2-(4,6-Dichloro-2-methyl-pyrimidin-5-yl)-pent-4-en-1-ol | 474103-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(4,6-Dichloro-2-methyl-pyrimidin-5-yl)-pent-4-en-1-ol
• 英文别名: 2-(4,6-Dichloro-2-methylpyrimidin-5-yl)pent-4-en-1-ol
• CAS: 474103-23-6
• 化学式: C₁₀H₁₂Cl₂N₂O
• 分子量: 247.124
• InChiKey: IQMWCVWLQPGOSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  46
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4,6-Dichloro-2-methyl-pyrimidin-5-yl)-pent-4-en-1-ol 在 咪唑 、 4-二甲氨基吡啶 、 sodium hydride 、 臭氧 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 111.0h， 生成 8-(2,4-Bis-trifluoromethyl-phenyl)-5-(tert-butyl-diphenyl-silanyloxymethyl)-4-chloro-2-methyl-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040
• 作为产物：
  描述：

  1,1,2-乙烷三羧酸三乙酯 在 甲醇 、 sodium 、 二异丁基氢化铝 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 54.83h， 生成 2-(4,6-Dichloro-2-methyl-pyrimidin-5-yl)-pent-4-en-1-ol
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040

文献信息

• [EN] TRI-AND TETRAAZA-ACENAPHTHYLEN DERIVATIVES AS CRF RECEPTOR ANTAGONISTS<br/>[FR] DERIVES TRI- ET TETRAAZA-ACENAPHTHYLENE UTILISES COMME ANTAGONISTES DU RECEPTEUR CRF
  申请人：NEUROCRINE INC

  公开号：WO2002094826A1

  公开（公告）日：2002-11-28

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure of formula (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, R1, R2, R4, R5, R6, A, X, and Y are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，其在治疗多种疾病方面具有用途，包括治疗温血动物中CRF过度分泌表现的疾病，例如中风。本发明的CRF受体拮抗剂具有以下结构式（I），包括立体异构体、前药和其药学上可接受的盐，其中R1、R2、R4、R5、R6、A、X和Y如本文所定义。还揭示了含有CRF受体拮抗剂与药学上可接受的载体组合的组合物，以及使用它们的方法。
• Crf receptor antagonists
  申请人：——

  公开号：US20040235871A1

  公开（公告）日：2004-11-25

  The present invention relates to tricyclic pyrimidines compounds of formula (I) including stereoisomers, prodrugs and pharmaceutically acceptable salts or solvates thereof wherein R is aryl or heteroaryl, wherein each of the above groups R may be substituted by 1 to 4 substituents independently selected from the group consisting of: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C1-C6 mono or dialkylamino, nitro, cyano and a group R 4 ; R 1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkyl, halo C1-C6 alkoxy, NH 2 halogen or cyano; R 2 is hydrogen or C(H) m (R 5 ) q (CH 2 ) p ZR 6 ; R 3 is hydrogen, C2-C6 alkenyl, C2-C6 alkynyl or [CH(R 5 )(CH 2 ) p ] m ZR 6 ; R 4 is C3-C7 cycloalkyl, which may contain one or more double bonds; aryl; or a 5-6 membered heterocycle; wherein each of the above groups R 4 may be substituted by one or more groups selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C1-C6 mono a or dialkylamino, nitro, and cyano; R 5 is hydrogen, C2-C6 alkenyl, C2-C6 alkynyl or (CH 2 ) p ZR 6 ; R 6 is C1-C6 alkyl, which may be substituted by one or more groups selected from halogen, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo C1-C6 alkoxy, C1-C6 alkoxy, C1-C6 mono or dialkylamino, nitro, cyano and a group R 4 ; Y and X are independently carbon or nitrogen; m and n are independently o or 1; p is 0 or an integer from 1 to 4; q is 1 or 2; Z is a bond, O NH or S; 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).

  本发明涉及公式（I）的三环嘧啶化合物，包括立体异构体，前药和其药学上可接受的盐或溶剂，其中R是芳基或杂环基，其中上述每个基团R可以被独立地选择为以下组之一的1至4个取代基所取代：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，C1-C6单烷基或二烷基氨基，硝基，氰基和基团R4; R1是氢，C1-C6烷基，C2-C6烯基，C2-C6炔基，卤代C1-C6烷基，卤代C1-C6烷氧基，NH2卤素或氰基; R2是氢或C（H）m（R5）q（CH2）pZR6; R3是氢，C2-C6烯基，C2-C6炔基或[CH（R5）（CH2）p] mZR6; R4是C3-C7环烷基，可以含有一个或多个双键; 芳基; 或5-6成员杂环; 其中上述每个基团R4可以被一个或多个从以下组中选择的基团所取代：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，C1-C6单烷基或二烷基氨基，硝基和氰基; R5是氢，C2-C6烯基，C2-C6炔基或（CH2）pZR6; R6是C1-C6烷基，可以被一个或多个从卤素，卤代C1-C6烷基，C2-C6烯基，C2-C6炔基，卤代C1-C6烷氧基，C1-C6烷氧基，C1-C6单烷基或二烷基氨基，硝基，氰基和基团R4中选择的基团所取代; Y和X独立地是碳或氮; m和n独立地是o或1; p是0或1至4的整数; q是1或2; Z是键，O NH或S; 本发明还涉及它们的制备方法，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。
• Tri-and tetraaza-acenaphthylen derivatives as crf receptor antagonists
  申请人：——

  公开号：US20040198726A1

  公开（公告）日：2004-10-07

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure of formula (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, R1, R2, R4, R5, R6, A, X, and Y are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same. 1

  本发明公开了CRF受体拮抗剂，这些拮抗剂可用于治疗多种疾病，包括治疗温血动物CRF分泌过多的疾病，如中风。本发明的 CRF 受体拮抗剂具有如下式（I）结构：包括其立体异构体、原药和药学上可接受的盐，R1、R2、R4、R5、R6、A、X 和 Y 如本文所定义。还公开了含有 CRF 受体拮抗剂与药学上可接受的载体结合的组合物，以及使用这些组合物的方法。 1
• CRF RECEPTOR ANTAGONISTS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1383498A1

  公开（公告）日：2004-01-28
• TRI- AND TETRAAZA-ACENAPHTHYLEN DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  申请人：Neurocrine Biosciences, Inc.

  公开号：EP1392689A1

  公开（公告）日：2004-03-03