Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1986-09-04
1988-10-11
Milestone, Norma S.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D32300
Patent
active
047772700
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The efficiency of feed utilization in domestic animals, especially the ruminants such as cattle and sheep, is of economic importance in the farming industry. For this reason, attempts have been made to increase the efficiency with which ruminants utilize their food.
As an aid to discovering methods of increasing the efficiency of feed utilization in ruminants, studies on the biochemical mechanisms by which ruminants digest and degrade food, particularly carbohydrates, has been widely studied. It is now known that carbohydrates are degraded in the rumen to monosaccharides, which are converted to pyruvates, and thence to acetates and propionates. Additionally acetates recombine in the rumen to some extent to form butyrates. These acetates, propionates and butyrates, collectively known as volatile fatty acids (or VFA's), are all used as energy sources by ruminants. However, the conversion of pyruvates to acetates involves chain-shortening by one carbon atom, and this carbon atom is lost in the form of methane gas. Thus the production of propionates from carbohydrates in the rumen of ruminant animals represents a more energy-efficient degradative pathway than the production of acetates and butyrates.
As a result, treatment of a ruminant so as to cause a shift in VFA ratios in the rumen towards increased rumen propionic acid (RPA) leads to a beneficial effect on ruminant growth for a given amount of food consumption. Thus there is increased efficiency of feed utilization.
BACKGROUND ART
Several, naturally-occuring, polyether antibiotics (e.g. monensin) have been reported to increase feed utilization in ruminants; U.S. Pat. No. 3,839,557. A variety of macrocyclic polyether compounds having a carboxy group directed into the polyether ring have been described in U.S. Pat. No. 3,965,116 and Journal of the American Chemcial Society, 97, 1257 (1975), but none of these compounds was reported to have feed utilization efficiency increasing properties.
DISCLOSURE OF INVENTION
This invention provides a series of new chemical compounds which increase rumen propionic acid production in ruminant animals when administered orally to ruminants, at a low level, daily. These new chemical compounds are macrocyclic polyether compounds, which have a 21-membered ring, containing six oxygen atoms, and also have a carboxy group directed towards the interior of the polyether ring.
More particularly, this invention provides a novel macrocyclic polyether compound selected from the group consisting of ##STR1## and the pharmaceutically-acceptable base salts thereof, wherein: R.sup.1 is selected from the group consisting of hydrogen and t-butyl; to 14 carbons, cycloalkyl having 5 to 8 carbons, phenyl, alkylphenyl having 1 to 4 carbons in said alkyl, 1-adamantyl, --C(R.sup.7).dbd.CH--C(CH.sub.3).sub.3, ##STR2## wherein R.sup.7 is hydrogen or alkyl having 1 to 8 carbons; R.sup.8 and R.sup.9 when taken separately are each hydrogen, alkyl having 1 to 3 carbons, alkoxy having 1 to 3 carbons or alkylthio having 1 to 3 carbons; R.sup.8 and R.sup.9 when taken together with the carbons to which they are attached form a fused benzo ring; and R.sup.10 is hydrogen, alkyl having 1 to 3 carbons, alkoxy having 1 to 3 carbons or alkylthio having 1 to 3 carbons; to 8 carbons, hydroxymethyl, methoxymethyl, ##STR3## wherein R.sup.11 is hydrogen, alkyl having 1 to 3 carbons, fluoro or chloro; R.sup.12 is hydrogen, alkyl having 1 to 3 carbons or alkylthio having 1 to 3 carbons; n is an integer from 0 to 3; and R.sup.13 and R.sup.14 are each hydrogen, alkyl having 1 to 3 carbons, alkoxy having 1 to 3 carbons, alkylthio having 1 to 3 carbons, fluoro, chloro, bromo, hydroxy, acetyl, acetamido, benzoyl or trifluoromethyl; 1 to 8 carbons; consisting of hydrogen, alkyl having 1 to 8 carbons, phenoxymethyl, chlorophenoxymethyl, 4-t-butylphenoxymethyl and thiophenoxymethyl; or R.sup.5 and R.sup.6 when taken together with the carbon atom to which they are attached form a cyclopentylidene, cyclohexylidene, 4-phenylcyclohexylidene, 4-t-butylcyclohexy
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Lumb J. Trevor
Milestone Norma S.
Pfizer Inc.
Richardson Peter C.
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