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    Aminopyrimidinyl compounds
    3.
    发明授权
    Aminopyrimidinyl compounds 有权

    公开(公告)号：US11197867B2

    公开(公告)日：2021-12-14

    申请号：US16920027

    申请日：2020-07-02

    Applicant: Pfizer Inc.

    Inventor： Andrew Fensome ,  Ariamala Gopalsamy ,  Brian S. Gerstenberger ,  Ivan Viktorovich Efremov ,  Zhao-Kui Wan ,  Betsy Pierce ,  Jean-Baptiste Telliez ,  John I. Trujillo ,  Liying Zhang ,  Li Xing ,  Eddine Saiah

    IPC: A61K31/506 ,  A61K31/55 ,  A61K45/06 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D487/08 ,  C07D519/00

    Abstract: A compound compound having the structure: or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 alkyl), CN, amino, alkylamino, dialkylamino, CF3, or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0—, and —(CRaRb)q—, where R0 is H or C1-C4 alkyl, and Ra and Rb are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, etc.; A′ is selected from the group consisting of a bond, C═O, —SO2—, —(C═O)NR0′, —NR0′(C═O)—, and —(CRa′Rb′)q—, where R0′ is H or C1-C4 alkyl, and Ra′ and Rb′ are independently hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, aryl, aryl(C1-C6 alkyl), heteroaryl, (C1-C6 alkyl)heteroaryl, heteroaryl(C1-C6 alkyl), and heterocyclic(C1-C6 alkyl); Z is —(CH2)h— or a bond, where one or more methylene units are optionally substituted by one or more C1-C3 alkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; R1 and R1′ are independently selected from the group consisting of hydrogen, deuterium, C1-C4 alkyl, C3-C6 cycloalkyl, aryl, heteroaryl, aryl(C1-C6 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 C1-C6 alkyl, halo, CN, C1-C4 alkylamino, C3-C6 cycloalkyl, etc.; R2 is selected from the group consisting of hydrogen, deuterium, C1-C6 alkyl, C3-C6 cycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; R3 is selected from the group consisting of hydrogen, deuterium, and amino; R4 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-C6 alkyl, heterocycloalkyl, halo, C3-C6 cycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C1-C6 alkyl, halo, CN, OH, alkoxy, amino, —CO2H, —(CO)NH2, —(CO)NH(C1-C6 alkyl), or —(CO)N(C1-C6 alkyl)2, 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-C6 alkyl, C1-C6 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.

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