FLUORINATED 2,6-DIALKYL-3,5-DICYANO-4-(1H-INDAZOL-5-YL)-1,4-DIHYDROPYRIDINES AND METHODS OF USE THEREOF

1 . A compound of formula (I)

wherein

R 1 is hydrogen or fluoro,

R 2 is (C 1 -C 5 )-alkyl optionally substituted with up to five fluoro atoms,

R 3 is hydrogen or fluoro,

R 4 is hydrogen or (C 1 -C 4 )-alkyl,

and

R 5 is hydrogen or methyl,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

2 . The compound of formula (I) according to claim 1 , wherein

R 1 is hydrogen or fluoro,

R 2 is (C 1 -C 4 )-alkyl optionally substituted with up to three fluoro atoms,

R 3 is hydrogen or fluoro,

R 4 is hydrogen, methyl or ethyl,

and

R 5 is hydrogen,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

3 . The compound of formula (I) according to claim 1 , wherein

R 1 is hydrogen or fluoro,

R 2 is methyl, ethyl, 2,2,2-trifluoroethyl, propyl, 3,3,3-trifluoropropyl or 2-methylpropyl,

R 3 is hydrogen or fluoro,

R 4 is hydrogen or methyl,

and

R 5 is hydrogen,

or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.

4 . A process for preparing a compound of formula (I) as defined in claim 1 , wherein an indazolyl aldehyde of formula (II)

wherein R 3 and R 4 have the meanings indicated in claim 1 ,

is reacted with a ketonitrile of formula (III)

or a sodium enolate thereof, wherein R 2 has the meaning indicated in claim 1 ,

in the presence of an acid, acid/base combination and/or dehydrating agent to give a compound of formula (IV)

wherein R 2 , R 3 and R 4 have the meanings indicated in claim 1 ,

and the latter is then condensed with an enaminonitrile of formula (V)

wherein R 1 has the meaning indicated in claim 1 ,

to give the compound of formula (I-A)

wherein R 1 , R 2 , R 3 and R 4 have the meanings indicated in claim 1 ,

optionally followed by dihydropyridine N-methylation employing a compound of formula (VI)

CH 3 —X  (VI),

wherein

X represents a leaving group,

in the presence of a base to give the compound of formula (I-B)

wherein R 1 , R 2 , R 3 and R 4 have the meanings indicated in claim 1 ,

and optionally followed by (i) separating the compound of (I-A) or (I-B) into its respective enantiomers and/or diastereomers, and/or (ii) converting the compound of (I-A) or (I-B) into its respective hydrates or solvates by treatment with the corresponding solvents.

5 . (canceled)

6 . (canceled)

7 . (canceled)

8 . A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable hydrate or solvate thereof, and a pharmaceutically acceptable excipient.

9 . The pharmaceutical composition of claim 8 further comprising one or more additional therapeutic agents.

10 . The pharmaceutical composition of claim 9 , wherein the additional therapeutic agent is an anti-tumor agent.

11 . (canceled)

12 . A method of treating or preventing a cell proliferative disorder in a mammal, comprising administering to a mammal in need thereof a therapeutically effective amount of one or more compounds as defined in claim 1 .

13 . The method of claim 12 , wherein the cell proliferative disorder is cancer.

14 . The method of claim 13 , wherein the cancer is a cancer of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head or neck, thyroid, parathyroid, or a distant metastasis of a solid tumor.

15 . The method of claim 13 , wherein the compound is administered in conjunction with surgery or radiation therapy.