Pfizer Inc.
AMINOPYRIMIDINYL COMPOUNDS

Abstract:

A compound having the structure: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.3-C.sub.6 cycloalkyl, aryl, heteroaryl, aryl(C.sub.1-C.sub.6 alkyl), CN, amino, alkylamino, dialkylamino, CF.sub.3, or hydroxyl; A is selected from the group consisting of a bond, C.dbd.O, --SO.sub.2--, --(C.dbd.O)NR.sub.0--, and --(CR.sub.aR.sub.b).sub.q--, where R.sub.0 is H or C.sub.1-C.sub.4 alkyl, and R.sub.a and R.sub.b are independently hydrogen, deuterium, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, aryl, aryl(C.sub.1-C.sub.6 alkyl), heteroaryl, (C.sub.1-C.sub.6 alkyl)heteroaryl, etc.; A' is selected from the group consisting of a bond, C.dbd.O, --SO.sub.2--, --(C.dbd.O)NR.sub.0', --NR.sub.0'(C.dbd.O)--, and --(CR.sub.a'R.sub.b').sub.q--, where R.sub.0' is H or C.sub.1-C.sub.4 alkyl, and R.sub.a' and R.sub.b' are independently hydrogen, deuterium, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, aryl, aryl(C.sub.1-C.sub.6 alkyl), heteroaryl, (C.sub.1-C.sub.6 alkyl)heteroaryl, heteroaryl(C.sub.1-C.sub.6 alkyl), and heterocyclic(C.sub.1-C.sub.6 alkyl); Z is --(CH.sub.2).sub.h-- or a bond, where one or more methylene units are optionally substituted by one or more C.sub.1-C.sub.3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R.sub.1 and R.sub.1' are independently selected from the group consisting of hydrogen, deuterium, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, aryl, heteroaryl, aryl(C.sub.1-C.sub.6 alkyl), CN, etc., 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-C.sub.6 alkyl, halo, CN, C.sub.1-C.sub.4 alkylamino, C.sub.3-C.sub.6 cycloalkyl, etc.; R.sub.2 is selected from the group consisting of hydrogen, deuterium, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R.sub.3 is selected from the group consisting of hydrogen, deuterium, and amino; R.sub.4 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 C.sub.1-C.sub.6 alkyl, heterocycloalkyl, halo, C.sub.3-C.sub.6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C.sub.1-C.sub.6 alkyl, halo, CN, OH, alkoxy, amino, --CO.sub.2H, --(CO)NH.sub.2, --(CO)NH(C.sub.1-C.sub.6 alkyl), or --(CO)N(C.sub.1-C.sub.6 alkyl).sub.2, and where said alkyl may be further substituted by one or more fluorine atoms; R.sub.5 is independently selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.