- Structure-Activity Relationship in the Leucettine Family of Kinase Inhibitors
-
The protein kinase DYRK1A is involved in Alzheimer's disease, Down syndrome, diabetes, viral infections, and leukemia. Leucettines, a family of 2-aminoimidazolin-4-ones derived from the marine sponge alkaloid Leucettamine B, have been developed as pharmacological inhibitors of DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases). We report here on the synthesis and structure-activity relationship (SAR) of 68 Leucettines. Leucettines were tested on 11 purified kinases and in 5 cellular assays: (1) CLK1 pre-mRNA splicing, (2) Threonine-212-Tau phosphorylation, (3) glutamate-induced cell death, (4) autophagy and (5) antagonism of ligand-activated cannabinoid receptor CB1. The Leucettine SAR observed for DYRK1A is essentially identical for CLK1, CLK4, DYRK1B, and DYRK2. DYRK3 and CLK3 are less sensitive to Leucettines. In contrast, the cellular SAR highlights correlations between inhibition of specific kinase targets and some but not all cellular effects. Leucettines deserve further development as potential therapeutics against various diseases on the basis of their molecular targets and cellular effects.
- Tahtouh, Tania,Durieu, Emilie,Villiers, Beno?t,Bruyère, Céline,Nguyen, Thu Lan,Fant, Xavier,Ahn, Kwang H.,Khurana, Leepakshi,Deau, Emmanuel,Lindberg, Mattias F.,Sévère, Elodie,Miege, Frédéric,Roche, Didier,Limanton, Emmanuelle,L’Helgoual’ch, Jean-Martial,Burgy, Guillaume,Guiheneuf, Solène,Herault, Yann,Kendall, Debra A.,Carreaux, Fran?ois,Bazureau, Jean-Pierre,Meijer, Laurent
-
supporting information
p. 1396 - 1417
(2022/01/03)
-
- Synthesis and exploration of configurational dynamics in equilibrating E/Z 2-aryliminothiazolidin-4-ones using NMR and estimation of thermodynamic parameters
-
In the present study, 2-aryliminothiazolidin-4-ones (3 and 5) were utilized as dynamic chemical systems, whose different states are modulated in a reversible fashion through specific chemical stimuli. The in-depth NMR investigation revealed that the magnitude of rotational energy barrier (ΔG?) is affected markedly by (1) the solvent polarity; (2) the electronic nature of the ring system present on the exocyclic CQN bond and (3) the temperature of the system. The derivatives of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one exist in two isomeric forms at room temperature in DMSO-d6: (2E,5Z,7E) ? (2Z,5Z,7E). The stereodynamics of the synthesized derivatives (5a-5t) has been investigated using variable temperature dynamic 1H-NMR (VT DNMR). The ΔG? values (≈15 kcal mol?1) estimated for the dynamic process depict a significant barrier between two forms in solution at ambient temperature. To go a step further, line shape analysis was also performed to get a clear understanding of the equilibration mechanism.
- Devi, Meena,Kumar, Parvin,Sindhu, Jayant,Singh, Rahul
-
p. 5012 - 5025
(2022/04/07)
-
- SO2F2-Mediated N-Alkylation of Imino-Thiazolidinones
-
The N-alkylation of ambident and weakly nucleophilic imino-thiazolidinones has been developed via substitution with alkyl fluorosulfonates. These reactive electrophiles are obtained through the transformation of nontoxic, economic, and commercially availa
- Santos, Laura,Donnard, Morgan,Panossian, Armen,Vors, Jean-Pierre,Jeschke, Peter,Bernier, David,Pazenok, Sergii,Leroux, Frédéric R.
-
p. 2012 - 2021
(2021/09/02)
-
- Design and microwave synthesis of new (5z) 5-arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5z) 2-amino-5-arylidene-1,3-thiazol-4(5h)-one as new inhibitors of protein kinase dyrk1a
-
Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradi
- Bazureau, Jean-Pierre,Bourahla, Khadidja,Carreaux, Fran?ois,Charlier, Thierry,Durieu, Emilie,Guihéneuf, Solène,Le Guével, Rémy,Limanton, Emmanuelle,Lozach, Olivier,Meijer, Laurent,Paquin, Ludovic,Rahmouni, Mustapha
-
-
- Synthesis of Novel Triazole Incorporated Thiazolone Motifs Having Promising Antityrosinase Activity through Green Nanocatalyst CuI-Fe3O4@SiO2 (TMS-EDTA)
-
In the present work, novel 5-((1-benzyl-1,2,3-triazol-4-yl)methoxybenzylidene)-2-(arylamino)thiazol-4-one thiazolone incorporated triazole derivatives have been designed as tyrosinase inhibitors. The compounds were synthesized through click reaction in good yield. Moreover, the antityrosinas activity of the synthesized derivatives was evaluated. In the search for establishing a click copper-catalyzed azide/alkyne cycloaddition (CuAAC) reaction under strict conditions, in terms of a novel air-stable, a recyclable and efficient magnetic catalyst was planned for new triazole derivatives as a well-organized copper iodide supported on the functionalized Fe3O4@SiO2 core-shell (CuI/Fe3O4@SiO2(TMS-EDTA) nanoparticles). The engineered nanocatalyst synthesized for the first time and characterized by different methods, including FT-IR spectroscopy, XRD, FESEM, EDX, TEM, TGA, and BET analysis. The excellent catalytic performance in ethanol with high surface area (351.7 m2g?1) and short reaction time for diverse functional groups (120–200 min), no use of toxic solvents, reusability of the catalyst, and using eco-friendly conditions are the advantageous of this work. Moreover,the nanocatalyst can be used at least five times without any significant decrease in the yield of the reaction. The thiazolidine-triazole derivatives 9a, 9c, 9e, and 9 g showed promising tyrosinase inhibitory activity with IC50 values in the range of 5.90–9.81 μM. The compounds were found to be considerably more potent tyrosinase inhibitors than the reference inhibitor kojic acid (IC50 = 18.36 μM).
- Darroudi, Mahdieh,Ranjbar, Sara,Esfandiar, Mohammad,Khoshneviszadeh, Mahsima,Hamzehloueian, Mahshid,Khoshneviszadeh, Mehdi,Sarrafi, Yaghoub
-
-
- Rhodium complex containing ortho-position carborane Schiff base ligand as well as preparation method and application thereof
-
The invention relates to a rhodium complex containing an ortho-position carborane Schiff base ligand as well as a preparation method and application thereof. The rhodium complex is prepared by the following steps: reacting ortho-position carborane diforma
- -
-
Paragraph 0033-0036; 0055-0058
(2020/09/30)
-
- New thiazolidine-2,4-dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity
-
Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine-2,4-dione framework (TZD-4) prompted us to explore compounds containing both the thiazolidine-2,4-dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene-based thiazolidine-2,4-dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine-resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD-4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD-4 against the P. falciparum parasite. All the synthesised compounds were non-toxic and often showed >90% viability of the HeLa cell line screened.
- Oderinlo, Ogunyemi O.,Tukulula, Matshawandile,Isaacs, Michelle,Hoppe, Heinrich C.,Taylor, Dale,Smith, Vincent J.,Khanye, Setshaba D.
-
-
- Design, synthesis and molecular docking studies of some thiazole clubbed heterocyclic compounds as possible anti-infective agents
-
The present work describes synthesis of a series of 5-((1-(4-(4-chlorophenyl)thiazol-2-yl)-3- aryl-1H-pyrazol-4-yl)methylene)-2-(arylimino)thiazolidin-4-one derivatives and their molecular docking and biological evaluation as possible antimalarial, anthelmintic and antimicrobial agents. The synthesis of compounds has been accomplished by adopting suitable synthetic methods. Structures of newly synthesized compounds were characterized and authenticated by spectral methods such as IR, 1H-NMR and mass spectra. Synthesized compounds were screened for their in vitro antimicrobial activity against selected bacterial strains and fungal strains viz. B. subtilis, S. aureus, E. coli, P. fluorescens, C. albicans, C. glabrata and antimalarial studies against P. falciparum. Titled compounds were also tested against Pheretima posthuma (earthworm) for their anthelmintic activity. Molecular docking was done to study the binding modes of the potent compounds against Escherichia coli (PDB ID: 1AB4) and Candida P450DM (PDB ID: 1EA1) enzymes. The results revealed that all the compounds exhibited moderate to significant antimicrobial activities. Antimalarial activity screening revealed that one compound 8i showed significant antimalarial activity with of IC50; 0.59 μg/mL as compared to standard drugs chloroquine (IC50= 0.020 μg/mL) and quinine (IC50; 0.268 μg/mL). The most active compound exhibited the mean paralysis time of 19.2 ± 0.9 min and mean death time of 31.7 ± 2.5 min. It can be concluded that some of the synthesized compounds have remarkable antiinfective, antimalarial and anthelmintic activity and are suitable candidates for further scientific exploration.
- Sharma, Prabodh Chander,Saini, Anil,Bansal, Kushal Kumar,Sharma, Archana,Gupta, Girish Kumar
-
p. 716 - 726
(2018/07/13)
-
- Synthesis of thiazolone derivatives as novel soybean 15-LOX inhibitors
-
Background: Thiazole derivatives are known as important sulfur containing heterocycles which are present in a wide range of biologically active natural products. Methods: A series of thiazolone derivatives were synthesized and evaluated for their soybean 15-LOX inhibitory activity. The title compounds were prepared by the reaction of 2-arylthiazol-4(5H)-ones and different aromatic aldehydes. All compounds were characterized and evaluated against soybean 15-LOX. Results: Among the synthesized thiazolone derivatives, 5-(4-methoxybenzylidene)-2-((2-methoxyphenyl) amino)thiazol-4(5H)-one (3l) was found to be the most active compound comparing with quercetin as the reference drug. Conclusion: It seems that prepared thiazolones having methoxy groups both on aryl and aminoaryl moieties can be considered for further drug discovery research.
- Mahdavi, Mohammad,Saeedi, Mina,Nadri, Hamid,Eghtedari, Mohammad,Gholizadeh, Sama,Hariri, Roshanak,Akbarzadeh, Tahmineh
-
p. 186 - 191
(2017/06/21)
-
- A 5 - (1 H - indole - 3 - methylene) - 1, 3 - thiazolidine - 4 - ketone derivative and its synthetic method and application
-
The invention relates to 5-(1H-indolyl-3-methylene)-1,3-thiazolidinyl-4-one derivatives, and a synthesis method and application thereof. By using ethanol and/or water as a solvent, substituted 2-substituted-imino-1,3-thiazolidinyl-4-one and 1H-indolyl-3-formaldehyde are subjected to reflux reaction under the catalytic condition of piperidine through intermolecular dehydration condensation reaction to form methylene linking group, thereby obtaining the 5-(1H-indolyl-3-methylene)-1,3-thiazolidinyl-4-one derivatives. The intermediate 2-substituted-iminothiazolidinyl-4-one is prepared by carrying out cyclization reaction on various monosubstituted ethyl thiocarbamide chloroacetates or chloroacetic acids in a low-boiling solvent under reflux conditions, and the intermediate 2-substituted-imino-3-substituted-1,3-thiazolidinyl-4-one is prepared by carrying out a green environment-friendly synthesis technique on various disubstituted symmetric thiocarbamides and chloroacetic acids. The bioactivity preliminary screening experiment result of all the target compounds on the enzyme molecular level indicates that the target products have certain inhibition activity on PTP1B and CDC25B to different degrees.
- -
-
Paragraph 0063; 0064; 0065
(2017/09/01)
-
- Design, synthesis and biological evaluation of 5-benzylidene-2-iminothiazolidin-4-ones as selective GSK-3β inhibitors
-
In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in?vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2–85?nM). Further, in?vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3.
- Arfeen, Minhajul,Bhagat, Shweta,Patel, Rahul,Prasad, Shivcharan,Roy, Ipsita,Chakraborti, Asit K.,Bharatam, Prasad V.
-
p. 727 - 736
(2016/07/19)
-
- Synthesis and pharmacological screening of some novel anti-hypertensive agents possessing 5-Benzylidene-2-(phenylimino)-thiazolidin-4-one ring
-
In the present study, fourteen derivatives comprising of 5-benzylidene-2-(phenylimino)-thiazolidin-4-one moiety were synthesized. The structures of synthesized compounds were established by elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data and tested for electrocardiographic, antiarrhythmic and antihypertensive activities. Compound 11 was found to be most potent in this series. The pharmacological results suggested that, the antiarrhythmic effects of these compounds were related to their Ca++ ion channel antagonistic properties, which are believed to be due to the presence of 5-benzilidine-2-(phenylimino)-thiazolidin-4-one moiety. The antihypertensive effect of β-blocker side chain is enhanced by the presence of less bulky aliphatic and heterocyclic tertiary amines.
- Bhalgat, Chetan M.,Darda, Pooja V.,Bothara, Kailash G.,Bhandari, Shashikant V.,Gandhi, Jotsna,Ramesh
-
p. 580 - 588
(2014/04/03)
-
- New thiazolidinyl analogs containing pyridine ring: Synthesis, biological evaluation and QSAR studies
-
A series of pyridine derivatives of thiazolidin-4-ones (4a-4o) has been synthesized. Structures of these compounds were established on the basis of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectral data. All the synthesized compounds have been evaluated for their anti-inflammatory and analgesic effects. The results showed that compound 2-[4-methylphenylimino]-5-(1H-pyridin-2-ylmethylidene)-1,3-thiazolidin-4-one (4d), 2-(2,4-dinitro-phenylhydrazinylidine)-5-(1H-pyridin-2-yl-methylidene)-1,3- thiazolidin-4-one (4h), and 2-[3-nitro-phenylimino]-5-(1H-pyridin-2-yl- methylidene)-1,3-thiazolidin-4-one (4j) exhibited good anti-inflammatory and analgesic activity. Compound 4h was found to be the most active compound of the series with an interesting dual anti-inflammatory and analgesic activity. Docking simulation was performed to position synthesized compounds into the active site of COX-2. The relationships of energy-based docking score with analgesic and anti-inflammatory activities were also investigated by linear regression method. The QSAR models with R 2 of 0.621 and 0.740 were developed for analgesic and anti-inflammatory activities, respectively.
- Ranga, Reetu,Sharma, Vikas,Kumar, Vipin
-
p. 1538 - 1548
(2013/07/26)
-
- Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3- alkyl-2-(alkylimino)thiazolidin-4-one chemotype
-
High affinity and selective S1P4 receptor (S1P4-R) small molecule agonists may be important proof-of-principle tools used to clarify the receptor biological function and effects to assess the therapeutic potential of the S1P4-R in diverse disease areas including treatment of viral infections and thrombocytopenia. A high-throughput screening campaign of the Molecular Libraries-Small Molecule Repository was carried out by our laboratories and identified (2Z,5Z)-5-((1-(2-fluorophenyl)-2,5-dimethyl-1H- pyrrol-3-yl)methylene)-3-methyl-2-(methylimino) thiazolidin-4-one as a promising S1P4-R agonist hit distinct from literature S1P4-R modulators. Rational chemical modifications of the hit allowed the identification of a promising lead molecule with low nanomolar S1P4-R agonist activity and exquisite selectivity over the other S1P 1-3,5-Rs family members. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P4-R signaling cascade and elucidate the molecular basis of the receptor function.
- Urbano, Mariangela,Guerrero, Miguel,Velaparthi, Subash,Crisp, Melissa,Chase, Peter,Hodder, Peter,Schaeffer, Marie-Therese,Brown, Steven,Rosen, Hugh,Roberts, Edward
-
scheme or table
p. 6739 - 6745
(2011/12/05)
-
- Synthesis of spiro-heterocycles with the thiazolidinone moiety from nitrilimines
-
The 2-phenylimino-1,3-thiazolidin-4-one 2 was obtained by thermal cyclization of 4-amino-5-phenyl-3,5-thiaaza-4-pentenoic acid 1 using DCC as dehydration agent. Treatment of 2-phenylimino-1,3-thiazolidin-4-one 2 with various hydrazonoyl halides 3 (nitrili
- Dalloul, Hany M.
-
experimental part
p. 196 - 201
(2010/04/24)
-
- Design, Synthesis and Pharmacological Screening of Novel Antihypertensive Agents Using Hybrid Approach
-
Eight derivatives of general formula 2-(2-(4-(3-((5-substituted methylene)-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydroxypropylamino)b enzoyl)hydrazinyl)-2-oxoethyl nitrate were synthesized and tested for electrocardiographic, antiarrhythmic, vasorelaxing and antihypertensive activity as well as for in-vitro nitric oxide (NO) releasing ability. Compound 8b 2-(2-(4-(3-(5-benzyliden-4-oxo-2-(phenylimino)thiazolidin-3-yl)-2-hydrox ypropylamino)benzoyl)hydrazinyl)-2-oxoethyl nitrate, was the most potent in this series. The pharmacological results suggested that the antiarrhythmic effects of these compounds were related to their adrenolytic properties which are believed to be due to the presence of the 5-(substituted)methylen-2-(phenylimino)thiazolidin-4-one moiety with less bulky, electron donating substituent on the phenyl ring at 5th position of the thiazolidin-4-one. In conclusion, most of the synthesized compounds were significantly potent as antiarrhythmic and antihypertensive; this might be due to the presence of different pharmacopores which might act at different locations with different mode of action. Further insights of the same can be obtained by doing investigation at receptor level. The potency of compounds 8a-8h were promising enough to continue further experiments.
- Bhandari, Shashikant V.,Bothara, Kailash G.,Patil, Ajit A.,Chitre, Trupti S.,Sarkate, Aniket P.,Gore, Suraj T.,Dangre, Sudarshan C.,Khachane, Chetan V.
-
experimental part
p. 390 - 400
(2011/02/25)
-
- THIAZOLIDINONE COMPOUNDS, AND METHODS OF MAKING AND USING SAME
-
Provided herein are thiazolidinone compounds, and methods of making and using the same. Such compounds may be used in inflammatory or immune-mediated disorders. The disclosure provides for treating respiratory or ocular disorders, treating arthritis, or may be used to treat cancer, such as prostate or breast cancer, or multiple myeloma.
- -
-
Page/Page column 74
(2009/04/25)
-
- Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells
-
Ten cytoselective compounds have been identified from 372 thiazolidinone analogues by applying iterative library approaches. These compounds selectively killed both non-small cell lung cancer cell line H460 and its paclitaxel-resistant variant H460taxR at an IC50 between 0.21 and 2.93 μM while showing much less toxicity to normal human fibroblasts at concentrations up to 195 μM. Structure-activity relationship studies revealed that (1) the nitrogen atom on the 4-thiazolidinone ring (ring B in Figure 1) cannot be substituted, (2) several substitutions on ring A are tolerated at various positions, and (3) the substitution on ring C is restricted to the -NMe2 group at the 4-position. A pharmacophore derived from active molecules suggested that two hydrogen bond acceptors and three hydrophobic regions were common features. Activities against P-gp-overexpressing and paclitaxel-resistant cell line H460taxR and modeling using a previously validated P-gp substrate pharmacophore suggested that active compounds were not likely P-gp substrates.
- Zhou, Hongyu,Wu, Shuhong,Zhai, Shumei,Liu, Aifeng,Sun, Ying,Li, Rongshi,Zhang, Ying,Ekins, Sean,Swaan, Peter W.,Fang, Bingliang,Zhang, Bin,Yan, Bing
-
p. 1242 - 1251
(2008/12/23)
-
- New methods for the synthesis of 2-aminothiazolones
-
(Chemical Equation Presented) Two new methods for the synthesis of 2-aminothiazolones from 2-(4-methoxybenzylthio)acetic acids are described. A single reagent and simple experimental conditions are used in the key tandem deprotection-cyclization process. In the first approach 2-aminothiazolones are directly accessed via cyclization of the corresponding N-acylisothioureas. The second complementary approach provides access to a variety of 2-thiomethylthiazolones via cyclization of N-acyldithioimidates. The product 2-thiomethylthiazolones are then efficiently converted to 2-aminothiazolones via amine displacement.
- Caille, Seb,Bercot, Eric A.,Cui, Sheng,Faul, Margaret M.
-
p. 2003 - 2006
(2008/09/20)
-
- Synthesis and activity of quinolinyl-methylene-thiazolinones as potent and selective cyclin-dependent kinase 1 inhibitors
-
A novel series of quinolinyl-methylene-thiazolinones has been identified as potent and selective cyclin-dependent kinase 1 (CDK1) inhibitors. Their synthesis and structure activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK1 activity in vitro, and block cell cycle progression in human tumor cell lines, suggesting a potential use as antitumor agents.
- Chen, Shaoqing,Chen, Li,Le, Nam T.,Zhao, Chunlin,Sidduri, Achyutharao,Lou, Jian Ping,Michoud, Christophe,Portland, Louis,Jackson, Nicole,Liu, Jin-Jun,Konzelmann, Fred,Chi, Feng,Tovar, Christian,Xiang, Qing,Chen, Yingsi,Wen, Yang,Vassilev, Lyubomir T.
-
p. 2134 - 2138
(2008/02/03)
-
- [4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: Synthesis and cytotoxic activity on selected human cancer cell lines
-
Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]-phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.
- Mahboobi, Siavosh,Sellmer, Andreas,H?cher, Heymo,Eichhorn, Emerich,B?r, Thomas,Schmidt, Mathias,Maier, Thomas,Stadlwieser, Josef F.,Beckers, Thomas L.
-
p. 5769 - 5776
(2007/10/03)
-
- Synthesis and biological evaluation of 7-N-(n-alkoxyphthalimido)-2hydroxy- 4-aryl-6-aryliminothiazolidino [2,3-b] pyrimidines and related compounds
-
Substituted aryl thioureas 1a-c react with chloroacetic acid in the presence of anhydrous sodium acetate to furnish 2-aryliminothiazolidin-4-ones 2a-c. Condensation of ω-bromoalkoxyphthalimides 3a-c with 2a-c give the corresponding alkoxyphthalimide derivatives of 2-aryliminothiazolidin-4-ones 4a-i. These on condensation with araldehydes 5a-c yield 3-N-(alkoxyphthalimido)- 5-arylidene-2-aryliminothiazolidin-4-ones 7a-a′. In an alternative route 5a-c react with 2a-c to give 6a-i, which could be cyclised with urea in the presence of sodium acetate to yield the corresponding thiazolidinopyrimidine 8a-i. 7a-a′ are also prepared from 6a-i with 3a-c, which give final compound 9a-a′ on cyclisation. Alternatively, 8a-i when condensed with 3a-c also furnish the compounds 9a-a′. Evaluation of antimalarial and antibacterial activity is also reported.
- Singh, Bhawani Singh,Mehta, Deepika,Baregama, Lalit K.,Talesara
-
p. 1306 - 1313
(2007/10/03)
-
- Use of 2,4-diaminothiazole derivatives
-
2,4-Diaminothiazole derivatives which inhibit GSK-3 (glycogen synthase kinase-3) and which are useful for the treatment and/or prevention disorders and diseases wherein an inhibition of GSK-3 is beneficial, especially especially Alzheimer's disease, bipolar disorder, IGT (impaired glucose tolerance), Type 1 diabetes, Type 2 diabetes and obesity.
- -
-
-
- Reaction of Methyl (Phenylhydrazonomethylthio)acetate with Sodium Methoxide
-
The reaction of methyl (phenylhydrazonomethylthio)acetate 1 with sodium methoxide in methanol at 30 deg C was found to give initially 5-oxo-4-phenyl-5,6-dihydro-1,3,4-thiadizine 2, which then rearranged to 2-(phenylimino)-4-oxothiazolidine 3 in quantitative yield via cleavage of the nitrogen-nitrogen bond.Keywords-methyl(phenylhydrazonomethylthio)acetate; 5-oxo-4-phenyl-5,6-dihydro-1,3,4-thiadiazine; 2-(phenylimino)-4-oxothiazolidine; ring contraction; nitrogen-nitrogen bond cleavage
- Matsubara, Yoshio,Nakamura, Toshiyuki,Yoshihara, Masakuni,Maeshima, Toshihisa
-
p. 3009 - 3011
(2007/10/02)
-
- SYNTHESIS AND STRUCTURE OF 4-PHENYL-1,3,4,4H-THIADIAZIN-5(6H)-ONE
-
4-Phenyl-1,3,4,4H-thiadiazin-5(6H)-one 2 was synthesized by the reaction of methyl carboxylatomethyl-N-anilinothioformimidate 1 with triethylamine in methanol and the structure of 2 was determined by X-ray analysis.The mechanism of formation 2 is discussed.
- Matsubara, Yoshio,Yoshihara, Masakuni,Nakanura, Toshiyuki,Yamada, Shigeji,Maeshima, Toshihisa
-
-