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Nature Communications May 2018Transition-metal-catalyzed diazo activation is a classical way to generate metal carbene, which are valuable intermediates in synthetic organic chemistry. An alternative...
Transition-metal-catalyzed diazo activation is a classical way to generate metal carbene, which are valuable intermediates in synthetic organic chemistry. An alternative iodine-catalyzed diazo activation is disclosed herein under either photo-initiated or thermal-initiated conditions, which represents an approach to enable carbene radical reactivity. This metal-free diazo activation strategy were successfully applied into olefin cyclopropanation and epoxidation, and applying this method to pyrrole synthesis under thermal-initiated conditions further demonstrates the unique reactivity using this method over typical metal-catalyzed conditions.
Topics: Alkenes; Catalysis; Chemistry, Organic; Iodine; Light; Methane; Pyrroles; Temperature
PubMed: 29773787
DOI: 10.1038/s41467-018-04331-4 -
BioMed Research International 2014A series of pyrrole and pyrrolopyrimidine derivatives were examined for their in vivo antihyperglycemic activity. Compounds Ia-c,e, and IVg showed promising...
A series of pyrrole and pyrrolopyrimidine derivatives were examined for their in vivo antihyperglycemic activity. Compounds Ia-c,e, and IVg showed promising antihyperglycemic activity equivalent to a well-known standard antihyperglycemic drug, Glimepiride (Amaryl, 4 mg/kg). In this paper, we examine and discuss the structure-activity relationships and antihyperglycemic activity of these compounds.
Topics: Animals; Diabetes Mellitus, Experimental; Drug Design; Hyperglycemia; Hypoglycemic Agents; Magnetic Resonance Spectroscopy; Male; Models, Chemical; Pyrimidines; Pyrroles; Rats; Rats, Wistar; Structure-Activity Relationship; Sucrose; Sulfonylurea Compounds; Temperature
PubMed: 25054134
DOI: 10.1155/2014/249780 -
Chemical Reviews Jan 2008
Review
Topics: Alkaloids; Animals; Humans; Invertebrates; Marine Biology; Oceans and Seas; Pyrroles; Structure-Activity Relationship
PubMed: 18095718
DOI: 10.1021/cr078199m -
Journal of Medicinal Chemistry Dec 2022We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) that exhibited the hallmarks of ferroptosis. Compound strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer...
We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) that exhibited the hallmarks of ferroptosis. Compound strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for normal human primary T lymphocytes at 0.1 μM. Analysis of the levels of lactoperoxidase, malondialdehyde, lactic acid, total glutathione, and ATP suggested that the in vivo inhibition of cancer cell proliferation by went through stimulation of oxidative stress injury and Fe accumulation. Quantitative polymerase chain reaction analysis of the mRNA expression in U-87 MG and SKOV-3 tumor tissues from -treated mice showed the presence of //// genes correlated with ferroptosis in both groups. Immunofluorescence staining revealed significantly lower expressions of proteins Ki67, CD31, and ferroptosis negative regulation proteins glutathione peroxidase 4 (GPX4) and FTH1. Compound was found to be metabolically stable when incubated with human liver microsomes.
Topics: Humans; Animals; Female; Mice; Tubulin Modulators; Tubulin; Pyrroles; Ovarian Neoplasms; Apoptosis; Cell Line, Tumor
PubMed: 36395526
DOI: 10.1021/acs.jmedchem.2c01457 -
Molecules (Basel, Switzerland) Sep 2023Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to...
Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC values below 10 μM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines.
Topics: Humans; Acridines; Pyrroles; Thiazolidines; Spectroscopy, Fourier Transform Infrared; Antineoplastic Agents; HCT116 Cells
PubMed: 37764394
DOI: 10.3390/molecules28186616 -
Internal Medicine (Tokyo, Japan) Apr 2024Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral...
Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral agent with strong and sustained acid-inhibitory activity. We clarified the effect of vonoprazan compared with oral PPIs in such patients. Methods We analyzed the Diagnosis Procedure Combination database. The primary outcome was rebleeding, and secondary outcomes were in-hospital mortality and in-hospital mortality after rebleeding. Propensity score matching was performed to balance the comparison groups, and logistic regression analyses were used to compare the outcomes between vonoprazan and oral PPIs. Patients Patients on vonoprazan or oral PPIs who underwent endoscopic hemostasis for UGIB between 2014 and 2019 were included. Results We enrolled 78,964 patients, of whom 27,101 and 51,863 were prescribed vonoprazan and a PPI, respectively. After propensity score matching, the rebleeding rate of vonoprazan did not significantly differ from that of oral PPIs [6.4% vs. 6.1%; odds ratio (OR), 1.05; 95% confidence interval (CI), 0.98-1.13]; similarly, the in-hospital mortality rate (1.4% vs. 1.5%; OR, 0.91; 95% CI, 0.79-1.05) and in-hospital mortality after rebleeding (0.3% vs. 0.2%; OR, 1.09; 95% CI, 0.78-1.54) also did not significantly differ between the groups. The acquired findings were robust across dose-restricted analyses and several sensitivity analyses. Conclusion Rebleeding and in-hospital mortality risks in patients on vonoprazan were similar to those in patients on oral PPIs. Considering the higher cost of vonoprazan, oral PPIs might be an optimal oral agent as an acid-suppressive therapy in such patients.
Topics: Humans; Proton Pump Inhibitors; Gastrointestinal Hemorrhage; Pyrroles; Sulfonamides
PubMed: 37558479
DOI: 10.2169/internalmedicine.2211-23 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2022The recent discovery of calix[3]pyrrole, a porphyrinogen-like tripyrrolic macrocycle, has provided an unprecedented strain-induced ring expansion reaction into...
The recent discovery of calix[3]pyrrole, a porphyrinogen-like tripyrrolic macrocycle, has provided an unprecedented strain-induced ring expansion reaction into calix[6]pyrrole. Here, we synthesized calix[n]furan[3-n]pyrrole (n=1∼3) macrocycles to investigate the reaction scope and mechanism of the ring expansion. Single crystal X-ray analysis and theoretical calculations revealed that macrocyclic ring strain increases as the number of inner NH sites increases. While calix[1]furan[2]pyrrole exhibited almost quantitative conversion into calix[2]furan[4]pyrrole within 5 minutes, less-strained calix[2]furan[1]pyrrole and calix[3]furan were inert. However, N-methylation of calix[2]furan[1]pyrrole induced a ring-expansion reaction that enabled the isolation of a linear reaction intermediate. The mechanism analysis revealed that the ring expansion consists of regioselective ring cleavage and subsequent cyclodimerization. This reaction was further utilized for synthesis of calix[6]-type macrocycles.
Topics: Calixarenes; Pyrroles
PubMed: 35137995
DOI: 10.1002/chem.202200056 -
Molecules (Basel, Switzerland) Oct 2022Multi-substituted pyrroles are synthesized from regiospecific aziridine ring-opening and subsequent intramolecular cyclization with a carbonyl group at the -position in...
Multi-substituted pyrroles are synthesized from regiospecific aziridine ring-opening and subsequent intramolecular cyclization with a carbonyl group at the -position in the presence of Lewis acid or protic acid. This method is highly atom economical where all the atoms of the reactants are incorporated into the final product with the removal of water. This new protocol is applied to the synthesis of various pyrroles, including natural products.
Topics: Pyrroles; Lewis Acids; Aziridines; Biological Products; Water
PubMed: 36296466
DOI: 10.3390/molecules27206869 -
Langmuir : the ACS Journal of Surfaces... Aug 2023Plasma polymerized pyrrole/iodine (PPPy/I) microparticles and bovine serum albumin (BSA) protein have shown interesting results in experimental models for the treatment...
Quartz Crystal Microbalance Application and Studies to Characterize the Interaction of Bovine Serum Albumin with Plasma Polymerized Pyrrole Surfaces: Implications for the Development of Biomaterials.
Plasma polymerized pyrrole/iodine (PPPy/I) microparticles and bovine serum albumin (BSA) protein have shown interesting results in experimental models for the treatment of traumatic spinal cord injury. By studying the interaction between BSA and PPPy/I by a quartz crystal microbalance (QCM) and docking, we obtained important results to elucidate possible cellular interactions and promote the use of these polymers as biomaterials. These measurements were also used to characterize the adsorption process using an equilibrium constant. In addition, atomic force microscopy (AFM) was used to obtain images of the QCM surface sensors before and after BSA adsorption. Furthermore, we carried out molecular dynamics simulations and molecular docking to characterize the molecular recognition between BSA and the previously reported PPPy/I structure. For this study, we used two combinatorial models that have not been tested. Thus, we could determine the electrostatic (Δ) and nonelectrostatic (Δ) components of the free binding energy (Δ). We demonstrated that BSA is adsorbed on PPPy/I with an adsorption constant of = 24.35 μ indicating high affinity. This observation combined with molecular docking and binding free energy calculations showed that the interaction between BSA and both combinatorial models of the PPPy structure is spontaneous.
Topics: Serum Albumin, Bovine; Biocompatible Materials; Molecular Docking Simulation; Quartz Crystal Microbalance Techniques; Pyrroles; Adsorption; Surface Properties
PubMed: 37526362
DOI: 10.1021/acs.langmuir.3c00308 -
Molecules (Basel, Switzerland) May 2023A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of...
A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of -sulfonyl-1,2,3-trizaoles with -enaminones. The imidazole ring was formed through a 1,1-insertion of the N-H bond to α-imino rhodium carbene, followed by a subsequent intramolecular 1,4-conjugate addition. This occurred when the -carbon atom of the amino group was bearing a methyl group. Additionally, the pyrrole ring was constructed by utilizing a phenyl substituent and undergoing intramolecular nucleophilic addition. The mild conditions, good tolerance towards functional groups, gram-scale synthesis capability, and ability to undergo valuable transformations of the products qualify this unique protocol as an efficient tool for the synthesis of -heterocycles.
Topics: Pyrroles; Triazoles; Catalysis; Rhodium
PubMed: 37298892
DOI: 10.3390/molecules28114416