915019-52-2

Usage

Uses

Used in Pharmaceutical Industry:
4-[(3-amino-6-bromo-4-quinolinyl)amino]-.alpha.,.alpha.-dimethyl-Benzeneacetonitrile is used as a reagent for the preparation of imidazo quinoline derivatives, which are employed as mTOR and PI3K-kinase inhibitors. These inhibitors are valuable in the development of drugs targeting various diseases, including cancer and immune disorders, due to their ability to regulate key cellular processes and signaling pathways.

InChI:InChI=1/C19H17BrN4/c1-19(2,11-21)12-3-6-14(7-4-12)24-18-15-9-13(20)5-8-17(15)23-10-16(18)22/h3-10H,22H2,1-2H3,(H,23,24)

Upstream product

• 145369-94-4 6-bromoquinolin-4-ol 
• 187278-01-9 5-(((4-bromophenyl)amino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 106-40-1 4-bromo-aniline 
• 74189-16-5 2-amino-5-bromobenzoic acid hydrochloride 
• 5794-88-7 5-Bromo-2-aminobenzoic acid 
• 853908-49-3 5-bromo-2-((2-nitroethenyl)amino)benzoic acid 
• 1201643-75-5 (E)-5-bromo-2-((2-nitrovinyl)amino)benzoic acid 
• 723281-72-9 6-bromo-4-chloro-3-nitroquinoline 
• 853908-50-6 6-bromo-3-nitroquinolin-4-ol 
• 71825-51-9 4-(2-cyanoprop-2-yl)-1-nitrobenzene 
• 115279-57-7 2-(4-aminophenyl)-2-methylpropionitrile 
• 915019-51-1 2-(4-((6-bromo-3-nitroquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile 

Downstream Products

• 915019-53-3 2-(4-(8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1395145-15-9 2-(4-(8-(2-aminobenzo[d]oxazol-5-yl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitril 
• 1260167-99-4 8-bromo-N-(2-chloroethyl)-1-(4-(2-cyanopropan-2-yl)phenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carbothioamide 
• 1260167-89-2 N-allyl-8-bromo-1-(4-(2-cyanopropan-2-yl)phenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carboxamide 
• 1260167-87-0 8-bromo-N-(2-chloroethyl)-1-(4-(2-cyanopropan-2-yl)phenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carboxamide 
• 1260167-85-8 8-bromo-N-(2-bromophenyl)-1-(4-(2-cyanopropan-2-yl)phenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carboxamide 
• 1260167-82-5 N-benzyl-8-bromo-1-(4-(2-cyanopropan-2-yl)phenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carboxamide 
• 1260167-80-3 8-bromo-1-(4-(2-cyanopropan-2-yl)phenyl)-N-(4-methoxyphenyl)-2-oxo-1H-imidazo[4,5-c]quinoline-3(2H)-carboxamide 
• 1260167-78-9 2-(4-(3-benzoyl-8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1260167-76-7 (E)-2-(4-(8-bromo-3-cinnamoyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1260167-74-5 2-(4-(8-bromo-2-oxo-3-(2-propylpentanoyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1260167-72-3 (E)-2-(4-(8-bromo-3-but-2-enoyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1260167-70-1 2-(4-(8-bromo-3-(morpholine-4-carbonyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 1260167-58-5 2-(4-(8-chloro-2-oxo-3-(m-tolylsulfonyl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 

Relevant academic research and scientific papers

Development of a Robust Synthesis of Dactolisib on a Commercial Manufacturing Scale

The development of the robust synthesis of 2-methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl]-phenyl]propionitrile (dactolisib) on a commercial scale is described. The key step is a Pd-catalyzed Suzuki coupling of 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile to 3-quinoline boronic acid. A special focus is placed on reducing the amount of Pd catalyst used in the Suzuki coupling and purifying the crude drug substance, including removing traces of Pd.

C26-LINKED RAPAMYCIN ANALOGS AS MTOR INHIBITORS

The present disclosure relates to mTOR inhibitors. Specifically, the embodiments are directed to compounds and compositions inhibiting mTOR, methods of treating diseases mediated by mTOR, and methods of synthesizing these compounds.

Design, synthesis and biological evaluation of novel phenylsulfonylurea derivatives as PI3K/mTOR dual inhibitors

Five series of novel phenylsulfonylurea derivatives, 19a–d, 20a–d, 21a–d, 22a–d and 23a–d, bearing 4-phenylaminoquinoline scaffold were designed, synthesized and their IC50 values against four cancer cell lines (HepG-2, A549, PC-3 and MCF-7) were evaluated. Most compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure–activity relationships (SARs) and pharmacological results indicated that introduction of 4-aminoquinoline scaffold and phenylsulfonylurea scaffold were beneficial for anti-tumor activity. Moreover, para-methoxyl substitution of 4-anilino moiety and para-halogen substitution of phenylsulfonylurea have different impacts on different series of compounds. Furthermore, the micromolecule group substitution in the 6-position of the quinoline ring have a slight impact on the cellular activity of the target compounds.

Design, synthesis, and antitumor evaluation of quinoline-imidazole derivatives

A series of compounds bearing quinoline-imidazole (8a–e, 9a–e, 10a–e, 11a–e, and 12a–e) not reported previously were designed and synthesized. The target compounds were evaluated for antitumor activity against A549, PC-3, HepG2, and MCF-7 cells by the MTT method, with NVP-BEZ235 being the positive control. Most compounds showed moderate activity and compound 12a showed the best activity against HepG2, A549, and PC-3 cells, with half-maximal inhibitory concentration (IC50) values of 2.42 ± 1.02 μM, 6.29 ± 0.99 μM, and 5.11 ± 1.00 μM, respectively, which was equal to NVP-BEZ235 (0.54 ± 0.13 μM, 0.36 ± 0.06 μM, 0.20 ± 0.01 μM). Besides, the IC50 value of 12a against the cell line WI-38 (human fetal lung fibroblasts) was 32.8 ± 1.23 μM, indicating that the target compounds were selective for cancer cells. So, 11a and 12a were evaluated against PI3Kα and mTOR to find out if the compounds acted through the PI3K-Akt-mTOR signal transduction pathway. The inhibition ratios to PI3Kα and mTOR were slightly lower than that of NVP-BEZ235, suggesting there may be some other mechanisms of action. The structure–activity relationships and docking study of 11a and 12a revealed that the latter was superior. Moreover, the target compounds showed better in vitro anticancer activity when the C-6 of the quinoline ring was replaced by a bromine atom.

Sulfonylurea compound as well as preparation method and application thereof

The invention discloses a sulfonylurea compound, geometrical isomers or pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and a preparation method thereof. The sulfonylurea compound, the pharmaceutically acceptable salts, hydrates or solvates serving as active ingredients are mixed with pharmaceutically acceptable carriers or excipients to prepare compositions and preparedinto clinically acceptable dosage forms. The invention further discloses application of the compounds in preparation of medicines for treating and/or preventing proliferative diseases, application inpreparation of medicines for treating and/or preventing cancers, and application in preparation of medicines for treating and/or prostatic cancer, lung cancer and breast cancer.

RAPAMYCIN ANALOGS AS MTOR INHIBITORS

The present disclosure relates to rapamycin analogs of the general Formula (I). The compounds are inhibitors of mTOR and thus useful for the treatment of cancer, immune-mediated diseases and age related conditions.

Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof

The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.

JAK PI3K/mTOR combination therapy

Provided herein is a combination therapy comprising a JAK kinase inhibitor and a dual PI3K/mTOR inhibitor, as well as methods of treating various cancers through the use of such a combination therapy.

Imidazole derivatives, its pharmaceutical composition and use thereof

Imidazolone compounds, pharmaceutically acceptable salts, solvates, polymorphs or prodrugs thereof are disclosed. Pharmaceutical compositions comprising above substances and uses for preventing and treating protein kinases related diseases, such as cancers, metabolic diseases, cardiovascular diseases and the like, are also disclosed.

COMBINATION OF KINASE INHIBITORS AND USES THEREOF

The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.