On September 16, 2010, Smaill, Jeffrey Bruce; Patterson, Adam Vorn; Denny, William Alexander; Wilson, William Robert; Lu, Guo-Liang; Anderson, Robert Forbes; Lee, Ho Huat; Ashoorzaden, Amir published a patent.Electric Literature of 175357-98-9 The title of the patent was Preparation of novel prodrug compounds containing a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger and their use as anti-proliferative agents. And the patent contained the following:
The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a pos. charge. Title compounds I [where X = neg. charged counterion; R1 = group of the formula -(CH2)nTr, wherein Tr = an aromatic nitroheterocycle or aromatic nitrocarbocycle and -(CH2)nTr acts as a reductively-activated fragmenting trigger, and n = 0-6; R2, R3, and R4 independently = aliphatic or aromatic groups of a tertiary amine kinase inhibitor, (R2)(R3)(R4)N; or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor; or one of R2, R3, and R4 may be absent and two of R2, R3, and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor] are claimed. For example, compound II was prepared via alkylation of (2E)-N-[4-(3-bromoanilino)-6-quinazolinyl]-4-(dimethylamino)-2-butenamide with 2-nitrobenzyl bromide. Select I were assayed for their ability to inhibit erbB1 tyrosine kinase and compound II was found to possess an IC50 value of 0.20 nM. The compounds of the invention are useful in treating proliferative diseases such as cancer. The experimental process involved the reaction of 4-Chloro-6-fluoropyrido[3,4-d]pyrimidine(cas: 175357-98-9).Electric Literature of 175357-98-9
The Article related to alkylammonium bromide derivative preparation kinase inhibitor antiproliferative agent, alkyl ammonium trifluoroacetate derivative preparation kinase inhibitor treatment cancer and other aspects.Electric Literature of 175357-98-9
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia