Imidazolyl Derivatives Research Articles

Azathioprine Hypersensitivity Syndrome in an Asian Woman

Azathioprine Hypersensitivity Syndrome in an Asian Woman

New 4H-thieno[3,2-b]pyrrole-5-carboxamides

A series of N-substituted 4H-thieno[3,2-b]pyrrole-5-carboxylic acids and their imidazolyl derivatives was synthesized. 4-Methyl-, 4-allyl-, and 4-benzyl derivatives of (4H-thieno[3,2-b]pyrrol-5-yl)carboxylic acid or their imidazolides were used in reactions with EtNH2 and indole sodium salt, providing the respective amides.

DEVELOPMENT OF A CREDIBLE QSAR AND K NEAREST NEIGHBOR MODELS FOR IMIDAZOLYL DERIVATIVES

Quantitative Structure-Activity Relationship studies were performed for correlating the imidazolyl derivatives and their activity using molecular modeling studies. The statistically significant best 2D model was having correlation coefficient = 0.8221 and cross-validated squared correlation coefficient = 0.7534 with external predictive ability of pred_r2 = 0.7716. Molecular field analysis was used to construct the best 3D-QSAR model showing good correlative and predictive capabilities in terms of q2 =0.6781 and pred_r2 =0.7299. The molecular field analysis (MFA) contour plots provided further understanding of the relationship between structural features of Imidazolyl derivatives and their activities which should be applicable to design newer potential antihypertensive agents.

Selective Imaging of Lipids in Adipocytes by Using an Imidazolyl Derivative of Perylene Bisimide.

A small molecule, perylene bisimide imidazolyl derivative (PBI-ID), has been identified and developed as a specific marker for labelling multifunctional fat bodies in various organisms, including Drosophila and mammalian adipocytes. Interestingly, PBI-ID neither labels the plasma membranes nor cell nuclei by trapping into it. A remarkable feature of unbound PBI-ID is diminished fluorescence, which reduces the background emission noise, while contrasting the bound state effectively.

Design and Synthesis of Some Imidazolyl Derivatives: Photophysical Studies and Application in the Detection of Anions

A fluorescent probe based on dicyanovinylphenanthroimidazole (DCPPI) has been designed and synthesized and its potential application to recognize F- and CN- ions via different channels have been tested in different mediums. DCPPI shows intramolecular charge transfer process and exhibit ratiometric response toward F- and CN- ions. The change in physicochemical properties of DCPPI in the presence of cyanide can be attributed to the formation of Michael type adduct, DCPPIA whereas both F- and CN- ions have shown affinities to interact with NH fragment of imidazolyl unit under the condition. The possible mode of interaction has been confirmed by absorption, emission, NMR and ESI-MS spectral data analysis.

Imidazolyl derivative of chitosan with high substitution degree: Synthesis, characterization and sorption properties

A method of synthesis of chitosan imidazolyl derivative – N-(5-methyl-4-imidazolyl)methylchitosan (IM-chitosan) with high degree of substitution (DS) via reaction with 5-methyl-4-imidazolylmethanol has been developed. This method enables one to obtain polymers with the DS up to 1.35 with simultaneous cross-linkage of the matrix. The chemical structure of the obtained IM-chitosan was characterized by FT-IR, 13C and 15N NMR spectroscopies. It was shown that cross-linkage of IM-chitosans occurred due to formation of N-glucoside derivatives. Sorption capacities of IM-chitosans toward transition metal ions have an extremal dependence on DS, which is less pronounced for Ag(I) ions in comparison with Cu(II) and Ni(II) ions. The decrease of sorption capacities for derivatives with DS 0.5–1.0 is attributed to steric hindrances for ion-binding due to increased stiffness of the polymer matrix at high DS as a result of cross-linking. Sorption capacities of IM-chitosans toward noble metal ions in 0.1M HCl gradually increase with DS, since higher swelling polymers in acidic media eliminates negative effect of cross-linking on availability of sorption sites.

ChemInform Abstract: Merger of Visible Light Induced Oxidation and Enantioselective Alkylation with a Chiral Iridium Catalyst.

AbstractChiral octahedral iridium(III) complex IBH having Δ‐configuration gives α‐diarylaminomethylated imidazolyl benzyl/alkyl ketones (III), (V) and (VII) in high yields with excellent enantioselectivities by photochemical reaction of corresponding imidazolyl derivatives with N,N‐diarylaminomethyltrimethylsilane (II).

Design and synthesis of some imidazolyl derivatives: Photophysical studies and application in detection of anions

Design and synthesis of some imidazolyl derivatives: Photophysical studies and application in detection of anions

Novel imidazolyl derivatives of 1,8-acridinedione as potential DNA-intercalating agents

The effect of twelve novel imidazolyl derivatives of 1,8-acridinedione (ligands) on calf thymus DNA was studied applying different biophysical techniques including UV-Vis spectrophotometry, CD spectropolarimetry and fluorimetric methods to gain deeper insights into the mechanism of interaction of the ligands with DNA. The binding parameters such as C50, K app, ΔGo (H2O) and m-value, followed by Scatchard analysis, indicate that among the tested ligands, four compounds; 12b, 13b, 12f and 13f, containing nitro and benzyl imidazole substituents, revealed uncompetitive intercalative mode of interaction with DNA. UV-Vis studies imply that the compounds bind cooperatively to DNA at the concentration range of 100-200 μM. Based on biophysical data, QSAR analysis, and docking simulations, we propose that in cytotoxic 1,8-acridinediones, the imidazole moiety is essential for pharmacological activity and the introduction of more flexible and electron-withdrawing substituents on the imidazole ring serves to enhance their DNA intercalating ability.

Synthesis, cytotoxicity and calcium antagonist activity of novel imidazolyl derivatives of 1,8-acridinediones

A series of novel imidazolyl derivatives of fully and partially hydrogenated 1,8-acridinediones were synthesized and assessed for their cytotoxic activity on four different human cancer cell lines (HeLa, MCF-7, LS-180, and Raji cells). Although being inactive on LS-180 and Raji cell lines, the compounds showed weak to moderate anti-tumor activities on other cell lines and their IC50 ranged from 31.7 to more than 100 μM. Among the synthesized compounds 12b, 13b, 12c and 13c, bearing an electronattracting substituent on the imidazole ring, and 12f and 13f, with a benzyl substituent, showed higher activities. Furthermore, the calcium channel antagonist activity of the derivatives, an undesired effect when these compounds are used as anti-tumor agents, was much lower than that of Nifedipine, a reference antagonist. Imidazolyl derivatives of 1,8-acridinedione represent an interesting template, showing promising biological properties. Further investigation on this chemical scaffold could potentially lead to the discovery of cytotoxic agents with low calcium channel blocking activity.

Synthesis of benzothiazole derivatives having acetamido and carbothioamido pharmacophore as anticonvulsant agents

A new series of N-(6-chlorobenzothiazol-2-yl)-2-substituted-acetamides (3a–h) and N-(6-chlorobenzothiazol-2-yl)-2-(substituted-benzylidene)hydrazinecarbothioamides (5a–h) were synthesized and characterized by IR, 1H NMR, mass and elemental analysis. In vivo anticonvulsant and acute toxicity screening of all the synthesized compounds showed morpholino (3f) and imidazolyl (3g) derivatives as promising anticonvulsant lead. Furthermore, In silico drug-likeness parameters have also been investigated for filtering out the likelihood of poor drug absorption or brain penetration. 3D four-point pharmacophore measurements of compounds were also carried out to match these with established anticonvulsants agents.

Design, Synthesis, and Biological Evaluation of Imidazolyl Derivatives of 4,7-Disubstituted Coumarins as Aromatase Inhibitors Selective over 17-α-Hydroxylase/C17−20 Lyase

The design, synthesis, and biological evaluation of a series of new aromatase (AR, CYP19) inhibitors bearing an imidazole ring linked to a 7-substituted coumarin scaffold at position 4 (or 3) are reported. Many compounds exhibited an aromatase inhibitory potency in the nanomolar range along with a high selectivity over 17-α-hydroxylase/C17-20 lyase (CYP17). The most potent AR inhibitor was the 7-(3,4-difluorophenoxy)-4-imidazolylmethyl coumarin 24 endowed with an IC(50) = 47 nM. Docking simulations on a selected number of coumarin derivatives allowed the identification of the most important interactions driving the binding and clearly indicated the allowed and disallowed regions for appropriate structural modifications of coumarins and closely related heterocyclic molecular scaffolds.

Tetrahedral silicon-centered imidazolyl derivatives: Promising candidates for OLEDs and fluorescence response of Ag (I) ion

A series of novel tetrahedral silicon-centered imidazolyl derivatives, Bis(4-(imidazol-1-yl)phenyl)dimethylsilane ( 1), Tri(4-(imidazol-1-yl)phenyl)methyl silane ( 2), Bis(4-(imidazol-1-yl)phenyl)diphenylsilane ( 3), Tri(4-(imidazol-1-yl)phenyl)phenylsilane ( 4), [Bis(4-(imidazol-1-yl)phenyl)](4-bromophenyl)phenylsilane ( 5) and [Tri(4-(imidazol-1-yl)phenyl)](4-bromophenyl)silane ( 6) have been synthesized and characterized by FTIR, 1H NMR, 13C NMR and mass spectroscopy. They all display high thermal stability, are fluorescent with emission in the region of violet to blue, and possess large HOMO-LUMO energy gaps ranging from 4.9585 to 5.1879 eV, which could be potentially used as blue emitters or hole blocking materials in OLEDs. Moreover, the metal ion titrations based on Ag (I) and compounds 1– 4 reveal that these ligands show distinguishable fluorescence response with increasing of Ag (I) ions.

Synthesis and antimicrobial screening of peptidyl derivatives of bromocoumarins/methylimidazoles.

In this investigation, it was of interest to synthesize novel series of peptide analogs of 3bromocoumarins and 2-methylimidazoles. Substituted coumarinyl-oxyacetic acids 1, 2 were synthesized by alkylation of corresponding hydroxycoumarins with chloroacetic acid. The imidazolyl derivatives 13, 14 were prepared by interaction of 2-methylimidazole with substituted/unsubstituted anthranilic acids. Coupling of compounds 1, 2, 13 and 14 with different amino acid methyl ester hydrochlorides, dipeptide, tripeptide and tetrapeptide methyl esters afforded novel coumarino/imidazolopeptide derivatives 3-10 and 15-22. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide to afford corresponding acid derivatives 11, 12 and 23, 24. The antibacterial and antifungal effects of synthesized peptide derivatives were studied against eight pathogenic microbes. Among the tested compounds, 19, 22 and its hydrolyzed analog 24 exhibited good antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae, Trichophyton mentagrophytes and Microsporum audouinii, and compounds 8, 10 and 12 displayed good antifungal activity against Candida albicans with minimum inhibitory concentration of 6.25 g/ml.

NG‐Acylated Aminothiazolylpropylguanidines as Potent and Selective Histamine H2 Receptor Agonists

The bioisosteric replacement of the guanidino group in arpromidine-like histamine H(2) receptor (H(2)R) agonists by an acylguanidine moiety is a useful approach to obtain potent H(2)R agonists with improved oral bioavailability and blood-brain barrier penetration. Unfortunately, the selectivity of such N(G)-acylated imidazolylpropylguanidines for the H(2)R is poor, in particular versus histamine H(3) (H(3)R) and H(4) receptors (H(4)R). This drawback appears to depend on the "privileged" imidazolylpropylguanidine structure. The 2-amino-4-methylthiazol-5-yl moiety is a bioisostere of the imidazole ring in the moderately potent H(2)R-selective histamine analogue amthamine. This approach was successfully applied to acylguanidine-type H(2)R agonists. The aminothiazoles are nearly equipotent to the corresponding imidazoles as H(2)R agonists. Compared with histamine, the potency is increased up to 40-fold on the guinea pig right atrium, and up to 125- and 280-fold in GTPase assays with human and guinea pig H(2)R-G(salphaS) fusion proteins expressed in Sf9 insect cells, respectively. Docking studies on H(2)R models support the hypothesis that 2-aminothiazolyl and imidazolyl derivatives interact with H(2)Rs as bioisosteres. In contrast to the imidazoles, the aminothiazoles are devoid of agonistic or relevant antagonistic effects on H(1), H(3), and H(4) receptors. Moreover, unlike amthamine, the 4-methyl group does not significantly contribute to the H(2)R agonism of N(G)-acylated 2-amino-4-methylthiazol-5-ylpropylguanidines.

Reactions of [Mo(≡CBr)(CO)2{HB(pzMe2)3}] (pz = pyrazol-1-yl) with Amines: Synthesis of Amino, Pyridinium, and Thiolato Carbyne Complexes

The reactions of the bromocarbyne complex [Mo(≡CBr)(CO)2{HB(pzMe2)3}] (pz = pyrazol-1-yl) with a range of secondary and heterocyclic amines have been investigated and found in each case to proceed via simple nucleophilic halide substitution to provide N-functionalized carbyne derivatives, some of which are not available via conventional approaches. With diethylamine or piperazine the simple dialkyaminocarbyne complexes [Mo(≡CNEt2)(CO)2{HB(pzMe2)3}] or [Mo{≡CN(C2H4)2NH}(CO)2{HB(pzMe2)3}] were obtained. With 4-N,N-dimethylaminopyridine the pyridiniumcarbyne salt [Mo(≡CNC5H4NMe2-4)(CO)2{HB(pzMe2)3}]Br was obtained; pyridine provided a complex intractable mixture and collidine failed to react. N-Methylimidazole provided the imidazolium derivative [Mo(≡CNC3H3NMe)(CO)2{HB(pzMe2)3}]Br, while N-(trimethylsilyl)imidazole gave the neutral imidazolyl derivative [Mo(≡CNC3H3N)(CO)2{HB(pzMe2)3}] and N,N′-bis(trimethylsilyl)imidazolium bromide. The sulfenamide HN(SPh)2 afforded the thiolatocarbyne complex [Mo(≡CSPh)(CO)2{HB(pzMe2)3}] rather than the expected aminocarbyne complex [Mo{≡CN(SPh)2}(CO)2{HB(pzMe2)3}], while HN(PPh2S)2 failed to react. The complex 1 is unreactive toward 1,8-diazabicycloundecene (DBU); however prolonged heating results in the formation of [DBUH][Mo(O)3{HB(pzMe2)3}] via base-induced hydrolysis/oxidation.

Novel Amidino-Substituted Thienyl- and Furylvinylbenzimidazole: Derivatives and Their Photochemical Conversion into Corresponding Diazacyclopenta[c]fluorenes. Synthesis, Interactions with DNA and RNA, and Antitumor Evaluation. 4

Synthesis of novel nonfused amidino-substituted thienyl- and furylvinylbenzimidazole: derivatives and their photochemical cyclization into corresponding diazacyclopenta[ c]fluorenes is described. All studied compounds showed prominent growth inhibitory effect. The fused compounds showed stronger activity than nonfused ones, whereby imidazolyl-substituted compound 11 proved to be the most active one. Besides, it induced strong G2/M arrest of the cell cycle followed by drastic apoptosis, which is in accordance with the DNA intercalative binding mode determined by the spectroscopic studies. Nonfused derivatives induced strong S phase arrest of the cell cycle followed by apoptosis that together with DNA minor groove binding mode pointed to topoisomerase I inhibition. In addition, all nonfused compounds revealed pronounced selectivity toward tumor cells in comparison with nontumor cells. On the basis of the presented results, both nonfused and fused thiophene-containing imidazolyl derivatives should be considered as promising lead compounds for further investigation.

Side‐Chain Modified Analogues of Histaprodifen: Asymmetric Synthesis and Histamine H1‐Receptor Activity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Side-chain modified analogues of histaprodifen: Asymmetric synthesis and histamine H 1-receptor activity

New analogues of histaprodifen with polar side chains have been stereoselectively synthesized and evaluated as histamine H 1-receptor agonists. As a key transformation the asymmetric aminohydroxylation has been used, which was successfully realized for the first time on an imidazolyl derivative. While all chiral analogues proved to be weak H 1-receptor antagonists, an achiral keto derivative of histaprodifen turned out to be the first 2-acylated histamine congener displaying partial H 1-receptor agonism (relative potency 12%).

Identification of potent non-peptide somatostatin antagonists with sst(3) selectivity.

Using a solution-phase parallel synthesis strategy, a series of non-peptide somatostatin analogues were prepared, and their binding affinities to the five human somatostatin receptor subtypes (sst(1-5)) were determined. Imidazolyl derivatives 2 were found to bind with moderate affinity but with high selectivity to the sst(3) receptor subtype. Further modifications of these structures led to a more potent class of ligands, the tetrahydro-beta-carboline derivatives 4. Among these, compounds 4k (BN81644) and 4n (BN81674) bind selectively and with high affinity to the sst(3) receptor subtype (K(i) = 0.64 and 0.92 nM, respectively). Furthermore, 4k and 4n reverse the inhibition of cyclic AMP accumulation induced by 1 nM somatostatin via sst(3) receptors, with IC(50) = 2.7 and 0.84 nM, respectively. The most potent compound 4n was shown to be a competitive antagonist of human sst(3) receptors by increasing the EC(50) of SRIF-14-mediated inhibition of cAMP accumulation with a K(B) of 2.8 nM (where K(B) is the concentration of antagonist that shifts the agonist dose-response 2-fold). These new derivatives are, to our knowledge, the first potent and highly selective non-peptide human sst(3) antagonists known and, as such, are useful tools for investigating the physiological role of sst(3) receptors.