wherein a when X is NH or N CH 3, R 3 is selected from chlorine and cyano; and b when X is O, R 3 is CN; iv a group CR 6 R 7 R 8 wherein R 6 and R 7 are each selected from hydrogen and methyl, and R 8 is selected from hydrogen, methyl, C 1 4 alkylsulphonylmethyl, hydroxymethyl and cyano; v a pyridazin 4 yl group optionally substituted by one or two substituents selected from methyl, ethyl, methoxy and ethoxy; vi a substituted imidazothiazole group wherein the substituents are selected from methyl, ethyl, amino, fluorine, chlorine, amino and methylamino; and vii an optionally substituted 1, 3 dihydro isoindol 2 yl or optionally substituted 2, 3 dihydro indol 1 yl group wherein the optional substituents in each case are selected from halogen, cyano, amino, C 1 4 mono and dialkylamino, CONH 2 or CONH C 1 4 alkyl C 1 4 alkyl and C 1 4 alkoxy wherein the C 1 4 alkyl and C 1 4 alkoxy groups are optionally substituted by hydroxy, methoxy, or amino; viii 3 pyridyl optionally substituted by one or two substituents selected from hydroxy, halogen, cyano, amino, C 4 4 mono and dialkylamino, CONH 2 or CONH C 1 4 alkyl, C 1 4 alkyl and C 1 4 alkoxy wherein the C 1 4 alkyl and C 1 4 alkoxy groups are optionally substituted by hydroxy, methoxy, or amino, but excluding the compounds 2 oxo 1, 2 dihydro pyridine 3 carboxylic acid 3 5 morpholin 4 ylmethyl 1H benzoimidazol 2 yl 1H pyrazol 4 yl amide and 2, 6 dimethoxy N 3 5 morpholin 4 ylmethyl 1H benzoimidazol 2 yl 1H pyrazol 4 yl nicotinamide; ix thiomorpholine or an S oxide or S, S dioxide thereof optionally substituted by one or two substitutents selected from halogen, cyano, amino, C 1 4 mono and dialkylamino, CONH 2 or CONH C 1 4 alkyl C 1 4 alkyl and C 1 4 alkoxy wherein the C 1 4 alkyl and C 1 4 alkoxy groups are optionally substituted by hydroxy, methoxy, or amino; and when E A is NR 2, R 1 is additionally selected from x 2 fluorophenyl, 3 fluorophenyl, 4 fluorophenyl, 2, 4 difluorophenyl, 3, 4 difluorophenyl, 2, 5 difluorophenyl, 3, 5 difluorophenyl, 2, 4, 6 trifluorophenyl, 2 methoxyphenyl, 5 chloro 2 methoxyphenyl, cyclohexyl, unsubstituted 4 tetrahydropyranyl and tert butyl; xi a group NR 10 R 11 where R 10 and R 11 are each C 1 4 alkyl or R 10 and R 11 are linked so that NR 10 R 11 forms a saturated heterocyclic group of 4 to 6 ring members optionally containing a second heteroatom ring member selected from O, N, S and SO 2, the heterocyclic group being optionally substituted by C 1 4 alkyl, amino or hydroxy; xii pyridone optionally substituted by one or two substituents selected from hydroxy, halogen, cyano, amino, C 1 4 mono and dialkylamino, CONH 2, CONH C 1 4 alkyl, C 1 4 alkyl and C 1 4 alkoxy wherein the C 1 4 alkyl and C 1 4 alkoxy groups are optionally substituted by hydroxy, methoxy, or amino; when E A is C CH 3 2 NR 2 or CH 2 NR 2, R 1 is additionally selected from xiii unsubstituted 2 furyl and 2, 6 difluorophenyl; and when E A is C CH 3 2 NR 2, R 1 is additionally selected from xiv unsubstituted phenyl; and when E is CH 2, R 1 is additionally selected from xv unsubstituted tetrahydropyran 4 yl; and B when M is a group D2 A is selected from a bond and a group NR 2 where R 2 is hydrogen or methyl; E is selected from a bond, CH 2, CH CN and C CH 3 2; R 1 is selected from xvi a 2 substituted 3 furyl group of the formula

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عضویت

The effects of hormonal treatment combined with radiation were studied in 466 patients 231 ZOLADEX flutamide radiation, 235 radiation alone with bulky primary tumors confined to the prostate stage B2 or extending beyond the capsule stage C, with or without pelvic node involvement