imidazolidines

Summary

Summary: Compounds based on reduced IMIDAZOLINES which contain no double bonds in the ring.

Top Publications

  1. Brooks R, Pong S, Izzo N, Moorehead T, Gopalakrishnan M, Triggle D. Interaction of azimilide with neurohumoral and channel receptors. Biochem Pharmacol. 2001;62:883-92 pubmed
    ..14 microM for carbachol). Azimilide's receptor interactions occur at concentrations from one to forty times those required to block cardiac delayed-rectifier channels but could contribute to the efficacy and safety of the drug. ..
  2. Lo A, Cheung A, Hung V, Yeung C, He Q, Chiu J, et al. Deletion of aldose reductase leads to protection against cerebral ischemic injury. J Cereb Blood Flow Metab. 2007;27:1496-509 pubmed
  3. Neves J, Botelho S, de Melo C, Pereira V, de Lima M, Pitta I, et al. Biological and immunological activity of new imidazolidines against adult worms of Schistosoma mansoni. Parasitol Res. 2010;107:531-8 pubmed publisher
    ..RZS-2) and LPSF/5-(4-fluoride-benzylidene-3-(4-nitrebenzyl)-4-thioxo-imidazolidin-2-one (RZS-5) imidazolidines, against adult worms of Schistosoma mansoni...
  4. Nagai N, Oike Y, Izumi Nagai K, Koto T, Satofuka S, Shinoda H, et al. Suppression of choroidal neovascularization by inhibiting angiotensin-converting enzyme: minimal role of bradykinin. Invest Ophthalmol Vis Sci. 2007;48:2321-6 pubmed
    ..The present study indicates the possibility of ACE inhibition as a novel therapeutic strategy to inhibit CNV. ..
  5. Obrosova I, Pacher P, Szabo C, Zsengeller Z, Hirooka H, Stevens M, et al. Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications. Diabetes. 2005;54:234-42 pubmed
    ..These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI. ..
  6. Ramana K, Willis M, White M, Horton J, Dimaio J, Srivastava D, et al. Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition. Circulation. 2006;114:1838-46 pubmed
  7. Reddy A, Srivastava S, Ramana K. Anti-inflammatory effect of aldose reductase inhibition in murine polymicrobial sepsis. Cytokine. 2009;48:170-6 pubmed publisher
    ..Our results showed that the inhibition of AR significantly prevented the polymicrobial sepsis-induced increase in inflammatory markers and thus indicate the use of AR inhibitors as anti-inflammatory agents. ..
  8. Yagihashi S, Mizukami H, Ogasawara S, Yamagishi S, Nukada H, Kato N, et al. The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice. J Pathol. 2010;220:530-41 pubmed publisher
    ..Thus, these findings suggest that the polyol pathway is implicated in AKI caused by ischaemic limb injury and that AR may be a potential therapeutic target for this condition. ..
  9. Fortin S, Wei L, Moreau E, Lacroix J, Côté M, Petitclerc E, et al. Design, synthesis, biological evaluation, and structure-activity relationships of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new tubulin inhibitors mimicking combretastatin A-4. J Med Chem. 2011;54:4559-80 pubmed publisher
    ..PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships...

More Information

Publications62

  1. Tammali R, Reddy A, Saxena A, Rychahou P, Evers B, Qiu S, et al. Inhibition of aldose reductase prevents colon cancer metastasis. Carcinogenesis. 2011;32:1259-67 pubmed publisher
    ..Thus, our results indicate that AR regulates cancer cell adhesion, invasion and migration events which initiate metastasis and therefore, AR inhibition could be a novel therapeutic approach for the prevention of colon cancer metastasis. ..
  2. Dagher Z, Park Y, Asnaghi V, Hoehn T, Gerhardinger C, Lorenzi M. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes. 2004;53:2404-11 pubmed
    ..Excess aldose reductase activity can be a mechanism for human diabetic retinopathy. ..
  3. Takahashi K, Mizukami H, Kamata K, Inaba W, Kato N, Hibi C, et al. Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat. PLoS ONE. 2012;7:e30134 pubmed publisher
    ..AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. ..
  4. Srivastava S, Ramana K, Bhatnagar A. Role of aldose reductase and oxidative damage in diabetes and the consequent potential for therapeutic options. Endocr Rev. 2005;26:380-92 pubmed
  5. Cheung A, Lo A, So K, Chung S, Chung S. Gene deletion and pharmacological inhibition of aldose reductase protect against retinal ischemic injury. Exp Eye Res. 2007;85:608-16 pubmed
    ..Therefore, AR inhibition should be considered for the treatment of retinal ischemic injury often observed in diabetic patients. ..
  6. Chen R, Iwai M, Wu L, Suzuki J, Min L, Shiuchi T, et al. Important role of nitric oxide in the effect of angiotensin-converting enzyme inhibitor imidapril on vascular injury. Hypertension. 2003;42:542-7 pubmed
    ..These results indicate that not only blockade of angiotensin II production but also activation of the bradykinin-NO system plays an important role in the beneficial effects of imidapril on vascular remodeling. ..
  7. Obrosova I, Minchenko A, Vasupuram R, White L, Abatan O, Kumagai A, et al. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Diabetes. 2003;52:864-71 pubmed
    ..In conclusion, increased AR activity contributes to retinal oxidative stress and VEGF protein overexpression in early diabetes. The findings justify the rationale for evaluation of fidarestat on diabetic retinopathy. ..
  8. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes. 2003;52:506-11 pubmed
    ..These findings have implications for how to evaluate the role of the polyol pathway in diabetic retinopathy. ..
  9. Hotta N, Toyota T, Matsuoka K, Shigeta Y, Kikkawa R, Kaneko T, et al. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care. 2001;24:1776-82 pubmed
    ..The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy. ..
  10. Oka M, Matsumoto Y, Sugiyama S, Tsuruta N, Matsushima M. A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography. J Med Chem. 2000;43:2479-83 pubmed
    ..Explanations for the differences between the observed activities of fidarestat and its stereoisomer 2 were suggested by computer modeling. ..
  11. Obrosova I, Van Huysen C, Fathallah L, Cao X, Greene D, Stevens M. An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. FASEB J. 2002;16:123-5 pubmed
    ..In conclusion, treatment with adequate doses of ARIs (that is, doses that completely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy. ..
  12. Fournier B, Bendeif E, Guillot B, Podjarny A, Lecomte C, Jelsch C. Charge density and electrostatic interactions of fidarestat, an inhibitor of human aldose reductase. J Am Chem Soc. 2009;131:10929-41 pubmed publisher
    ..Accurate estimation of electrostatic interaction energy between inhibitors and the main residues of the protein active site is derived from this high detail level of the electron density. ..
  13. Shukla N, Malladi S, Day V, David S. Preliminary evaluation of a 3H imidazoquinoline library as dual TLR7/TLR8 antagonists. Bioorg Med Chem. 2011;19:3801-11 pubmed publisher
    ..Our preliminary results suggest that alkylation with electron-rich substituents on the quinoline N5, or conversely, elimination of the fixed charge of the resultant quaternary amine on the quinolinium may yield more active compounds. ..
  14. Snider B, Wu X. Synthesis of (-)-chaetominine. Org Lett. 2007;9:4913-5 pubmed
    ..The tricyclic hydroxy imidazolidinone was converted to chaetominine in seven steps in 22% overall yield. The key step was the construction of the delta-lactam by heating an amino ester with a catalytic amount of DMAP in toluene at reflux. ..
  15. Monteiro P, Gala S, Nobre S, Carreira R, Goncalves L, Providencia L. Impact of imidapril on cardiac mitochondrial function in an ex-vivo animal model of global myocardial ischemia. Rev Port Cardiol. 2005;24:53-61 pubmed
  16. Zhang F, Liu H, Li Y, Liu H. Novel synthesis of methyl 4,6-O-benzylidenespiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'-imidazolidine] and its homologue and sugar-gamma-butyrolactam derivatives from methyl 4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose. Carbohydr Res. 2010;345:839-43 pubmed publisher
    ..These sugar-gamma-butyrolactam derivatives are potential GABA receptor ligands. ..
  17. Li H, Widenhoefer R. Gold(I)-catalyzed intramolecular dihydroamination of allenes with N,N'-disubstituted ureas to form bicyclic imidazolidin-2-ones. Org Lett. 2009;11:2671-4 pubmed publisher
    ..Gold-catalyzed dihydroamination was effective for a number of N-delta- and N-gamma-allenyl ureas to form the corresponding bicyclic imidazolidin-2-ones in good yield with high diastereoselectivity. ..
  18. Hirose T, Sunazuka T, Tsuchiya S, Tanaka T, Kojima Y, Mori R, et al. Total synthesis and determination of the absolute configuration of guadinomines B and C2. Chemistry. 2008;14:8220-38 pubmed publisher
    ..The novel feature of our method is an intramolecular S(N)2 cyclization that uses PPh(3) and I(2) to construct the unique 5-membered cyclic guanidine substructure. ..
  19. Hausman D, Cambron R, Sakr A. Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity. Int J Pharm. 2005;298:80-90 pubmed
    ..The on-line Raman blend uniformity results were also significantly correlated (p-value < 0.05) to the HPLC uniformity results of thief samples. ..
  20. Ichihara A, Suzuki F, Nakagawa T, Kaneshiro Y, Takemitsu T, Sakoda M, et al. Prorenin receptor blockade inhibits development of glomerulosclerosis in diabetic angiotensin II type 1a receptor-deficient mice. J Am Soc Nephrol. 2006;17:1950-61 pubmed
    ..It is not only AngII but also intraglomerular activation of MAPK by the receptor-associated prorenin that plays a pivotal role in diabetic nephropathy. ..
  21. Malone S, Perry G, Segal R, Dahrouge S, Crook J. Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study. BJU Int. 2005;96:514-20 pubmed
    ..IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period. ..
  22. Thanusu J, Kanagarajan V, Gopalakrishnan M. Synthesis, spectral analysis and in vitro microbiological evaluation of 3-(3-alkyl-2,6-diarylpiperin-4-ylidene)-2-thioxoimidazolidin-4-ones as a new class of antibacterial and antifungal agents. Bioorg Med Chem Lett. 2010;20:713-7 pubmed publisher
  23. Caviness G, Labadia M, Giblin P, Woska J, Last Barney K, Jeanfavre D, et al. The determination and correlation of molecular and cellular equilibrium Kd and kinetic k(off) values for small molecule allosteric antagonists of LFA-1. Biochem Pharmacol. 2007;74:98-106 pubmed
    ..Nevertheless, the results presented herein show that the K(d) and k(off)'s determined in molecular assays can be used as predictors of LFA-1 receptor occupancy in ex vivo assays. ..
  24. Nakashima T, Hattori N, Okimoto M, Yanagida J, Kohno N. Nicergoline improves dysphagia by upregulating substance P in the elderly. Medicine (Baltimore). 2011;90:279-83 pubmed publisher
    ..In conclusion, nicergoline has a comparable effect to ACE inhibitors for improving dysphagia. Nicergoline might be a novel regimen for the treatment of dysphagia in the elderly who are not treatable with ACE inhibitors. ..
  25. Wang Y, Xie Y, Wei P, King R, Schaefer H, Schleyer P, et al. Carbene-stabilized diphosphorus. J Am Chem Soc. 2008;130:14970-1 pubmed publisher
    ..The nature of the bonding in 1 and 2 was delineated by DFT computations. ..
  26. Sabourin C, Robert J, Robert Piessard S, Carbonnelle D, Lang F. Synthesis and evaluation of disubstituted N1- and N3-imidazolidin-2-ones acting as potential immunosuppressive agents. J Enzyme Inhib Med Chem. 2004;19:459-65 pubmed
  27. Zhang Q, Guan J, Sacci J, Ager A, Ellis W, Milhous W, et al. Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives. J Med Chem. 2005;48:6472-81 pubmed
  28. Palma Gámiz J, Pego M, Contreras E, Anglada M, Martínez J, Esquerra E, et al. A twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Mult. Clin Ther. 2006;28:2040-51 pubmed
    ..Both treatments were well tolerated. ..
  29. Wang H, Jia Y, Gao P, Cheng Y, Cheng M, Lu C, et al. Synthesis, radioprotective activity and pharmacokinetics characteristic of a new stable nitronyl nitroxyl radical-NIT2011. Biochimie. 2013;95:1574-81 pubmed publisher
    ..5% in mice. The LD50 of NIT2011 was 1510 mg/kg in mice by oral administration. Thus, NIT2011 has potential in being developed as an oral dosage form, safe and effective radioprotective agent. ..
  30. Wildum S, Paulsen D, Thede K, Ruebsamen Schaeff H, Zimmermann H. In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2013;57:5320-9 pubmed publisher
    ..Taken together, these data show that AIC292 represents a molecule with the antiviral properties of a novel NNRTI for the treatment of HIV-1 infection. ..
  31. Stavniichuk R, Shevalye H, Hirooka H, Nadler J, Obrosova I. Interplay of sorbitol pathway of glucose metabolism, 12/15-lipoxygenase, and mitogen-activated protein kinases in the pathogenesis of diabetic peripheral neuropathy. Biochem Pharmacol. 2012;83:932-40 pubmed publisher
  32. Hattori T, Matsubara A, Taniguchi K, Ogura Y. Aldose reductase inhibitor fidarestat attenuates leukocyte-endothelial interactions in experimental diabetic rat retina in vivo. Curr Eye Res. 2010;35:146-54 pubmed publisher
    ..In this study, we investigated the effect of fidarestat on leukocyte-endothelial cell interactions in an in vivo experimental model for diabetic retina...
  33. Carlson M. Azimilide dihydrochloride. Expert Rev Cardiovasc Ther. 2005;3:387-91 pubmed
    ..Clinical trials have utilized once-daily dosing. These trials have tested the use of the drug for patients with supraventricular and ventricular arrhythmias. ..
  34. Watanabe Y, Kimura J. Inhibitory effect of azimilide on Na+/Ca2+ exchange current in guinea-pig cardiac myocytes. J Pharmacol Sci. 2010;114:111-4 pubmed
    ..Delayed afterdepolarization induced by electrical stimulation with ouabain disappeared in the presence of 30 µM azimilide. We conclude that azimilide inhibits NCX at supratherapeutic concentrations. ..
  35. Patwardhan A, Pulgam V, Zhang Y, Wulff W. Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377. Angew Chem Int Ed Engl. 2005;44:6169-72 pubmed
  36. Sakamoto K, Sugimoto K, Sudoh T, Fujimura A. Different effects of imidapril and enalapril on aminopeptidase P activity in the mouse trachea. Hypertens Res. 2005;28:243-7 pubmed
  37. Garcia Martinez C, Hernandez G, Biba M, Welch C. Determination of enantiomeric composition of (-)-(R)-2-tert-butyltetrahydroimidazolidin-4-one by polarimetry, 1H NMR, and chiral SFC. Chirality. 2005;17:212-7 pubmed
    ..Our data suggest that solute self-association in chloroform might be independent of enantiomeric composition. ..
  38. Abou Seri S, Farag N, Hassan G. Novel diphenylamine 2,4'-dicarboxamide based azoles as potential epidermal growth factor receptor inhibitors: synthesis and biological activity. Chem Pharm Bull (Tokyo). 2011;59:1124-32 pubmed
    ..In summary, the newly synthesized compounds provide promising new lead for the future design and development of anticancer agents of potential EGFR-TK inhibitory activity. ..
  39. Pejchal V, Stepánková S, Padelková Z, Imramovsky A, Jampilek J. 1,3-substituted imidazolidine-2,4,5-triones: synthesis and inhibition of cholinergic enzymes. Molecules. 2011;16:7565-82 pubmed publisher
    ..For all the studied compounds, the relationships between the lipophilicity and the chemical structure as well as their structure-activity relationships are discussed. ..
  40. Li H, Huang S, Wang Y, Huo C. Oxidative Dehydrogenative [2 + 3]-Cyclization of Glycine Esters with Aziridines Leading to Imidazolidines. Org Lett. 2017;: pubmed publisher
    ..A series of complex imidazolidines were produced under mild and simple reaction conditions...
  41. Pitta M, Silva A, Neves J, Silva P, Irmão J, Malagueno E, et al. New imidazolidinic bioisosters: potential candidates for antischistosomal drugs. Mem Inst Oswaldo Cruz. 2006;101 Suppl 1:313-6 pubmed
    ..These observations suggest a strong electronic contribution of the arylazo grouping in the biological response. ..
  42. Hoang C, Bouillère F, Johannesen S, Zulauf A, Panel C, Pouilhès A, et al. Amino acid homologation by the Blaise reaction: a new entry into nitrogen heterocycles. J Org Chem. 2009;74:4177-87 pubmed publisher
    ..Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described. ..
  43. Kagabu S, Ishihara R, Hieda Y, Nishimura K, Naruse Y. Insecticidal and neuroblocking potencies of variants of the imidazolidine moiety of imidacloprid-related neonicotinoids and the relationship to partition coefficient and charge density on the pharmacophore. J Agric Food Chem. 2007;55:812-8 pubmed
    ..The equation for the insecticidal versus neuroblocking potencies indicated that both potencies are related proportionally with each other when the other factors are the same. ..
  44. Arrowsmith M, Hill M, Kociok Köhn G. Group 2 Catalysis for the Atom-Efficient Synthesis of Imidazolidine and Thiazolidine Derivatives. Chemistry. 2015;21:10548-57 pubmed publisher
    A wide variety of functionalised imidazolidine-2-ones and -thiones, 2-imino-imidazolidines and thiazolidine-2-thiones have been synthesised under very mild reaction conditions by using simple and cost-effective alkaline earth bis(amide) ..
  45. Swain S, Shih Y, Tsay S, Jacob J, Lin C, Hwang K, et al. Aryne-Induced Novel Tandem 1,2-Addition/(3+2) Cycloaddition to Generate Imidazolidines and Pyrrolidines. Angew Chem Int Ed Engl. 2015;54:9926-30 pubmed publisher
    A new "single-flask" method was developed for the synthesis of imidazolidines and pyrrolidines with high stereoselectivity. First, a Schiff base was arylated with an aryne...
  46. Langenhuijsen J, van Lin E, Hoffmann A, Spitters Post I, Alfred Witjes J, Kaanders J, et al. Neoadjuvant androgen deprivation for prostate volume reduction: the optimal duration in prostate cancer radiotherapy. Urol Oncol. 2011;29:52-7 pubmed publisher
    ..Therefore, the optimal duration of neoadjuvant androgen deprivation to reduce prostate volume before prostate cancer radiotherapy is 6 months. In small prostates 3 months of hormonal treatment may be enough for maximal volume reduction. ..
  47. Miake J, Kurata Y, Iizuka K, Furuichi H, Manabe K, Sasaki N, et al. State-dependent blocking actions of azimilide dihydrochlo-ride (NE-10064) on human cardiac Na(+) channels. Circ J. 2004;68:703-11 pubmed
    ..6 micromol/L). These experimental and simulation studies suggest that azimilide blocks the human cardiac Na(+) channel in both the activated and inactivated states. ..
  48. Muthusamy S, Kumar S. Copper(I) catalyzed diastereoselective multicomponent synthesis of spiroindolo-pyrrolidines/-imidazolidines/-triazolidines from diazoamides via azomethine ylides. Org Biomol Chem. 2016;14:2228-40 pubmed publisher
    ..Single-crystal X-ray analyses were performed to establish unambiguously the structure and stereochemistry of spiroheterocyclic ring systems. ..
  49. Rakowitz D, Angerer H, Matuszczak B. Synthesis and aldose reductase inhibitory activities of novel O-substituted hydroxyphenylacetic acid derivatives. Arch Pharm (Weinheim). 2006;339:547-58 pubmed
    ..This result demonstrates that within these series, this moiety is a useful surrogate for the 4-bromo-2-fluorobenzyl residue which can be often found in potent aldose reductase inhibitors. ..
  50. Feng Y, Liu G, Yue F, Wang J. N-[(2-Phenyl-2H-1,2,3-triazol-4-yl)methylene]-2-(2-(2-phenyl-2H-1,2,3-triazol-4-yl)-3-{2-[(2-phenyl-2H-1,2,3-triazol-4-yl)methyleneamino]ethyl}imidazolidin-1-yl)ethanamine. Acta Crystallogr C. 2008;64:o426-7 pubmed publisher
    ..Both sides of each of the three aromatic arms take part in these interactions, forming a neat three-dimensional array structure. ..
  51. Yadav U, Srivastava S, Ramana K. Prevention of VEGF-induced growth and tube formation in human retinal endothelial cells by aldose reductase inhibition. J Diabetes Complications. 2012;26:369-77 pubmed publisher
  52. Patel H, Sarra J, Caruso F, Rossi M, Doshi U, Stephani R. Synthesis and anticonvulsant activity of new N-1',N-3'-disubstituted-2'H,3H,5'H-spiro-(2-benzofuran-1,4'-imidazolidine)-2',3,5'-triones. Bioorg Med Chem Lett. 2006;16:4644-7 pubmed
    ..Compound 3o (the N-1'-p-nitrophenyl, N-3'-ethyl derivative) in the N-1'-aryl, N-3'-alkyl disubstituted series exhibited maximum activity with ED(50) of 41.8 mg/kg in scPTZ convulsion model. ..
  53. Manßen M, Adler C, Beckhaus R. Flexible Structural Features of Pentafulvene Titanium Derivatives: Isolation and Characterization of NHC Complexes. Chemistry. 2016;22:4405-7 pubmed publisher