Pfizer Corporation

Jean-Baptiste Telliez

John Isidro Trujillo

Matthew Frank Brown

Mark Edward Flanagan

Adam Matthew Gilbert

Ariamala Gopalsamy

Eddine Saiah

Matthew Merrill Hayward

Atli Thorarensen

Li Huang Xing

Ivan Viktorovich Efremov

Rayomand Jal Unwalla

Ye Che

Liying Zhang

Zhao-Kui Wan

Brian Stephen Gerstenberger

Andrew Fensome

Agustin Casimiro-Garcia

Betsy Susan Pierce

Jotham Wadsworth Coe

Justin Ian Montgomery

Jonathan David Langille

Sidney Xi Liang

The present invention provides a method for treating alopecia using certain pharmaceutically active pyrrolo[2,3-d]pyrimidinyl acrylamides having the structure: or a pharmaceutically acceptable salt thereof, as set forth in the Description.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

A compound compound having the structure: or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C-Calkyl, C-Calkoxy, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), CN, amino, alkylamino, dialkylamino, CF, or hydroxyl; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, &#x2014;(C&#x2550;O)NR&#x2014;, and &#x2014;(CRR)&#x2014;, where Ris H or C-Calkyl, and Rand Rare independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, &#x2014;(C&#x2550;O)NR&#x2032;, &#x2014;NR&#x2032;(C&#x2550;O)&#x2014;, and &#x2014;(CR&#x2032;R&#x2032;)&#x2014;, where R&#x2032; is H or C-Calkyl, and R&#x2032; and R&#x2032; are independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, heteroaryl(C-Calkyl), and heterocyclic(C-Calkyl); Z is &#x2014;(CH)&#x2014; or a bond, where one or more methylene units are optionally substituted by one or more C-Calkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; Rand R&#x2032; are independently selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), 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-Calkyl, halo, CN, C-Calkylamino, C-Ccycloalkyl, etc.; Ris selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; Ris selected from the group consisting of hydrogen, deuterium, and amino; Ris 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-Calkyl, heterocycloalkyl, halo, C-Ccycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C-Calkyl, halo, CN, OH, alkoxy, amino, &#x2014;COH, &#x2014;(CO)NH, &#x2014;(CO)NH(C-Calkyl), or &#x2014;(CO)N(C-Calkyl), and where said alkyl may be further substituted by one or more fluorine atoms; Ris independently selected from the group consisting of hydrogen, C-Calkyl, C-Calkoxy, 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.

Aminopyrimidinyl compounds

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylam ides and analogues thereof, having the structure: or a pharmaceutically acceptable salt thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

A compound having the structure: or an acceptable salt thereof, wherein X is N or CR, where R is hydrogen, alkyl, etc.; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, etc.; Z is &#x2014;(CH)&#x2014; or a bond, etc.; Rand Rare independently selected from the group consisting of hydrogen, alkyl, etc.; Ris selected from hydrogen, alkyl, etc.; Ris selected from the group consisting of hydrogen, and amino; Ris monocyclic or bicyclic, etc.; Ris independently selected from hydrogen, alkyl, etc.; h, j, k, m, n and q are integers as defined in the specification. 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.

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides, and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Pyrrolo[2,3-D]pyrimidinyl, pyrrolo[2,3-B]pyrazinyl, pyrrolo[2,3-B]pyridinyl acrylamides and epoxides thereof

A compound having the structure: or an acceptable salt thereof, wherein X is N or CR, where R is hydrogen, alkyl, etc.; A is selected from the group consisting of a bond, C&#x2550;O, &#x2014;SO&#x2014;, etc.; A' is selected from the group consisting of a bond, C&#x2550;O, etc.; Z is &#x2014;(CH)&#x2014; or a bond, etc.; Rand R&#x2032; are independently selected from the group consisting of hydrogen, alkyl, etc.; Ris selected from hydrogen, alkyl, etc.; Ris selected from the group consisting of hydrogen, and amino; Ris monocyclic or bicyclic, etc.; Ris independently selected from hydrogen, alkyl, etc.; h, j, k, m, n and q are integers as defined in the specification. 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.

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof, having the structure: or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer or diastereomer thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

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Lexington, MA, United States of America

Jean-Baptiste Telliez