2-Amino-5-nitroimidazoles

Abstract

Notes described above for 7a ( = 2, 4) except that the vols of H20 and DMF were increased 2.5-3 times.IV. S,S'-3,8-Diazaundecamethylenebis (dihydrogen phosphorothioate) (8a) was prepared by the procedure used for the prepn of 7a ( = 2,4).V. N,N'-(trans-l, 4-Cyclohexylene )bis(<S-2-aminoethyl sodium hydrogen phosphorothioate) (12a, = 0).-Powd 11a = 0) (4.90 g, 10.0 mmoles) was added in portions to a stirred partial soln of Na3SP03 (3.60 g, 20.0 mmoles) in H20 (20 ml). More H20 (20 ml) was added, but soln had not occurred after 1 hr of stirring. Addnl H20 (40 ml) caused complete soln. After 10 min the soln was treated with EtOH to cause pptn of cryst product, which was collected and repptd from H20 soln with EtOH. The collected product, washed with EtOH and Et20, was air-dried.7, Ar'-(irares-1,4-Cyclohexylene dimethylene jbis.S-2-aminoethyl lithium hydrogen phosphorothioate) (12a, = 1).-Gradual addn of powd 11a (re = 1) (7.51 g, 14.5 mmoles ) to a stirred soln of Li3SP03-6H20 (6.72 g, 28.0 mmoles) in H20 (75 ml) and DMAC (50 ml) was followed by a 3-hr stirring period. The resulting nearly clear soln was filtered and added dropwise to stirred EtOH (600 ml) to ppt hydrated 12a (re = 1) as white solid, which was collected, washed with EtOH, air-dried, and then equilibrated at const 58% relative humidity.VI. A>Y'-(czs-l,4-Cyclohexyienedimethylene)bis(S-2-aminoethyl lithium hydrogen phosphorothioate) (13a) was prepd in the manner described for 12a (re = 1). 2,2'-[<rares-l,4-Cyclohexylenebis(methyleneimino)]diethanethiol Dihydrochloride (14a).-A soln of 12a( = 1)-5.5H20 (4.00 g, 7.50 mmoles) in 3 AT HC1 (20 ml) was heated at 90-95°f or 10 min. Diln with EtOH afforded cryst 14a, which was collected under N2, washed with EtOH followed by Et20, and dried in vacuo (25-30°, P205); yield 86% (2.16 g), mp indefinite (gradual decompn at elevated temp without melting). Anal. C, H, N, S, SH. 2,2'-[«s-l,4-Cyclohexylenebis(methyleneimino)]diethanethiol Dihydrochloride (14b).-Hydrolysis of 13a-4.5H20 (5.00 g, 9.70 mmoles) in 3 A7 HC1 (25 ml) at 90-95°for 15 min was followed by diln with EtOH (250 ml) followed by Et20 (250 ml); cryst 14b sepd gradually. After refrign (4 hr), the product was collected under N2, washed successively with EtOH-Et20 soln (1:1), cold EtOH, then Et20, and dried in vacuo (25-30°, P203); yield 63%(2.06 g), mp 232-233°dec. Anal. (Ci2H26N2S2 2HC1) C, , N, S. A7,A7'-Polymethylenebis(S-2-aminoethyl thioacetate) dihydrobromides (6d; re = 8, 9) were prepd by treatment of AcSNa (prepd in situ from freshly distd AcSH and NaHC03 or NaOMe) with 5a (re = 8,9) in DMF in a manner similar to that described earlier for the prepn of S-2-(2-piperidyl)ethyl thioacetate • 2HBr.14 The products were recrystd several times from EtOH. The yield of pure 6d (re = 8), mp 209-210°, was 20%; that of pure 6d (re = 9), mp 210-213°, was 29%. Anal. [Ci6H32N202S2•2HBr, 6d (re = 8)] C, H, Br, N, S. [CnH31N202S2-2HBr, 6d (re = 9)] C, H, Br, N, S.

Effect of the O6 Substituent on Misincorporation Kinetics Catalyzed by DNA Polymerases at O6-Methylguanine and O6-Benzylguanine

“…Then, the resulting k obs values were plotted as a function of [dNTP] and fit to a hyperbola using the equation k obs = [ k pol [dNTP]/([dNTP] + K d )], where k pol is the maximal rate of nucleotide incorporation and is the ground-state binding constant for dNTP. The values for incorporation of the correct (Figure ) and incorrect dNTPs (Figure ) for the three 24-mer/36-mer duplexes were determined for RT but not for T7 - 4 Determination of by analysis of dCTP concentration dependence of the pre-steady-state burst rate.…”

“…Maintenance of genomic integrity is essential for cell survival, and the stability of DNA can be compromised with exposure to exogenous and endogenous chemicals of varying structure ( , ). Once inside the cell, a chemical can be subsequently activated to a potent electrophile ( , ), which can then react with DNA to yield a covalent modification of the nucleotide base, i.e., a DNA adduct ().…”

“…Maintenance of genomic integrity is essential for cell survival, and the stability of DNA can be compromised with exposure to exogenous and endogenous chemicals of varying structure ( , ). Once inside the cell, a chemical can be subsequently activated to a potent electrophile ( , ), which can then react with DNA to yield a covalent modification of the nucleotide base, i.e., a DNA adduct (). Because many DNA lesions have potent miscoding abilities, mutations can result if the lesion escapes repair and the polymerase inserts an incorrect nucleotide opposite the adduct during replication ( − ).…”

Analysis of Nucleotide Insertion and Extension at 8-Oxo-7,8-dihydroguanine by Replicative T7 Polymerase exo- and Human Immunodeficiency Virus-1 Reverse Transcriptase Using Steady-State and Pre-Steady-State Kinetics

“…Exposure of cells to exogenous and endogenous sources of reactive chemicals and oxygen species leads to the formation of DNA adducts (Miller & Miller, 1966, 1971. DNA adducts, via their miscoding potential when replicated by DNA polymerases, are precursors to mutagenic events which, if unrepaired, can contribute to carcinogenesis (Basu & Essigmann, 1988Feig & Loeb, 1994).…”

Advanced Topics on Radiosensitizers of Hypoxic Cells

“…68 73 These reactions proceed readily with no evidence of any additional replacement of the nitro group (Fig. 23).…”