Pharmaceutical compositions and methods of transporting compounds across biological membrane

A method of transporting a therapeutically significant compound across a biological membrane comprising contacting a biological membrane with a therapeutically significant compound in the presence of an effective amount of a second compound of the formula:

• ##STR26## in which A is O, OH, OR.sup.6, NR.sup.7 R.sup.8, N.sub.3, NHCOR.sup.7, OCOAr, O--CO--OR.sup.9, OCOR.sup.9, NHCH.sub.2 C.sub.6.sub.H.sub.5, and in which Ar is phenyl or phenyl substituted with 1-3 groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkyl or C.sub.1 -C.sub.3 alkoxy;
• "a" is a single bond in the alpha or beta configuration with the proviso that when A=0, "a" is a double bond;
• R.sup.5 is CO.sub.2 R.sup.10, CH.sub.2 OR.sup.9, CONH.sub.2, CONHR.sup.7, CONR.sup.7 R.sup.8, CO--S--R.sup.10, CH.sub.2 S(O).sub.p --S--R.sup.10, CH.sub.2 NH.sub.2, CH.sub.2 NHR.sup.7, CH.sub.2 NR.sup.7 R.sup.8, CH.sub.2 --SO(O).sub.p --S--R.sup.10 ;
• R.sup.6 is a glycosyl moiety comprising 1-10 monosaccharide units in which the glycosidic linkage at the anomeric carbon of each monosaccharide unit is independently alpha or beta;
• R.sup.7 and R.sup.8, independently are H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl,
• C.sub.4 -C.sub.10 alkylcycloalkyl, phenyl, benzyl, or, taken together are (CH.sub.2).sub.f, where f=3-6;
• R.sup.9 is H, or C.sub.1 -C.sub.3 alkyl;
• R.sup.10 is H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkenyl, C.sub.1 -C.sub.10 alkynyl, C.sub.6 H.sub.5 or CH.sub.2 C.sub.6 H.sub.5 ;
• p is 0, 1 or 2;
• n is 0, 1 or 2;
• or a pharmaceutically suitable salt thereof.

A pharmaceutical composition comprising:

• a) an effective amount of a compound of the formula:
• ##STR27## in which A is O, OH, OR.sup.6, NR.sup.7 R.sup.8, N.sub.3, NHCOR.sup.7, OCOAr, O--CO--OR.sup.9, OCOR.sup.9, NHCH.sub.2 C.sub.6 H.sub.5, and in which Ar is phenyl or phenyl substituted with 1-3 groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkyl or C.sub.1 -C.sub.3 alkoxy;
• "a" is a single bond in the alpha or beta configuration with the proviso that when A=0, "a" is a double bond;
• R.sup.5 is CO.sub.2 R.sup.10, CH.sub.2 OR.sup.9, CONH.sub.2, CONHR.sup.7, CONR.sup.7 R.sup.8, CO--S--R.sup.10, CH.sub.2 S(O).sub.p --S--R.sup.10, CH.sub.2 NH.sub.2, CH.sub.2 NHR.sup.7, CH.sub.2 NR.sup.7 R.sup.8, CH.sub.2 --SO(O).sub.p --S--R.sup.10 ;
• R.sup.6 is a glycosyl moiety comprising 1-10 monosaccharide units in which the glycosidic linkage at the anomeric carbon of each monosaccharide unit is independently alpha or beta;
• R.sup.7 and R.sup.8, independently are H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.4 -C.sub.10 alkylcycloalkyl, phenyl, benzyl, or, taken together are (CH.sub.2).sub.f, where f=3-6;
• R.sup.9 is H, or C.sub.1 -C.sub.3 alkyl;
• R.sup.10 is H, C.sub.1 -C.sub.10 alkyl, C.sub.1 -C.sub.10 alkenyl, C.sub.1 -C.sub.10 alkynyl, C.sub.6 H.sub.5 or CH.sub.2 C.sub.6 H.sub.5 ;
• p is 0, 1 or 2;
• n is 0, 1 or 2;
• or a pharmaceutically suitable salt thereof;
• b) an effective amount of a therapeutically significant compound;
• and
• c) a pharmaceutically acceptable carrier.