Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1995-04-05
1997-10-28
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514 76, 514114, 558166, 558169, A61K 3166, C07F 902
Patent
active
056818297
DESCRIPTION:
BRIEF SUMMARY
1. FIELD OF THE INVENTION
This invention relates to new classes of phosphocholine derivatives as well as to various methods for preparing these compounds--including synthetic, enzymatic and extractive using certain plants. The phosphocholine derivatives of the invention are non-toxic and exhibit substantial antifungal activity in slowing fungal growth and in killing fungi.
2. BACKGROUND OF THE INVENTION
The plant species Irlbachia alata has been used as an anti-infective agent in the Peruvian Amazon region. The leaves are squeezed and the liquid is applied to infected skin sores. The same liquid from the leaves is applied to skin problems and skin fungal infections. It is utilized to treat vaginal yeast infections.
Irlbachia alata is one species of 10-12 species of the plant family Gentianaceae. These species occur in tropical South America especially in the Amazon and Negro River basins. The plants in the genus Irlbachia are generally low herbs characteristically with 3-5 plinerved leaves. The most consistent diagnostic feature for the genus is the pollen morphology.
A reference to Irlbachia alata and related species was made in 1775 by the French scientist Fusee Aublet (Aublet, F. 1775, Histoire des Plantes de la Guiane Francoise, Didot, Paris). The ethnobotanical notes from this reference were subsequently compiled and republished in English. Aublet noted the following about two species in the genus Irlbachia:
Irlbachia Alata The entire plant is bitter. It is used to clear obstructions; I (Aublet) have used it with good results. The species is called "Bois creux" (Hollow wood) by the Creoles.
Irlbachia Pururascens All parts of this plant are bitter. It is used as an apertif and to reduce fever.
3. SUMMARY OF THE INVENTION
We have discovered a class of phosphocholine derivatives (Class I) having extraordinary antifungal activity.
Structurally, these compounds are phosphocholine derivatives (1 or 2-deacyl-phosphatidyl cholines) in which the 1 or 2-OH-group of the glycerol moiety has been glycosylated with glucose, galactose, arabinose, mannose, rhamnose or another sugar. The basic chemical structure may be drawn as follows: ##STR1## wherein one of R or R' is a sugar moiety and the other is an acyl or sugar moiety.
The molecular backbone common to all members of this class of compounds is drawn above. The acyl-group can be any long-chain fatty acid, while the sugar unit can be any of the sugars commonly found in plants, including but not limited to glucose, galactose, arabinose, mannose, rhamnose, or another naturally occurring sugar.
We have additionally found a structurally related class of phosphocholine derivatives of similar or greater antifungal activity than the above-discussed class of phosphocholine derivatives (i.e., Class I).
One novel class of phosphocholine derivatives (Class II) having antifungal activity has the basic structure shown below: ##STR2## where Q is C2 to C30 alkyl, alkenyl, alkynyl, branched alkyl, branched alkenyl, or branched alkynyl; CF.sub.2, or N-R.sub.1 ; branched alkenyl, or branched alkynyl radicals of C1 to C20 chain lengths; are independently or together cycloalkyl or bridged cycloalkyl radicals of ring size C3 to C20, or cylcoalkenyl, bridged cycloalkenyl or cyclo(polyene)radicals of ring size C4 to C20, cycloalkynyl, bridged cycloalkeynl or cyclo(polyalkynyl)radicals of ring size C8 to C20; alkynyl, cycloalkyl, bridged cycloalkyl, cycloalkenyl or cycloalkynyl radicals containing C1 to C20 carbon atoms; branched alkyl, branched alkenyl, branched alkynyl, cycloalkyl, bridged cycloalkyl, cycloalkenyl, bridged cycloalkenyl or cycloalkynyl radicals containing C1 to C20 carbon atoms, or any protecting group described in the book "Protecting Groups in Organic Synthesis" by Theodora Greene and Peter G. M. Wuts.
Another class of phosphocholine derivatives (Class III) having antifungal activity has the following structures: ##STR3## where AA, BB, DD are independent of each other, equal to each other, or interchanged as shown above, the central carbon atom can be either t
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Bierer Donald E.
Bruening Reimar C.
Dener Jeffrey M.
Jolad Shivanand D.
King Steven
Peselev Elli
Shaman Pharmaceuticals, Inc.
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