Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1992-02-21
1995-08-29
Robinson, Douglas W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 2671, 536 2674, 536 2711, 536 2713, 536 272, 536 2721, 536 2723, 536 276, 536 2761, 536 2762, 536 2763, 536 277, 536 278, 536 2781, C07H 1916
Patent
active
054461391
DESCRIPTION:
BRIEF SUMMARY
The invention concerns nucleoside and nucleotide derivatives, processes for the preparation of these compounds, as well as their use in the sequencing of nucleic acids.
The subject of the present invention are new nucleoside and nucleotide derivatives of the general formula I ##STR2## in which Ba signifies an indolyl (A), benzimidazolyl (B), pyrrolopyridinyl (C), imidazopyridinyl (D), triazolopyrimidinyl (E), imidazotriazinyl (F) or imidazopyrimidinyl (G) radical, ##STR3## whereby R.sup.1, R.sup.2, R.sup.3, which can be the same or different, signify hydrogen, halogen, a C.sub.1 -C.sub.7 -alkyl, C.sub.2 -C.sub.7 -alkenyl, hydroxyl, mercapto, C.sub.1 -C.sub.7 -alkylthio, C.sub.1 -C.sub.7 -alkoxy, C.sub.2 -C.sub.7 -alkenyloxy, ar-C.sub.1 -C.sub.5 -alkyl, ar-C.sub.2 -C.sub.5 -alkenyl, ar-C.sub.1 -C.sub.5 -alkoxy, ar-C.sub.2 -C.sub.5 -alkenyloxy, aryloxy, nitro, amino-C.sub.1 -C.sub.7 -alkyl, C.sub.1 -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl, di-C.sub. -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl, amino, a substituted amino group --NHR.sup.4 or --N(R.sup.4).sub.2 or an imino group --N.dbd.CH--R.sup.4, whereby R.sup.4 can signify a C.sub.1 -C.sub.7 -alkyl, C.sub.2 -C.sub.7 -alkenyl, C.sub.3 -C.sub.7 -cycloalkyl, C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.7 -alkyl, C.sub.3 -C.sub.7 -cycloalkenyl, C.sub.1 -C.sub.7 -alkoxy-C.sub.1 -C.sub.7 -alkyl, halogen-C.sub.1 -C.sub.7 -alkyl-, hydroxy-C.sub.1 -C.sub.7 -alkyl-, ar-C.sub. 1 -C.sub.5 -alkyl, ar-C.sub.2 -C.sub.5 -alkenyl, hetaryl-C.sub.1 -C.sub.5 -alkyl or hetaryl-C.sub.2 -C.sub.5 -alkenyl group, whereby the aryl and hetaryl moieties can be substituted one, two or three times by C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.1 -C.sub.6 -alkoxy, halogen or hydroxyl, or R.sup.4 can signify an amino-C.sub.1 -C.sub.7 -alkyl, C.sub.1 -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl or di-C.sub.1 -C.sub.7 -alkylamino-C.sub.1 -C.sub.7 -alkyl group and, in the case of the --NHR.sup.4 and --N.dbd.CH--R.sup.4 group, R.sup.4 can additionally be an mino, C.sub.1 -C.sub.7 -alkylamino, di-C.sub.1 -C.sub.7 -alkylamino or C.sub.1 -C.sub.7 -alkoxy group or, in the case of the --N(R.sup.4).sub.2 group, the two nitrogen substituents R.sup.4 together form a C.sub.1 -C.sub.7 -alkylidene radical which, in turn, can be substituted by a C.sub.1 -C.sub.7 -alkoxy, C.sub.1 -C.sub.7 -alkylamino or di-C.sub.1 -C.sub.7 -alkylamino group, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 in each case signify hydrogen or one or two of the residues R.sup.5, R.sup.6, R.sup.7 and R.sup.8 signify hydroxyl, halogen, cyano, azido or a substituted amino group --NHR.sup.4 or --N(R.sup.4).sub.2 or R.sup.5 and R.sup.7 can together represent a further bond between C-2' and C-3' and Y represents hydrogen or a C.sub.1 -C.sub.7 -alkylcarbonyl, monophosphate, diphosphate or triphosphate group, whereby "aryl" is to signify a phenyl or naphthyl group and "hetaryl" a furanyl, thienyl or pyridyl group, with the proviso that hydrogen atom or a hydroxyl group, halogen or azido group, cannot be a chlorine or amino group and R.sup.6 cannot be a hydrogen or chlorine atom and R.sup.5 and R.sup.7 cannot together form a bond; N.sup.8 - or N.sup.9 -regioisomers (purine nomenclature), tautomers and salts, as well as nucleic acids which contain compounds of the formula I as constructional units.
Similar compounds of the formula I are known from EP-A-286,028. The present compounds according to the invention differ structurally from the known compounds by the bases given in the definition of Ba.
The compounds of the general formula I are preponderantly new compounds.
From the prior art are already known a plurality of ribofuranosyl derivatives (R.sup.6 =R.sup.8 =OH), as well as the corresponding 2'-desoxyribofuranosyl derivatives (R.sup.6 =OH; R.sup.8 =H) which, however, are not included by the present invention due to the disclaimer a).
Furthermore, from the literature (Bioorg. Khim., 13, 1375, 1987) are known benzimidazoles unsubstituted in the base moiety (base type B) which contain, in the sugar moiety in the 3'-position ha
REFERENCES:
Journal of Synthetic Organic Chemistry, Verlag et al., pp. 410-411, 04 Apr. 1985.
Nucleosides and Nucleotides, vol. 6, No. 5, Dekker Inc., Sweeney et al., pp. 387-409, 1979.
Journal of Medicinal Chemistry, vol. 25, No. 1, Montgomery et al., pp. 96-98, Jan. 1982.
Sanger et al., Proc. Nat. Acad. Sci., USA, vol. 74, pp. 5463-5467 (1977).
Bourgeouis Werner
Gumbiowski Rainer
Koch Edith
Konig Bernhard
Mertens Alfred
Boehringer Mannheim GmbH
Robinson Douglas W.
Wilson James O.
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