Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity.
A series of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines where the 2-substituent was H, F, Cl, CF3, CH3, CH2CH3, NH2, NHCH3, N(CH3)2, SCH3, or SO2CH3 was synthesized and tested for antirhinovirus activity to evaluate the effect of 2-substituents on antiviral activity. Intuitive and quantitative structure-activity relationship (QSAR) analysis showed that optimum antirhinovirus serotype 1B activity was associated with 9-benzylpurines that contained a C-2 lipophilic, electron-withdrawing substituent. The most active compound, 6-(dimethylamino)-9-(4-methylbenzyl)-2-(trifluoromethyl)-9H-purine (14), had an IC50 = 0.03 microM against serotype 1B, but its activity against 18 other serotypes was not uniform; the IC50s ranged over 260-fold.
Kelley
J L
JL
Division of Organic Chemistry, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Linn
J A
JA
Selway
J W
JW
D000998:Antiviral Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D011687:Purines