Abstract: This invention provides compounds of formula I having the structure ##STR1## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, each, independently, hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aralkoxy, trifluroalkoxy, alkanoyloxy, hydroxy, halo, trifluoromethyl, cyano, amino, mono- or di-alkylamino, alkanamido, or alkanesulfonamido;R.sub.5 is hydrogen, alkyl, alkenyl, alkoxyalkyl or alkylcycloalkyl;R.sub.6 is hydrogen, alkyl or alkenyl;X is oxygen or carbon;A is oxygen or NZ;Z is hydroxyl, alkoxy, aryloxy, carboxyalkyloxy of 2-7 carbon atoms, arylamino, or alkylsulfonyamino of 1-6 carbon atoms;or a pharmaceutically acceptable salt thereof, which are useful in the treatment of arthritic disorders, colorectal cancer, and Alzheimer's disease.

Abstract: There are disclosed compounds of the formula: ##STR1## wherein X is --CH.sub.2 R;Y is --O-- or --S--;R.sup.1 and R.sup.2 are each, independently, hydrogen or lower alkyl;or a pharmaceutically acceptable salt thereof;which by virtue of their ability to inhibit PLA.sub.2, are of use as antiinflammatory agents and there is also disclosed a method for the treatment of immunoinflammatory conditions, such as allergy, anaphylaxis, asthma and inflammation in mammals.

Abstract: This invention comprises the compound of 42-Epimer Rapamycin of the following structural formula: ##STR1## as well as pharmaceutical compositions containing 42-Epi-Rapamycin and its use in methods for inducing immunosuppression and methods for treating transplantation rejection, graft vs. host disease, autoimmune diseases, diseases of inflammation, solid tumors, fungal infections, adult T-cell leukemia/lymphomas and hyperproliferative vascular disorders.

Abstract: There are disclosed compounds of the formula: ##STR1## wherein X is O;R.sup.1 and R.sup.2 are each, independently, hydrogen, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.20 cycloalkyl, phenylloweralkyl, or substituted phenylloweralkyl substituted by halo, lower alkyl, lower alkoxy, halo lower alkyl, amino, monoloweralkylamino, diloweralkylamino or sulfonamido;A is O, S, NR, or a chemical bond;R, if present, is hydrogen or loweralkyl;m is 0-15;n is 3-12;p is 0-15,where m+p=2-15;and the pharmacologically acceptable salts thereof. Also disclosed is a method for treating immunoimmflammatory conditions in mammals which comprises administering to a mammal so afflicted an effective amount of a compound having the formula above wherein X, R.sup.1, R.sup.2, A, R, if present, m and p are as listed above and n=3-12 and m+p=2-15.

Abstract: A compound of the structure ##STR1## wherein R.sup.1 is ##STR2## R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or --CO.sub.2 R.sup.8 ;R.sup.4 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, aminoalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, or --CO.sub.2 R.sup.8 ;R.sup.5 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, or --CO.sub.2 R.sup.8 ;R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.7 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, fluorenylmethyl, or Ar;Y is O or S;X is .dbd.N--O--(CH.sub.2).sub.f --Z or .dbd.N--O--Ar;Z is hydrogen, alkenyl, alkynyl, alkoxy, cyano, fluoro, trifluoromethyl, --NR.sup.5 R.sup.

Abstract: There are disclosed compounds of the formula: ##STR1## wherein X is NR;R is hydrogen or lower alkyl;R.sup.1 and R.sup.2 are each, independently, hydrogen, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.20 cycloalkyl, phenylloweralkyl, or substituted phenylloweralkyl substituted by halo, lower alkyl, lower alkoxy, halo lower alkyl, amino, monoloweralkylamino, diloweralkylamino or sulfonamido;A is O, S, NR, or a chemical bond;m is 0-15;n is 0-20;p is 0-15,where m+p.ltoreq.15;and the pharmacologically acceptable salts thereof, which by virtue of their ability to inhibit PLA.sub.2, are of use as antiinflammatory agents and there is also disclosed a method for the treatment of immunoinflammatory conditions, such as allergy, anaphylaxis, asthma and inflammation in mammals, as well as in the modulation of PAF-mediated biological processes, such as embryonic implantation, thus making the compounds useful as antifertility agents.

Abstract: A compound of the structure ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, (CH.sub.2).sub.p NR.sup.9 R.sup.10, mono-, di-, or tri-hydroxyalkyl, aralkyl, or aryl; ##STR4## R.sup.7, R.sup.8, R.sup.9, and R.sup.10 are each, independently, hydrogen or alkyl;Y is CH or N:m is 0-4; n is 0-4; p is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases, and diseases of inflammation, by virtue of its antitumor activity useful in treating tumors, and by virtue of its antifungal activity is useful in treating fungal infections.

Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen, --CONH.sub.a --{{(CR.sup.3 R.sup.4).sub.m (--A--(CR.sup.5 R.sup.6).sub.n).sub.p }.sub.q --B}.sub.r ; --SO.sub.2 R.sup.7 ; --SO.sub.3 H; --CHR.sup.8 O(CH.sub.2).sub.t R.sup.9 ; or ##STR2## R.sup.3, R.sup.4, R.sup.5, R.sup.6, and B are each, independently, hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylalkyl, cycloalkyl, --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, --OSO.sub.3 R.sup.10, --NR.sup.10 R.sup.11, --NHCOR.sup.10, --NHSO.sub.2 R.sup.10, or Ar;X is .dbd.NOR.sup.12 or .dbd.NNR.sup.12 R.sup.13 ;Y is O, .dbd.NOR.sup.12, or .dbd.NNR.sup.12 R.sup.13 ;R.sup.7, R.sup.12, and R.sup.13 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, arylalkyl;R.sup.8, R.sup.9, R.sup.10, and R.sup.

Abstract: A compound of the structure ##STR1## wherein R.sup.1 is ##STR2## R.sup.2 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.3 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or --CO.sub.2 R.sup.8 ;R.sup.4 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, Ar, aminoalkyl, thioalkyl, alkylthioalkyl, hydroxyalkyl, or --CO.sub.2 R.sup.8 ;R.sup.5 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, At, or --CO.sub.2 R.sup.8 ;R.sup.6 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.7 is alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, or Ar;R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, arylalkyl, fluorenylmethyl, orAr;Y is O or S;X is .dbd.N--O--(CH.sub.2).sub.f --Z or .dbd.N--O--Ar;Z is hydrogen, alkenyl, alkynyl, alkoxy, cyano, fluoro, trifluoromethyl, --NR.sup.5 R.sup.

Abstract: There are disclosed compounds of the formula: ##STR1## wherein X is O, S or NR;R is hydrogen or lower alkyl;R.sup.1 and R.sup.2 are each, independently, hydrogen, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.20 cycloalkyl, phenylloweralkyl, or substituted phenylloweralkyl substituted by halo, lower alkyl, lower alkoxy, halo lower alkyl, amino, monoloweralkylamino, diloweralkylamino or sulfonamido;A is O, S, NR, or a chemical bond;m is 0-15;n is 0-20;p is 0-15,where m+p.ltoreq.15;and the pharmacologically acceptable salts thereof, which by virtue of their ability to inhibit PLA.sub.2, are of use as antiinflammatory agents and there is also disclosed a method for the treatment of immunoinflammatory conditions, such as allergy, anaphylaxis, asthma and inflammation in mammals, as well as in the modulation of PAF-mediated biological processes, such as embryonic implantation, thus making the compounds useful as antifertility agents.

Abstract: A compound of the structure ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, alkyl, aralkyl, or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid;X is ##STR4## O, or S; R.sup.7 and R.sup.8 are each, independently, hydrogen or alkyl;Y is CH or N;m is 0-4; n is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs.

Abstract: This invention provides a method of treating immunoinflammatory bowel disease in a mammal in need thereof which comprises administering an antiimmunoinflammatory amount of rapamycin, alone or in combination with cyclosporin A. As such, rapamycin, alone or in combination with cyclosporin A, is useful in treating bowel diseases such as ulcerative colitis, Crohn's disease, ulcerative proctitis, and the like.

Abstract: This invention provides a method of treating immunionflammatory skin disease in a mammal in need thereof which comprises administering an antiimmunoinflammatory amount of rapamycin, alone or in combination with cyclosporin A, orally, parenterally, intranasally, intrabronchially, topically, transdermally, or rectally. As such, rapamycin, alone or in combination with cyclosporin A, is useful in treating skin diseases such as psoriasis, atopic dermatitis, contact dermatitis, eczematous dermatitis, seborrheic dermatitis, Lichen planus, Pemphigus, bulus pemphigoid, Epidermolysis bullosa, urticaria, angioedemas, vasculitides, erythemas, cutaneous eosinphilias, and the like.

Abstract: There are disclosed compounds of the formula: ##STR1## wherein X is --CH.sub.2 R;R is ##STR2## and further when Y=S, R may also be --(CH.sub.2).sub.e CH.sub.3 ; Y is --O--or --S--;R.sup.1 and R.sup.2 are each, independently, hydrogen or lower alkyl;R.sup.3 is indolyl, furyl, phenyl or phenyl optionally mono- or disubstituted independently by alkyl of 1-7 carbon atoms, --C(CH.sub.3).sub.3, --C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3, --C(CH.sub.3).sub.2 CH.sub.2 CH.sub.3, haloloweralkyl, perfluoroalkyl, lower alkoxy, aryl alkoxy, halo or nitro;R.sup.4 and R.sup.5 are, independently, --COCH.sub.2 R.sup.7, --CO.sub.2 R.sup.7, --CONHR.sup.7, geranyl or CH.sub.2 R.sup.3 ;R.sup.6 is hydrogen or lower alkyl;R.sup.7 is geranyl and any moiety selected from R other than ##STR3## A and B are, independently, --O--, --S-- or --NR.sup.6 --; and a is 0-8;b is 1-10 when Y=S, and 2-10 when Y=O;c is 1-3;d is 0-9; ande is 3-18;which by virtue of their ability to inhibit PLA.sub.

Abstract: A compound of the structure ##STR1## where R.sup.1, R.sup.2, and R.sup.3 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1, R.sup.2, and R.sup.3 are not all hydrogen; R.sup.4 is --(CH.sub.2).sub.m X(CH.sub.2).sub.n CO.sub.2 R.sup.5 or ##STR3## R.sup.5 and R.sup.6 are each, independently, alkyl, aralkyl, or phenyl which is optionally mono-, di-, or tri-substituted with a substituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid;X is ##STR4## R.sup.7 and R.sup.8 are each, independently, hydrogen or alkyl; Y is CH or N;m is 0-4; n is 0-4;with the proviso that m and n are not both 0 when X is O or S;or a pharmaceutically acceptable salt thereof, which is by virtue of its immunosuppresive activity is useful in treating transplantation rejection, host vs.

Abstract: Derivatives of Rapamycin where the hydroxy group at position 31 and/or 42 are reacted with acetal forming reagents have been shown to have immunosuppressant and antifungal properties. These derivatives are represented by the formula: ##STR1## wherein R.sup.1 and R.sup.2 independently are hydrogen, --CH.sub.2 YX, --C(CH.sub.3).sub.2 YX, --CH.sub.2 (CH.sub.3)YX, or L;Y is O or S; X is --CH.sub.3, --(CH.sub.2).sub.n CH.sub.3, --CH.sub.2 C.sub.6 H.sub.6, --(CH.sub.2).sub.2 OCH.sub.3, --CH.sub.2 Cl.sub.3 or --CH.sub.2 CH.sub.2 Si(CH.sub.3).sub.3 and L is selected from tetrahydrofuran-2-yl, tetrahydrothiophen-2-yl, tetrahydrothiopyran-2-yl, tetrahydropyran-2-yl, 4-methoxytetrahydropyran-2-yl, 4-methoxytetrahydrothiopyran-2-yl, or 4-methoxytetrahydrothiopyran-S, S-dioxide-2-yl with a proviso that R.sup.1 and R.sup.2 cannot simultaneously be hydrogen and n is 1-5.

Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or ##STR2## with the proviso that R.sup.1 and R.sup.2 are not both hydrogen; R.sup.3 is hydrogen, alkyl, aralkyl, --(CH.sub.2).sub.q CO.sub.2 R.sup.6,--(CH.sub.2).sub.r NR.sup.7 CO.sub.2 R.sup.8, carbamylalkyl, aminoalkyl, hydroxyalkyl, guanylalkyl, mercaptoalkyl, alkylthioalkyl, indolylmethyl, hydroxyphenyklmethyl, imidazoylmethyl or phenyl which is optionally mono-, di-, or tri-substituted with a sustituent selected from alkyl, alkoxy, hydroxy, cyano, halo, nitro, carbalkoxy, trifluoromethyl, amino, or a carboxylic acid;R.sup.4 and R.sup.7 are each, independently, hydrogen, alkyl, or aralkyl;R.sup.5, R.sup.6, and R.sup.

Abstract: A compound of the structure ##STR1## wherein R.sup.1 and R.sup.2 are each independently, hydrogen or ##STR2## X is --(CH.sub.2).sub.m -- or --Ar--; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl, --(CH.sub.2).sub.n --Ar, --(CH.sub.2).sub.p --NR.sup.5 R.sup.6, or --(CH.sub.2).sub.p --N.sup.+ R.sup.5 R.sup.6 R.sup.7 Y.sup.- ; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, or --(CH.sub.2).sub.n --Ar; Ar is an optionally substituted group selected from ##STR3## in which the optional substituents are selected from the group consisting of alkyl, aralkyl, alkoxy, cyano, halo, nitro, carbalkoxy, or perfluoroalkyl; R.sup.7 is alkyl; Y is a halide, sulfate, phosphate, or p-toluenesulfonate anion; m=1-6; n=1-6; p=1-6; with the proviso that R.sup.1 and R.sup.2 are not both hydrogen; or a pharmaceutically acceptable salt thereof, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs.

Abstract: Reduction of rapamycin with DIBAL furnishes either the 15-hydroxyrapamycin or 15,27-bis(hydroxy)rapamycin, depending upon the reaction conditions, having the general structure ##STR1## where Y is --CO-- --CH(OH)--. The compounds of this invention are useful in treating transplant rejection, host vs. graft disease, autoimmune diseases, diseases of inflammation, and fungal infections.

Abstract: There are disclosed a method for the treatment or prevention of immunoinflammatory conditions by administering to a mammal an effective amount of a compound having the formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are each, independently, hydrogen, alkyl, aralkyl, aryl, or ##STR2## X is alkyl, aryl, or -NR.sup.5 R.sup.6 ; R.sup.5 and R.sup.6 are each independently hydrogen, alkyl, or aryl; aryl is ##STR3## where the dotted line represents an optional double bond; R.sup.7, and R.sup.8 and R.sup.9 are each, independently, hydrogen, alkyl, hydroxy, alkoxy, carbalkoxy, halo, nitro, amino, cyano, trifluoromethyl, or a carboxylic acid;n=1-3;or a pharmaceutically acceptable salt thereof.