27038-81-9

Upstream product

• 6972-82-3 5,6-diamino-1-methyluracil 
• 298-12-4 Glyoxilic acid 
• 79-14-1 glycolic Acid 

Downstream Products

• 1416209-36-3 2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile 
• 1416209-37-4 4-(2-chlorophenyl)-2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-5,6,7,8-tetrahydroquinoline-3-carbonitrile 
• 1416209-38-5 1-methyl-3-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile 
• 1416209-40-9 1-methyl-3-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}-thio)-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbonitrile 
• 1416209-42-1 6-tert-butyl-2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-5,6,7,8-tetrahydroquinoline-3-carbonitrile 
• 1416209-43-2 4,6-dimethyl-2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)nicotinonitrile 
• 1416209-44-3 4-(4-chlorophenyl)-2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-5,6,7,8-tetrahydroquinoline-3-carbonitrile 
• 1416209-45-4 2-({[3-methyl-2,6-dioxo-7-(2-oxo-2-phenylethyl)-2,3,6,7-tetrahydro-1H-purin-8-yl]methyl}thio)-4,6-diphenylnicotinonitrile 
• 1170005-16-9 C₁₅H₁₃ClN₄O₃ 
• 1416209-46-5 1-methyl-7-phenyl-10,11,12,13,14,15-hexahydro-1H-cycloocta[5'',6'']pyrido[3'',2'':4',5']thieno-[3',2':5,6][1,4]diazepino[7,1-f]purine-2,4(3H,6H)-dione 
• 1416209-47-6 9-(2-chlorophenyl)-1-methyl-7-phenyl-10,11,12,13-tetrahydro-1H-purino[7'',8'':1',7'][1,4]diazepino-[5',6':4,5]thieno[2,3-b]quinoline-2,4(3H,6H)-dione 
• 1416209-48-7 2,14-dimethyl-8-phenyl-3,4,5,6-tetrahydro-9H-purino[7'',8'':1',7'][1,4]diazepino[5',6':4,5]thieno-[2,3-c]isoquinoline-11,13(12H,14H)-dione 
• 1416209-52-3 C₂₉H₂₈N₆O₂S 
• 1416209-53-4 1,9,11-trimethyl-7-phenyl-1H-pyrido[3'',2'':4',5']thieno[3',2':5,6][1,4]diazepino[7,1-f]purine-2,4(3H,6H)-dione 

Relevant academic research and scientific papers

8-Benzylaminoxanthine scaffold variations for selective ligands acting on adenosine A2A receptors. Design, synthesis and biological evaluation

A library of 34 novel compounds based on a xanthine scaffold was explored in biological studies for interaction with adenosine receptors (ARs). Structural modifications of the xanthine core were introduced in the 8-position (benzylamino and benzyloxy substitution) as well as at N1, N3, and N7 (small alkyl residues), thereby improving affinity and selectivity for the A2A AR. The compounds were characterized by radioligand binding assays, and our study resulted in the development of the potent A2A AR ligands including 8-((6-chloro-2-fluoro-3-methoxybenzyl)amino)-1-ethyl-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (12d; Ki human A2AAR: 68.5 nM) and 8-((2-chlorobenzyl)amino)-1-ethyl-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (12h; Ki human A2AAR: 71.1 nM). Moreover, dual A1/A2AAR ligands were identified in the group of 1,3-diethyl-7-methylxanthine derivatives. Compound 14b displayed Ki values of 52.2 nM for the A1AR and 167 nM for the A2AAR. Selected A2AAR ligands were further evaluated as inactive for inhibition of monoamine oxidase A, B and isoforms of phosphodiesterase-4B1, -10A, which represent classical targets for xanthine derivatives. Therefore, the developed 8-benzylaminoxanthine scaffold seems to be highly selective for AR activity and relevant for potent and selective A2A ligands. Compound 12d with high selectivity for ARs, especially for the A2AAR subtype, evaluated in animal models of inflammation has shown anti-inflammatory activity. Investigated compounds were found to display high selectivity and may therefore be of high interest for further development as drugs for treating cancer or neurodegenerative diseases.

Purine compound, intermediate, preparation method and its application

The invention discloses a xanthine compound I, wherein R1 is 2-cyanophenyl or hydrogen; R2 is 2-cyanobenzyl; R3 is amino or wherein n=2-4, m=2-3, D is H or NH2 and E is CH2 or NH. A preparation method of the xanthine compound I comprises the following steps of: performing nucleophilic substitution reaction on a compound II and R3H; or (1) performing the nucleophilic substitution reaction on the compound II and R-3-tert-oxyacyl aminopiperidine; and (2) removing a tert-oxyacyl protecting group. The invention further discloses any intermediate of the xanthine compound I, wherein R1 and R2 are as described above. The invention further relates to an application of the xanthine compound I in preparation of a DPP-4 (dipeptidyl peptidase-4) enzyme activity inhibitor or medicaments for treating and/or preventing relevant diseases by inhibiting a DPP-4 enzyme. The xanthine compound I disclosed by the invention provides a new direction for research and development of the DPP-4 inhibitor, and has important significance in development of the potential DPP-4 inhibitors. Formula III, formula II and formula I are shown in the specification.

Synthesis and biological evaluation of xanthine derivatives on dipeptidyl peptidase 4

A series of xanthine derivatives in which a methylene was inserted at position 8 of xanthine scaffold was synthesized and evaluated as inhibitors of dipeptidyl peptidase 4 (DPP-4) for the treatment of type 2 diabetes. As the results of structure-activity relationship (SAR) study of the series, the compounds with 4-methylquinazoline- 2-yl-methyl group at N-1 position and 2-aminoethylaminomethyl group gave better activities. Compounds H4 and H9 showed good DPP-4 inhibition and more than 100-fold selectivity over DPP-7 and DPP-8.