(±)-3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid | 51145-64-3

• 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: (±)-3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid
• 英文别名: 3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid；3-amino-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid；3-amino-3'-carboxytetrahydrocarbazole；3-amino-1,2,3,4-tetrahydro-carbazole-3-carboxylic acid；(3RS)-3-amino-2,3,4,9-tetrahydro-1H-3-carbazolecarboxylic acid；3-Amino-1,2,3,4-tetrahydrocarbazol-3-carboxylsaeure；3-amino-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid
• CAS: 51145-64-3
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: HEWZVFOZKYOIAF-UHFFFAOYSA-N

物化性质

• 沸点：
  480.5±45.0 °C(Predicted)
• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  79.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (±)-3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid 在 sodium hydroxide 、 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 生成 (R)-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid
  参考文献：
  名称：

  固相合成取代的3-氨基-3'-羧基-四氢咔唑

  摘要：

  已经开发了两种相关的固相合成路线，其允许合成3-氨基-3'-羧基取代的四氢咔唑衍生物。可以在氨基和羧基官能团以及在四氢咔唑部分的氮和芳环上引入多样性。两种途径均依赖于Fmoc保护的1-氨基-4-氧代环己酮羧酸作为中心核心元素。羧基官能团的衍生可通过胺实现，氨基官能团的衍生可通过与卤代烷，异氰酸酯，活化的醇，磺酸氯或羧酸的反应来实现。四氢咔唑支架是通过费歇尔吲哚与苯基肼衍生物的环化反应生成的，从而在芳族部分引入了多样性。

  DOI：

  10.1016/j.tetlet.2004.12.058
• 作为产物：
  描述：

  2-乙烯基-1H-吲哚 在 盐酸 、 二氯乙基铝 作用下， 以 水 、 甲苯 为溶剂， 反应 9.0h， 生成 (±)-3-amino-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of constrained analogues of tryptophan

  摘要：

  一种路易斯酸催化的对映选择性[4 + 2]环加成反应，涉及乙烯基吲哚和甲基2-乙酰氨基丙烯酸酯，生成甲基3-乙酰氨基-1,2,3,4-四氢咔唑-3-羧酸酯衍生物。在水解条件下处理所得的环加成产物，可制备一系列具有C-3上自由氨基酸功能的化合物库，属于约束色氨酸类似物。

  DOI：

  10.3762/bjoc.11.216

文献信息

• Novel tetrahydrocarbazole derivatives having improved biological action and improved solubility as ligands of G-protein coupled receptors (GPCRs)
  申请人：Paulini Klaus

  公开号：US20060014818A1

  公开（公告）日：2006-01-19

  The present invention provides novel tetrahydrocarbazole derivatives which have improved properties and which can be employed as inhibitors of GPCRs. This results in the possibility of using the novel compounds to treat pathological conditions whose severity depends on the pathobiochemical effect of GPCRs. The compounds of the invention act in particular via an antagonistic inhibition of the LHRH receptor. The invention further provides medicaments which comprise one or more of the novel compounds as active ingredient. The medicaments are suitable in particular to be employed in an oral dosage form for a mammal, in particular a human.

  本发明提供了新颖的四氢咔唑衍生物，具有改进的性能，并可用作GPCR的抑制剂。这导致可以利用这些新型化合物来治疗病理条件，其严重程度取决于GPCR的病理生物化学效应。本发明的化合物特别通过对LHRH受体的拮抗性抑制发挥作用。本发明还提供了包含一种或多种新型化合物作为活性成分的药物。这些药物特别适合用于口服剂型，用于哺乳动物，特别是人类。
• Tetrahydrocarbazol derivatives as ligands for G-protein-coupled receptors (GPCR)
  申请人：ZENTARIS AG

  公开号：US20030232873A1

  公开（公告）日：2003-12-18

  This invention provides new tetrahydrocarbazole derivatives that act as ligands for G-protein-coupled receptors (GPCR), especially as antagonists of the gonadotropin-releasing hormone (GnRH). A pharmaceutical composition that contains these new tetrahydrocarbazole derivatives as well as a process for the production of the new tetrahydrocarbazole derivatives are also provided. Moreover, this invention relates to the administration of tetrahydrocarbazole derivatives for treating pathologic conditions that are mediated by GPCR, especially for inhibiting GnRH, in mammals, especially humans, who require such an administration, as well as the use of tetrahydrocarbazole derivatives for the production of a pharmaceutical agent for treating GPCR-mediated pathologic conditions, especially for inhibiting GnRH.

  这项发明提供了作为G蛋白偶联受体（GPCR）配体的新四氢咔唑衍生物，特别是作为促性腺激素释放激素（GnRH）的拮抗剂。还提供了一种含有这些新四氢咔唑衍生物的药物组合物，以及一种生产这些新四氢咔唑衍生物的方法。此外，这项发明涉及给哺乳动物，特别是人类，需要这种给药的通过四氢咔唑衍生物治疗GPCR介导的病理状况，特别是抑制GnRH的治疗，以及利用四氢咔唑衍生物生产用于治疗GPCR介导的病理状况，特别是抑制GnRH的药物的用途。
• PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION
  申请人：PETZELBAUER Peter

  公开号：US20100081787A1

  公开（公告）日：2010-04-01

  Peptides, peptidomimetics and derivatives thereof of the general formula I: H 2 N-GHRPX 1 - β -X 4 X 5 X 6 X 7 X 8 X 9 X 10 -X 11 (I), in which X 1 -X 10 denote one of the 20 genetically coded amino acids, wherein X 8 , X 9 and X 10 may also denote a single chemical bond; X 11 denotes OR 1 in which R 1 equals hydrogen or (C 1 -C 10 ) alkyl NR 2 R 3 with R 2 and R 3 are equal or different and denote hydrogen, (C 1 -C 10 ) alkyl, or a residue —W-PEG 5-60K , in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y-Z-PEG 5-60K , in which Y denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R and Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, and β denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.

  通用公式I：H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11(I)中的肽、肽类似物和衍生物，其中X1-X10表示20种遗传编码的氨基酸之一，其中X8、X9和X10也可以表示单一化学键；X11表示OR1，其中R1等于氢或(C1-C10)烷基NR2R3，其中R2和R3相同或不同，表示氢、(C1-C10)烷基，或者残基—W-PEG5-60K，其中PEG残基通过适当的间隔物W连接到N-原子，或者残基NH—Y-Z-PEG5-60K，其中Y表示化学键或来自S、C、K或R组的遗传编码氨基酸，Z表示间隔物，通过该间隔物可以连接聚乙二醇（PEG）残基，并且它们的生理上可接受的盐，β表示氨基酸或诱导肽骨架中弯曲或转弯的肽类或肽类似元素。
• NOVEL TETRAHYDROCARBAZOLE DERIVATIVES AS LIGANDS OF G-PROTEIN COUPLED RECEPTORS
  申请人：SCHUSTER Tilmann

  公开号：US20120122763A1

  公开（公告）日：2012-05-17

  The present invention provides novel tetrahydrocarbazole compounds according to formula (I) as ligands of G-protein coupled receptors (GPCR) which are useful in the treatment and/or prophylaxis of physiological and/or pathological conditions in mammals mediated by GPCR or of physiological and/or pathological conditions which can be treated by modulation of these receptors.

  本发明提供了新型四氢咔唑化合物，其符合公式（I），作为G蛋白偶联受体（GPCR）的配体，可用于治疗和/或预防哺乳动物由GPCR介导的生理和/或病理状况，或可以通过调节这些受体来治疗的生理和/或病理状况。
• Novel Tetrahydrocarbazole Derivatives as Ligands of G-protein Coupled Receptors
  申请人：Æterna Zentaris GmbH

  公开号：EP1988098A1

  公开（公告）日：2008-11-05

  The present invention provides novel tetrahydrocarbazole derivatives according to formula (I) as ligands of G-protein coupled receptors (GPCR). The compounds of the invention are useful in the treatment and/or prophylaxis of physiological and/or pathological conditions in mammals, preferably humans, which are mediated by GPCR or of physiological and/or pathological conditions which can be treated by modulation of these receptors. The present invention further provides LHRH receptor antagonists that can be used for the modulation of these receptors and are useful for treating above conditions, in particular prostate cancer, breast cancer, uterine cancer, endometrial cancer, cervical cancer, ovarian cancer, benign prostate hyperplasia (BPH), endometriosis, uterine fibroids, uterine myomas, endometrium hyperplasia, dysmenorrhoea, dysfunctional uterine bleeding (menorrhagia, metrorrhagia), pubertas praecox, hirsutism, polycystic ovary syndrome, hormone-dependent tumor diseases, HIV infections or AIDS, neurological or neurodegenerative disorders, ARC (AIDS related complex), Kaposi sarcoma, tumors originating from the brain and/or nervous system and/or meninges, dementia, Alzheimer's disease, nausea and vomiting, pain, inflammations, rheumatic and arthritic pathological states.

  本发明提供了公式（I）的新型四氢咔唑衍生物，作为G蛋白偶联受体（GPCR）的配体。本发明的化合物可用于治疗和/或预防哺乳动物，尤其是人类的生理和/或病理状况，这些状况是由GPCR介导的或可以通过调节这些受体来治疗的生理和/或病理状况。本发明还提供了LHRH受体拮抗剂，可用于调节这些受体，对于治疗上述疾病，特别是前列腺癌、乳腺癌、子宫癌、子宫内膜癌、宫颈癌、卵巢癌、良性前列腺增生（BPH）、子宫内膜异位症、子宫肌瘤、子宫内膜增生、痛经、功能性子宫出血（月经过多、子宫出血）、早发性青春期、多毛症、多囊卵巢综合征、激素依赖性肿瘤疾病、HIV感染或艾滋病、神经或神经退行性疾病、ARC（艾滋病相关综合征）、卡波西肉瘤、起源于大脑和/或神经系统和/或脑膜的肿瘤、痴呆症、阿尔茨海默病、恶心和呕吐、疼痛、炎症、风湿和关节病理状态都很有用。