4-(chloromethyl)-5-methyl-2-phenylthiazol | 178611-25-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(chloromethyl)-5-methyl-2-phenylthiazol
• 英文别名: 4-(chloromethyl)-5-methyl-2-phenyl-1,3-thiazole；4-chloromethyl-5-methyl-2-phenylthiazole；4-chloromethyl-5-methyl-2-phenyl-1,3-thiazole；4-(chloromethyl)-5-methyl-2-phenylthiazole；Thiazole, 4-(chloromethyl)-5-methyl-2-phenyl-
• CAS: 178611-25-1
• 化学式: C₁₁H₁₀ClNS
• 分子量: 223.726
• InChiKey: CTUDUOQFFJZATC-UHFFFAOYSA-N

物化性质

• 沸点：
  365.6±34.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(chloromethyl)-5-methyl-2-phenylthiazol 在 sodium azide 、 potassium carbonate 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-{3-[4-(5-Methyl-2-phenyl-thiazol-4-ylmethoxy)-phenyl]-propyl}-1H-tetrazole
  参考文献：
  名称：

  Novel 5-Substituted-1H-tetrazole Derivatives as Potent Glucose and Lipid Lowering Agents.

  摘要：

  合成了一系列含有噁唑基团的5-(4-烷氧基苯基烷基)-1H-四唑衍生物，并在两种遗传性肥胖和糖尿病动物模型（KKAy小鼠和Wistar肥胖大鼠）中评估了它们的抗糖尿病效果。合成是通过相应的腈与叠氮化合物反应环化进行的。大量的5-(4-烷氧基苯基烷基)-1H-四唑在KKAy小鼠中显示出强大的降血糖和降脂活性。特别是5-[3-[6-(5-甲基-2-苯基-4-噁唑基甲氧基)-3-吡啶基]丙基]-1H-四唑显示出强大的降血糖活性（ED25=0.0839 mg⋅kg−1⋅d−1），比盐酸吡格列酮（ED25=6.0 mg⋅kg−1⋅d−1）活性高出72倍。该化合物在Wistar肥胖大鼠中也显示出强大的降血糖（ED25=0.0873 mg⋅kg−1⋅d−1）和降脂效果（ED25=0.0277 mg⋅kg−1⋅d−1）。该化合物的抗糖尿病效果被认为是因为它对过氧化物酶体增殖物激活受体γ（PPARγ）具有强大的激动活性（EC50=6.75 nM）。

  DOI：

  10.1248/cpb.50.100
• 作为产物：
  描述：

  4,5-dimethyl-2-phenyl-1,3-thiazole hydrochlorate 在 三乙胺 、 N-氯代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以83%的产率得到4-(chloromethyl)-5-methyl-2-phenylthiazol
  参考文献：
  名称：

  Highly regioselective direct halogenation: a simple and efficient method for preparing 4-halomethyl-5-methyl-2-aryl-1,3-thiazoles

  摘要：

  An unprecedented C4-methyl regioselective halogenation of 4,5-dimethyl-2-aryl-1,3-thiazoles (1) has been accomplished. The reaction of compound 1 with N-chlorosuccinimide and N-bromosuccinimide under mild conditions provides an efficient and operationally simple method for obtaining 4-chloromethyl-5-methyl-2-aryl-1,3-thiazoles (2) and 4-bromomethyl-5-methyl-2-aryl-1,3-thiazoles (3), respectively, in good yields without the formation of 4-methyl-5-halomethyl regioisomers. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.10.113

文献信息

• Novel 5-Substituted 2,4-Thiazolidinedione and 2,4-Oxazolidinedione Derivatives as Insulin Sensitizers with Antidiabetic Activities
  作者：Yu Momose、Tsuyoshi Maekawa、Tohru Yamano、Mitsuru Kawada、Hiroyuki Odaka、Hitoshi Ikeda、Takashi Sohda

  DOI：10.1021/jm010490l

  日期：2002.3.1

  Two novel classes of 2,4-thiazolidinediones and 2,4-oxazolidinediones with an omega-(azolylalkoxyphenyl)alkyl substituent at the 5-position were prepared and their antidiabetic effects were evaluated in two genetically obese and diabetic animal models, KKA(y) mice and Wistar fatty rats. A large number of the 2,4-thia(oxa)zolidinediones showed potent glucose- and lipid-lowering activities. The antidiabetic

  制备了在5位具有ω-（偶氮基烷氧基苯基）烷基取代基的两类新的2,4-噻唑烷二酮和2,4-恶唑烷二酮，并在两个遗传性肥胖和糖尿病动物模型KKA（y）中评估了它们的抗糖尿病作用小鼠和Wistar脂肪大鼠。大量的2,4-硫杂恶唑烷二酮显示出有效的降糖和降脂活性。2,4-恶唑烷二酮的抗糖尿病活性优于2,4-噻唑烷二酮的抗糖尿病活性。在这些化合物中，5- [3- [4- [2-（2-呋喃基）-5-甲基-4-恶唑基甲氧基] -3-甲氧基苯基]丙基] -2，4-恶唑烷二酮的两种对映体（64）就活性而言，最有趣的化合物是通过使用固定化脂肪酶对相应的α-羟基戊酸酯（26）进行不对称O-乙酰化合成的，然后将恶唑烷二酮环环化。（R）-（+）-64比（S）-（-）-64（ED25> 1.5 mg / kg / d）表现出更强的降糖活性（有效剂量（ED）25 = 0.561 mg / kg / d） ）或吡格列酮（ED25
• FIVE-MEMBERED HETEROCYCLIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1541564A1

  公开（公告）日：2005-06-15

  The present invention provides a compound represented by the formula: wherein R1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is -(CH2)n-Z1- or -Z1-(CH2)n- (n is an integer of 0 to 8, Z1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R2 is a hydrogen atom, a cyano group, -PO(OR9)(OR10) (R9 and R10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R9 and R10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供了一种由以下式表示的化合物： 其中R1是可选择地取代的5-成员杂环基团；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q是具有1到20个碳原子的二价碳氢基团；环A是一个芳香环，可选择地进一步具有1到3个取代基；Z是-(CH2)n-Z1-或-Z1-(CH2)n-（n是0到8的整数，Z1是键，氧原子，硫原子等）；环B是一个含氮杂环，可选择地进一步具有1到3个取代基；W是键或具有1到20个碳原子的二价碳氢基团；R2是氢原子，氰基，-PO(OR9)(OR10)（R9和R10相同或不同，每个是氢原子或可选择地取代的碳氢基团，R9和R10可选择地结合形成可选择地取代的环）等，或其盐，具有优越的减少脂肪组织重量的作用，降糖作用和降脂作用，并且作为预防或治疗肥胖症，糖尿病，高脂血症，糖耐量受损，高血压等的药剂是有用的。
• Neovascularization inhibitors
  申请人：——

  公开号：US20030134884A1

  公开（公告）日：2003-07-17

  An angiogenesis inhibitor containing a compound represented by the formula 1 wherein R 4 is an optionally substituted hydrocarbon group and the like; Xa is a bond and the like; k is an integer of 1 to 3; Ya is an oxygen atom and the like; ring Ea is a benzene ring optionally having additional substituent(s); p is an integer of 1 to 8; R 5 is a hydrogen atom and the like; q is an integer of 0 to 6; r is 0 or 1; R 8 is a hydroxy group and the like; and R 6 and R 7 are hydrogen atoms and the like, or a salt thereof is useful as an agent for the prophylaxis or treatment of tumor and the like.

  一种含有由下式表示的化合物的血管生成抑制剂 其中R4是可选择地取代的碳氢基团等；Xa是键等；k是1到3的整数；Ya是氧原子等；环Ea是苯环，可选择地具有额外的取代基；p是1到8的整数；R5是氢原子等；q是0到6的整数；r为0或1；R8是羟基等；R6和R7是氢原子等，或其盐，可用作预防或治疗肿瘤等的药剂。
• Oxazolidinedione derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05932601A1

  公开（公告）日：1999-08-03

  2,4-Oxazolidinedione derivative represented by the formula: ##STR1## wherein R stands for an optionally substituted hydrocarbon residue or heterocyclic group; Y stands for a group represented by --CO--, --CH(OH)-- or --NR.sup.3 -- (wherein R.sup.3 stands for an optionally substituted alkyl group); m is 0 or 1; n is 0, 1 or 2; A stands for a C.sub.1-7 divalent aliphatic hydrocarbon group; R.sup.1 stands for hydrogen or an alkyl group; ring E stands for a benzene ring having 1 or 2 substituents; L and M respectively stand for hydrogen, or L and M may optionally be combined with each other to form a bond; with a proviso that the partial formula: ##STR2## does not include the formula: ##STR3## wherein R' stands for an alkyl group; or a salt thereof, which has excellent actions of lowering blood sugar and lipid in blood.

  该公式代表的2,4-噁唑烷二酮衍生物：其中R代表可选择取代的碳氢残基或杂环基团；Y代表一个由--CO--, --CH(OH)--或--NR.sup.3--（其中R.sup.3代表可选择取代的烷基基团）表示的基团；m为0或1；n为0, 1或2；A代表一个C.sub.1-7二价脂肪族碳氢基团；R.sup.1代表氢原子或烷基基团；环E代表具有1或2个取代基的苯环；L和M分别代表氢原子，或L和M可以选择性地结合在一起形成一个键；但是，部分公式不包括公式：其中R'代表烷基基团；或其盐，具有降低血糖和血脂的优秀作用。
• Studies on Non-Thiazolidinedione Antidiabetic Agents. 2. Novel Oxyiminoalkanoic Acid Derivatives as Potent Glucose and Lipid Lowering Agents.
  作者：Hiroshi Imoto、Yasuo Sugiyama、Hiroyuki Kimura、Yu Momose

  DOI：10.1248/cpb.51.138

  日期：——

  We previously reported that (Z)-2-4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino}-2-(4-phenoxyphenyl)acetic acid (3) showed potent glucose and lipid lowering effects in genetically obese and diabetic mice, KKAy. This compound also showed transcriptional activity for peroxisome proliferator-activated receptor (PPAR)-γ. We expanded on the structure–activity relationships of oxyiminoalkanoic acid derivatives based on this transcriptional activity (in vitro). Insertion of a carbon chain between the imino carbon and the carboxyl moiety of (Z)-2-4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino}-2-phenylacetic acid (2) resulted in a marked increase in transcriptional activity at PPARγ. In vivo potencies of synthesized compounds, which showed strong functional activity at PPARγ, were tested using KKAy mice. Among these compounds, (E)-4-4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino}-4-phenylbutyric acid (27) exhibited marked glucose and lipid lowering activity while showing no significant body weight gain. Compound (27) (TAK-559) showed favorable pharmacokinetic properties with good absorption and duration, and was considered as an attractive candidate for further evaluation.

  我们之前报道过，(Z)-2-4-[(5-甲基-2-苯基-1,3-恶唑-4-基)甲氧基]苄氧亚胺}-2-(4-苯氧基苯基)乙酸 (3) 在基因肥胖和糖尿病小鼠 KKAy 中表现出显著的降糖和降脂效果。该化合物还显示出对过氧化物酶体增殖物激活受体 (PPAR)-γ 的转录活性。我们基于这种转录活性（体外）扩展了氧亚胺烷酸衍生物的结构—活性关系。在 (Z)-2-4-[(5-甲基-2-苯基-1,3-恶唑-4-基)甲氧基]苄氧亚胺}-2-苯基乙酸 (2) 的亚胺碳与羧基之间插入碳链，显著提高了 PPARγ 的转录活性。合成化合物在 KKAy 小鼠中进行了体内效能测试，这些化合物在 PPARγ 上显示出强的功能活性。在这些化合物中，(E)-4-4-[(5-甲基-2-苯基-1,3-恶唑-4-基)甲氧基]苄氧亚胺}-4-苯基丁酸 (27) 展示了显著的降糖和降脂活性，同时未显示出明显的体重增加。化合物 (27) (TAK-559) 显示出良好的药代动力学特性，具备良好的吸收和持续时间，因此被认为是进一步评估的有吸引力的候选者。