4'-iodo-N-methyl-biphenyl-4-carboxamide | 1006378-69-3

• 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'-iodo-N-methyl-biphenyl-4-carboxamide
• 英文别名: 4-(4-iodophenyl)-N-methylbenzamide
• CAS: 1006378-69-3
• 化学式: C₁₄H₁₂INO
• 分子量: 337.16
• InChiKey: RGJXTKIVPCROGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4'-iodo-N-methyl-biphenyl-4-carboxamide 、 2,4-二氧代-1,3,8-三氮杂螺[4,5]癸烷-8-甲酸叔丁酯 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 C₂₆H₃₀N₄O₅
  参考文献：
  名称：

  1,3,8-Triazaspiro[4.5]decane-2,4-diones as Efficacious Pan-Inhibitors of Hypoxia-Inducible Factor Prolyl Hydroxylase 1–3 (HIF PHD1–3) for the Treatment of Anemia

  摘要：

  The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.

  DOI：

  10.1021/jm201542d

文献信息

• Palladium-Catalyzed Synthesis of Functionalized Tetraarylphosphonium Salts
  作者：David Marcoux、André B. Charette

  DOI：10.1021/jo702355c

  日期：2008.1.1

  An efficient method to synthesize functionalized tetraarylphosphonium salts is described. This palladium-catalyzed coupling reaction between aryl iodides, bromides, or triflates and triphenylphosphine generates phosphonium salts in high yields. The coupling is compatible with a variety of functional groups such as alcohols, ketones, aldehydes, phenols, and amides.

  描述了一种合成官能化的四芳基phosph盐的有效方法。芳基碘化物，溴化物或三氟甲磺酸酯与三苯基膦之间的钯催化的偶联反应可高收率地生成phospho盐。该偶联与多种官能团如醇，酮，醛，酚和酰胺兼容。
• [EN] ABHD6 ANTAGONISTS FOR PROMOTING BROWNING OF WHITE ADIPOSE TISSUE AND BROWN ADIPOSE TISSUE FUNCTIONALITY<br/>[FR] ANTAGONISTES ABHD6 FAVORISANT LE BRUNISSEMENT DES TISSUS ADIPEUX BLANCS ET FONCTIONNALITÉ DES TISSUS ADIPEUX BRUNS
  申请人：VAL CHUM LTD PARTNERSHIP

  公开号：WO2015127559A1

  公开（公告）日：2015-09-03

  The present disclosure relates to compounds of formula I : compositions containing same and methods for treating or preventing a condition associated with brown adipose tissue dysfunction in a subject and/or for converting white adipose tissue into beige/brite adipose tissue.

  本公开涉及式I的化合物：包含相同化合物的组合物，以及用于治疗或预防与棕色脂肪组织功能障碍有关的疾病状态的方法，以及将白色脂肪组织转化为褐色/亮褐色脂肪组织的方法。
• SPIROCYCLIC COMPOUNDS AS TRYPTOPHAN HYDROXYLASE INHIBITORS
  申请人：Roivant Sciences GmbH

  公开号：US20180092918A1

  公开（公告）日：2018-04-05

  The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.