Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors

1. An enantiomerically pure compound of formula 1

wherein:

Y is CR 12 ;

R 1 is 5-12 membered heteroaryl; and each hydrogen in R 1 is optionally replaced by one or more R 3 groups;

R 2 is hydrogen;

each R 3 is independently halogen, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —S(O) m R 4 , —SO 2 NR 4 R 5 , —S(O) 2 OR 4 , —NO 2 , —NR 4 R 5 , —(CR 6 R 7 ) n OR 4 , —CN, —C(O)R 4 , —OC(O)R 4 , —O(CR 6 R 7 ) n R 4 , —NR 4 C(O)R 5 , —(CR 6 R 7 ) n C(O)OR 4 , —(CR 6 R 7 ) n C(O)NR 4 R 5 , —(CR 6 R 7 ) n NCR 4 R 5 , —C(═NR 6 )NR 4 R 5 , —NR 4 C(O)NR 5 R 6 , or —NR 4 S(O) p R 5 , each hydrogen in R 3 is optionally replaced by R 8 , and R 3 groups on adjacent atoms may combine to form a C 6-12 aryl, 5-12 membered heteroaryl, C 3-12 cycloalkyl or 3-12 membered heteroalicyclic group;

each R 4 , R 5 , R 6 and R 7 is independently hydrogen, halogen, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R 4 , R 5 , R 6 and R 7 bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R 4 , R 5 , R 6 and R 7 bound to the same carbon atom may be combined to form a C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R 4 , R 5 , R 6 and R 7 is optionally replaced by R 8 ;

each R 8 is independently halogen, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —NH 2 , —CN, —OH, —O—C 1-12 alkyl, —O—(CH 2 ) n C 3-12 cycloalkyl, —O—(CH 2 ) n C 6-12 aryl, —O—(CH 2 ) n (3-12 membered heteroalicyclic) or —O—(CH 2 ) n (5-12 membered heteroaryl); and each hydrogen in R 8 is optionally replaced by R 11 ;

each R 11 is independently halogen, C 1-12 alkyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —O—C 1-12 alkyl, —O—(CH 2 ) n C 3-12 cycloalkyl, —O—(CH 2 ) n C 6-12 aryl, —O—(CH 2 ) n (3-12 membered heteroalicyclic), —O—(CH 2 ) n (5-12 membered heteroaryl) or —CN, and each hydrogen in R 11 is optionally substituted by halogen, —OH, —CN, —C 1-12 alkyl which may be partially or fully halogenated, or —O—C 1-12 alkyl which may be partially or fully halogenated;

R 12 is hydrogen;

each m is independently 0, 1 or 2;

each n is independently 0, 1, 2, 3 or 4; and

each p is independently 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 1 is a furan, thiophene, pyrrole, thiazole, imidazole pyrazole, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, or triazine, and each hydrogen in R 1 is optionally replaced by R 3 .

3. An enantiomerically pure compound of formula 1a

wherein:

Y is CH;

R 1 is pyrazole; and each hydrogen in R 1 is optionally replaced by R 3 ;

each R 3 is independently 3-12 membered heteroalicyclic, and each hydrogen in R 3 is optionally replaced by R 8 ;

each R 8 is independently halogen, C 1-12 alkyl, C 2-12 alkenyl, C 2-12 alkynyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —NH 2 , —CN, —OH, —O—C 1-12 alkyl, —O—(CH 2 ) n C 3-12 cycloalkyl, —O—(CH 2 ) n C 6-12 aryl, —O—(CH 2 ) n (3-12 membered heteroalicyclic) or —O—(CH 2 ) n (5-12 membered heteroaryl); and each hydrogen in R 8 is optionally replaced by R 11 ;

each R 11 is independently halogen, C 1-12 alkyl, C 3-12 cycloalkyl, C 6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —O—C 1-12 alkyl, —O—(CH 2 ) n C 3-12 cycloalkyl, —O—(CH 2 ) n C 6-12 aryl, —O—(CH 2 ) n (3-12 membered heteroalicyclic), —O—(CH 2 ) n (5-12 membered heteroaryl) or —CN, and each hydrogen in R 11 is optionally substituted by halogen, —OH, —CN, —C 1-12 alkyl which may be partially or fully halogenated, or —O—C 1-12 alkyl which may be partially or fully halogenated; and

each n is independently 0, 1, 2, 3 or 4;

or a pharmaceutically acceptable salt thereof.

4. An enantiomerically pure compound selected from the group consisting of 3[(R)-1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-2-ylamine; 1-[4-(4-{6-Amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl]-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidin-1-yl]-2-hydroxy-ethanone; and 3-[(R)-1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine; or a pharmaceutically acceptable salt thereof.