Patent TN-2017000044-A1 (TN)
Title: Aminopyrimidinyl compounds as jak inhibitors
Inventor: EFREMOV IVAN VIKTOROVICH
IPC: C07D519/00
Filed: 2015-08-07
Abstract: A compound having the structure:  or a pharmaceutically acceptable sait thereof, wherein X is N or CR, where R ishydrogen, deuterium,C<sub>1</sub>-C<sub>4</sub> alkyl, C<sub>1</sub>-C<sub>4</sub> alkoxy, C<sub>3</sub>-C<sub>6</sub> cycloalkyl, aryl, heteroaryl, aryl(C1-C<sub>6</sub>alkyl), CN, amino, alkylamino,dialkylamino, CF<sub>3</sub>, or hydroxyl; A is selected from the groupconsisting of a bond, C=O, --SO<sub>2</sub>--, -(C=O)NRo'--, and --(CR<sub>a</sub>R<sub>b</sub>)<sub>q</sub>-, where Ro is H or C<sub>1</sub>-C<sub>4</sub> alkyl, and Ra and Rb are independently hydrogen, deuterium, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>3</sub>-C<sub>6 </sub>cycloalkyl, aryl, aryl(C<sub>1</sub>-C<sub>6</sub> alkyl), heteroaryl, (C<sub>1</sub>-C<sub>6</sub> alkyl)heteroaryl, <em>etc.;</em> A' isselected from the group consisting of a bond, C=O, --SO<sub>2</sub>-, --(C=O)NRo', -NR<sub>0</sub>'(C=O)--, and --(CRa'Rb')q--, where Ro' is H or C<sub>1</sub>-C<sub>4</sub> alkyl, and R<sub>a'</sub> and R<sub>b</sub>' are independently hydrogen, deuterium, C<sub>1</sub>-C<sub>6</sub> alkyl, C<sub>3</sub>-C<sub>6</sub>cycloalkyl, aryl, aryl(C<sub>1</sub>-C<sub>6</sub> alkyl), heteroaryl, (C<sub>1</sub>-C<sub>6</sub> alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C<sub>1</sub>-C<sub>6</sub> alkyl); Z is --(CH<sub>2</sub>)n- or a bond, where one or more methylene units are optionally substituted by one or more C<sub>1</sub>-C<sub>3</sub> alkyl, CN, OH, methoxy,or halo, and where said alkyl may be substituted by one or more fluorine atoms; R<sub>1</sub> and R<sub>1</sub>' are independentlyselected from the group consisting of hydrogen, deuterium, C<sub>1</sub>C<sub>4 </sub>alkyl, C<sub>3</sub>-C<sub>6</sub> cycloalkyl, aryl, heteroaryl, aryl(C<sub>1</sub>-C<sub>6</sub> alkyl), CN,<em>etc.,</em> wherein said alkyl, aryl, cycloalkyl, heterocyclic,or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C<sub>1</sub>-C<sub>6</sub> alkyl, halo, CN, C<sub>1</sub>-C<sub>4 </sub>alkylamino, C<sub>3</sub>-C<sub>6 </sub>cycloalkyl, <em>etc.;</em> R<sub>2</sub> is selected from the group consisting of hydrogen, deuterium, C<sub>1</sub>-C<sub>6</sub> alkyl, C<sub>3</sub>-C<sub>6</sub> cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R<sub>3</sub> is selected from the group consisting of hydrogen, deuterium, and amino; R<sub>4</sub> is monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C1-Cs alkyl, heterocycloalkyl, halo, C3-C<sub>6</sub>cycloalkyl, <em>etc.,</em> where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C<sub>1</sub>-C<sub>6</sub> alkyl, halo, CN, OH,alkoxy, amino, --CO<sub>2</sub>H, --(CO)NH<sub>2</sub>, --(CO)NH(C<sub>1</sub>-C<sub>6</sub> alkyl), or --(CO)N(C<sub>1</sub>-C<sub>6 </sub>alkyl)<sub>2</sub>, and where said alkyl may be further substituted by one or more fluorine atoms; R5 is independently selected from the group consisting of hydrogen, C1-Ca alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, and hydroxyl; <em>h</em> is 1, 2 or 3; <em>j</em> and <em>k</em> are independently 0, 1, 2, or 3; <em>m</em> and <em>n</em>are independently 0, 1 or 2; and, <em>q</em> is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors andpharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.