Claims for Patent: 6,982,265

Summary for Patent: 6,982,265

Title:	Pyrrolotriazine inhibitors of kinases
Abstract:	The present invention provides compounds of formula I ##STR00001## and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.
Inventor(s):	Hunt; John T. (Princeton, NJ), Bhide; Rajeev S. (Langhorne, PA), Borzilleri; Robert Michael (New Hope, PA), Qian; Ligang (Hopewell, NJ)
Assignee:	Bristol Myers Squibb Company (Princeton, NJ)
Application Number:	09/573,829
Patent Claims:	1. A compound of formula I ##STR00150## its enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X and Y are independently O, OCO, S, SO SO.sub.2, CO, CO.sub.2, NR.sup.10, NR.sup.11CO, NR.sup.12CONR.sup.13, NR.sup.14CO.sub.2, NR.sup.15SO.sub.2, NR.sup.15SO.sub.2, NR.sup.16SO.sub.2NR.sup.17, SO.sub.2NR.sup.18, CONR.sup.19, halogen, nitro, cyano, or X or Y are absent; Z is O, S, N, or CR.sup.20; R.sup.1 is hydrogen, CH.sub.3, OH, OCH.sub.3, SH, SCH.sub.3, OCOR.sup.21, SOR.sup.22, SO.sub.2R.sup.23, SO.sub.2NR.sup.24R.sup.25, CO.sub.2R.sup.26, CONR.sup.27R.sup.28, NH.sub.2, NR.sup.29SO.sub.2NR.sup.30R.sup.31, NR.sup.32SO.sub.2R.sup.33, NR.sup.34COR.sup.35, NR.sup.36CO.sub.2R.sup.37, NR.sup.38CONR.sup.39R.sup.40, halogen, nitro, or cyano; R.sup.2 and R.sup.3 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl, heterocycloalkyl or substituted heterocycloalkyl, or when X is halo, nitro or cyano R.sup.2 is absent or when Y is halo, nitro or cyano R.sup.3 is absent; R.sup.4 is alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl; R.sup.5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, or substituted aralkyl; or R.sup.4 and R.sup.5 may together form an optionally substituted monocyclic 5 7 membered saturated or unsaturated carbocyclic or heterocyclic ring, or an optionally substituted bicyclic 7 11 membered saturated or unsaturated heterocyclic ring, except that when Z is O or S, R.sup.5 is absent; R.sup.6 is hydrogen, alkyl, substituted alkyl, substituted aryl, heterocyclo, substituted heterocyclo, NR.sup.7R.sup.8, OR.sup.9 or halogen; R.sup.7 is selected from the group consisting of hydrogen, C.sub.2 C.sub.20 alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.21, R.sup.24, R.sup.25, R.sup.26, R.sup.27, R.sup.28, R.sup.29, R.sup.30, R.sup.31, R.sup.32, R.sup.34, R.sup.35, R.sup.36, R.sup.38, R.sup.39 and R.sup.40 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.22, R.sup.23, R.sup.33 and R.sup.37 are independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; and R.sup.20 is selected from the group consisting of hydrogen, lower alkyl and substituted alkyl, or R.sup.20 is absent if the carbon to which it is attached is part of an unsaturated aryl or heteroaryl ring; with the provisos that: a. R.sup.2 may not be hydrogen if X is SO, SO.sub.2, NR.sup.13CO.sub.2, or NR.sup.14SO.sub.2, b. R.sup.3 may not be hydrogen if Y is SO, SO.sub.2, NR.sup.13 CO.sub.2, or NR.sup.14SO.sub.2. 2. A compound selected from the group consisting of: N-(4-Chlorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine; 2-Methyl-5-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)phenol; 7-Bromo-N-(4-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine; N-(4-Chloro-2-fluorophenyl)pyrrolo[2,1-f][1,2,4}triazin-4-amine; 2-Methyl-5-[(6-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol; N-(4-Bromo-2-fluorophenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine; 2-Methyl-5-[(5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]phenol; 5-[[2-(Dimethylamino)pyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2-methylphe- nol; 5-[(5,7-Dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphen- ol; 5-[(6-Ethyl-5,7-dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-met- hylphenol; 5-[(5,6-Dimethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-meth- ylphenol; 2-Methyl-5-[(7-methylpyrrolo[2,1-f][1,2,4}triazin-4-yl)amino]phe- nol; N-(4-Bromo-2-fluorophenyl)-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-ami- ne; N-(4-Bromo-2-fluorophenyl)-7-methylpyrrolo[2,1-f][1,2,4]triazin-4-amin- e; 1-[2,3-Dihydro-6-(pyrrolo[2,1-f][1,2,4]triazin-4-ylamino)-1H-indol-1-yl- ]ethanone; N-(4-Bromo-2-fluorophenyl)-6-methylpyrrolo[2,1-f][1,2,4]triazin- -4-amine; 5-[(5-Ethylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphen- ol; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triaz- ine-6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-methanol; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid; 1-[[4-[(3-Hydroxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]tria- zin-6-yl]carbonyl]4-methylpiperazine; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-[2-(1-pyrrolidinyl)ethyl]p- yrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-phenylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; 4-[(3-Methoxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 2-Methyl-5-[5-methyl-6-(1H-1,2,4-triazol-1-ylmethyl)pyrrolo[2,1-f][1,2,4]- triazin-4-yl]amino]phenol; 4-[(3-Cyanophenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4}triazine-6-carboxyl- ic acid methyl ester; 4-[(3-Carboxyphenyl)amino]-5-methylpyrrolo[2,1-fl[1,2,4]triazine-6-carbox- ylic acid methyl ester; 4-[3-(Acetylamino)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid methyl ester; 4-[(3-Fluoro-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f[1,2,4]triazine-6- -carboxylic acid methyl ester; 5-Methyl-4-[(4-methyl-3-nitrophenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 5-Methyl-4-[[4-methyl-3-[(methylsulfonyl)amino]phenyl]amino]pyrrolo[2,1-f- ][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[(3-Cyano-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(1-Acetyl-2,3-dihydro-1H-indol-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,- 4}triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-1H-indol-1-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-car- boxylic acid methyl ester; 4-[(3-Amino-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(4-Bromo-2-fluorophenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(2,3-Dihydro-1H-indol-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid methyl ester; 5-Methyl-4-(5-quinolinylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)pyrrolo[2,1-f][1,2,4}triazine-6-carbox- ylic acid methyl ester; 4-[(3,4-Dimethylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-car- boxylic acid methyl ester; 4-[[5-(Hydroxymethyl)-2-methylphenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid methyl ester; 4-(1H-Indazol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxyl- ic acid methyl ester; 4-[(4-Bromo-3-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(4-Chloro-3-nitrophenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(2,3-Dihydro-1,4-benzodioxin-6-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4}- triazine-6-carboxylic acid methyl ester; 5-Methyl-4-[(5-methyl-2-pyridinyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid methyl ester; 4-[(1H-Benzotriazol-5-yl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid methyl ester; 5-Methyl-4-[[2-methyl-5-[(methylsulfonyl)amino]phenyl]amino]pyrrolo[2,1-f- ][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[(1,2-Dihydro-4-methyl-2-oxo-7-quinolinyl)amino]-5-methylpyrrolo[2,1-f]- [1,2,4]triazine-6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-methylphenyl)methylamino]-5-methylpyrrolo[2,1-f][1,2,4}tr- iazine-6-carboxylic acid methyl ester; 4-[(3-Hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carbox- ylic acid methyl ester; 4-[[2-(Aminosulfonyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; [4-[(3-Hydroxy-4-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin- -6-yl]carbamic acid phenylmethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4}triazine- -6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-methoxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid methyl ester; 4-[(3-Hydroxy-2-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-(2-Benzothiazolylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxy- lic acid methyl ester; 4-[[3-Hydroxy-4-[(phenylsulfonyl)amino]phenyl]amino]-5-methylpyrrolo[2,1-- f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[[3-(Aminosulfonyl)-4-methylphenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4}- triazine-6-carboxylic acid methyl ester; 4-[(2,3-Dihydro-1,3-dioxo-1H-isoindol-5-yl)amino]-5-methylpyrrolo[2,1-f][- 1,2,4]triazine-6-carboxylic acid methyl ester; 4-[[3-(Hydroxymethyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 4-(1H-Indol-6-ylamino)-5-methylpyrrolo[2,1-f][1,2,4}triazine-6-carboxylic acid methyl ester; 5-[(6-Amino-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphen- ol; 4-[(3-Carboxy-4-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]tria- zine-6-carboxylic acid methyl ester; 4-(3-Hydroxyphenoxy)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 5-Methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carbox- ylic acid methyl ester; 5-Methyl-4-[(1,2,3,4-tetrahydro-1,4-dioxo-6-phthalazinyl)amino]pyrrolo[2,- 1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[[3-(Hydroxysulfonyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid methyl ester; 4-[[3-[(Butylamino)sulfonyl]phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]tr- iazine-6-carboxylic acid methyl ester; 4-[[3-(Aminosulfonyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methoxypyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid ethyl ester; 4-[[3-(Hydrazinocarbonyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triaz- ine-6-carboxylic acid methyl ester; 5-Methyl-4-[[3-[(methylsulfonyl)amino]phenyl]amino]pyrrolo[2,1-f][1,2,4]t- riazine-6-carboxylic acid methyl ester; 5-Ethyl-4-[(3-hydroxy-4-methylphenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid ethyl ester; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]pyrrolo[2,1-f][1,2,4}triazine-6-c- arboxylic acid ethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-ethylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid ethyl ester; 4-[(4-Bromo-2-fluorophenyl)amino]-5-methoxypyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid ethyl ester; 4-[(4-Bromo-2-fluorophenyl)amino]-5-methoxy-N-[2-(1-pyrrolidinyl)ethyl]py- rrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(4-Bromo-2-fluorophenyl)amino]-5-methoxy-N-methyl-N-[2-(1-pyrrolidinyl- ) ethyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(6-Methoxy-3-pyridinyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-- carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methoxypyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid ethyl ester; 5-Methoxy-4-[(6-methoxy-3-pyridinyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6- -carboxylic acid ethyl ester; 5-Ethyl-4-[(4-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxy- lic acid ethyl ester; 4-[(3-Amino-4-methylphenyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-- carboxylic acid ethyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]pyrrolo[2,1-fl[1,2,4]triazine-5,6-dica- rboxylic acid diethyl ester; 5-Ethyl-4-[[4-methyl-3-[(methylsulfonyl)amino]phenyl]amino]pyrrolo[2,1-f]- [1,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-benzimidazol-1-yl)-5-methylpyrrolo[2,1-fl[1,2,4]t- riazine-6-carboxylic acid methyl ester; 5-Methyl-4-(1,2,3,4-tetrahydro-3-oxo-1-quinoxalinyl)pyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid methyl ester; 5-Methyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid methyl ester; 4-[[6-(Acetylamino)-3-pyridinyl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triaz- ine-6-carboxylic acid methyl ester; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]-N-[2-(1-pyrrolidinyl)ethyl]pyrro- lo[2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]-N-methyl-N-[2-(1-pyrrolidinyl)et- hyl]pyrrolo[2,1 f][1,2,4]triazine-6-carboxamide; 4-[(6-Chloro-3-pyridinyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-ca- rboxylic acid ethyl ester; 5-Ethyl-4-(1H-indazol-6-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxyli- c acid ethyl ester; 4-[(6-Methoxy-3-pyridinyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-- carboxylic acid ethyl ester; [4-[(6-Methoxy-3-pyridinyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazin-6-y- l]carbamic acid phenylmethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid; 4-Hydroxy-5-methoxypyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; 4-[2,3-Dihydro-5-[(methylsulfonyl)amino]-2-oxo-1H-indol-3-yl]-5-me- thylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 5-Ethyl-4-[(4-hydroxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxy- lic acid ethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-6-carbox- ylic acid methyl ester; 5-Methyl-4-(1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxyl- ic acid methyl ester; 4-[(4-Methoxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carbox- ylic acid methyl ester; 4-[(3,4-Dimethoxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-ca- rboxylic acid methyl ester; 5-Methyl-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-(2,3-Dihydro-3-oxo-1H-indazol-2-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazi- ne-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-3-oxo-1H-indazol-1-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazi- ne-6-carboxylic acid methyl ester; 4-[6-Fluoro-2-hydroxy-1H-indol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid methyl ester; 4-[6-Bromo-2-hydroxy-1H-indol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-[5-(Aminosulfonyl)-2,3-dihydro-2-oxo-1H-indol-3-yl]-5-methylpyrrolo[2,1- -f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[2,3-Dihydro-5-[[[2-(4-morpholinyl)ethyl]amino]sulfonyl]-2-oxo-1H-indol- -3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[2,3-Dihydro-2-oxo-5-[[[2-(1-pyrrolidinyl)ethyl]amino]sulfonyl]-- 1H-indol-3-yl]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-(5-Fluoro-2,3-dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4- ]triazine-6-carboxylic acid methyl ester; 4-[2,3-Dihydro-2-oxo-6-(trifluoromethyl)-1H-indol-3-yl]-5-methylpyrrolo[2- ,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)pyrrolo[2,1-f][1,2,4]triazine-5,6-dica- rboxylic acid diethyl ester; 4-[2,3-Dihydro-6-(methylsulfonyl)-2-oxo-1H-indol-3-yl]-5-methylpyrrolo[2,- 1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[5-[(Dimethylamino)sulfonyl]-2,3-dihydro-2-oxo-1H-indol-3-yl]-5-methylp- yrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[5-(Aminocarbonyl)-2,3-dihydro-2-oxo-1H-indol-3-yl]-5-methylpyrrolo[2,1- -f][1,2,4]triazine-6-carboxylic acid methyl ester; [4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazin- -6-yl]carbamic acid phenylmethyl ester; 4-(5-Cyano-2,3-dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-6-methyl-2-oxo-1H-pyrazolo[2,3-d]pyrimidin-3-yl)-5-methylp- yrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-pyrazolo[2,3-b]pyridin-3-yl)-5-methylpyrrolo[2,1-- f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N,5-dimethyl-N-[2-(1-pyrrolidinyl)eth- yl]pyrrolo [2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[2-(1-pyrrolidinyl)ethyl]p- yrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(4-morpholinyl)propyl]p- yrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[2-(4-morpholinyl)ethyl]py- rrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N-[[[3-(dimethylamino)propyl]amino]ca- rbonyl]-N-ethyl-5-methylpyrrolo[2,1-f][1,2,4}triazine-6-carboxamide; 4-[2,3-Dihydro-5-[[(2-hydroxyethyl)amino]sulfonyl]-2-oxo-1H-indol-3-yl]-5- -methylpyrrolo[2,1 f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[2,3-Dihydro-5-(4-morpholinylsulfonyl)-2-oxo-1H-indol-3-yl]-5-methylpyr- rolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[2,3-Dihydro-5-[(methylamino)sulfonyl]-2-OxO-1H-indol-3-yl]-5-methylpyr- rolo[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; 4-[(3-Bromophenyl)amino]-5-ethylpyrrolo[2,1-f[1,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-[(4-phenoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxy- lic acid ethyl ester; 5-Ethyl-4-[[1-(phenylmethyl)-1H-indazol-4-yl]amino]pyrrolo[2,1-f][1,2,4]t- riazine-6-carboxylic acid ethyl ester; 4-(6-Cyano-2,3-dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid methyl ester; 4-(2,5-Dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)-5-methylpyrrolo[2,1-f][1,2- ,4]triazine-6-carboxylic acid methyl ester; 3-(6-Amino-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)-1,3-dihydro-2H-indo- l-2-one; 3-(6-Amino-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)-1,3-dihydro- -2H-indol-2-one; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-[3-(4-morpholinyl)propyl]p- yrrolo [2,1-f][1,2,4]triazine-6-carboxamide; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]-N'-[2-(4-morpholinyl)ethyl]urea; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]-N'-[3-(4-morpholinyl)propyl]urea; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]-N'-[4-(4-morpholinyl)butyl]urea; 5-Ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]t- riazine-6-methanol; 4-(2,3-Dihydro-1-methyl-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4- ]triazine-6-carboxylic acid methyl ester; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]-N-[2-(1-pyrrolidinyl)ethyl]pyrro- lo[2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-4-[(6-methoxy-3-pyridinyl)amino]-N-methyl-N-[2-(1-pyrrolidinyl)et- hyl]pyrrolo [2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-N-[3-(1H-imidazol-1-yl)propyl]-4-[[1-(phenylmethyl)-1H-indazol-5-- yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(1-pyrrolidinyl)propyl]- pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(4-methyl-1-piperazinyl- )propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(1H-1,2,3-triazol-1-yl)- propyl]pyrrolo[2,1 f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(2H-1,2,3-triazol-2-yl)- propyl]pyrrolo[2,1 f][1,2,4}triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(1H-1,2,4-triazol-1-yl) propyl]pyrrolo[2,1 f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(2-methyl-1H-imidazol-1- -yl) propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[4-(4-morpholinyl)butyl]py- rrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N,5-dimethyl-N-[3-(4-morpholinyl)prop- yl]pyrrolo [2,1-f][1,2,4]triazine-6-carboxamide; 4-(6-Fluoro-2,3-dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(4-morpholinyl- ) propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-N-[2-(4-morpholinyl)ethyl]-4-[[1-(phenylmethyl)-1H-indazol-5-yl]a- mino]pyrrolo[2,1 f][1,2,4]triazine-6-carboxamide; 5-Ethyl-N-[6-[3-(1H-imidazol-1-yl)propyl]-2-pyridinyl]-4-[[1-(phenylmethy- l)-1H-indazol-5-yl]amino}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(5-Fluoro-2,3-dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[3-(4-morpholinyl- )propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(3-Hydroxy-4-methoxyphenyl)-5-methyl-N-[3-(4-morpholinyl)propyl]pyrrolo- [2,1-f][1,2,4]triazine-6-carboxamide; 7-Bromo-5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f]- [1,2,4]triazine-6-carboxylic acid ethyl ester; 7-Bromo-5-ethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f]- [1,2,4]triazine-6-methanol; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]-4-morpholinebutanamide; 5-Ethyl-6-[[2-4(4-morpholinyl)ethyoxy]methyl]-N-[1-(phenylmethyl)-1H-inda- zol-5-yl]pyrrolo[2,1-f][1,2,4]triazin-4-amine; 7-Bromo-5-ethyl-N-[2-(4-morpholinyl)ethyl]-4-[[1-(phenylmethyl)-1H-indazo- l-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N,5-dimethylpyrrolo[2,1-f][1,2,4]tria- zine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methoxy-N-[3-(1H-1,2,4-triazol-1-yl- )propyl]pyrrolo[2,1-f][1,2,4}triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methoxy-N-[3-(4-morpholinyl)propyl]- pyrrolo [2,1-f][1,2,4]triazine-6-carboxamide; 4-[(4-Bromophenyl)amino]-5-methyl-N-[3-(4-morpholinyl)propyl]pyrrolo[2,1-- f][1,2,4]triazine-6-carboxamide; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]-2-methylpropanamide; 3-[6-(Dimethylamino)-7-(hydroxymethyl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-4-yl]1,3-dihydro-2H-indol-2-one; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triaz- in-6-yl]methanesulfonamide; 3-(5,6-Dimethoxypyrrolo[2,1-f][1,2,4]triazin-4-yl)-1,3-dihydro-2H-indol-2- -one; N-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]- triazin-6-yl]-4-morpholinepropanesulfonamide; [4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methoxypyrrolo[2,1-f][1,2,4]triazi- n-6-yl}carbamic acid phenylmethyl ester; 4-[5-(Aminosulfonyl)-2,3-dihydro-2-oxo-1H-indol-3-yl]-5-methyl-N-[3-(4-mo- rpholinyl)propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 1,3-Dihydro-3-[5-methoxy-6-[[4-(4-methyl-1-piperazinyl)butyl]amino]pyrrol- o[2,1-f][1,2,4]triazin-4-yl]-2H-indol-2-one; 3-(6-Amino-5-methoxypyrrolo[2,1-f][1,2,4]triazin-4-yl)-1,3-dihydro-2H-ind- ol-2-one; 1,3-Dihydro-3-[5-methoxy-6-[[4-(4-morpholinyl)butyl]amino]pyrrol- o[2,1-f][1,2,4}triazin-4-yl]-2H-indol-2-one; 4-[(3-Hydroxy-5-methylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-[(4-Ethyl-3-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 1,3-Dihydro-3-[5-methyl-6-[2-(1H-1,2,4-triazol-1-yl)ethoxy]pyrrolo[2,1-f]- [1,2,4]triazin-4-yl]-2H-indol-2-one; 5-[(5,6-Dimethoxypyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]-2-methylphenol; 4-[(4-Bromo-3-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 4-[[3-Hydroxy-4-(1-methylethyl)phenyl]amino]-5-methylpyrrolo[2,1-f][1,2,4- ]triazine-6-carboxylic acid methyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-propanoic acid methyl ester; 4-[(4-Hydroxy-2-naphthalenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-[(4-Carboxy-3-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin- e-6-carboxylic acid methyl ester; 4-[(3-Chloro-4-fluorophenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 4-[(3-Chloro-4-fluorophenyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]tnazine-6-- carboxylic acid ethyl ester; 1,3-Dihydro-3-(6-methoxy-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)-2H-in- dol-2-one; 4-[(3-Chloro-4-fluorophenyl)amino]pyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-[3-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4}tr- iazin-6-yl]-1 -oxopropyl]morpholine; 1-[3-[4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methylpyrrolo[2,1-f][1,2,4]tr- iazin-6-yl]-1 oxopropyl]-4-methylpiperazine; 4-[[1-(Phenylmethyl)-1H-indazol-5-yl]amino]-5-ethylpyrrolo[2,1-f][1,2,4]t- riazine-6-carboxylic acid ethyl ester; 4-[[1-(Phenylmethyl)-1H-indazol-5-yl]amino]-5-propylpyrrolo[2,1-f][1,2,4]- triazine-6-carboxylic acid ethyl ester; 4-[(4-Bromophenyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carboxyli- c acid ethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5,6-dimethoxypyrrolo[2,1-f][,1,2,4]tr- iazine-7-carboxylic acid methyl ester; 4-[(4-Butyl-3-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-propylphenyl)amino]-5-methylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid methyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-propylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N-(2-methoxyethyl)-5-methylpyrrolo[2,- 1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-N-(3-methoxypropyl)-5-methylpyrrolo[2- ,1-f][1,2,4]triazine-6-carboxamide; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-methyl-N-[(tetrahydro-2-furanyl)met- hyl]pyrrolo[2,1 f][1,2,4]triazine-6-carboxamide; 5-Ethoxy-4-[(3-hydroxy-4-methylphenyl)amino}pyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; 4-[(4-Ethyl-3-hydroxyphenyl)amino]-5-methyl-N-[3-(4-morpholinyl)propyl]py- rrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(4-Bromo-3-hydroxyphenyl)amino]-5-methyl-N-[3-(4-morpholinyl)propyl]py- rrolo[2,1 f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-[3-(2H-1,2,3-triazol-2-yl)- propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-4-(phenylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-(methylphenylamino)pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-(1,2,3,4-tetrahydro-2-isoquinolinyl)pyrrolo[2,1-f][1,2,4]triazi- ne-6-carboxylic acid ethyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-N-(3-methoxypropyl)-5-methylpyrrolo[2- ,1-f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-[3-(4-methyl-1-piperazinyl- ) propyl]pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-N,5-dimethylpyrrolo[2,1-f][1,2,4]tria- zine-6-carboxamide; N-[2-(Dimethylamino)ethyl]-4-[(3-hydroxy-4-methylphenyl)amino]-5-methylpy- rrolo[2,1 f][1,2,4]triazine-6-carboxamide; 5-Ethyl-4-(1,2,3,4-tetrahydro-1-quinolinyl)pyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid ethyl ester; 5-Ethyl-4-[(phenylmethyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; 4-(2,3-Dihydro-2-oxo-1H-indol-3-yl)-5-ethoxypyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-[3-(1-pyrrolidinyl)propyl]- pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 5-Ethyl-4-(2-phenyl ethyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; N-[4-(Dimethylamino)butyl]-4-[(3-hydroxy-4-methylphenyl)amino]-5-methylpy- rrolo[2, 1-f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-(1-methylethyl)pyrrolo[2,1-f][1,2,4- ]triazine-6-carboxylic acid ethyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-methyl-N-13-(methylsulfonyl)propyl]- pyrrolo[2, 1-fi[1,2,4]triazine-6-carboxamide; 4-[(3-Chloro-4-fluorophenyl)methyl]-5-(1-methylethyl)pyrrolo[2,1-fl[1,2,4- ]triazine-6-carboxylic acid ethyl ester; [4-[(3-Chloro-4-fluorophenyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazin-6- -yl]carbamic acid phenylmethyl ester; 5-(1-Methylethyl)-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-- f][1,2,4]triazine-6-carboxylic acid ethyl ester; 4-(Butylamino)-5-ethylpyrrolo[2,1-fi][1,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-1(2-methoxyethyl)amino]pyrrolo[2,1-f][1,2,4]triazine-6-carboxyl- ic acid ethyl ester; 5-Ethyl-4-(4-morpholinyl)pyrrolo[2,1-fill,2,4]triazine-6-carboxylic acid ethyl ester; 5-Ethyl-4-[13-(1H-imidazol-1-yl)propyl]amino]pyrrolo[2,1-f][1,2,4}triazin- e-6-carboxylic acid ethyl ester; 2-Methyl-5-[[5-methyl-6-[3-(2H-1,2,3-triazol-2-yl)propoxy]pyrrolo[2,1-f][- 1,2,4]triazin-4-yl]amino]phenol; 1,3-Dihydro-3-[5-methyoxy-6-(phenylmethoxy)pyrrolo[2,1-f][1,2,4]triazin-4- -yl]-2H-indol-2-one; 5-Ethyl-4-[[(1S)-1-phenylethyl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carb- oxylic acid ethyl ester; 5-Ethyl-4-[[(1R)-1-phenylethyl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-carb- oxylic acid ethyl ester; 5-Ethyl-4-[[2-(2-pyridinyl)ethyl]amino]pyrrolo[2,1-f][1,2,4]triazine-6-ca- rboxylic acid ethyl ester; 4-[(4-Cyano-3-hydroxyphenyl)amino]-5-methylpyrrolo[2,1-f]1,2,4]triazine-6- -carboxylic acid methyl ester; 4-[(Cyclohexylmethyl)amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-carbox- ylic acid ethyl ester; 4-[[(4-Cyanocyclohexyl)methyl]amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; 4-[(3-Chloro-4-fluorophenyl)amino]-5-(phenylmethyl)pyrrolo[2,1-f][1,2,4]t- riazine-6-carboxylic acid ethyl ester; 5-(Phenylmethyl)-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f- ][1,2,4]triazine-6-carboxylic acid ethyl ester; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-(phenylmethyl)pyrrolo[2,1-f][1,2,4}- triazine-6-carboxylic acid ethyl ester; 4-1[(4-Bromophenyl)methyl]amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid ethyl ester; 5-Ethyl-4-[(trans-4-hydroxycyclohexyl)amino]pyrrolo[2,1-f][1,2,4]triazine- -6-carboxylic acid ethyl ester; N-(3-Bromophenyl)-5-methyl-6-[3-(2H-1,2,3-triazol-2-yl)propoxy]pyrrolo[2,- 1-f][1,2,4]triazin-4-amine; N-(4-Bromo-2-fluorophenyl)-5-methyl-6-[3-(2H-1,2,3-triazol-2-yl)propoxy]p- yrrolo[2,1-f][1,2,4]triazin-4-amine; 1,3-Dihydro-3-[5-methyl-6-[3-(2H-1,2,4-triazol-2-yl)propoxy]pyrrolo[2,1-f- ][1,2,4]triazin-4-yl]2H-indol-2-one; 5-Ethyl-4-[[(1-hydroxycyclohexyl)methyl]amino]pyrrolo[2,1-f][1,2,4]triazi- ne-6-carboxylic acid ethyl ester; 4-[[(3-Bromophenyl)methyl]amino]-5-ethyl pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester; 4-[[(2-Bromophenyl)methyl]amino]-5-ethylpyrrolo[2,1-f][1,2,4]triazine-6-c- arboxylic acid ethyl ester; 5-Ethyl-N,N-dimethyl-4-[[1-(phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2- ,1-f][1,2,4}triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-N-[3-(4-morpholinyl)propyll-5-propylp- yrrolo[2,1-f][1,2,4]triazine-6-carboxamide; 4-[(3-Hydroxy-4-methylphenyl)amino]-5-propyl-N-[3-(1-pyrrolidinyl)propyl}- pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide; N-(3-Bromophenyl)-5-methyl-6-[3-(4-morpholinyl)propyl]pyrrolo[2,1-f][1,2,- 4]triazin-4-amine; 4-(3-Chloro-4-fluorophenyl)amino]-5-[3-(phenylmethoxy)propyl]pyrrol o[2,1-f][1,2,4]triazine-6-carboxylic acid methyl ester; and 4-[[1-(Phenylmethyl)-1H-indazol-5-yl]amino]pyrrolo[2,1-f][1,2,4]triazine-- 6-carboxylic acid methyl ester; and pharmaceutically acceptable salts thereof. 3. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. 4. A pharmaceutical composition comprising a compound of claim 1 a compound of formula I ##STR00151## its enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X and Y are independently O, OCO, S, SO, SO.sub.2, CO, CO.sub.2, NR.sup.10, NR.sup.11CO, NR.sup.12CONR.sup.13, NR.sup.14CO.sub.2, NR.sup.15SO.sub.2, NR.sup.16SO.sub.2NR.sup.17, SO.sub.2NR.sup.18, CONR.sup.19, halogen, nitro, cyano, or X or Y are absent; Z is O, S, N, or CR.sup.20, R.sup.1 is hydrogen, CH.sub.3, OH, OCH.sub.3, SH, SCH.sub.3, OCOR.sup.21, SOR.sup.22, SO.sub.2 R.sup.23, SO.sub.2NR.sup.24R.sup.25, CO.sub.2R.sup.26, CONR.sup.27R.sup.28, NH.sub.2, NR.sup.29SO.sub.2NR.sup.30R.sup.31, NR.sup.32 SO.sub.2R.sup.33, NR.sup.34COR.sup.35, NR.sup.36CO.sub.2R.sup.37, NR.sup.38CONR.sup.39R.sup.40, halogen, nitro, or cyano; R.sup.2 and R.sup.3 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl, heterocycloalkyl or substituted heterocycloalkyl, or when X is halo, nitro or cyano R.sup.2 is absent or when Y is halo, nitro or cyano R.sup.3 is absent; R.sup.4 and R.sup.5 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl; or R.sup.4 and R.sup.5 may together form an optionally substituted monocyclic 5-7 membered saturated or unsaturated carbocyclic or heterocyclic ring, or an optionally substituted bicyclic 7 11 membered saturated or unsaturated heterocyclic ring, except that when Z is O or S, R.sup.5 is absent, or when Z is nitrogen, R.sup.4 and R.sup.5 are not both hydrogen; R.sup.6 is hydrogen, alkyl, substituted alkyl, substituted aryl, heterocyclo, substituted heterocyclo, NR.sup.7R.sup.8, OR.sup.9 or halogen; R.sup.7 is selected from the group consisting of hydrogen, C.sub.2 C.sub.20 alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.21, R.sup.24, R.sup.25, R.sup.26, R.sup.27, R.sup.28, R.sup.29, R.sup.30, R.sup.31, R.sup.32, R.sup.34, R.sup.35, R.sup.36, R.sup.38, R.sup.39 and R.sup.40 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.22, R.sup.23, R.sup.33 and R.sup.37 are independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; and R.sup.20 is selected from the group consisting of hydrogen, lower alkyl and substituted alkyl, or R.sup.20 is absent if the carbon to which it is attached is part of an unsaturated aryl or heteroaryl ring; with the provisos that: a. R.sup.2 may not be hydrogen if X is SO, SO.sub.2, NR.sup.13CO.sub.2, or NR.sup.14SO.sub.2 b. R.sup.3 may not be hydrogen if Y is SO, SO.sub.2, NR.sup.13CO.sub.2, or NR.sup.14SO.sub.2; in combination with pharmaceutically acceptable carrier and an anti-cancer or cytotoxic agent formulated as a fixed dose. 5. The pharmaceutical composition as recited in claim 4, wherein said anticancer or cytotoxic agent is selected from the group consisting of: taxoxifen, toremifen, raloxifene, droloxifene, iodoxyfene, megestrol acetate, anastrozole, letrazole, borazole, exemestane, flutamide, nilutamide, bicalutamide, cyproterone acetate, goserelin acetate, luprolide, finasteride, herceptin, methotrexate, 5-fluorouracil, cytosine arabinoside, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin, mithramycin, cisplatin, carboplatin, melphalan, chlorambucil, busulphan, cyclophosphamide, ifosfamide, nitrosoureas, thiotephan, vincristine, taxol, taxotere, etoposide, teiposide, amsacrine, irinotecan, topotecan and an epothilone. 6. A method for producing an antitangiogenic effect which comprises administering to a warm-blooded species in need thereof, an effective antiangiogenic producing amount of a compound of claim 1. 7. A compound of formula I ##STR00152## its enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X and Y are independently O, OCO, S, SO SO.sub.2, CO, CO.sub.2, NR.sup.10, NR.sup.11CO, NR.sup.12CoNR.sup.13, NR.sup.14CO.sub.2, NR.sup.15SO.sub.2, NR.sup.16SO.sub.2NR.sup.17, SO.sub.2NR.sup.18, CONR.sup.19, halogen, nitro, cyano, or X or Y are absent; Z is O, S, N, or CR.sup.20; R.sup.1 is hydrogen, CH.sub.3, OH, OCH.sub.3, SH, SCH.sub.3, OCOR.sup.21, SOR.sup.22, SO.sub.2R.sup.23, SO.sub.2NR.sup.24R.sup.25, CO.sub.2R.sup.26, CoNR.sup.27R.sup.28, NH.sub.2, NR.sup.29SO.sub.2NR.sup.30R.sup.31, NR.sup.32SO.sub.2R.sup.33, NR.sup.34 COR.sup.35, NR.sup.36CO.sub.2R.sup.37, NR.sup.38CONR.sup.39R.sup.40, halogen, nitro, or cyano; R.sup.2 and R.sup.3 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl, heterocycloalkyl or substituted heterocycloalkyl, or when X is halo, nitro or cyano R.sup.2 is absent or when Y is halo, nitro or cyano R.sup.3 is absent; R.sup.4 is heterocyclo or substituted heterocylco, R.sup.5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, or substituted aralkyl; except that when Z is O or S, R.sup.5 is absent; R.sup.6 is hydrogen, alkyl, substituted alkyl, substituted aryl, heterocyclo, substituted heterocyclo, NR.sup.7R.sup.8, OR.sup.9 or halogen; R.sup.7 is selected from the group consisting of hydrogen, C.sub.2 C.sub.20 alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.21, R.sup.24, R.sup.25, R.sup.26, R.sup.27, R.sup.28, R.sup.29, R.sup.30, R.sup.31, R.sup.32, R.sup.34, R.sup.35, R.sup.36, R.sup.38, R.sup.39 and R.sup.40 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo, R.sup.22, R.sup.23, R.sup.33 and R.sup.37 are independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo; and R.sup.20 is selected from the group consisting of hydrogen, lower alkyl and substituted alkyl, or R.sup.20 is absent if the carbon to which it is attached is part of an unsaturated aryl or heteroaryl ring; with the provisos that: a. R.sup.2 may not be hydrogen if X is SO, SO.sub.2, NR.sup.13CO.sub.2, or NR.sup.14SO.sub.2, b. R.sup.3 may not be hydrogen if Y is SO, SO.sub.2, NR.sup.13CO.sub.2, or NR.sup.14SO.sub.2. 8. The compound of claim 7, wherein R.sup.4 is a substituted 7 to 11 membered bicyclic ring system which has at least one heteroatom in at least one carbon atom-containing ring. 9. The compound of claim 8, wherein R4 is substituted indolyl.

Details for Patent 6,982,265

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2019-05-21
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2019-05-21