2-[4-[2-(oxazolo[4,5-b]pyridin-2-ylthio)ethyl]piperazin-1-yl]-N-(2,4-bis(methylthio)-6-methyl-3-pyridyl)acetamide | 217094-22-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[4-[2-(oxazolo[4,5-b]pyridin-2-ylthio)ethyl]piperazin-1-yl]-N-(2,4-bis(methylthio)-6-methyl-3-pyridyl)acetamide
• 英文别名: N-[2,4-bis(methylthio)-6-methyl-pyridin-3-yl]-2-[4-[2-(oxazolo[4,5-b]pyridin-2-ylthio)ethyl]piperazin-1-yl]acetamide；N-[2,4-bis(methylthio)-6-methyl-3pyridyl]-2-[4-[2-(oxazolo[4,5-b]pyridin-2-ylthio)ethyl]piperazin-1-yl]acetamide；1-Piperazineacetamide, N-(6-methyl-2,4-bis(methylthio)-3-pyridinyl)-4-(2-(oxazolo(4,5-b)pyridin-2-ylthio)ethyl)-；N-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]-2-[4-[2-([1,3]oxazolo[4,5-b]pyridin-2-ylsulfanyl)ethyl]piperazin-1-yl]acetamide
• CAS: 217094-22-9
• 化学式: C₂₂H₂₈N₆O₂S₃
• 分子量: 504.701
• InChiKey: XYHAZQCTATWYDN-UHFFFAOYSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  10

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 4-二甲氨基吡啶 、 18-冠醚-6 、 potassium carbonate 、 N,N-二甲基苯胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 40.0h， 生成 2-[4-[2-(oxazolo[4,5-b]pyridin-2-ylthio)ethyl]piperazin-1-yl]-N-(2,4-bis(methylthio)-6-methyl-3-pyridyl)acetamide
  参考文献：
  名称：

  临床候选2-（4-（2-（（1 H-苯并[ d ]咪唑-2-基）硫代）乙基）哌嗪-1-基）-N-（6-甲基-2,4-bis （甲硫基）吡啶-3-基）乙酰胺盐酸盐[K-604]，水溶性酰基辅酶A：胆固醇O-酰基转移酶-1抑制剂

  摘要：

  2-（4-（2-（（（1 H-苯并[ d ]咪唑-2-基]硫代]乙基]哌嗪-1-基] -N-（6-甲基-2,4-双（甲硫基）]吡啶-3-基）乙酰胺盐酸盐（K-604，2）已被确定为人类酰基辅酶A的水性可溶强效抑制剂：胆固醇ö -acyltransferase（ACAT，也称为这项方案）-1表现出229倍对人ACAT-1的选择性高于对人ACAT-2的选择性。在我们的分子设计中，在头部（吡啶基乙酰胺）和尾部（苯并咪唑）之间的连接基中插入哌嗪单元代替6-亚甲基链导致水溶解度显着提高（最高19 mg / mL） pH 1.2时）和口服吸收的显着改善（C max为2为1100倍比的更高1与先前选择的化合物，相比于禁食的狗）1。在确保药理作用和安全性之后，我们指定2个临床候选药物，命名为K-604。考虑到ACAT抑制剂在过去的临床试验中的治疗结果，我们认为K-604将可用于治疗涉及ACAT-1过表达的不治之症。

  DOI：

  10.1021/acs.jmedchem.8b01256

文献信息

• 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。
• Novel cyclic diamine compounds and medicine containing the same
  申请人：Kowa Company, Ltd.

  公开号：US20040038987A1

  公开（公告）日：2004-02-26

  The present invention offers novel cyclic diamine compounds and a pharmaceutical composition containing the same. The present invention relates to a compound represented by the formula (I) or salt(s) or solvate(s) thereof. 1 (In the formula, 2 is an optionally substituted divalent residue of benzene, pyridine, cyclohexane or naphthalene or is a vinylene group where Ar is an optionally substituted aryl group; X is —NH—, oxygen atom or sulfur atom; Y is —NR 1 —, oxygen atom, sulfur atom, sulfoxide or sulfone; Z is a single bond or —NR 2 —; R 1 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; R 2 is hydrogen atom, optionally substituted lower alkyl group, optionally substituted aryl group or optionally substituted silyl lower alkyl group; l is an integer of from 0 to 15; m is an integer of 2 or 3; and n is an integer of from 0 to 3). The compound of the present invention is useful as a pharmaceutical composition, particuarly as an inhibitor of acyl coenzyme A cholesterol acyltransferase (ACAT).

  本发明提供了新颖的环状二胺化合物以及含有该化合物的药物组合物。本发明涉及由式(I)表示的化合物或其盐或溶剂化合物。(在该式中，2是苯、吡啶、环己烷或萘的可选择取代的二价残基，或者是Ar为可选择取代芳基的乙烯基；X为—NH—、氧原子或硫原子；Y为—NR1—、氧原子、硫原子、亚砜或砜；Z为单键或—NR2—；R1为氢原子、可选择取代的较低烷基、可选择取代的芳基或可选择取代的硅烷较低烷基；R2为氢原子、可选择取代的较低烷基、可选择取代的芳基或可选择取代的硅烷较低烷基；l为0到15的整数；m为2或3的整数；n为0到3的整数)。本发明的化合物可用作药物组合物，特别是作为酰辅酶A胆固醇酰基转移酶(ACAT)的抑制剂。
• VASCULAR WALL-SELECTIVE ACAT INHIBITOR
  申请人：Kowa Company Ltd.

  公开号：EP1431294A1

  公开（公告）日：2004-06-23

  It is intended to provide a novel compound, which sustains an ACAT inhibitory activity and a macrophage-selectivity to a certain degree as a practically usable drug and can maintain an excellent oral absorption property and a favorable drug concentration in case of tested in vivo; a process for producing the same; medicinal compositions comprising the same and its intermediate. Namely, 2-[4-[2-(7-trifuoromethylbenzoxazol-2-ylthio)-ethyl]piperazin-1-yl]-N-(2,6-diisopropyl-4-hydroxyphenyl)-acetamide represented by the following formula: salts thereof or solvates of the same; and medicinal compositions comprising the compound represented by the above formula, salts thereof or solvates of the same together with pharmaceutically acceptable carriers.

  本发明旨在提供一种新型化合物，该化合物具有抑制ACAT活性和对巨噬细胞选择性在一定程度上作为一种实用药物，并且在体内测试时能够保持出色的口服吸收性能和有利的药物浓度；以及生产该化合物的方法；包含该化合物及其中间体的药用组合物。即以下式所示的2-[4-[2-(7-三氟甲基苯并噁唑-2-基硫基)-乙基]哌嗪-1-基]-N-(2,6-二异丙基-4-羟基苯基)-乙酰胺：其盐或其溶剂；以及包含上述式所代表的化合物、其盐或其溶剂以及药用可接受载体的药用组合物。