112088-84-3Relevant academic research and scientific papers
Synthesis and anticonvulsant activity of novel purine derivatives
Wang, Shi-Ben,Jin, Peng,Li, Fu-Nan,Quan, Zhe-Shan
, p. 574 - 583 (2015/03/14)
A series of new purines containing triazole and other heterocycle substituents was synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotarod neurotoxicity (TOX) tests. Among the compounds studied, 9-decyl-6-(1H-1,2,4-triazol-1-yl)-9H-purine (5e) was the most potent compound, with a median effective dose of 23.4 mg/kg and a high protective index of more than 25.6 after intraperitoneal administration in mice. Compound 5e showed significant oral activity against MESinduced seizures in mice, with an ED50 of 39.4 mg/kg and a PI above 31.6. These results demonstrate that compound 5e possesses better anticonvulsant activity and is safer than the commercially available drugs carbamazepine and valproate in MES, scPTZ and TOX models.
Synthesis and evaluation of anticonvulsant and antidepressant activities of 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives
Wang, Shi-Ben,Deng, Xian-Qing,Liu, Da-Chuan,Zhang, Hong-Jian,Quan, Zhe-Shan
, p. 4619 - 4626 (2016/02/20)
Seventeen 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives were synthesized, and their anticonvulsant and antidepressant activities were evaluated in a mouse model. The anticonvulsant effect and neurotoxicity of the compounds were evaluated with a maximal electroshock test and a rotated test in mice, respectively. Most of the compounds had anticonvulsant activity; among the compounds studied, 7-(3-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3h) was found to be the most potent compound with a median effective dose (ED50) value of 28.9 mg/kg and a protective index value of 15.8, possessing better anticonvulsant activity and higher safety than the marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound 3h was tested in pentylenetetrazole-induced seizures tests, and the results suggest that compound 3h exerts anticonvulsant activity through a GABA-mediated mechanism. Forced swimming test showed that at a dose of 40 mg/kg, five compounds have significant antidepressant activity, the most active compound was 7-(2-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3g), which decreased immobility time by 56 %.
Synthesis, biological activity, and SAR of antimycobacterial 9-aryl-, 9-arylsulfonyl-, and 9-benzyl-6-(2-furyl)purines
Bakkestuen, Anne Kristin,Gundersen, Lise-Lotte,Utenova, Bibigul T.
, p. 2710 - 2723 (2007/10/03)
9-Aryl-, 9-arylsulfonyl- and 9-benzyl-6-(2-furyl)purines were synthesized by N-alkylation or N-arylation of the purine followed by Stille coupling to introduce the furyl substituent in the 6-position and the compounds screened for activity against Mycobac
Design, synthesis and structure-activity relationships of a series of 9-substituted adenine derivatives as selective phosphodiesterase type-4 inhibitors
Raboisson, Pierre,Lugnier, Claire,Muller, Christian,Reimund, Jean-Marie,Schultz, Dominique,Pinna, Guillaume,Le Bec, Alain,Basaran, Helene,Desaubry, Laurent,Gaudiot, Francois,Seloum, Mohamed,Bourguignon, Jean-Jacques
, p. 199 - 214 (2007/10/03)
Adenine derivatives substituted in position 9 have been demonstrated to have potent cyclic nucleotide phosphodiesterase (PDE) inhibition properties with high selectivity toward PDE-4. Starting from our initial lead compound 9-(2-fluorobenzyl)-N6-methyl-2-trifluoromethyladenine (4, NCS613), we designed and synthesized a new series of 9-substituted derivatives for developing structure-activity relationship studies. This new series of derivatives showed increased potencies and better selectivity profiles. Structural modifications were achieved in parallel on three different positions of the adenine ring, and led to the following observations: (i) introduction of a lipophilic substituent such as trifluoromethyl, n-propyl group or iodine in the C-2 position is favourable for both the PDE-4 inhibitory activity and the selectivity towards other isoenzymes; (ii) functionalization of the N9 benzyl group with a 2-methoxy substituent led to remarkably more active compounds; (iii) replacement of the N6-methylamino moiety by other amino groups is detrimental to the activity. Among all derivatives prepared, the 9-(2-methoxybenzyl)-N6-methyl-2-trifluoromethyladenine (9r), 9-(2-methoxybenzyl)-N6-methyl-2-n-propyladenine (9s), and the 2-iodo-9-(2-methoxybenzyl)-N6-methyladenine (13b) were found to be the most potent inhibitors within this series (PDE-4-IC50=1.4, 7.0, and 0.096 nM, respectively). Compared to our reference compound 4, which showed an IC50 of 42 nM, the derivative 13b was found 450-fold more potent. Moreover, 2-iodo-9-(2-methoxybenzyl)-N6-methyladenine (13b) and 9-(2-methoxybenzyl)-N6-methyl-2-trifluoromethyladenine (9r), were at least 50 000-150 000 times more selective for the PDE-4 than for the other PDE families. Additionally, these new derivatives showed improved efficiency in inhibiting the TNFα release from mononuclear cells from healthy subjects (e.g. adenines 7l, 9s and 13b). Thus, compounds 7l, 9r, 9s and 13b are among the most potent and selective PDE-4 inhibitors reported so far and represent very promising pharmacological tools for a better understanding of the signal transduction involving cyclic AMP within the cell: this pathway is implicated in the physiology and the pathophysiology of inflammation, asthma and autoimmune disorders.
6-(Alkylamino)-9-benzyl-9H-purines. A New Class of Anticonvulsant Agents
Kelley, James L.,Krochmal, Mark P.,Linn, James A.,McLean, Ed W.,Soroko, Francis E.
, p. 606 - 612 (2007/10/02)
Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats.Most compounds were prepared in three steps from 5-amino-4,6-dichloropyrimidine or in two steps via alkylation of 6-chloropurine.Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethylamino)purine.Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents.
