4-[4-(4-甲基苯基)-1,3-噻唑-2-基]-2-丙基吡啶 | 125256-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-[4-(4-甲基苯基)-1,3-噻唑-2-基]-2-丙基吡啶
• 中文别名: 脂肪抑制素
• 英文名称: 2-(2-propylpyridin-4-yl)-4-p-tolylthiazole
• 英文别名: fatostatin A；fatostatin；125B11；FST；2-propyl-4-(4-p-tolylthiazol-2-yl)pyridine；4-(4-methylphenyl)-2-(2-propylpyridin-4-yl)-1,3-thiazole
• CAS: 125256-00-0
• 化学式: C₁₈H₁₈N₂S
• 分子量: 294.42
• InChiKey: ZROSUBKIGBSZCG-UHFFFAOYSA-N

物化性质

• 沸点：
  474.3±55.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)
• 溶解度：
  溶于 DMSO（高达 25 mg/ml）。

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934100090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8℃

制备方法与用途

生物活性

Fatostatin (125B11) 是一种二芳基噻唑衍生物，是Sterol regulatory element binding proteins (SREBPs) 活化的特异性抑制剂。它能够结合SCAP（SREBP cleavage-activating protein），并抑制SREBP从ER到高尔基体的转运。Fatostatin 可以抑制癌细胞的生长，并增强癌细胞的凋亡。

靶点

Target	Value
SREBP

体外研究

• Fatostatin (125B11)（0.1-1 μM，3天）能抑制非依赖于IGF1信号通路的去势抵抗性前列腺癌细胞增殖（IC50 = 0.1 μM），并抑制胰岛素诱导的3T3-L1细胞分化。
• Fatostatin 直接与SCAP结合，并以2.5和10 μM的IC50浓度阻止哺乳动物细胞中ER到高尔基体的转运。

细胞增殖实验

参数	值
细胞系	DU-145
浓度（μM）	0.1, 1
孵育时间（天）	3
结果	抑制IGF1诱导的生长，IC50 = 0.1 μM。

体内研究

• Fatostatin (125B11)（30 mg/kg，150 μL腹腔注射，连续28天）能减少肥胖小鼠（ob/ob）的脂肪积累，并通过降低甘油三酯储存改善脂肪肝，同时降低了高血糖。

实验数据

实验参数	值
动物模型	四至五周龄雄性C57BL/6J肥胖(ob/ob)小鼠
用药剂量（mg/kg）	30
给药方式	腹腔注射
连续给药天数	28
结果	在不受控饮食条件下，阻断肥胖ob/ob小鼠体重、血糖和肝脏脂肪堆积的增加。

反应信息

• 作为产物：
  描述：

  4-氰基-2-丙基吡啶 在 magnesium chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 4-[4-(4-甲基苯基)-1,3-噻唑-2-基]-2-丙基吡啶
  参考文献：
  名称：

  Diarylthiazole: An Antimycobacterial Scaffold Potentially Targeting PrrB-PrrA Two-Component System

  摘要：

  Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

  DOI：

  10.1021/jm500833f

文献信息

• Programmed synthesis of arylthiazoles through sequential C–H couplings
  作者：Satoshi Tani、Takahiro N. Uehara、Junichiro Yamaguchi、Kenichiro Itami

  DOI：10.1039/c3sc52199k

  日期：——

  A programmed synthesis of privileged arylthiazoles via sequential C–H couplings catalyzed by palladium or nickel catalysts has been accomplished. This versatile protocol can supply all possible arylthiazole substitution patterns (2-aryl, 4-aryl, 5-aryl, 2,4-diaryl, 2,5-diaryl, 4,5-diaryl, and 2,4,5-triaryl) from an unfunctionalized thiazole platform by 11 distinct synthetic routes. We have generated

  特权arylthiazoles的编程合成通过由钯或镍催化剂催化顺序C-H偶合已经完成。该通用协议可提供所有可能的芳基噻唑取代方式（2-芳基，4-芳基，5-芳基，2,4-二芳基，2,5-二芳基，4,5-二芳基和2,4,5-三芳基）通过11种不同的合成途径从未官能化的噻唑平台上合成 使用这种方法，我们已经生成了150多种芳基噻唑。我们已经将该方法应用于脂肪抑制素（SREBP抑制剂）的快速合成，并且已证明克级合成三芳基噻唑。
• HETEROCYCLICALLY SUBSTITUTED METHOXYPHENYL DERIVATIVES WITH AN OXO GROUP, PROCESSES FOR PREPARATION THEREOF AND USE THEREOF AS MEDICAMENTS
  申请人：KEIL Stefanie

  公开号：US20120004165A1

  公开（公告）日：2012-01-05

  Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments The invention relates to heterocyclically substituted methoxyphenyl derivatives with an oxo group, and to physiologically compatible salts thereof. The invention relates to compounds of the formula I in which R1, R2, R3, R4, R10, X, n, B 1 , B 2 , B 3 and B 4 are each defined as specified, and to the physiologically compatible salts thereof. The compounds are suitable, for example, for treatment of diabetes.

  含有氧代基的杂环取代甲氧基苯基衍生物，其制备方法及用途作为药物。该发明涉及含有氧代基的杂环取代甲氧基苯基衍生物，以及其生理兼容盐。该发明涉及以下式I的化合物 其中R1、R2、R3、R4、R10、X、n、B1、B2、B3和B4分别如规定所定义，以及其生理兼容盐。这些化合物适用于例如糖尿病的治疗。
• 6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
  申请人：SANOFI

  公开号：US20130150340A1

  公开（公告）日：2013-06-13

  The present invention relates to 1H-pyrazolo[3,4-b]pyridine compounds of the formula I, in which R 1 , R 2 , R 3 and R 4 are defined as indicated below. The compounds of the formula I are kinase inhibitors, and are useful for the treatment of diseases associated with diabetes and diabetic complications, such as, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy, for example. The invention furthermore relates to the use of compounds of the formula I, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式I的1H-吡唑并[3,4-b]吡啶化合物，其中R1、R2、R3和R4如下所示。式I的化合物是激酶抑制剂，对于治疗与糖尿病及糖尿病并发症相关的疾病，如糖尿病肾病、糖尿病神经病变和糖尿病视网膜病变等，具有用处。此外，本发明还涉及将式I的化合物用作药物中的活性成分，以及包含它们的药物组合物。
• [EN] 6-(4-HYDROXY-PHENYL)-1H-PYRAZOLO[3,4-B]PYRIDINE-4-CARBOXYLIC ACID AMIDE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS D'AMIDE DE L'ACIDE 6-(4-HYDROXY-PHÉNYL)-1H-PYRAZOLO[3,4-B]PYRIDINE-4-CARBOXYLIQUE EN TANT QU'INHIBITEURS DE KINASES
  申请人：SANOFI SA

  公开号：WO2013060636A1

  公开（公告）日：2013-05-02

  The present invention relates to 1 H-pyrazolo[3,4-b]pyridine compounds of the formula (I) in which R1, R2, R3 and R4 are defined as indicated below. The compounds of the formula I are protein kinase C (PKC) inhibitors, and are useful for the treatment of diseases associated with diabetes and diabetic complications, such as, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy, for example. The invention furthermore relates to the use of compounds of the formula, in particular as active ingredients in pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式(I)的1H-吡唑并[3,4-b]吡啶化合物，其中R1、R2、R3和R4的定义如下所示。式I的化合物是蛋白激酶C（PKC）抑制剂，对于治疗与糖尿病及糖尿病并发症相关的疾病，如糖尿病肾病、糖尿病神经病变和糖尿病视网膜病变等，具有益处。此外，本发明还涉及利用该式化合物，特别是作为药物中的活性成分以及包含它们的药物组合物。
• Heterocyclic Compounds and Methods of Use
  申请人：Medivation Technologies LLC

  公开号：US20180051013A1

  公开（公告）日：2018-02-22

  This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists.

  这份披露提供了化合物和使用这些化合物治疗代谢性疾病和增生性疾病的方法，包括与激素受体拮抗剂一起给予这些化合物的方法。