5-烯丙基-4,6-二氯-2-甲基嘧啶 | 85826-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-烯丙基-4,6-二氯-2-甲基嘧啶
• 英文名称: 5-Allyl-2-methyl-4,6-dichloropyrimidine
• 英文别名: 5-allyl-4,6-dichloro-2-methylpyrimidine；4,6-dichloro-2-methyl-5-(2-propen-1-yl)pyrimidine；4,6-dichloro-2-methyl-5-prop-2-enylpyrimidine
• CAS: 85826-33-1
• 化学式: C₈H₈Cl₂N₂
• 分子量: 203.071
• InChiKey: APGYFDQRXYNDHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-烯丙基-4,6-二氯-2-甲基嘧啶 在 氨 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以50.1%的产率得到5-Allyl-4-amino-2-methyl-6-chloropyrimidine
  参考文献：
  名称：

  Synthesis and biological activity of allylpyrimidines and their derivatives

  摘要：

  DOI：

  10.1007/bf00765165
• 作为产物：
  描述：

  烯丙基丙二酸二乙酯 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 41.0h， 生成 5-烯丙基-4,6-二氯-2-甲基嘧啶
  参考文献：
  名称：

  Discovery of 6,7-Dihydro-5H-pyrrolo[2,3-a]pyrimidines as Orally Available G Protein-Coupled Receptor 119 Agonists

  摘要：

  GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

  DOI：

  10.1021/jm301404a

文献信息

• [EN] CONDENSED N-HETEROCYCLIC COMPOUNDS AND THEIR USE AS CRF RECEPTOR ANTAGONISTS<br/>[FR] COMPOSES N-HETEROCYCLIQUES CONDENSES ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR CRF
  申请人：SB PHARMCO INC

  公开号：WO2004094419A1

  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 .alkenyl, ,C2-C6 -alkynyl,-halo-C1=C6 -aIkoxy,-=C(O)RZ,-nitro, -hydroxy, =NR3R4i cyano, and or a group Z; R, 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, NR3R4or cyano; D, G is -C- optionally substituted; A is -C- optionally substituted; X is carbon or-nitrogen; Y is nitrogen or -C- optionally substituted; W is a 4-8 carbocyclic 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 NR14, S(O)m, carbonyl, and such ring may be further substituted by I to 8 substituents; Z is a 5-6 membered heterocycle or a phenyl, which may be substituted by I to 8 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).

  本发明提供了化合物的公式(I)，包括立体异构体、前药和其药学上可接受的盐或溶剂（公式(I)），其中虚线可能表示双键；R是芳基或杂环芳基，每个都可以由1到4个J组成，所选自：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)RZ、硝基、羟基、=NR3R4i氰基，或Z组；R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C1-C6烷氧基、卤素、NR3R4或氰基；D，G是可选取代的-C-；A是可选取代的-C-；X是碳或氮；Y是氮或可选取代的-C-；W是一个4-8碳环成员环，可以饱和或含有一到三个双键，其中：-一个碳原子被羰基或S(O)m取代；和-一到四个碳原子可以选择性地被氧、氮或NR14、S(O)m、羰基取代，这样的环可能进一步由1到8个取代基取代；Z是一个5-6成员杂环或苯基，可以由1到8个取代基取代；m是一个从0到2的整数，用于它们的制备方法，含有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。
• A concise, efficient and versatile synthesis of amino-substituted benzo[<i>b</i>]pyrimido[5,4-<i>f</i>]azepines: synthesis and spectroscopic characterization, together with the molecular and supramolecular structures of three products and one intermediate
  作者：Lina M. Acosta Quintero、Isidro Burgos、Alirio Palma、Justo Cobo、Christopher Glidewell

  DOI：10.1107/s2053229618002176

  日期：2018.3.1

  products and one intermediate have been determined. In each of N,2,6,11‐tetramethyl‐N‐phenyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepin‐4‐amine, C22H24N5, (III), 4‐(1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, which crystallizes as a 0.374‐hydrate, C21H19N5·0.374H2O, (VIIIa), and 6,7,9,11‐tetramethyl‐4‐(5‐methyl‐1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5

  描述了氨基取代的苯并[ b ]嘧啶基[5,4- f ]氮杂环庚烷的简明，有效和通用的合成方法：从5-烯丙基-4,6-二氯嘧啶开始，该合成涉及碱催化的氨解反应，然后进行分子内Friedel–Crafts环化。据报道有四种新的氨基取代的苯并[ b ]嘧啶基[5,4- f ]氮杂ze，所有产物和反应中间体均已通过IR，1 H和13 C NMR光谱学和质谱法进行了全面表征，以及已经确定了三种产物和一种中间体的超分子结构。在每个N，2,6,11-四甲基-N-苯基-6,11-二氢-5中H-苯并[ b ]嘧啶基[5,4 - f ] azepin-4-胺，C 22 H 24 N 5，（III），4-（1 H-苯并[ d ]咪唑-1-基）-6， 11‐二甲基‐6,11‐二氢‐5 H‐苯并[ b ]嘧啶基[5,4‐ f ]氮杂，其结晶为0.374−水合物，C 21 H 19 N 5 ·0.374H 2 O，（VIII
• Synthesis of Pyrimidine-Fused Benzazepines from 5-Allyl-4,6-dichloropyrimidines
  作者：Lina M. Acosta-Quintero、Jorge Jurado、Manuel Nogueras、Alirio Palma、Justo Cobo

  DOI：10.1002/ejoc.201500632

  日期：2015.8

  A detailed examination of the synthesis of functionalized 6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines 4 is described. Base-promoted aromatic nucleophilic substitution of 5-allyl-4,6-dichloropyrimidines 1a–c with different N-substituted anilines and indoline gave the corresponding aminolysis products 3a–p, which on acid-promoted intramolecular Friedel–Crafts cyclization produced the target polysubstituted

  描述了功能化 6,11-二氢-5H-苯并 [b] 嘧啶并 [5,4-f] 氮杂 4 合成的详细检查。用不同的 N-取代苯胺和二氢吲哚对 5-烯丙基-4,6-二氯嘧啶 1a-c 进行碱促进的芳香亲核取代得到相应的氨解产物 3a-p，在酸促进的分子内 Friedel-Crafts 环化作用下产生目标多取代6,11-二氢-5H-苯并[b]嘧啶并[5,4-f]氮杂4a-p，产率中等至极高。
• CRF receptor antagonists and methods relating thereto
  申请人：Neurocrine Biosciences, Inc.

  公开号：US06514982B1

  公开（公告）日：2003-02-04

  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: including stereoisomers and pharmaceutically acceptable salts thereof, wherein n, m, A, B, C, R, R1, R2 and Ar 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

  本发明披露了CRF受体拮抗剂，其在治疗各种疾病中具有用途，包括治疗表现为暖血动物中CRF过分分泌的疾病，如中风。本发明的CRF受体拮抗剂具有以下结构：包括其立体异构体和药学上可接受的盐，其中n、m、A、B、C、R、R1、R2和Ar的定义如本文所述。还披露了含有CRF受体拮抗剂的组合物，以及使用这些组合物的方法。
• [EN] CRF RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR DE CRF
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2001087885A1

  公开（公告）日：2001-11-22

  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 (I) including stereoisomers and pharmaceutically acceptable salts thereof, wherein n, m, A, B, C, R, R1, R2 and Ar 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分泌过多的疾病，例如中风。本发明的CRF受体拮抗剂具有以下结构（I），包括立体异构体和其药学上可接受的盐，其中n，m，A，B，C，R，R1，R2和Ar如本文所定义。本发明还揭示了包含CRF受体拮抗剂和药学上可接受的载体的组合物，以及使用它们的方法。