807639-63-0

Upstream product

• 2508-29-4 5-hydroxypentylamine 
• 5551-12-2 4-bromo-2-nitrobenzaldehyde 

Downstream Products

• 1056010-57-1 carbamic acid, [(4-bromo-2-nitrophenyl)methyl](5-hydroxypentyl)-, 1,1-dimethylethyl ester 
• 1007591-21-0 carbamic acid, [5-(acetyloxy)pentyl][(2-amino-4-bromo-phenyl)methyl]-, 1,1-dimethylethyl ester 
• 890532-74-8 1-pentanol, 5-[[(4-bromo-2-nitrophenyl)methyl]methylamino]-, acetate (ester) 
• 807639-64-1 carbamic acid, [5-(acetyloxy)pentyl][(4-bromo-2-nitrophenyl)methyl]-, 1,1-dimethylethyl ester 
• 807640-15-9 carbamic acid, [[2-[[6-(acetyloxy)-7-methoxy-4-quinazolinyl]amino]-4-bromophenyl]methyl](5-chloroxypentyl)-, phenylmethyl ester 
• 807639-69-6 1-pentanol,5-[[(4-bromo-2-nitrophenyl)methyl]methylamino]- 
• 807640-12-6 carbamic acid, [(4-bromo-2-nitrophenyl)methyl](5-hydroxypentyl)-, phenylmethyl ester 

Relevant academic research and scientific papers

USE OF MTKI 1 FOR TREATING OR PREVENTING BONE CANCER

The present invention is concerned with the finding that the macrocyclic quinazoline derivative 4,6-ethanediylidenepyrimido[4,5-b][6,1,12]benzoxadiazacyclo-pentadecine, 17-bromo-8,9,10,11,12,13, 14,19-octahydro-20-methoxy-13-methyl-, described as compound 22 in PCT publication WO2004/105765, is useful in the manufacture of a medicament for the treatment or prevention of bone cancers and methods for killing bone cancer cells, including osteosarcomas, chondrosarcomas, myeloma bone disease and osteolytic bone metastases from other primary sites. It accordingly provides methods for treating, preventing, delaying or mitigating bone cancer, or for preventing and treating of bone loss associated with cancer metastases.

VEGFR3 INHIBITORS

The present invention relates to the use of some of the macrocyclic quinazoline derivatives described in PCT publication WO2004/105765 as inhibitors of VEGFR3 mediated biological activities, especially those activities which are mediated by VEGFR3 ligands VEGF-C and/or VEGF-D.

MTKI QUINAZOLINE DERIVATIVES

The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents -C3-9alkyl-,-C1-5alkyl-NR13-C1-5alkyl-, -C1-5alkyl-NR14-CO-C1-5alkyl-, -C1-2alkyl-NR21-H2-CO-NH-C1-3alkyl- or -C1-2alkyl-NR23-CO-CR16R17-NH-; X1 represents O or -O-C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, -CO-C1-2alkyl or NR12-C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1; R3 represents hydrogen or cyano; R4 represents Ar4-C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl ; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydrogen, C1-4alkyl or R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R23 represents C1-4alkyl and R23 represents hydrogen when R16 and R17 taken together with the carbon atom to which they are attached from a C3-6cycloalkyl; R25, R26, R27 and R28 each independently represent hydrogen or C1-4alkylcarbonyl; Het1 represents 2-bora-l,3-dioxolanyl; Het2 represents piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl or 1,1-dioxothiomorpholinyl wherein said Het2 is optionally substituted with C1-4alkyloxycarbonyl or NR27R28-C1-4alkyl; Ar4 and Ar5 represents phenyl; Ar6 represents phenyl optionally substituted with nitro.

3-CYANO-QUINOLINE DERIVATIVES WITH ANTIPROLIFERATIVE ACTIVITY

The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof. Compounds of formula (I) inhibit tyrosine kinase enzymes.

MACROCYCLIC QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS

The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents O, CH2, NH or S; in particular Z represents NH; Y represents -C3-9alkyl-, -C3-9alkenyl-, -C3-9alkynyl-, -C3-7alkyl-CO-NH- optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4 alkyloxycarbonylamino-, -C3-7alkenyl-CO-NH- optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-oxy-C1-5alkyl-, -C1-5alkyl NR13-, -C1-5alkyl-, -C1-5alkyl-NR14-CO-C1-5alkyl-, -C1-5alkyl-CO NR15-C1-5alkyl-, -C1-6alkyl-CO-NH-, -C1-6alkyl-NH-CO-, -C1-3alkyl-NH-CS-Het20-, -C1-3alkyl-NH-CO-Het20-, -C1-2alkyl-CO-Het21-CO-, -Het22-CH2-CO-NH-C1-3alkyl-, -CO-NH-C1-6alkyl-, -NH-CO-C1-6alkyl-, -CO-C1-7alkyl-, -C1-7alkyl-CO-, -C1-6alkyl-CO-C1-6alkyl-, -C1-2alkyl-NH-CO-CR16R17-NH-, -C1-2alkyl-CO-NH-CR18R19-CO-, -C1-2alkyl-CO-NR20-C1-3alkyl-CO-, C1-2alkyl-NR21-CH2-CO-NH-C1-3alkyl-, or -NR22-CO-C1-3alkyl-NH-; X1 represents a direct bond, O or -O-C1-2alkyl-, CO, -CO-C1-2alkyl-, NR11, -NR11-C1-2alkyl-, CH2-, -O-N=CH- or -C1-2alkyl-; X2 represents a direct bond, O, -O-C1-2alkyl-, CO, -CO-C1-2alkyl-, NR12, -NR12-C1-2alkyl-, -CH2-, -O-N=CH- or -C1-2alkyl-. The growth inhibitory effect anti-tumour activity of the present compounds has been demonstrated in vitro, in enzymatic assays on the receptor tyrosine kinase EGFR.