72816-88-7Relevant articles and documents
Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors
Shelke, Rupesh U.,Degani, Mariam S.,Raju, Archana,Ray, Mukti Kanta,Rajan, Mysore G. R.
, p. 602 - 613 (2016/08/28)
Fragment-based drug design was used to identify Mycobacterium tuberculosis (Mtb) dihydrofolate reductase (DHFR) inhibitors. Screening of ligands against the Mtb DHFR enzyme resulted in the identification of multiple fragment hits with IC50 values in the range of 38–90 μM versus Mtb DHFR and minimum inhibitory concentration (MIC) values in the range of 31.5–125 μg/mL. These fragment scaffolds would be useful for anti-tubercular drug design.
Therapeutic compounds for inhibiting interleukin-12 signals and method for using same
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, (2008/06/13)
Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula: Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
Imidazo[2,1-i]purin-5-ones and related tricyclic water-soluble purine derivatives: Potent A2A- and A3-adenosine receptor antagonistst
Müller, Christa E.,Thorand, Mark,Qurishi, Ramatullah,Diekmann, Martina,Jacobson, Kenneth A.,Padgett, William L.,Daly, John W.
, p. 3440 - 3450 (2007/10/03)
A series of tricyclic imidazo[2,1-i]purinones and ring-enlarged analogues derived from xanthine derivatives have been prepared as adenosine receptor (AR) antagonists. In comparison with xanthines, the tricyclic compounds exhibit increased water solubility due to a basic nitrogen atom, which can be protonated under physiological conditions. Substituents were introduced that confer high affinity for A2A or A3 ARs, respectively. A new capillary electrophoresis method was developed for the determination of the enantiomeric purity of selected chiral products using native and modified β-cyclodextrins as chiral discriminators. The compounds were investigated in radioligand binding assays at rat brain A1 and A2A ARs. Selected compounds were additionally investigated in radioligand binding assays at human recombinant A3 ARS and in functional studies (adenylate cyclase assays) at A1 ARs of rat fat cell membranes, A2A ARs of rat PC 12 cell membranes, and mouse A2B ARs of NIH 3T3 cell membranes. Structure-activity relationships were similar to those of corresponding xanthine derivatives. The 2-styrylimidazopurinones were less potent at A2A ARs as compared to 8-styrylxanthine derivatives. The most potent compound at A2A ARs was (S)-1,4-dimethyl-8-ethyl-2-styryl- imidazo[2,1-i]purinone (S-25) exhibiting a Ki value of 424 nM at rat A2A ARs. The compound was highly selective for A2A receptors vs A1 and A3 ARs. Selectivity vs A2B ARs, however, was low. Among the 1-unsubstituted 2-phenyl-imidazo[2,1-i]purin-5-one derivatives, very potent and highly selective antagonists for human A3 ARs were identified. The most potent A3 antagonist of the present series was (R)-4-methyl-8-ethyl-2-phenyl-imidazo[2,1-i]purin-5-one (R-24) exhibiting a Ki value of 2.3 nM and high selectivity for A3 receptors vs all other AR subtypes.
