20314-83-4

Upstream product

• 621-79-4 cinnamamide 
• 140-10-3 (E)-3-phenylacrylic acid 
• 100-52-7 benzaldehyde 

Downstream Products

• 93325-82-7 4-phenyl-2-styrylthiazole 
• 93326-72-8 4-(4-nitro-phenyl)-2-styryl-thiazole 
• 111600-99-8 4-phenyl-2-styrylthiazole 
• 155294-63-6 2-styryl-4-hydroxymethylthiazole 
• 178610-29-2 4-chloromethyl-2-[(E)-2-phenylethenyl]thiazole 
• 57182-83-9 3-isopropyl-2-phenyl-6-trans-styryl-2,3-dihydro-[1,3,5]thiadiazin-4-one 
• 128596-17-8 N-Acetyl-N-((4R,5S,6S)-5-cyano-4,6-diphenyl-5,6-dihydro-4H-thiopyran-2-yl)-acetamide 

Relevant academic research and scientific papers

Structure-activity relationship study of thiazolyl-hydroxamate derivatives as selective histone deacetylase 6 inhibitors

Several human diseases are associated with aberrant epigenetic pathways mediated by histone deacetylases (HDACs), especially HDAC6, a class IIb HDACs, which has emerged as an attractive target for neurodegenerative and autoimmune disease therapeutics. In a previous study, we developed the novel HDAC6-selective inhibitor 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) and showed that it has anti-sepsis activity in vivo. In this study, we conducted structure-activity relationship (SAR) studies to optimize the activity and selectivity of HDAC6, synthesizing its derivatives with various aliphatic linker sizes and cap structures. We identified 6u ((E)-N-hydroxy-3-(2-(4-fluorostyryl)thiazol-4-yl)propanamide), which has nanomolar inhibition activity and a 126-fold selectivity for HDAC6 over HDAC1. Through the docking analyses of 6u against HDAC subtypes, we revealed the importance of the optimal aliphatic linker size, as well as the electronic substituent effect and rigidity of the aryl cap group. Thus, we suggest a new rationale for the design of HDAC6-selective inhibitors.

Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity

Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 μM for HDAC6 versus 13.8 μM for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-α and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents.

Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives

Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the “Lipinski rule of 5”, have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1-yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.

Synthesis and biological evaluation of (E)-cinnamic acid, (E)-2-styrylthiazole and (E)-2-[2-(naphthalen-1-yl)vinyl]thiazole derivatives

Cinnamyl- and thiazole-based compounds have been shown to exhibit diverse medicinal properties and a series of twelve (E)-2-styrylthiazole and (E)-2-[(naphthalen-1-yl)vinyl]thiazole derivatives, which are conjugates of both systems and which satisfy the "Lipinski rule of 5", have been synthesised and subjected to in vitro biological screening. While insignificant inhibition (60-98% viability at 10 μM) of HeLa (cervical cancer) cells was noted, all five of the (E)-2-[naphthalen-1- yl)vinyl]thiazole derivatives proved remarkably active against SH-SY5Y (neuroblastoma) cells with IC50 values ranging from 2.09 to 8.64 μM. Two of the seven (E)-2-styrylthiazoles were found to be moderately active (with IC50 values of 10.8 and 11.7 mM), whereas the remaining five analogues exhibit significant proliferation of SH-SY5Y cells (with IC50 values of 180-1000 mM). The results warrant further studies on the effects of styrylthiazoles on the differentiation and extension of SH-SY5Y cells in order to assess their activity in neurological degenerative diseases.

Single-step microwave-mediated synthesis of oxazoles and thiazoles from 3-oxetanone: A synthetic and computational study

The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of (hydroxymethyl)oxazoles and (hydroxymethyl)thiazoles. The reactions use a sustainable solvent and only require short reaction times. These are highly competitive methods for the construction of two classes of valuable heteroarenes, which bear a useful locus for further elaboration. Electronic structure calculations have shown that the order of events involves chalcogen atom attack at sp3 carbon and alkyl-oxygen cleavage. The critical role of acid catalysis was shown clearly, and the importance of acid strength was demonstrated. The calculated barriers were also fully consistent with the observed order of thioamide and amide reactivity. Spontaneous ring opening involves a modest degree of C-O cleavage, moderating the extent of strain relief. On the acid-catalysed pathway, C-O cleavage is less extensive still, but proton transfer to the nucleofuge is well advanced with the carboxylic acid catalysts, and essentially complete with methanesulfonic acid. Open sesame: The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of oxazoles and thiazoles. The reactions use a sustainable solvent, require only short reaction times and represent a highly competitive method for the construction of two classes of valuable heteroarenes. Electronic structure calculations have been used to probe a range of potential reaction mechanisms (see figure). Copyright

GENERATION AND CYCLOADDITIONS OF 2-(N-ACYLAMINO)-1-THIA-1,3-DIENES. STRUCTURAL INVESTIGATIONS USING NMR METHODS. PART I.

A method has been developed for the efficient generation of 2-(N-acylamino)-1-thia-1,3-dienes.These novel hetero-dienes, which are generated via acylation of the corresponding thioamides, undergo irreversible regio- and stereospecific Diels-Alder addition to the starting thioamides to yield 6-(N-acylamino)-3,4-dihydro-2H-thiopyrans.The regiochemistry, relative configurations and the major solution conformations of the thiopyrans 4a-c and 10 have been determined using NMR techniques.In addition, it has been found that these systems exhibit a number of unique physical and chemical properties.

Studies on Organophosphorus Compounds. XXXVIII. Synthesis of 2,3-Unsaturated O-Alkyl Thioesters, 2,3-Unsaturated Thioamides and Tetrahydro-2H-1,3,2-thiazaphosphorin-4-one 2-Sulfides

Ethyl 2-butenoate (ethyl crotonate), ethyl 3-phenyl-2-propenoate (ethyl cinnamate), methyl2-cyano-3-phenyl-2-propenoate, and ethyl 2-cyano-3,3-diphenyl-2-propenoate, react with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, 1, at 140 deg C in xylene under formation of the corresponding O-alkyl thioesters.N-Unsubstituted, N-substituted, and N,N-disubstituted 3-phenyl-2-propenamides (cinnamamides) as well as N,N-disubstituted 2-butenamides (crotonamides) give the corresponding thioamides when treated with 1 in toluene at 60 deg C. 2-Propenamide, 2-butenamide, and 3-methyl-2-butenamide give, however, 2H-1,3,2-thiazaphosphorin-4-ones, 10-12, after recation with 1 in HMPA at 60 deg C.The 6-methyl derivative, 11, was separated in the cis and trans forms and spectroscopic data of these isomers and X-ray crystallographic data of trans-11 are given.The 2H-1,3,2-thiazaphosphorin-4-one, 10, is readily transformed into the corresponding 4-thione by reaction with 1 at 90 deg C in toluene.