- 1-benzoyl-3-(4-nitrophenyl)thiourea
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In the molecules of the title compound, C14H11N3O3S, there is an intramolecular N-H...O hydrogen bond [2.635 (3) A] between the amide N and benzoyl O atoms which completes a nearly planar six-membered ring in the central part of the molecule. The benzene rings of the benzoyl and nitrophenyl moieties form angles of 30.5 (4) and 35.7 (4)°, respectively, with the plane of this hydrogen-bonded ring. In the crystal, molecules are connected into infinite zigzag chains by N-H...O bonds and these chains are linked across centres of symmetry by weak N-H...S interactions, thus forming a two-dimensional network. Van der Waals interactions between layers lead to a crystal structure with one very short axis (4 A).
- Zhang, De-Chun,Zhang, Yan-Qiu,Cao, Yang,Zhao, Bo
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- Benzoylthioureas: Design, synthesis and antimycobacterial evaluation
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Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed. In this context, thiourea derivatives have a wide range of biological activities, including anti-TB. This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea as a pharmacophore group. Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of fifty-nine benzoylthioureas derivatives. Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship study of this series of compounds has been performed. Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1 and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the para-position in benzene ring plays an important role in the antitubercular activity of Series A. These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2 and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general, Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles. Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the first line anti-TB drug ethambutol and 0.65 times less active than isoxyl.
- Abreu, Lethícia O.,Bispo, Marcelle L. F.,Brito, Tiago O.,Gomes, Karen M.,Louren?o, Maria C. S.,Macedo, Fernando,Pereira, Patricia M. L.,Tisher, Cesar A.,Yamada-Ogatta, Sueli F.,de Fátima, ?ngelo
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- Design, synthesis and algicides activities of thiourea derivatives as the novel scaffold aldolase inhibitors
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By using a new Fragment-Based Virtual Screen strategy, two series of novel FBA-II inhibitors (thiourea derivatives) were de novo discovered based on the active site of fructose-1, 6-bisphosphate aldolase from Cyanobacterial (CyFBA). In comparison, most of the N-(2-benzoylhydrazine-1-carbonothioyl) benzamide derivatives (L14~L22) exhibit higher CyFBA-II inhibitory activities compared to N-(phenylcarbamothioyl) benzamide derivatives (L1~L13). Especially, compound L14 not only shows higher CyFBA-II activity (Ki = 0.65 μM), but also exhibits most potent in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.09 ppm), higher (7-fold) than that of our previous inhibitor (EC50 = 0.6 ppm). The binding modes of compound L14 and CyFBA-II were further elucidated by jointly using DOX computational protocol, MM-PBSA and site-directed mutagenesis assays. The positive results suggest that strategy adopted in this study was promising to rapidly discovery the potent inhibitors with novel scaffolds. The satisfactory algicide activities suggest that the thiourea derivatives is very likely to be a promising lead for the development of novel specific algicides to solve Cyanobacterial harmful algal blooms (CHABs).
- Xiao, Shan,Wei, Lin,Hong, Zongqin,Rao, Li,Ren, Yanliang,Wan, Jian,Feng, Lingling
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p. 805 - 812
(2019/02/03)
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- N, N′ N″-trisubstituted guanidines: Synthesis, characterization and evaluation of their leishmanicidal activity
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Leishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000–30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, 1H and 13C NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC50-ama 5.6 μM; SI = 131.8) and LQOF-G7 (IC50-ama 7.1 μM; SI = 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis.
- do Espírito Santo, Rafael Dias,Velásquez, ángela María Arenas,Passianoto, Luana Vitorino Gushiken,Sepulveda, Alex Arbey Lopera,da Costa Clementino, Leandro,Assis, Renata Pires,Baviera, Amanda Martins,Kalaba, Predrag,dos Santos, Fábio Neves,éberlin, Marcos Nogueira,da Silva, Gil Valdo José,Zehl, Martin,Lubec, Gert,Graminha, Márcia Aparecida Silva,González, Eduardo René Pérez
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p. 116 - 128
(2019/03/26)
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- Synthesis, characterization and chemosensitivity studies of half-sandwich ruthenium, rhodium and iridium complexes containing к1(S) and к2(N,S) aroylthiourea ligands
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The reaction of [(p-cymene)RuCl2]2 and [Cp*MCl2]2 (M = Rh/Ir) metal precursors with aroylthiourea ligands (L1-L3) yielded a series of neutral mono-dentate complexes 1–9. The neutral mono-dentate coordination of aroylthiourea with metals via S atom was confirmed by single crystal X-ray diffraction study. Further reaction of mono-dentate complexes 1–9 with excess NaN3 in polar solvent resulted in the formation of highly strained four member ring к2(N,S) azido complexes 10–18. Further these complexes were treated with activated alkynes to isolate triazole complexes, but unfortunately the reaction was unsuccessful. All these complexes were fully characterized by various spectroscopic techniques. The molecular structures of the representative complexes have been determined by single crystal X-ray diffraction studies. The molecular structures of the complexes revealed typical piano stool geometry around the metal center. The chemosensitivity activities of the complexes 1–9 evaluated against the cancer cell line HCT-116 (human colorectal carcinoma) and ARPE-19 (human retinal epithelial cells) cell line. Of these, complex 3 was the most potent and whilst its potency was less than cisplatin, its selectivity for cancer as opposed to non-cancer cell lines in vitro was comparable to cisplatin.
- Lapasam, Agreeda,Hussain, Omar,Phillips, Roger M.,Kaminsky, Werner,Kollipara, Mohan Rao
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p. 272 - 280
(2018/11/26)
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- Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines
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An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC50 values of about half that of the IC50 of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.
- Gon?alves, Itamar Luís,Rockenbach, Liliana,Das Neves, Gustavo Machado,G?ethel, Gabriela,Nascimento, Fabiana,Porto Kagami, Luciano,Figueiró, Fabrício,Oliveira De Azambuja, Gabriel,De Fraga Dias, Amanda,Amaro, Andressa,De Souza, Lauro Mera,Da Rocha Pitta, Ivan,Avila, Daiana Silva,Kawano, Daniel Fábio,Garcia, Solange Cristina,Battastini, Ana Maria Oliveira,Eifler-Lima, Vera Lucia
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p. 995 - 1010
(2018/06/27)
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- Benzoylguanidines as Anion-Responsive Systems
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A series of benzoylguanidinium salts was prepared and the changes in UV/Vis spectra, triggered by the presence of anions, were investigated. All compounds undergo deprotonation with basic anions like dihydrogenphosphate and acetate in acetonitrile. The most pronounced spectral changes were obtained by deprotonation of N1-benzoyl-N3-(p-nitrophenyl) guanidinium chloride which shows the naked-eye visible color change from colorless to yellow. Measured pKa(BH+) in acetonitrile ranges from 12–16, which is comparable to the pyridinium cations. The proton transfer equilibria were also tested in acetonitrile/water mixture where all but the most acidic derivatives showed pKa(BH+) of 4–6 units which corresponds to apparent association constants of 104–106 dm3 mol?1. UV/Vis spectra of neutral and protonated forms were modelled by the TD-DFT approach using CAM-B3LYP and PBE0 functionals and compared to CC2 results. In the case of CAM-B3LYP, a parameter ω, defining amount of long-range exchange correction, was varied to achieve the best agreement with the experimental spectra. The optimized ω parameters are 0.10 a0?1 for neutral benzoylguanidines and 0.20 a0?1 for neutral nitrobenzoyl and protonated systems. The larger ω parameter in the latter is ascribed to more pronounced charge transfer character of the HOMO-LUMO transition – the one responsible for the lowest energy absorption band.
- Antol, Ivana,Bare?i?, Luka,Glasovac, Zoran,Margeti?, Davor
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p. 845 - 854
(2018/10/05)
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- Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against: Klebsiella pneumoniae
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A series of fused bicyclic 2-aminothiazolyl compounds were synthesized and evaluated for their synergistic effects with polymyxin B (PB) against Klebsiella pneumoniae (SIPI-KPN-1712). Some of the synthesized compounds exhibited synergistic activity. When 4 μg ml-1 compound B1 was combined with PB, it showed potent antibacterial activity, achieving 64-fold reduction of the MIC of PB. Furthermore, compound B1 showed prominent synergistic efficacy in both concentration gradient and time-kill curves in vitro. In addition, B1 combined with PB also exhibited synergistic and partial synergistic effect against E. coli (ATCC25922 and its clinical isolates), Acinetobacter baumannii (ATCC19606 and its clinical isolates), and Pseudomonas aeruginosa (Pae-1399).
- Wang, Rong,Hou, Shuang,Dong, Xiaojing,Chen, Daijie,Shao, Lei,Qian, Liujia,Li, Zhong,Xu, Xiaoyong
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p. 2060 - 2066
(2017/11/22)
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- Synthesis and antitumor evaluation of 5-(benzo[: D] [1,3]dioxol-5-ylmethyl)-4-(tert -butyl)- N -arylthiazol-2-amines
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A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1-C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.
- Wu,Fang,Tang,Xiao,Ye,Li,Hu
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p. 1768 - 1774
(2016/09/28)
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- Synthesis and Cytotoxicity in Vitro of N-Aryl-4-(Tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine
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A series of novel N-aryl-4-(tert-butyl)-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amines were synthesized in a green way. H2O2-NaBr Brominating circulatory system was used in the synthesis of the key intermediate in a mild condition. All of the target compounds were confirmed by1H NMR and elemental analysis and tested for their cytotoxicity against two different human cancer cell lines. The cytotoxicity assay revealed that some of the title compounds showed moderate to strong cytotoxic activities. Compound 2i was the most potent compound with the IC50 values of 9 μMagainst Hela cells and 15 μMagainst Bel-7402 cells, respectively.
- Ye, Jiao,Xiao, Meng-Wu,Xie, Xuan-Qing,Qiu, Shen-Yi,Dai, Ming-Chong,Li, Wan,Shen, Fang,Hu, Ai-Xi
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p. 627 - 631
(2018/01/18)
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- A simple one-pot methodology for the synthesis of substituted benzoylguanidines from benzoylthioureas using tert-butyl hydroperoxide
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The potential of tert-butyl hydroperoxide as a reagent in the guanylation of benzoylthioureas in the presence of amines has been evaluated in a systematic study involving substrates bearing N2-substituents with different electronic properties. The results show that tBuOOH is a suitable and robust reagent for the synthesis of either N1,N2,N3-tri- and tetrasubstituted or N1,N2-disubstituted guanidines from N2-substituted N1-benzoylthioureas and N1-benzoylthioureas, respectively. The recrystallised guanylation adducts were readily obtained in good yields and at high purity levels after a simple one-pot reaction procedure. The crystal structures of two novel benzoylguanidines are provided.
- Esteves, Henrique,De Fátima, ?ngelo,Castro, Rosane De P.,Sabino, José R.,MacEdo, Fernando,Brito, Tiago Oliveira
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supporting information
p. 6872 - 6874
(2015/11/27)
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- Design, syntheses and evaluation of benzoylthioureas as urease inhibitors of agricultural interest
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Urea is one of the most used nitrogen fertilizers worldwide. However, occurrence of urea hydrolysis to ammonia and carbon dioxide on soil surface, catalyzed by soil ureases, considerably reduces nitrogen availability to crops. In this study, we describe the design, synthesis and screening of sixty five benzoylthioureas (BTUs) for their ability to inhibit purified jack bean and soil ureases. BTUs were readily obtained in one pot, two steps synthesis with no need of cumbersome procedures for product purification. In vitro assays revealed BTUs 11, 12, 14, 19-22 and 37 as the most active jack bean urease inhibitors. Such BTUs were found to be able to bind to both catalytic and allosteric sites of urease, acting therefore as mixed-type inhibitors. Out of 28 compounds that effectively inhibited soil ureases activity, BTUs 3, 6, 10, 12, 16, 19 and 22 were determined to be more potent than the reference inhibitor N-(butyl) thiophosphoric triamide (NBPT; 40%). The other 22 BTUs were as potent as NBPT on soil ureases. The temperature-tolerance of BTUs, along with their ability to inhibit soil ureases, makes of this class of compounds potential additive for urea-based fertilizers.
- Brito, Tiago O.,Souza, Aline X.,Mota, Yane C. C.,Morais, Vinicius S. S.,De Souza, Leandro T.,De Fátima, ?ngelo,Macedo, Fernando,Modolo, Luzia V.
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p. 44507 - 44515
(2015/06/02)
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- Synthesis, Chemical Characterization, DNA Interaction and Antioxidant, Studies of New Nitrosubstituted Thioureas and Their Copper Complexes
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In the present work new nitro substituted thioureas, and their copper complexes have been synthesized and characterized by FTIR and multinuclear NMR techniques. Some of the compounds namely 1-benzoyl-3-(4-chloro-3-nitrophenyl) thiourea (A-1), 1-benzoyl-3-(4-chloro-3-nitrophenyl) thiourea (A-2) and 1-benzoyl-3-(2-methoxy-4-nitrophenyl) thiourea (A-2) have also been characterized by single crystal XRD. All the synthesized compounds have been screened for DNA binding potencies (using cyclic voltametry, UV-vis spectroscopy) and free radical scavanging activities.
- Patujo, Jahangeer,Badshah, Amin,Hussain, Raja Azadar,Tahir, Muhammad Nawaz,Tahir, Shaista,Rauf, Muhammad Khawar
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p. 1020 - 1027
(2015/12/01)
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- Synthesis of new 2-aminoimidazolones with antiproliferative activity via base promoted amino-β-lactam rearrangement
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A facile and efficient transformation of amino-β-lactam guanidines to 2-aminoimidazolones is described. The base-promoted transformation proceeds in two steps, with the rearrangement of four-membered β-lactam ring to five-membered imidazolone and subsequent E1cB elimination and formation of double bond at the 4-position of imidazolone ring, which is supported with quantum chemical calculations. The benzoylaminoimidazolone and 2-aminoimidazolone products are obtained in high yields. The benzoylaminoimidazolone products show antiproliferative activity in HCT116 (colon carcinoma) and H460 (lung carcinoma) cell lines.
- Dra?i?, Tonko,Vazdar, Katarina,Vazdar, Mario,Crossed D Signakovi?, Marijana,Mikecin, Ana-Matea,Kralj, Marijeta,Malnar, Martina,He?imovi?, Silva,Habu?, Ivan
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p. 9202 - 9215
(2015/11/27)
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- Experimental NMR and MS study of benzoylguanidines. Investigation of E/Z isomerism
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Molecules containing the guanidinic nuclei possess several pharmacological applications, and knowing the preferred isomers of a potential drug is important to understand the way it operates pharmacologically. Benzoylguanidines were synthesized in satisfactory to good yields and characterized by NMR, Electrospray Ionization Mass Spectrometry (ESI-MS) and Fourrier Transform InfraRed Spectroscopy techniques (FTIR). E/Z isomerism of the guanidines was studied and confirmed by NMR analysis in solution (1H-13C Heteronuclear Single Quantum Coherence (HSQC) and Heteronuclear Multiple-Bond Correlation (HMBC), 1H-15N HMBC, 1H- 1H Correlation Spectroscopy (COSY) and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments) at low temperatures. Compounds with p-Cl and p-Br aniline moiety exist mainly as Z isomer with a small proportion of E isomer, whereas compounds with p-NO2 moiety showed a decrease in proportion of isomer Z. The results are important for the application of these molecules as enzymatic inhibitors. Copyright
- Santo, Rafael Dias Do Espirito,Simas, Rosineide Costa,Magalhaes, Alvicler,Santos, Vanessa Goncalves Dos,Regiani, Thais,Isler, Ana Cristina,Martins, Natiza Graziele,Eberlin, Marcos Nogueira,Gonzalez, Eduardo Rene Perez
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p. 315 - 321
(2013/05/09)
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- Facile synthesis, antibacterial activity and molecular properties prediction of some new 1, 3-dihydroimidazol-2-thione derivatives
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Present communication deals with the study of antibacterial activity and molecular properties prediction of some new 1, 3-dihydroimidazol-2-thione derivatives (1b-6b) obtained by cyclo-condensation reaction between 1-benzoyl-3-(substituted phenyl) thioureas (A) with triethylamine in the presence of bromine. The structures of these newly synthesized compounds were confirmed by their chemical, spectral and elemental analysis. All the compounds exhibited weak to moderate in-vitro antibacterial activity against representative Gram-positive and Gram-negative microorganisms. It was found that different substitution pattern on core bioactive scaffold 1, 3-dihydroimidazol-2-thione causes a dramatic variation in antibacterial profile. Target compounds were further subjected to molecular properties prediction and drug-likeness by Molinspiration and found in compliance with Lipinski 'Rule of Five' (Ro5) and presented a good drug-likeness score with no violations.
- Junejo, Julfikar Ali,Ghosh, Surajit Kumar,Shaikh, Mutahar,Gahtori, Prashant,Singh, Udaya Pratap
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p. 763 - 768
(2012/05/05)
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- Antimicrobial activity and structural study of disubstituted Thiourea Derivatives
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The antimicrobial activity of six N-phenyl- and fourteen N-benzoylthiourea derivatives were evaluated from their Minimal Inhibitory Concentration (MIC) values using the microdilution procedure against ten microorganisms. Most of the compounds exhibited selective activity against fungi and Gram-positive bacteria, which were very effectively inhibited by some of the tested thioureas. Additionally, SAR considerations and four novel X-ray diffraction structures of N-benzoylthioureas are included. Springer-Verlag 2007.
- Cunha, Silvio,MacEdo Jr., Fernando C.,Costa, Giselle A. N.,Rodrigues Jr., Manoel T.,Verde, Rosival B. V.,De Souza Neta, Lourdes C.,Vencato, Ivo,Lariucci, Carlito,Sa, Fernando P.
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p. 511 - 516
(2008/02/03)
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- A convenient and efficient method for the synthesis of mono- and N,N-disubstituted thioureas
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A convenient method for the synthesis of mono- and N,N-disubstituted thioureas by the debenzoylation of N-substituted- and N,N-disubstituted- N′-benzoylthioureas with hydrazine hydrate under solvent-free conditions has been developed. N-Substituted-N′-benzoylthioureas and hydrazine hydrate were mixed, and stirred at room temperature without a solvent to give the corresponding N-substituted thioureas in high yields.
- Kodomari, Mitsuo,Suzuki, Masato,Tanigawa, Keiko,Aoyama, Tadashi
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p. 5841 - 5843
(2007/10/03)
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- One-pot three-step synthesis of 3-aryl-2-benzoylimino-4-thiazolidinones in the ionic liquid [bmim+][PF6-]
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3-Aryl-2-acylimino-4-thiazolidinones are efficiently formed in 1-n-butyl-3-methylimidazolium hexafluorophosphate [bmim][PF6] as solvent in a one-pot three-step procedure. The ionic solvent could be recovered and recycled four times with no diminution in yields.
- Peng, Yanqing,Song, Gonghua,Huang, Feifei
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p. 676 - 678
(2007/10/03)
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- Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents
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A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, σ or μ) having high statistical significance > 99.9% (F2,22 > 15.0; F2,22α:0.001 = 11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.
- Saxena, Anil K.,Pandey, Suresh K.,Seth,Singh,Dikshit,Carpy
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p. 2025 - 2034
(2007/10/03)
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- Substituted N-phenylisothioureas: Potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity
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S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L,-arginine.
- Shearer, Barry G.,Lee, Shuliang,Oplinger, Jeffrey A.,Frick, Lloyd W.,Garvey, Edward P.,Furfine, Eric S.
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p. 1901 - 1905
(2007/10/03)
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- Improved Procedures for the Preparation of Cycloalkyl-, Arylalkyl-, and Arylthioureas
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An improved procedure for the preparation of arylthioureas consists of the reaction of benzoyl isothiocyanate with anilines in acetone and debenzoylation of the resultant N-aryl-N'-benzoylthioureas with 5percent aqueous sodium hydroxide.Bicycloalkylthioureas and N-(arylalkyl)thioureas (e.g. 9H-9-fluorenylthiourea) are directly prepared from the corresponding isothiocyanates and ammonia.
- Rasmussen, C. R.,Villani, F. J.,Weaner, L. E.,Reynolds, B. E.,Hood, A. R.,et al.
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p. 456 - 459
(2007/10/02)
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- KINETICS AND MECHANISM OF METHANOLYSIS OF BENZOYL DERIVATIVES OF SUBSTITUTED PHENYLUREAS AND PHENYLTHIOUREAS
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The methanolysis rate constants and dissociation constants have been measured of benzoyl derivatives of substituted phenylureas and phenylthioureas.The dissociation constants of the thio derivatives are higher by 1 order of magnitude and the rate constants are higher by 2 orders of magnitude than the respective values of the oxygen analogues.Logarithms of the rate and dissociation constants have been correlated with Hammett ? constant; the ρ constant of the methanolysis of the oxygen derivatives is almost 2 * higher than that of the thio derivatives, which is explained by a change in the rate-limiting step.Methylation of the phenyl nitrogen atom increases the acidity by almost 2 orders of magnitude.This effect is due obviously to steric hindrance to the conjugation with the adjacent carbonyl or thiocarbonyl group.
- Kavalek, Jaromir,El Bahaie, Said,Sterba, Vojeslav
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p. 2103 - 2110
(2007/10/02)
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