19 results match your criteria imidazolidinedione compound

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2,4-Thiazolidinediones as PTP 1B Inhibitors: A Mini Review (2012-2018).

Mini Rev Med Chem 2019 ;19(7):591-598

School of Pharmaceutical Sciences, Guru Ghasidas Central University, Bilaspur- 495 009 (C.G.), India.

2,4-thiazolidinedione (TZD) scaffold is a synthetic versatile scaffold explored by medicinal chemists for the discovery of novel molecules for the target-specific approach to treat or manage number of deadly ailments. PTP 1B is the negative regulator of insulin signaling cascade, and its diminished activity results in abolishment of insulin resistance associated with T2DM. The present review focused on the seven years journey (2012-2018) of TZDs as PTP 1B inhibitors with the insight into the amendments in the structural framework of TZD scaffold in order to optimize/design potential PTP 1B inhibitors. Read More

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Improving Relative Bioavailability of Oral Imidazolidinedione by Reducing Particle Size Using Homogenization and Ultra-Sonication.

Mil Med 2019 03;184(Suppl 1):106-113

Experimental Therapeutics Branch, Walter Reed Army Institute of Research 503 Robert Grant Ave., Silver Spring, MD.

Particle size is an important determinant of gastrointestinal absorption of compounds administrated orally. The present study evaluates the effect of a reduction in particle size assessed by homogenization, sonication, and homogenization plus sonication on the bioavailability of imidazolidinedione (IZ), an antimalarial compound with known causal prophylactic activity and radical cure of relapsing malaria. Formulations were administrated intragastrically to mice, and blood samples were collected for LC-MS/MS analysis. Read More

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Membrane-Active Hydantoin Derivatives as Antibiotic Agents.

J Med Chem 2017 10 6;60(20):8456-8465. Epub 2017 Oct 6.

Department of Chemistry, University of South Florida , 4202 E. Fowler Ave, Tampa, Florida 33620, United States.

Hydantoin (imidazolidinedione) derivatives such as nitrofurantoin are small molecules that have aroused considerable interest recently due to their low rate of bacterial resistance. However, their moderate antimicrobial activity may hamper their application combating antibiotic resistance in the long run. Herein, we report the design of bacterial membrane-active hydantoin derivatives, from which we identified compounds that show much more potent antimicrobial activity than nitrofurantoin against a panel of clinically relevant Gram-positive and Gram-negative bacterial strains. Read More

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October 2017

Antimanic Efficacy of a Novel Kv3 Potassium Channel Modulator.

Neuropsychopharmacology 2018 Jan 31;43(2):435-444. Epub 2017 Aug 31.

Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Kv3.1 and Kv3.2 voltage-gated potassium channels are expressed on parvalbumin-positive GABAergic interneurons in corticolimbic brain regions and contribute to high-frequency neural firing. Read More

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January 2018

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

J Neurophysiol 2016 07 6;116(1):106-21. Epub 2016 Apr 6.

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut;

Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3. Read More

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Matrix isolation infrared spectra and photochemistry of hydantoin.

J Phys Chem A 2013 Jan 22;117(4):726-34. Epub 2013 Jan 22.

Department of Chemistry, University of Coimbra, P-3004-535 Coimbra, Portugal.

Hydantoin (C(3)H(4)N(2)O(2), 2,4-imidazolidinedione) was isolated in argon matrix at 10 K and its infrared spectrum and unimolecular photochemistry were investigated. The molecular structure of the compound was studied both at the DFT(B3LYP) and MP2 levels of approximation with valence triple- and quadruple-ζ basis sets (6-311++G(d,p); cc-pVQZ). It was concluded that the minima in the potential energy surfaces of the molecule correspond to C(1) symmetry structures. Read More

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January 2013

Design of novel β-carboline derivatives with pendant 5-bromothienyl and their evaluation as phosphodiesterase-5 inhibitors.

Arch Pharm (Weinheim) 2013 Jan;346(1):23-33

Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.

New derivatives with the tetrahydro-β-carboline-imidazolidinedione and tetrahydro-β-carboline-piperazinedione scaffolds and a pendant bromothienyl moiety at C-5/C-6 were synthesized and tested for their ability to inhibit PDE5 in vitro. The following SAR can be concluded: The tetracyclic scaffold is essential for PDE5 inhibition; the ethyl group is the most suitable among the adopted N-substituents on the terminal ring (hydantoin/piperazinedione); the appropriate stereochemistry of C-5/C-6 derived from the aldehyde rather than C-11a/C-12a derived from tryptophan appears crucial for inhibition of PDE5; surprisingly, derivatives with the hydantoin terminal ring are more active than their analogs with the piperazinedione ring; the selectivity versus PDE5 relative to PDE11 with cGMP as a substrate is mainly a function of the substitution and stereochemistry pattern of the external ring, in other words of the interaction with the H-loop residues of the isozymes. Thirteen derivatives showed PDE5 inhibitory activity with IC(50) values in the range of 0. Read More

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January 2013

Novel conformationally constrained analogues of agomelatine as new melatoninergic ligands.

Molecules 2012 Dec 24;18(1):154-66. Epub 2012 Dec 24.

University of Lille Nord de France, F-59000 Lille, France.

Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT₁ and MT₂ melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compound 5), oxazolidinone (compound 7a), pyrrolidinone (compound 7b), imidazolidinedione (compound 12), thiazole (compounds 13 and 14) and isoxazole moieties (compound 15) led to a decrease of the melatoninergic binding affinities, particularly at MT₁. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT₂ receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT₂-selectivity. Read More

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December 2012

Solution-phase parallel syntheses of herbicidal 1-phenyl-2,4,5- imidazolidinetriones and 2-thioxo-4,5-imidazolidinediones.

Comb Chem High Throughput Screen 2013 Jan;16(1):78-82

State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Research Institute of Chemical Industry Co. Ltd., Shenyang, China.

In order to find new herbicidally active compounds, a fifteen-member library, focusing on the variation of 3- position substituents of 2,4,5-imidazolidine-trione or 2-thioxo-4,5-imidazolidinedione, was designed and prepared in parallel by the reaction of various ureas or thioureas with oxalyl chloride using solution-phase technology. An interesting and, to the best of our knowledge, unprecedented finding is that a by-product of 1-phenyl-3-propylcarbodiimide was formed during the addition of oxalyl chloride into the solution of 1-phenyl-3-propylthiourea in the presence of triethylamine in dichloromethane. It has been shown that the herbicidal activity of 2,4,5-imidazolidinetriones is about the same as that of their analogous 2-thioxo-4,5-imidazolidinediones. Read More

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January 2013

Identification of volatiles from the secretions and excretions of African wild dogs (Lycaon pictus).

J Chem Ecol 2012 Nov 6;38(11):1450-61. Epub 2012 Nov 6.

Paul G Allen Family Foundation Laboratory for Wildlife Chemistry, Botswana Predator Conservation Trust, Private Bag 13, Maun, Botswana.

Gas chromatography/mass spectrometry was used to identify 103 organic compounds from urine, feces, anal glands, and preputial glands of free-ranging African wild dogs, Lycaon pictus. Aliphatic acids were the dominant class of compound in all materials. In addition to aliphatic acids, urine contained dimethyl sulfone, 1,3-propanediol, benzoic acid, 1-methyl-2,4-imidazolidinedione, and squalene as major components: feces contained indole and cholesterol; and both contained 2-piperidone, phenol, 4-methyl phenol, benzeneacetic acid, and benzenepropanoic acid and other compounds. Read More

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November 2012

Synthesis and antidiabetic activity of 2,4-thiazolidindione, imidazolidinedione and 2-thioxo-imidazolidine-4-one derivatives bearing 6-methyl chromonyl pharmacophore.

J Enzyme Inhib Med Chem 2013 Dec 12;28(6):1205-10. Epub 2012 Oct 12.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University , Tandogan, Ankara , Turkey.

Numerous compounds have been prepared in order to improve the pharmacological profile of insulinotropic activities. In the present paper, we report the synthesis and the in vitro insulin releasing activity of the 6-methyl-chromonyl-2,4-thiazolidinediones (IIIa-c, IVa-c, Va-c). Compounds IIIb, IIIc, IVa-c, Va and Vc (at lower concentration; 0. Read More

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December 2013

1-[4-(3-{[5-(4-Chloro-phen-yl)furan-2-yl]methyl-idene-amino}-2,5-dioxoimidazol-idin-1-yl)but-yl]-4-methyl-piperazine-1,4-diium dichloride hemihydrate.

Acta Crystallogr Sect E Struct Rep Online 2011 Jan 12;67(Pt 2):o320. Epub 2011 Jan 12.

The title compound, C(23)H(30)ClN(5)O(3) (2+)·2Cl(-)·0.5H(2)O, was synthesized by N-alkyl-ation of 1-({[5-(4-chloro-phen-yl)-2-furan-yl]methyl-ene}amino)-2,4-imidazolidinedione with 1-bromo-4-chloro-butane, and N-methyl-piperazine. In the crystal, the cations, anions and water mol-ecules are linked by O-H⋯Cl and N-H⋯Cl hydrogen bonds. Read More

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January 2011

Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site.

Chem Biol 2011 Feb;18(2):177-86

Oncology Research and Development, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA.

c-Abl kinase activity is regulated by a unique mechanism involving the formation of an autoinhibited conformation in which the N-terminal myristoyl group binds intramolecularly to the myristoyl binding site on the kinase domain and induces the bending of the αI helix that creates a docking surface for the SH2 domain. Here, we report a small-molecule c-Abl activator, DPH, that displays potent enzymatic and cellular activity in stimulating c-Abl activation. Structural analyses indicate that DPH binds to the myristoyl binding site and prevents the formation of the bent conformation of the αI helix through steric hindrance, a mode of action distinct from the previously identified allosteric c-Abl inhibitor, GNF-2, that also binds to the myristoyl binding site. Read More

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February 2011

Synthesis and primary cytotoxicity evaluation of new 5-bromo-3-substituted-hydrazono-1H-2-indolinones.

Arch Pharm (Weinheim) 2002 Aug;335(8):374-80

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Istanbul, Istanbul, Turkey.

In this study a new series of 5-bromo-3-[(3-substituted-5-methyl-4-thiazolidinone-2-ylidene)-hydrazono]-1H-2-indolinones (3a-i) and 5-bromo-3-[(2-thioxo-3-substituted-4, 5-imidazolidinedione-1-yl)imino]-1H-2-indolinones (4a-f) was synthesized by the cyclization of 5-bromo-3-(N-substituted-thiosemicarbazono)-1H-2-indolinones (2a-i)with ethyl 2-bromopropionate in anhydrous ethanolic medium and oxalyl cloride in anhydrous diethyl ether, respectively. Six compounds chosen as prototypes were evaluated in the 3-cell line, one dose in vitro primary cytotoxicity assay. Four of them were evaluated against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions. Read More

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Acta Crystallogr C 1995 Jun;51 ( Pt 6):1221-3

Department of Chemistry, Ohio State University, Columbus 43210, USA.

The major product formed in the thermolysis of 5-diazouracil in thiophene at 423-433 K has been identified as the unexpected compound (Z)-5-(2-thienylmethylene)-2,4-imidazolidinedione, C8H6N2O2S, by X-ray analysis. The molecule is a hydantoin derivative with a thienylmethylene group substituted at the 5-position. The structure is disordered in that the thiophene ring exists in two orientations which are related by an approximate 180 degree rotation about the C(6)-C(7) bond. Read More

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Blockade of human IsK channels expressed in Xenopus oocytes by the novel class III antiarrhythmic NE-10064.

Eur J Pharmacol 1994 Oct;264(1):33-7

Physiologisches Institut I, Eberhard-Karls-Universität Tübingen, Germany.

cRNA encoding the human IsK protein was injected into Xenopus oocytes and the expressed channels were investigated using the two-microelectrode voltage-clamp method. The novel class III antiarrhythmic NE-10064 (1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]-amino]-3- [4-(4-methyl-1-piperazinyl)-butyl]-2,4-imidazolidinedione dihydrochloride) was tested for its ability to block these channels. The compound displayed potent inhibitory effects with an EC50 of 5. Read More

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October 1994

1,3-disubstituted 2-thioxo-4,5-imidazolidinediones and 2,4,5-imidazolidinetriones and their anticonvulsant activity.

Pol J Pharmacol Pharm 1990 Jan-Feb;42(1):59-68

Department of Organic Chemistry, Jagiellonian University, Kraków, Poland.

New unsymmetrically 1,3-disubstituted derivatives of 2-thioxo-4,5-imidazolidinedione (3, 5-7, 9-12) and 2,4,5-imidazolidinetrione (2, 8, 13-15) were synthesized by condensation of the respective thioureas and ureas with oxalyl chloride. They were screened for their central, mainly anticonvulsant activity and only compound 8 revealed antianxiety and antiepileptic properties. Read More

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Synthesis and antimicrobial activity of some new 2,5-imidazolidinediones.

Pharmazie 1989 Nov;44(11):765-7

Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo.

1,3-Diphenyl-4-thione-2,5-imidazolidinedione (3) was reacted with amino compounds and o-diamines to give 1,3-diphenyl-4-substituted imino-2,5-imidazolinediones (4a-m) and 1,3-diphenyl-1H-imidazo[4,5-b]quinoxaline-2(3H)-ones (5a-c), respectively. Condensation of 3 with hydrazines afforded the corresponding hydrazone derivatives (6a-c). Reaction of 6a with acetyl chloride, aromatic aldehydes, arylsulphonyl chlorides, phthalic acid anhydrides and isocyanates or thiocyanates furnished 6d, furnished the acetyl-amido derivative 6b, the benzylidenimino derivatives 7a-d, the arylsulphonamido derivatives 8a-b, the phthalimido derivatives 9a-b and the ureido and thioureido derivatives 10a-b, respectively. Read More

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November 1989

NTP Toxicology and Carcinogenesis Studies of Nitrofurantoin (CAS No. 67-20-9) in F344/N Rats and B6C3F1 Mice (Feed Studies).


Natl Toxicol Program Tech Rep Ser 1989 Sep;341:1-218

Nitrofurantoin was studied and evaluated because of its widespread use as a drug for treating urinary tract infections in humans, its structural relationship to known carcinogenic 5-nitrofuran compounds, and the lack of adequate studies to assess its carcinogenicity. Toxicology and carcinogenesis studies of nitrofurantoin were conducted by administering nitrofurantoin (greater than 99% pure) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, or 2 years. Fourteen-Day and Thirteen-Week Studies: None of the rats (at dietary concentrations up to 20,000 ppm) died before the end of the 14-day studies. Read More

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September 1989
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