23-Ester derivatives of DMT and method of using same

Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated via claimed linking group – bond – chelating agent,...

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536 71, A61K 3171, C07H 1708

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043966136

ABSTRACT:
23-Ester derivatives of demycinosyltylosin (DMT) of the formula: ##STR1## wherein R is selected from hydrogen, optionally substituted C.sub.1 -C.sub.5 -alkanoyl or optionally substituted benzoyl, phenylacetyl, or phenylpropionyl; and R.sup.1 is an acyl group selected from: ##STR2## p is 0 or 1; m and n are integers from 0 to 4; R.sup.2 is hydrogen, halo, C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.8 -cycloalkyl, phenyl, C.sub.5 -C.sub.8 -cycloalkenyl, naphthyl, indenyl, tetralinyl, decalinyl, adamantyl, cinnoxacinyl, a monocyclic heterocyclic ring system comprising 3 to 8 atoms or a bicyclic heterocyclic ring system comprising 6 to 11 atoms, provided that at least 1 atom of the ring system is carbon and at least 1 atom of the ring system is a heteroatom selected from O, N, and S; and wherein R.sup.2 and the connecting alkyl groups --(CH.sub.2).sub.m -- and --(CH.sub.2).sub.n -- are optionally substituted by one or two halo, methyl, ethyl, methoxy, amino, N-protected-amino, methylamino, dimethylamino, nitro, acetoxy, acetamido, azido, carbomethoxy, carboxamido, cyano, or hydroxyl groups, provided that, if the substituent is other than halo or alkyl, there can be no more than one substituent on any connecting --CH.sub.2 -- group; X is O, S, --NH--, --N(CH.sub.3)--, --C.tbd.C--, --CH.dbd.CH--, --C(CH.sub.3).dbd.CH--, --CH.dbd.C(CH.sub.3)-- or --C(CH.sub.3).dbd.C(CH.sub.3)--; R.sup.3 and R.sup.4 are C.sub.1 -C.sub.5 -alkyl or optionally substituted phenyl or benzyl; and salts thereof are useful antibiotics or intermediates to antibiotics.

REFERENCES:
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patent: 4092473 (1978-05-01), Okamoto et al.
patent: 4205163 (1980-05-01), Mori et al.
patent: 4321361 (1982-03-01), Baltz et al.
Derwent Abstract 66634C/38 of Japanese Kokai J5 5043-013, Mar. 26, 1980, (Sanraku Ocean).
A. A. Nagel et al., "Selective Cleavage of the Mycinose Sugar from the Macrolide Antibiotic Tylosin: A Unique Glycosidic Scission," J. Org. Chem. 44 (12), 2050-2052 (1979).
A. Tanaka et al., "Synthesis of Recyclized Macrolide Antibiotics and Related Derivatives from Mycaminosyl Tylonolide", Bull. Soc. Chem. Soc. Japan 54, 3837-3845 (1981).
A. Tanaka et al., "Synthesis of 4'-Deoxymycaminosyl Tylonolide", J. Antibiotics 34, 1374-1376 (1981).
A. Tanaka et al., "Syntheses of Derivatives of 4'-Deoxymycaminosyl Tylonolide and Mycaminosyl Tylonolide Modified at C-23", J. Antibiotics 34, 1377-1380, (1981).
S. Omura, Derwent Abstract 82541D/45 of Japanese Kokai J56122-397, Sep. 25, 1981.

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