methyl 4-(4-aminophenyl)thiophene-2-carboxylate | 666721-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: methyl 4-(4-aminophenyl)thiophene-2-carboxylate
• 英文别名: methyl 4-(4-aminophenyl)thiophen-2-carboxylate
• CAS: 666721-42-2
• 化学式: C₁₂H₁₁NO₂S
• 分子量: 233.291
• InChiKey: UACIGSPILIWNLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-(4-aminophenyl)thiophene-2-carboxylate 在 sodium nitrite 、 copper(ll) bromide 作用下， 以 水 、 氢溴酸 为溶剂， 反应 2.0h， 以40%的产率得到4-(4-溴苯基)-2-噻吩羧酸甲酯
  参考文献：
  名称：

  Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them

  摘要：

  公式（I）所选的化合物如下： 其中： X代表氧或硫， Y代表氧，-NH-或-N（C1-C6）烷基-， Ra代表氢，卤素，（C1-C3）烷基，羟基或（C1-C3）甲氧基， Rb代表氢，卤素或（C1-C3）烷基， A代表苯基，吡啶基，（C5-C6）环烷基或（C5-C6）环烯基， R1和R2分别代表从氢，卤素，氰基，硝基，卤代烷基，卤代甲氧基，烷基，烯基，炔基，-OR4，-NR4R5，-S（O）nR4，-C（O）R4，-CO2R4，-O—C（O）R4，-C（O）NR4R5，-NR5—C（O）R4，-NR5—SO2R4，-T-CN，-T-OR4，-T-OCF3，-T-NR4R5，-T-S（O）nR4，-T-C（O）R4，-T-CO2R4，-T-O—C（O）R4，-T-C（O）NR4R5，-T-NR4—C（O）R5，-T-NR4—SO2R5，-R6和-T-R6中选择的基团，其中n，T，R4，R5和R6如描述中所定义， R3代表-R7或-U-R11基团，其中R7代表氢，烷基，芳基，环烷基或杂环烷基，U代表线性或支链烷基链，R11如描述中所定义， 它们的光学异构体或它们与药学上可接受的酸或碱形成的加合盐，以及它们作为金属蛋白酶抑制剂，更具体地是金属蛋白酶-12的抑制剂的用途。

  公开号：

  US20040072871A1
• 作为产物：
  描述：

  methyl 4-(4-nitrophenyl)thiophene-2-carboxylate 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 50.0 ℃ 、1.0 MPa 条件下， 反应 5.0h， 以88%的产率得到methyl 4-(4-aminophenyl)thiophene-2-carboxylate
  参考文献：
  名称：

  [EN] THIOPHENE AMINO ACID DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  [FR] DERIVES D'ACIDE AMINE THIOPHENIQUE, LEUR PROCEDE DE PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT

  摘要：

  化合物的化学式（I）中：R1和R2可以相同也可以不同，分别表示从以下选定的基团中选择的基团：氢、卤素、氰基、硝基、卤代（C1-C6）烷基、卤代（C1-C6）氧基、（C1-C6）烷基、（C2-C6）烯基、（C2-C6）炔基、-OR4、-NR4R5、-S（O）nR4、-C（O）R4、-CO2R4、-O-C（O）R4、-C（O）NR4R5、-NR5-C（O）R4、-NR5-SO2R4、-T-CN、-T-OR4、-T-OCF3、-T-NR4R5、-T-S（O）nR4、-T-C（O）R4、-T-CO2 R4、-T-O-C（O）R4、-T-C（O）NR4 R5、-T-NR5-C（O）R4、-T-NR5-SO2R4、-R6和-T-R6其中n、T、R4、R5和R6如描述中所定义；m表示0到4之间的整数；p表示0到4之间的整数；q表示0到4之间的整数；R7表示从芳基、环烷基和杂环中选择的基团，这些基团可以选择性地被取代；R8表示从羧基、（C1-C6）烷氧羰基、（C1-C7）酰基、羟基（C1-C6）烷基羰基、（C1-C6）烷氧基（C1-C6）烷基羰基、四唑基、氨基、氨基羰基和氨基（C1-C6）烷基羰基中选定的基团；其异构体及其与药用酸或碱形成的可接受的加合盐，以及用于治疗与金属蛋白酶抑制相关的病理的药物组合物。

  公开号：

  WO2005003115A1

文献信息

• [EN] 5-FLUORO-THIOPEN-COMPOUNDS,THE PROCESS FOR THEIR PREPARATION,THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE AS METALLOPOTENASES INHIBITORS<br/>[FR] COMPOSES 5-FLUORO-THIOPHENE, LEUR PROCEDE DE PREPARATION, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET LEURS APPLICATIONS A TITRE D'INHIBITEURS DE METALLOPROTEASES
  申请人：WARNER LAMBERT CO

  公开号：WO2005003114A1

  公开（公告）日：2005-01-13

  Compounds of formula (I) in which R1 represent a group selected from halo(C1-C6)alkoxy, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, phenyl, cyclohexyl and a heterocycle, each of these groups being optionally substituted with one or two groups as defined in the description, R2 represents a group -U-R4 in which U represents a linear (C1-C4)alkylene chain optionally substituted with a group selected from carboxyl, carboxy(C1-C6)alkyl-, (C1-C6)alkyloxycarbonyl and (C 1-C6)alkyloxycarbonyl(C1-C6)alkyl-,o R4 represents a phenyl, cyclohexyl or morpholin-4-yl group, each of these groups being optionally substituted with one or two groups as defined in the description, the optical isomers thereof or the addition salts thereof with a pharmaceutically acceptable acid or base,and pharmaceutical compositions containing them, which are useful for treating pathologies associated with an inhibition of metalloproteases, and more specifically an inhibition of metalloprotease

  化合物(I)的化学式中，R1代表从卤(C1-C6)烷氧基，(C1-C6)烷基，(C1-C6)烷氧基，(C1-C6)烷基硫醚，苯基，环己基和杂环中选择的一个基团，这些基团可以选择性地用定义中的一个或两个基团进行取代，R2代表一个-U-R4基团，其中U代表一个线性的(C1-C4)烷基链，该链可以选择性地用从羧基，羧基(C1-C6)烷基，(C1-C6)烷氧羰基和(C1-C6)烷氧羰基(C1-C6)烷基中选择的一个基团进行取代，R4代表苯基，环己基或吗啡啉-4-基团，这些基团可以选择性地用定义中的一个或两个基团进行取代，它们的光学异构体或与药学上可接受的酸或碱形成的加合物，以及包含它们的制药组合物，这些化合物在治疗与金属蛋白酶抑制有关的病理过程中非常有用，更具体地说是金属蛋白酶抑制。
• Thiophene amino acid derivatives, process for preparing them and pharmaceutical compositions containing them
  申请人：Compere Delphine

  公开号：US20050014816A1

  公开（公告）日：2005-01-20

  The invention provides compounds of Formula (I), stereoisomers thereof, or pharmaceutically acceptable salts of said compounds or stereoisomers, wherein R 1 , R 2 , m, p, q, R 7 and R 8 are as defined below, as well as compositions comprising the same, processes for making the same, and methods of using the same to treat a variety of diseases, including, those requiring interaction with metalloproteases, and more specifically with macrophage metalloelastase (MMP-12), and for the prevention and treatment of respiratory pathologies such as chronic obstructive bronchopneumopathy (COPD), emphysema, chronic bronchitis, chronic pulmonary inflammation, asthma, cystic fibrosis, acute respiratory distress syndrome (ARDS), respiratory allergies including allergic rhinitis, and also diseases associated with the production of TNFα including severe fibrotic pulmonary disease, pulmonary sarcoidosis and silicosis. The compounds of the present invention also show inhibitory activity on metalloprotease-13 (MMP-13), making them useful for the treatment of pathologies involving this enzyme, such as cancer, osteoporosis, osteoarthritis, arthritis, rheumatoid arthritis, atherosclerosis, multiple sclerosis and cardiac insufficiency.

  本发明提供式（I）的化合物，其立体异构体，或所述化合物或立体异构体的药学上可接受的盐，其中R1，R2，m，p，q，R7和R8如下所定义，以及包含其的组合物，制备其的方法，以及使用其治疗各种疾病的方法，包括需要与金属蛋白酶相互作用的疾病，更具体地与巨噬细胞金属弹性蛋白酶（MMP-12）相互作用的疾病，并用于预防和治疗呼吸道病理学，例如慢性阻塞性支气管肺病（COPD），肺气肿，慢性支气管炎，慢性肺炎炎症，哮喘，囊性纤维化，急性呼吸窘迫综合症（ARDS），呼吸道过敏，包括过敏性鼻炎，以及与产生TNFα相关的疾病，包括严重纤维化肺病，肺结节病和硅肺。本发明的化合物还显示对金属蛋白酶-13（MMP-13）的抑制活性，使其在治疗涉及该酶的病理学，例如癌症，骨质疏松症，骨关节炎，关节炎，类风湿性关节炎，动脉硬化，多发性硬化和心脏功能不全方面有用。
• Matrix metalloproteinase inhibitors and methods for identification of lead compounds
  申请人：——

  公开号：US20040171543A1

  公开（公告）日：2004-09-02

  The invention relates to compounds that are selective inhibitors of matrix metalloproteinases, to pharmaceutical compositions containing them and to their use in the prevention and/or treatment of MMP-associated diseases. The invention also relates to methods for identification of lead compounds that are selective inhibitors of matrix metalloproteinases. The compounds have the properties that they: (a) bind allosterically to a matrix metalloproteinase or small group of metallic metalloproteinases; (b) bind into at least the S1′ pocket, at least the S1″ pocket (as defined) or at least the S1′ pocket and the S1″ pocket of said matrix metalloproteinase; and (c) exhibit selectivity for a matrix metalloproteinase or group of matrix metalloproteinases other than MMP-13.

  本发明涉及选择性抑制基质金属蛋白酶的化合物，包括含有它们的药物组成物，以及它们在预防和/或治疗与MMP相关的疾病中的应用。本发明还涉及识别选择性抑制基质金属蛋白酶的先导化合物的方法。这些化合物具有以下特性：(a)与基质金属蛋白酶或少量金属金属蛋白酶发生异构作用；(b)至少结合于所述基质金属蛋白酶的S1'口袋、至少结合于S1"口袋（如定义所述）或至少结合于所述基质金属蛋白酶的S1'口袋和S1"口袋；以及(c)表现出选择性，对MMP-13以外的基质金属蛋白酶或基质金属蛋白酶组具有选择性。
• [EN] MATRIX METALLOPROTEINASE INHIBITORS AND METHODS FOR IDENTIFICATION OF LEAD COMPOUNDS<br/>[FR] INHIBITEURS DE METALLOPROTEINASE MATRICIELLE ET PROCEDES D'IDENTIFICATION DE COMPOSES CHEFS DE FILE
  申请人：WARNER LAMBERT CO

  公开号：WO2004014381A2

  公开（公告）日：2004-02-19
• Fluorothiophene derivatives, process for preparing them and pharmaceutical compositions containing them
  申请人：Compere Delphine

  公开号：US20050014817A1

  公开（公告）日：2005-01-20

  The invention provides compounds of Formula (I), stereoisomers thereof, or pharmaceutically acceptable salts of said compounds or stereoisomers wherein R1 and R2 are as defined herein as well as compositions comprising the same, processes for making the same, and methods of using the same to treat a variety of diseases, including, those requiring interaction with metalloproteases, and more specifically with macrophage metalloelastase (MMP-12), and for the prevention and treatment of respiratory pathologies such as chronic obstructive bronchopneumopathy (COPD), emphysema, chronic bronchitis, chronic pulmonary inflammation, asthma, cystic fibrosis, acute respiratory distress syndrome (ARDS), respiratory allergies including allergic rhinitis, and also diseases associated with the production of TNFα including severe fibrotic pulmonary disease, pulmonary sarcoidosis and silicosis. The compounds of the present invention also show inhibitory activity on metalloprotease-13 (MMP-13), making them useful for the treatment of pathologies involving this enzyme, such as cancer, osteoporosis, osteoarthritis, arthritis, rheumatoid arthritis, atherosclerosis, multiple sclerosis and cardiac insufficiency.