220509-98-8

Upstream product

• 132898-96-5 5-chlorosulfonylisatin 
• 174213-76-4 (S)-2-(phenoxymethyl)-pyrrolidine 
• 93783-15-4 3,3-dichloro-2-oxoindoline-5-sulfonyl chloride 
• 91-56-5 indole-2,3-dione 
• 69610-40-8 N-(tert-butoxycarbonyl)-L-prolinol 
• 174213-51-5 (S)-tert-butyl 2-(phenoxymethyl)pyrrolidine-1-carboxylate 
• 80789-74-8 5-isatinsulfonic acid sodium salt 
• 23356-96-9 (S)-1-Pyrrolidin-2-yl-methanol 
• 86661-32-7 (S)-tert-butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate 

Downstream Products

• 220510-28-1 (S)-1-Methyl-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione 
• 872254-19-8 (S)-1-(4-Hydroxybenzyl)-5-(2-phenoxymethyl-pyrrolidine-1-sulfonyl)-1H-indole-2,3-dione 
• 1092522-44-5 (S)-5-(2-((2,4-difluorophenoxy)methyl)pyrrolidin-1-ylsulfonyl)-1-(prop-2-ynyl)indoline-2,3-dione 
• 91-56-5 indole-2,3-dione 
• 1092522-45-6 (S)-1-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)-5-(2-(phenoxymethyl)pyrrolidin-1-ylsulfonyl)indoline-2,3-dione 
• 1304773-34-9 (S)-1-(4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzyl)-5-(2-(phenoxymethyl)pyrrolidin-1-ylsulfonyl)indoline-2,3-dione 
• 1304773-33-8 (S)-1-(4-(2-(2-fluoroethoxy)ethoxy)benzyl)-5-(2-(phenoxymethyl)pyrrolidin-1-ylsulfonyl)indoline-2,3-dione 
• 1092522-43-4 (S)-5-((2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl)-1-(prop-2-yn-1-yl)indoline-2,3-dione 
• 899818-51-0 (S)-(+)-1-([11C]methyl)-5-[1-(2-phenoxymethylpyrrolidinyl)sulfonyl]isatin 

Relevant academic research and scientific papers

Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors

ABTRACT: In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound 20d showed moderate inhibitory activity against caspase-3 and ?7 in?vitro compared to Ac-DEVD-CHO (IC50 = 0.016 ± 0.002 μM). Among the studied compounds, some active inhibitors with IC50s in the range of 2.33–116.91 μM were identified. The activity of compound 20d was rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped π-π and pi-cation interactions. The introduction of compound 20d with good caspase inhibitory activity will help researchers to find more potent agents.

3,4-Dihydropyrimido(1,2-a)indol-10(2H)-ones as potent non-peptidic inhibitors of caspase-3

Cysteine-dependant aspartyl protease (caspase) activation has been implicated as a part of the signal transduction pathway leading to apoptosis. It has been postulated that caspase-3 inhibition could attenuate cell damage after an ischemic event and thereby providing for a novel neuroprotective treatment for stroke. As part of a program to develop a small molecule inhibitor of caspase-3, a novel series of 3,4-dihydropyrimido(1,2-a)indol-10(2H)-ones (pyrimidoindolones) was identified. The synthesis, biological evaluation and structure-activity relationships of the pyrimidoindolones are described.

ISATIN ANALOGUES AND USES THEREFOR

Novel isatin analogues, including isatin analogues comprising Michael Acceptors (IMAs) are disclosed. Further disclosed are methods of synthesis of the isatin analogues, and uses of the analogues, including inhibition of caspase-3 and caspase-7, and in vi

Design, synthesis, and biological characterization of a caspase 3/7 selective isatin labeled with 2-[18f]fluoroethylazide

Imaging of programmed cell death (apoptosis) is important in the assessment of therapeutic response in oncology and for diagnosis in cardiac and neurodegenerative disorders. The executioner caspases 3 and 7 ultimately effect cellular death, thus providing

Isatin sulfonamide analogs containing a Michael addition acceptor: A new class of caspase 3/7 inhibitors

A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the executioner caspases, caspase-3 and c

Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis

A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its inhibition toward recombinant human caspase-3 and other caspases was determined. This compound showed high potency for inhibiting caspase-3 and -7, and high selectivity again

5-Pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis

Caspases are the unique enzymes responsible for the execution of the cell death program and may represent an exclusive target for the specific molecular imaging of apoptosis in vivo. 5-Pyrrolidinylsulfonyl isatins represent potent nonpeptidyl caspase inhibitors that may be suitable for the development of caspase binding radioligands (CBRs). (S)-5-[1-(2-Methoxymethylpyrrolidinyl) sulfonyl]isatin (7) served as a lead compound for modification of its N-1-position. Corresponding pairs of N-1-substituted 2-methoxymethyl- and 2-phenoxymethylpyrrolidinyl derivatives were examined in vitro by biochemical caspase inhibition assays. All target compounds possess high in vitro caspase inhibition potencies in the nanomolar to subnanomolar range for caspase-3 (Ki = 0.2-56.1 nM). As shown for compound (S)-1-(4-(2-fluoroethoxy) benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (35), the class of N-1-substituted 5-pyrrolidinylsulfonyl isatins competitively inhibits caspase-3. All caspase inhibitors show selectivity for the effector caspases-3 and -7 in vitro. The 2-methoxymethylpyrrolidinyl versions of the isatins appear to possess superior caspase inhibition potencies in cellular apoptosis inhibition assays compared with the 2-phenoxymethylpyrrolidinyl inhibitors.

Pyrimidoindolones and methods for using same

Novel pyrimidoindolone compounds are disclosed. Methods of using the pyrimidoindolone compounds and compositions containing the compounds in the treatment and/or prevention of disease and other conditions related to inflammation, neurodegeneration, osteoarthritis and apoptosis are also disclosed.

N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: Synthesis, in vitro activity, and molecular modeling studies

A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspas

Potent and selective nonpeptide inhibitors of caspases 3 and 7

5-Dialkylaminosulfonylisatins have been identified as potent, nonpeptide inhibitors of caspases 3 and 7. The most active compound within this series (34) inhibited caspases 3 and 7 in the 2-6 nM range and exhibited approximately 1000-fold selectivity for caspases 3 and 7 versus a panel of five other caspases (1, 2, 4, 6, and 8) and was at least 20-fold more selective versus caspase 9. Sequence alignments of the active site residues of the caspases strongly suggest that the basis of this selectivity is due to binding in the S2 subsite comprised of residues Tyr204, Trp206, and Phe256 which are unique to caspases 3 and 7. These compounds inhibit apoptosis in three cell-based models: human Jurkat T cells, human chondrocytes, and mouse bone marrow neutrophils.