21236-97-5

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Chemical Properties

Off-White to Yellow Solid

Upstream product

• 94940-32-6 6-amino-2-methoxy-3-methylpyrimidin-4(3H)-one 
• 873-83-6 4-Amino-2,6-dihydroxypyrimidine 
• 74-88-4 methyl iodide 
• 54030-56-7 6-amino-3-methyl-2-(methylthio)pyrimidin-4(3H)-one 
• 138895-26-8 tris(trimethylsilyl) 6-aminouracil 
• 110472-85-0 Ethyl 3-amino-3-(3-methylureido)propenoate 
• 372-09-8 cyanoacetic acid 
• 598-50-5 N-Methylurea 

Downstream Products

• 53727-29-0 1-phenyl-3-methyl-barbituric acid 
• 123506-49-0 7-Amino-3-methyl-2,4-dioxo-5-phenyl-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester 
• 123506-55-8 7-Amino-3-methyl-2,4-dioxo-5-phenyl-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid amide 
• 19893-78-8 5-Acetylamino-6-amino-3-methyluracil 
• 85438-96-6 5-Acetylamino-6-formylamino-3-methyluracil 
• 1544274-04-5 3-methyl-5,6-diphenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-07-8 5-(4-chlorophenyl)-3-methyl-6-phenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-09-0 3-methyl-6-phenyl-7-thioxo-5-p-tolyl-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-11-4 5-(4-methoxyphenyl)-3-methyl-6-phenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-17-0 5-(4-bromophenyl)-3-methyl-6-phenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-14-7 3-methyl-5-(4-nitrophenyl)-6-phenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 1544274-22-7 5-(2-bromophenyl)-3-methyl-6-phenyl-7-thioxo-1,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidine-2,4-dione 
• 95548-68-8 7-Amino-3-methyl-2,4-dioxo-5-phenyl-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carbonitrile 
• 142168-87-4 3-methyl-6-nitropyrido<2,3-d>pyrimidine-2,4-dione 

Relevant academic research and scientific papers

Aryl spiro compound containing formamidine as well as preparation method and application of aryl spiro compound

The invention belongs to the field of medicinal chemistry, and particularly relates to an aryl spiro compound containing formamidine as well as a preparation method and application of the aryl spiro compound. The invention relates to three aryl spiro compounds as shown in general formulas I-III and pharmaceutically acceptable salts, enantiomers, non-isomers, tautomers, solvates, polymorphic substances or prodrugs thereof. On the basis that SHP099 is used as a lead compound, a brand new compound with guanidyl at the tail end is prepared, and the problems that an existing SHP2 inhibitor is single in structural framework and the like are solved. The aryl spiro compound has the important significance of providing many modification sites and providing a basis for later structural modification. Meanwhile, the embodiment of the invention proves that the compound has an allosteric inhibition effect on SHP2 phosphatase, and a skeleton support is provided for subsequent development of an SHP2 phosphatase inhibitor.

SHP2 INHIBITORS AND USES THEREOF

Compounds of Formula 1 as inhibitors of protein tyrosine phosphatase SHP2 are disclosed. The pharmaceutical compositions comprising compounds of Formula 1, methods of synthesis of these compounds, methods of treatment for diseases associated with the aberrant activity of SHP2 such as cancer using these compounds or compositions containing these compounds are also disclosed.

Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents

A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 μM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners 6a-b and 9-16. Hydroxyimino-phenethyl scaffold compounds 17-24 were more active than the hydroxyimino-ethyl phenyl acetamide 7a-b derivatives. Compounds 18–20 and 22-24 exhibited inhibition of EGFR with IC50 ranging from 0.32 to 2.88 μM. Compounds 18-20 and 22-24 increased the level of active caspase 3 by 4–8 folds, compared to the control cells in Panc-1 cell lines compared to doxorubicin as a reference drug. Compounds 18, 22 and 23 were the most caspase-3 inducers. Compounds 22 and 23 increased the levels of caspase-8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of cytochrome c levels in Panc-1 human pancreas cancer cells. Compound 23 exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of Panc-1 cell line. The drug likeness profiles of compounds 18-20 and 22-24 were predicted to have good to excellent drug likeness profiles specially compounds 18-20 and 23. Finally molecular docking study was performed at the EGFR active site to suggest thier possible binding mode. The hydroxyimino-phenethyl scaffold compounds 17-24 represent an interesting starting point to optimize their pharmacokinetics and pharmacodynamics profiles.

EGFR inhibitors and apoptotic inducers: Design, synthesis, anticancer activity and docking studies of novel xanthine derivatives carrying chalcone moiety as hybrid molecules

One of the helpful ways to improve the effectiveness of anticancer agents and weaken drug resistance is to use hybrid molecules. therefore, the current study intended to introduce 20 novel xanthine/chalcone hybrids 9–28 of promising anticancer activity. Compounds 10, 11, 13, 14, 16, 20 and 23 exhibited potent inhibition of cancer cells growth with IC50 ranging from 1.0 ± 0.1 to 3.5 ± 0.4 μM compared to doxorubicin with IC50 ranging from 0.90 ± 0.62 to 1.41 ± 0.58 μM and that compounds 11 and 16 were the best. To verify the mechanism of their anticancer activity, compounds 10, 11, 13, 14, 16, 20 and 23 were evaluated for their EGFR inhibitory effect. The study results revealed that compound 11 showed IC50 = 0.3 μM on the target enzyme which is more potent than staurosporine reference drug (IC50 = 0.4 μM). Accordingly, the apoptotic effect of the most potent compounds 11 was extensively investigated and showed a marked increase in Bax level up to 29 folds, and down-regulation in Bcl2 to 0.28 fold, in comparison to the control. Furthermore, the effect of compound 11 on Caspases 3 and 8 was evaluated and was found to increase their levels by 8 and 14 folds, respectively. Also, the effect of compound 11 on the cell cycle and its cytotoxic effect were examined. Moreover, a molecular docking study was adopted to confirm mechanism of action.

MARKER COMPOUNDS OF LEPTOSPERMUM HONEYS AND METHODS OF ISOLATION AND ASSAYING THEREOF

Described herein are novel isolated compounds from Leptospermum honey and methods of assay thereof for use in the verification of the place of origin, authenticity and content of Leptospermum honeys such as mānuka honey. The inventors screened flower nectar and honeys of various floral types found in New Zealand to identify chemicals that were either unique to or in significantly higher concentrations in mānuka nectar and mono-floral mānuka honey compared to other predominantly mono-floral nectars and honeys. As a result of the screening exercise, the inventors discovered a marker compounds that could distinguish Leptospermum honey nectar and honey from other floral sources.

Isolation, Structural Elucidation, and Synthesis of Lepteridine from Manuka (Leptospermum scoparium) Honey

Manuka honey, made from the nectar of Leptospermum scoparium, has garnered scientific and economical interest due to its nonperoxide antibacterial activity. Biomarkers for genuine manuka honey are increasingly in demand due to the presence of counterfeit manuka honey. This work reports the identification of a compound previously unreported in manuka honey by HPLC, and determination of the structure of the as 3,6,7-trimethyllumazine using NMR, MS, IR, and UV/vis spectroscopy. This assignment was confirmed by total synthesis. The natural product, renamed lepteridine, was only observed in manuka honeys and could potentially serve as a biomarker for genuine manuka honey.

SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF

Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

Synthesis and pharmacological evaluation of novel 1,3,8- and 1,3,7,8-substituted xanthines as adenosine receptor antagonists

A number of novel xanthines bearing a variety of substituents at positions 1, 3, 7 and 8 were prepared and evaluated for their binding affinity to the human adenosine receptor A1, A2A, A2B and A3 subtypes. Several of the 1,3,8- and 1,3,7,8-substituted xanthines showed moderate-to-high affinity at human A2B and A1 receptors, with the most active compound (14q) having a pKi of 7.57 nM for hA2B receptors and a selectivity over hA2A receptors of 8.1-fold and hA1 receptors of 3.7-fold.

XANTHINE DERIVATIVES AS A2B ADENOSINE RECEPTOR ANTAGONISTS

Disclosed are compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.

A2B adenosine receptor antagonists

Disclosed are novel compounds that are A2B adenosine receptor antagonists, useful for treating various disease states, including asthma and diarrhea.