Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity

Kelley, James L.; Linn, James A.; Selway, J. W. T.

doi:10.1021/jm00121a039

Cited by 29 publications

(11 citation statements)

References 6 publications

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“…7 For 7-benzyl-2-chloropurine, 1 H NMR (CDCl 3 , 300 MHz): δ 5.44 (s, 2H), 7.27-7.44 (m, 5H), 8.31 (s, 1H), 8.55 (s, 1H). 9-Benzyl-N-methyl-9H-purin-2-amine (5b; modified from the literature 10,11 ). To a 350 mL glasswalled pressure vessel was added 9-benzyl-2-chloropurine (0.084 g, 0.34 mmol), 40% aqueous methylamine (0.90 mL, 10 mmol), and absolute ethanol (10 mL).…”

Section: Synthetic Detailsmentioning

confidence: 99%

Synthesis, Photophysical Behavior, and Electronic Structure of Push−Pull Purines

et al. 2008

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"Push-pull" purines have been synthesized by the introduction of electron-accepting functional groups (A = CN, CO(2)Me, and CONHR) to the heterocyclic C(8) position to complement typical electron-donating substituents at C(2) (D(1)) and C(6) (D(2)). The donor-acceptor purines show significantly altered, and overall improved photophysical properties relative to their acceptor-free precursors (A = H); these include red-shifted (20-50 nm) absorption maxima, highly solvatochromic emission profiles (em lambda(max) from 355-466 nm depending on substitution pattern and solvent) with excellent linear correlations between emission energy and solvent polarity (E(T)(N)), improved photochemical stability upon continuous irradiation, and enhanced (up to 2500%) fluorescence quantum yields. Comprehensive structure-property studies show how the absorption/emission maxima and quantum yields depend on donor and acceptor structure, relative donor position (C(2) or C(6)), and solvent (1,4-dioxane, dichloromethane, acetonitrile, methanol, and in some cases water). Further insight regarding electronic structure comes from a quantitative treatment of the solvent-dependent emission data (that provides Delta mu(ge) values ranging from 1.9 to 3.4 D) and DFT (B3LYP/6-311++G**) electronic structure calculations. X-ray crystal structures of several derivatives showcase the molecular recognition capabilities of the donor-acceptor chromophores that overall have photophysical and structural properties suitable for applications in biosensing and materials.

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Section: Synthetic Detailsmentioning

confidence: 99%

Synthesis, Photophysical Behavior, and Electronic Structure of Push−Pull Purines

et al. 2008

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“…The DISMAX (7, Fig. 1) program searches the maxima or minima of a given parametric QSAR equation, and allows the [31]. Mahalanobis distance based index (see text).…”

Section: T4e Dismax Programmentioning

confidence: 99%

The EDISFAR Programs. Rational Drug Series Design

Pastor

Alvarez‐Buiila

1991

Quant. Struct.‐Act. Relat.

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The computer package EDISFAR is described. The programs can manage physico‐chemical information from a database (MONOBASE) of the fragment parameters classically used in drug design, providing assistance in the use of the techniques related with the Hansch‐Fujita analysis. The user can make design of exploring series of bioactive compounds, using a great variety of techniques, and once a QSAR model has been obtained, can calculate optimum derivatives using the parameters of the MONOBASE. The program has been designed emphasizing its flexibility, accessibility by the practical chemist, and compatibility with other statistics programs or computers.

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“…The residue was purified by flash chromatography, using 97:3 chloroform-methanol as eluent. Recrystallization from ethyl acetate-ether gave 6.85 g (89%) of 9: mp 122-124 °C; UV Xmax 228 nm (e 18 300) and 270 (c 13 900) at pH 7, 229 (c 20900) and 270 (e 9800) at pH 12; NMR (DMSO-d6) 1.76 (s, CH3), 1.99 (m, 3-H), 2.17 (m, 3-H), 2.42 (s, CH3), 3.34 (m, 5-H), 3.60 (m, 5-H), 3.71 (m, CH20), 4.0-4.2 (m, 2-H), 4.8-5.0 (m, 4-H), 7.47 (d, J = 7.5 Hz, Ph), 7.55 (s, pyrimidine), 7.75 (d, J = 7.5 Hz, Ph); MS (Cl) m/e 380 ( + 1), 362 ( + 1 -H20), 253 ( -1 -Thy), 222 ( -1 -Thy -CH2OH). Anal.…”

Section: Trans-4-hydroxy-d-proline Ethyl Ester Hydrochloride (3)mentioning

confidence: 99%

Replacement of 3'-CH group by nitrogen in the carbocyclic analog of thymidine

Orgel²

1989

J. Med. Chem.

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We have prepared (4R)-4-thyminyl-D-prolinol, an analogue of 3'-deoxythymidine in which the sugar has been replaced by D-prolinol. This strongly basic secondary amine has been converted to the corresponding hydroxylamine, an analogue of either thymidine or 2'-deoxyxylofuranosylthymine. We have also synthesized a number of simple derivatives of the amine for testing in vitro activity against herpes simplex 1 (HSV-1), human immunodeficiency virus 1 (HIV-1), and a panel of human tumor cell lines. Among these compounds, the hydroxylamine 12 proved active against the human tumor cell lines of breast, colon, and lung origin, with IC50 values of 0.08, 14.02, and 6.91 microM, respectively.

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Synthesis and structure-activity relationships of 2-substituted-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purines with antirhinovirus activity

Cited by 29 publications

References 6 publications

Synthesis, Photophysical Behavior, and Electronic Structure of Push−Pull Purines

Synthesis, Photophysical Behavior, and Electronic Structure of Push−Pull Purines

The EDISFAR Programs. Rational Drug Series Design

Replacement of 3'-CH group by nitrogen in the carbocyclic analog of thymidine

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