amidines

Summary

Summary: Derivatives of oxoacids RnE(=O)OH in which the hydroxy group is replaced by an amino group and the oxo group is replaced by =NR. Amidines include carboxamidines, sulfinamidines and phosphinamidines.

Top Publications

  1. Dekorver K, Johnson W, Zhang Y, Hsung R, Dai H, Deng J, et al. N-allyl-N-sulfonyl ynamides as synthetic precursors to amidines and vinylogous amidines. An unexpected N-to-C 1,3-sulfonyl shift in nitrile synthesis. J Org Chem. 2011;76:5092-103 pubmed publisher
    ..Collectively, this work showcases the rich array of chemistry one can discover using these ynamides. ..
  2. McGowan M, McAvoy C, Buchwald S. Palladium-catalyzed N-monoarylation of amidines and a one-pot synthesis of quinazoline derivatives. Org Lett. 2012;14:3800-3 pubmed publisher
    A method for the Pd-catalyzed N-arylation of both aryl and alkyl amidines with a wide range of aryl bromides, chlorides, and triflates is described...
  3. Biswas K, Greaney M. Insertion of arynes into thioureas: a new amidine synthesis. Org Lett. 2011;13:4946-9 pubmed publisher
    ..The reaction contrasts with that of ureas, which proceeds via benzyne ?-insertion into the C-N bond, and represents a new, operationally simple route to functionalized amidines.
  4. Foster J, Carmines P, Pollock J. PP2B-dependent NO production in the medullary thick ascending limb during diabetes. Am J Physiol Renal Physiol. 2009;297:F471-80 pubmed publisher
    ..In conclusion, while NO bioavailability in mTALs is reduced during diabetes, free radical scavenging with tempol unmasks increased NO production that involves PP2B-dependent activation of NOS1 and NOS2...
  5. Ma B, Wang Y, Peng J, Zhu Q. Synthesis of quinazolin-4(3H)-ones via Pd(II)-catalyzed intramolecular C(sp2)-H carboxamidation of N-arylamidines. J Org Chem. 2011;76:6362-6 pubmed publisher
    ..Compared with existing approaches to quinazolin-4(3H)-ones, the current strategy features atom-economy and step-efficiency. ..
  6. Castanedo G, Seng P, Blaquiere N, Trapp S, Staben S. Rapid synthesis of 1,3,5-substituted 1,2,4-triazoles from carboxylic acids, amidines, and hydrazines. J Org Chem. 2011;76:1177-9 pubmed publisher
    ..synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of carboxylic acids, primary amidines, and monosubstituted hydrazines...
  7. Sävmarker J, Rydfjord J, Gising J, Odell L, Larhed M. Direct palladium(II)-catalyzed synthesis of arylamidines from aryltrifluoroborates. Org Lett. 2012;14:2394-7 pubmed publisher
    ..The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O(2)CCF(3)), 6-methyl-2,2'-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields...
  8. Slack J, Causey C, Thompson P. Protein arginine deiminase 4: a target for an epigenetic cancer therapy. Cell Mol Life Sci. 2011;68:709-20 pubmed publisher
    ..Taken together, these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease. ..
  9. Kotthaus J, Steinmetzer T, Van De Locht A, Clement B. Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes). J Enzyme Inhib Med Chem. 2011;26:115-22 pubmed publisher
    ..In order to improve oral bioavailability of these drugs, prodrug principles such as the conversion of amidines into amidoximes may be applied...

More Information

Publications62

  1. Batista D, Batista M, de Oliveira G, do Amaral P, Lannes Vieira J, Britto C, et al. Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas' disease treatment. Antimicrob Agents Chemother. 2010;54:2940-52 pubmed publisher
    ..Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment. ..
  2. Nhili R, Peixoto P, Depauw S, Flajollet S, Dezitter X, Munde M, et al. Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines. Nucleic Acids Res. 2013;41:125-38 pubmed publisher
    ..These data showed for the first time the ERG/DNA complex modulation, both in vitro and in cells, by a heterocyclic diamidine that specifically targets a portion of the ERG DNA recognition site. ..
  3. Soeiro M, Werbovetz K, Boykin D, Wilson W, Wang M, Hemphill A. Novel amidines and analogues as promising agents against intracellular parasites: a systematic review. Parasitology. 2013;140:929-51 pubmed publisher
    ..This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a ..
  4. Bardosh K, Waiswa C, Welburn S. Conflict of interest: use of pyrethroids and amidines against tsetse and ticks in zoonotic sleeping sickness endemic areas of Uganda. Parasit Vectors. 2013;6:204 pubmed publisher
    ..The private veterinary market is divided between products only effective against ticks (amidines) and those effective against both ticks and tsetse (pyrethroids)...
  5. Kimura A, Nishikawa H, Nomura N, Mitsuyama J, Fukumoto S, Inoue N, et al. In vitro and in vivo antimalarial activities of T-2307, a novel arylamidine. Antimicrob Agents Chemother. 2012;56:2191-3 pubmed publisher
    ..17 ?M, respectively. T-2307 at 2.5 to 10 mg/kg of body weight/day exhibited activity against blood stage and liver stage parasites in rodent malaria models. In conclusion, T-2307 exhibited in vitro and in vivo antimalarial activity. ..
  6. Cortes H, Muller N, Boykin D, Stephens C, Hemphill A. In vitro effects of arylimidamides against Besnoitia besnoiti infection in Vero cells. Parasitology. 2011;138:583-92 pubmed publisher
    ..These results show that arylimidamides such as DB811 could potentially become an important addition to the anti-parasitic arsenal for food animal production, especially in cattle. ..
  7. Fang J, Silverman R. A cellular model for screening neuronal nitric oxide synthase inhibitors. Anal Biochem. 2009;390:74-8 pubmed publisher
    ..The cell-based assay provides more information than in vitro assays regarding the bioavailability of NOS inhibitors, and it is suitable for high-throughput screening. ..
  8. Batista D, Batista M, de Oliveira G, Britto C, Rodrigues A, Stephens C, et al. Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo. PLoS ONE. 2011;6:e22155 pubmed publisher
    ..Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ?13% of surviving animals. ..
  9. Brzozowski M, Alcantara S, Iravani M, Rose S, Jenner P. The effect of nNOS inhibitors on toxin-induced cell death in dopaminergic cell lines depends on the extent of enzyme expression. Brain Res. 2011;1404:21-30 pubmed publisher
    ..nNOS is protective against toxic insult when produced endogenously. When nNOS is overexpressed, it becomes neurotoxic to cells suggesting that inhibition of nNOS may be a promising strategy to prevent cell death in PD. ..
  10. Corr M, Gibson K, Kennedy A, Murphy J. Amidine dications: isolation and [Fe]-hydrogenase-related hydrogenation. J Am Chem Soc. 2009;131:9174-5 pubmed publisher
  11. Tevis D, Kumar A, Stephens C, Boykin D, Wilson W. Large, sequence-dependent effects on DNA conformation by minor groove binding compounds. Nucleic Acids Res. 2009;37:5550-8 pubmed publisher
    ..interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly...
  12. Yan G, Brouwer K, Pollack G, Wang M, Tidwell R, Hall J, et al. Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models. J Pharmacol Exp Ther. 2011;337:503-12 pubmed publisher
    ..A higher f(u,L) explained, in part, the enhanced perfusate AUC of CPD-0801 compared with furamidine in IPLs. SCH predicted the disposition of prodrug/metabolite in IPLs. ..
  13. Pacheco M, Da Silva C, de Souza E, Batista M, da Silva P, Kumar A, et al. Trypanosoma cruzi: activity of heterocyclic cationic molecules in vitro. Exp Parasitol. 2009;123:73-80 pubmed publisher
    ..cruzi infection. ..
  14. Liu Y, Chai Y, Kumar A, Tidwell R, Boykin D, Wilson W. Designed compounds for recognition of 10 base pairs of DNA with two at binding sites. J Am Chem Soc. 2012;134:5290-9 pubmed publisher
    ..The results are supported by mass spectrometry and circular dichroism, and models to explain the different binding modes are presented. ..
  15. Okano A, James R, Pierce J, Xie J, Boger D. Silver(I)-promoted conversion of thioamides to amidines: divergent synthesis of a key series of vancomycin aglycon residue 4 amidines that clarify binding behavior to model ligands. J Am Chem Soc. 2012;134:8790-3 pubmed publisher
    Development of a general Ag(I)-promoted reaction for the conversion of thioamides to amidines is disclosed...
  16. Wang M, Zhu X, Srivastava A, Liu Q, Sweat J, Pandharkar T, et al. Novel arylimidamides for treatment of visceral leishmaniasis. Antimicrob Agents Chemother. 2010;54:2507-16 pubmed publisher
  17. Da Silva C, Junqueira A, Lima M, Romanha A, Sales Junior P, Stephens C, et al. In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi. J Antimicrob Chemother. 2011;66:1295-7 pubmed publisher
    ..94 ?M) and to prevent blood bank infection (gentian violet IC??=?30.6 ?M). AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease. ..
  18. Chen X, Orser B, MacDonald J. Design and screening of ASIC inhibitors based on aromatic diamidines for combating neurological disorders. Eur J Pharmacol. 2010;648:15-23 pubmed publisher
    ..Further studies may lead to a drug with therapeutic value and extend the therapeutic scope of aromatic diamidines to combat neurological diseases. ..
  19. Liu Y, Kumar A, Depauw S, Nhili R, David Cordonnier M, Lee M, et al. Water-mediated binding of agents that target the DNA minor groove. J Am Chem Soc. 2011;133:10171-83 pubmed publisher
    ..DB921 has a benzimidazole-biphenyl system with terminal amidines that results in a linear conformation that does not possess the appropriate radius of curvature to match the ..
  20. Miao Y, Lee M, Parkinson G, Batista Parra A, Ismail M, Neidle S, et al. Out-of-shape DNA minor groove binders: induced fit interactions of heterocyclic dications with the DNA minor groove. Biochemistry. 2005;44:14701-8 pubmed
    DB921 and DB911 are benzimidazole-biphenyl isomers with terminal charged amidines. DB911 has a central meta-substituted phenyl that gives it a shape similar to those of known minor groove binding compounds...
  21. Stone E, Schaller T, Bianchi H, Person M, Fast W. Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase. Biochemistry. 2005;44:13744-52 pubmed
    ..Likewise, 2-chloroacetamidine may potentially find wide applicability as a general pharmacophore useful in delineating characteristics of the amidinotransferase superfamily. ..
  22. Kotthaus J, Schade D, Muschick N, Beitz E, Clement B. Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads. Bioorg Med Chem. 2008;16:10205-9 pubmed publisher
    ..the binding pocket of the guanidine-moiety was investigated by screening differently substituted guanidines, amidines and isothioureas in order to collect information on possible binding modes in the active site...
  23. Tafani M, Schito L, Anwar T, Indelicato M, Sale P, Di Vito M, et al. Induction of autophagic cell death by a novel molecule is increased by hypoxia. Autophagy. 2008;4:1042-53 pubmed
    ..These results indicate that activation of the autophagic pathway in hypoxic cells by the new molecule CR 3294, as well as by TFP or SW, can have potentially important implications for cancer treatment. ..
  24. Kan W, Hsu J, Schwacha M, Choudhry M, Raju R, Bland K, et al. Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury. J Appl Physiol (1985). 2008;105:1076-82 pubmed publisher
    ..These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions...
  25. El Mas M, Fan M, Abdel Rahman A. Endotoxemia-mediated induction of cardiac inducible nitric-oxide synthase expression accounts for the hypotensive effect of ethanol in female rats. J Pharmacol Exp Ther. 2008;324:368-75 pubmed
    ..These findings yield insight into the mechanistic role of endotoxin-myocardial iNOS signaling in the cardiodepressant action of ethanol, which accounts for its hypotensive effect in conscious female rats...
  26. Silva C, Meuser M, De Souza E, Meirelles M, Stephens C, Som P, et al. Cellular effects of reversed amidines on Trypanosoma cruzi. Antimicrob Agents Chemother. 2007;51:3803-9 pubmed
    ..both in vitro and in vivo, our present aim was to evaluate the cellular effects in vitro of three reversed amidines (DB889, DB702, and DB786) and one diguanidine (DB711) against both amastigotes and bloodstream trypomastigotes of ..
  27. Munde M, Lee M, Neidle S, Arafa R, Boykin D, Liu Y, et al. Induced fit conformational changes of a "reversed amidine" heterocycle: optimized interactions in a DNA minor groove complex. J Am Chem Soc. 2007;129:5688-98 pubmed
    ..reverse system has a larger dihedral angle as well as a modified spatial relationship with the groove relative to amidines. Because of the large dihedral, the reversed amidines should have reduced binding to DNA relative to similar ..
  28. Tang Y, Liu Z. Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes. Bioorg Med Chem. 2007;15:1903-13 pubmed
    ..These findings may be useful for the development of agents for various ROS-mediated diseases in vivo. ..
  29. Luo Y, Arita K, Bhatia M, Knuckley B, Lee Y, Stallcup M, et al. Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry. 2006;45:11727-36 pubmed
    ..In addition, they represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder. ..
  30. Mozziconacci O, Williams T, SCHONEICH C. Intramolecular hydrogen transfer reactions of thiyl radicals from glutathione: formation of carbon-centered radical at Glu, Cys, and Gly. Chem Res Toxicol. 2012;25:1842-61 pubmed publisher
  31. Akhtar M, Yar M, Khan A, Ali Z, Haider M. Recent advances in the synthesis and anticancer activity of molecules other than nitrogen containing heterocyclic moeities. Mini Rev Med Chem. 2016;: pubmed
    ..Napthalenes amides/amidines, furan, podophyllotoxin, platinum compounds, steroids, and urea which form the core part or along with other N-..
  32. Corr M, Roydhouse M, Gibson K, Zhou S, Kennedy A, Murphy J. Amidine dications as superelectrophiles. J Am Chem Soc. 2009;131:17980-5 pubmed publisher
    ..Extending the scope of the reactions, a tricationic 2,6-bis(dimethylalkylammonium)pyridinium salt has also been prepared and characterized and its reactivity as a methylating agent assessed in comparison with that of the dications. ..
  33. Ban K, Santora R, Kozar R. Enteral arginine modulates inhibition of AP-1/c-Jun by SP600125 in the postischemic gut. Mol Cell Biochem. 2011;347:191-9 pubmed publisher
    ..Our data suggest that AP-1 inhibition mitigates the injurious inflammatory effects of arginine in the postischemic gut. Further investigation into the pathologic role of enteral arginine in the postischemic gut is warranted. ..
  34. Gou L, Zhang L, Yin C, Jia G, Yin X, Zhuang X, et al. Protective effect of L-citrulline against acute gastric mucosal lesions induced by ischemia-reperfusion in rats. Can J Physiol Pharmacol. 2011;89:317-27 pubmed publisher
  35. Simonsson R, Stenhagen G, Ericsson C, Elmore C. Synthesis of ximelagatran, melagatran, hydroxymelagatran, and ethylmelagatran in H-3 labeled form. J Labelled Comp Radiopharm. 2013;56:334-7 pubmed publisher
    ..The tritiated product was then converted into the four target compounds to afford them in high purity and specific activity. ..
  36. Ermolayev V, Cathomen T, Merk J, Friedrich M, Hartig W, Harms G, et al. Impaired axonal transport in motor neurons correlates with clinical prion disease. PLoS Pathog. 2009;5:e1000558 pubmed publisher
    ..These findings suggest novel targets for therapeutic and diagnostic approaches in the early stages of prion disease. ..
  37. Hondoh A, Ishida Y, Ugawa S, Ueda T, Shibata Y, Yamada T, et al. Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose-petrosal ganglion complex. Brain Res. 2010;1319:60-9 pubmed publisher
  38. Watson S, Nelson M, Wildering W. Redox agents modulate neuronal activity and reproduce physiological aspects of neuronal aging. Neurobiol Aging. 2012;33:149-61 pubmed publisher
  39. Renic M, Kumar S, Gebremedhin D, Florence M, Gerges N, Falck J, et al. Protective effect of 20-HETE inhibition in a model of oxygen-glucose deprivation in hippocampal slice cultures. Am J Physiol Heart Circ Physiol. 2012;302:H1285-93 pubmed publisher
    ..The protective effect of 20-HETE inhibitors is associated with a decrease in superoxide production and activation of caspase-3. ..
  40. Perrotta I, Carito V, Russo E, Tripepi S, Aquila S, Donato G. Macrophage autophagy and oxidative stress: an ultrastructural and immunoelectron microscopical study. Oxid Med Cell Longev. 2011;2011:282739 pubmed publisher
    ..Our data provide evidence that oxidative stress induces autophagy in macrophages. We demonstrate, for the first time by immunoelectron microscopy, the subcellular localization of beclin-1 in autophagic cells. ..
  41. Willis V, Gizinski A, Banda N, Causey C, Knuckley B, Cordova K, et al. N-?-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis. J Immunol. 2011;186:4396-404 pubmed publisher
    ..Cl-amidine may represent a novel class of disease-modifying agents that modulate aberrant citrullination, and perhaps other immune processes, necessary for the development of inflammatory arthritis. ..
  42. Feng J, Liu Z. Feruloylacetone as the model compound of half-curcumin: synthesis and antioxidant properties. Eur J Med Chem. 2011;46:1198-206 pubmed publisher
    ..The obtained results revealed that the antioxidant capacity of half-curcumin was derived from the phenolic-OH and the conjugated linkage between phenolic and enolic-OH. The enolic-OH itself cannot trap radicals. ..
  43. Slack J, Causey C, Luo Y, Thompson P. Development and use of clickable activity based protein profiling agents for protein arginine deiminase 4. ACS Chem Biol. 2011;6:466-76 pubmed publisher
    ..These probes will undoubtedly prove to be powerful tools that can be used to dissect the factors controlling the dynamics of PAD4 expression, activity, and function. ..
  44. Roe N, Ren J. Akt2 knockout mitigates chronic iNOS inhibition-induced cardiomyocyte atrophy and contractile dysfunction despite persistent insulin resistance. Toxicol Lett. 2011;207:222-31 pubmed publisher
    ..Taken together, these data indicated that an essential role of iNOS in the maintenance of cardiac morphology and function possibly through an Akt2-dependent mechanism. ..
  45. Iyaguchi D. Inhibition mechanism of trypsin by Schiff base metal chelate inhibitors. Yakugaku Zasshi. 2011;131:1299-303 pubmed
  46. Steinmetzer T, Kotthaus J, Schade D, van de Locht A, Clement B. Metabolism and distribution of two highly potent and selective peptidomimetic inhibitors of matriptase. Xenobiotica. 2010;40:93-101 pubmed publisher
    ..In summary, this work clarifies both the metabolism and distribution of two new matriptase inhibitors and demonstrates important metabolic differences between human enzymes and those from commonly used laboratory animals. ..
  47. Abreu P, Castro H, Paes de Carvalho R, Rodrigues C, Giongo V, Paixão I, et al. Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives. Chem Biol Drug Des. 2013;81:185-97 pubmed publisher
    ..reported as N-methyl-D-aspartic acid receptor antagonists, and used this data to rationally design the triazolyl-amidines. The best (quantitative) structure-activity relationship model constructed by multiple linear regression analysis ..
  48. Ito H, Ikeda M, Hasegawa T, Furusho Y, Yashima E. Synthesis of complementary double-stranded helical oligomers through chiral and achiral amidinium-carboxylate salt bridges and chiral amplification in their double-helix formation. J Am Chem Soc. 2011;133:3419-32 pubmed publisher
  49. Cornacchia D, Pellicani R, Intini F, Pacifico C, Natile G. Solution behavior of amidine complexes: an unexpected cis/trans isomerization and formation of di- and trinuclear platinum(III) and platinum(II) species. Inorg Chem. 2009;48:10800-10 pubmed publisher
    ..Complexes 1 and 2 have been characterized by means of IR and NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray crystallography. ..
  50. Asikin Y, Takahashi M, Mishima T, Mizu M, Takara K, Wada K. Antioxidant activity of sugarcane molasses against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced peroxyl radicals. Food Chem. 2013;141:466-72 pubmed publisher
    ..Ten phenolic constituents were identified in the fractions, including known antioxidative compounds, viz., schaftoside, isoschaftoside, ferulic acid, p-coumaric acid, and p-hydroxybenzaldehyde. ..
  51. An X, Zhuo H, Wang Y, Li Q. Competition between hydrogen bonds and halogen bonds in complexes of formamidine and hypohalous acids. J Mol Model. 2013;19:4529-35 pubmed publisher
    ..The structures, properties, and interaction nature in these complexes have been understood with natural bond orbital (NBO) and atoms in molecules (AIM) theories. ..
  52. Sinclair W, Leane M, Clarke G, Dennis A, Tobyn M, Timmins P. Physical stability and recrystallization kinetics of amorphous ibipinabant drug product by fourier transform raman spectroscopy. J Pharm Sci. 2011;100:4687-99 pubmed publisher
    ..The analysis showed that the JMA equation could describe the process very well, and indicated that the recrystallization kinetics observed was a two-step process with an induction period (nucleation) followed by rod-like crystal growth. ..
  53. Hantgan R, Stahle M. Integrin priming dynamics: mechanisms of integrin antagonist-promoted alphaIIbbeta3:PAC-1 molecular recognition. Biochemistry. 2009;48:8355-65 pubmed publisher