- Synthesis and anticonvulsant activity of novel purine derivatives
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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.
- Wang, Shi-Ben,Jin, Peng,Li, Fu-Nan,Quan, Zhe-Shan
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p. 574 - 583
(2015/03/14)
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- Synthesis and evaluation of anticonvulsant and antidepressant activities of 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives
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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 %.
- Wang, Shi-Ben,Deng, Xian-Qing,Liu, Da-Chuan,Zhang, Hong-Jian,Quan, Zhe-Shan
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p. 4619 - 4626
(2016/02/20)
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- Synthesis, C-13 NMR, and X-ray crystal structure of N6,N9-octamethylenepurinecyclophane
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The synthesis and structure determination of N6,N9-octamethylenepurine cyclophane by single crystal X-ray diffraction is reported.The cyclophane was prepared from 6-chloropurine and 8-aminooctanoic acid as starting materials.The aminooctyl fragment was first attached to N9 of 6-chloropurine by means of the Mitsunobu reaction and cyclization to the cyclophane effected by nucleophilic attack of the amino group at the C6 position and displacement of chloride ion.Reversing the reaction strategy did not result in formation of the cyclophane.Crystals of the cyclophane were monoclinic, P21/n, a = 9.620(3), b = 12.266(3), c = 11.994(2), Angstroem, β = 111.25(2) deg, Z = 4.Intensities were measured with a Nicolet P3 diffractometer and MoKα radiation at room temperature.The structure was solved by direct methods and refined to R = 0.0683, Rw = 0.0493 based on 1730 reflections.The molecule shows some strain, but bond lenghts and angles are normal.Attempts to relieve the strain are made by a small distortion of the purine rings and bending of the N6 and C8' atoms out of the planes to which they are attached (0.314(4), 0.459(5) Angstroem).Further, the N6,H6,C1' group is twisted by 30 deg from the pyrimidine plane and the torsion angles in the aliphatic chain are distorted from the idealized 60, 120, 180 deg (average, 13.6 deg; range 5.1-24.9 deg).These distortions result in some weakening of the ?-bonding in the adenine moiety. Key words: purinophane synthesis, nucleophilic aromatic substitution, conformational analysis, crystal structure.
- Bell, R. A.,Faggiani, R.,Hunter, H. N.,Lock, C. J. L.
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p. 186 - 196
(2007/10/02)
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