4068-58-0Relevant articles and documents
Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines
Morrison, Rick,Al-Rawi, Jasim M.A.,Jennings, Ian G.,Thompson, Philip E.,Angove, Michael J.
, p. 326 - 339 (2016/02/18)
The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3-benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2-hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50 = 0.034 μM) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8-(naphthalen-1-yl) a potent and quite selective PI3Kδ inhibitor (IC50 = 0.64 μM). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1-yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation.
Stable Polymorphic Forms of Compound as Hypoxia Mimetics, and Uses Thereof
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Paragraph 0091; 0135; 0136, (2014/12/09)
The polymorphic forms of the compound of Formula I, the preparation thereof including the preparation of the intermediates, the pharmaceutical compositions thereof and the uses of a polymorph above in the manufacture of medicaments for treating a disease,
NEW COMPOUNDS II
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Page/Page column 85, (2008/06/13)
Compounds of formula I, wherein Y = H, -OH, halo, -OC1-6alkyl, -C1-6alkyl, the two latter optionally substituted with halo, -CN, -OH, -CF3, -NH2; Rl = -C3-6cycloaUcyl, heterocycloalkyl, aryl, alkylaryl, heteroaryl, -C3-6-alkyl, optionally substituted with halo, -CN, -OH, -CF3, -OCF3, -NH2, -CONH2; M = -C(O)-, -C(H2)-, -CH(OR3)-, -N(Ra)-, -S(O)r-, heteroaryl and a bond; wherein Ra = H or C1-6alkyl and r = 0, 1 or 2; R2 = H, halo, -CN, or D = -C1-6alkyl, C3-6cycloalkyl, heterocycloalkyl, -N(CH3)2, aryl, alkylaryl, heteroaryl, and heterocyclic groups; where D is optionally substituted with G = halo, -NO2, -CN, -OH, -CF3, -OCF3, -NH2, -CONH2, -COOH, aryl, heteroaryl, heterocyclic groups, -C1-6alkyl, -C1-6alkoxy, heterocycloalkyl, and C1-6alkylcarboxylate; where D may be connected to G by L = -C(O)-, -S-, or -S(O2)-; and G may be further substituted with substituents selected from halo, -NO2, -CN, -OH, -CH3, -OCH3, -CF3, -OCF3, -NH2, -CONH2, -COOH, C1-6alkylcarboxylate; and R3 = -OH or C1-6alkoxy.