4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxylic acid | 666721-06-8

• 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: 4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxylic acid
• CAS: 666721-06-8
• 化学式: C₁₂H₇F₃O₃S
• 分子量: 288.247
• InChiKey: MGIKFAMSBAYDSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 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：
  74.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxylic acid 在 草酰氯 作用下， 以 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-[4-(trifluoromnethoxy)phenyl]thiophene-2-carbonyl chloride
  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：

  4-溴-2-噻吩甲醛 在 sodium hydroxide 、 potassium phosphate 、 四(三苯基膦)钯 、 silver nitrate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 生成 4-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxylic acid
  参考文献：
  名称：

  Structure-based design and synthesis of novel non-zinc chelating MMP-12 inhibitors

  摘要：

  A new class of MMP-12 inhibitors was discovered and optimized using structure-based drug design methods. Modeling studies using a known MMP-12 crystal structure identified a new interaction mode for these new MMP-12 inhibitors. Further optimization resulted in the discovery of a compound displaying nanomolar activity against MMP-12 and which was co-crystallized with MMP-12. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.079

文献信息

• Novel thiophene derivatives, their process of preparation and the pharmaceutical compositions which comprise them
  申请人：——

  公开号：US20040072871A1

  公开（公告）日：2004-04-15

  A compound of formula (I) selected from: 1 wherein: X represents oxygen or sulphur, Y represents oxygen, —NH— or —N(C 1 -C 6 )alkyl-, R a represents hydrogen, halogen, (C 1 -C 3 )alkyl, hydroxyl or (C 1 -C 3 )alkoxy, R b represents hydrogen, halogen or (C 1 -C 3 )alkyl, A represents phenyl, pyridyl, (C 5 -C 6 )cycloalkyl or (C 5 -C 6 )cycloalkenyl, R 1 and R 2 each represent a group selected from hydrogen, halogen, cyano, nitro, haloalkyl, haloalkoxy, alkyl, alkenyl, alkynyl, —OR 4 , —NR 4 R 5 , —S(O) n R 4 , —C(O)R 4 , —CO 2 R 4 , —O—C(O)R 4 , —C(O)NR 4 R 5 , —NR 5 —C(O)R 4 , —NR 5 —SO 2 R 4 , -T-CN, -T-OR 4 , -T-OCF 3 , -T- NR 4 R 5 , -T-S(O) n R 4 , -T-C(O)R 4 , -T-CO 2 R 4 , -T-O—C(O)R 4 , -T-C(O)NR 4 R 5 , -T-NR 4 —C(O)R 5 , -T-NR 4 —SO 2 R 5 , —R 6 and -T-R 6 in which n, T, R 4 , R 5 and R 6 are as defined in the description, R 3 represents an —R 7 or —U—R 11 group in which R 7 represents hydrogen, alkyl, aryl, cycloalkyl or heterocycle, U represents a linear or branched alkylene chain and R 11 is defined in the description, their optical isomers or their addition salts with a pharmaceutically acceptable acid or base, and their use as inhibitor of metalloproteinase and more specifically of metalloproteinase-12.

  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。
• [EN] THIOPHENE AMINO ACID DERIVATIVES, PROCESS FOR PREPARING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] DERIVES D'ACIDE AMINE THIOPHENIQUE, LEUR PROCEDE DE PREPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：WARNER LAMBERT CO

  公开号：WO2005003115A1

  公开（公告）日：2005-01-13

  Compounds of formula (I), in which: R1 and R2, which may be identical or different, independently of each other, each represent a group selected from: hydrogen, halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, -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 and -T-R6 in which n, T, R4, R5 and R6 are as defined in the description ; m represents an integer between 0 and 4 inclusive ; p represents an integer between 0 and 4 inclusive ; q represents an integer between 0 and 4 inclusive ; R7 represents a group selected from aryl, cycloalkyl and a heterocycle, each of these groups being optionally substituted; R8 represents a group selected from carboxyl, (C1-C6)alkoxycarbonyl, (C1-C7)acyl, hydroxy(C1-C6)alkylcarbonyl, (C1-C6)alkoxy(C1-C6)alkylcarbonyl, tetrazole, amino, aminocarbonyl and amino(C1-C6)alkylcarbonyl; the isomers thereof and the addition salts thereof with a pharmaceutically acceptable acid or base, and the pharmaceutical compositions which are useful for treating pathologies associated with an inhibition of metalloproteases.

  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。
• [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。
• 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.