In organic chemistry, atoms other than carbon and hydrogen are generally referred to as heteroatoms. The most common heteroatoms are nitrogen, oxygen and sulfur. Now I present to you an article called Optimization of 6,7-Disubstituted-4-(arylamino)quinoline-3-carbonitriles as Orally Active, Irreversible Inhibitors of Human Epidermal Growth Factor Receptor-2 Kinase Activity, published in 2005-02-24, which mentions a compound: 23856-20-4, mainly applied to quinolinecarbonitrile arylamino preparation inhibitor HER2 EGFR kinase antitumor; quinoline cyano arylamino preparation inhibitor HER2 EGFR kinase antitumor; human epidermal growth factor receptor kinase inhibitor irreversible preparation, Electric Literature of C14H11N3O2.
A series of new 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles, e.g. I (R1 = H, Cl; R2 = PhCH2O, 1-imidazolyl, 2-furylmethoxy, etc.; R3 = Cl, CN, PhCH2O; R4 = Me, Et; R5 = Me, R6 = Me, HOCH2CH2; R5R6N = azetidinyl, piperidinyl, thiomorpholinyl, etc.) that function as irreversible inhibitors of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) kinases have been prepared These compounds demonstrated enhanced activities for inhibiting HER-2 kinase and the growth of HER-2 pos. cells compared to the EGFR kinase inhibitor I [R1 = H; R2 = F; R3 = Cl; R4 = Et; R5 = R6 = Me; (EKB-569)]. Three synthetic routes were used to prepare these compounds They were prepared mostly by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or by amination of 4-chloro-6-(crotonamido)quinoline-3-carbonitriles with monocyclic or bicyclic anilines. The third route was developed to prepare a key intermediate, 6-acetamido-4-chloroquinoline-3-carbonitrile, that involved a safer cyclization step. It was shown that attaching a large lipophilic group at the para position of the 4-(arylamino) ring results in improved potency for inhibiting HER-2 kinase. The importance of a basic dialkylamino group at the end of the Michael acceptor for activity, due to intramol. catalysis of the Michael addition has also been demonstrated. This, along with improved water solubility, resulted in compounds with enhanced biol. properties. The mol. modeling results consistent with the proposed mechanism of inhibition are presented. Binding studies of one compound, I [R1 = H; R2 = 2-pyridylmethoxy; R3 = Cl; R4 = Et; R5 = R6 = Me; (HKI-272)] (C-14 radiolabeled), showed that it binds irreversibly to HER-2 protein in BT474 cells. Furthermore, it demonstrated excellent oral activity, especially in HER-2 overexpressing xenografts. Compound HKI-272 was selected for further studies and is currently in phase I clin. trials for the treatment of cancer.
Here is just a brief introduction to this compound(23856-20-4)Electric Literature of C14H11N3O2, more information about the compound(1-Benzyl-5-nitro-1H-indazole) is in the article, you can click the link below.
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Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI