717-88-4

Usage

Chemical compound

2-Amino-6-benzylpyrimidin-4(1H)-one

Class of organic compounds

Pyrimidine

Structure

Heterocyclic aromatic compound with a pyrimidine ring (six carbon atoms and four nitrogen atoms)

Functional groups

Amino group at the 2-position and benzyl group at the 6-position

Uses

Intermediate in the synthesis of pharmaceuticals and agrochemicals

Importance

Valuable in drug discovery and development, as well as in the creation of new materials and compounds

InChI:InChI=1/C11H11N3O/c12-11-13-9(7-10(15)14-11)6-8-4-2-1-3-5-8/h1-5,7H,6H2,(H3,12,13,14,15)

Upstream product

• 50-01-1 guanidine hydrochloride 
• 37779-49-0 methyl 3-oxo-4-phenylbutanoate 

Downstream Products

• 1046448-70-7 (R)-benzyl-6-(3-methylaminopyrrolidin-1-yl)pyrimidin-2-ylamine 
• 1046449-68-6 4-((R)-3-aminopyrrolidin-1-yl)-6-benzylpyrimidin-2-ylamine 

Relevant academic research and scientific papers

Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H 4 receptor antagonists

This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.

CHEMICAL COMPOUNDS

The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.