Pyrrolo[2,3-B]pyridine derivatives active as kinase inhibitors
Compounds which are pyrrolo[2,3-b]pyridine derivatives or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases and neurodegenerative disorders; also disclosed is a process under SPS conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.
1. A compound of formula (I)
wherein
R is selected from the group consisting of —R a , —COR a , —CONR a R b , —SO 2 R a and —COOR a ;
R 1 is —NR c R d or —OR c ;
wherein R a , R b , R c and R d are the same or different and are each independently hydrogen or a group, optionally further substituted, which is straight or branched C 1 -C 6 alkyl, straight or branched C 2 -C 6 alkenyl, straight or branched C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 6 alkyl, an aryl, aryl C 1 -C 6 alkyl, a heterocycle and heterocycle C 1 -C 6 alkyl or, taken together with the nitrogen atom to which they are bonded, R a and R b as well as R c and R d form a 1,3-dioxolane, pyran, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, tetrahydrofuran, hexamethyleneimine, 1,4-hexahydrodiazepine or azetidine group;
R 2 is a group, optionally further substituted, selected from the group consisting of straight or branched C 1 -C 6 alkyl, straight or branched C 2 -C 6 alkenyl, straight or branched C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl C 1 -C 6 alkyl, aryl, aryl C 1 -C 6 alkyl, heterocycle and heterocycle C 1 -C 6 alkyl;
wherein any of R a , R b , R c , R d or R 2 is independently optionally substituted by halogen, nitro, oxo groups, carboxy, cyano, alkyl, perfluoroalkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl, amino groups, carbonylamino groups, hydroxy groups, carbonyl groups or sulfurated groups;
wherein said aryl is selected from the group consisting of phenyl, indanyl, biphenyl, α- or β-naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, imidazolyl, imidazopyridyl, 1,2-methylenedioxyphenyl, thiazolyl, isothiazolyl, pyrrolyl, pyrrolyl-phenyl, furyl, phenyl-furyl, benzotetrahydrofuranyl, oxazolyl, isoxazolyl, pyrazolyl, chromenyl, thienyl, benzothienyl, isoindolinyl, benzoimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, benzofurazanyl, 1,2,3-triazolyl and 1-phenyl-1,2,3-triazolyl;
wherein said heterocycle is selected from the group consisting of 1,3-dioxolane, pyran, pyrrolidine, pyrroline, imadazoline, imidazolidine, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, tetrahydrofuran, hexamethyleneimine, 1,4-hexahydrodiazepine and azetidine;
or isomers, tautomers, carriers, and pharmaceutically acceptable salts thereof.
2. The compound of formula (I) according to claim 1 wherein R 1 is a group —NR c R d and R c and R d are both hydrogen atoms or one of them is a hydrogen atom and the remaining one of R c or R d is alkyl or alkenyl group or it is an optionally substituted aryl or arylalkyl group.
3. The compound of formula (I) according to claim 1 , wherein R is hydrogen atom or a group —SO 2 R a , wherein R a is a straight or branched alkyl or optionally substituted aryl or arylalkyl group.
4. The compound of formula (I) according to claim 1 , wherein R is —COR a , wherein R a is a straight or branched alkyl, cycloalkyl or optionally substituted aryl or arylalkyl group.
5. The compound of formula (I) according to claim 1 wherein R is —CONR a R b where one of R a and R b is a hydrogen atom and the other of R a and R b is a straight or branched alkyl, optionally substituted aryl or arylalkyl group.
6. The compound of formula (I) according to claim 1 wherein R is —CONR a R b wherein R a and R b form, together with the nitrogen atom to which they are bonded, a pipertdine, piperazine or morpholine ring.
7. The compound of formula (I) according to claim 1 wherein R 2 is alkyl, alkenyl, cycloalkyl, cycloalkyl-alkyl or an optionally substituted aryl or arylalkyl group.
8. A compound of formula (I) according to claim 1 wherein said compound has the formula:
wherein fragments A, B, and C in the formula recited above are denoted by codes A1- A9, B1- B15 and C1- C9, as follows:
Fragment
Code
A1
A2
A3
A4
A5
A6
A7
A8
A9
TABLE II
B groups
Fragment
Code
B1
B2
B3
B4
B5
B6
B7
B8
B9
B10
B11
B12
H
B13
B14
B15
TABLE III
C groups
Fragment
Code
C1
C2
C3
C4
C5
C6
C7
C8
C9
9. The compound of formula (I) according to claim 8 wherein
fragments A, B and C are as defined in claim 8 , and wherein the compound is:
A3-M-B5-C2
A3-M-B6-C2
A4-M-B5-C2
A4-M-B6-C2
A7-M-B5-C2
A7-M-B6-C2
A6-M-B5-C2
A6-M-B6-C2
A1-M-B5-C2
A1-M-B6-C2
A5-M-B5-C2
A5-M-B6-C2
A8-M-B5-C2
A8-M-B6-C2
A2-M-B5-C2
A2-M-B6-C2
A3-M-B5-C5
A3-M-B6-C5
A4-M-B5-C5
A4-M-B6-C5
A7-M-B5-C5
A7-M-B6-C5
A6-M-B5-C5
A6-M-B6-C5
A1-M-B5-C5
A1-M-B6-C5
A5-M-B5-C5
A5-M-B6-C5
A8-M-B5-C5
A8-M-B6-C5
A2-M-B5-C5
A2-M-B6-C5
A3-M-B1-C2
A3-M-B4-C2
A4-M-B1-C2
A4-M-B4-C2
A7-M-B1-C2
A7-M-B4-C2
A6-M-B1-C2
A6-M-B4-C2
Al-M-B1-C2
Al-M-B4-C2
A5-M-B1-C2
A5-M-B4-C2
A8-M-B1-C2
A8-M-B4-C2
A2-M-B1-C2
A3-M-B1-C5
A3-M-B4-C5
A4-M-B1-C5
A4-M-B4-C5
A7-M-B1-C5
A7-M-B4-C5
A6-M-B1-C5
A6-M-B4-C5
A1-M-B1-C5
A1-M-B4-C5
A5-M-B1-C5
A5-M-B4-C5
A8-M-B1-C5
A8-M-B4-C5
A2-M-B1-C5
A2-M-B4-C5
A3-M-B9-C2
A3-M-B10-C2
A4-M-B10-C2
A1-M-B10-C2
A5-M-B10-C2
A3-M-B9-C5
A7-M-B9-C5
A1-M-B9-C5
A1-M-B10-C5
A9-M-B5-C1
A9-M-B7-C1
A9-M-B5-C2
A9-M-B7-C2
A9-M-B5-C3
A9-M-B7-C3
A9-M-B8-C3
A9-M-B5-C4
A9-M-B5-C5
A9-M-B5-C6
A9-M-B7-C6
A9-M-B8-C6
A9-M-B5-C7
A9-M-B6-C7
A9-M-B8-C7
A9-M-B5-C8
A9-M-B7-C8
A9-M-B8-C8
A9-M-B13-C2
A9-M-B13-C5
A9-M-B13 -C6
A9-M-B13-C8
A9-M-B1-C1
A9-M-134-C2
A9-M-B3-C3
A9-M-B1-C4
A9-M-B3-C4
A9-M-B1-C5
A9-M-B3-C5
A9-M-B4-C5
A9-M-B2-C6
A9-M-B3-C6
A9-M-B4-C6
A9-M-B3-C7
A9-M-B 1-C8
A9-M-B2-C8
A9-M-B3-C8
or
A9-M-B4-C8.