Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-12-22
1998-02-10
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 71, A61K 3170
Patent
active
057169390
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention is concerned with new antibiotics. In particular, this invention relates to compounds which are amide derivatives of the macrolide antibiotics rosaramicin, repromicin, tylosin, 5-O-mycaminosyltylonolide, 4'-deoxy-5-O-mycaminosyltylonolide, desmycosin, lactenocin, O-demethyllactenocin, cirramycin A.sub.1, 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 (Streptococcus suis); and for all of the above mentioned hosts, infections by Mycoplasma spp.
BACKGROUND ART
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 al., U.S. Pat. No. 4,920,103; Tao et al., U.S. Pat. No. 4,921,947; Kirst et al., U.K. Patent Application GB 2135670A.
C-20 reductive amination products of the above macrolides are disclosed in U.S. patent application Ser. No. 07/914,242, filed Jul. 15, 1992 now abandoned in favor of co-pending U.S. patent application Ser. No. 07/996,243, filed Dec. 23, 1993 and assigned to the assignee hereof. C-20 Wittig reaction products of the above macrolides are disclosed in co-pending U.S. patent application Ser. No. 08/032,901, filed Mar. 18, 1993 and in co-pending U.S. patent application Ser. No. 08/145,456, filed Oct. 29, 1993, which is a continuation-in-part of U.S. patent application Ser. No. 08/032,901, both of which are assigned to the assignee hereof.
DISCLOSURE OF THE INVENTION
This invention is concerned with new antibiotics which are amide derivatives of the macrolides repromicin, rosaramicin, tylosin, 5-O-mycaminosyltylonolide, 4'-deoxy-5-O-mycaminosyltylonolide, desmycosin, lactenocin, O-demethyllactenocin, cirramycin A.sub.1, 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 or II ##STR2## and the pharmaceutically acceptable salts thereof wherein m is 1 or 2; ##STR3## wherein a is 1 or 2; of hydrogen, (C.sub.1 -C.sub.4)alkyl, an aminoacyl group and a dipeptidyl group; group are independently selected from the group consisting of the D- or L- form, when applicable, of alanyl, arginyl, asparagyl, aspartyl acid, cysteinyl, cystyl, glutamyl acid, glutamyl, glycyl, histi
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Lundy Kristin Marie
Vu Chi B.
Benson Gregg C.
Kight John
Lee Howard C.
Pfizer Inc.
Richardson Peter C.
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