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
• Article Data: 9

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

(7R)-2-Chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-6(5H)-pteridinone is used as a reactant in the synthetic preparation of dihydroimidazolo-pteridine derivatives as novel Polo-like kinase-1 (PLK1) inhibitors and potential antitumor agents.

Upstream product

• 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 
• 947667-22-3 Methyl (2R)-2-(isopropylamino) butanoate 

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-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.

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.