2-[4-(1,1-dimethylethyl)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid | 187999-17-3

• 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: 2-[4-(1,1-dimethylethyl)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
• 英文别名: 2-(4-Tert-butylphenyl)-4-methylthiazole-5-carboxylic acid；2-(4-tert-butylphenyl)-4-methyl-1,3-thiazole-5-carboxylic acid
• CAS: 187999-17-3
• 化学式: C₁₅H₁₇NO₂S
• mdl: MFCD06857936
• 分子量: 275.371
• InChiKey: WZEOPRZZRQYSDA-UHFFFAOYSA-N

物化性质

• 沸点：
  437.9±47.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(1,1-dimethylethyl)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2-methyl-2-[4-{[(4-methyl-2-[4-tertbutylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x
• 作为产物：
  描述：

  4-叔丁基苯甲酰胺 在 sodium hydroxide 、 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 26.5h， 生成 2-[4-(1,1-dimethylethyl)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• [EN] INDOLE DERIVATIVES USEFUL AS PPAR ACTIVATORS<br/>[FR] DÉRIVÉS D'INDOLE UTILES COMME ACTIVATEURS DE PPAR
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009047240A1

  公开（公告）日：2009-04-16

  There is provided according to the invention novel compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: (I) useful as PPAR activators.

  根据本发明提供了化合物的新颖结构式(I)或其药学上可接受的盐或溶剂：(I)，可用作PPAR激活剂。
• New Azole Antifungals. 2. Synthesis and Antifungal Activity of Heterocyclecarboxamide Derivatives of 3-Amino-2-aryl-1-azolyl-2-butanol
  作者：Javier Bartroli、Enric Turmo、Mònica Algueró、Eulàlia Boncompte、Maria L. Vericat、Lourdes Conte、Joaquim Ramis、Manuel Merlos、Julián García-Rafanell、Javier Forn

  DOI：10.1021/jm970726e

  日期：1998.5.1

  A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl. group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.
• US5888941A
  申请人：——

  公开号：US5888941A

  公开（公告）日：1999-03-30
• [EN] NEW CARBOXAMIDES WITH ANTIFUNGAL ACTIVITY<br/>[FR] NOUVEAUX CARBOXAMIDES A ACTIVITE ANTIFONGIQUE
  申请人：J. URIACH & CIA. S.A.

  公开号：WO1997005131A1

  公开（公告）日：1997-02-13

  (EN) Compounds of general formula (I) and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.(FR) Les composés de la formule générale (I) et leurs sels et solvates sont des agents antifongiques. Ils sont utiles dans le traitement de différentes infections fongiques. L'invention concerne également des compositions pharmaceutiques comprenant ces composés et des procédés permettant leur préparation.