39639-45-7

Upstream product

• 108-91-8 cyclohexylamine 
• 5451-40-1 2,6 dichloropurine 
• 5451-40-1 2,6-dichloro-7H-purine 
• 146196-11-4 2-chloro-6-(cyclohexylamino)-9-(2'-deoxy-β-D-erythro-pentofuranosyl)-9H-purine 

Downstream Products

• 669003-63-8 [2-chloro-9-(2-chloro-ethyl)-purin-6-yl]-cyclohexyl-amine 
• 1007555-97-6 C₁₇H₂₄ClN₅ 
• 1007555-98-7 C₁₈H₂₀ClN₅ 
• 1007555-99-8 C₁₄H₂₀ClN₅ 
• 1063332-09-1 cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-9H-purin-6-yl]-amine 
• 863202-25-9 MRS 3767 
• 669003-60-5 (2-chloro-9-cyclopentyl-purin-6-yl)-cyclohexyl-amine 
• 789488-36-4 N⁽⁶⁾-cyclohexyl-N⁽²⁾-(4-methoxyphenyl)-9H-purine-2, 6-diamine 
• 778603-83-1 {2-chloro-9-[2-(4-methyl-piperazin-1-yl)-ethyl]-9H-purin-6-yl}-cyclohexyl-amine 
• 1026173-33-0 (2-chloro-9-{2-[(2-methoxy-ethyl)-methyl-amino]-ethyl}-9H-purin-6-yl)-cyclohexyl-amine 
• 925254-29-1 2-chloro-N-cyclohexyl-9-methyl-9H-purin-6-amine 

Relevant academic research and scientific papers

Synthesis of 2,6-diamino-substituted purine derivatives and evaluation of cell cycle arrest in breast and colorectal cancer cells

Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2-phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis. In all cases the HN(9) tautomer resulted more stable than the HN(7) form, but the most stable conformations changed in different solvents. Molecules 1-3 were evaluated on MCF-7 breast and HCT116 colorectal cancer cell lines showing that, while being less cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in G2/M phase in all the cell lines used, similar concentrations of 1-3 were effective only in cells where p53 was deleted or down-regulated. Therefore, our findings support a potential selective role of these structurally simplified, reversine-related molecules in p53-defective cancer cells.

Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead for Trypanosoma brucei Inhibitors

Human African trypanosomiasis (HAT), or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and transmitted through the bite of infected tsetse flies. The disease is considered fatal if left untreated. To identify new chemotypes against Trypanosoma brucei, previously we identified 797 potent kinase-targeting inhibitors grouped into 59 clusters plus 53 singleton compounds with at least 100-fold selectivity over HepG2 cells. From this set of hits, a cluster of diaminopurine-derived compounds was identified. Herein, we report our medicinal chemistry investigation involving the exploration of structure-activity and structure-property relationships around one of the high-throughput screening (HTS) hits, N2-(thiophen-3-yl)-N6-(2,2,2-trifluoroethyl)-9H-purine-2,6-diamine (1, NEU-1106). This work led to the identification of a potent lead compound (4aa, NEU-4854) with improved in vitro absorption, distribution, metabolism, and excretion (ADME) properties, which was progressed into proof-of-concept translation of in vitro antiparasitic activity to in vivo efficacy.

Design, synthesis and biological evaluation of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent Kinase2 (CDK2) dual inhibitors against malignant cancer

In the current study, we have designed and synthesized a series of novel histone deacetylase1/2 (HDAC1/2) and cyclin-dependent kinase2 (CDK2) dual inhibitors by integrating purine-based pharmacophore into the recognition cap group of CS055. The representative compound 14d with excellent antiproliferative activities towards five solid cancer cells, showed potent inhibitory activities against HDAC1, HDAC2 and CDK2 with IC50 values of 70.7 nM, 23.1 nM and 0.80 μM, respectively. Besides, compound 14d could effectively block the cell cycle in the G2/M phase and induce apoptosis, which might be related to increasing intracellular ROS levels. Importantly, compound 14d exhibited desirable pharmacokinetic (PK) properties with the intraperitoneal bioavailability of 50.8percent in ICR mice, and potent in vivo antitumor activity in the HCT116 xenograft model. Therefore, compound 14d could be considered as a promising lead compound for the development of multitargeting anticancer agents.

HETEROCYCLIC HYDROXAMIC ACIDS AS PROTEIN DEACETYLASE INHIBITORS AND DUAL PROTEIN DEACETYLASE-PROTEIN KINASE INHIBITORS AND METHODS OF USE THEREOF

The present invention relates to novel hydroxamic acids which are specific histone deacetylase (HDAC) inhibitors and/or TTK/Mpsl kinase inhibitors, including pharmaceutically acceptable salts thereof, which are useful for modulating HDAC and/or TTK/Mpsl k

INHIBITORS OF BRUTON'S TYROSINE KINASE

This application discloses compounds according to generic Formula (I) wherein all variables are defined as described herein, which inhibit BTK. The compounds disclosed herein are useful to modulate the activity of BTK and treat diseases associated with ex

Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse.

Synthesis and screening of 2,6-diamino-substituted purine derivatives as potential cardiomyogenesis inducing agents

The synthesis of 2,6-diamino-substituted purines is reported starting from 2,6-dichloropurine via two subsequent selective nucleophilic substitution reactions. The first substitution takes place selectively in 6-, the second in 2-position. The compounds w

COMPOUNDS AND THERAPEUTIC USES THEREOF

The invention relates to compounds, pharmaceutical compositions, and uses thereof, including therapeutic uses thereof, such as methods useful for treating cancer.

PURINYL DERIVATIVES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS

This invention relates to novel purinyl derivatives and their use as potassium channel modulating agents. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels.

Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB

Human African trypanosomiasis (HAT), a major health concern in sub-Saharan Africa, is caused by the protozoan parasite Trypanosoma brucei. Recent studies have shown that a cathepsin B like protease, TbcatB, is essential to the survival of T. brucei in vit