34572-28-6Relevant academic research and scientific papers
Evodiamine prodrug containing indole quinone unit as well as preparation method and application thereof
-
Paragraph 0018; 0022, (2021/10/30)
The invention relates to an evodiamine prodrug containing an indole quinone unit as well as a preparation method and application thereof. The invention synthesizes a series of strong active evodiamine derivatives with indole quinine units, has strong anti-proliferative activity on non-small cell lung cancer (non-small cell lung cancer, NSCLC), and has dosage and time dependence. In-vitro experiments evaluate their biological activity, suggesting that the synthesized compounds have a strong inhibitory activity on lung cancer strains. Through molecular docking analysis, the binding affinity of the ligand to the active site of the target protein is predicted, and the interaction ability of the ligand and the protein is strong.
INDQ/NO, a bioreductively activated nitric oxide prodrug
Sharma, Kavita,Iyer, Aishwarya,Sengupta, Kundan,Chakrapani, Harinath
, p. 2636 - 2639 (2013/07/19)
The design, synthesis, and development of INDQ/NO, a novel nitric oxide (NO) prodrug targeted by a bioreductive trigger, are described. INDQ/NO, an indolequinone-diazeniumdiolate is found to be metabolized to produce NO by DT-diaphorase, a bioreductive enzyme that is overexpressed in certain cancers and hypoxic tumors. Cell-based assays revealed that INDQ/NO induces DNA damage and is a potent inhibitor of cancer cell proliferation.
SEPIAPTERIN REDUCTASE INHIBITORS FOR THE TREATMENT OF PAIN
-
Page/Page column 67, (2011/05/05)
Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and pro-drugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain)
Novel benzofuran-3-one indole inhibitors of PI3 kinase-α and the mammalian target of rapamycin: Hit to lead studies
Bursavich, Matthew G.,Brooijmans, Natasja,Feldberg, Lawrence,Hollander, Irwin,Kim, Stephen,Lombardi, Sabrina,Park, Kaapjoo,Mallon, Robert,Gilbert, Adam M.
scheme or table, p. 2586 - 2590 (2010/06/19)
A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110α (PI3K-α), good pharmaceutical properties, selectivity versus p110γ (PI3K-γ), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-α and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells.
1H NMR studies on the reductively triggered release of heterocyclic and steroid drugs from 4,7-dioxoindole-3-methyl prodrugs
Ferrer, Sandra,Naughton, Declan P.,Threadgill, Michael D.
, p. 3445 - 3454 (2007/10/03)
Hypoxia is a feature of several disease states, including cancer and rheumatoid arthritis. Prodrug systems which, after bioreduction, selectively release active drugs in these tissues may be important in therapy. An improved preparation of 1,2-dimethyl-3-hydroxymethyl-5-methoxyindole-4,7-dione was developed. Mitsunobu coupling with (5-substituted) isoquinolin-1-ones (potent inhibitors of poly(ADP-ribose)polymerase) gave 1-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethoxy)isoquinolines and N-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethyl)isoquinolin-1-ones. Similar coupling with the anticancer drug pentamethylmelamine gave its potential prodrug 1,2-dimethyl-3-(N-(4,6-bis(dimethylamino)-1,3,5-triazin-2-yl)-N- methylaminomethyl)-5-methoxyindole-4,7-dione. Treatment of sodium prednisolone hemisuccinate with 3-chloromethyl-1,2-dimethyl-5-methoxyindole-4,7-dione gave an analogous candidate prodrug of the anti-inflammatory drug prednisolone. In a chemical model system for bioreduction, SnCl2 in CDCl3/CD3OD triggered rapid stoichiometric release of isoquinolin-1-ones from the O-linked prodrugs but not from the N-linked analogues. Use of this system allowed the release process to be monitored in situ by 1H NMR spectroscopy. Diethyl hydrazine-1,2-dicarboxylate was found to reduce SnIV to SnII, making the overall reductive release catalytic in tin. The reduced (hydroquinone) prodrug may have a short lifetime under these reductive conditions, meaning that only good leaving groups are expelled. Thus 1-(1,2-dimethyl-4,7-dioxo-5-methoxyindol-3-ylmethoxy)isoquinolines and analogues may be useful as reductively triggered prodrugs.
2-cyclopropylindoloquinones and their analogues as bioreductively activated antitumor agents: Structure-activity in vitro and efficacy in vivo
Naylor, Matthew A.,Jaffar, Mohammed,Nolan, John,Stephens, Miriam A.,Butler, Susan,Patel, Kantilal B.,Everett, Steven A.,Adams, Gerald E.,Stratford, Ian J.
, p. 2335 - 2346 (2007/10/03)
A series of 2-cycloalkyl- and 2-alkyl-3-(hydroxymethyl)-1- methylindoloquinones and corresponding carbamates have been synthesized and substituted in the 5-position with a variety of substituted and unsubstituted aziridines. Cytotoxicity against hypoxic c
