330550-92-0

Upstream product

• 1003-03-8 Cyclopentamine 
• 49845-33-2 2,4-Dichloro-5-nitropyrimidine 

Downstream Products

• 877661-65-9 4-(4-cyclopentylamino-5-nitro-pyrimidin-2-ylamino)-3-methoxy-benzoic acid benzyl ester 
• 330550-98-6 N⁴-cyclopentyl-N²-(4-(4-methylpiperazin-1-yl)phenyl)-5-nitropyrimidine-2,4-diamine 
• 330551-01-4 tert-butyl 4-(4-((4-(cyclopentylamino)-5-nitropyrimidin-2-yl)amino)phenyl) piperazine-1-carboxylate 
• 1124329-09-4 4-((9-cyclopentyl-7-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide 
• 1350545-54-8 4-cyclopentylamino-2-(4-((4-methylpiperazin-1-yl)methyl)phenylamino)-5-nitropyrimidine 
• 1350545-53-7 4-cyclopentylamino-2-(4-((4-ethylpiperazin-1-yl)methyl)phenylamino)-5-nitropyrimidine 
• 1350545-52-6 4-cyclopentylamino-2-(4-(2-methoxyethoxy)phenylamino)-5-nitropyrimidine 
• 1350545-51-5 4-cyclopentylamino-2-(4-(4-morpholinylmethyl)phenylamino)-5-nitropyrimidine 
• 1350545-45-7 4-(4-cyclopentylamino-5-nitropyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 
• 1350545-78-6 4-cyclopentylamino-2-(4-((4-methylpiperazin-1-yl)methyl)phenylamino)-5-aminopyrimidine 
• 1350545-77-5 4-cyclopentylamino-2-(4-((4-ethylpiperazin-1-yl)methyl)phenylamino)-5-aminopyrimidine 
• 1350545-76-4 4-cyclopentylamino-2-(4-(2-methoxyethoxy)phenylamino)-5-aminopyrimidine 
• 1350545-75-3 4-cyclopentylamino-2-(4-(4-morpholinylmethyl)phenylamino)-5-aminopyrimidine 
• 1350545-69-5 4-(4-cyclopentylamino-5-aminopyrimidin-2-ylamino)-N-(4-methylpiperazin-1-yl)benzamide 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a hydrazone moiety as potent PLK1 inhibitors

A series of novel pteridinone derivatives possessing a hydrazone moiety were designed, synthesized and evaluated for their biological activity. Most of the synthesized compounds demonstrated moderate to excellent activity against A549, HCT116 and PC-3 cancer cell lines. In particular, compound L19 exhibited the most potent antiproliferative effects on three cell lines with IC50 values of 3.23 μM, 4.36 μM and 8.20 μM, respectively. In kinase assays, the compound L19 also showed potent inhibition activity toward PLK1 with % inhibition values of 75.1. Further mechanism studies revealed that compound L19 significantly inhibited proliferation of HCT-116 cell lines, induced a great decrease in mitochondrial membrane potential resulting in apoptosis of cancer cells, inhibited the migration of tumor cells, and arrested G1 phase of HCT116 cells.

Aminopurine based JNK inhibitors for the prevention of ischemia reperfusion injury

In this Letter we describe the optimization of an aminopurine lead (1) with modest potency and poor overall kinase selectivity which led to the identification of a series of potent, selective JNK inhibitors. Improvement in kinase selectivity was enabled by introduction of an aliphatic side chain at the C-2 position. CC-359 (2) was selected as a potential clinical candidate for diseases manifested by ischemia reperfusion injury.

Pteridinone compound and application thereof

The invention relates to a pteridinone compound. The chemical structure of the compound is shown as a formula (I). The pteridinone compound provided by the invention can inhibit cyclin dependent kinases (CDKs), especially CDK4 and CDK6, and has a remarkable effect of controlling proliferation of tumor cells of mammary gland, cervix uteri or colon, so that the compound can be used for preparing antitumor drugs.

Design, synthesis and antiproliferative activity of novel 2,4-diamino-5-methyleneaminopyrimidine derivatives as potential anticancer agents

In order to discover new anticancer agents, 25 novel 2,4-diamino-5-methyleneaminopyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Among them, compared with 5-FU, compound 7i exhibited 4.9-, 2.9-,

The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5- a]pyridin-6-yl)amino]-9-(tetrahydro-2 H-pyran-4-yl)-7,9-dihydro-8 H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor

DNA-PK is a key component within the DNA damage response, as it is responsible for recognizing and repairing double-strand DNA breaks (DSBs) via non-homologous end joining. Historically it has been challenging to identify inhibitors of the DNA-PK catalyti

Compound containing pteridinone skeleton, preparation method and application thereof

The invention belongs to the technical field of medicines, and relates to a pteridinone skeleton-containing compound represented by a general formula I, and a preparation method thereof, and a pharmaceutical composition taking the compound represented by the general formula I as an active ingredient, wherein the substituent groups R1, R2, R3, R4, A, A and A are defined in the specification. The invention also relates to application of the compound represented by the general formula I and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug and the pharmaceutical composition thereof in preparation of drugs for treating and/or preventing cancers and other proliferative diseases.

Preparation method of dihydropteridine diketone skeleton-containing derivative and application thereof

The invention relates to dihydropteridine dione derivatives as shown in a general formula I and optical isomers, pharmaceutically acceptable salts, solvates or prodrugs thereof, preparation methods ofthe dihydropteridine dione derivatives and the optical isomers, the pharmaceutically acceptable salts, the solvates or the prodrugs, and a pharmaceutical composition taking compounds as shown in thegeneral formula I as active ingredients, wherein substituent groups R1, R2, R3 and Ar have meanings given in the specification. The invention also relates to a compound shown in the general formula I,which has a strong PLK1 inhibition effect. The invention also relates to an application of the compounds and optical isomers and pharmaceutically acceptable salts thereof in preparation of medicinesfor treating and/or preventing diseases caused by abnormal expression of PLK1, and particularly relates to the application of the compounds in preparation of medicines for treating and/or preventing cancers.

Discovery of potent small molecule PROTACs targeting mutant EGFR

Epidermal growth factor receptor (EGFR) is an important therapeutic target for the treatment of non-small cell lung cancer. A number of efficacious EGFR tyrosine kinase inhibitors have been developed. However, acquired drug resistance largely encumbered their clinical practicability. Therefore, there is an urgent need to develop new therapeutic regime. Herein, we designed and synthesized a set of EGFR-targeting small molecule PROTACs which showed promising efficacy. In particular, VHL-recruiting compound P3 showed potent anti-proliferative activity against HCC827 and H1975 cell lines with IC50 values of 0.83 and 203.01 nM, respectively. Furthermore, both EGFRdel19 and EGFRL858R/T790M could be significantly induced to be degraded under treatment of P3 with DC50 values of 0.51 and 126.2 nM, respectively. Compound P3 was able to dramatically suppress EGFR pathway signal transduction. Moreover, compound P3 could significantly induce cell apoptosis, arrest cell cycle and suppress cell colony formation. In addition, we identified that ubiquitination was indispensable in the degradation process, and found that the degradation was related to autophagy. Our work would provide an alternative approach for development of potentially effective EGFR degraders and give a new clue for investigation of PROTAC-induced protein degradation.

Design, synthesis and biological evaluation of novel pteridinone derivatives as potent dual inhibitors of PLK1 and BRD4

To develop novel simultaneous inhibition of PLK1 and BRD4 bromodomain by a single molecule, three series of novel pteridinone derivatives were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against A549, HCT116, PC-3 and MCF-7 cell lines. The most promising compound III4 showed high antiproliferative effects on four cell lines with IC50 values of 1.27 μM, 1.36 μM, 3.85 μM and 4.06 μM, respectively. The enzymatic assay identified III4 as a potent PLK1 and BRD4 dual inhibitor with % inhibition values of 96.6 and 59.1, respectively. Furthermore, to clarify the anticancer mechanism of the target compounds, explorations in the bioactivity were conducted. The results showed that compound III4 obviously inhibited the proliferation of HCT-116 cell lines, induced a great decrease in the mitochondrial membrane potential leading to apoptosis of cancer cells, suppressed the migration of tumor cells, and arrested the S phase of HCT116 cells.

Design, synthesis and biological evaluation of novel 7-amino-[1,2,4]triazolo[4,3-f]pteridinone, and 7-aminotetrazolo[1,5-f]pteridinone derivative as potent antitumor agents

To develop novel therapeutic agents with anticancer activities, two series of novel 7-amino-[1,2,4]triazolo[4,3-f]pteridinone, and 7-aminotetrazolo[1,5-f]pteridinone derivatives were designed and synthesized. All compounds were tested for anti-proliferative activities against five cancer cell lines. The structure-activity relationships (SARs) studies were conducted through the variation in two regions, the moiety of A ring and the terminal aniline B on pteridinone core. 1-Methyl-1,2,4-triazole derivative L7 with 2,6-dimethylpiperazine showed the most potent antiproliferative activity against A549, PC-3, HCT116, MCF-7 and MDA-MB-231 cell lines with IC50 values of 0.16 μM, 0.30 μM, 0.51 μM, 0.30 μM, and 0.70 μM, respectively. Combined with the results of the molecular docking and enzymatic studies, the PLK1 was very likely to be one of the drug targets of compound L7. Furthermore, to clarify the anticancer mechanism of compound L7, further explorations in the bioactivity were conducted. The results showed that compound L7 obviously inhibited proliferation of A549 cell lines, induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells, suppressed the migration of tumor cells, and arrested G1 phase of A549 cells.