Phosphorylcarbamates of rapamycin and oxime derivatives thereof

A compound of the structure ##STR7## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, or ##STR8## R.sup.3 and R.sup.4 are each, independently, hydrogen, Ar, or --(CR.sup.6 R.sup.7).sub.a Y(CR.sup.8 R.sup.9).sub.b Z, or R.sup.3 and R.sup.4 may be taken together to form a 5-7 membered ring;

• wherein when R.sup.3 and R.sup.4 are taken together to form a 5-7 membered ring, R.sup.3 R.sup.4 are --(CH.sub.2).sub.2 --, or --(CH.sub.2).sub.3 --, or --(CH.sub.2).sub.4 --;
• R.sup.5 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, alkoxyalkyl of 2-7 carbon atoms, arylalkyl of 7-10 carbon atoms, cycloalkyl of 3-8 carbon atoms, or Ar;
• R.sup.6, R.sup.7, R.sup.8, and R.sup.9, are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, alkylthioalkyl of 2-12 carbon atoms, alkylaminoalkyl of 2-12 carbon atoms, dialkylaminoalkyl of 3-12 carbon atoms, arylalkyl of 7-10 carbon atoms, cycloalkyl of 3-8 carbon atoms, --OR.sup.10, --SR.sup.10, halogen, --CN, --NO.sub.2, --CF.sub.3, --COR .sup.10, --CO.sub.2 R.sup.10, --CONHR.sup.10, --SO.sub.2 R.sup.10, --SO.sub.3 R.sup.10, --OSO.sub.3 R.sup.10, --NR.sup.10 R.sup.11, --NHCOR.sup.10, --NHCO.sub.2 R.sup.10, --NHSO.sub.2 R.sup.10, --NHSO.sub.3 R .sup.10, or Ar;
• X is O or NOR.sup.12 ;
• Y is --O--, --CH.sub.2 --, --NR.sup.13 --, --S--, --S(O)--, --S(O).sub.2 --, or --C(O)--;
• R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, or arylalkyl of 7-10 carbon atoms;
• Z is hydrogen, alkyl of 1-6 carbon atoms, or Ar;
• Ar is a phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, quinoxalyl, thienyl, thionaphthyl, furyl, benzofuryl, benzodioxyl, benzoxazolyl, benzoisoxazolyl, indolyl, thiazolyl, isoxazolyl, pyrimidinyl, pyrazinyl, benzopyranyl, benz[b]thiophenolyl, benzimidazolyl, benzthiazolyl, benzodioxolyl, piperidyl, morpholinyl, piperazinyl, tetrahydrofuranyl, or pyrrolidinyl group which may be optionally mono-, di-, or tri-substituted with a group selected from alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, cyano, halo, hydroxy, nitro, carbalkoxy of 2-carbon atoms, trifluoromethyl, amino, dialkylamino of 1-6 carbon atoms per alkyl group, dialkylaminoalkyl of 3-12 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, alkylthio of 1-6 carbon atoms, --SO.sub.3 H, --PO.sub.3 H, and --CO.sub.2 H;
• wherein the aryl moiety of the arylalkyl group of R.sup.5 , R.sup.6 , R.sup.7 , R.sup.8 , R.sup.9 R.sup.10, R.sup.11, R.sup.12, and R.sup.13 is selected from the group consisting of phenyl naphthyl, pyridyl quinolyl, isoquinolyl, quinoxalyl, thienyl, thionaphthyl, furyl, benzofuryl, benzodioxyl, benzoxazolyl, benzoisoxazolyl, indolyl, thiazolyl, isoxazolyl, pyrimidinyl, pyrazinyl, benzopyranyl, benz[b]thiophenolyl, benzimidazolyl, benzthiazolyl, benzodioxolyl, piperidyl, morpholinyl, piperazinyl, tetrahydrofuranyl, and pyrrolidinyl;
• a=1-6 and;
• b=0-6;
• or a pharmaceutically acceptable salt thereof, with the proviso that R.sup.1 and R.sup.2 are not both hydrogen;
• and further provided that when a is greater than 1, each of the (CR.sup.6 R.sup.7) subunits may be the same or different and when b is greater than 1, each of the (CR.sup.8 R.sup.9) may be the same or different.