1201643-75-5

Upstream product

• 75-52-5 nitromethane 
• 74189-16-5 2-amino-5-bromobenzoic acid hydrochloride 
• 1201643-74-4 (E)-N-hydroxy-2-nitroethenamine 
• 5794-88-7 5-Bromo-2-aminobenzoic acid 
• 5653-21-4 metazonic acid 
• 118-92-3 anthranilic acid 
• 187963-80-0 nitromethane 

Downstream Products

• 853908-50-6 6-bromo-3-nitroquinolin-4-ol 
• 1201646-91-4 2-methyl-2-(4-((3'-nitro[3,6-biquinolin]-4'-yl)amino)-phenyl)propanenitrile 
• 1201646-92-5 2-(4-((3'-amino[3,6'-biquinolin]-4'-yl)amino)phenyl)-2-methyl propanenitrile 

Relevant academic research and scientific papers

Discovery of Potent and Selective Inhibitors of Cdc2-Like Kinase 1 (CLK1) as a New Class of Autophagy Inducers

Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound 25 was solved, and the potency and kinase selectivity of compound 25 were interpreted. Compound 25 was able to induce autophagy in in vitro assays and displayed significant hepatoprotective effects in the acetaminophen (APAP)-induced liver injury mouse model. Collectively, due to its potency and selectivity, compound 25 could be used as a chemical probe or agent in future mechanism-of-action or autophagy-related disease therapy studies.

IMIDAZO[4,5-C]QUINOLINE COMPOUNDS AND THEIR USE AS ATM KINASE INHIBITORS

The present invention relates to imidazo[4,5-c]quinoline compounds and to their use in the inhibition, regulation and/or modulation of signal transduction by ATM kinase and, in particular, for the treatment of ATM mediated diseases, especially cancer.

Novel quinoline-derived mTOR inhibitors with remarkable enzymatic and cellular activities: Design, synthesis and biological evaluation

Herein, we reported the preparation and in vitro development of a novel series of quinoline-based mTOR inhibitors, some of which were obtained via introducing a ring-opening strategy. As for enzymatic activity, more than half of these quinoline derivatives exhibited moderate to potent inhibition against mTOR. Among them, six compounds showed IC50 values below 50 nM. In particular, several quinolines exhibited remarkably enhanced anti-proliferative activities against all the three tested tumor cell lines in contrast to the initial lead 9. As a representative in this series, compound 24 demonstrated IC50 values of 0.11, 0.17 and 0.04 μM against HCT-116, PC-3 and MCF-7 cell lines, respectively. Besides, compounds 17 and 24 were identified to be selective over class I PI3Ks. Further Western blot analysis validated the dual inhibition of mTORC1 and mTORC2 as a result of compound 24 treatment in the MCF-7 cell line, which was beneficial for conquering the S6K/IRS1/PI3K negative feedback loop. Moreover, acceptable stability was displayed by compound 17, another representative of this series, in simulated intestinal fluid (SIF), simulated gastric fluid (SGF), as well as rat liver microsome (RLM). By virtue of the favorable biological profiles, several quinolines merit further in vivo investigation.

IMIDAZO [4,5-C]QUINOLINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF TUMORS AND/OR INFLAMMATION

The present invention provides the compounds of formula (I): (I) The present invention relates to imidazo[4,5-c]quinoline derivatives of formula (I), process for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases mediated by phosphatidylinositol-3-kinase (PBK) and/or mammalian target of rapamycin (mTOR) and/or tumor necrosis factor-α (TNF-oc) and/or interleukin-6 (IL-6), particularly in the treatment of cancer and inflammation.

PHOSPHATIDYLINOSITOL 3 KINASE INHIBITORS

Provided are compounds according to Formula (I), or stereoisomer, prodrug, polymorph, or pharmaceutically acceptable salt forms thereof, wherein X, Y, R1, R6 , R7, and R8 are as defined, which compounds are effective inhibitors of PI3-kinase and/or other medically and clinically relevant kinases. Also provided are pharmaceutical compositions and methods of using the compounds and compositions as PB -kinase and kinase inhibitors. More particularly, the compounds of the invention provide treatments and therapeutics for human diseases regulated by, or associated with, the activity of, PI3-kinases and/or protein kinases, or mutant or variant forms thereof.

SALTS AND CRYSTALL FORMS OF 2-METHYL-2-[4-(3-METHYL-2-OXO-8-QUINOLIN-3-YL-2,3-DIHYDRO-IMIDAZO[4,5-C]QUINOLIN-1-YL)-PHENYL]-PROPIONITRILE

The invention relates to particular crystalline forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, its hydrates and solvates, its salts and hydrates and solvates of its salts, certain processes for their preparation, pharmaceutical compositions containing these crystalline forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.

IMIDAZOQUINOLINES AS LIPID KINASE INHIBITORS

The invention relates to novel organic compounds of formula (I) processes for the preparation thereof, the application thereof in a process for the treatment of the human or animal body, the use thereof - alone or in combination with one or more other pharmaceutically active compounds - for the treatment of an inflammatory or obstructive airway disease, such as asthma, disorders commonly occurring in connection with transplantation, or a proliferative disease, such as a tumor disease.