10357-68-3

Usage

Uses

8-Bromoxanthine is used to study Arsenite-?inhibited xanthine oxidase.

InChI:InChI=1/C5H3BrN4O2/c6-4-7-1-2(8-4)9-5(12)10-3(1)11/h1H,(H2,7,8,9,10,11,12)

Upstream product

• 69-89-6 xanthin 

Downstream Products

• 2476-54-2 8-thioxo-8,9-dihydro-1H-purine-2,6(3H,7H)-dione 

Relevant academic research and scientific papers

Development of a carbon-11 PET radiotracer for imaging TRPC5 in the brain

The transient receptor potential channel subfamily member 5 (TRPC5) is a calcium permeable cation channel widely expressed in the brain. Accumulating evidence indicates that it plays a crucial role in psychiatric disorders including depression and anxiety. Positron emission tomography (PET) combined with a TRPC5 specific radioligand may provide a unique tool to investigate the functions of TRPC5 in animal disease models to guide drug development targeting TRPC5. To develop a TRPC5 PET radiotracer, the potent TRPC5 inhibitor HC608 was chosen for C-11 radiosynthesis through the N-demethyl amide precursor 7 reacting with [11C]methyl iodide. Under optimized conditions, [11C]HC608 was achieved with good radiochemical yield (25 ± 5%), high chemical and radiochemical purity (>99%), and high specific activity (204-377 GBq μmol-1, decay corrected to the end of bombardment, EOB). The in vitro autoradiography study revealed that [11C]HC608 specifically binds to TRPC5. Moreover, initial in vivo evaluation of [11C]HC608 performed in rodents and the microPET study in the brain of non-human primates further demonstrated that [11C]HC608 was able to penetrate the blood brain barrier and sufficiently accumulate in the brain. These results suggest that [11C]HC608 has the potential to be a PET tracer for imaging TRPC5 in vivo.

Diversifying the xanthine scaffold for potential phosphodiesterase 9A inhibitors: synthesis and validation

Xanthine and its derivatives have been a great area of interest for the development of potent bioactive agents. In this study, two synthesis routes have been developed for 1,3,8-tri substituted xanthine derivatives. The synthesis routes exploits “xanthine” as precursor molecule as it represents maximum unsubstituted sites for maximum possible substitutions. This study divulged the reactivity pattern of three –NH groups at N1, N3 and N7 position of xanthine in the order of N7 > N3 > N1, which helped in carrying out regio-selective N-alkylation reaction at different –NH sites of xanthine. Selective protection and selective deprotection at N3 and/or N7 sites of xanthine were the key strategies for developing two synthesis schemes. Eight newly synthesized compounds C1-8 were evaluated for their biological activity against Phosphodiesterase 9A. All the compounds were found to be promising inhibitors. To gain further insight for mode of interaction with Phosphodiesterase 9A, these compounds were subjected to docking studies. The present study provides insight into the potential of ‘xanthine’ to contribute to the structural diversification of xanthine derivatives in the drug development process. Xanthine based chemical synthesis is shown to be a cost effective, fast, and highly productive method. This work can be extrapolated to find various selective xanthine based inhibitors targeting other enzymes. [Figure not available: see fulltext.]

SUBSTITUTED XANTHINE DERIVATIVES

The present invention relates to compounds of formula (I) a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels. R1, R2, R3, R4 and R5 have meanings given in the description.

A compound and its preparation and use

The invention provides a compound disclosed as Formula I or a pharmaceutically acceptable salt thereof, and a preparation method and application thereof. The new compound provided by the invention can effectively inhibit dipeptidyl peptidase-IV (DPP-IV) activity with better effects than the existing DPP-IV enzyme inhibitor Linagliptin; and meanwhile, the compound has the advantages of higher selectivity for DPP-IV, higher safety and lower toxic or side effect on the DPP inhibitor, and thus, provides a new medicine option for treating or/and preventing diseases related to DPP-IV enzyme activity.

AZACYCLOHEXANE DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE

Azacyclohexane derivatives of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.