433226-16-5Relevant academic research and scientific papers
Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors
Hasegawa, Masaichi,Nishigaki, Naohiko,Washio, Yoshiaki,Kano, Kazuya,Harris, Philip A.,Sato, Hideyuki,Mori, Ichiro,West, Rob I.,Shibahara, Megumi,Toyoda, Hiroko,Wang, Liping,Nolte, Robert T.,Veal, James M.,Cheung, Mui
, p. 4453 - 4470 (2008/02/13)
We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.
NON-NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS
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Page/Page column 43-44, (2008/06/13)
Compounds of the formula Z: where; A is CH or N; R1 is a substituent to a carbon atom in the ring containing A selected from -S(=O)pRa, where Ra is -C1-C4 alkyl, -ORx, -NRxRx, -NHNRxRx, - NHNHC(=O)ORx, -NRxOH; -C(=O)-Rb, where Rb is -CT-C4-alkyl, ORx, -NRxRx, -NHNRxRx, -NHC1-C3-alkyl-C(=O)Orx -NRxRc, where Rc is H, C1-C4 alkyl, -NRxRx; -C(=0)Rd, -CN, S(=O)pRx where Rd is Rd is C1-C4-alkyl, -ORx, -NRxRx C1-C3-alkyl-O-Cl-C3alkylC(=O)ORx, -C1-C3-alkyl-COORx; -C1-C3alkyl-OH or C1-C4 alkyl ethers or esters thereof (O-Cl-C3alkyl)q-O-Rx a 5 or 6 membered aromatic ring having 1-3 hetero atoms p is 1 or 2; Rx is independently selected from H, C1-C4 alkyl or acetyl; or a pair of Rx can together with the adjacent N atom form a ring; L is -0-, -S(=O),- or -CH2-, where r is 0, 1 or 2; R3-R7 are substituents as defined in the specification; X is -(CR8R8')n-D-(CR8R8')m-; D is a bond, -NR9-, -0-, -S-, -S(=0)- or -S(=0)2-; and pharmaceutically acceptable salts and prodrugs thereof, have utility as HIV antivirals.
Chemical compounds
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, (2008/06/13)
Benzimidazole derivatives, which are useful as TIE-2 and/or VEGFR2 inhibitors are described herein. The described invention also includes methods of making such benzimidazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.
