(7S,9S)-6,9,11-三羟基-9-(2-羟基乙酰基)-7-[5-羟基-4-[(2S)-2-甲氧基吗啉-4-基]-6-甲基四氢吡喃-2-基]氧基-4-甲氧基-8,10-二氢-7H-并四苯-5,12-二酮 | 108943-08-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 中文名称: (7S,9S)-6,9,11-三羟基-9-(2-羟基乙酰基)-7-[5-羟基-4-[(2S)-2-甲氧基吗啉-4-基]-6-甲基四氢吡喃-2-基]氧基-4-甲氧基-8,10-二氢-7H-并四苯-5,12-二酮
• 英文名称: 3'-deamino-3'-[2''(S)-methoxy-4''-morpholinyl]doxorubicin hydrochloride
• 英文别名: Nemorubicin hydrochloride；(7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-7-[(2R,4S,5S,6S)-5-hydroxy-4-[(2S)-2-methoxymorpholin-4-yl]-6-methyloxan-2-yl]oxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
• CAS: 108943-08-4
• 化学式: C₃₂H₃₇NO₁₃*ClH
• 分子量: 680.106
• InChiKey: DSXDXWLGVADASF-QQFKZXDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  47
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  202
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (7S,9S)-6,9,11-三羟基-9-(2-羟基乙酰基)-7-[5-羟基-4-[(2S)-2-甲氧基吗啉-4-基]-6-甲基四氢吡喃-2-基]氧基-4-甲氧基-8,10-二氢-7H-并四苯-5,12-二酮 在 三羟甲基氨基甲烷 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 0.08h， 生成 PNU-159682
  参考文献：
  名称：

  In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: A comparison with human liver microsomes

  摘要：

  We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU159682 is also produced in these species, and to identify the CYP form(s) responsible for its formation; (2) to compare the animal metabolism of MMDX with that by human liver microsomes (HLMs), in order to determine which animal species is closest to human beings; (3) to explore whether differences in PNU-159682 formation are responsible for previously reported species- and sex-related differences in MMDX host toxicity. The animal metabolism of MMDX proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form. However, there were marked quantitative inter- and intra-species differences in kinetic parameters. The mouse and the male rat exhibited V,,, and intrinsic metabolic clearance (CLint) values closest to those of human beings, suggesting that these species are the most suitable animal models to investigate MMDX biotransformation. A close inverse correlation was found between MMDX CLint and previously reported values of MMDX LD50 for animals of the species, sex and strain tested here, indicating that differences in the in vivo toxicity of MMDX are most probably due to sex- and species-related differences in the extent of PNU-159682 formation. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2008.07.003

文献信息

• モルホリニルアントラサイクリン誘導体および脱メチル化剤を含む、抗腫瘍性組合せ
  申请人：ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ

  公开号：JP2011513274A

  公开（公告）日：2011-04-28

  本発明では、モルホリニルアントラサイクリン誘導体、特にメトキシモルホリノドキソルビシン誘導体または薬学的に許容されるこの塩および脱メチル化剤の、抗腫瘍作用を有する組合せが提供される。また、前記組合せの、転移の治療または予防、腫瘍の治療における使用、ならびにそのようなメトキシモルホリノドキソルビシン誘導体に耐性な細胞における耐性を解消するための使用も提供される。

  本发明提供了具有抗肿瘤作用的吗啉基蒽环类衍生物，特别是甲氧吗啉多柔比星衍生物或其药学上可接受的盐与去甲基化剂的组合物。本发明还提供了上述组合物在治疗或预防转移、治疗肿瘤以及消除对此类甲氧吗啉基莫多巴霉素衍生物有抗药性的细胞的抗药性方面的用途。
• Embolization particulates for occluding a blood vessel
  申请人：ACCURATE MEDICAL THERAPEUTICS LTD.

  公开号：US10456235B2

  公开（公告）日：2019-10-29

  Injectable embolization particulates (e.g., particles, microstructures, beads) employed in embolization procedures, for facilitating blood vessel occlusion. Exemplary embolization particulates for occluding a blood vessel include a plurality of embolization beads, each bead having a plurality of outwardly protruding portions, wherein, upon a first one and a second one of the beads accumulating against a boundary of the blood vessel, protruding portions of the first bead are configured to intermesh with protruding portions of the second bead, so as to occlude the blood vessel. Also disclosed are compositions of embolization particulates including a plurality of shaped embolization beads, and methods for embolizing or occluding a blood vessel using embolization particulates or compositions thereof. Embolization particulates have particular shapes for facilitating blood vessel occlusion while preventing or diminishing back flow (reflux) of embolic material, and may be coated or impregnated with therapeutic agents or radioactive isotopes, for increasing desirable therapeutic effects.

  在栓塞手术中使用的可注射栓塞微粒（如颗粒、微结构、珠子），用于促进血管闭塞。用于闭塞血管的示例性栓塞微粒包括多个栓塞珠，每个栓塞珠具有多个向外突出的部分，其中，当第一颗和第二颗栓塞珠聚集到血管的边界时，第一颗栓塞珠的突出部分被配置为与第二颗栓塞珠的突出部分相互啮合，从而闭塞血管。还公开了栓塞微粒的组合物，包括多个形状的栓塞珠，以及使用栓塞微粒或其组合物栓塞或闭塞血管的方法。栓塞微粒具有特殊形状，可促进血管闭塞，同时防止或减少栓塞材料的回流，还可涂覆或浸渍治疗剂或放射性同位素，以提高理想的治疗效果。
• Chemoembolization composition comprising anti-angiogenic agents
  申请人：CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS

  公开号：US10537643B2

  公开（公告）日：2020-01-21

  The invention relates to chemoembolization compositions for anti-angiogenic agent delivery. The invention further relates to a method of preparing chemoembolization compositions and to the use of chemoembolization compositions in the method for treating solid tumour cancers.

  本发明涉及用于输送抗血管生成剂的化疗栓塞组合物。本发明还涉及一种制备化疗栓塞组合物的方法，以及在治疗实体瘤癌症的方法中使用化疗栓塞组合物。
• METHOD FOR TREATING LIVER CANCER BY INTRAHEPATIC ADMINISTRATION OF NEMORUBICIN
  申请人：Pharmacia Italia S.p.A.

  公开号：EP1596874A1

  公开（公告）日：2005-11-23
• CRYSTALLINE NEMORUBICIN HYDROCHLORIDE
  申请人：Nerviano Medical Sciences S.r.l.

  公开号：EP2049530A2

  公开（公告）日：2009-04-22