193001-44-4Relevant articles and documents
QUINOLINE OR QUINAZOLINE DERIVATIVES WITH APOPTOSIS INDUCING ACTIVITY ON CELLS
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, (2012/03/26)
Provided is a pharmaceutical composition comprising, as an active ingredient, a quinoline or quinazoline derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate, and a solvate thereof, which is effective in the prevention and treatment of a cancer, inflammation, autoimmune diseases or neurodegenerative disorders which are induced by the overexpression of inhibitor of apoptosis proteins (IAPs).
Quinazoline derivatives
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, (2008/06/13)
The invention concerns quinazoline derivatives of Formula I wherein each of m, R1, n, R2 and R3 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.
Chemical compounds
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Example 1, (2010/11/29)
The invention relates to quinazoline derivatives of the formula: [wherein: Y1represents —O—, —S—, —CH2—, —SO—, —SO2—, —NR5CO—, —CONR6—, —SO2NR7—, —NR8SO2— or —NR9— (wherein R5, R6, R8and R9each independently represents hydrogen, alkyl or alkoxyalkyl); R1represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, alkyl, alkoxy, alkylthio, amino or alkylamino. R2represents hydrogen, hydroxy, halogeno, alkyl, alkoxy, trifluoromethyl, cyano, amino or nitro; m is an integer from 1 to 5; R3represents hydroxy, halogeno, alkyl, alkoxy, alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4represents a group which is or which contains an optionally substituted pyridone, phenyl or aromatic heterocyclic group] and salts thereof; processes for their preparation and pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Oxindole derivatives
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, (2008/06/13)
The invention relates to compounds of formula (I), wherein: R2represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, {overscore (N)}—C1-4alkylcarbamoyl, {overscore (N)},{overscore (N)}-di(C1-4alkyl)carbamoyl, aminosulphonyl, {overscore (N)}—C1-4alkylaminosulphonyl, {overscore (N)},{overscore (N)}-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, or a group R4X1wherein X1represents a direct bond, C2-4alkanoyl, —CONR5R6—, —SO2NR7R8— or —SO2R9— (wherein R5and R7, each independently represents hydrogen or C1-2alkyl and R6, R8and R9each independently represents C1-4alkyl and wherein R4is linked to R6, R8or R9) and R4represents an optionally substituted group selected from phenyl and a 5 or 6-membered heterocyclic group; n is an integer from 0 to 4, R1represents hydrogen, C1-4alkyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-4alkanoyl; m is an integer from 0 to 4; and R3represents hydroxy, halogeno, nitro, trifluoromethyl, C1-3alkyl, cyano, amino or R10X2(wherein X2represents a direct bond, —CH2—, or a single or double heteroatom linker group including —S—, —SO— and —NR15— (wherein R15represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R10is an alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R10is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF and FGF, properties of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Quinazoline derivatives as VEGF inhibitors
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, (2008/06/13)
The invention relates to quinazoline derivatives of formula (I) STR1wherein: Z represents --O--, --NH-- or --S--; m is an integer from 1 to 5; R 1 represents hydrogen, hydroxy, halogeno, nitro, trifluorometlyl, cyano, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylthio or NR 5 R 6 (wherein R 5 and R 6, which may be the same or different, each represents hydrogen or C 1-3 alkyl); R 2 represents hydrogen, hydroxy, halogeno, methoxy, amino, or nitro; R 3 represents hydroxy, halogeno, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X 1 represents --O--, --CH 2 --, --S--, --SO--, SO 2 --, --NR 6 --, NR 8 CO--, --CONR 9 --SO 2 NR 10 -- or --NR 11 SO 2 --, (wherein R 7, R 8, R 9, R 10 and R 11 each represents C 1-3 alkyl, C 1-3 alkoxyC 2-3 alkyl); R 4 represents a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted 5 or 6 membered saturated carbocylic or heterocyclic group; and salts thereof, processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient the compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Oxindolylquinazoline derivatives as angiogenesis inhibitors
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, (2008/06/13)
The invention relates to compounds of formula (I) and salts thereof as further defined herein, wherein ring Z is a 6-membered heterocyclic ring containing 1 to 3 nitrogen atoms, and the use of such compounds and salts to inhibit the effects of VEGF and FGF, and in the treatment of a number of disease states including cancer and rheumatoid arthritis.
Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors
Hennequin, Laurent F.,Thomas, Andrew P.,Johnstone, Craig,Stokes, Elaine S. E.,Plé, Patrick A.,Lohmann, Jean-Jacques M.,Ogilvie, Donald J.,Dukes, Mike,Wedge, Steve R.,Curwen, Jon O.,Kendrew, Jane,Lambert-Van Der Brempt, Christine
, p. 5369 - 5389 (2007/10/03)
A series of substituted 4-anilinoquinazolines and related compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt and KDR) tyrosine kinase activity. Enzyme screening indicated that a narrow structure-activity relationship (SAR) existed for the bicyclic ring system, with quinazolines, quinolines, and cinnolines having activity and with quinazolines and quinolines generally being preferred. Substitution of the aniline was investigated and clearly indicated that small lipophilic substituents such as halogens or methyl were preferred at the C-4' position. Small substituents such as hydrogen and fluorine are preferred at the C-2' position. Introduction of a hydroxyl group at the meta position of the aniline produced the most potent inhibitors of Flt and KDR tyrosine kinases activity with IC50 values in the nanomolar range (e.g. 10, 12, 13, 16, and 18). Investigation of the quinazoline C-6 and C-7 positions indicates that a large range of substituents are tolerated at C-7, whereas variation at the C-6 is more restricted. At C-7, neutral, basic, and heteroaromatic side chains led to very potent compounds, as illustrated by the methoxyethoxy derivative 13 (IC50 2 nM). Our inhibitors proved to be very selective inhibitors of Flt and KDR tyrosine kinase activity when compared to that associated with the FGF receptor (50- to 3800-fold). Observed enzyme profiles translated well with respect to potency and selectivity for inhibition of growth factor stimulated proliferation of human umbilical vein endothelial cells (HUVECs). Oral administration of selected compounds to mice produced total plasma levels 6 h after dosing of between 3 and 49 μM. In vivo efficacy was demonstrated in a rat uterine oedema assay where significant activity was achieved at 60 mg/kg with the meta hydroxy anilinoquinazoline 10. Inhibition of growth of human tumors in athymic mice has also been demonstrated: compound 34 inhibited the growth of established Calu-6 lung carcinoma xenograft by 75% (P 0.001, one tailed t-test) following daily oral administration of 100 mg/kg for 21 days.
