945397-01-3

Upstream product

• 945397-00-2 N-(3,5-dimorpholin-4-ylphenyl)formamide 
• 97229-11-3 4-chloro-2-methanesulfonylpyrimidine 
• 2265-94-3 1,3-difluoro-5-nitrobenzene 
• 220954-17-6 4,4’-(5-nitro-1,3-phenylene)dimorpholine 

Downstream Products

• 1051901-06-4 4-chloro-N-(3,5-dimorpholin-4-ylphenyl)-N-[(4-methoxyphenyl)methyl]pyrimidin-2-amine 
• 1051899-45-6 N-(3,5-dimorpholin-4-ylphenyl)-N'-methyl-pyrimidine-2,4-diamine 
• 1051897-08-5 N-(3,5-dimorpholin-4-ylphenyl)-N'-(3-methoxyphenyl)-N'-methyl-pyrimidine-2,4-diamine 
• 945396-67-8 N-(3,5-dimorpholin-4-ylphenyl)-N'-(1H-indol-4-yl)pyrimidine-2,4-diamine 
• 945396-60-1 N-(3,5-dimorpholinophenyl)-N'-(3-methyl-1H-indazol-4-yl)pyrimidine-2,4-diamine 
• 945396-59-8 N'-(3-chloro-1H-indazol-4-yl)-N-(3,5-dimorpholinophenyl)pyrimidine-2,4-diamine 
• 945396-69-0 N'-(1H-benzotriazol-4-yl)-N-(3,5-dimorpholin-4-ylphenyl)pyrimidine-2,4-diamine 
• 945396-71-4 N-(3,5-dimorpholin-4-ylphenyl)-N'-(1H-indazol-7-yl)pyrimidine-2,4-diamine 
• 945396-58-7 N²-(3,5-dimorpholinophenyl)-N⁴-(1H-indazol-4-yl)pyrimidine-2,4-diamine 
• 1051897-31-4 N'-(4-chlorophenyl)-N-(3,5-dimorpholin-4-ylphenyl)-N'-methyl-pyrimidine-2,4-diamine 
• 1051898-81-7 N₂-(3,5-dimorpholinophenyl)-N₄-isopropyl-N₄-(3-methoxyphenyl)pyrimidine-2,4-diamine 
• 1051897-42-7 N'-(2,3-difluorophenyl)-N-(3,5-dimorpholin-4-ylphenyl)-N'-methyl-pyrimidine-2,4-diamine 
• 1051899-64-9 N₂-(3,5-dimorpholinophenyl)-N₂-(4-methoxybenzyl)-N₄-(3-methoxyphenyl)pyrimidine-2,4-diamine 
• 1051899-65-0 N₂-(3,5-dimorpholinophenyl)-N₄-isopropyl-N₂-(4-methoxybenzyl)-N₄-(3-methoxyphenyl)pyrimidine-2,4-diamine 

Relevant academic research and scientific papers

PYRIMIDINE DERIVATIVES

The invention concerns benzamide compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, ring A, n, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4, and/or EphA2 and/or Src kinases.

Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series

Optimization of our bis-anilino-pyrimidine series of EphB4 kinase inhibitors led to the discovery of compound 12 which incorporates a key m-hydroxymethylene group on the C4 aniline. 12 displays a good kinase selectivity profile, good physical properties a

Inhibitors of the tyrosine kinase EphB4. Part 3: Identification of non-benzodioxole-based kinase inhibitors

Starting from the initial bis-anilinopyrimidine 1, good potency against EphB4 was retained when benzodioxole at C-4 was replaced by an indazole. The key interactions of the indazole with the protein were characterised by crystallographic studies. Further optimisation led to compound 20, a potent inhibitor of the EphB4 and Src kinases with good pharmacokinetics in various preclinical species and high fraction unbound in plasma. Compound 20 may be used as a tool for evaluating the potential of EphB4 kinase inhibitors in vivo.

2,4-DIAMINO-PYRIMIDINE DERIVATIVES

The invention concerns compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, Q, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation ofsuch compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.

NOVEL PYRIMIDINE DERIVATIVES 698

The invention concerns compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, n, R2, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4 kinases.