2-Methoxy-4-(1H-pyrazol-1-yl)aniline | 786700-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-Methoxy-4-(1H-pyrazol-1-yl)aniline
• 英文别名: 2-methoxy-4-pyrazol-1-ylaniline
• CAS: 786700-69-4
• 化学式: C₁₀H₁₁N₃O
• 分子量: 189.217
• InChiKey: LQYCWFDQDGDZNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  53.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Methoxy-4-(1H-pyrazol-1-yl)aniline 、 4-氯丁酰氯 在 dipotassium hydrogenphosphate 作用下， 以 二氯甲烷 为溶剂， 生成 4-chloro-N-(2-methoxy-4-pyrazol-1-ylphenyl)butanamide
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Novel Druglike Corticotropin-Releasing Factor 1 Antagonists

  摘要：

  To identify new CRF1 receptor antagonists, an attempt to modify the bis-hetherocycle moiety present in the top region of the dihydropirrole[2,3]pyridine template was made following new pharmacophoric hypothesis on the CRF1 receptor antagonists binding pocket. In particular, the 2-thiazole ring, present in the previous series of compounds, was replaced by more hydrophilic non aromatic hetherocycles able to make appropriate H-bond interactions with amino acid residues Thr192 and Tyr195. This exploration, followed by an accurate analysis of the substitution of the pendant aryl ring, enabled to identify in vitro potent compounds showing excellent pharmacokinetics and outstanding in vivo activity in animal models of anxiety, both in rodents and primates.

  DOI：

  10.1021/jm800744m
• 作为产物：
  描述：

  4-溴-2-甲氧基苯胺 、 吡唑 、 potassium carbonate 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 氯化钠 在 碘化亚铜 氮气 、 乙酸乙酯 、 Sodium sulfate-III 、 crude product 、 silica gel 、 cHex EtOAc 作用下， 以 N-甲基吡咯烷酮 、 乙酸乙酯 为溶剂， 反应 3.0h， 以to give the title compound as a brown oil (336 mg, 90%)的产率得到2-Methoxy-4-(1H-pyrazol-1-yl)aniline
  参考文献：
  名称：

  Condensed n-heterocyclic compounds and their use as crf receptor antagonists

  摘要：

  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。

  公开号：

  US20070004708A1

文献信息

• [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。
• 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：SB Pharmaco Puerto Rico Inc.

  公开号：US07427630B2

  公开（公告）日：2008-09-23

  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 corticotrophin-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，以及制备它们的方法，包括含有它们的制药组合物和它们在治疗由促肾上腺皮质释放因子（CRF）介导的病症中的应用。
• EP1611133A1
  申请人：——

  公开号：EP1611133A1

  公开（公告）日：2006-01-04
• US7427630B2
  申请人：——

  公开号：US7427630B2

  公开（公告）日：2008-09-23