889877-77-4

Basic information

• Product Name: (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one
• Synonyms: (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one;(7R)-2-Chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-6(5H)-pteridinone;(R)-2-Chloro-7-ethyl-8-isopropyl-7,8-dihydro-5H-pteridin-6-one;Volasertib(BI6727)-A4;2-Chloro-7-ethyl-8-isopropyl-7,8-dihydro-5H-pteridin-6-one
• CAS NO: 889877-77-4
• Molecular Formula: C11H15ClN4O
• Molecular Weight: 254.72
• Mol File: 889877-77-4.mol

Chemical Properties

• Boiling Point: 465.668 °C at 760 mmHg
• Flash Point: 235.428 °C
• Appearance: /
• Density: 1.224
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• CAS DataBase Reference: (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one(889877-77-4)
• EPA Substance Registry System: (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one(889877-77-4)

Safety Data

• Hazardous Substances Data: 889877-77-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one is used as a key reactant in the synthetic preparation of dihydroimidazolo-pteridine derivatives. These derivatives have emerged as novel Polo-like kinase-1 (PLK1) inhibitors, which hold promise as potential antitumor agents. By targeting the PLK1 enzyme, which plays a crucial role in cell division and proliferation, these inhibitors can disrupt the cell cycle and impede the growth of cancer cells, offering a new avenue for cancer treatment.

Upstream product

• 947667-22-3 Methyl (2R)-2-(isopropylamino) butanoate 
• 946161-16-6 methyl (2R)-2-[(2-chloro-5-nitropyrimidin-4-yl)(propan-2-yl)amino]butanoate 
• 64-19-7 acetic acid 
• 947586-41-6 methyl (2R)-2-(propan-2-ylamino)butanoate hydrochloride 

Downstream Products

• 877676-50-1 2-chloro-7-ethyl-7,8-dihydro-5-methyl-8-(1-methylethyl)-(7R)-6(5H)-pteridinone 
• 1214265-78-7 (R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-3-methoxybenzoic acid 
• 1214265-80-1 (R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid 
• 1333493-13-2 BI2536 

Relevant articles and documents

A practical chromatography-free synthesis of a 5,6-dihydroimidazolo[1,5-f]pteridine derivative as a polo-like kinase-1 inhibitor

A practical chromatography-free synthesis of a potent polo-like kinase-1 inhibitor possessing a unique 5,6-dihydroimidazolo[1,5-f]pteridine structure has been developed. We showed that key cyanoimidazole ring formation could be conducted at benign temperature and obtained a chiral 5,6-dihydroimidazolo[1,5-f]pteridine derivative in good yield without epimerization. An aniline derivative containing a trans 1,4-cyclohexyl diamine structure was prepared by a synthesis that makes use of defined stereocenters of commercially available trans-cyclohexane-1,4-diamine via selective piperazine ring formation from a primary diamine. A coupling reaction of the 3-chloro-5,6-dihydroimidazolo[1,5-f]pteridine derivative and the aniline derivative in the endgame was closely investigated, and good yields were achieved both by palladium-catalyzed amination and acid-promoted coupling under benign reaction conditions. As a result of these investigations, the polo-like kinase-1 inhibitor was successfully obtained in a practical way without concern for generation/separation of stereoisomers.

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.

Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors

Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]pteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits >7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model.

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.

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

Process for the manufacture of fused piperazin-2-one derivatives

Disclsoed are processes for the preparation of fused piperazin-2-one derivatives of general formula (I) wherein the groups R1 to R5, A1 and A2 have the meanings given in the claims and in the description, particularly the preparation of 7,8-dihydro-5H-pteridin-6-one derivatives and intermediates thereof.