101622-51-9

Usage

Uses

Used in Pharmaceutical Industry:
OLOMOUCINE is used as an anticancer agent for its ability to inhibit cyclin-dependent kinases and induce G1 arrest, playing a crucial role in the development of targeted cancer therapies.
Used in Drug Development:
OLOMOUCINE is utilized as a lead compound in drug development for its potential to modulate cell cycle progression, offering a promising avenue for the creation of novel therapeutic agents.
Used in Research Applications:
As a purine derivative with specific biochemical properties, OLOMOUCINE is used in research settings to study the mechanisms of cell cycle regulation and the development of new strategies for cancer treatment.
Used in Chemical Synthesis:
Due to its unique chemical structure, OLOMOUCINE serves as a key intermediate in the synthesis of other bioactive compounds, contributing to the advancement of medicinal chemistry.

Biological Activity

Cyclin-dependent kinase inhibitor that competes for the ATP binding site of the kinase. Selectively inhibits cdc2/cyclin B (IC 50 = 7 μ M), cdk2/cyclin A (IC 50 = 7 μ M), cdk2/cyclin E (IC 50 = 7 μ M), cdk/p35 kinase (IC 50 = 3 μ M)? and ERK1/MAP kinase (IC 50 = 25 μ M). Arrests human fibroblasts in the G1 phase.

Biochem/physiol Actions

Olomoucine is a purine derivative which inhibits cyclin-dependent kinases and induces G arrest.

Enzyme inhibitor

This ATP site-competitive purine derivative (FW = 298.35 g/mol; CAS 101622-51-9), systematically named 6-benzylamino-2-[2-hydroxyethylamino]- 9-methylpurine, is a potent inhibitor of cyclin-dependent kinases, with an IC50 value of 7 μM for both cdk1 and cdk2 and an IC50 value of 3 μM for cdk5, arresting cells in G1. Olomoucine also inhibits cytokinin 7b-glucosyltransferase.

references

[1]. vesel j, havlicek l, strnad m, et al. inhibition of cyclin-dependent kinases by purine analogues. eur j biochem. 1994 sep 1;224(2):771-86.[2]. abraham rt, acquarone m, andersen a, et al. cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases. biol cell. 1995;83(2-3):105-20.[3]. tian ds, xie mj, yu zy, et al. cell cycle inhibition attenuates microglia induced inflammatory response and alleviates neuronal cell death after spinal cord injury in rats. brain res. 2007 mar 2;1135(1):177-85.

InChI:InChI=1/C15H18N6O/c1-21-10-18-12-13(17-9-11-5-3-2-4-6-11)19-15(16-7-8-22)20-14(12)21/h2-6,10,22H,7-9H2,1H3,(H2,16,17,19,20)

Upstream product

• 101622-53-1 2-chloro-6-benzylamino-9-methylpurine 
• 141-43-5 ethanolamine 
• 74-88-4 methyl iodide 
• 67-56-1 methanol 
• 1651-29-2 6-chloro-2-fluoropurine 
• 74-89-5 methylamine 
• 100-46-9 benzylamine 
• 1979-96-0 4,6-dichloro-2-(methylthio)-5-nitropyrimidine 
• 149-73-5 trimethyl orthoformate 
• 5502-78-3 9-Methylguanine 
• 5451-40-1 2,6 dichloropurine 
• 2382-10-7 2,6-dichloro-9-methyl-9H-purine 
• 39639-47-9 N⁶-benzyl-2-chloroadenine 
• 158982-11-7 2-amino-6-benzylamino-9-purine 

Relevant academic research and scientific papers

Novel solid-phase preparation of 2,6,9-trisubstituted purines for combinatorial library generation

A novel procedure for the preparation of 2,6,9-trisubstituted purine libraries has been developed.

Utility of 4,6-dichloro-2-(methylthio)-5-nitropyrimidine. An efficient solid-phase synthesis of olomoucine

4,6-Dichloro-2-(methylthio)-5-nitropyrimidine has been utilized as a building block for an efficient nine-step synthesis of olomoucine. The methodology reported herein is applicable to the regiocontrolled solution and solid-phase synthesis of libraries of highly substituted purines, as well as other related scaffolds.

An efficient direct amination of cyclic amides and cyclic ureas

An efficient one-step amination of cyclic amides and ureas has been developed. Treatment of cyclic amides and cyclic ureas with BOP in the presence of DBU in various solvents led to the formation of cyclic amidines and cyclic guanidines in good to excellent yields. Concise syntheses of biologically intriguing kinetin and potent kinase inhibitor olomoucin were thus achieved in just one and two steps, respectively.

The scope and mechanism of phosphonium-mediated SNAr reactions in heterocyclic amides and ureas

(Chemical Equation Presented) An efficient "one-step" synthesis of cyclic amidines and guanidines has been developed. Treatment of cyclic amides and ureas with benzotriazol-l-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), base, and nitrogen nucleophiles leads to the formation of the corresponding cyclic amidines and guanidines, typically in good to excellent yields. This method has also been used to prepare heteroaryl ethers and thioethers using phenol and thiophenol nucleophiles. Time course NMR and HPLC-MS studies have facilitated explicit characterization of the proposed intermediates (the phosphonium salt and HOBt adduct); the data reveal a stepwise reaction pathway.

Synthesis and activity of 2,6,9-trisubstituted purines

The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented.

SUBSTITUTED XANTHINES AND CYTOKININ ANALOGUES AS INHIBITORS OF CYTOKININ N-GLUCOSYLATION

A series of 3-substituted xanthines, 2-(2-hydroxy-2-methylpropylamino)-9-methyl-6-benzylaminopurine and 7-benzylaminooxazolopyrimidine were synthesized as potential inhibitors of cytokinin N-glucosylation.In maize leaf segments the latter compound

INHIBITORS OF TWO ENZYMES WHICH METABOLIZE CYTOKININS

Compounds which inhibit the natural metabolic inactivation of cytokinins are cosiderable physiological significance.In this study, inhibitors have been found for two enzymes which form glucose and alanine conjugates of cytokinin bases, namely, cytokinin 7-glucosyltransferase and β-(9-cytokinin)alanine synthase.The most effective inhibitors found for the former enzyme were the cytokinin analogues 3-methyl-7-n-pentylaminopyrazolopyrimidine, which acted competitively (Ki 22 μM), and the diaminopurine, 6-benzylamino-2-(2-hydroxyethylamino)-9-methylpurine (Ki 3.3 μM).However these compounds were ineffective as inhibitors of the cytokinin-alanine sythase which was inhibited competitively by IAA (Ki 70 μM) and related compounds, especially 5,7-dichloro-IAA (Ki 0.4 μM).Certain urea derivatives were moderately effective inhibitors of the enzymes (Ki ca 100 μM). Key Word Index - Cytokinins; metabolism; cytokinin 7-glucosyltransferase; β-(9-cytokinin)alanine synthase; N6-substituted adenines; auxins; indoleacetic acid.