1165809-20-0

Upstream product

• 574-17-4 1-acetyl-1H-indole-2,3-dione 
• 79-19-6 thiosemicarbazide 
• 62-53-3 aniline 
• 91-56-5 indole-2,3-dione 
• 42366-35-8 hydroxyimino-N-phenylacetamide 
• 110829-23-7 Z-3-thiosemicarbazone of 1-acetylisatin 

Downstream Products

• 22915-25-9 2-(Isatin-3-azino)-4-thiazolidinone 
• 22915-26-0 3-{[4-Oxo-5-[1-phenyl-meth-(Z)-ylidene]-thiazolidin-(2E)-ylidene]-hydrazono}-1,3-dihydro-indol-2-one 
• 92756-11-1 3-{(Z)-5-Oxo-4-[1-phenyl-meth-(Z)-ylidene]-2-thioxo-imidazolidin-1-ylimino}-1,3-dihydro-indol-2-one 
• 22915-27-1 3-{[5-[1-(4-Chloro-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2E)-ylidene]-hydrazono}-1,3-dihydro-indol-2-one 
• 92756-08-6 3-{[5-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2E)-ylidene]-hydrazono}-1,3-dihydro-indol-2-one 
• 92756-10-0 3-[(5-(4-chlorobenzylidene)-2-thioxoimidazolidin-4-one-3-yl)imino]-indole-2-one 
• 22915-30-6 3-{[5-[1-(4-Dimethylamino-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2E)-ylidene]-hydrazono}-1,3-dihydro-indol-2-one 
• 92756-13-3 3-{(Z)-4-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-5-oxo-2-thioxo-imidazolidin-1-ylimino}-1,3-dihydro-indol-2-one 
• 92756-12-2 3-{(Z)-4-[1-(4-Dimethylamino-phenyl)-meth-(Z)-ylidene]-5-oxo-2-thioxo-imidazolidin-1-ylimino}-1,3-dihydro-indol-2-one 
• 22915-28-2 3-{[5-[1-(4-Nitro-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2E)-ylidene]-hydrazono}-1,3-dihydro-indol-2-one 
• 92756-09-7 3-{(Z)-4-[1-(4-Nitro-phenyl)-meth-(Z)-ylidene]-5-oxo-2-thioxo-imidazolidin-1-ylimino}-1,3-dihydro-indol-2-one 
• 1198306-49-8 3-(2-(5-[(4-chlorophenyl)diazenyl]-4-methylthiazol-2-yl)hydrazono)indolin-2-one 
• 1198306-50-1 3-(2-(5-[(4-bromophenyl)diazenyl]-4-methylthiazol-2-yl)hydrazono)indolin-2-one 
• 1198306-48-7 3-(2-(4-methyl-5-(phenyldiazenyl)thiazol-2-yl)hydrazono)indolin-2-one 

Relevant academic research and scientific papers

(3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro- 1H -indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase

The HIV-1 Reverse Transcriptase (RT) is a validated and deeply explored biological target for the treatment of AIDS. However, only drugs targeting the RT-associated DNA polymerase (DP) function have been approved for clinical use.We designed and synthesised a new generation of HIV-1 RT inhibitors, based on the (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one scaffold. These compounds are active towards both RT-associated functions, DNA polymerase and ribonuclease H. The structure, biological activity and mode of action of the new derivatives have been investigated. In particular, the nature of the aromatic group in the position 4 of the thiazole ring plays a key role in the modulation of the activity towards the two RT-associated functions.

Design, synthesis and in silico insights of new 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives with potent anticancer and multi-kinase inhibitory activities

Aiming to obtain an efficient anti-proliferative activity, structure- and ligand-based drug design approaches were expanded and utilized to design and refine a small compound library. Subsequently, thirty-two 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives were selected for synthesis based on the characteristic pharmacophoric features required for PI3K and B-Raf oncogenes inhibition. All the synthesized compounds were evaluated for their in vitro anticancer activity. Compounds 17 and 22c displayed an acceptable potent activity according to the DTP-NCI and were further evaluated in the NCI five doses assay. To validate our design, compounds with the highest mean growth inhibition percent were screened against the target PI3Kα and B-RafV600E to confirm their multi-kinase activity. The tested compounds showed promising multi-kinase activity. Compounds 17 and 22c anticancer effectiveness and multi-kinase activity against PI3Kα and B-RafV600E were consolidated by the inhibition of B-RafWT, EGFR and VEGFR-2 with IC50 in the sub-micromolar range. Further investigations on the most potent compounds 17 and 22c were carried out by studying their safety on normal cell line, in silico profiling and predicted ADME characteristics.

Structural improvement of new thiazolyl-isatin derivatives produces potent and selective trypanocidal and leishmanicidal compounds

Neglected diseases are a group of transmissible diseases that occur mostly in countries in tropical climates. Among this group, Chagas disease and leishmaniasis stand out, considered threats to global health. Treatment for these diseases is limited. Therefore, there is a need for new therapies against these diseases. In this sense, our proposal consisted of developing two series of compounds, using a molecular hybridization of the heterocyclic isatin and thiazole. The isatin and thiazole ring are important scaffold for several biological disorders, including antiparasitic ones. Herein, thiazolyl-isatin has been synthesized from respective thiosemicarbazone or phenyl-thiosemicarbazone, being some of these new thiazolyl-isatin toxic for trypomastigotes without affecting macrophages viability. From this series, compounds 2e (IC50 = 4.43 μM), 2j (IC50 = 2.05 μM), 2l (IC50 = 4.12 μM) and 2m (1.72 μM) showed the best anti-T. cruzi activity for trypomastigote form presenting a selectivity index higher than Benznidazole (BZN). Compounds 2j, 2l and 2m were able to induce a significantly labelling compatible with necrosis in trypomastigotes. Analysis by scanning electron microscopy showed that T. cruzi trypomastigote cells treated with the compound 2m from IC50 concentrations, promoted changes in the shape, flagella and surface of body causing of the parasite dead. Concerning leishmanicidal evaluation against L. amazonensis and L. infantum, compounds 2l (IC50 = 7.36 and 7.97 μM, respectively) and 2m (6.17 and 6.04 μM, respectively) showed the best activity for promastigote form, besides showed a higher selectivity than Miltefosine. Thus, compounds 2l and 2m showed dual in vitro trypanosomicidal and leishmanicidal activities. A structural activity relationship study showed that thiazolyl-isatin derivatives from phenyl-thiosemicarbazone (2a-m) were, in general, more active than thiazolyl-isatin derivatives from thiosemicarbazone (1a-g). Crystallography studies revealed a different configuration between series 1a-g and 2a-m. The configuration and spatial arrangement divergent between the two sub-series could explain the improved biological activity profile of 2a-m sub-series.

Multifunctional thiosemicarbazones and deconstructed analogues as a strategy to study the involvement of metal chelation, Sigma-2 (σ2) receptor and P-gp protein in the cytotoxic action: In vitro and in vivo activity in pancreatic tumors

The aggressiveness of pancreatic cancer urgently requires more efficient treatment options. Because the sigma-2 (σ2) receptor was recently proposed as a promising target for pancreatic cancer therapy, we explored our previously developed multifunctional thiosemicarbazones, designed to synergistically impair cell energy levels, by targeting σ2 and P-gp proteins and chelating Iron. A deconstruction approach was herein applied by removing one function at a time from the potent multifunctional thiosemicarbazones 1 and 2, to investigate the contribution to cytotoxicity of each target involved. The results from in vitro (panel of pancreatic tumor cells) and in vivo experiments (C57BL/6 bearing KP02 tumor), suggest that while the multifunctional activity was not required for the antitumor activity of these thiosemicarbazones, σ2-targeting appeared to allow alternative tumor cell death mechanisms, leading to potent and less toxic off-targets toxicities compared to other thiosemicarbazones devoid of σ2-targeting.

Identification and preliminary structure–activity relationships of 1-Indanone derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein. The preliminary SAR was further explored and the binding mode with IDO1 protein was predicted by experiment along with molecular docking. Subsequent ADME properties of these active compounds were analyzed in silico, and the results showed good pharmacokinetic efficiencies. We believe this study contributes a lot to the structural diversity for the future development of highly potent IDO1 inhibitors.

Synthesis, biological evaluation, and molecular docking studies of novel isatin-thiazole derivatives as α-glucosidase inhibitors

A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro α-glucosidase inhibitory activity. These compounds displayed a varying degree of α-glucosidase inhibitory activity with IC50 ranging from 5.36 ± 0.13 to 35.76 ± 0.31 μm as compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μm). Among the series, compound 6p bearing a hydroxyl group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the N1-positions of the 5-methylisatin displayed the highest inhibitory activity with an IC50 value of 5.36 ± 0.13 μm. Molecular docking studies revealed the existence of hydrophobic interaction, CH-π interaction, arene-anion interaction, arene-cation interaction, and hydrogen bond between these compounds and α-glucosidase enzyme.

Synthesis, cytoprotective and anti-Tumor activities of Isatin Schiff bases

A series of simple isatin Schiff bases were synthesized through the condensation reaction. These isatin Schiff bases were characterized by NMR and MS, and the structure was discussed. Then, the cytoprotective and anti-Tumor activities of these compounds were evaluated. The results show that several compounds show protection activity on the apoptosis of PC12 cells induced by H2O2, which are more effective than that of (±) α-Tocophreol (VE) and isatin. Besides, some compounds also show more potent anti-Tumor activity against A549 and P388 cell lines than that of isatin.

Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents

Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.

Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain

While commercial isatins were practically inactive against the target proteases, thiosemicarbazone derivatives were found to be active. The most active compound from the series displayed an inhibitory IC50 value of 1 μM against rhodesain. One thiosemicarbazone was found to be active against all three proteases with inhibitory IC50 values of 10 μM or less. A combination of N-benzylation and appropriate substitution on the aromatic portion of the isatin scaffold was generally found to be beneficial especially against cruzain for ketone inhibitors.

Synthesis of some heterocycles of expected biological activity through the action of isatin-3-thiosemicarbazone on acetylenic ketones and esters

Isatin-3-thiosemicarbazone (1) reacted with 1-aryl-3-phenylprop-2-yn-1-ones (2a-c) in n-butanol to give 4-aryl-6-phenyl-2-[2-oxo-2H,3H-benzo(b) pyrrolidine-3-iminyl]-imino-2H-1,3-thiazines (3a-c). Similar treatment of 1 with acetylenic esters (4a-c) gave the 6-substituted derivatives of 2-imino-3-[2-oxo-2H,3H-benzo(b)pyrrolidine-3-iminyl]-2,3-dihydro-4-oxo-1,3- thiazine (5a-c). Treatment of 1 with 4a-c in the presence of sodium ethoxide in ethanol gave the 6-substituted derivatives of 3-[2-oxo-2H,3H-benzo(b)pyrrolidine-3-iminyl]-4-oxo-2-thioxo-1,2,4- trihydropyrimidine (6a-c). However, when 1 was refluxed with 1-p-chlorophenyl-3-phenylprop-2-yn-1-one (2b) in ethanol it gave a mixture of 2,4,6-tris[2-oxo-2H,3H-benzo(b)pyrrolidine-3-iminyl] amino-1,3,5-triazine (7) and Z,Z-3,3′-thiodi(1-p-chlorophenyl-3-phenylprop-2-en-1-one) (8). The aziridine imine derivative (9) and the pyrazole derivatives (10a and b) were the only isolated products upon treatment of 3c, 6a, and 6c and 3a and 3b with hydrazine hydrate, respectively. Structures of all new compounds are evidenced by microanalytical and spectral data.