6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthoic acid | 426219-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthoic acid
• 英文别名: 6-(7-Hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-7-yl)-2-naphthoic acid；6-(7-hydroxy-5,6-dihydropyrrolo[1,2-c]imidazol-7-yl)naphthalene-2-carboxylic acid
• CAS: 426219-54-7
• 化学式: C₁₇H₁₄N₂O₃
• 分子量: 294.31
• InChiKey: URHAUKBLWGZRED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthamide
  参考文献：
  名称：

  EP1854463

  摘要：

  公开号：
• 作为产物：
  描述：

  1-(1H-imidazol-5-yl)prop-2-en-1-one 在 正丁基锂 、 氢溴酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 6.33h， 生成 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-2-naphthoic acid
  参考文献：
  名称：

  1,1-Diarylalkenes as anticancer agents: Dual inhibitors of tubulin polymerization and phosphodiesterase 4

  摘要：

  A series of 1,1-diarylalkene derivatives were prepared to optimize the properties of CC-5079 (1), a dual inhibitor of tubulin polymerization and phosphodiesterase 4 (PDE4). By using the 3-ethoxy-4-methoxyphenyl PDE4 pharmacophore as one of the aromatic rings, a significant improvement in PDE4 inhibition was achieved. Compound 28 was identified as a dual inhibitor with potent PDE4 (IC(50) = 54 nM) and antitubulin activity (HCT-116 IC(50) = 34 nM and tubulin polymerization IC(50) similar to 1 mu M). While the nitrile group at the alkene terminus was generally required for potent antiproliferative activity, its replacement was tolerated if there was a hydroxyl or amino group on one of the aryl rings. Conveniently, this group could also serve as a handle for amino acid derivatization to improve the compounds' solubility. The glycinamide analog 45 showed significant efficacy in the HCT-116 xenograft model, with 64% inhibition of tumor growth upon dosing at 20 mg/kg qd. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.068

文献信息

• Novel imidazole derivatives, production method thereof and use thereof
  申请人：——

  公开号：US20040033935A1

  公开（公告）日：2004-02-19

  The present invention provides a compound having a steroid C 17,20 -lyase-inhibitory activity and useful for the therapy and prophylaxis of tumor such as prostatism, breast cancer and the like, and a method for efficiently separating an optically active compound of this compound from a mixture of optical isomers thereof, a compound of the formula: 1 wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof, and a method for obtaining an optically active compound by optically resolving a mixture of optical isomers by the use of a resolving agent such as tartranilic acid and the like.

  本发明提供一种具有类固醇C17,20-裂解酶抑制活性的化合物，用于治疗和预防前列腺癌、乳腺癌等肿瘤，以及一种有效地从其光学异构体混合物中分离出该化合物的光学活性化合物的方法，该化合物的化学式为：1其中每个符号如规范中定义，其盐或前药，以及通过使用像酞氨酸等分离剂对光学异构体混合物进行光学分离来获得光学活性化合物的方法。
• COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
  申请人：Zhang Jiazhong

  公开号：US20110263595A1

  公开（公告）日：2011-10-27

  Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metasteses, gastrointestinal stromal tumors, and giant cell tumors.

  描述了化合物及其盐、配方、共轭物、衍生物、形式和用途。在某些方面和实施例中，所述化合物或其盐、配方、共轭物、衍生物、形式对Fms、Kit、Flt3、TrkA、TrkB和TrkC激酶蛋白中的一个或多个具有活性。还描述了使用方法，用于治疗与Fms、Kit、Flt3、TrkA、TrkB和TrkC中的一个或多个活性相关的疾病和症状，包括类风湿性关节炎、骨关节炎、骨质疏松症、周围假体周围骨溶解、系统性硬化、脱髓鞘疾病、多发性硬化症、沙科特-玛丽-屈氏综合征、肌萎缩性侧索硬化、阿尔茨海默病、帕金森病、全球性缺血、溃疡性结肠炎、克罗恩病、免疫性血小板减少性紫癜、动脉粥样硬化、系统性红斑狼疮、自体移植的骨髓准备、移植排斥、肾小球肾炎、间质性肾炎、狼疮性肾炎、肾小管坏死、糖尿病性肾病、肾肥大、I型糖尿病、急性疼痛、炎症性疼痛、神经病性疼痛、急性髓样白血病、黑色素瘤、多发性骨髓瘤、乳腺癌、前列腺癌、胰腺癌、肺癌、卵巢癌、胶质瘤、胶质母细胞瘤、神经纤维瘤病、骨转移性溶骨病、脑转移瘤、胃肠道间质瘤和巨细胞瘤。
• [EN] NOVEL IMIDAZOLE DERIVATIVES, PRODUCTION METHOD THEREOF AND USE THEREOF<br/>[FR] NOUVEAUX DERIVES IMIDAZOLE, PROCEDE DE PRODUCTION CORRESPONDANT ET UTILISATION DE CES DERIVES
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2002040484A2

  公开（公告）日：2002-05-23

  The present invention provides a compound having a steroid C17,20-lyase-inhibitory activity and useful for the therapy and prophylaxis of tumor such as prostatism, breast cancer and the like, and a method for efficiently separating an optically active compound of this compound from a mixture of optical isomers thereof, a compound of the formula:wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof, and a method for obtaining an optically active compound by optically resolving a mixture of optical isomers by the use of a resolving agent such as tartranilic acid and the like.

  本发明提供了一种具有类固醇C17,20-裂解酶抑制活性的化合物，用于治疗和预防肿瘤，例如前列腺癌、乳腺癌等，并提供了一种从其光学异构体混合物中高效分离出该化合物的光学活性化合物的方法，该化合物的式为：其中每个符号如规范中所定义，其盐或前药，以及通过使用像酞磺酸等分离剂对光学异构体混合物进行光学分离以获得光学活性化合物的方法。
• Imidazole derivatives, production method thereof and use thereof
  申请人：Takeda Pharmaceutical Company, Ltd.

  公开号：US07141598B2

  公开（公告）日：2006-11-28

  The present invention provides a compound having a steroid C17,20-lyase-inhibitory activity and useful for the therapy and prophylaxis of tumor such as prostatism, breast cancer and the like, and a method for efficiently separating an optically active compound of this compound from a mixture of optical isomers thereof, a compound of the formula: wherein each symbol is as defined in the specification, a salt thereof or a prodrug thereof, and a method for obtaining an optically active compound by optically resolving a mixture of optical isomers by the use of a resolving agent such as tartranilic acid and the like.

  本发明提供了一种具有类固醇C17,20-裂解酶抑制活性的化合物，可用于治疗和预防肿瘤，如前列腺癌、乳腺癌等，以及一种从其光学异构物混合物中高效分离出该化合物的光学活性化合物的方法，该化合物的公式如下：其中每个符号如规范中所定义，其盐或前药，以及通过使用像是苯甲酸等分离剂光学分离光学异构体混合物来获得光学活性化合物的方法。
• Release-Control Composition
  申请人：Ishida Hajime

  公开号：US20090053308A1

  公开（公告）日：2009-02-26

  The present invention relates to a controlled release capsule preparation for oral administration, which contains (i) a granule containing a physiologically active substance which is a compound represented by the formula: wherein n is an integer of 1 to 3, and Ar is an aromatic ring optionally having substituent(s), or a salt thereof, and a hydrophilic polymer, and coated with an enteric coating agent and the like, and (ii) a fluidizer. According to the present invention, a controlled release composition for oral administration of an imidazole derivative, which has steroid C 17,20 -lyase inhibiting activity and which has remarkably improved sustainability of the blood concentration, is provided.

  本发明涉及一种口服控释胶囊制剂，其包含（i）一种颗粒，其中包含一种生理活性物质，该物质是由以下公式表示的化合物：其中n是1至3的整数，Ar是一种芳香环，可以具有取代基，或其盐，以及一种亲水性聚合物，并涂有肠溶涂层剂等；（ii）一种流动剂。根据本发明，提供了一种具有类固醇C17,20-裂解酶抑制活性并具有显着改善血浓度持久性的咪唑衍生物口服控释组合物。