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Chemical Reviews May 2022The replacement of one or more pyrrolic building block(s) of a porphyrin by a nonpyrrolic heterocycle leads to the formation of so-called pyrrole-modified porphyrins... (Review)
Review
The replacement of one or more pyrrolic building block(s) of a porphyrin by a nonpyrrolic heterocycle leads to the formation of so-called pyrrole-modified porphyrins (PMPs), porphyrinoids of broad structural variability. The wide range of coordination environments (type, number, charge, and architecture of the donor atoms) that the pyrrole-modified frameworks provide to the central metal ions, the frequent presence of donor atoms at their periphery, and their often observed nonplanarity or conformational flexibility distinguish the complexes of the PMPs clearly from those of the traditional square-planar, dianionic, N-coordinating (hydro)porphyrins. Their different coordination properties suggest their utilization in areas beyond which regular metalloporphyrins are suitable. Following a general introduction to the synthetic methodologies available to generate pyrrole-modified porphyrins, their general structure, history, coordination chemistry, and optical properties, this Review highlights the chemical, electronic (optical), and structural differences of specific classes of metalloporphyrinoids containing nonpyrrolic heterocycles. The focus is on macrocycles with similar "tetrapyrrolic" architectures as porphyrins, thusly excluding the majority of expanded porphyrins. We highlight the relevance and application of these metal complexes in biological and technical fields as chemosensors, catalysts, photochemotherapeutics, or imaging agents. This Review provides an introduction to the field of metallo-PMPs as well as a comprehensive snapshot of the current state of the art of their synthesis, structures, and properties. It also aims to provide encouragement for the further study of these intriguing and structurally versatile metalloporphyrinoids.
Topics: Coordination Complexes; Metalloporphyrins; Molecular Conformation; Porphyrins; Pyrroles
PubMed: 35302354
DOI: 10.1021/acs.chemrev.1c00694 -
Nanomedicine (London, England) Oct 2020This article is written to provide an up-to-date review of pyrrole-based biomedical materials. Porphyrins and other tetrapyrrolic molecules possess unique magnetic,... (Review)
Review
This article is written to provide an up-to-date review of pyrrole-based biomedical materials. Porphyrins and other tetrapyrrolic molecules possess unique magnetic, optical and other photophysical properties that make them useful for bioimaging and therapy. This review touches briefly on some of the synthetic strategies to obtain porphyrin- and tetrapyrrole-based nanoparticles, as well as the variety of applications in which crosslinked, self-assembled, porphyrin-coated and other nanoparticles are utilized. We explore examples of these nanoparticles' applications in photothermal therapy, drug delivery, photodynamic therapy, stimuli response, fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, computed tomography and positron emission tomography. We anticipate that this review will provide a comprehensive summary of pyrrole-derived nanoparticles and provide a guideline for their further development.
Topics: Nanoparticles; Optical Imaging; Photochemotherapy; Porphyrins; Pyrroles
PubMed: 32975469
DOI: 10.2217/nnm-2020-0125 -
The American Journal of Gastroenterology Aug 2023
Topics: Humans; Rifabutin; Cost-Benefit Analysis; Anti-Bacterial Agents; Pyrroles; Drug Therapy, Combination; Proton Pump Inhibitors; Helicobacter pylori
PubMed: 37094105
DOI: 10.14309/ajg.0000000000002248 -
Alimentary Pharmacology & Therapeutics Dec 2023
Topics: Humans; Gastroesophageal Reflux; Proton Pump Inhibitors; Pyrroles; Sulfonamides
PubMed: 37986601
DOI: 10.1111/apt.17737 -
The Medical Letter on Drugs and... Dec 2023
Topics: Humans; Esophagitis; Proton Pump Inhibitors; Pyrroles; Sulfonamides; Esomeprazole
PubMed: 38133593
DOI: 10.58347/tml.2023.1692b -
Bioorganic & Medicinal Chemistry May 2018Pyrrole-imidazole polyamides (Py-Im polyamides) are cell-permeable compounds that bind to the minor groove of double-stranded DNA in a sequence-specific manner without... (Review)
Review
Pyrrole-imidazole polyamides (Py-Im polyamides) are cell-permeable compounds that bind to the minor groove of double-stranded DNA in a sequence-specific manner without causing denaturation of the DNA. These compounds can be used to control gene expression and to stain specific sequences in cells. Here, we review the history, structural variations, and functional investigations of Py-Im polyamides.
Topics: Animals; DNA; Gene Expression Regulation; Humans; Imidazoles; Molecular Structure; Nylons; Pyrroles; Transcriptional Activation
PubMed: 29439914
DOI: 10.1016/j.bmc.2018.01.026 -
Future Medicinal Chemistry 2015
Topics: Antiviral Agents; DNA, Viral; Humans; Imidazoles; Microbial Sensitivity Tests; Nylons; Pyrroles; Virus Diseases; Viruses
PubMed: 26496156
DOI: 10.4155/fmc.15.120 -
Journal of Pharmacy & Pharmaceutical... 2022With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents... (Review)
Review
With the significant increase of patients suffering from different types of cancer, it is evident that prompt measures in the development of novel and effective agents need to be taken. Pyrrole moiety has been found in various active compounds with anti-inflammatory, antiseptic, antibacterial, lipid-lowering and anticancer properties. Recent advances in the exploration of highly active and selective cytotoxic structures containing pyrrole motifs have shown promising data for future investigations. Accordingly, this review presents an overview of recent developments in the pyrrole derivatives as anticancer agents, with a main focus towards the key moieties required for the anti-tumor activities. Pyrrole molecules comprising prominent targeting capacities against microtubule polymerization, tyrosine kinases, cytochrome p450 family 1, histone deacetylase and bcl-2 proteins were reported. In addition, several mechanisms of action, such as apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others were analyzed. Furthermore, in most of the discussed cases we provided synthesis schemes of the mentioned molecules. Overall, the utilization of pyrrole scaffold for the design and synthesis of novel anticancer drugs could be a promising approach for future investigations.
Topics: Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cytochrome P-450 Enzyme System; Genes, bcl-2; Histone Deacetylases; Humans; Microtubules; Protein-Tyrosine Kinases; Pyrroles; Structure-Activity Relationship
PubMed: 34995473
DOI: 10.18433/jpps32417 -
Advances in Therapy Jul 2016Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux... (Review)
Review
UNLABELLED
Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux disease, and for the eradication of Helicobacter pylori. However, the therapeutic efficacy of conventional PPIs is considered limited because: (1) they are unstable under acidic conditions and require an enteric-coated formulation in clinical use; (2) they show high interindividual variability in pharmacokinetics due to genetic polymorphisms of cytochrome P450 (CYP) 2C19 metabolism; (3) they have a relatively slow onset of pharmacological action and may require several doses to achieve optimal acid suppression and symptom relief; and (4) they often do not provide stable suppression of gastric acid secretion over 24 h. Vonoprazan fumarate (TAK-438, hereinafter referred to as "vonoprazan") is a new potassium-competitive acid blocker (P-CAB) developed to resolve the above limitations of conventional PPIs. Various physicochemical data have shown that vonoprazan has a high solubility and stability over a broad pH range in aqueous conditions. In addition, vonoprazan has a more potent and longer-lasting acid suppression effect than the conventional PPI, lansoprazole. Preclinical pharmacokinetic studies have shown that vonoprazan is accumulated and retained in the stomach for more than 24 h, even after it is eliminated from the plasma. From these findings, we propose that vonoprazan, which possesses a novel mode of action, can improve on the outcomes seen with conventional PPI-based treatments for acid-related diseases.
FUNDING
This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.
Topics: Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Hydrogen-Ion Concentration; Pyrroles; Sulfonamides
PubMed: 27287852
DOI: 10.1007/s12325-016-0345-2 -
Journal of the American Chemical Society Aug 2021Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores,...
Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles.
Topics: Azirines; Carbon; Density Functional Theory; Indoles; Molecular Structure; Pyrroles
PubMed: 34286965
DOI: 10.1021/jacs.1c06287