The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C?1-3?alkyl; X?1? represents -O-; R2 is selected from one of the following three groups: 1) C?1-5?alkylR?3? (wherein R3 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C?1-4?alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR?3? (wherein R3 is as defined hereinbefore); 3) C?2-5?alkynylR?3? (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; 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.

Quinazoline derivatives as VEGF inhibitors

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Heterocyclic compounds and uses thereof

The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or -NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents -O-, -CH2-, -S-, -SO-, -SO2-, -NR7CO-, -CONR8-, -SO2NR9-, -NR10SO2- or -NR11- (wherein R7, R8, R9, R10 and R11 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); R4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or 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 group selected from alkyl and a 5 or 6 membered saturated carbocyclic 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.

Quinazoline derivatives and pharmaceutical compositions containing them

The present invention relates to immunosuppressant, process for their production, their uses and pharmaceutical compositions containing them. The invention provides a novel class of compounds useful in the treatment or prevention of diseases or disorders mediated by lymphocyte interactions, particularly diseases associated with EDG receptor mediated signal transduction.

Immunosuppressant compounds and compositions

Phosphatidylinositol (PI) 3-kinase inhibitor compounds (I), their pharmaceutically acceptable salts, and prodrugs thereof ; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.

Pyrimidine derivatives used as pi-3 kinase inhibitors

The invention relates to compounds of formula (I), wherein r is 0 to 2, n is 0 to 2; m is 0 to 4; R1 and R2 (i) are in each case a lower alkyl, or (ii) together form a bridge in subformula (I*) or (iii) together form a bridge in subformula (I**), wherein one or two of the ring members T1, T2, T3, and T4 are nitrogen, and the remainder are in each case CH; A, B, D, and E are N or CH, wherein not more than 2 of these radicals are N; G is lower alkylene, acyloxy- or hydroxy-lower alkylene, -CH2-O-, -CH2-S-, -CH2-NH-, oxa, thia, or imino; Q is methyl; R is H or lower alkyl; X is imino, oxa, or thia; Y is aryl, pyridyl, or (un)substituted cycloalkyl; and Z is mono- or disubstituted amino, halogen, alkyl, substituted alkyl, hydroxy, etherified or esterified hydroxy, nitro, cyano, carboxy, esterified carboxy, alkanoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl, amidino, guanidino, mercapto, sulfo, phenylthio, phenyl-lower alkylthio, alkylphenylthio, phenylsulfinyl, phenyl-lower alkylsulfinyl, alkylphenylsulfinyl, phenylsulfonyl, phenyl-lower alkylsulfonyl, or alkylphenylsulfonyl; and wherein the bonds characterized by a wavy line are either single or double bonds; or an N-oxide of said compound with the stipulation that, if Y is pyridyl or unsubstituted cycloalkyl, X is imino, and the remaining radicals are as defined, then G is selected from the group comprising lower alkylene, -CH2-O-, -CH2-S-, oxa and thia; or a salt thereof. The compounds inhibit angiogenesis.

Phthalazines with angiogenesis inhibiting activity

The invention relates to compounds of formula I, wherein r is 0 to 2, n is 0 to 2; m is 0 to 4; R 1 and R 2 (i) are in each case a lower alkyl, or (ii) together form a bridge in subformula I* or (iii) together form a bridge in subformula I** wherein one or two of the ring members T 1 , T 2 , T 3 , and T 4 are nitrogen, and the remainder are in each case CH; A, B, D, and E are N or CH, wherein not more than 2 of these radicals are N; G is lower alkylene, acyloxy- or hydroxy-lower alkylene, —CH 2 —O—, —CH 2 —S—, —CH 2 —NH—, oxa, thia, or imino; Q is methyl; R is H or lower alkyl; X is imino, oxa, or thia; Y is aryl, pyridyl, or (un)substituted cycloalkyl; and Z is mono- or disubstited amino, halogen, alkyl, substituted alkyl, hydroxy, etherified or esterified hydroxy, nitro, cyano, carboxy, esterified carboxy, alkanoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl, amidino, guanidino, mercapto, sulfo, phenylthio, phenyl-lower alkylthio, alkylphenylthio, phenylsulfinyl, phenyl-lower alkylsulfinyl, alkylphenylsulfinyl, phenylsulfonyl, phenyl-lower alkylsulfonyl, or alkylphenylsulfony; and wherein the bonds characterized by a wavy line are either single or double bonds; or an N-oxide of said compound with the stipulation that, if Y is pyridyl or unsubstituted cycloalkyl, X is imino, and the remaining radicals are as defined, then G is selected from the group comprising lower alkylene, —CH 2 —O—, —CH 2 —S—, oxa and thia; or a salt thereof The compounds inhibit angiogenesis

Pyrido-, pyrimido-, pyridazo- and pyrazo- pyridazines having angiogenesis inhibiting activity

In the present invention, there are disclosed pyridazine derivatives of the general formula I, in which r is 0 to 2, n is 0 to 2; m is 0 to 4; Ri1 and Ri2 (i) are in each case a lower alkyl, or (ii) together form a bridge of the general formula I* or (iii) together form a bridge of the general formula I**, wherein one or two of the ring members Ti1, Ti2, Ti3, and Ti4 are nitrogen, and the remainder are in each case CH; A, B, D, and E are N or CH, wherein not more than 2 of these radicals are N; G represents a lower alkylene, acyloxy- or hydroxy-lower alkylene, -CHi2-O-, -CHi2-S-, -CHi2-NH-, oxa, thia, or imino; Q denotes methyl; R represents H or lower alkyl; X represents imino, oxa, or thia; Y denotes aryl, pyridyl, or (un)substituted cycloalkyl; and Z is mono- or disubstituted amino, halogen, alkyl, substituted alkyl, hydroxy, etherified or esterified hydroxy, nitro, cyano, carboxy, esterified carboxy, alkanoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl, amidino, guanidino, mercapto, sulfo, phenylthio, phenyl-lower alkylthio, alkylphenylthio, phenylsulfinyl, phenyl-lower alkylsulfinyl, alkylphenylsulfinyl, phenylsulfonyl, phenyl-lower alkylsulfonyl, or alkylphenylsulfonyl; and wherein the bonds characterized by a wavy line are either single or double bonds; or an N-oxide of said compound with the proviso that, if Y is pyridyl or unsubstituted cycloalkyl, X is imino, and the remaining radicals are as defined, then G is selected from the group comprising lower alkylene, -CHi2-O-, -CHi2-S-, oxa and thia; or a salt thereof The above-described derivatives inhibit angiogenesis Disclosed is also a process for preparing such derivatives as well as pharmaceutical compositions containing them

Pyridazine derivatives exhibiting inhibiting activity to angiogenesis, process of their preparation, their use and pharmaceutical compositions in which the derivatives are comprised

Frei Jorg

Papers

Phthalazines with angiogenesis inhibiting activity

Pyrido-, pyrimido-, pyridazo- and pyrazo- pyridazines having angiogenesis inhibiting activity

Pyridazine derivatives exhibiting inhibiting activity to angiogenesis, process of their preparation, their use and pharmaceutical compositions in which the derivatives are comprised