- Tris(2-aminoethyl)amine, a suitable spacer for phosphate and sulphate receptors
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Tris(2-aminoethyl)amine and cis-1,3,5-tris(aminomethyl)cyclohexane have been checked as spacers for phosphate receptors.Ureas are better binding arms then thioureas for these spacers while the combination of this first functional group with chromenone fra
- Raposo, Cesar,Almaraz, Marta,Martin, Mercedes,Weinrich, Volker,Mussons, M Luisa,et al.
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Read Online
- Practical one-pot amidation of N -Alloc-, N -Boc-, and N -Cbz protected amines under mild conditions
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A facile one-pot synthesis of amides from N-Alloc-, N-Boc-, and N-Cbz-protected amines has been described. The reactions involve the use of isocyanate intermediates, which are generated in situ in the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, to react with Grignard reagents to produce the corresponding amides. Using this reaction protocol, a variety of N-Alloc-, N-Boc-, and N-Cbz-protected aliphatic amines and aryl amines were efficiently converted to amides with high yields. This method is highly effective for the synthesis of amides and offers a promising approach for facile amidation.
- Hong, Wan Pyo,Tran, Van Hieu,Kim, Hee-Kwon
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p. 15890 - 15895
(2021/05/19)
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- Chloride transport activities of trans- and cis-amide-linked bisureas
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Of the bisurea compounds linked through trans- and cis-benzanilide spacers, the cis-amide derivatives were found to be effective in chloride transport, using which a stimuli-responsive mobile carrier was devised. This journal is
- Park, Eun Bit,Jeong, Kyu-Sung
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supporting information
p. 9197 - 9200
(2015/06/02)
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- Synthesis of unsymmetrical biaryl ureas from N-carbamoylimidazoles: Kinetics and application
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N-Carbamoylimidazoles dissociate in solution to yield imidazole and an isocyanate that may be reacted with another aryl amine to form an unsymmetrical biaryl urea. This paper investigates the reaction kinetics and the influence of electron withdrawing/donating substituents on the reaction of N-carbamoylimidazoles with aniline. The overall reaction mechanism involves two zwitterionic intermediates, formed during dissociation and upon reaction of the liberated isocyanate with aniline. The rate limiting step for the reaction is a base catalysed proton transfer from the second zwitterionic intermediate. Although electron withdrawing substituents on the aryl group hinder dissociation, they significantly increase reaction rates compared to compounds bearing electron donating substituents. The imidazole liberated upon dissociation catalyses the rate determining step so that reactions of dissociated N-carbamoylimidazoles proceed more rapidly than those involving only isocyanates. In addition, the imidazole eliminates the need for anhydrous reaction conditions. The N-carbamoylimidazole methodology was demonstrated by preparing sorafenib, a biaryl urea kinase inhibitor, in good yield and excellent purity.
- Rawling, Tristan,McDonagh, Andrew M.,Tattam, Bruce,Murray, Michael
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experimental part
p. 6065 - 6070
(2012/09/22)
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- Inhibitors of Dengue virus and West Nile virus proteases based on the aminobenzamide scaffold
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Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses that cause significant morbidity and mortality. There is no approved vaccine or antiviral drugs for human use to date. In this study, a series of functionalized meta and para aminobenzamide derivatives were synthesized and subsequently screened in vitro against Dengue virus and West Nile virus proteases. Four active compounds were identified which showed comparable activity toward the two proteases and shared in common a meta or para(phenoxy)phenyl group. The inhibition constants (Ki) for the most potent compound 7n against Dengue and West Nile virus proteases were 8.77 and 5.55 μM, respectively. The kinetics data support a competitive mode of inhibition of both proteases by compound 7n. This conclusion is further supported by molecular modeling. This study reveals a new chemical scaffold which is amenable to further optimization to yield potent inhibitors of the viral proteases via the combined utilization of iterative medicinal chemistry/structure-activity relationship studies and in vitro screening.
- Aravapalli, Sridhar,Lai, Huiguo,Teramoto, Tadahisa,Alliston, Kevin R.,Lushington, Gerald H.,Ferguson, Eron L.,Padmanabhan,Groutas, William C.
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experimental part
p. 4140 - 4148
(2012/09/08)
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- DNA-templated release of functional molecules with an azide-reduction- triggered immolative linker
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Nucleic acid templated reactions have attracted significant attention for nucleic acid sensing. Herein we report a general design which extends the potential of nucleic acid templated reactions to unleash the function of a broad diversity of small molecules such as a transcription factor agonist, a cytotoxic or a fluorophore.
- Gorska, Katarzyna,Manicardi, Alex,Barluenga, Sofia,Winssinger, Nicolas
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supporting information; experimental part
p. 4364 - 4366
(2011/06/19)
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- Organosilicon synthesis of isocyanates: III. Synthesis of aliphatic, carbocyclic, aromatic, and alkylaromatic isocyanatocatboxylic acid esters
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A series of aminoacid esters was prepared by treating the aminoacid suspensions in ethanol with thionyl chloride. Best conversion of aminoacid esters to corresponding isocyanates was achieved in the case of aromatic and carbocyclic aminoesters by phosgeneation of their N-silyl derivatives, and in the case of aliphatic and alkylaromatic aminoesters by phosgeneation of O-silyl or N,O-bissilylurethanes on their basis. In the last case additional step of esterification of the by-products isocyanatoalkylcarboxylic acid chlorides is required after phosgeneation. Unusual generation of cynnamates and intramolecular N→O-migration of trimethylsilyl group in the solutions of silylated alkylaromatic β-aminoacid esters were found. Pleiades Publishing, Inc., 2006.
- Lebedev,Lebedeva,Sheludyakov,Ovcharuk,Kovaleva,Ustinova
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p. 1069 - 1080
(2008/02/05)
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- Tyrosine kinase inhibitors. 4. Structure-activity relationships among N- and 3-substituted 2,2'-dithiobis(1H-indoles) for in vitro inhibition of receptor and nonreceptor protein tyrosine kinases
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A series of 3-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC50s 1-20 μM), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60(v-src). A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N- thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60(v-src) kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC50s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol- containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.
- Palmer,Rewcastle,Thompson,Boyd,Showalter,Sercel,Fry,Kraker,Denny
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- Quantitative Structure-Activity Relationships of Insecticidal Pyrazolines
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Methyl 3-(4-chlorophenyl)-4-methyl-1--2-pyrazoline-4-carboxylates and related compounds were prepared. Their convulsant activity was determined as the minimum dose required to bring about the symptom within 1 h after injection against male adult American cockroaches, Periplaneta americana (L.). Insecticidal activity with metabolic inhibitors for oxidation and hydrolysis was measured 24 h after injection of the test compounds. Variations in each of the activities were analysed by using physicochemical substituent parameters and regression analysis. The findings indicated that the greater the hydrophobicity and the more the electron-withdrawing property of the substituents, the higher were the activities. Variations in each of the two activities were parabolically related to the STERIMOL width parameter with an optimum value of about zero.
- Hasan, Riaz,Nishimura, Keiichiro,Ueno, Tamio
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p. 291 - 298
(2007/10/03)
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