IP Library › Granted Patent US 12,312,336
Granted Patent B2
US 12,312,336 · App. 17/213,036 · Granted May 27, 2025

Inhibitors of RAF kinases

Inventors: Stephen W. Kaldor (San Diego, CA); Toufike Kanouni (Rancho Santa Fe, CA); John Tyhonas (San Diego, CA); Eric Murphy (San Marcos, CA)
Assignee: PIERRE FABRE MÉDICAMENT
C07D403/12C07D401/12C07D401/14C07D403/14C07D405/14C07D413/14
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,312,336
App. No.
17/213,036
Granted
May 27, 2025
Kind
B2
Abstract

Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

Claims (161)

1. A compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:

(3S)—N-(3-(6-((3,3-difluorocyclopentyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((R)-3,3-difluorocyclopentyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((S)-3,3-difluorocyclopentyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,3S)-3-hydroxycyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,3R)-3-hydroxycyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((3-hydroxyoxetan-3-yl)methyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-(2-((3,3-difluorocyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-3,3-difluorocyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-3,3-difluorocyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[3-(2-[[(cis-3-hydroxycyclopentyl]amino]-6-(morpholin-4-yl)pyrimidin-4-yl)-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,3R)-3-hydroxycyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,3S)-3-hydroxycyclopentyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(3-hydroxyazetidin-1-yl)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(3-hydroxyazetidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(S)—N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(S)—N-(3-(2-((2-hydroxyethyl)(methyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-((2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(S)—N-(3-(2-(((R)-2-hydroxypropyl)(methyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(3,6-dihydro-2H-pyran-4-yl)-6-(((R)-2-hydroxypropyl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-((2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(S)—N-(3-(2-(((S)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(3,6-dihydro-2H-pyran-4-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,3R)-3-hydroxy-3-methylcyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,3S)-3-hydroxy-3-methylcyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,4R)-4-hydroxy-4-methylcyclohexyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,4S)-4-hydroxy-4-methylcyclohexyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(3-hydroxy-3-methylazetidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(isopropylamino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(tert-butylamino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1-hydroxy-2-methylpropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(oxetan-3-ylamino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(((R)-tetrahydrofuran-3-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(((S)-tetrahydrofuran-3-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(((R)-tetrahydro-2H-pyran-3-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-((tetrahydro-2H-pyran-4-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,3R)-3-hydroxycyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,3S)-3-hydroxycyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-hydroxybutan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-methoxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-2-methoxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(((S)-tetrahydro-2H-pyran-3-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(4-methyl-3-(2-((3-methyltetrahydrofuran-3-yl)amino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1-(hydroxymethyl)cyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((3-(hydroxymethyl)oxetan-3-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-((3-methyloxetan-3-yl)amino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-((4-methyltetrahydro-2H-pyran-4-yl)amino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1-(hydroxymethyl)cyclopropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1R,3S)-3-hydroxy-1-methylcyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,3R)-3-hydroxy-1-methylcyclobutyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((2R,3R)-3-hydroxybutan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-(2-((1-cyanopropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((1S,4R)-4-hydroxy-1-methylcyclohexyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

And(S)—N-(3-(2-(((1R,4S)-4-hydroxy-1-methylcyclohexyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1,3-dihydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-amino-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-(methylamino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-(3-oxomorpholino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-acetamido-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(3-fluoro-2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(3-fluoro-6-(((R)-1-hydroxypropan-2-yl)amino)-2-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((2S,3R)-3-hydroxy-2-methylazetidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((2S,3S)-3-hydroxy-2-methylazetidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-morpholino-6-(((S)-1,1,1-trifluoro-3-hydroxypropan-2-yl)amino)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(2-hydroxy-2-methylpropanamido)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(2-fluoro-5-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(2-fluoro-5-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide;

(S)—N-(3-(2-(2,5-dihydrofuran-3-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-(tetrahydrofuran-3-yl)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-1-hydroxypropan-2-yl)amino)-6-(1H-pyrazol-4-yl)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((R)-1-hydroxypropan-2-yl)amino)-[2,4′-bipyridin]-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2′-amino-6-(((R)-1-hydroxypropan-2-yl)amino)-[2,4′-bipyridin]-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2′-cyano-6-(((R)-1-hydroxypropan-2-yl)amino)-[2,4′-bipyridin]-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1R,6S)-3-oxabicyclo[4.1.0]heptan-6-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1S,6R)-3-oxabicyclo[4.1.0]heptan-6-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1S,5R)-3-oxabicyclo[3.1.0]hexan-1-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((1R,5S)-3-oxabicyclo[3.1.0]hexan-1-yl)-6-(((R)-1-hydroxypropan-2-yl)amino)pyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((R)-2-hydroxypropyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(6-(((R)-2-hydroxypropyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((S)-2-hydroxypropyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-((2-hydroxyethyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((S)-1-hydroxypropan-2-yl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-((2-hydroxy-2-methylpropyl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((2-hydroxy-2-methylpropyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(6-(((R)-1-hydroxypropan-2-yl)amino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-1-hydroxypropan-2-yl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(2-((S)-3-hydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-3-hydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-(((S)-2-hydroxypropyl)amino)-6-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(3R)-3-aminopyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(3S)-3-aminopyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(3R)-3-aminopiperidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(3S)-3-aminopiperidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[4-methyl-3-[2-(morpholin-4-yl)-6-(2-oxopyrrolidin-1-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(3R)-3-hydroxypyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[4-methyl-3-[2-(3-methyl-2-oxoimidazolidin-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[4-methyl-3-[2-(N-methylacetamido)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[3-[2-methanesulfonamido-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[3-[2-(3-hydroxy-2-oxopyrrolidin-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[4-methyl-3-[2-(morpholin-4-yl)-6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(5R)-5-hydroxy-2-oxopiperidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(4-methyl-3-(2-morpholino-6-(2-oxo-3-azabicyclo[3.1.0]hexan-3-yl)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((3S,4S)-3-fluoro-4-hydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[3-[2-cyclopropanesulfonamido-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2 trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-3-amino-2-oxopyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-4-amino-2-oxopyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-3-amino-3-methylpyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-3-amino-3-methylpiperidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-[2-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-[3-[2-(1,1-dioxo-1lambda6,2-thiazolidin-2-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((R)-4-amino-2-oxopyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((R)-3,3-difluoro-4-hydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-3,3-difluoro-4-hydroxypyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-(2-((1R)-1-amino-3-azabicyclo[3.1.0]hexan-3-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-(2-((1S)-1-amino-3-azabicyclo[3.1.0]hexan-3-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((R)-4-amino-2-oxopyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((R)-4-amino-3,3-difluoropyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(2-((S)-4-amino-3,3-difluoropyrrolidin-1-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-{2-[(3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-(3-{2-[(3S,4S)-3-amino-4-hydroxypyrrolidin-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-(((R)-1-(methylamino)-1-oxopropan-2-yl)amino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(S)—N-(4-methyl-3-(2-(((S)-1-(methylamino)-1-oxopropan-2-yl)amino)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-{3-[2-ethanesulfonamido-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;

(3S)—N-{4-methyl-3-[2-(morpholin-4-yl)-6-(propane-2-sulfonamido)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide; and

(3S)—N-{4-methyl-3-[2-(1-methylcyclopropanesulfonamido)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

2. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (S)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

3. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

4. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

5. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (R)—N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide.

6. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (R)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide.

7. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (R)—N-(3-(2-((2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

8. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

9. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (S)—N-(3-(2-(((S)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

10. The compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, wherein the compound is: (S)—N-(3-(2-(((R)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, or(S)—N-(3-(2-(((S)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

11. A pharmaceutical composition comprising a compound of claim 1 , or pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

12. The pharmaceutical composition of claim 11 , wherein the compound is: (S)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

13. The pharmaceutical composition of claim 11 , wherein the compound is: (S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

14. The pharmaceutical composition of claim 11 , wherein the compound is: (R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

15. The pharmaceutical composition of claim 11 , wherein the compound is: (R)—N-(3-(2-((2-hydroxyethyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide.

16. The pharmaceutical composition of claim 11 , wherein the compound is: (R)—N-(3-(2-(((R)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethoxy)pyrrolidine-1-carboxamide.

17. The pharmaceutical composition of claim 11 , wherein the compound is: (R)—N-(3-(2-((2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

18. The pharmaceutical composition of claim 11 , wherein the compound is: (R)—N-(3-(2-((1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)-2,5-dihydro-1H-pyrrole-1-carboxamide.

19. The pharmaceutical composition of claim 11 , wherein the compound is: (S)—N-(3-(2-(((S)-2-hydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

20. The pharmaceutical composition of claim 11 , wherein the compound is: (S)—N-(3-(2-(((R)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, or(S)—N-(3-(2-(((S)-2,3-dihydroxypropyl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE CORRECT THE RECEIVING PARTY DATA COMPANY NAME IS: PIERRE FABRE MEDICAMENT PREVIOUSLY RECORDED AT REEL: 66638 FRAME: 147. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Sep 11, 2024
From: KINNATE BIOPHARMA INC.
To: PIERRE FABRE MÉDICAMENT
Reel/Frame 068939/0656 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2024
From: KINNATE BIOPHARMA INC.
To: PIERRE FABRE MÉDICAMENT, SAS
Reel/Frame 066638/0147 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 26, 2021
From: KALDOR, STEPHEN W.; KANOUNI, TOUFIKE; TYHONAS, JOHN; MURPHY, ERIC
To: KINNATE BIOPHARMA INC.
Reel/Frame 055742/0262 →
Continuity (4)
Continuation 17079152 · Oct 23, 2020
Provisional Application 63044898 · Jun 26, 2020
Provisional Application 62925596 · Oct 24, 2019
Related Publication 20210300904A1 · Sep 30, 2021
References Cited (94)
US 5846514A · Foster et al. · 1998 [cited by applicant]
US 6334997B1 · Foster et al. · 2002 [cited by applicant]
US 9694016B2 · Aversa et al. · 2017 [cited by applicant]
US 10927111B2 · Kaldaor et al. · 2021 [cited by applicant]
US 11098031B1 · Kaldor · 2021 [cited by examiner]
US 11377431B2 · Kaldor et al. · 2022 [cited by applicant]
US 11407737B2 · Kaldor et al. · 2022 [cited by applicant]
US 20040157827A1 · Pevarello et al. · 2004 [cited by applicant]
US 20050256174A1 · Wood et al. · 2005 [cited by applicant]
US 20070054916A1 · Patel et al. · 2007 [cited by applicant]
US 20070244120A1 · Dumas et al. · 2007 [cited by applicant]
US 20080114006A1 · Flynn et al. · 2008 [cited by applicant]
US 20090036419A1 · Chen et al. · 2009 [cited by applicant]
US 20090054436A1 · Borzilleri et al. · 2009 [cited by applicant]
US 20110183997A1 · Chianelli et al. · 2011 [cited by applicant]
US 20120040951A1 · Chuaqui et al. · 2012 [cited by applicant]
US 20140275003A1 · Barsanti et al. · 2014 [cited by applicant]
US 20150119392A1 · Flynn et al. · 2015 [cited by applicant]
US 20160075727A1 · Burger et al. · 2016 [cited by applicant]
US 20170260207A1 · Aversa et al. · 2017 [cited by applicant]
US 20190175606A1 · Aversa et al. · 2019 [cited by applicant]
US 20190175609A1 · Caponigro et al. · 2019 [cited by applicant]
US 20190358236A1 · Caponigro et al. · 2019 [cited by applicant]
US 20200347052A1 · Kaldor et al. · 2020 [cited by applicant]
US 20210246135A1 · Kaldor et al. · 2021 [cited by applicant]
US 20220340543A1 · Kaldor et al. · 2022 [cited by applicant]
US 20220356160A1 · Kaldor et al. · 2022 [cited by applicant]
US 20230081390A1 · Kaldaor et al. · 2023 [cited by applicant]
US 20230255977A1 · Franovic et al. · 2023 [cited by applicant]
EP 2112150B1 · 2013 [cited by applicant]
JP 2016517417A · 2016 [cited by applicant]
JP 2017526720A · 2017 [cited by applicant]
JP 2017528475A · 2017 [cited by applicant]
JP 2022525885A · 2022 [cited by applicant]
WO WO03068229A1 · 2003 [cited by applicant]
WO WO2006071940A2 · 2006 [cited by applicant]
WO WO2008034008A2 · 2008 [cited by applicant]
WO WO2013184119A1 · 2013 [cited by applicant]
WO WO2014151616A1 · 2014 [cited by applicant]
WO WO2016038583A1 · 2016 [cited by applicant]
WO WO2016038581A1 · 2016 [cited by applicant]
WO WO2016038582A1 · 2016 [cited by applicant]
WO WO2020168172A1 · 2020 [cited by applicant]
WO WO2020198058A1 · 2020 [cited by applicant]
WO WO2020227020A1 · 2020 [cited by applicant]
WO WO2021081375A1 · 2021 [cited by applicant]
WO WO2022060996A1 · 2022 [cited by applicant]
WO WO2022081469A1 · 2022 [cited by applicant]
WO WO2022226221A1 · 2022 [cited by applicant]
WO WO2022226261A1 · 2022 [cited by applicant]
CAS Chemical Structure Search #3191415 Updated (Apr. 2020). [cited by applicant]
CAS Chemical Structure Search dated Apr. 24, 2019 . [cited by applicant]
Henry et al. Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino) pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activit… [cited by applicant]
PCT/US2020/030786 International Search Report and Written Opinion dated Sep. 14, 2020. [cited by applicant]
PCT/US2020/030786 Invitation to Pay Additional Fees dated Jul. 14, 2020. [cited by applicant]
Lv et al. Design, synthesis and biological evaluation of novel 4-alkynylquinoline derivatives as PI3K/mTOR dual inhibitors. Eur J Med Chem 99:36-50 (2015). [cited by applicant]
Nishiguchi et al. Design and Discovery of N-(2-Methyl-5′-morpholino-6′-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3′-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Tar… [cited by applicant]
PCT/US2021/050690 International Search Report and Written Opinion dated Dec. 27, 2021. [cited by applicant]
PCT/US2021/054403 International Search Report and Written Opinion dated Dec. 28, 2021. [cited by applicant]
Ramurthy et al. Design and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mu… [cited by applicant]
Reg/Caplus and Marpat. Science IP Report dated Sep. 17, 2020. [cited by applicant]
Anastassiadis et al. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol. 29(11):1039-45 (2011). [cited by applicant]
Berge et al. Pharmaceutical Salts. Journal of Pharmaceutical Sciences 66(1):1-19 (Jan. 1977). [cited by applicant]
Evans. Synthesis of radiolabeled compounds. J Radioanal Chem 64(1-2):9-32 (1981). [cited by applicant]
Kabalka et al. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates. Tetrahedron 45(21):6601-6621 (1989). [cited by applicant]
PCT/US2020/024009 International Search Report and Written Opinion dated Jul. 28, 2020. [cited by applicant]
PCT/US2020/024009 Invitation to Pay Additional Fees dated Jun. 2, 2020. [cited by applicant]
PCT/US2020/057132 International Search Report and Written Opinion dated Feb. 9, 2021. [cited by applicant]
PCT/US2020/057132 Invitation to Pay Additional Fees dated Dec. 8, 2020. [cited by applicant]
Rosse. Pyridyl Isonicotinamide Inhibitors of RAF Kinase. ACS Med. Chem. Lett. 7:1022-1023 (2016). [cited by applicant]
Science IP Report dated Jul. 13, 2020 (873 pgs). [cited by applicant]
CAS Search dated Apr. 26, 2023. [cited by applicant]
Chapman et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. New England Journal of Medicine 364(26):2507-2516 (2011). [cited by applicant]
Chemical Structure Search report data Feb. 27, 2019. [cited by applicant]
Davies et al. Mutations of the BRAF Gene in Human Cancer. Nature 417:949-954 (2002). [cited by applicant]
Hauschild et al. Dabrafenib in BRAF-mutated Metastatic Melanoma: A Multicentre, Open-Label, Phase 3 Randomised Controlled Trial. Lancet 380(9839):358-65 (2012). [cited by applicant]
Kania et al. The Discovery of Exarafenib (KIN-2787), a Solution to the Challenges of Pan-RAF kinase Inhibition. PowerPoint presentation at Winter Conference on Medicinal & Bioorganic Chemistry (Jan. 2023). [cited by applicant]
Kinnate Biopharma. RAF Clinico-Genomic Landscape Study PowerPoint. (Nov. 2021). [cited by applicant]
Manabe. Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human BRAF-alteration driven non-small cell lung cancer (NSCLC). Presentation from IASLC 2022 Targeted Therapies of L… [cited by applicant]
McKean et al. Design and rationale of a first in human (FIH) phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF- and NRAS-mutation positive solid tumors. A… [cited by applicant]
Miller et al. Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human RAF/RAS mutant melanoma. American Association for Cancer Research Poster #2674 (2022). [cited by applicant]
Owsley et al. Prevalence of class I-III BRAF mutations among 114,662 cancer patients in a large genomic database. Exp Biol Med (Maywood) 246(1):31-39 (2021). [cited by applicant]
PCT/US2022/025815 International Search Report and Written Opinion dated Jul. 28, 2022. [cited by applicant]
PCT/US2022/025875 International Search Report and Written Opinion dated Jul. 25, 2022. [cited by applicant]
Severson et al. Occurrence of BRAF class II and III alterations is common across solid tumors and is associated with inferior clinical outcomes in NSCLC and melanoma. American Association for Cancer Research Poster #412… [cited by applicant]
Severson et al. Real-World Clinical Genomic Analysis of Patients with BRAF Mutated Cancers Identifies BRAF Class II and III as a Population of Unmet Medical Need. ESMO Targeted Anticancer Therapies Congress 2022. Poster… [cited by applicant]
Spira et al. A Phase 1 Clinical Trial Evaluating Monotherapy With Exarafenib (KIN-2787), a Highly Selective Pan-RAF Inhibitor, in BRAF-Altered Solid Tumors and NRAS-Mutant Melanoma. PowerPoint Presentation American Asso… [cited by applicant]
Subbiah et al. Pan-Cancer Efficacy of Vemurafenib in BRAF V600-Mutant Non-Melanoma Cancers. Cancer Discov 10(5):657-663 (2020). [cited by applicant]
U.S. Appl. No. 17/167,599 Office Action dated Oct. 31, 2022. [cited by applicant]
U.S. Appl. No. 17/738,327 Office Action dated Apr. 18, 2023. [cited by applicant]
U.S. Appl. No. 18/296,726 Office Action dated Jul. 18, 2023. [cited by applicant]
Wang et al. Exarafenib (KIN-2787) is a potent, selective pan-RAF inhibitor with activity in preclinical models of BRAF Class II/III mutant and NRAS mutant melanoma. American Association for Cancer Research Annual Meetin… [cited by applicant]
Yaeger et al. Targeting Alterations in the RAF-MEK Pathway. Cancer Discov 9(3):329-341 (2019). [cited by applicant]
Japanese Office Action for Japanese Application No. 2022-523904, dated Sep. 19, 2024, with English translation. [cited by applicant]
Cited By (1)
US 12,569,496