877676-50-1

Usage

Uses

Used in Pharmaceutical Industry:
(R)-2-chloro-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one is used as a key intermediate in the synthesis of selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors. These inhibitors are of significant interest due to their potential role in reducing α-synuclein phosphorylation in the rat brain, which may have implications for the treatment of neurodegenerative disorders such as Parkinson's disease.

Upstream product

• 889877-77-4 (7R)-2-chloro-7-ethyl-8-(propan-2-yl)-7,8-dihydropteridin-6(5H)-one 
• 616-38-6 carbonic acid dimethyl ester 
• 80-48-8 methyl p-toluene sulfonate 
• 946161-16-6 methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)(propan-2-yl)amino]butanoate 
• 947667-22-3 Methyl (2R)-2-(isopropylamino) butanoate 
• 74-88-4 methyl iodide 
• 512-56-1 trimethyl phosphite 

Downstream Products

• 755038-65-4 N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)6-oxo-2-pteridinyl]amino]-3-methoxy-benzamide 
• 1313518-61-4 (R)-7-ethyl-8-isopropyl-5-methyl-2-(2-phenyl-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one 
• 1313518-97-6 (R)-7-ethyl-8-isopropyl-5-methyl-2-(5-phenyl-1H-pyrazol-1-yl)-7,8-dihydropteridin-6(5H)-one 
• 1313518-99-8 (R)-7-ethyl-8-isopropyl-5-methyl-2-(5-phenyl-1H-1,2,4-triazol-1-yl)-7,8-dihydropteridin-6(5H)-one 
• 1313519-06-0 (R)-7-ethyl-8-isopropyl-5-methyl-2-(2-phenyl-4,5-dihydro-1H-imidazol-1-yl)-7,8-dihydropteridin-6(5H)-one 
• 1280665-36-2 N-[(trans)-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 
• 1280665-47-5 N-[(cis)-4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-7-[[(7R)-7-ethyl-8-isopropyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-2,3-dihydrobenzofuran-4-carboxamide 
• 1333493-13-2 BI2536 
• 755038-65-4 Volasertib 

Relevant academic research and scientific papers

PTERIDINONE COMPOUNDS AND USES THEREOF

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof for treating cellular proliferative disorders (e.g., cancer).

Structure-Guided Design and Development of Potent and Selective Dual Bromodomain 4 (BRD4)/Polo-like Kinase 1 (PLK1) Inhibitors

The simultaneous inhibition of polo-like kinase 1 (PLK1) and BRD4 bromodomain by a single molecule could lead to the development of an effective therapeutic strategy for a variety of diseases in which PLK1 and BRD4 are implicated. Compound 23 has been found to be a potent dual kinase-bromodomain inhibitor (BRD4-BD1 IC50 = 28 nM, PLK1 IC50 = 40 nM). Compound 6 was found to be the most selective PLK1 inhibitor over BRD4 in our series (BRD4-BD1 IC50 = 2579 nM, PLK1 IC50 = 9.9 nM). Molecular docking studies with 23 and BRD4-BD1/PLK1 as well as with 6 corroborate the biochemical assay results.

Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors

Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-α-synuclein levels in the cerebral cortex.

DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.

DIHYDROPTERIDINONE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Dihydroperidinone derivatives, preparation process and pharmaceutical use thereof are disclosed. Specially, new dihydroperidinone derivatives represented by general formula (I), wherein each substituent of the general formula (I) is defined as in the description, their preparation process, pharmaceutical compositions comprising said derivatives and their use as therapeutical agents, especially as Plk kinase inhibitors are disclosed.

PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE

The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

CRYSTALLINE FORM OF A DIHYDROPTERIDIONE DERIVATIVE

The present invention relates to a crystalline form a dihydropteridione derivative, namely a crystalline form of the free base N- [trans-4- [4- (cyclopropylmethyl) - 1-piperazinyl] cyclohexyl] -4- [[(7R) -7-ethyl-5, 6. 7, 8 - tetrahydro - 5 -methyl - 8 -

TRIHYDROCHLORIDE FORMS OF A DIHYDROPTERIDINONE DERIVATIVE AND PROCESSES FOR PREPARATION

The present invention relates to a specific salt of a dihydropteridione derivative, namely the trihydrochloride salt of the compound N-[trans-4-[4-(cyclopropylmethyl)-1- piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl