4-(methylamino)-2-(trifluoromethyl)benzonitrile | 208122-06-9

• 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: 4-(methylamino)-2-(trifluoromethyl)benzonitrile
• CAS: 208122-06-9
• 化学式: C₉H₇F₃N₂
• 分子量: 200.163
• InChiKey: ZOOQTZBWYPVCFN-UHFFFAOYSA-N

物化性质

• 沸点：
  287.6±40.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(methylamino)-2-(trifluoromethyl)benzonitrile 在 Rh₂[(N-(4-dodecylphenyl)sulfonyl)-(S)-prolinate]4 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 54.5h， 生成 N-[4-cyano-3-(trifluoromethyl)phenyl]-2-(1H-indol-3-yl)-N-methylacetamide
  参考文献：
  名称：

  通过分子间反应进行活性定向合成：将片段开发为一系列雄激素受体激动剂

  摘要：

  活性定向合成（ADS）是一种新的发现方法，其中生物活性分子与相关合成并行出现，被用来将弱结合片段开发成新型雄激素受体激动剂。利用类胡萝卜素化合物的混杂分子间反应可以高效地探索化学空间。制备了四种底物，并在 326 个反应中进行利用，以探索不同的化学空间；仅在生物活性的指导下，仅纯化了 9 个反应的产物，就发现了多种新型激动剂，其活性提高了 125 倍。值得注意的是，一种激动剂源自一种新颖的对映选择性转化；这是第一次仅根据产品的生物活性发现不对称反应。结果表明，ADS 是先导化合物生成工具包的重要补充，能够高效、快速地发现新颖且可合成的生物活性化学型。

  DOI：

  10.1002/anie.201506944
• 作为产物：
  描述：

  4-氨基-2-三氟甲基苯甲腈 、 原甲酸三甲酯 在 硫酸 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 5.5h， 以49%的产率得到4-(methylamino)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  N′-3-(Trifluoromethyl)phenyl Derivatives of N-Aryl-N′-methylguanidines as Prospective PET Radioligands for the Open Channel of the N-Methyl-d-aspartate (NMDA) Receptor: Synthesis and Structure–Affinity Relationships

  摘要：

  N-Methyl-D-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain. NMDA receptors in the activated "open channel" state would be useful for research on such disorders and for the development of novel therapies,: To date, no radioligands have Shown well-validated efficacy for imaging NMDA receptors in human subjects. In order to discover improved radioligands for PET imaging, we explored structure affinity relationships in N'-3-(trifluoromethyl)phenyl derivatives of N-aryl-N'-methylguanidines, seeking high affinity and moderate lipophilicity, plus necessary amenability for labeling with a positron-emitter, either carbon-11 or fluorine-18. Among a diverse set of 80 prepared N'-3-(trifluoromethyl)phenyl derivatives, four of these compounds (13, 19, 20, and 36) displayed desirable low nanomolar affinity for inhibition of [H-3](+)-MK801 at the PCP binding site and are of interest for candidate PET radioligand development.

  DOI：

  10.1021/acs.jmedchem.5b01510

文献信息

• [EN] ANTHELMINTIC AGENTS AND THEIR USE<br/>[FR] AGENTS ANTHELMINTHIQUES ET LEUR UTILISATION
  申请人：INTERVET INT BV

  公开号：WO2010146083A1

  公开（公告）日：2010-12-23

  This invention is directed to compounds of the formula (I) and salts therefore that are generally useful as anthelmintic agents or as intermediates in processes for making anthelmintic agents. This invention also is directed to processes for making the compounds of this invention, pharmaceutical compositions and kits comprising the compounds of this invention, uses of the compounds of this invention to make medicaments, and treatments comprising the administration of the compounds of this invention to animals in need of the treatments.

  这项发明涉及通式（I）的化合物及其盐，通常可用作驱虫剂或作为制备驱虫剂的中间体。这项发明还涉及制备这些化合物的方法，包括这些化合物的药物组合物和试剂盒，利用这些化合物制备药物的用途，以及将这些化合物用于给予需要治疗的动物的治疗。
• [EN] Substituted urea-octatydroindols as antagonists of melanin concentrating hormone receptor 1 (MCH1R)<br/>[FR] UREE-OCTAHYDROINDOLES SUBSTITUES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR 1 DE L'HORMONE CONCENTRANT LA MELANINE (MCH1R)
  申请人：BIOVITRUM AB

  公开号：WO2005051381A1

  公开（公告）日：2005-06-09

  The invention relates to compounds of the general formula (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, R9, Ar, and X are as defined in the description, or a pharmaceutically acceptable salt, hydrates, geometrical isomers, racemates, tautomers, optical isomers, N-oxides and prodrug forms thereof. The compounds may be used for the treatment or prophylaxis of disorders related to the MCH1R receptor and for modulation of appetite. The invention also relates to such use as well as to pharmaceutical formulations comprising a compound of formula (I).

  该发明涉及通式（I）的化合物，其中R0、R1、R2、R3、R4、R5、R6、R7、R8、R9、Ar和X如描述中所定义，或其药学上可接受的盐、水合物、几何异构体、消旋体、互变异构体、光学异构体、N-氧化物及其前药形式。这些化合物可用于治疗或预防与MCH1R受体相关的疾病，并用于调节食欲。该发明还涉及该用途以及包含通式（I）化合物的药物配方。
• Efficient Approaches for the Synthesis of Diverse α-Diazo Amides
  作者：Adam Nelson、Shiao Chow、Adam I. Green、Christopher Arter、Samuel Liver、Abbie Leggott、Luke Trask、George Karageorgis、Stuart Warriner

  DOI：10.1055/s-0039-1690905

  日期：2020.6

  chemistry can be exploited for the synthesis of diverse ranges of small molecules from α-diazo carbonyl compounds. In this paper, three synthetic approaches to α-diazo amides are described, and their scope and limitations are determined. On the basis of these synthetic studies, recommendations are provided to assist the selection of the most appropriate approach for specific classes of product. The

  金属催化的类胡萝卜素化学可用于从α-重氮羰基化合物合成各种范围的小分子。本文描述了三种合成α-重氮酰胺的方法，并确定了它们的范围和局限性。在这些综合研究的基础上，提供了建议，以帮助针对特定类别的产品选择最合适的方法。各种不同的α-重氮乙酰胺的实用，有效的合成方法有望促进发现许多不同类别的生物活性小分子。
• [EN] SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF<br/>[FR] LIGANDS DE SARD - COMPOSÉS DE DÉGRADATION SÉLECTIFS DE RÉCEPTEURS DES ANDROGÈNES - ET MÉTHODES D'UTILISATION
  申请人：UNIV TENNESSEE RES FOUND

  公开号：WO2017214634A1

  公开（公告）日：2017-12-14

  This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

  该发明涉及吡咯、吡唑、咪唑、三唑和吗啉基选择性雄激素受体降解剂（SARD）化合物，包括含有杂环苯胺环的合成前体、R-异构体以及非羟基化和/或非手性的丙酰胺，以及在治疗前列腺癌、晚期前列腺癌、去势耐药性前列腺癌、三阴性乳腺癌、其他表达雄激素受体的癌症、雄激素性脱发或其他高雄激素皮肤疾病、肯尼迪病、肌萎缩性侧索硬化（ALS）、腹主动脉瘤和子宫肌瘤等方面的制药组合物和用途，以及用于降低受试者中雄激素受体全长（AR-FL）的水平，包括致病性或耐药突变、AR-剪接变体（AR-SV）和AR的致病性多谷氨酸（polyQ）多态性的方法。
• ABA RECEPTOR AGONISTS THAT MODULATE TRANSPIRATION
  申请人：The Regents of the University of California

  公开号：US20180146666A1

  公开（公告）日：2018-05-31

  The present invention provides agonist compounds that activate ABA receptors, agricultural formulations comprising the agonist compounds, and methods of use for the compounds and formulations. The agricultural formulations are useful for inducing ABA responses in plant vegetative tissues, reducing abiotic stress in plants, and inhibiting germination of plant seeds. The compounds are also useful for inducing expression of ABA-responsive genes in cells that express endogenous or heterologous ABA receptors.

  本发明提供了激活ABA受体的激动剂化合物，包括这些激动剂化合物的农业配方，以及这些化合物和配方的使用方法。这些农业配方可用于诱导植物的叶绿组织产生ABA反应，减轻植物的非生物胁迫，抑制植物种子的萌发。这些化合物还可用于诱导表达在表达内源或异源ABA受体的细胞中的ABA响应基因。