1286738-66-6

Upstream product

• 185040-34-0 (4-ethylamino-2-methanesulfanyl-pyrimidin-5-yl)-methanol 
• 185040-33-9 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 1261606-45-4 (4-bromo-2-chlorophenyl)acetic acid ethyl ester 
• 185040-35-1 4-ethylamino-2-methylthiopyrimidine-5-carboxaldehyde 
• 916516-89-7 2-(4-bromo-2-chlorophenyl)acetic acid 
• 67197-54-0 2-(4-bromo-2-chlorophenyl)acetonitrile 
• 89720-77-4 4-bromo-1-bromomethyl-2-chlorobenzene 
• 185315-48-4 (4-bromo-2-chlorophenyl)methanol 
• 59748-90-2 4-Bromo-2-chloro-benzoic Acid 

Downstream Products

• 1428760-85-3 3-chloro-4-[8-ethyl-2-(methylsulfanyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl]benzonitrile 
• 1428760-89-7 6-(2-chloro-4-(2-methylthiazol-5-yl)phenyl)-8-ethyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1428758-45-5 C₂₉H₂₉ClN₈O 
• 1330065-78-5 C₃₀H₃₀ClN₇OS 
• 1428760-83-1 3-chloro-4-(8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)benzonitrile 
• 1428759-01-6 C₂₇H₂₇ClN₁₀O 
• 1428760-84-2 3-chloro-4-(8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)-N-hydroxybenzimidamide 
• 1428760-86-4 3-chloro-4-[8-ethyl-2-(methylsulfanyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl]-N'-hydroxy-1-benzenecarboximidamide 
• 1428760-87-5 6-[2-chloro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-8-ethyl-2-(methylsulfanyl)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1428760-88-6 6-[2-chloro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-8-ethyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1428759-09-4 6-[2-chloro-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]-8-ethyl-2-[4-(4-methylpiperazino)anilino]pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1428759-13-0 C₂₈H₂₆ClN₇O₂ 
• 1428760-90-0 6-(2-chloro-4-(2-methyl-1,3-thiazol-5-yl)phenyl)-8-ethyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1428759-18-5 C₃₂H₃₃ClN₆OS 

Relevant academic research and scientific papers

Chemically Diverse Group i p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window

p21-activated kinase 1 (PAK1) has an important role in transducing signals in several oncogenic pathways. The concept of inhibiting this kinase has garnered significant interest over the past decade, particularly for targeting cancers associated with PAK1 amplification. Animal studies with the selective group I PAK (pan-PAK1, 2, 3) inhibitor G-5555 from the pyrido[2,3-d]pyrimidin-7-one class uncovered acute toxicity with a narrow therapeutic window. To attempt mitigating the toxicity, we introduced significant structural changes, culminating in the discovery of the potent pyridone side chain analogue G-9791. Mouse tolerability studies with this compound, other members of this series, and compounds from two structurally distinct classes revealed persistent toxicity and a correlation of minimum toxic concentrations and PAK1/2 mediated cellular potencies. Broad screening of selected PAK inhibitors revealed PAK1, 2, and 3 as the only overlapping targets. Our data suggest acute cardiovascular toxicity resulting from the inhibition of PAK2, which may be enhanced by PAK1 inhibition, and cautions against continued pursuit of pan-group I PAK inhibitors in drug discovery.

8-ETHYL-6-(ARYL)PYRIDO [2,3-D]PYRIMIDIN-7(8H) -ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER

Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.