2004-63-9

Upstream product

• 626-34-6 ethyl 3-aminobut-2-enoate 
• 16469-68-4 1-(4-methoxyphenyl)-2-propyn-1-one 
• 141-97-9 ethyl acetoacetate 
• 18096-70-3 3-dimethylamino-4'-methoxyacrylophenone 
• 19115-30-1 1-(4-methoxyphenyl)-2-propyn-1-ol 
• 1224695-45-7 (2Z,4E)-2-amino-3-ethoxycarbonyl-6-(4-methoxyphenyl)hexadien-6-one 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 100-07-2 4-methoxy-benzoyl chloride 
• 99048-48-3 1‐(4‐methoxyphenyl)‐3‐(trimethylsilyl)prop‐2‐yn‐1‐one 
• 626-34-6 ethyl aminocrotonate 
• 51080-14-9 1-(6-(4-methoxyphenyl)-2-methylpyridin-3-yl)ethan-1-one 
• 24680-50-0 4-methoxy-trans-cinnamaldehyde 
• 1609547-62-7 C₁₆H₁₈O₄ 
• 18096-70-3 3-(dimethylamino)-1-(4-methoxyphenyl)prop-2-en-1-one 

Relevant academic research and scientific papers

Synthesis, in vitro biological evaluation and in silico studies of certain arylnicotinic acids conjugated with aryl (thio)semicarbazides as a novel class of anti-leishmanial agents

Herein we introduce new compounds as conjugates of arylnicotinic acids with aryl (thio)semicarbazide derivatives. Based on a structure-guided approach, they were designed to possess anti-leishmanial activity through anti-folate mechanism, via targeting Le

Pyridine-ureas as potential anticancer agents: Synthesis and in vitro biological evaluation

In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas 8a-n were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds 8e and 8n were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 μM after 48 h treatment; 0.11 and 0.80 μM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 μM). Moreover, eight selected pyridines 8b, 8d, 8e, 8i, 8j and 8l-n were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines 8b and 8e proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both 8b and 8e exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for 8b; 12-78%, GI for 8e; 15-91%). Pyridines 8b and 8e were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 μM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.

Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase

In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 ± 2.5 μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.

Consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz syntheses of tri- and tetrasubstituted pyridines

The concatenation of the modified Sonogashira alkynone synthesis and the Bagley-Bohlmann-Rahtz pyridine synthesis gives novel consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz (cBBR) syntheses of tri- and tetrasubstituted pyridines in a one-pot fashion. With these processes 15 differently substituted 3-ethoxycarbonyl 2-methylpyridines can be readily obtained in modest to moderate yields.

Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides

Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.

Visible-light-promoted iminyl-radical formation from Acyl oximes: A unified approach to pyridines, quinolines, and phenanthridines

A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3] as a photoredox catalyst, the acyl oximes were converted by 1 e- reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.

Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents

A hybrid pharmacophore approach was adopted to design and synthesize new series of isatin-pyridine hybrids. All the newly prepared hybrids (5a-o, 8 and 11a-d) were in vitro evaluated for their anti-proliferative activity against three human cancer cell lines, namely HepG2 hepatocellular carcinoma, A549 lung cancer and MCF-7 breast cancer. Compound 8 emerged as the most active member against HepG2 cell line (ICinf50/inf = 2.5 ± 0.39 μM), with 2.7-fold increased activity than the reference drug, doxorubicin (ICinf50/inf = 6.9 ± 2.05 μM). Whilst, compound 11c was found to be the most potent counterpart against A549 and MCF-7 cell lines with ICinf50/inf values of 10.8 ± 1.15 and 6.3 ± 0.79, respectively. The weightiness of the utilization of non-cleavable linker, as the chalcone linker, and simplification of the first group, was explored via the SAR study. Furthermore, a QSAR model was built to explore the structural requirements controlling the cytotoxic activities. Notably, the predicted activities by the QSAR model were very close to those experimentally observed, hinting that this model could be safely applied for prediction of more efficacious hits comprising the same skeletal framework. Finally, a theoretical kinetic study was established to predict the ADME of the active hybrids.

Bohlmann-Rahtz cyclodehydration of aminodienones to pyridines using N-iodosuccinimide

Cyclodehydration of Bohlmann-Rahtz aminodienone intermediates using N-iodosuccinimide as a Lewis acid proceeds at low temperature under very mild conditions to give the corresponding 2, 3,6-trisubstituted pyridines in high yield and with total regiocontrol.

A highly efficient regioselective one-pot synthesis of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones using K5CoW12O40·3H2O as a heterogeneous recyclable catalyst

A systematic investigation into the regioselective one-pot, three-component condensation of enaminones 1a-g, β-dicarbonyl compounds 2a-c, and ammonium acetate in the presence of a catalytic amount of K5CoW12O40·3H2O (0.01 equiv or 1.0 mol %) under solvent free conditions, as well as in refluxing isopropanol, has been reported. The reaction was highly efficient to produce 2,3,6-trisubstituted pyridines 3a-g, 4a-g, and novel 2,7,7-trisubstituted-5,6,7,8-tetrahydroquinoline-5-ones 5a-g in excellent yields. The present procedure offers advantages of short reaction time, simple work-up, and the catalyst exhibited remarkable reusable activity.

Iodine-catalysed Bohlmann-Rahtz cyclodehydration reactions

The cyclodehydration of Bohlmann-Rahtz aminodienones is catalysed by iodine in ethanol at room temperature to give 2,3,6-trisubstituted pyridines in excellent yield, with total regiocontrol and without the need for chromatographic purification.