Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-09-11
1997-10-14
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 71, A61K 3170, C07H 1708
Patent
active
056772874
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention is concerned with new antibiotics. In particular, this invention relates to compounds which are derivatives of the macrolide antibiotics repromicin, rosaramicin, 5-mycaminosyltylonolide, desmycosin, lactenocin, O-demethyllactenocin, 4'-deoxymycaminosyltylonolide and 23-deoxymycaminosyltylonolide; to the pharmaceutically-acceptable acid addition salts of such derivatives; to a method of using such derivatives in the treatment of illnesses in animals caused by bacterial and mycoplasmic pathogens; and to pharmaceutical compositions useful therefor. The term "animals" includes mammals, fish and birds.
There are numerous agents known to combat bacterial infectious diseases in animals, but for many specific diseases the current agents of choice leave much to be desired. In some instances the agents may not persist long enough in the host and, therefore, require frequent dosing to maintain therapeutically effective blood and/or tissue levels. For meat producing animals (cattle, poultry, sheep and swine) this will require considerable labor intensive animal handling which is costly to the producer. In other cases, the agent may be poorly tolerated or even toxic to the host at therapeutically effective doses. Agents with increased potency, a longer half-life, an increased therapeutic index and a broader spectrum of antibacterial activity as well as agents with greater oral absorption would improve the scope of animal diseases that could be more effectively treated. Thus, the need for new antibacterial and anti-mycoplasmic agents with improved properties endures.
Diseases of particular concern are: bovine respiratory disease, the principal causative bacterial pathogens of which are Pasteurella haemolytica, P. multocida and Haemophilus somnus; pasteurellosis in swine, goats, sheep and poultry (P. multocida); swine pleuropneumonia (Actinobacillus pleuropneumoniae); swine streptococcus infections (Streptocoocus suis); and for all of the above mentioned hosts, infections by Mycoplasma spp.
Derivatives of tylosin and its related macrolides have been shown to be effective against infections in poultry, cattle and pigs caused by certain gram-positive and gram-negative bacteria: Kirst et el., U.S. Pat. No. 4,920,103; Tao et el., U.S. Pat. No. 4,921,947; Kirst et el., U.K. Patent Application GB 2135670A. C-20 reductive amination products of the above macrolides are disclosed in copending U.S. patent applications, Ser. No. 07/914,242, filed Jul. 15, 1992, and Ser. No. 07/996,243, filed Dec. 23, 1993.
SUMMARY OF THE INVENTION
This invention is concerned with new antibiotics which are derivatives of the macrolides repromicin, rosaramicin, 5-mycaminosyltylonolide, desmycosin, lactenocin, O-demethyllactenocin, 4'-deoxymycaminosyltylonolide and 23-deoxymycaminosyltylonolide and to the acid addition salts of such derivatives. These new antibiotics have enhanced potency against bacterial pathogens over the parent compounds and are active against mycoplasmic pathogens.
The compounds of the present invention and their pharmaceutically-acceptable salts are of the formula I ##STR1## or the formula II ##STR2## and the pharmaceutically-acceptable salts thereof wherein iodo, OX.sup.1, SX.sup.1, ##STR3## azetidin-1 -yl, pyrrolidin-1 -yl, piperidin-1 -yl, 3,3-dimethylpiperidin-1 -yl, hexahydroazepin-1 -yl, octahydroazocin-1 -yl, octahydroindol-1 -yl, 1,3,3a,4,7,7a-hexahydroisoindol-2-yl, decahydroquinol-1 -yl, decahydroisoquinol-2-yl, 1,2,3,4-tetrahydroisoquinol-2-yl, 1,2,3,6-tetrahydropyridin-1-yl, 4-alkylpiperazin-1-yl having 1 to 4 carbons in the alkyl portion, morpholine, 2,6-dimethylmorpholin4-yl, thiomorpholino, and ##STR4## where R.sup.3 and R.sup.4 are independently selected from the group consisting of H, alkyl having 1 to 4 carbons, hydroxyalkyl having 2 to 4 carbons, cycloalkyl having 3 to 8 carbons, alkenyl having 3 to 4 carbons, optionally substituted benzyl, alkoxyalkyl having 1 to 4 carbons in the alkoxy portion and 2 to 4 carbons in the alkyl portion and alkoxyalkoxyalkyl having
REFERENCES:
patent: 4920103 (1990-04-01), Kirst et al.
patent: 4921947 (1990-05-01), Tao et al.
patent: 5545624 (1996-08-01), Hecker et al.
H. A. Kirst et al., J. of Antibiotics, vol. XL, No. 6, 1987, pp. 823-842.
K. Funaishi et al., J. of Antibiotics, vol. XLIII, No. 8, 1990, pp. 938-947.
A. Tanaka et al., J. of Antibiotics, vol. XXXIV, No. 10, 1981, pp. 1374-1376.
Benson Gregg C.
Conway John D.
Peselev Elli
Pfizer Inc.
Richardson P. C.
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