Pfizer Corporation

Inhibitaxin Limited

Pharmacia & Upjohn Company

Dafydd Rhys Owen

Stephen Wayne Wright

Xiaojing Yang

Matthew Frank Brown

Matthew Merrill Hayward

Li Huang Xing

Jamison Bryce Tuttle

Brian Stephen Gerstenberger

Andrew Fensome

Matthew Forrest Sammons

Alpay Dermenci

Patrick Robert Verhoest

Martin Youngjin Pettersson

Matthew Richard Reese

Qingyi Yang

Christoph Martin Dehnhardt

Robert Steven Kania

Joseph Walter Strohbach

Eddine Saiah

John Paul Mathias

Andrew Simon Bell

David Hepworth

Karl Richard Gibson

Christoph Wolfgang Zapf

Arthur Lee

Nikolaos Papaioannou

Katherine Lin Lee

Frank Eldridge Lovering

John David Trzupek

Michael John Palmer

Seungil Han

Lori Krim Gavrin

David Graham Brown

Christophe Philippe Allais

Liuqing Wei

John Nicholas Freskos

David Louis Brown

Thomas Edward Rogers

Yvette M Fobian

Michael B Tollefson

Robert Owen Hughes

Robert Louis Hoffman

Brent V Mischke

E Jon Jacobsen

Christopher Gordon Barber

David Nathan Abraham Fox

Todd M Maddux

Ian Roger Marsh

Felix Vajdos

Samir Kulkarni

Suman Luthra

Anil Mahadeo Rane

Klimentina Dimitrova Pencheva

Andrew Ian Morrell

Carol Ann Winslow

John M Molyneaux

John K Walker

Lisa Rosemary Thompson

Jonathan Richard Lillis

Christopher Phillips

Martyn David Ticehurst

Joseph B Moon

Padmavani Bezawada

Rohit Jaini

Emma Louise Hawking

Andrew John Thiel

Matthew Nathan O'Brien Laramy

Hwang Fun Lu

D Joseph Rogier, Jr

Steven E Heasley

Bradley Paul Sullivan

The invention relates to compounds of formula I wherein Rand Rare as defined herein, pharmaceutical compositions comprising the compounds and methods of treating COVID-19 in a patient by administering therapeutically effective amounts of the compounds and methods of inhibiting or preventing replication of SARS-COV-2 with the compound.

Compounds and method of treating COVID-19

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, A' and A″ are independently O, C═O, C—R′ or N—R″, where R′ and R″ may independently be H, amino, —NRCOR, COR, —CONRR, C-Calkyl, or hydroxy(C-Calkyl), and R″ may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A′ and A″ is O or C═O; Rand R are independently H, Br, Cl, F, or C-Calkyl; Ris H, C-Calkyl, or hydroxy(C-Calkyl); Ris selected from the group consisting of H, C-Calkyl, C-Calkoxy, hydroxy(C-Calkyl), phenyl(C-Calkyl), formyl, heteroaryl, heterocyclic, —COR, —OCOR, —COOR, —NRCOR, —CONRR, and —(CH)—W, where W is cyano, hydroxy, C-Ccycloalkyl, —SONRR, and —SO—R, where Ris C-Calkyl, C-Ccycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C-Calkyl; X is C—Ror N, where Rmay be H or C-Calkyl; Rand Rare independently H, amino, C-Calkyl, or hydroxy(C-Calkyl); R, Rand Rare each independently H, C-Calkyl, C-Calkoxy(C-Calkyl), or C-Ccycloalkyl, said C-Calkyl is optionally substituted by halo, CN or hydroxy; or, Rand Rtogether with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C-Calkyl; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.

Pyrazolo[1,5-a]pyrazin-4-yl derivatives

The invention relates to compounds of formula I wherein R, Rand - - - - - are as defined herein, pharmaceutical compositions comprising the compounds and methods of treating COVID-19 in a patient by administering therapeutically effective amounts of the compounds and methods of inhibiting or preventing replication of SARS-CoV-2 with the compounds.

Compounds and methods for the treatment of COVID-19

The invention relates to compounds of Formula I&#x2033; wherein R, R, R, R, p, q and q' are as defined herein, pharmaceutical compositions comprising the compounds, methods of treating coronavirus infection such as COVID-19 in a patient by administering therapeutically effective amounts of the compounds, and methods of inhibiting or preventing replication of coronaviruses such as SARS-CoV-2 with the compounds.

Nitrile-containing antiviral compounds

There is a method for treating a psoriasis. A compound is administered in a therapeutically effective amount to a subject suffering therefrom. The compound has the structure or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof.

A compound having the structure: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein variables are 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 thereof with other therapeutic agents.

Pyrazolo[1,5-A]pyrazin-4-yl and related derivatives

A compound compound having the structure: or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt, wherein A, A' and A&#x2033; are independently O, C&#x2550;O, C&#x2014;R&#x2032; or N&#x2014;R&#x2033;, where R&#x2032; and R&#x2033; may independently be H, amino, &#x2014;NRCOR, COR, &#x2014;CONRR, C-Calkyl, or hydroxy(C-Calkyl), and R&#x2033; may be present or absent, and is present where the rules of valency permit, and where not more than one of A, A&#x2032; and A&#x2033; is O or C&#x2550;O; Rand R are independently H, Br, Cl, F, or C-Calkyl; Ris H, C-Calkyl, or hydroxy(C-Calkyl); Ris selected from the group consisting of H, C-Calkyl, C-Calkoxy, hydroxy(C-Calkyl), phenyl(C-Calkyl), formyl, heteroaryl, heterocyclic, &#x2014;COR, &#x2014;OCOR, &#x2014;COOR, &#x2014;NRCOR, &#x2014;CONRR, and &#x2014;(CH)&#x2014;W, where W is cyano, hydroxy, C-Ccycloalkyl, &#x2014;SONRR, and &#x2014;SO&#x2014;R, where Ris C-Calkyl, C-Ccycloalkyl, heteroaryl, or heterocyclic; wherein each of said alkyl, cycloalkyl, heterocyclic, or heteroaryl may be unsubstituted or substituted by halo, cyano, hydroxy, or C-Calkyl; X is C&#x2014;Ror N, where Rmay be H or C-Calkyl; Rand Rare independently H, amino, C-Calkyl, or hydroxy(C-Calkyl); R, Rand Rare each independently H, C-Calkyl, C-Calkoxy(C-Calkyl), or C-Ccycloalkyl, said C-Calkyl is optionally substituted by halo, CN or hydroxy; or, Rand Rtogether with the atom bonded thereto form a 5- or 6-membered ring, said ring being optionally substituted by halo, hydroxy, CN, or C-Calkyl; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.

Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

Bicyclic-fused heteroaryl or aryl compounds as IRAK4 modulators

Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed. 

A compound having the structure: or a pharmaceutically acceptable salt thereof, wherein A, A' and A&#x2033; are independently O, C&#x2550;O, etc.; Rand R are independently H, Br, Cl, F, or C-Calkyl; Ris H, C-Calkyl, or hydroxy(C-Calkyl); Ris selected from the group consisting of H, C-Calkyl, C-Calkoxy, etc.; R, Rand Rare each independently H, C-Calkyl, C-Calkoxy(C-Calkyl), etc.; and, n is 0, 1, 2 or 3. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations thereof with other therapeutic agents.

Pyrazolo[1,5-A]PYRAZIN-4-YL derivatives

The invention provides compounds of formula I, wherein: The compounds are useful as pharmaceuticals, particularly in the treatment of fibrotic diseases, cancer and pain.

Substituted pyridazines for the treatment of pain

The invention provides compounds of formula I, (I) wherein: R represents a cyclic group selected from phenyl, heteroaryl, heterocyclyl and C 3-6 cycloalkyl; 10 wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C -6 alkyl optionally substituted with 1-3 halogen atoms, phenyl, C -6 alkoxy optionally substituted with 1-3 halogen atoms, cyano, heteroaryl 1a and heterocyclyl 1a; and wherein each cyclic group is optionally fused to a benzene ring or a 5- or 16-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl and heterocyclyl 1a may additionally be substituted with &#x2550;O; 20 X represents a bond or C -6 alkylene (which may be straight or branched); R 2 represents H or C -6 alkyl; R 3 represents H or C -6 alkyl; Y represents a bond or C -6 alkylene (which may be straight or branched, and optionally substituted with OH or CF 3); 2 R 4 represents a cyclic group selected from phenyl, heteroaryl 4, heterocyclyl 4 and C 3-6 cycloalkyl; wherein each cyclic group is optionally substituted with from 1 to 3 substituents selected from halo, C -6 alkyl optionally substituted with 1-3 halogen atoms, TET01063WO 4 phenyl, C -6 alkyl substituted with phenyl, C -6 alkoxy optionally substituted with -3 halogen atoms, cyano, heteroaryl 4a and heterocyclyl 4a; and wherein each cyclic group is optionally fused to benzene ring or a 5- or 6-membered heteroaromatic or heterocyclic ring each containing from 1 to 3 heteroatoms (selected from N, O and S); and when the group is substituted the substitution may occur anywhere on the optionally fused ring system as a whole; and wherein heterocyclyl 4 and heterocyclyl 4a may additionally be substituted with &#x2550;O; heteroaryl, heteroaryl 1a, heteroaryl 4 and heteroaryl 4a independently represent a 5- or 6-membered heteroaryl group containing from 1 to 3 heteroatoms (selected from N, O and 10 S); and heterocyclyl, heterocyclyl 1a, heterocyclyl 4 and heterocyclyl 4a independently represent a 5- or 6-membered heterocyclyl group containing from 1 to 3 heteroatoms (selected from N, O and S); and pharmaceutically acceptable salts and solvates thereof. 1 The compounds are useful as pharmaceuticals, particularly in the treatment of fibrotic diseases, cancer and pain. 

The present invention relates to dipeptide enkephalin analogues of Formula (I) and their tautomers, ionic forms and pharmaceutically acceptable salts, and their use in medicine, in particular as opioid agonists. 

Enkephalin analogues

Growing community of inventors

Concord, MA, United States of America

Dafydd Rhys Owen