175277-03-9

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate is used as an intermediate in the production of GW 501516 and its derivatives for the development of new drugs. Its chemical properties make it a valuable component in the synthesis process, contributing to the creation of medications with potential therapeutic benefits.
As an intermediate, Ethyl 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate is essential in the synthesis of GW 501516, a compound with potential applications in the treatment of various medical conditions. Its role in the pharmaceutical industry highlights the importance of its chemical properties and the need for further research and development in this area.

InChI:InChI=1/C14H12F3NO2S/c1-3-20-13(19)11-8(2)18-12(21-11)9-4-6-10(7-5-9)14(15,16)17/h4-7H,3H2,1-2H3

Upstream product

• 72505-21-6 4-trifluoromethylbenzthioamide 
• 609-15-4 ethyl 2-chloro-3-oxo-butyrate 
• 84911-18-2 ethyl 2-bromoacetoacetate 
• 7210-76-6 ethyl-2-amino-4-methylthiazole-5-carboxylate 
• 53137-15-8 ethyl 2-iodo-4-methylthiazole-5-carboxylate 
• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 638-07-3 ethyl (2-chloroaceto)acetate 
• 1514-09-6 4-(trifluoromethyl)benzothioic S-acid 
• 1891-90-3 p-trifluoromethylbenzamide 

Downstream Products

• 144059-86-9 4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylic acid 
• 444612-58-2 4-bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester 
• 1384111-08-3 ethyl 2-(4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carboxamido)acetate 

Relevant academic research and scientific papers

Synthesis of thiazole linked chalcones and their pyrimidine analogues as anticancer agents

A series of nine novel thiazole linked chalcones, (E)-3-(4-methyl-2-(4(trifluoromethyl)phenyl)thiazol-5-yl)-1-phenylprop-2-en-1-one derivatives 7–15 were synthesized. To establish the structure–activity relationship (SAR), furthermore, the corresponding, ring-closed pyrimidine analogs 17–23 were synthesized. The derivatives thus obtained were evaluated for their anti-cancer activity against three genetically different colorectal cancer (CRC) cell lines. Thiazole derivatives 7, 9, and10 showed anti-cancer activity with GI50 values ranging from 0.19 to 100 μM. Importantly, compounds 7 and 10 outperformed the standard drug cisplatin in the tested cell lines and thus show promise for further optimization. Some of pyrimidine derivatives retain activity comparable to cisplatin in the HT-29 cell line, e.g. compounds 17 and 18 with IC50 of 25?μM, however, none of these compounds demonstrated improved antiproliferative activity as compared with the starting thiazole, thus the enone linker was critical for obtaining more active compounds in this series.

Synthesis and Evaluation of PPARδAgonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis

We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ(PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay. Six compounds were selected for in vivo studies in an ovariectomized mouse model of human postmenopausal osteoporosis. Four compounds improved bone density in vivo, with two (12d and 31a) having activity comparable to that of GW0742, a well-studied PPARδ-selective agonist. 31a (2-methyl-4-[N-methyl-N-[5-methylene-4-methyl-2-[4-(trifluoromethyl)phenyl]thiazole]]aminocinnamic acid) had the highest selectivity for PPARδcompared to other subtypes, its selectivity far exceeding that of GW0742. Our results confirm that PPARδis a new drug target for possible treatment of osteoporosis via in situ manipulation of MSCs.

Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells

Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 μM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.

Synthesis of Novel Thiazolyl Hydrazine Derivatives and Their Antifungal Activity

A series of novel thiazolyl hydrazine derivatives 3a-3o were synthesized and evaluated for their in vitro antifungal activity against six phytopathogenic strains, namely, Botryosphaeria dothidea (B. d.), Gibberella sanbinetti (G. s.), Fusarium oxysporum (F. o.), Thanatephorus cucumeris (T. c.), Sclerotinia sclerotiorum (S. s.), and Verticillium dahliae (V. d.), by the classical mycelial growth rate method. Biological assessment results showed that most of these target compounds showed good antifungal activity toward tested strains. Especially, compound 3l showed excellent antifungal activities against B. d. and G. s. with relatively lower EC50 values of 0.59 and 0.69 μg/mL, respectively, which were extremely superior to those of commercial fungicides fluopyram, boscalid, and hymexazol and were comparable to those of carbendazim. Given the excellent bioactivity of designed compounds, this kind of thiazolyl hydrazine framework can provide a suitable point for exploring highly efficient antifungal agents.

Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agents

The free fatty acid receptor 1 (FFA1 or GPR40) and peroxisome proliferator-activated receptor δ (PPARδ) have attracted a lot of attention due to their role in promoting insulin secretion and sensibility, respectively, which are two major features of diabetes. Therefore, the dual FFA1/PPARδ agonists would increase insulin secretion and sensibility by FFA1 and PPARδ activation. In this study, we hybrid FFA1 agonist AM-4668 with PPARδ agonist GW501516, leading to the identification of orally bioavailable dual agonist 32, which revealed high selectivity over other PPARs. Moreover, compound 32 exhibited good pharmacokinetic profiles with high plasma concentration, sustained half-life and low clearance in vivo. During the hypoglycemic test, a dual agonist 32 enhanced the tolerance of ob/ob mice for glucose loading in a dose-dependent manner. Our results suggest that dual FFA1/PPARδ agonist could be a valuable therapy for type 2 diabetes.

miRNA biosynthesis inhibitor

The invention provides a compound shown as a formula I, or a conformational isomer thereof, or an optical isomer thereof, or a pharmaceutically acceptable salt thereof. The compound can be tightly combined with related binding proteins in an miRNA biosynthesis process and can effectively inhibit the synthesis of miRNA-21. The prepared active compound provided by the invention can be used as an miRNA-21 inhibitor, and further as a potential drug for treating malignant tumors. The formula I is shown in the description.

Biphenyl heterocyclic derivatives, their preparation and their use as medicaments (by machine translation)

The present invention relates to a novel biphenyl heterocyclic derivative represented by a general formula (I) and a preparation method thereof and use of a pharmaceutical composition containing the derivative for preparation of a drug for treating diabetes. The biphenyl heterocyclic derivative has extremely excellent hypoglycemic activity in vivo, and excellent in vivo safety and low liver toxicity risk of the compound having such a structure are unexpectedly found, and the novel biphenyl heterocyclic derivative may be used for preventing or treating diabetes.

Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes

The free fatty acid receptor 1 (FFA1/GPR40) has attracted interest as a novel target for the treatment of type 2 diabetes. Several series of FFA1 agonists including TAK-875, the most advanced compound terminated in phase III studies due to concerns about liver toxicity, have been hampered by relatively high molecular weight and lipophilicity. Aiming to develop potent FFA1 agonists with low risk of liver toxicity by decreasing the lipophilicity, the middle phenyl of TAK-875 was replaced by 11 polar five-membered heteroaromatics. Subsequently, systematic exploration of SAR and application of molecular modeling, leads to the identification of compound 44, which was an excellent FFA1 agonist with robustly hypoglycemic effect both in normal and type 2 diabetic mice, low risks of hypoglycemia and liver toxicity even at the twice molar dose of TAK-875. Meanwhile, two important findings were noted. First, the methyl group in our thiazole series occupied a small hydrophobic subpocket which had no interactions with TAK-875. Furthermore, the agonistic activity revealed a good correlation with the dihedral angle between thiazole core and the terminal benzene ring. These results promote the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists.

New hydrazones bearing thiazole scaffold: Synthesis, characterization, antimicrobial, and antioxidant investigation

New series of hydrazones 5-18 were synthesized, in good yields, by reacting 4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carbohydrazide with differently substituted benzaldehyde. The resulting compounds were characterized via elemental analysis, physico-chemical and spectral data. An antimicrobial screening was done, using Gram (+), Gram (-) bacteria and one fungal strain. Tested molecules displayed moderate-to-good growth inhibition activity. 2,2-Diphenyl-1-picrylhydrazide assay was used to test the antioxidant properties of the compounds. Monohydroxy (14-16), para-fluorine (13) and 2,4-dichlorine (17) derivatives exhibited better free-radical scavenging ability than the other investigated molecules.

Synthesis, biological evaluation and molecular modeling studies of the PPARβ/δ antagonist CC618

Herein, we describe the synthesis, biological evaluation and molecular docking of the selective PPARβ/δ antagonist (4-methyl-2-(4-(trifluoromethyl)phenyl)-N-(2-(5-(trifluoromethyl)-pyridin-2-ylsulfonyl)ethyl)thiazole-5-carboxamide)), CC618. Results from in vitro luciferase reporter gene assays against the three known human PPAR subtypes revealed that CC618 selectively antagonizes agonist-induced PPARβ/δ activity with an IC50 Combining double low line 10.0 μM. As observed by LC-MS/MS analysis of tryptic digests, the treatment of PPARβ/δ with CC618 leads to a covalent modification of Cys249, located centrally in the PPARβ/δ ligand binding pocket, corresponding to the conversion of its thiol moiety to a 5-trifluoromethyl-2-pyridylthioether. Finally, molecular docking is employed to shed light on the mode of action of the antagonist and its structural consequences for the PPARβ/δ ligand binding pocket.