2-(difluoromethyl)-4-(methyloxy)aniline | 727993-36-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(difluoromethyl)-4-(methyloxy)aniline
• 英文别名: 2-(Difluoromethyl)-4-methoxyaniline
• CAS: 727993-36-4
• 化学式: C₈H₉F₂NO
• mdl: MFCD11042616
• 分子量: 173.162
• InChiKey: LOWSWBJBXLTLHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(difluoromethyl)-4-(methyloxy)aniline 、 2-chloro-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]pyridine 在 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 2-二环己基磷-2'-甲基联苯 作用下， 以 乙二醇二甲醚 为溶剂， 100.0 ℃ 、413.69 kPa 条件下， 反应 0.67h， 生成 N-[2-(difluoromethyl)-4-(methyloxy)phenyl]-3-(2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}ethyl)-6-methyl-4-[3-(1,3-thiazol-2-yl)-1H-pyrazol-1-yl]-2-pyridinamine
  参考文献：
  名称：

  Dihydropyrrole[2,3-d]pyridine Derivatives as Novel Corticotropin-Releasing Factor-1 Antagonists: Mapping of the Receptor Binding Pocket by in Silico Docking Studies

  摘要：

  In an effort to discover novel CRF-1 receptor antagonists exhibiting improved physicochemical properties, a dihydropirrole[2,3]pyridine scaffold was designed and explored in terms of the SAR of the substitution at the pendent phenyl ring and the nature of the heterocyclic moieties present in the upper region of the molecule. Selective and potent compounds have been discovered endowed with reduced ClogP with respect to compounds known in the literature. Of particular relevance was the finding that the in vitro affinity of the series was maintained by reducing the overall lipophilicity. The results achieved by this exploration enabled the formulation of a novel hypothesis on the nature of the receptor binding pocket of this class of CRF-1 receptor antagonists, making use of in silico docking studies of the putative nonpeptidic antagonist binding site set up in house by homology modeling techniques.

  DOI：

  10.1021/jm800743q
• 作为产物：
  描述：

  2-(difluoromethyl)-4-(methyloxy)-2-nitrobenzene 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以20%的产率得到2-(difluoromethyl)-4-(methyloxy)aniline
  参考文献：
  名称：

  [EN] HETEROARYL- SUBSTITUTED PYRROLO` 2, 3- B! PYRIDINE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  [FR] DERIVES PYRROLO[2,3-B]PYRIDINE A SUBSTITUTION HETEROARYLE UTILISES COMME ANTAGONISTES DES RECEPTEURS DU CRF

  摘要：

  本发明提供了化合物的公式（I），包括立体异构体、前药和其药用可接受的盐或溶剂，以及其制备方法，包含它们的药物组合物，以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。

  公开号：

  WO2004062665A1

文献信息

• [EN] COMPOUNDS AS HEPATITIS C VIRUS (HCV) INHIBITORS AND USES THEREOF IN MEDICINE<br/>[FR] COMPOSÉS EN TANT QU'INHIBITEURS DU VIRUS DE L'HÉPATITE C (VHC) ET LEURS UTILISATIONS EN MÉDECINE
  申请人：SUNSHINE LAKE PHARMA CO LTD

  公开号：WO2015197028A1

  公开（公告）日：2015-12-30

  Provided herein are compounds of Formula (I), or a stereoisomer, a geometric isomer, an enantiomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which are used in the treatment of HCV infection or hepatitis C. Provided herein also are pharmaceutical compositions containing such compounds and methods of using the compound of the present invention or pharmaceutical compositions thereof to treat HCV infection or hepatitis C.

  本文提供了式（I）的化合物，或其立体异构体、几何异构体、对映体、互变异构体、N-氧化物、水合物、溶剂合物、代谢物、药学上可接受的盐或其前药，用于治疗HCV感染或丙型肝炎。本文还提供了含有这些化合物的药物组合物以及使用本发明的化合物或其药物组合物治疗HCV感染或丙型肝炎的方法。
• [EN] CONDENSED N-HETEROCYCLIC COMPOUNDS AND THEIR USE AS CRF RECEPTOR ANTAGONISTS<br/>[FR] DERIVES BICYCLIQUES, LEUR PREPARATION, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET LEUR USAGE THERAPEUTIQUE
  申请人：SB PHARMCO INC

  公开号：WO2004094420A1

  公开（公告）日：2004-11-04

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof (Formula (I)) wherein the dashed line may represent a double bond; R is aryl or heteroaryl, each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 lkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, -C(O)R2, nitro, hydroxy, -NR3R4, cyano and or a group Z; R1 is hydrogen, C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo Cl­-C6 alkoxy, halogen, NR3R4 or cyano; D, G is.-C- optionally substituted; X is carbon or nitrogen; Y is nitrogen or -C- optionally substituted; W is a 4-8 membered ring, which may be saturated or may contain one to three double bonds, and in which: - one carbon atom is replaced by a carbonyl or S(O)m; and - one to four carbon atoms may optionally be replaced by oxygen, nitrogen or NR12, S(O)m, carbonyl, and such ring may be further substituted by 1 to 8 substituents; Z is a 5-6 membered heterocycle, which may be substituted by 1 to 8 R5 groups or a phenyl ring, which may be substituted by 1 to 4 substituents; m is an integer from 0 to 2. to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了式（I）的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂化物（式（I））其中虚线可以表示双键；R是芳基或杂环芳基，每个基团可以被1-4个J基团所取代，所述J基团选择自：卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷氧基、-C（O）R2、硝基、羟基、-NR3R4、氰基或Z基团；R1是氢、C3-C7环烷基、C1-C6烷基、C1-C6烷氧基、C1-C6硫代烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷基、卤代Cl-C6烷氧基、卤素、NR3R4或氰基；D、G是可选取代的-C-；X是碳或氮；Y是氮或可选取代的-C-；W是4-8成员环，可以饱和或含有1-3个双键，其中：-一个碳原子被羰基或S（O）m取代；-一个到四个碳原子可以选择性地被氧、氮或NR12、S（O）m、羰基取代，该环可能进一步被1-8个取代基所取代；Z是5-6成员杂环，可以被1-8个R5基团所取代或苯环，可以被1-4个取代基所取代；m是0到2的整数。本发明还涉及其制备方法、含有它们的制药组合物以及它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。
• Heteroaryl-substituted pyrrolo'2,3-b1 pyridine derivatives as crf receptor antagonists
  申请人：Castiglioni Emiliano

  公开号：US20070066640A1

  公开（公告）日：2007-03-22

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供公式（I）的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂化物，以及其制备过程、含有它们的制药组合物和它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的用途。
• Condensed n-heterocyclic compounds and their use as crf receptor antagonists
  申请人：Andreotti Daniele

  公开号：US20070004708A1

  公开（公告）日：2007-01-04

  The present invention provides compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof (Formula (I)) wherein the dashed line may represent a double bond; R is aryl or heteroaryl, each of which may be substituted by 1 to 4 groups J selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 lkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, —C(O)R 2 , nitro, hydroxy, —NR 3 R 4 , cyano and or a group Z; R 1 is hydrogen, C3-C7 cycloalkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 thioalkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, halogen, NR 3 R 4 or cyano; D, G is —C— optionally substituted; X is carbon or nitrogen; Y is nitrogen or —C— optionally substituted; W is a 4-8 membered ring, which may be saturated or may contain one to three double bonds, and in which:—one carbon atom is replaced by a carbonyl or S(O) m ; and—one to four carbon atoms may optionally be replaced by oxygen, nitrogen or NR 12 , S(O) m , carbonyl, and such ring may be further substituted by 1 to 8 substituents; Z is a 5-6 membered heterocycle, which may be substituted by 1 to 8 R 5 groups or a phenyl ring, which may be substituted by 1 to 4 substituents; m is an integer from 0 to 2. to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了式(I)的化合物，包括立体异构体、前药和其药学上可接受的盐或溶剂合物（式(I)），其中虚线可表示双键；R为芳基或杂环芳基，每个都可以被1到4个J基团替代，所述J基团选自：卤素、C1-C6烷基、C1-C6烷氧基、卤代C1-C6烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷氧基、—C(O)R2、硝基、羟基、—NR3R4、氰基或Z基；R1为氢、C3-C7环烷基、C1-C6烷基、C1-C6烷氧基、C1-C6硫代烷基、C2-C6烯基、C2-C6炔基、卤代C1-C6烷基、卤代C1-C6烷氧基、卤素、NR3R4或氰基；D、G为可选取代的—C—；X为碳或氮；Y为氮或可选取代的—C—；W为4-8个成员的环，可以饱和或含有1-3个双键，在其中：—一个碳原子被羰基或S（O）m所取代；—1-4个碳原子可以被氧、氮或NR12、S（O）m、羰基所取代，并且该环可以进一步被1-8个取代基所取代；Z为5-6个成员的杂环，可以被1-8个R5基团或苯环所取代，该苯环可以被1-4个取代基所取代；m为0-2的整数。本发明还提供了制备这些化合物的方法，以及含有它们的药物组合物，并用于治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病。
• Condensed N-Heterocyclic Compounds and their Use as CRF Receptor Antagonists
  申请人：Andreotti Daniele

  公开号：US20110172255A1

  公开（公告）日：2011-07-14

  The present invention provides compounds of formula (I), processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of conditions mediated by corticotropin-releasing factor (CRF).

  本发明提供了式（I）的化合物，以及制备它们的方法，包含它们的制药组合物和它们在治疗由促肾上腺皮质激素释放因子（CRF）介导的疾病中的应用。