105161-35-1

Upstream product

• 449811-60-3 1,3-diethoxy-2-formylpropionitrile potassium salt 
• 17356-08-0 thiourea 
• 149139-41-3 α-cyano-β-dimethylaminoacrolein 

Downstream Products

• 1280218-07-6 6-(2,4-difluorophenoxy)-8H-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1280218-26-9 6-(2,4-difluorophenoxy)-2-methylsulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-13-4 [6-(2,4-difluorophenoxy)-7-oxo-2-(tetrahydropyran-4-ylamino)-7H-pyrido[2,3-d]pyrimidin-8-yl]acetonitrile 
• 1280218-48-5 [6-(2,4-difluorophenoxy)-2-methanesulfonyl-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-yl]acetonitrile 
• 1280218-47-4 [6-(2,4-difluorophenoxy)-2-methylsulfanyl-7-oxo-7H-pyrido[2,3-d]pyrimidin-8-yl]acetonitrile 
• 1280218-22-5 6-(2,4-difluorophenoxy)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-12-3 6-(2,4-difluorophenoxy)-8-((S)-2,3-dihydroxypropyl)-2-(tetrahydropyran-4-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-46-3 6-(2,4-difluorophenoxy)-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-2-(tetrahydropyran-4-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-45-2 6-(2,4-difluorophenoxy)-8-((S)-2,2-dimethyl[1,3]dioxolan-4-ylmethyl)-2-methanesulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-44-1 6-(2,4-difluorophenoxy)-8-((S)-2,2-dimethyl[1,3]dioxolan-4-ylmethyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-11-2 6-(2,4-difluorophenoxy)-8-(2-hydroxy-2-methylpropyl)-2-(tetrahydropyran-4-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-43-0 6-(2,4-difluorophenoxy)-8-(2-hydroxy-2-methylpropyl)-2-methanesulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-42-9 6-(2,4-difluorophenoxy)-8-(2-hydroxy-2-methylpropyl)-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one 
• 1280218-09-8 6-(2,4-difluorophenoxy)-8-(3-methanesulfonylpropyl)-2-(tetrahydropyran-4-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one 

Relevant academic research and scientific papers

Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl) propylamino]-8-methyl-8 H -pyrido[2,3- d ]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2 H -pyran-4-ylamino)pyrido[2,3- d ]pyrimidin-7(8 H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase

The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.

6-ALKOXY-PYRIDO-PYRIMIDINES AS P-38 MAP KINASE INHIBITORS

The present invention provides compounds of Formula (I), wherein R1 is alkyl, cycloalkyl, cycloakylalkyl, or -CH2-alkenyl, X1 is O, NH, N(alkyl), S or -C(=O), Z is N or CH; and R2 and R3 are as define

SYNTHESIS WITH NITRILES: 92. SYNTHESIS OF 5-FORMYLCYTOSINE DERIVATIVES

The reactivity of 3-dimethylamino-2-formylpropenenitrile (1) with various amino compounds is studied.Thus, condensation of 1 with anilines gives the corresponding azomethines (2a-c).Reaction of 1 with thiourea and guanidine resp., leads to 5-formylthiocyt