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US 7,608,603 B2Granted
Substituted pyrazolo[3,4-D]pyrimidines as p38 MAP kinase inhibitors
AssigneeRoche Palo Alto LLC
InventorsNolan James Dewdney, Tobias Gabriel, Kristen Lynn McCaleb
Life of this patent
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Abstract
Compounds of formula Ia, Ib, Ic, Id, Ie, If, Ig or Ih: wherein X and Y are nitrogen or one of X and Y is nitrogen and the other is CRg, and W, D, E, R4, R5, R6 and Rg are as defined herein. Also disclosed are methods of making the subject compounds and methods of using the compounds in the treatment of p38 MAP kinase-mediated diseases.
Claims10
A compound of formula Ia:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- R1 is optionally substituted phenyl;
- R2 is optionally substituted phenyl
- R4 is hydroxyalkyl, alkoxyalkyl or alkylsulfonylalkyl
- R5 is hydrogen, —C(═O)—Rc, —(O═)P(ORd)2, —S(═O)2ORd, or a mono-, di- or tri-peptide;
- wherein
- Rc is —(CH2)p—C(═O)—Re;
- wherein
- Re is hydrogen, hydroxy, alkoxy or amine;
- p is 2 or 3;
- Rd is hydrogen, alkyl, an alkali metal ion or an alkaline earth metal ion;
- X and Y are nitrogen;
- D is —(CR 7R8)n—;
- wherein
- n is from 1 to 3;
- R7 and R8 each independently is hydrogen or alkyl;
- W is a bond or NRi;
- Ri is hydrogen;
- A is O;
- and
- k is 0.
19 more elements
The compound of claim2, wherein R7 and R8 are hydrogen.
A compound selected from the group consisting of:
- Succinic acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-hydroxyl-propylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- Succinic acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-hydroxyl-2-methyl-propylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- Succinic acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-methanesulfonyl-ethylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- [3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-methanesulfonyl-ethylamino)-pyrazolo[3,4-d]pyrirnidin-1-yl]-methanol;
- Phosphoric acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-methanesulfonyl-ethylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- Succinic acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- [3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-methanol;
- 1-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-hydroxymethyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol;
- 1-[3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1-hydroxymethyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylarmino]-2-methyl-propan-2-ol;
- Phosphoric acid mono-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-hydroxy-propylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl] ester;
- 2-Amino-3-methyl-butyric acid 3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2-methanesulfonyl-ethylamino)-pyrazolo[3,4-d]pyrimidin-1-ylmethyl ester;
- Phosphoric acid mono-{2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl} ester;
- Phosphoric acid mono-{2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylarnino]-1-methyl-ethyl } ester;
- and
- 2-Amino-3-methyl-butyric acid 2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl ester.
12 more elements
Dependencies are inferred from the claim text.