-
Expert Opinion on Therapeutic Patents Sep 2017The benzopyran derivatives present a wide variety of biological activity and behaviour. At the same time the benzopyran derivatives support their use as therapeutic... (Review)
Review
The benzopyran derivatives present a wide variety of biological activity and behaviour. At the same time the benzopyran derivatives support their use as therapeutic agents for multiple diseases. Their structural characteristics correlated to physicochemical properties seem to define the extent of the biological activity. Areas covered: This review summarizes new patents published on new benzopyran derivatives from 2009 to 2016. Expert opinion: Many benzopyran derivatives have vivo/vitro biological responses. Their clinical evaluation will be critical to assess therapeutic utility. The compounds containing benzopyran moiety is well defined as lead compounds for design of new more promising molecules.
Topics: Animals; Benzopyrans; Drug Design; Humans; Patents as Topic; Structure-Activity Relationship
PubMed: 28627270
DOI: 10.1080/13543776.2017.1338687 -
Mini Reviews in Medicinal Chemistry Oct 2013Benzopyran derivatives are the potassium channel openers (KCOs) having antihypertensive, cardio-protective, myocardial protectors, powerful peripheral vasodilators and... (Review)
Review
Benzopyran derivatives are the potassium channel openers (KCOs) having antihypertensive, cardio-protective, myocardial protectors, powerful peripheral vasodilators and anti-ischemic activity. Their usage as anti-ischemic including angina, hypertension and diabetes is thought to be due to the stimulation of KATP channels which are contemplated to produce vasorelaxation and myocardial protection. It is observed that potassium channels are involved in mediating the cardio-protective effects of pre-conditioning in animal models and man. KCOs protect heart from an ischemic insult without contribution from vasodilatation. This review provides an overview of the characteristics of KCOs and their actions on subtypes used widely for the treatments of various diseases including hypertension, cardiac ischemia, arrhythmia, smooth muscle relaxation, diabetes, cardio-protective and anti-angiogenic activities.
Topics: Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Benzopyrans; Blood Pressure; Cardiotonic Agents; Heart; Humans; Ischemia; KATP Channels; Muscle Relaxation; Vasodilator Agents
PubMed: 24032515
DOI: 10.2174/13895575113136660084 -
Acta Crystallographica. Section C,... Jul 1989C16H12O3, Mr = 252.3, orthorhombic, Pna21, a = 6.633 (3), b = 13.367 (2), c = 14.056 (2) A, V = 1246.3 (9) A3, Z = 4, Dx = 1.344 g cm-3, lambda (Cu K alpha) = 1.54184 A,...
C16H12O3, Mr = 252.3, orthorhombic, Pna21, a = 6.633 (3), b = 13.367 (2), c = 14.056 (2) A, V = 1246.3 (9) A3, Z = 4, Dx = 1.344 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 7.17 cm-1, F(000) = 528, T = 296 K, R = 0.027 for 2337 observations (of 2508 unique date). The average deviation from planarity is 0.013 (1) A with a maximum of 0.028 (1) A for the fused-rings system, and 0.003 (1) A with a maximum of 0.005 (1) A for the methoxyphenyl ring. The dihedral angle between the two systems is 4.7 (3) degrees. The methoxyphenyl ring is pushed away from the vinyl proton and towards the endocyclic O atom; the bond angles are 130.13 (9) and 110.13 (8) degrees, respectively.
Topics: Benzopyrans; Chemical Phenomena; Chemistry, Physical; Crystallization; Crystallography; Molecular Structure
PubMed: 2610990
DOI: 10.1107/s0108270188014660 -
Bioorganic & Medicinal Chemistry Dec 2019We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski's rule-of-five compliant. In order to confirm key structural features to...
We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski's rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head ("carboxylic group") tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes.
Topics: Benzopyrans; Drug Discovery; Molecular Structure; PPAR alpha; PPAR gamma; Structure-Activity Relationship
PubMed: 31703893
DOI: 10.1016/j.bmc.2019.115162 -
The Journal of Biological Chemistry 2021Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic...
Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia and is associated with increased morbidity and mortality. Currently approved AF antiarrhythmic drugs have limited efficacy and/or carry the risk of ventricular proarrhythmia. The cardiac acetylcholine activated inwardly rectifying K current (I), composed of Kir3.1/Kir3.4 heterotetrameric and Kir3.4 homotetrameric channel subunits, is one of the best validated atrial-specific ion channels. Previous research pointed to a series of benzopyran derivatives with potential for treatment of arrhythmias, but their mechanism of action was not defined. Here, we characterize one of these compounds termed Benzopyran-G1 (BP-G1) and report that it selectively inhibits the Kir3.1 (GIRK1 or G1) subunit of the K channel. Homology modeling, molecular docking, and molecular dynamics simulations predicted that BP-G1 inhibits the I channel by blocking the central cavity pore. We identified the unique F137 residue of Kir3.1 as the critical determinant for the I-selective response to BP-G1. The compound interacts with Kir3.1 residues E141 and D173 through hydrogen bonds that proved critical for its inhibitory activity. BP-G1 effectively blocked the I channel response to carbachol in an in vivo rodent model and displayed good selectivity and pharmacokinetic properties. Thus, BP-G1 is a potent and selective small-molecule inhibitor targeting Kir3.1-containing channels and is a useful tool for investigating the role of Kir3.1 heteromeric channels in vivo. The mechanism reported here could provide the molecular basis for future discovery of novel, selective I channel blockers to treat atrial fibrillation with minimal side effects.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Benzopyrans; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Ion Channel Gating; Mice; Molecular Docking Simulation
PubMed: 33713702
DOI: 10.1016/j.jbc.2021.100535 -
Chemistry & Biodiversity Jun 2020Two new benzopyran derivatives, (2R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol and...
Two new benzopyran derivatives, (2R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol and (2S,4R,2'S,4'R)-4,4'-oxybis(5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran), and a new aliphatic compound, (3E,5Z,8S,10E)-8-hydroxytrideca-3,5,10,12-tetraen-2-one, together with three known benzopyran derivatives, were obtained from a mangrove endophytic fungus Penicillium citrinum QJF-22 collected in Hainan island. Their structures were determined by analysis of spectroscopic data and the relative configuration of (2R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol was also confirmed by single-crystal X-ray diffraction. The absolute configurations of four compounds were established by comparison of ECD spectra to calculations. The configuration of (3E,5Z,8S,10E)-8-hydroxytrideca-3,5,10,12-tetraen-2-one was confirmed by comparison of optical value to the similar compound. The configurations of the compounds (2S,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol and (2R,4R)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol were first determined. (3R,4S)-3,4,8-Trihydroxy-3,4-dihydronaphthalen-1(2H)-one exhibited moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC of 44.7 μM, and without cytotoxicity to RAW264.7 cells within 50 μM.
Topics: Animals; Benzopyrans; Cell Survival; Circular Dichroism; Crystallography, X-Ray; Fatty Acids; Lipopolysaccharides; Macrophages; Magnetic Resonance Spectroscopy; Mice; Molecular Conformation; Nitric Oxide; Penicillium; RAW 264.7 Cells; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism
PubMed: 32267070
DOI: 10.1002/cbdv.202000192 -
Natural Product Research May 2019Five new benzopyran derivatives (-) and a new natural product () were isolated from endophytic in and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one...
Five new benzopyran derivatives (-) and a new natural product () were isolated from endophytic in and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (), 7-O-α-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (), 7-O-α-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (), daldinium A (). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.
Topics: Anti-Infective Agents; Bacteria; Benzopyrans; Candida albicans; Dendrobium; Microbial Sensitivity Tests; Molecular Structure
PubMed: 29272956
DOI: 10.1080/14786419.2017.1419236 -
Organic & Biomolecular Chemistry Feb 2024Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological... (Review)
Review
Benzopyrans (BZPs) are among the most privileged and influential small O-heterocycles that form the core of many natural compounds, commercial drugs, biological compositions, agrochemicals, and functional materials. BZPs are divided into six general categories including coumarins, chromans, 2-chromenes, 4-chromenes, chromones, and 4-chromanones, each of which is abundant in many plants and foods. These oxygenated heterocyclic compounds are fascinating motifs and have extensive applications in biology and materials science. Hence, numerous efforts have been made to develop innovative approaches for their extraction and synthesis. However, most of them are step-by-step or multi-step strategies that suffer from waste material generation and a tedious extraction process. Isocyanide-based multicomponent reactions (I-MCRs) offer a highly efficient method for overcoming these problems. The I-MCR is a simple and environmentally friendly one-pot domino procedure that does not require intermediate isolation or workup and is generally more efficient in material usage. This review covers all research articles related to I-MCRs for synthesizing BZP derivatives from the beginning to the middle of the year 2023. This strategy will be useful for organic and pharmaceutical chemists to design new drugs and optimize the synthesis steps of biological compounds and commercial drugs with benzopyran cores.
Topics: Cyanides; Benzopyrans; Heterocyclic Compounds
PubMed: 38251960
DOI: 10.1039/d3ob01671d -
European Journal of Pharmaceutical... Jan 2019The benzopyran HP1, a compound isolated from Hypericum polyanthemum, has demonstrated significant opioid-mediated antinociceptive activity after its oral administration....
The benzopyran HP1, a compound isolated from Hypericum polyanthemum, has demonstrated significant opioid-mediated antinociceptive activity after its oral administration. Despite the pharmacological potential, the poor aqueous solubility limits the oral absorption of this compound. For this reason, HP1 has been alternatively incorporated in lipid-based drug delivery systems. Given that nanoemulsions showed higher antinociceptive action than the free compound in a previous report, in this study, the main objective was to investigate the intestinal transport mechanisms of this system. The Ussing chamber model and rat jejunum were selected for this purpose. The apparent permeability coefficient of HP1 increased approximately 5.3 times after its incorporation in nanoemulsions. Considering that the absorptive transport of HP1 was significantly higher than the secretory transport, the participation of active transporters was suggested. The amount of HP1 in the acceptor chamber was reduced during permeability assays performed at 4 °C, supporting the hypothesis that active transporters are involved in the intestinal transport of this compound. The amount of free fatty acids released from nanoemulsion was approximately 60% after 90 min, demonstrating that part of this system is disassembled before absorption. Nanoemulsion constituents would be able to form new structures with biological constituents, leading to a rapid solubilization of HP1. A mucoadhesion rate of 50% was achieved by nanoemulsion after 30 min, which would also contribute to explain the higher absorption of this system. The particle size of the nanoemulsion is also compatible with endocytosis-mediated transport. Taken together, these results suggest that nanoemulsions containing HP1 could be efficiently delivered to humans considering that different absorption mechanisms are exploited.
Topics: Adhesiveness; Animals; Benzopyrans; Emulsions; In Vitro Techniques; Intestinal Absorption; Jejunum; Male; Nanostructures; Permeability; Rats, Wistar
PubMed: 30393196
DOI: 10.1016/j.ejps.2018.10.024 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Jan 2024Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous...
Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous resin, silica gel, and C_(18) reversed-phase column chromatography, as well as HPLC as follows: macrophylloside G(1), macrophylloside D(2), 5-formyl-2,3-dihydroisocoumarin(3),(+)-medicarpin(4),(+)-syringaresinol(5), liquiritigenin(6),(3R)-sativanone(7),(3R)-3'-O-methylviolanone(8), 4,2',4'-trihydroxychalcone(9), latifolin(10), gentioxepine(11), 6α-hydroxycyclonerolidol(12), and ethyl linoleate(13). Compound 1 was a new benzopyran glycoside. Compounds 4, 6-10, 12, and 13 were isolated for the first time from Gentiana plants. Compounds 1 and 2 showed promising hepatoprotective activity against D-GalN-induced AML12 cell damage at the concentration of 10 μmol·L~(-1), and compound 2 exhibited more significant activity than silybin at the same concentration.
Topics: Gentiana; Glycosides; Benzopyrans; Glucosides; Cardiac Glycosides; Ethers
PubMed: 38403317
DOI: 10.19540/j.cnki.cjcmm.20230815.201