US 8,912,200 B2Granted

Alkynyl substituted pyrimidinyl-pyrroles active as kinases inhibitors

AssigneeNerviano Medical Sciences S.R.L.

InventorsMaria Gabriella Brasca, Jay Aaron Bertrand, Paola Gnocchi, Ilaria Motto, Marcella Nesi, Achille Panzeri, Paola Vianello

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Abstract

The present invention relates to alkynyl substituted pyrimidinyl-pyrrole compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular Jak and/or Src family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such compounds or the pharmaceutical compositions containing them.

Claims9

Dependent claims

A compound of formula (I):

wherein:
one selected from R1 and R2 is hydrogen and the other is ethynyl-R7, wherein:
R7 is hydrogen, trialkylsylyl or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C7 cycloalkyl, cycloalkyl-alkyl, aryl, aryl-alkyl, heterocyclyl and heterocyclyl-alkyl;
R3 and R4 are independently hydrogen or an optionally substituted group selected from straight or branched C1-C6 alkyl, straight or branched C2-C6 alkenyl, straight or branched C2-C6 alkynyl, C3-C7 cycloalkyl, cycloalkyl-alkyl, aryl, arylalkyl, heterocyclyl and heterocyclyl-alkyl, or R3 and R4, taken together with the nitrogen atom to which they are bonded, may form an optionally substituted 5 to 7 membered heterocyclyl group optionally containing one additional heteroatom selected from N, O and S;
R5 is an optionally substituted aryl;
R6 is hydrogen, an optionally substituted straight or branched C1-C6 alkyl or NR8R9, wherein:
R8 and R9 are independently hydrogen or an optionally substituted group selected from straight or branched C1-C6 alkyl, C3-C7 cycloalkyl, cycloalkyl-alkyl, heterocyclyl and heterocyclyl-alkyl, or R8 and R9, taken together with the nitrogen atom to which they are bonded, may form an optionally substituted 5 to 7 membered heterocyclyl group optionally containing one additional heteroatom selected from N, O and S;
or a pharmaceutically acceptable salt thereof.

5 more elements

A compound or a pharmaceutically acceptable salt thereof which is selected from the group consisting of:

5-[2-Amino-5-(phenylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 1),
5-{2-Amino-5-[(3-hydroxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 2),
5-{2-Amino-5-[(4-methoxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 3),
5-{2-amino-5-[(3-aminophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 4),
5-{2-Amino-5-[(2-methoxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 5),
5-{2-Amino-5-[(2-aminophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 6),
5-{2-Amino-5-[(2,4-difluorophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 7),
5-{2-Amino-5-[(4-aminophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 8),
5-{2-Amino-5-[(5-amino-2-methoxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 9),
5-{2-Amino-5-[(4-amino-2-methoxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 10),
5-(2-Amino-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 11),
5-[2-Amino-5-({3-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 12),
5-(2-Amino-5-{[3-(tetrahydro-2H-pyran-4-ylamino)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 13),
tert-Butyl (2-{[3-({2-amino-4-[4-carbamoyl-5-(5-chloro-2-methylphenyl)-1H-pyrrol-2-yl]pyrimidin-5-yl}ethynyl)phenyl]amino}ethyl)carbamate (compd. 14),
5-[2-Amino-5-({3-[(2-hydroxyethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 15),
5-[2-Amino-5-({4-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 16),
tert-Butyl 3-({[3-({2-amino-4-[4-carbamoyl-5-(5-chloro-2-methylphenyl)-1H-pyrrol-2-yl]pyrimidin-5-yl}ethynyl)phenyl]amino}methyl)azetidine-1-carboxylate (compd. 17),
5-(2-Amino-5-{[4-(tetrahydro-2H-pyran-4-ylamino)phenyl]ethynyl}primidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 18),
5-[2-Amino-5-({4-[(2-hydroxyethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 19),
tert-Butyl 3-({[4-({2-amino-4-[4-carbamoyl-5-(5-chloro-2-methylphenyl)-1H-pyrrol-2-yl]pyrimidin-5-yl}ethynyl)phenyl]amino}methyl)azetidine-1-carboxylate (compd. 20),
tert-Butyl (2-{[4-({2-amino-4-[4-carbamoyl-5-(5-chloro-2-methylphenyl)-1H-pyrrol-2-yl]pyrimidin-5-yl}ethynyl)phenyl]amino}ethyl)carbamate (compd. 21),
5-[2-Amino-5-({2-methoxy-5-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 22),
5-{2-Amino-5-[(4-formylphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 23),
5-[2-Amino-5-({3-[(4-methylpiperazin-1-yl)methyl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 24),
5-[2-Amino-5-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 25),
5-[2-Amino-5-({4-[4-(pyrrolidin-1-yl)piperidin-1-yl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 26),
5-[2-Amino-5-({3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 27),
5-(2-Amino-5-{[4-(4-hydroxypiperidin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 28),
5-[2-Amino-5-({2-methoxy-4-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 29),
5-{2-Amino-5-[3-(1,1-dioxidothiomorpholin-4-yl)prop-1-yn-1-yl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 30),
5-[2-Amino-5-({4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 31),
5-[2-Amino-5-({3-[(1-methylpiperidin-4-yl)oxy]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 32),
N-[3-({2-Amino-4-[4-carbamoyl-5-(5-chloro-2-methylphenyl)-1H-pyrrol-2-yl]pyrimidin-5-yl}ethynyl)-4-methoxyphenyl]-1-methylpiperidine-4-carboxamide (compd. 33),
5-(2-Amino-5-{[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 34),
5-{2-Amino-5-[(5-bromo-2-methoxyphenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 35),
5-[2-Amino-5-(cyclohexylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 36),
5-[2-Amino-5-({2-methoxy-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 37),
5-[2-Amino-5-(cyclopropylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 38),
5-[2-Amino-5-(3,3-dimethylbut-1-yn-1-yl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 39),
5-{2-Amino-5-[(4-bromophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 40),
5-{2-Amino-5-[(4-bromo-2-fluorophenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 41),
5-(2-Amino-5-{[2-fluoro-4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 42),
5-[2-Amino-5-({2-[(2-hydroxyethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 43),
5-{2-Amino-5-[3-(dimethylamino)prop-1-yn-1-yl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 44),
5-{2-Amino-5-[(2-{2-(dimethylamino)ethyl]amino}phenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 45),
5-(2-Amino-5-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 46),
5-(2-Amino-5-{[3-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 47),
5-[2-Amino-5-({4-[(1-methylpiperidin-4-yl)oxy]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 48),
5-(2-Amino-5-{[2-fluoro-5-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 49),
5-{2-Amino-5-[3-(4-methylpiperazin-1-yl)prop-1-yn-1-yl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 50),
5-(2-Amino-5-{3-[(1-methylpiperidin-4-yl)oxy]prop-1-yn-1-yl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 51),
5-[2-Amino-5-({2-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide] (compd. 52),
5-[2-Amino-5-(pyridin-3-ylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 53),
5-[2-Amino-5-(3-hydroxy-3-methylbut-1-yn-1-yl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 54),
5-[2-Amino-5-(3-hydroxybut-1-yn-1-yl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 55),
5-(2-Amino-5-{3-[benzyl(methyl)amino]prop-1-yn-1-yl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 56),
5-[2-Amino-5-(phenylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-N-methyl-1H-pyrrole-3-carboxamide (compd. 57),
5-(2-Amino-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-N-methyl-1H-pyrrole-3-carboxamide (compd. 58),
5-[2-Amino-5-({4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 59),
5-[2-Amino-5-({4-[4-(dimethylamino)piperidin-1-yl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 60),
5-[2-Amino-5-({3-[(azetidin-3-ylmethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 61),
5-[2-Amino-5-({4-[(azetidin-3-ylmethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 62),
5-[2-Amino-5-({3-[(2-aminoethyl)amino]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 63),
5-{2-Amino-5-[(3-{[(1-methyl azetidin-3-yl)methyl]amino}phenyl)ethynyl]pyrimidin-4-yl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 64),
5-[2-Amino-5-({4-[(4-methylpiperazin-1-yl)methyl]phenyl}ethynyl)pyrimidin-4-yl]-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 65),
5-(2-Amino-5-{[4-(pyrrolidin-1-ylmethyl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 66),
5-(2-Amino-5-{[4-(piperidin-1-ylmethyl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 67),
5-(2-Amino-5-ethynylpyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 68),
5-(2-Amino-pyrimidin-4-yl)-2-(5-chloro-2-methyl-phenyl)-4-phenylethynyl-1H-pyrrole-3-carboxamide (compd. 69),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(3-hydroxyphenyl)ethml]-1H-pyrrole-3-carboxamide (compd. 70),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(4-methoxyphenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 71),
4-[(3-Aminophenyl)ethynyl]-5-(2-aminoprimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 72),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(2-methoxyphenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 73),
[(2-Aminophenyl)ethynyl]-4-(2-Amino-phenylethynyl)-5-(2-amino-pyrimidin-4-yl)-2-(5-chloro-2-methyl-phenyl)-1H-pyrrole-3-carboxamide (compd. 74),
4-[(4-amino-2-methoxyphenyl)ethynyl]-5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 75),
4-[(4-Aminophenyl)ethynyl]-5-(2-amino-pyrimidin-4-yl)-2-(5-chloro-2-methyl-phenyl)-1H-pyrrole-3-carboxamide (compd. 76),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(2-methylphenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 77),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(4-fluorophenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 78),
4-[(5-Amino-2-methoxyphenyl)ethynyl]-5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 79),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({3-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 80),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({3-[(4-methylpiperazin-1-yl)methyl]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 81),
4-({3-[(2-Aminoethyl)amino]phenyl}ethynyl)-5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 82),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 83),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({2-[2-hydroxyethyl)amino]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 84),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[2-fluoro-4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 85),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[2-methoxy-5-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 86),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[(2-{[2-(dimethylamino)ethyl]amino}phenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 87),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-[3-(dimethylamino)prop-1-yn-1-yl]-1H-pyrrole-3-carboxamide carboxamide (compd. 88),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 89),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[3-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide carboxamide (compd. 90),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({3-[(1-methylpiperidin-4-yl)oxy]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 91),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({4-[(1-methylpiperidin-4-yl)oxy]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 92),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[2-fluoro-5-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 93),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({2-[(1-methylpiperidin-4-yl)amino]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 94),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 95),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({4-[4-(dimethylamino)piperidin-1-yl]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 96),
5-(2-Aminopyrimidin-4-yl)-4-{[4-(1,4′-bipiperidin-1′-yl)phenyl]ethynyl}-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide (compd. 97),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({4-[4-(pyrrolidin-1-yl)piperidin-1-yl]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 98),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-{[4-(piperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 99),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-4-({4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 100),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-4-[(2-{[2-(dimethylamino)ethyl]amino}phenyl)ethynyl]-1H-pyrrole-3-carboxamide (compd. 101),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-4-({3-[(1-methylpiperidin-4-yl)oxy]phenyl}ethynyl)-1H-pyrrole-3-carboxamide (compd. 102),
5-(2-Aminopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-4-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 103),
2-(5-Chloro-2-methylphenyl)-5-[2-(methylamino)-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl]-1H-pyrrole-3-carboxamide (compd. 104),
2-(5-Chloro-2-methylphenyl)-5-(5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-1H-pyrrole-3-carboxamide (compd. 105),
2-(5-Chloro-2-methylphenyl)-5-(2-methyl-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-1H-pyrrole-3-carboxamide (compd. 106),
2-(5-Chloro-2-methylphenyl)-5-[2-(methylamino)pyrimidin-4-yl]-4-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-1H-pyrrole-3-carboxamide (compd. 107),
2-(5-Chloro-2-methylphenyl)-4-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-5-(pyrimidin-4-yl)-1H-pyrrole-3-carboxamide (compd. 108),
2-(5-Chloro-2-methylphenyl)-4-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}-5-(2-methylpyrimidin-4-yl)-1H-pyrrole-3-carboxamide (compd. 109),
5-(2-Amino-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-1H-pyrrole-3-carboxamide (compd. 110),
5-[2-Amino-5-(phenylethynyl)pyrimidin-4-yl]-2-(5-chloro-2-ethylphenyl)-N-methyl-1H-pyrrole-3-carboxamide (compd. 111) and
5-(2-Amino-5-{[4-(4-methylpiperazin-1-yl)phenyl]ethynyl}pyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-N-methyl-1H-pyrrole-3-carboxamide (compd. 112).

109 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/235,477Filed 18 Jul 2012
Priority: EP 1117573628 Jul 2011
Published: US 2014/0194406 A110 Jul 2014
Granted: 16 Dec 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61K 31/541
Having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame: non-condensed thiazines containing…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents

Family

US 2014/0194406 A1Pre-grant publication · published 10 Jul 2014
US 8,912,200 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

14/235,477Filed 18 Jul 2012

Priority

EP 1117573628 Jul 2011

Published

US 2014/0194406 A110 Jul 2014

Granted

16 Dec 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61K 31/541
Having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame: non-condensed thiazines containing…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 35/00
Antineoplastic agents