Carbamates of rapamycin

A method of inducing immunosuppression by administering an immunosuppressive amount of a compound having the structure ##STR30## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, or --CONH--[(CR.sup.3 R.sup.4).sub.m (--A--(CR.sup.5 R.sup.6).sub.n).sub.p ].sub.q --B;

• R.sup.3, R.sup.4, R.sup.5, and, R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, cycloalkyl of 3-8 carbon atoms, --OR.sup.7, --SR.sup.7, halogen, --CN, --NO.sub.2, --CF.sub.3, --COR.sub.7, --CONH.sub.2, --SO.sub.2 R.sub.7, --OSO.sub.3 R.sup.7, --NR.sup.7 R.sup.8, --NHCOR.sup.7, --NHSO.sub.2 R.sup.8, or Ar;
• B is hydroxy, --SR.sup.7, --CN, --COR.sub.7, --CONH.sub.2, --OSO.sub.3 R.sup.7, --NR.sup.7 R.sup.8, --NHCOR.sup.7, --NHSO.sub.2 R.sup.8, or Ar;
• A is --CH.sub.2 --, --NR.sup.7 --, --O--, --S--, --PR.sup.7 --, or --P(O)(R.sup.7)--;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, or Ar;
• Ar is naphthyl, pyridyl, quinolyl, isoquinolyl, quinoxalyl, thienyl, thionaphthyl, furyl, benzofuryl, benzodioxyl, benzoxazolyl, benzoisoxazolyl, or benzodioxolyl;
• wherein the Ar group may be optionally mono-, di-, or tri- substituted with a group selected from alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, alkoxy of 1-6 carbon atoms, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, amino, dialkylamino of 1-6 carbon atoms per alkyl group, alkylthio of 1-6 carbon atoms, --SO.sub.3 H, --PO.sub.3 H, and --CO.sub.2 H;
• with the proviso that R.sup.1 and R.sup.2 are not both hydrogen;
• m=0-6;
• n=0-6;
• p=0-1;
• q=0-1;
• or a pharmaceutically acceptable salt thereof.

A pharmaceutical composition for use as an immunosuppressive agent comprising an immunosuppressive amount of a compound of the structure ##STR31## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, or --CONH--[(CR.sup.3 R.sup.4).sub.m (--A--(CR.sup.5 R.sup.6).sub.n).sub.p ].sub.q --B;

• R.sup.3, R.sup.4, R.sup.5, and, R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, cycloalkyl of 3-8 carbon atoms, --OR.sup.7, --SR.sup.7, halogen, --CN, --NO.sub.2, --CF.sub.3, --COR.sub.7, --CONH.sub.2, --SO.sub.2 R.sub.7, --OSO.sub.3 R.sup.7, --NR.sup.7 R.sup.8, --NHCOR.sup.7, --NHSO.sub.2 R.sup.8, or Ar;
• B is hydroxy, --SR.sup.7, --CN, --COR.sub.7, --CONH.sub.2, --OSO.sub.3 R.sup.7, --NR.sup.7 R.sup.8, --NHCOR.sup.7, --NHSO.sub.2 R.sup.8, or Ar;
• A is --CH.sub.2 --, --NR.sup.7 --, --O--, --S--, --PR.sup.7 --, or --P(O)(R.sup.7)--;
• R.sup.7 and R.sup.8 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, or Ar;
• Ar is naphthyl, pyridyl, quinolyl, isoquinolyl, quinoxalyl, thienyl, thionaphthyl, furyl, benzofuryl, benzodioxyl, benzoxazolyl, benzoisoxazolyl, or benzodioxolyl;
• wherein the Ar group may be optionally mono-, di-, or tri- substituted with a group selected from alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, alkoxy of 1-6 carbon atoms, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, amino, dialkylamino of 1-6 carbon atoms per alkyl group, alkylthio of 1-6 carbon atoms, --SO.sub.3 H, --PO.sub.3 H, and --CO.sub.2 H;
• with the proviso that R.sup.1 and R.sup.2 are not both hydrogen;
• m=0-6;
• n=0-6;
• p=0-1;
• q=0-1;
• or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.

A compound of the structure ##STR32## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, or --CONH--(CR.sup.3 R.sup.4).sub.m --B;

• B is pyridyl which may be optionally mono-, di-, or tri-substituted with a group selected from alkyl of 1-6 carbon atoms, phenylalkyl of 7-10 carbon atoms, piperazinylalkyl of 7-10 carbon atoms, piperidinylalkyl of 7-10 carbon atoms, pyridylalkyl of 7-10 carbon atoms, alkoxy of 1-6 carbon atoms, cyano, halo, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, amino, dialkylamino of 1-6 carbon atoms per alkyl group, alkylthio of 1-6 carbon atoms, --SO.sub.3 H, --PO.sub.3 H, and --CO.sub.2 H;
• R.sup.3 and R.sup.4 are each, independently, hydrogen or alkyl of 1-6 carbon atoms;
• and
• m=0-6;
• with the proviso that R.sup.1 and R.sup.2 not both hydrogen, or a pharmaceutically acceptable salt thereof.