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US 10,329,294 B2Granted
Pyrazolopyrimidine inhibitors of IRAK4 activity
AssigneeMerck Sharp & Dohme Corp.
InventorsJongwon Lim, Michael D. Altman, Jason D. Brubaker, Craig R. Gibeau
Life of this patent
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Abstract
The present invention relates to pyrazolopyrimidine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.
Claims5
A compound of Formula I:
- wherein:
- Ring A is pyrazolyl, pyridinyl, thiophenyl, furanyl or phenyl;
- n is 0, 1 or 2;
- R1 is independently selected from:
- (C1-C4)alkyl, cyclopropyl, oxadiazolyl, pyridinyl, oxazolyl, triazolyl, pyriminidyl, CF3, CHF2, CN and halo, said alkyl, cyclopropyl, oxadiazolyl, pyridinyl, oxazolyl, triazolyl and pyriminidyl are optionally substituted with halo, OH, CH3, and OCH3;
- R2 is H and R3 is independently selected from:
- cyclohexyl, cycloheptyl, piperidinyl and azepanyl each optionally substituted with one or more F, OH, N(Rb)2, or morpholinyl, or R2 and R3 can be taken together with the nitrogen to which they are attached to form a heterocyclyl selected from piperazinyl, diazepanyl, diazabicyclooctyl, diazabicycloheptyl, diazaspirononyl, hexahydropyrrolopyrazinyl, piperidinyl, diazabicyclononyl, oxadiazabicyclodecyl and diazatricyclodecyl, said heterocyclyl optionally substituted with one or more substituents selected from Ra;
- Ra is independently selected from (C1-C4)alkyl, cyclopropyl, CF3, CHF2, OH, F and NH2, said alkyl optionally substituted with cyclopropyl or CF3;
- and
- Rb is independently selected from H and methyl;
- or a pharmaceutically acceptable salt thereof.
8 more elements
A compound which is selected from:
- 5-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
- 5-[(5S)-5-amino-3,3-difluoropiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
- 5-[(4R)- or (4.5)-(5-amino-3,3-difluoropiperidin-1-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazolo-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
- 5-[(3R,5R)-3-amino-5-:fluoropiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide;
- and
- 5-(((1R,2S)-2-Aminocyclohexyl)amino)-N-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide;
- or a pharmaceutically acceptable salt thereof.
4 more elements
Dependencies are inferred from the claim text.