hydron;9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one;chloride;dihydrate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: hydron;9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one;chloride;dihydrate
• 化学式: C18H24ClN3O3
• mdl: MFCD00374371
• 分子量: 365.9
• InChiKey: VRSLTNZJOUZKLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.35
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  41.8
• 氢给体数：
  3
• 氢受体数：
  4

ADMET

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用概述：奥丹泽琼（Ondansetron）常用于剖宫产期间和之后的恶心治疗，通常通过静脉注射4至8毫克。在剖宫产期间和之后使用奥丹泽琼似乎不会影响哺乳的开始。在这种设置中或在接受奥丹泽琼产后药代动力学研究的女性中，没有报告对婴儿有不良影响。对于哺乳期母亲在产后即时设置之外使用奥丹泽琼的研究不够充分，但该药物被标记为适用于1个月大的婴儿。计算机模型显示，乳汁中的量远低于这一剂量。无需特殊预防措施。 对哺乳婴儿的影响：在一项对78名接受奥丹泽琼静脉注射产后女性的药代动力学研究中，没有报告她们的哺乳婴儿出现不良影响。 对哺乳和乳汁的影响：一项随机双盲研究比较了剖宫产后作为预防术后恶心和呕吐的安慰剂与静脉注射奥丹泽琼4毫克。两组之间第一次哺乳的时间没有差异。 在一项回顾性研究中，比较了接受剖宫产的三组女性：115名在麻醉前和分娩期间使用右美托咪定（dexmedetomidine），109名在麻醉前和分娩期间使用生理盐水，并在分娩后使用右美托咪定，以及168名在麻醉前和分娩期间使用生理盐水。所有女性根据需要和拆线前接受4毫克奥丹泽琼。各组女性平均消耗的奥丹泽琼总量在6毫克至9毫克之间。各组第一次产生乳汁的时间相似（25至28分钟）。

◉ Summary of Use during Lactation:Ondansetron is frequently used for nausea during and after cesarean section, usually in doses of 4 to 8 mg intravenously. Use during and after cesarean section appears to not affect the onset of breastfeeding. No adverse infant effects have been reported in this setting or among women who received ondansetron postpartum in a pharmacokinetic study. Use of ondansetron in nursing mothers beyond the immediate postpartum setting has not been studied well, but the drug is labeled for use in infants as young as 1 month of age. A computer model demonstrated that the amounts in milk are much less than this dose. No special precautions are required. ◉ Effects in Breastfed Infants:In a pharmacokinetic study of 78 women who received ondansetron intravenously postpartum, no adverse effects were reported in their breastfed infants. ◉ Effects on Lactation and Breastmilk:A randomized, double-blind study compared placebo to intravenous ondansetron 4 mg given after cesarean section as prophylaxis for postoperative nausea and vomiting. There was no difference in the time of the first breastfeeding between the two groups. In a retrospective study of women undergoing cesarean section deliveries, 3 regimens were compared: dexmedetomidine before anesthesia and during delivery (n = 115), normal saline before anesthesia and during delivery and dexmedetomidine after delivery (n = 109), and normal saline before anesthesia and during delivery (n = 168). All women received ondansetron 4 mg as needed and before removal of sutures. The average total amount of ondansetron consumed in the women ranged from 6 mg to 9 mg in the various groups. The time to first production of milk was similar in all groups (25 to 28 minutes).

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  hydron;9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one;chloride;dihydrate 在 solvent 作用下， 以 toluene ethanol 为溶剂， 10.0~50.0 ℃ 、13.51 MPa 条件下， 反应 8.0h， 以to give 1.4 g of ondansetron hydrochloride Form A的产率得到盐酸枢复宁
  参考文献：
  名称：

  Novel crystal and solvate forms of ondansetron hydrochloride and processes for their preparation

  摘要：

  本发明提供了新型的奥曲肽盐酸盐结晶多态形式和溶剂化物。同时还提供了制备和相互转化多态形式的过程。此外，还提供了使用新型多态形式和水合物的制药组合物和治疗方法。

  公开号：

  US20020107275A1
• 作为产物：
  描述：

  昂丹司琼 、 盐酸 在 乙醇 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以to give 32.6 g of title compound (yield 90%)的产率得到hydron;9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4-one;chloride;dihydrate
  参考文献：
  名称：

  Process for preparing 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazole-1-yl)methyl]-4H-carbazol-4-one or its salt

  摘要：

  1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮或其盐可通过在溶剂中存在酸、烷基硅酰卤化物化合物或酰卤化物化合物的情况下，将2式化合物与3式化合物和4式化合物反应，高产率地制备，因此，这种创新的过程可以有利地应用于大规模生产。

  公开号：

  US07521565B2

文献信息

• Medicaments
  申请人：Glaxo Group Limited

  公开号：US04929632A1

  公开（公告）日：1990-05-29

  The invention relates to the use of compounds of the general formula (I) ##STR1## wherein R.sup.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-(C.sub.1-4) alkyl, C.sub.3-6 alkenyl, C.sub.3-10 alkynyl, phenyl or phenyl-C.sub.1-3 alkyl group; and one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl - C.sub.1-3 alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates thereof, for the relief of nausea and vomiting and/or the promotion of gastric emptying and for the manufacture of a medicament for this purpose. Promotion of gastric emptying may be for the relief of gastro-intestinal disorders associated with gastric stasis or may be of advantage in radiological examination procedures. The invention also relates to a product containing a therapeutic agent liable to induce nausea and vomiting, e.g. a cytostatic agent such as a cyclophosphamide, an alkylating agent or a platinum complex, and a compound of the general formula (I) as a combined preparation for simultaneous separate or sequential use in therapy.

  本发明涉及使用具有通式(I)的化合物，其中R1代表氢原子或C1-10烷基，C3-7环烷基，C3-7环烷基-(C1-4)烷基，C3-6烯基，C3-10炔基，苯基或苯基-C1-3烷基；R2、R3和R4所代表的基团中的一个是氢原子或C1-6烷基，C3-7环烷基，C2-6烯基或苯基-C1-3烷基，另外两个可能相同也可能不同的基团分别代表氢原子或C1-6烷基；以及其生理上可接受的盐和溶剂，用于缓解恶心和呕吐和/或促进胃排空并用于制造用于此目的的药物。促进胃排空可以用于缓解与胃滞留相关的胃肠道疾病，也可以在放射学检查过程中具有优势。本发明还涉及含有易引起恶心和呕吐的治疗剂，例如细胞毒性剂，如环磷酰胺，烷化剂或铂络合物，以及具有通式(I)的化合物作为联合制剂的产品，用于同时、分离或顺序使用于治疗中。
• Ondansetron forms and processes of making the same
  申请人：——

  公开号：US20040198794A1

  公开（公告）日：2004-10-07

  Ondansetron forms are identified and processes for making the same are provided. The ondansetron can be used in various pharmaceutical applications.

  奥替赛龙的形式已被确定，并提供了制造这些形式的过程。奥替赛龙可用于各种药物应用。
• 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition
  申请人：Glaxo Group Limited

  公开号：US04695578A1

  公开（公告）日：1987-09-22

  The invention relates to compounds of formula (I). ##STR1## wherein R.sub.1 represents a hydrogen atom or a C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-6 alkenyl, C.sub.3-7 cycloalkyl-(C.sub.1-4) alkyl, C.sub.3-10 alkynyl, phenyl or phenyl-C.sub.1-3 alkyl group, and one of the groups represented by R.sup.2, R.sup.3 and R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-6 alkenyl or phenyl-(C.sub.1-3) alkyl group and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C.sub.1-6 alkyl group; and physiologically acceptable salts and solvates, e.g. hydrates thereof. The compounds are potent selective antagonists at "neuronal" 5-hydroxytryptamine receptors and are useful in the treatment of migraine and psychotic disorders such as schizophrenia.

  本发明涉及式(I)的化合物。其中，R.sub.1代表氢原子或C.sub.1-10烷基，C.sub.3-7环烷基，C.sub.3-6烯基，C.sub.3-7环烷基-(C.sub.1-4)烷基，C.sub.3-10炔基，苯基或苯基-C.sub.1-3烷基基团，而由R.sup.2、R.sup.3和R.sup.4表示的三个基团中的一个是氢原子或C.sub.1-6烷基，C.sub.3-7环烷基，C.sub.2-6烯基或苯基-(C.sub.1-3)烷基基团，其余两个可能相同也可能不同的基团表示氢原子或C.sub.1-6烷基；以及其生理上可接受的盐和溶剂，例如水合物。这些化合物是“神经元”5-羟色胺受体的有效选择性拮抗剂，可用于治疗偏头痛和精神疾病，如精神分裂症。
• Process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one and ondansetron therefrom
  申请人：Gutman Daniella

  公开号：US20060041004A1

  公开（公告）日：2006-02-23

  The present invention provides a rapid, high-yielding process for preparing 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one from 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one without using a secondary amine as a catalyst, and without using glacial acetic acid as a solvent. The present invention further provides a rapid, high-yielding process for preparing ondansetron from 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one without using alumina as a catalyst.

  本发明提供了一种快速、高产的制备1,2,3,9-四氢-9-甲基-3-亚甲基-4H-咔唑-4-酮的方法，该方法不使用次级胺作为催化剂，也不使用冰乙酸作为溶剂，同时本发明还提供了一种快速、高产的制备昂丹司琼的方法，该方法不使用氧化铝作为催化剂，而是从1,2,3,9-四氢-9-甲基-3-亚甲基-4H-咔唑-4-酮开始制备。
• Method of medical treatment
  申请人：Glaxo Group Limited

  公开号：US04835173A1

  公开（公告）日：1989-05-30

  The invention relates to the use of 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carba zol-4-one and physiologically acceptable salts and solvates thereof in the treatment of depression.

  本发明涉及使用1,2,3,9-四氢-9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-4H-咔唑-4-酮及其生理上可接受的盐和溶剂，用于治疗抑郁症。