Patent TN-2016000503-A1 (TN)
Title: Pyrazolopyridines and pyrazolopyrimidines
Inventor: COE JOTHAM WADSWORTH
IPC: C07D487/04
Filed: 2015-04-30
Abstract: A compound having the structure:   or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A and A' are independently C or N, where C may be unsubstituted or substituted by halo or C<sub>1</sub>-C<sub>6</sub> alkyl; R and R<sup>0</sup> are independently selected from the group consisting of H, C<sub>1</sub>-C<sub>6</sub> alkyl, hydroxy(C<sub>1</sub>-C<sub>6</sub> alkyl), phenyl(C<sub>1</sub>-C<sub>6</sub> alkyl), and -(CH<sub>2</sub>)<sub>n</sub>-W, where W is C<sub>3</sub>-C<sub>8</sub> cycloalkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1 -3 N, S and/or 0 atoms, -SO<sub>2</sub>-R', -NHSO<sub>2</sub>-R', -NR"SO<sub>2</sub>-R' and SR', where R' and R" are independently C<sub>1</sub>-C<sub>6</sub> alkyl or C<sub>3</sub>-C<sub>8</sub>cycloalkyl, etc.; wherein each of said alkyl, cycloalkyl, heterocyclic, phenyl, naphthyl or heteroaryl may be unsubstituted or substituted by phenyl, heteroaryl, etc.; or, R and R<sub>0</sub> and the N atom to which they are bonded together form a monocyclic or bicyclic heterocyclic ring which may be unsubstituted or substituted by (a) halo, hydroxy, heteroaryl, C<sub>1</sub>-C<sub>6</sub> alkyl, C<sub>1</sub>-C<sub>6</sub> alkoxy, etc., or (b) -(CH<sub>2</sub>)<sub>n</sub>-W, where W is C<sub>3</sub>-C<sub>8</sub>cycloalkyl, phenyl, etc.; R<sup>1 </sup>is H, halo or cyano; R<sup>2</sup> and R<sup>2' </sup>are independently H, C<sub>1</sub>-C<sub>6</sub> alkyl, cyano, C<sub>1</sub>-C<sub>6</sub> alkoxy, C<sub>1</sub>-C<sub>6</sub> alkylthio, or C<sub>3</sub>-C<sub>8</sub> cycloalkyl where alkyl, alkoxy, or cycloalkyl is optionally substituted by one or more fluorine atoms; X is a bond, -CO-, -CONH-, -S0<sub>2</sub>-, -SONH-, or -(CH<sub>2</sub>)<sub>m</sub>-; R<sup>3</sup> is H, C<sub>1</sub>-C<sub>4</sub> alkyl, phenyl, naphthyl, 5- or 6-membered heteroaryl or heterocyclic containing 1 -3 N atoms, a 5-membered heteroaryl or heterocyclic, etc., or (c) 2 O or S atoms and 0-2 N atoms; wherein each of said phenyl, naphthyl, heteroaryl or heterocyclic is optionally substituted by alkyl, 1 substituent -Y-R<sup>4</sup> and/or 1 -4 substituents each independently selected from R<sup>5</sup>; with the proviso that when X is -CO- or -SO<sub>2</sub>-, R<sup>3</sup> is not H; Y is a bond, -(CH<sub>2</sub>)<sub>m</sub>- or -O-; R<sup>4</sup> is (a) H, C<sub>1</sub>-C<sub>6</sub> alkyl, C<sub>3</sub>-C<sub>8</sub> cycloalkl, halo, oxo, -OR<sup>6</sup>, -NR<sup>7</sup>R<sup>8</sup>, -SR<sup>6,</sup> -SOR<sup>9</sup>, -SO<sub>2</sub>R<sup>9</sup>, -COR<sup>6</sup>, -OCOR<sup>6</sup>, -COOR<sup>6</sup>, -NR<sup>6</sup>COR<sup>6</sup>, -CONR<sup>7</sup>R<sup>8</sup>, etc.; (b) phenyl or naphthyl, said phenyl and naphthyl being optionally substituted with 1 -5 substituents selected from C<sub>1</sub>-C<sub>6</sub> alkyl, C<sub>3</sub>-C<sub>8</sub> cycloalkyl, halo, cyano, -OR<sup>6</sup>, -NR<sup>7</sup>R<sup>8,</sup> etc.; or (c) a 3 to 8-membered saturated or partially unsaturated monocyclic heteroaryl, etc.; R<sup>6</sup> is H, C<sub>1</sub>-C<sub>6</sub> alkyl or C<sub>3</sub>-C<sub>8</sub> cycloalkyl, etc.; R<sup>7</sup> and R<sup>8</sup> are each independently H, C<sub>1</sub>-C<sub>6</sub> alkyl or C<sub>3</sub>-C<sub>8</sub> cycloalkyl or are taken together with the nitrogen atom to which they are attached to form a 4-, 5- or 6-membered saturated heterocyclic ring containing 1 -2 nitrogen atoms or 1 nitrogen and 1 oxygen atom, said C<sub>1</sub>-C<sub>6</sub> alkyl is optionally substituted by C<sub>3</sub>-C<sub>8</sub> cycloalkyl, ha lo, etc., and said heterocyclic ring being optionally substituted by one or more C<sub>1</sub>-C<sub>6</sub> alkyl or C<sub>3</sub>-C<sub>8</sub> cycloalkyli groups; R<sup>9</sup> is C<sub>1</sub>-C<sub>6</sub> alkyl or C<sub>3</sub>-C<sub>8</sub>cycloalkyl; and, <em>m</em> and <em>n</em> are independently 0, 1, 2 or 3. The invention also relates to pharmaceutically acceptable salts of these compounds and to pharmaceutically acceptable solvates thereof; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly asthma and COPD.