1-benzyl-1-[3-(pyrazol-3-yl)benzyl]-3-[2,6-bis(methylthio)-4-methylpyridin-3-yl]urea | 179053-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-benzyl-1-[3-(pyrazol-3-yl)benzyl]-3-[2,6-bis(methylthio)-4-methylpyridin-3-yl]urea
• 英文别名: Urea, N'-(6-methyl-2,4-bis(methylthio)-3-pyridinyl)-N-(phenylmethyl)-N-((3-(1H-pyrazol-3-yl)phenyl)methyl)-；1-benzyl-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]-1-[[3-(1H-pyrazol-5-yl)phenyl]methyl]urea
• CAS: 179053-90-8
• 化学式: C₂₆H₂₇N₅OS₂
• 分子量: 489.665
• InChiKey: XCMUCRXXBCAKCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-甲基-2,4-双(甲基硫代)-3-吡啶胺 在 N,N-二甲基苯胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 1-benzyl-1-[3-(pyrazol-3-yl)benzyl]-3-[2,6-bis(methylthio)-4-methylpyridin-3-yl]urea
  参考文献：
  名称：

  FR186054的合成，X射线晶体结构和生物学活性-带有吡唑环的酰基CoA：胆固醇O-酰基转移酶（ACAT）的新型有效口服活性抑制剂。

  摘要：

  描述了FR186054（2c）的合成，单晶X射线结构分析和生物学活性，FR186054（2c）是一种新型的，有效的，口服有效的酰基-CoA：胆固醇O-酰基转移酶抑制剂（ACAT），含有吡唑环。不论给药方法如何，该化合物均显示出优异的体外功效，表明与其他ACAT抑制剂相比具有优越的特性。

  DOI：

  10.1016/s0960-894x(97)10191-3

文献信息

• Inhibitors of Acyl-CoA:Cholesterol <i>O</i>-Acyltransferase. 2. Identification and Structure−Activity Relationships of a Novel Series of <i>N</i>-Alkyl-<i>N</i>-(heteroaryl-substituted benzyl)-<i>N‘</i>-arylureas
  作者：Akira Tanaka、Takeshi Terasawa、Hiroyuki Hagihara、Yuri Sakuma、Noriko Ishibe、Masae Sawada、Hisashi Takasugi、Hirokazu Tanaka

  DOI：10.1021/jm9800853

  日期：1998.6.1

  tuted benzyl)-N'-arylurea and related derivatives represented by 2 and 3 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl group of this trisubstituted urea (i.e. 3, Ar1 =

  制备了一系列N-烷基-N-（杂芳基取代的苄基）-N'-芳基脲和相关的衍生物（用2和3表示），并对其在体外和体外抑制酰基辅酶A：胆固醇O-酰基转移酶的能力进行了评估。降低体内胆固醇喂养大鼠的血浆胆固醇水平。在这些新型化合物中，3型系列更为出色。该三取代脲的N-苄基上的吡唑-3-基（即3，Ar1 =吡唑-3-基）被鉴定为杂芳环，提供了良好的生物活性。通过优化与N-烷基（R）和N-芳基（Ar3）的组合的结果，化合物3aq（FR186054）被确定为一种新型的口服有效ACAT抑制剂，在胆固醇喂养的大鼠中表现出有效的体外ACAT抑制活性（兔子肠道微粒体IC50 = 99 nM）和出色的降胆固醇作用，而与给药方式无关（ED50 = 0.046 mg / kg，通过饮食给药，ED50 = 0. 44 mg /通过在PEG400载体中的管饲法施用1kg）。此外，一项毒理学研究表明，以10 mg / kg
• Novel Phosphinic Acid-Containing Thyromimetics
  申请人：Erion Mark D.

  公开号：US20090028925A1

  公开（公告）日：2009-01-29

  The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.

  本发明涉及含有磷酸基T3拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟拟
• [EN] THYROID HORMONE RECEPTOR AGONIST AND USE THEREOF<br/>[FR] AGONISTE DU RÉCEPTEUR DES HORMONES THYROÏDIENNES ET SON UTILISATION
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2017184811A1

  公开（公告）日：2017-10-26

  A thyroid hormone receptor agonist and its use in the treatment of a disease associated thyroid hormone receptor beta are described. The compound can be effective in lowering cholesterol with minimum or no adverse effects on the heart or thyroid hormone axis.

  描述了一种甲状腺激素受体激动剂及其在治疗与甲状腺激素受体β相关的疾病中的应用。该化合物可以有效降低胆固醇，对心脏或甲状腺激素轴的不良影响最小或没有。
• [EN] PHOSPHORUS-CONTAINING THYROID HORMONE RECEPTOR AGONISTS AND METHODS OF USE<br/>[FR] AGONISTES DES RÉCEPTEURS DES HORMONES THYROÏDIENNES CONTENANT DU PHOSPHORE ET MÉTHODES D'UTILISATION
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2011038207A1

  公开（公告）日：2011-03-31

  The present invention relates to sulfonic acid containing compounds that bind to thyroid receptors in the liver. Activation of these receptors results in modulation of gene expression of genes regulated by thyroid hormones. The compounds can be used to treat diseases and disorders including metabolic diseases such as NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, and metabolic syndrome X.

  本发明涉及含有磺酸基团的化合物，能够与肝脏中的甲状腺受体结合。激活这些受体会导致对甲状腺激素调控的基因表达的调节。这些化合物可用于治疗包括NASH、高胆固醇血症和高脂血症在内的代谢性疾病，以及相关病症，如动脉粥样硬化、冠心病、糖耐量受损和代谢综合征X。
• [EN] NOVEL SULFONIC ACID-CONTAINING THYROMIMETICS, AND METHODS FOR THEIR USE<br/>[FR] NOUVEAUX THYROMIMETIQUES CONTENANT DE L'ACIDE SULFONIQUE ET METHODES D'UTILISATION ASSOCIEES
  申请人：METABASIS THERAPEUTICS INC

  公开号：WO2010093601A1

  公开（公告）日：2010-08-19

  The present invention relates to sulfonic acid containing compounds of formula IB, in which G, R1, R3 and T are as defined in the claims, that bind to thyroid receptors in the liver. Activation of these receptors results in modulation of gene expression of genes regulated by thyroid hormones. The compounds can be used to treat diseases and disorders including metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome X and diabetes.

  本发明涉及公式IB的含有磺酸基团的化合物，其中G、R1、R3和T如权利要求中所定义，这些化合物与肝脏中的甲状腺受体结合。激活这些受体会导致通过甲状腺激素调节的基因表达的调节。这些化合物可用于治疗包括肥胖、NASH、高胆固醇血症和高脂血症在内的代谢性疾病以及相关疾病和疾患，如动脉粥样硬化、冠心病、糖耐量受损、代谢综合征X和糖尿病。