(E)-3-溴-4-氧代-4-(4-甲氧基苯基)丁-2-烯酸 | 5711-40-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (E)-3-溴-4-氧代-4-(4-甲氧基苯基)丁-2-烯酸
• 中文别名: 溴美酸
• 英文名称: cis-β-4-Methoxy-benzoyl-β-brom-acrylsaeure
• 英文别名: Bromebric acid；(E)-3-bromo-4-(4-methoxyphenyl)-4-oxobut-2-enoic acid
• CAS: 5711-40-0
• 化学式: C₁₁H₉BrO₄
• 分子量: 285.094
• InChiKey: UPZFHUODAYGHDZ-RMKNXTFCSA-N

物化性质

• 物理描述：
  Cytembena is a white to off-white powder. (NTP, 1992)
• 熔点：
  500 to 505 °F (NTP, 1992)
• 溶解度：
  50 to 100 mg/mL at 70° F (NTP, 1992)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

塞特本纳被兔肝微粒体去甲基化，并在存在谷胱甘肽和NADPH的情况下，通过100,000-G上清液组分去溴化和饱和。代谢物的结构通过质谱法暂时确定。

CYTEMBENA WAS DEMETHYLATED BY RABBIT LIVER MICROSOMES & WAS DEBROMINATED & SATURATED BY 100,000-G SUPERNATANT FRACTION IN PRESENCE OF GLUTATHIONE & NADPH. STRUCTURES OF METABOLITES TENTATIVELY IDENTIFIED BY MASS SPECTROMETRY.

来源:Hazardous Substances Data Bank (HSDB)

代谢

CYTEMBENA与包括谷胱甘肽和半胱氨酸在内的硫醇化合物迅速发生反应，导致硫的烷基化。CYTEMBENA和谷胱甘肽的产物被分离并测试了其细胞毒性；它不如游离的CYTEMBENA有效。这个反应可能是一种解毒过程。

CYTEMBENA UNDERGOES RAPID REACTION WITH THIOL COMPD INCL GLUTATHIONE & CYSTEINE, RESULTING IN ALKYLATION OF SULFUR. PRODUCT OF CYTEMBENA & GLUTATHIONE WAS ISOLATED & TESTED FOR CYTOTOXICITY; IT WAS LESS EFFECTIVE THAN FREE CYTEMBENA. REACTION MAY BE DETOXIFICATION PROCESS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

17例对第3阶段和第4阶段的烷化剂有抵抗性的卵巢癌患者接受了塞特明贝治疗，剂量为每天两次，每次200毫克/平方米，每隔5周连续治疗5天。除了一名患者外，所有患者都出现了恶心和呕吐，其中3名患者有轻度腹泻，2名患者出现了脱发。

17 PT WITH STAGES 3 & 4 ALKYLATING AGENT RESISTANT OVARIAN CARCINOMAS WERE TREATED WITH CYTEMBENA IN DOSES OF 200 MG/SQ M TWICE DAILY FOR 5 DAYS EVERY 5 WK. NAUSEA & VOMITING OCCURRED IN ALL EXCEPT 1 PT, & 3 PT HAD MILD DIARRHEA. 2 HAD ALOPECIA.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

22位患者连续5天每天接受静脉注射。毒性反应与剂量相关，在300毫克/平方米时变得显著；出现恶心和呕吐。在475毫克/平方米的剂量下，出现了高血压、心动过速、胸痛和心电图变化。

22 PT RECEIVED DAILY IV INJECTIONS FOR 5 DAYS. TOXICITY WAS DOSE RELATED, BECOMING PROMINENT @ 300 MG/SQ M; NAUSEA & VOMITING WERE SEEN. HYPERTENSION, TACHYCARDIA, CHEST PAIN, & ECG CHANGES OCCURRED @ DOSES OF 475 MG/SQ M.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

30名组织学上证实为晚期卵巢或乳腺癌的女性患者接受了赛替麦宾治疗，剂量为每天250毫克/平方米，连续5天，每周重复一次。没有发现造血毒性。恶心、呕吐和自主神经风暴现象是限制剂量的因素。

30 WOMEN WITH HISTOLOGICALLY PROVEN ADVANCED OVARIAN OR BREAST CANCER WERE TREATED WITH CYTEMBENA, DOSE OF 250 MG/SQ M/DAY FOR 5 DAYS REPEATED @ WEEKLY INTERVALS. NO HEMOPOIETIC TOXICITY. NAUSEA & VOMITING & AUTONOMIC STORM PHENOMENON ARE DOSE-LIMITING FACTORS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

多种恶性肿瘤患者接受了20毫克/千克的赛特本钠静脉注射。赛特本钠治疗24小时后，异常中期的频率和染色体断裂的情况较低。

PT WITH VARIOUS TYPES OF MALIGNANCY RECEIVED 20 MG CYTEMBENA/KG, IV. THE FREQUENCY OF ABNORMAL METAPHASES & CHROMOSOMAL BREAKS 24 HR AFTER CYTEMBENA TREATMENT WAS LOW.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

长期静脉注射12.5-200毫克/千克/天和6.25-50毫克/千克/天的药物在狗和猴子身上，损害了远端肾小管，并且耗尽了淋巴组织的生殖细胞元素；在高剂量下产生了呕吐、厌食和体重减轻。在猴子身上还观察到了骨髓和肝脏的涉及。

CHRONIC IV ADMIN OF 12.5-200 & 6.25-50 MG/KG/DAY IN DOGS & MONKEYS DAMAGED DISTAL RENAL TUBULES, & DEPLETED GERMINAL CELLULAR ELEMENTS OF LYMPHOID TISSUES; @ HIGH DOSES PRODUCED EMESIS, ANOREXIA, & WT LOSS. BONE MARROW & LIVER INVOLVEMENT NOTED IN MONKEYS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在正常受试者中，单次静脉注射200毫克后15小时内，肾脏排泄量约为给药剂量的7.8%。在肾功能受损的患者中，尿排泄量较少，并且与内生肌酐清除率下降直接相关。

IN NORMAL SUBJECTS RENAL EXCRETION WAS APPROX 7.8% OF GIVEN DOSE IN 15 HR FOLLOWING SINGLE IV INJECTION OF 200 MG. IN PT WITH IMPAIRED RENAL FUNCTION, URINARY EXCRETION WAS LESS & DIRECTLY CORRELATED WITH DECR IN ENDOGENOUS CREATININE CLEARANCE RATE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当给予14C标记的赛特明贝钠时，大鼠在24小时内排泄了超过70%，而狗排泄了超过50%的放射性剂量；大部分标记物在尿液中找到。24小时后，肾脏保留了最高的放射性水平。

WHEN (14)C-LABELED CYTEMBENA WAS ADMIN, RATS EXCRETED GREATER THAN 70% & DOGS GREATER THAN 50% OF RADIOACTIVE DOSE IN 24 HR; MOST OF LABEL WAS FOUND IN URINE. KIDNEY RETAINED HIGHEST LEVEL OF RADIOACTIVITY AFTER 24 HR.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (E)-3-溴-4-氧代-4-(4-甲氧基苯基)丁-2-烯酸 在 ammonium hydroxide 、 ammonium chloride 、 一水合肼 作用下， 以 乙二醇 为溶剂， 184.0 ℃ 、2.58 MPa 条件下， 反应 2.5h， 生成 4-氨基-3-(4-甲氧基苯基)-1H-哒嗪-6-酮
  参考文献：
  名称：

  哒嗪。十五。合成6-芳基-5-氨基-3（2 H）-哒嗪酮作为潜在的血小板凝集抑制剂† ‡

  摘要：

  已经制备了几个在哒嗪核的5-位具有氨基的3（2 H）-哒嗪酮。从粘氯酸和粘溴酸得到的6-芳基-5-卤代-3（2 H）-哒嗪酮导致相应的5-烷基氨基-3（2 H）-哒嗪酮，其被测试为血小板聚集抑制剂。

  DOI：

  10.1002/jhet.5570350634
• 作为产物：
  描述：

  4-(4'-methoxyphenyl)-2,3-dibromocrotonolactone 在 水 、 magnesium oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.25h， 以76%的产率得到(E)-3-溴-4-氧代-4-(4-甲氧基苯基)丁-2-烯酸
  参考文献：
  名称：

  哒嗪。十五。合成6-芳基-5-氨基-3（2 H）-哒嗪酮作为潜在的血小板凝集抑制剂† ‡

  摘要：

  已经制备了几个在哒嗪核的5-位具有氨基的3（2 H）-哒嗪酮。从粘氯酸和粘溴酸得到的6-芳基-5-卤代-3（2 H）-哒嗪酮导致相应的5-烷基氨基-3（2 H）-哒嗪酮，其被测试为血小板聚集抑制剂。

  DOI：

  10.1002/jhet.5570350634

文献信息

• Composition comprising covalent conjugates of chitosan and an acidic drug for parenteral administration
  申请人：The Jordanian Pharmaceutical Manufacturing Co.

  公开号：EP1955711A1

  公开（公告）日：2008-08-13

  The present invention relates to a composition comprising an aqueous solvent and a conjugate of at least one hydrophilic polymer having a primary amine functional group, a derivative or monomer thereof and at least one acidic drug; a method for its preparation and use thereof

  本发明涉及一种组合物，包括水性溶剂和至少一个具有一级胺官能团的亲水性聚合物的共轭物，其衍生物或单体以及至少一种酸性药物；其制备方法和使用方法。
• Composition comprising chitosan and an acidic drug for oral controlled release
  申请人：The Jordanian Pharmaceutical Manufacturing Co.

  公开号：EP1955693A1

  公开（公告）日：2008-08-13

  The present invention relates to a composition comprising an aqueous solvent and a conjugate of at least one hydrophilic polymer having a primary amine functional group, a derivative or monomer thereof and at least one acidic drug; a method for its preparation and use thereof.

  本发明涉及一种组合物，包括水性溶剂和至少一种含有一种主要胺基官能团的亲水性聚合物、其衍生物或单体与至少一种酸性药物结合物；以及其制备方法和使用方法。
• Aqueous composition comprising chitosan and an acidic drug
  申请人：The Jordanian Pharmaceutical Manufacturing Co.

  公开号：EP1955710A1

  公开（公告）日：2008-08-13

  The present invention relates to a composition comprising an aqueous solvent and a conjugate of at least one hydrophilic polymer having a primary amine functional group, a derivative or monomer thereof and at least one acidic drug; a method for its preparation and use thereof.

  本发明涉及一种组合物，包括水性溶剂和至少一个具有初级胺官能团的亲水性聚合物共轭物，其衍生物或单体以及至少一种酸性药物；以及其制备方法和使用方法。
• Controlled release oral drug delivery system
  申请人：The Jordanian Pharmaceutical Manufacturing Co.

  公开号：EP1721602A1

  公开（公告）日：2006-11-15

  The invention relates to a molecular ionic complex formed between an acidic pharmaceutical drug or its salt or solvate and glucosamine, chondroitin, hyaluronic acid or heparin or its salts or derivatives. The complex can provide for a liquid oral controlled drug delivery. For example, ibuprofen sodium complex with glucosamine sulfate potassium (GSP) was found to have a zero order controlled drug delivery when given orally to rabbits.

  本发明涉及一种由酸性药物或其盐或溶剂与葡萄糖胺、软骨素、透明质酸或肝素或其盐或衍生物形成的分子离子复合物。该复合物可提供液体口服控制药物释放。例如，发现当将布洛芬钠与硫酸葡萄糖胺钾（GSP）形成复合物后，口服给兔子时具有零级控制药物释放。
• Diagnostic/therapeutic agents
  申请人：Klaveness Jo

  公开号：US20050002865A1

  公开（公告）日：2005-01-06

  Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.

  可定位的诊断和/或治疗活性剂，例如超声对比剂，包括悬浮在水载体液中的报告物，该报告物包含含气体或生成气体的材料，该剂能够与目标形成至少两种结合对。