Some 2-Substituted Aminopurines and Purine Analogs<sup>1</sup>

Cresswell, R. M.; Strauss, T.; Brown, George Bosworth

doi:10.1021/jm00342a050

Cited by 4 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6-Amino-2-chloropurine ( 3 ), when reacted with ethanolamine, afforded 6-amino-2-[(2-hydroxyethyl)amino]purine ( 5 ), the structure of which was confirmed by 1 H and 13 C NMR (including DEPT 135 exp), MS, and elemental analysis, although our melting point and UV maxima differed from those reported in the literature …”

Section: Chemistrymentioning

confidence: 40%

“…5 : decolorized and crystallized from water; yield 51%; mp 259−260 °C (differs from that given in the literature, 247−248 °C or over 300 °C 8 ); likewise UV λ max (pH 1) 245 (sh), 289, (pH 13) 290 disagree with previously described results, i.e., water (pH 1.1) 249, 298, water (pH 12.4) 263 (sh), 286; MS and NMR spectra are in accordance with the proposed structure; MS (AEI-MS 902) 194 (M + , 21),163 (100), 150 (26), 134 (42), 121 (11); 1 H NMR (270 MHz, DMSO) 3.30 (2H, t, J = 6.0, CH 2 ), 3.48 (2H, t, J = 6.0, CH 2 ), 4.67 (1H, br s, exch with D 2 O, OH), 6.02 (1H, t, J = 5.0, exch with D 2 O, NH), 6.64 (2H, s, exch with D 2 O, NH 2 ), 7.67 (1H, s, H-8), 12.14 (1H, br s, exch with D 2 O, H-9). Anal.…”

Section: Methodsmentioning

confidence: 53%

“…7 : hydrochloride; yield 46%; mp over 330 °C; UV λ max (pH 1) 267, (pH 13) 265; TLC 1 M solution of NH 3 in CHCl 3 −MeOH (95:5), one spot R f 0.3 identical with the sample prepared from 2,6-dichloro-9-methylpurine according to ref . Anal.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

et al. 1997

View full text Add to dashboard Cite

Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in which it behaves as a hydrogen bond acceptor. Olomoucine (6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-methylpurine, OC), roscovitine (6-(benzylamino)-2(R)-[[1-(hydroxymethyl)propyl]amino]-9-isopropylpur ine), and other N6,2,9-trisubstituted adenines were found to exert a strong inhibitory effect on the p34cdc2/cyclin B kinase. Removal or change of the side chain at position 2 or the hydrophobic group at position 9 dramatically decreased the inhibitory activity of olomoucine or roscovitine. Inhibition of cdk with OC and related compounds clearly arrests cell proliferation of many tumor cell lines at G1/S and G2/M transitions and also triggers apoptosis in the target tumor cells in vitro and in vivo. Thus, from a pharmacological point of view, OC may represent a model compound for a new class of antimitotic and antitumor drugs.

show abstract

Section: Chemistrymentioning

confidence: 40%

Section: Methodsmentioning

confidence: 53%

See 1 more Smart Citation

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Analysis of chemical modification possibilities suggests adenine substitution at the C8 position is the most facile. Therefore, we first obtained 8-bromoadenine (8BrA) from adenine, then transformed 8BrA into 6-amino-7( H )-purine-8(9 H )-thione (8SA), and finally converted 8SA to 8-methylthioadenine . Designing this potentially radiosensitive derivative, i.e., a system of high susceptibility to DEA, we considered the Hammett inductive constant of a substituent (for the −SCH 3 group it amounts to 0.25, which implies that such a modification of adenine should lead to thermodynamically stable radical anion).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we first obtained 8-bromoadenine (8BrA) from adenine, then transformed 8BrA into 6-amino-7( H )-purine-8(9 H )-thione (8SA), and finally converted 8SA to 8-methylthioadenine. 18 Designing this potentially radiosensitive derivative, i.e., a system of high susceptibility to DEA, we considered the Hammett inductive constant of a substituent (for the −SCH 3 group it amounts to 0.25, 19 which implies that such a modification of adenine should lead to thermodynamically stable radical anion 20 ). Additionally, the S–C bond energy is similar to that of the C–Br bond, suggesting, thus, a low-barrier dissociation, 21 a second requirement for efficient DEA.…”

Section: Introductionmentioning

confidence: 99%

Surprising Radiolytic Stability of 8-Thiomethyladenine in an Aqueous Solution

Datta,

Szczyrba,

Zdrowowicz

et al. 2024

J. Phys. Chem. B

View full text Add to dashboard Cite

8-Thiomethyladenine (ASCH 3 ), a potentially radiosensitizing modified nucleobase, has been synthesized in a reaction between 8-thioadenine and methyl iodide. Despite favorable dissociative electron attachment (DEA) characteristics, the radiolysis of an aqueous solution of ASCH 3 with a dose of X-ray amounting to as much as 300 Gy leads to no effects. Nevertheless, crossed electron-molecule beam experiments in the gas phase on ASCH 3 confirm the theoretical findings regarding the stability of its radical anion, namely, the most abundant reaction channel is related to the dissociation of the S-CH 3 bond in the respective anion. Furthermore, electroninduced degradation of ASCH 3 has been observed in aprotic acetonitrile, which is strong evidence for the involvement of proton transfer (PT) in stabilizing the radical anion in an aqueous solution. These findings demonstrate that PT in water can be the main player in deciding the radiosensitizing properties of modified nucleobases/nucleosides.

show abstract

Syntheses from Pyrimidines

1971

Chemistry of Heterocyclic Compounds: A Series of Monographs

View full text Add to dashboard Cite

Coupling of 4,5-diiodophthalonitrile with rerr-butyldimethylsilylacetylene and a palladium catalyst gave 4,5-bis(rerr-butyldimethylsilylethynyl)phthalonitrile. Cleavage of the silyl moiety with tetftibutylammonium fluoride gave 4,5-diethynylphthalonitrile, while condensation in 2-N,N-dimethylami-noethanol without or with Zn(OAc)2 gave metal-free 2,3,8,9,16,17,23,24-wtakis(tert-butyldimethylsilylethy-nyl)phthalocyanine or its zinc derivative. Cleavage of the silyl groups of the zinc derivative gave an insoluble product whose tH NMR spectrum was indicative of 2,3,9,10,16,17,23,?A.-octaettrynylphthalocyaninato zinc(Il). Bromination of phthalonitrile withN,lV{ibromoisocyanuric acid gave a separable mixture of 3,6-,3,21-and 4,S-dibromophthalonitrile along with the monobromophthalonitrites. Coupling of 3,4dibromophalonitrile with ren-butylacetylene gave 3,4-bis(ren-butylethynyl)phthalonitrile, which on condensation with lithium l-pentanolate gave 1,2,8,9,15,16,22,23-octzkjs(3,3-dimethyl-l-butynyl)phthalocyanins as a single isomer, the first known 1,2,8,9,15.16,22,23-octasubstituted phthalocyanine.

show abstract

Some 2-Substituted Aminopurines and Purine Analogs¹

Cited by 4 publications

References 1 publication

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

Surprising Radiolytic Stability of 8-Thiomethyladenine in an Aqueous Solution

Syntheses from Pyrimidines

Contact Info

Product

Resources

About

Some 2-Substituted Aminopurines and Purine Analogs1

Cited by 4 publications

References 1 publication

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

Cytokinin-Derived Cyclin-Dependent Kinase Inhibitors: Synthesis and cdc2 Inhibitory Activity of Olomoucine and Related Compounds

Surprising Radiolytic Stability of 8-Thiomethyladenine in an Aqueous Solution

Syntheses from Pyrimidines

Contact Info

Product

Resources

About

Some 2-Substituted Aminopurines and Purine Analogs¹