3-(5-bromo-thiophen-2-yl)-3-(3-fluoro-phenyl)-2,2-dimethyl-propionic acid methyl ester | 1025664-04-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(5-bromo-thiophen-2-yl)-3-(3-fluoro-phenyl)-2,2-dimethyl-propionic acid methyl ester
• 英文别名: Methyl 3-(5-bromothiophen-2-yl)-3-(3-fluorophenyl)-2,2-dimethyl-propanoate；methyl 3-(5-bromothiophen-2-yl)-3-(3-fluorophenyl)-2,2-dimethylpropanoate
• CAS: 1025664-04-3
• 化学式: C₁₆H₁₆BrFO₂S
• 分子量: 371.27
• InChiKey: KVRZJIOFJLHXQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(5-bromo-thiophen-2-yl)-3-(3-fluoro-phenyl)-2,2-dimethyl-propionic acid methyl ester 在 甲醇 、 氢氧化钾 、 水 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 以86%的产率得到3-(5-溴-噻吩-2-基)-3-(3-氟-苯基)-2,2-二甲基-丙酸
  参考文献：
  名称：

  WO2008/57859

  摘要：

  公开号：
• 作为产物：
  描述：

  1-甲氧基-1-(三甲基甲硅氧基)-2-甲基-1-丙烯 、 (5-bromo-thiophen-2-yl)-(3-fluoro-phenyl)-methanol 在 四氯化钛 、 水 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 3.17h， 以87.5%的产率得到3-(5-bromo-thiophen-2-yl)-3-(3-fluoro-phenyl)-2,2-dimethyl-propionic acid methyl ester
  参考文献：
  名称：

  WO2008/57859

  摘要：

  公开号：

文献信息

• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KAPPABETA ACTIVITY AND USE THEREOF
  申请人：Yang Bingwei Vera

  公开号：US20100004219A1

  公开（公告）日：2010-01-07

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory or immune associated diseases or disorders having the structure of formula I or an enantiomer, diastereomer, tautomer, or a pharmaceutically-acceptable salt, thereof, wherein: A is a 5-, 6-, or 7-membered heterocyclo or heteroaryl, each containing 1, 2, or 3 heteroatoms selected from N, O, and S and substituted with one to four groups, R 1 , R 2 , R 3 , and/or R 4 , provided that (i) A is not tetrazole or (ii) if A is thienyl or furanyl then Z is selected from a group other than succinimido or thalimido; M is selected from alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl; Ma is a linker between C and M and is selected from a bond and C 1 -C 3 alkylene; Q is selected from (i) hydrogen, halogen, nitro, cyano, hydroxy, C 1 -4alkyl, and substituted C 1 -4 alkyl; or (ii) Q is combined with R6 and with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO 2 , and N which ring may be optionally substituted with 0-2 R 5 groups or carbonyl; and Z is selected from alkyl, CF 3 , OH, cycloalkyl, heterocyclo, aryl, heteroaryl, —C(═O)NR 8 R 9 , —C(═O)R 8 , —C(NCN)NR 8 R 9 , —C(═O)OR 8 , —SO 2 R 8 , and —SO2NR8R9. M a , Z a , R 1 , R 2 , R 3 , R5 a , R 6 , R 7 , R 8 , R 9 and R 22 are as defined herein. Also provided are pharmaceutical compositions, combinations and methods of treating metabolic and inflammatory or immune associated diseases or disorders using said compounds.

  本发明提供了一些新型非甾体化合物，其可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括代谢和炎症或免疫相关疾病或障碍。该化合物具有公式I或其对映异构体、顺反异构体、互变异构体或药学上可接受的盐，其中：A是5、6或7元杂环或杂环芳基，每个都含有1、2或3个从N、O和S中选择的杂原子，并取代有1至4个基团R1、R2、R3和/或R4，但（i）A不是四氮唑或（ii）如果A是噻吩基或呋喃基，则Z是选择自除琥珀酰亚胺或萘酰亚胺之外的一组；M选择自烷基、环烷基、芳基、杂环烷和杂环芳基；Ma是C和M之间的连接器，选择自键和C1-C3烷基；Q选择自（i）氢、卤素、硝基、氰基、羟基、C1-4烷基和取代的C1-4烷基；或（ii）Q与R6以及它们附着的碳原子结合形成3-至6元环烷基；或（iii）Q和M与它们附着的碳原子结合形成3-至7元环，其中包含1-2个杂原子，这些杂原子独立地选择自O、S、SO2和N的群，该环可以选择性地取代0-2个R5基团或羰基；Z选择自烷基、CF3、OH、环烷基、杂环烷基、芳基、杂环芳基、-C（=O）NR8R9、-C（=O）R8、-C（NCN）NR8R9、-C（=O）OR8、-SO2R8和-SO2NR8R9。Ma、Za、R1、R2、R3、R5a、R6、R7、R8、R9和R22的定义如本文所述。还提供了使用所述化合物的制药组合物和治疗代谢和炎症或免疫相关疾病或障碍的方法。
• Modulators of glucocorticoid receptor, AP-1, and/or NF-kappabeta activity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US08222247B2

  公开（公告）日：2012-07-17

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory or immune associated diseases or disorders having the structure of formula I or an enantiomer, diastereomer, tautomer, or a pharmaceutically-acceptable salt, thereof, wherein: A is a 5-, 6-, or 7-membered heterocyclo or heteroaryl, each containing 1, 2, or 3 heteroatoms selected from N, O, and S and substituted with one to four groups, R1, R2, R3, and/or R4; provided that (i) A is not tetrazole or (ii) if A is thienyl or furanyl then Z M is selected from alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl; Z is selected from alkyl, CF3, OH, cycloalkyl, heterocyclo, aryl, heteroaryl, —C(═O)NR8R9, —C(═O)R8, —C(NCN)NR8R9, —C(═O)OR8, —SO2R8, and —SO2NR8R9. Also provided are pharmaceutical compositions, combinations and methods of treating metabolic and inflammatory or immune associated diseases or disorders using said compounds.

  提供了新型非甾体化合物，用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括代谢性和炎症或免疫相关的疾病或障碍，其结构具有公式I或其对映异构体、顺异构体、互变异构体或其药学上可接受的盐，其中：A是5、6或7元杂环或杂环芳基，每个含有1、2或3个从N、O和S中选择的杂原子，并取代有一个到四个基团，R1、R2、R3和/或R4；前提是（i）A不是四唑或（ii）如果A是噻吩基或呋喃基，则Z M从烷基、环烷基、芳基、杂环烷基和杂环芳基中选择；Z从烷基、CF3、OH、环烷基、杂环烷基、芳基、杂环芳基、-C（═O）NR8R9、-C（═O）R8、-C（NCN）NR8R9、-C（═O）OR8、-SO2R8和-SO2NR8R9中选择。还提供了药物组合物、组合物和使用所述化合物治疗代谢性和炎症或免疫相关的疾病或障碍的方法。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1 AND/OR NF-KAPPAB ACTIVITY AND USE THEREOF
  申请人：Bristol-Myers Squibb Company

  公开号：EP2078015B1

  公开（公告）日：2012-03-21
• US8222247B2
  申请人：——

  公开号：US8222247B2

  公开（公告）日：2012-07-17
• [EN] MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF<br/>[FR] MODULATEURS DE RÉCEPTEUR DE GLUCOCORTICOÏDE, DE L'ACTIVITÉ D'AP-1 ET/OU DU NF-KB ET LEUR UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2008057859A2

  公开（公告）日：2008-05-15

  [EN] Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-?B activity, including metabolic and inflammatory or immune associated diseases or disorders having the structure of formula I or an enantiomer, diastereomer, tautomer, or a pharmaceutically-acceptable salt, thereof, wherein: A is a 5-, 6-, or 7-membered heterocyclo or heteroaryl, each containing 1, 2, or 3 heteroatoms selected from N, O, and S and substituted with one to four groups, R₁, R₂, R₃, and/or R₄, provided that (i) A is not tetrazole or (ii) if A is thienyl or furanyl then Z is selected from a group other than succinimido or thalimido; M is selected from alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl; Ma is a linker between C and M and is selected from a bond and C₁-C₃alkylene; Q is selected from (i) hydrogen, halogen, nitro, cyano, hydroxy, C₁-4alkyl, and substituted C₁-4 alkyl; or (ii) Q is combined with R6 and with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO₂, and N which ring may be optionally substituted with 0-2 R₅ groups or carbonyl; and Z is selected from alkyl, CF₃, OH, cycloalkyl, heterocyclo, aryl, heteroaryl, -C(=O)NR₈R₉, -C(=O)R₈, -C(NCN)NR₈R₉, -C(=O)OR₈, -SO₂R₈, and -SO2NR8R9. M_a, Z_a, R₁, R₂, R₃, R5_a, R₆, R₇, R₈, R₉ and R₂₂ are as defined herein. Also provided are pharmaceutical compositions, combinations and methods of treating metabolic and inflammatory or immune associated diseases or disorders using said compounds.
  [FR] L'invention concerne de nouveaux composés non stéroïdiens qui sont utiles pour le traitement de maladies associées à la modulation du récepteur de glucocorticoïde, de l'activité d'AP-1 et/ou du NF-?B, y compris des maladies ou des troubles métaboliques et inflammatoires ou immuns associés ayant la structure de la formule I ou un énantiomère, diastéréomère, tautomère, ou un sel pharmaceutiquement acceptable de ceux-ci, où : A est un groupe hétérocyclo ou un hétéroaryle ayant 5,6 ou 7 éléments, chacun contenant 1, 2 ou 3 hétéroatomes sélectionnés parmi N, O et S, et remplacé par un à quatre groupes, R₁, R₂, R₃, et/ou R₄, à condition que (i) A ne soit pas du tétrazole, ou (ii) si A est du thiényle ou du furanyle, alors Z est sélectionné parmi un groupe autre que succinimido ou thalimido ; M est sélectionné parmi un groupe alkyle, cycloalkyle, aryle, hétérocyclo, et hétéroaryle ; Ma est un élément de liaison entre C et M et est sélectionné parmi une liaison et un groupe alkylène en C₁-C₃ ; Q est sélectionné parmi (i) de l'hydrogène, de l'halogène, les groupes nitro, cyano, hydroxy, un groupe alkyle en C_1-4, et un groupe alkyle en C_1-4 substitué ; ou (ii) Q est combiné avec R⁶ avec les atomes de carbone sur lesquels ils sont fixés pour former un cycloalkyle à 3 à 6 éléments ; ou (iii) Q et M sont combinés avec le ou les atomes de carbone sur lesquels ils sont fixés pour former un cycle à 3 à 7 éléments contenant 1 à 2 hétéroatomes qui sont sélectionnés indépendamment dans le groupe constitué de O, S, SO₂, et N, lequel cycle peut être remplacé facultativement par 0 à 2 groupes R₅ ou carbonyle ; et Z est sélectionné parmi un groupe alkyle, CF₃, OH, cycloalkyle, hétérocyclo, aryle, hétéroaryle, -C(=O)NR₈R₉, -C(=O)R₈, -C(NCN)NR₈R₉, -C(=O)OR₈, -SO₂R₈ et -SO₂NR₈R₉. M_a, Z_a, R₁, R₂, R₃, R5_a, R₆, R₇, R₈, R₉ et R₂₂ sont tels que définis ici. Des compositions pharmaceutiques, combinaisons et procédés de traitement de maladies et de troubles métaboliques et inflammatoires ou immuns associés utilisant ces composés sont également fournis.