98294-08-7Relevant academic research and scientific papers
NOVEL COMPOUNDS USEFUL AS POLY(ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS
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Paragraph 189, (2021/11/06)
The present invention provides novel poly(ADP-ribose) polymerase (PARP) inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods for the treatment, prevention and/or amelioration of PARP mediated diseases or disorders using them. In particular, the compounds described herein are useful for the treatment of carcinoma of the breast, ovarian cancer, carcinoma of the liver, carcinoma of the lung, small cell lung cancer, esophageal cancer, gall bladder cancer, pancreatic cancer and stomach cancer.
SUBSTITUTED 1-BENZYLINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF MUSCARINIC ACETYLCHOLINE M1 RECEPTORS
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Paragraph 0505, (2014/07/22)
In one aspect, the invention relates to substituted 1-benzylindolin-2-one analog compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M
Diverse reactivity in microwave-promoted catalyst-free coupling of substituted anilines with ethyl trifluoropyruvate and biological evaluation
Zhang, Chen,Zhuang, Dao-Min,Li, Jia,Chen, Si-Yuan,Du, Xiao-Long,Wang, Jian-Yong,Li, Jing-Yun,Jiang, Biao,Yao, Jian-Hua
, p. 5621 - 5633 (2013/09/12)
Diverse reactivity by coupling of substituted anilines with ethyl trifluoropyruvate was developed under microwave irradiation without catalysts to generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The plausible mechanism for obtaining different products was proposed. Furthermore, the anti-HIV activity of aromatic hydroxy trifluoromethyl esters was first reported. The best inhibitory activity against wild-type HIV-1 IIIB was exemplified by trifluoromethyloxindole 3q with an IC50 = 5.8 μM, which also displayed potential activity against Y181C mutant virus with an IC50 = 7.5 μM. More significantly, the activities of oxindoles 3q and 3r to inhibit K103N/Y181C double mutant HIV-1 reverse transcriptase (RT) are probably similar to that of the second-generation nonnucleoside inhibitor HBY 097 by docking calculation.
SUBSTITUTED 1-BENZYLINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF MUSCARINIC ACETYLCHOLINE M1 RECEPTORS
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Paragraph 00463, (2013/07/19)
In one aspect, the invention relates to substituted l-benzylindolin-2-one analog compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor Mi (mAChR Mi); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Design, synthesis, and biological evaluation of new 3-hydroxy-2-oxo-3- trifluoromethylindole as potential HIV-1 reverse transcriptase inhibitors
Boechat, Nubia,Kover, Warner B.,Bastos, Monica M.,Romeiro, Nelilma C.,Silva, Alessa S. C.,Santos, Fernanda C.,Valverde, Alessandra L.,Azevedo, Maria L. G.,Wollinger, Wagner,Souza, Thiago M. L.,De Souza, Silmara Lucia Oliveira,De Frugulhetti, Izabel Christina P. P.
, p. 492 - 510 (2008/04/01)
The trifluoromethyl group (CF3) is present in commercially available drugs of various therapeutic classes owing to its ability to modify and frequently improve their biological activities. Efavirenz is a trifluoromethylated inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that shows good results in anti-HIV chemotherapy. With the objective of developing efficient non-nucleoside compounds, we have designed and synthesized some new 3-hydroxy-2-oxo-3-trifluoromethylindole as potential RT inhibitors. We used different substituted isatins as starting materials. The final products contain the group CF3, present in Efavirenz, and a pharmacophoric group, oxoindole. We have used molecular docking with HIV-1 RT as a tool to design putative non-nucleoside reverse transcriptase inhibitors (NNRTIs). Based on the calculation results obtained, a series of new 3-hydroxy-2-oxo-3-trifluoromethylindoles were synthesized as a novel class of potential RT inhibitors. The results showed that these compounds are capable of important interactions with the NNRT binding site, which encouraged us to submit them for biological assay. All compounds studied are significantly active in the RNA-dependent DNA-polymerase (RDDP) assay, and were not toxic toward the Vero cell line. Hence, the designed molecules represent good starting structures for further modification and structure-activity relationship (SAR) studies. Birklaewser 2007.
Design, synthesis, and evaluation of analogues of 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide as orally available general anesthetics
Choudhury-Mukherjee, Indrani,Schenck, Hilary A.,Cechova, Sylvia,Pajewski, Thomas N.,Kapur, Jaideep,Ellena, Jeffrey,Cafiso, David S.,Brown, Milton L.
, p. 2494 - 2501 (2007/10/03)
We have recently discovered a novel class of compounds that have oral general anesthetic activity, potent anticonvulsant activity, and minimal hemodynamic effects. The 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide (1) demonstrated potent ability to reduce the minimum alveolar concentration (MAC) of isoflurane, with no effects on heart rate or blood pressure at therapeutic concentrations. Analogue 1 also had potent oral anticonvulsant activity against maximal electroshock (MES) and subcutaneous metrazol (scMET) models with a therapeutic index of 10 for MES activity. In this study, we further synthesized nine new racemic analogues and evaluated these compounds for effects on isoflurane MAC reduction and blood pressure. Preliminary data demonstrate potent reduction in the isoflurane MAC for two new compounds. Current mechanistic studies were unrevealing for effects on voltage-gated ion channels as a putative mechanism. Liposomal partitioning studies using 19F NMR reveal that the aromatic region partitions into the core of the lipid. This partitioning correlated with general anesthetic activity of this class of compounds. Further, compound 1 was used at a concentration of 1 mM and slightly enhanced GABAA current in hippocampal neurons at 10 μM. Altogether, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide exhibited excellent oral general anesthetic activity and appears devoid of significant side effects (i.e., alterations in blood pressure or heart rate).
