesyltransferases (FTases) and Plasmodium falciparum. Geranylamine analogue 11 exhibited the most potent activity towards FTases (IC50 0.017-0.031 mu M) and malaria (IC50 0.53-0.62 mu M). (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of biotinylated xestoquinone that retains inhibitory activity against Ca2+ ATPase of skeletal muscle myosin
  作者：Mitsuhiro Nakamura、Takahiko Kakuda、Yuichi Oba、Makoto Ojika、Hideshi Nakamura

  DOI：10.1016/s0968-0896(03)00276-1

  日期：2003.7

  Xestoquinone isolated from a marine sponge binds to skeletal muscle myosin and inhibits its Ca2+ ATPase activity. In this study, we first examined xestoquinone and its analogues to assess the relationships between structure and myosin Ca2+ ATPase inhibitory activity. On the basis of the resultant data, we then designed a biotinylated xestoquinone analogue. Xestoquinone and its analogues were derived from extracts of the marine sponge Xestospongia sapra. Four xestoquinone analogues with a quinone structure significantly inhibited Ca2+ ATPase activity. In contrast, four xestoquinone analogues in which the quinone structure was converted to a quinol dimethyl ether did not inhibit Ca2+ ATPase activity. This suggests that the quinone moiety is essential for inhibitory activity. Then, we synthesized a biotinylated xestoquinone in which a biotin tag was introduced to a site far from the quinone moiety, and this molecule exhibited stronger inhibitory activity than that of xestoquinone. This biotinylated xestoquinone could be useful as a probe in studies of the xestoquinone-myosin binding mode. (C) 2003 Elsevier Science Ltd. All rights reserved.
• SCHMITZ, FRANCIS J.;BLOOR, STEPHEN J., J. ORG. CHEM., 53,(1988) N 17, C. 3922-3925
  作者：SCHMITZ, FRANCIS J.、BLOOR, STEPHEN J.

  DOI：——

  日期：——
• TREATMENT OF TROP-2 EXPRESSING TRIPLE NEGATIVE BREAST CANCER WITH SACITUZUMAB GOVITECAN AND A RAD51 INHIBITOR
  申请人：Immunomedics, Inc.

  公开号：EP3600283A1

  公开（公告）日：2020-02-05