4-hydroxy-7-methoxy-2-(1-pyrazolyl)quinoline | 300831-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-hydroxy-7-methoxy-2-(1-pyrazolyl)quinoline
• 英文别名: 7-methoxy-2-pyrazol-1-yl-quinolin-4-ol；7-Methoxy-2-(1H-pyrazol-1-yl)-4-quinolinol；7-methoxy-2-pyrazol-1-yl-1H-quinolin-4-one
• CAS: 300831-01-0
• 化学式: C₁₃H₁₁N₃O₂
• 分子量: 241.249
• InChiKey: ORPPIUVCWZYIQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  472.7±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸甲酯 、 4-hydroxy-7-methoxy-2-(1-pyrazolyl)quinoline 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以69%的产率得到4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2S-methyl ester
  参考文献：
  名称：

  WO2007/5838

  摘要：

  公开号：
• 作为产物：
  描述：

  4-benzyloxy-2-(chloro)-7-methoxyquinoline 在 吡唑 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 4-hydroxy-7-methoxy-2-(1-pyrazolyl)quinoline
  参考文献：
  名称：

  Macrocyclic peptides active against the hepatitis C virus

  摘要：

  本发明涵盖了在体外和细胞内对丙型肝炎病毒NS3蛋白酶具有活性的公式I的大环化合物，其中W、R21、R22、R3、R4、D和A如本文所定义，或其药用可接受的盐或酯。

  公开号：

  US06608027B1

文献信息

• Macrocyclic peptides active against the hepatitis C virus
  申请人：Boehringer Ingelheim (Canada) Ltd

  公开号：US06608027B1

  公开（公告）日：2003-08-19

  The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.

  本发明涵盖了在体外和细胞内对丙型肝炎病毒NS3蛋白酶具有活性的公式I的大环化合物，其中W、R21、R22、R3、R4、D和A如本文所定义，或其药用可接受的盐或酯。
• INHIBITORS OF CATHEPSIN B
  申请人：Holsinger Leslie

  公开号：US20090203629A1

  公开（公告）日：2009-08-13

  The present invention is directed to a method of using compounds of Formula (I) to inhibit Cathepsin B. Specifically the compounds of the present invention are useful as therapeutic agents for the treatment of tumor invasion, metastasis, Alzheimer's Disease, arthritis, inflammatory diseases such as chronic and acute pancreatitis, inflammatory airway disease, and bone and joint disorders, including osteoporosis, osteoarthritis, rheumatoid arthritis, psoriasis, and other autoimmune disorders, liver fibrosis, including liver fibrosis associated with HCV, all types of steatosis (including non-alcoholic steatohepatitis) and alcohol-associated steatohepatitis, non-alcoholic fatty liver disease, forms of pulmonary fibrosis including idiopathic pulmonary fibrosis, pathological diagnosis of interstitial pneumonia following lung biopsy, renal fibrosis, cardiac fibrosis, retinal angiogenesis and fibrosis/gliosis in the eye, schleroderma, and systemic sclerosis. The compounds of Formula (I) are also useful for treating subjects with both HCV and fibrosis in a mammal, particularly liver fibrosis, and subjects affirmatively diagnosed or at risk for both HCV and liver fibrosis.

  本发明涉及一种使用化合物I的方法来抑制蛋白酶B。具体地说，本发明的化合物可用作治疗肿瘤侵袭、转移、阿尔茨海默病、关节炎、慢性和急性胰腺炎、炎症性疾病（如慢性和急性胰腺炎、炎症性气道疾病、骨骼和关节疾病，包括骨质疏松症、骨关节炎、类风湿性关节炎、牛皮癣和其他自身免疫性疾病、包括与丙型肝炎病毒相关的肝纤维化、所有类型的脂肪变性（包括非酒精性脂肪肝炎）和酒精相关性脂肪肝炎、非酒精性脂肪肝病、包括特发性肺纤维化、肺活检后的间质性肺炎病理诊断、肾脏纤维化、心脏纤维化、视网膜血管生成和眼部纤维化/胶质增生、硬皮病和全身性硬化症等疾病的治疗剂。化合物I也适用于治疗哺乳动物中同时患有丙型肝炎病毒和纤维化的受试者，特别是肝纤维化，以及已经确诊或有患有丙型肝炎病毒和肝纤维化风险的受试者。
• [EN] MACROCYCLIC PEPTIDES ACTIVE AGAINST THE HEPATITIS C VIRUS<br/>[FR] PEPTIDES MACROCYCLIQUES ACTIFS CONTRE LE VIRUS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM CA LTD

  公开号：WO2000059929A1

  公开（公告）日：2000-10-12

  The present invention covers macrocyclic compounds of formula (I) active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus wherein W is CH or N; R21 is H, halo, C¿1-6? alkyl, cycloalkyl, haloalkyl, C1-6 alkoxy, cycloalkoxy, hydroxy, or N(R?23)¿2, wherein each R23 is independently H, C¿1-6? alkyl or cycloalkoxy; and R?22¿ is H, halo, C¿1-6? alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 thioalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, C2-7 alkoxyalkyl, C3-6 cycloalkyl, C6 or 10 aryl or Het, wherein Het is a five-, six-, or seven-membered saturated or unsaturated heterocycle containing from one to four heteroatoms selected from nitrogen, oxygen and sulfur; said cycloalkyl, aryl or Het being substituted with R?24¿, wherein R24 is H, C¿1-6? alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, NO2, N(R?25)¿2, NH-C(O)-R25; or NH-C(O)-NH-R25, wherein each R25 is independently: H, C¿1-6? alkyl or C3-6 cycloalkyl; or R?24¿ is NH-C(O)-OR26 wherein R26 is C¿1-6? alkyl or C3-6 cycloalkyl; R?3¿ is hydroxy, NH¿2?, or a group of formula -NH-R?31¿, wherein R31 is C6 or 10 aryl, heteroaryl, -C(O)-R32, -C(O)-OR32 or -C(O)-NHR32, wherein R32 is: C¿1-6? alkyl or C3-6 cycloalkyl; D is a 5 to 10-atom saturated or unsaturated alkylene chain optionally containing one to three heteroatoms independently selected from: O, S, or N-R?41¿, wherein R41 is H, C¿1-6? alkyl, cycloalkyl or -C(O)-R?42¿, wherein R42 is C¿1-6? alkyl, cycloalkyl or C6 or 10 aryl; R?4¿ is H or from one to three substituents at any carbon atom of said chain D, said substituent independently selected from the group consisting of: C¿1-6? alkyl, C1-6 haloalkyl, C1-6 alkoxy, hydroxy, halo, amino, oxo, thio or C1-6 thioalkyl, and A is an amide of formula -C(O)-NH-R?5¿, wherein R5 is selected from the group consisting of: C¿1-8? alkyl, C3-6 cycloalkyl, C6 or 10 aryl or C7-16 aralkyl; or A is a carboxylic acid or a pharmaceutically acceptable salt or ester thereof.

  本发明涵盖了式（I）的大环化合物，该化合物在体外和细胞试验中对丙型肝炎病毒的NS3蛋白酶具有活性，其中W为CH或N; R21为H，卤素，C1-6烷基，环烷基，卤代烷基，C1-6烷氧基，环烷氧基，羟基或N（R23）2，其中每个R23独立地为H，C1-6烷基或环烷氧基; R22为H，卤素，C1-6烷基，C3-6环烷基，C1-6卤代烷基，C1-6硫代烷基，C1-6烷氧基，C3-6环烷氧基，C2-7烷氧基烷基，C3-6环烷基，C6或10芳基或Het，其中Het是含有1至4个从氮，氧和硫选择的杂原子的五元，六元或七元饱和或不饱和杂环; 所述的环烷基，芳基或Het被R24取代，其中R24为H，C1-6烷基，C3-6环烷基，C1-6烷氧基，C3-6环烷氧基，NO2，N（R25）2，NH-C（O）-R25; 或NH-C（O）-NH-R25，其中每个R25独立地为：H，C1-6烷基或C3-6环烷基; 或R24为NH-C（O）-OR26，其中R26为C1-6烷基或C3-6环烷基; R3为羟基，NH2或式-NH-R31的基团，其中R31为C6或10芳基，杂芳基，-C（O）-R32，-C（O）-OR32或-C（O）-NHR32，其中R32为：C1-6烷基或C3-6环烷基; D为5至10个原子的饱和或不饱和烷基链，可选地包含从O，S或N-R41中独立选择的1至3个杂原子，其中R41为H，C1-6烷基，环烷基或-C（O）-R42，其中R42为C1-6烷基，环烷基或C6或10芳基; R4为H或在链D的任何碳原子上的1至3个取代基，所述取代基独立地选择自以下群：C1-6烷基，C1-6卤代烷基，C1-6烷氧基，羟基，卤素，氨基，氧代，硫代或C1-6硫代烷基; A为式-C（O）-NH-R5的酰胺，其中R5选择自以下群：C1-8烷基，C3-6环烷基，C6或10芳基或C7-16芳基烷基; 或A为羧酸或其药学上可接受的盐或酯。
• HCV Inhibitors
  申请人：Graupe Michael

  公开号：US20070054864A1

  公开（公告）日：2007-03-08

  The present invention is directed to compounds that are antiviral agents. Specifically the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

  本发明涉及抗病毒剂化合物。具体而言，本发明的化合物抑制HCV的复制，因此可用于治疗丙型肝炎感染。本发明还涉及包含这些化合物的制药组合物以及制备它们的过程。
• ANTIVIRAL COMPOUNDS
  申请人：Cho Aesop

  公开号：US20120190866A1

  公开（公告）日：2012-07-26

  The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及抗病毒化合物、含有这些化合物的组合物以及包括这些化合物的治疗方法，以及用于制备这些化合物的过程和中间体。