# US 2014/0194406 A1 · Alkynyl substituted pyrimidinyl-pyrroles active as kinases inhibitors

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- Number: US 2014/0194406 A1
- Document ID: US20140194406A1
- Status: Published application
- Kind: A1
- Application number: 14/235,477
- Filed: 2012-07-18
- Published: 2014-07-10
- Earliest claimed: 2011-07-28
- Assignees: Nerviano Medical Sciences S.R.L.
- Inventors: Maria Gabriella Brasca; Jay Aaron Bertrand; Paola Gnocchi; Ilaria Motto; Marcella Nesi; Achille Panzeri; Paola Vianello
- Web page: https://patentgrep.com/patent/US20140194406A1

## CPC

- A61K 31/541: Non-condensed thiazines containing further heterocyclic rings
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## 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.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

A compound of formula (I) as defined in claim 1 wherein:
R1 is ethynyl-R7 and R2 is hydrogen.

### Claim 3 (depends on 2)

A compound of formula (I) as defined in claim 2 wherein:
R3 and R4 are independently hydrogen 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.

### Claim 4 (depends on 2)

A compound of formula (I) as defined in claim 2 wherein:
R7 is an optionally substituted aryl.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

A compound of formula (I) as defined in claim 1 wherein:
R1 is hydrogen and R2 is ethynyl-R7.

### Claim 7 (depends on 6)

A compound of formula (I) as defined in claim 6 wherein:
R3 and R4 are independently hydrogen 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.

### Claim 8

(canceled)

### Claim 9

(canceled)

### Claim 10

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}pyrimidin-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)ethynyl]-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-aminopyrimidin-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).

### Claim 11 (depends on 1)

A process for preparing a compound of formula (I) as defined in claim 1 or the pharmaceutically acceptable salts thereof, characterized in that the process comprises the following steps:
Step 1: metal-catalyzed coupling reactions of a halo derivative of formula (II)
wherein R6 is as defined in claim 1, with an optionally substituted aryl boronic acid of formula (IIIa) or an optionally substituted aryl boronic-ester of formula (IIIb):
wherein R5 is as defined in claim 1;
Step 2: hydrolysis under basic conditions of the resultant compound of formula (IV)
wherein R5 and R6 are as defined above;
Step 3: regioselective mono-halogenation of the resultant carboxylic acid of formula (V)
wherein R5 and R6 are as defined above;
Step 4: amidation of the resultant mono-halogenated carboxylic acid of formula (VI)
wherein R5 and R6 are as defined above and X is a halogen, through reaction with a derivative of formula (VII)
NHR3R4 (VII)
wherein R3 and R4 are as defined in claim 1;
Step 5: metal-catalyzed coupling reactions of the resultant mono-halogenated carboxamide of formula (VIII)
wherein R3, R4, R5 and R6 are as defined above and X is a halogen, through reaction with a derivative of formula (IX):
≡R7 (IX)
wherein R7 is as defined in claim 1, to give a compound of formula (I)
wherein R1 is ethynyl-R7, R2 is hydrogen, R3, R4, R5, R6 and R7 are as defined above; alternatively
Step 6: amidation of the carboxylic acid of formula (V) as defined above, through reaction with an amine of formula (VII) as defined above;
Step 7: regioselective introduction of a protecting group on the pyrrole nitrogen of the resultant carboxamide of formula (X)
wherein R3, R4, R5 and R6 are as defined above.
Step 8: regioselective mono-halogenation of the resultant protected compound of formula (XI)
wherein R3, R4, R5 and R6 are as defined above, and PG is a protecting group such as SEM, Boc.
Step 9: metal-catalyzed coupling reaction of the resultant mono-halogenated carboxamide of formula (XII)
wherein R3, R4, R5, R6 and PG are as defined above, and X is a halogen, through reaction with a derivative of formula (IX) as defined above;
Step 10: deprotection of the resultant compound of formula (XIII)
wherein R1 is ethynyl-R7, R3, R4, R5, R7 and PG are as defined above, to give a compound of formula (I)
wherein R1 is ethynyl-R7, R2 is hydrogen, R3, R4, R5, R6 and R7 are as defined above; alternatively,
Step 11: regioselective introduction of a protecting group on the pyrrole nitrogen of the carboxylic ester of formula (IV) as defined above;
Step 12: regioselective mono-halogenation of the resultant protected carboxylic ester of formula (XIV)
wherein R5, R6 and PG are as defined above;
Step 13: metal-catalyzed coupling reaction of the resultant mono-halogenated carboxylic ester of formula (XV)
wherein R5, R6, X and PG are as defined above, through reaction with a derivative of formula (IX)′
≡R7′ (IX)′
wherein R7′ is trialkylsylyl;
Step 14: hydrolysis under basic conditions of the resultant trialkylsilyl-protected alkyne of formula (XVI)
wherein R5, R6 and PG are as defined above;
Step 15: amidation of the resultant carboxylic acid of formula (XVII)
wherein R5, R6 and PG are as defined above, through reaction with an amine derivative of formula (VII) as defined above;
either
Step 16: metal-catalyzed coupling reaction of the terminal alkyne of the resultant carboxamide of formula (XVIII)
wherein R3, R4, R5, R6 and PG are as defined above, through reaction with a halo derivative of formula (XIX):
X′—R7″ (XIX)
wherein R7″ is an optionally substituted aryl group and X′ is bromine or iodine;
Step 17: then deprotection of the resultant compound of formula (XX)
wherein R7″, R3, R4, R5, R6 and PG are as defined above, to give a compound of general formula (I)
wherein R1 is optionally substituted arylethynyl, R2 is hydrogen, R3, R4, R5 and R6 are as defined above;
or
Step 17a: direct deprotection of the terminal alkyne compound of formula (XVIII) as defined above, to give a compound of general formula (I)
wherein R1 is ethynyl, R2 is hydrogen, R3, R4, R5 and R6 are as defined above; alternatively
Step 18: metal-catalyzed coupling reaction of a halo derivative of formula (XXI)
wherein R3, R4, R5, R6, X and PG are as defined above, through reaction with a derivative of formula (XXII)
NHR10R11 (XXII)
wherein R10 and R11 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 R10 and R11, 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;
Step 19: deprotection of the resultant compound of formula (XXIII)
wherein R3, R4, R5, R6, R10, R11 and PG are as defined above, to give a compound of general formula (I)
wherein R1 is amino-aryl-ethynyl, R2 is hydrogen, R3, R4, R5 and R6 are as defined above; alternatively,
Step 20: regioselective mono-halogenation of a compound of formula (X) as defined above;
Step 21: metal-catalyzed coupling reaction of the resultant halo derivative of formula (XXIV)
wherein R3, R4, R5, R6 and X are as defined above, through reaction with a derivative of formula (IX) as defined above, to give a compound of formula (I)
wherein R1 is hydrogen, R2 is ethynyl-R7, R3, R4, R5, R6 and R7 are as defined above; alternatively,
Step 22: regioselective mono-halogenation of the carboxylic ester of formula (IV) as defined above;
Step 23: hydrolysis under basic conditions of the resultant compound of formula (XXV)
wherein R5 and R6 are as defined above and X is a halogen;
Step 24: amidation of the resultant mono-halogenated carboxylic acid of formula (VI) as defined above through reaction with a derivative of formula (VII) as defined above;
Step 25: metal-catalyzed coupling reactions of the resultant mono-halogenated carboxamide of formula (VIII) as defined above through reaction with a derivative of formula (IX) as defined above to give a compound of formula (I)
wherein R1 is ethynyl-R7, R2 is hydrogen, R3, R4, R5, R6 and R7 are as defined above;
optionally converting a compound of formula (I) into another different compound of formula (I), and, if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof or converting a salt into the free compound of formula (I).

### Claim 12 (depends on 1)

A method for treating a disease caused by and/or associated with a dysregulated protein kinase activity which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I) as defined in claim 1.

### Claim 13 (depends on 12)

The method according to claim 12 for treating a disease caused by and/or associated with a dysregulated JAK and/or Src family kinases activity.

### Claim 14 (depends on 12)

The method according to claim 12 wherein the disease is selected from the group consisting of cancer, cell proliferative disorders, viral infections, immune-related disorders, neurodegenerative disorders, cardiovascular diseases and bone related diseases.

### Claim 15 (depends on 14)

The method according to claim 14 wherein the cancer is selected from the group consisting of carcinoma such as bladder, breast, brain, colon, kidney, liver, lung, including small cell lung cancer, head and neck, esophagus, gall-bladder, ovary, uterine, pancreas, stomach, cervix, thyroid, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage including leukaemia, T and B acute lymphoblastic leukemia (ALL), including DS-ALL, B-cell lymphoma, T-cell-lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Multiple Myeloma, hairy cell lymphoma, Burkett's lymphoma and mantle cell lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukaemias, acute megakaryoblastic leukaemia, myelodysplastic syndrome and promyelocytic leukaemia, myeloproliferative disorders like Polycythemia Vera (PV), Essential Thrombocythemia (ET), Primary myelofibrosis and myelofibrosis secondary to PV and ET, chronic myelomonocytic leukaemia; tumors of mesenchymal origin, including sarcoma, fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including astrocytoma neuroblastoma, glioma and schwannomas; other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, thyroid follicular cancer, Kaposi's sarcoma, mesothelioma.

### Claim 16 (depends on 14)

The method according to claim 14 wherein the cell proliferative disorder is selected from the group consisting of benign prostate hyperplasia, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis, glomerulonephritis and post-surgical stenosis and restenosis.

### Claim 17 (depends on 14)

The method according to claim 14 wherein the viral infection comprises the prevention of AIDS development in HIV-infected individuals.

### Claim 18 (depends on 14)

The method according to claim 14 wherein the immune-related disorder is selected from the group consisting of transplant rejection, skin disorders like psoriasis, allergies, asthma and autoimmune-mediated diseases such as rheumatoid arthritis (RA), systemic lupus erythethatosus (SLE), Crohn's disease and amyotrophic lateral sclerosis.

### Claim 19 (depends on 14)

The method according to claim 14 wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, degenerative nerve diseases, encephalitis, Stroke, Parkinson's Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease), Huntington's Disease, Pick's Disease.

### Claim 20 (depends on 14)

The method according to claim 14 wherein the cardiovascular disease is selected from the group consisting of atherosclerosis primary or secondary to diabetes, heart attack and stroke.

### Claim 21 (depends on 14)

The method according to claim 14 wherein the bone loss disease is selected from the group consisting of osteoporosis and bone metastasis.

### Claim 22 (depends on 12)

The method according to claim 12 further comprising subjecting the mammal in need thereof to a radiation therapy or chemotherapy regimen in combination with at least one cytostatic or cytotoxic agent.

### Claim 23

(canceled)

### Claim 24

(canceled)

### Claim 25 (depends on 1)

An in vitro method for inhibiting the JAK and/or Src family kinase proteins activity which comprises contacting the said protein with an effective amount of a compound of formula (I) as defined in claim 1.

### Claim 26 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, and at least one pharmaceutically acceptable excipient, carrier and/or diluent.

### Claim 27 (depends on 26)

A pharmaceutical composition according to claim 26 further comprising one or more chemotherapeutic agents.

### Claim 28 (depends on 1)

A product comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy.

### Claim 29

(canceled)

### Claim 30

(canceled)

### Claim 31

(canceled)

### Claim 32 (depends on 1)

An intermediate mono-halogenated carboxamide of formula (VIII)
wherein R3, R4, R5 and R6 are as defined in claim 1 and X is a halogen.