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Claims for Patent: RE44768

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Claims for Patent: RE44768

Title:Rapamycin hydroxyesters
Abstract: A compound of the structure ##STR00001## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3R.sup.4-).sub.fOR.sup.10, --CF.sub.3, --F, or CO.sub.2R.sup.11; R.sup.8 and R.sup.9 are each, independently, hydrogen, alkyl, alkenyl, alkynyl, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4-).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl, alkenyl, alkynyl, tri-(alkyl)silyl, tri-(alkyl)silylethyl, triphenylmethyl, benzyl, alkoxymethyl, tri-(alkyl)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl, alkenyl, alkynyl, or phenylalkyl; X is 5-(2,2-dialkyl)[1,3]dioxanyl, 5-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2-dialkyl)[1,3]dioxanyl, 4-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2dialkyl)[1,3]dioxalanyl, or 4-(2,2-dicycloalkyl)[1,3]dioxalanyl; b=0-6; d=0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl group, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.
Inventor(s): Skotnicki; Jerauld S. (Allentown, NJ), Leone; Christina L. (Princeton, NJ), Schiehser; Guy A. (Yardley, PA)
Assignee: Wyeth LLC (Madison, NJ)
Application Number:13/931,400
Patent Claims: 1. A compound of the structure ##STR00005## wherein R.sup.1 and R.sup.2are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2--7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3--F, or--CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6 ; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1, wherein R.sup.2 is hydrogen or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2, wherein b=0 and d=0 or a pharmaceutically acceptable salt thereof.

4. The compound of claim 3, wherein R.sup.8 and R.sup.9 are each, independently hydrogen, alkyl, or --(CR.sup.3R.sup.4-).sub.fOR.sup.10, or are taken together to form X or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 which is rapamycin 42-ester with (tetrahydropyran-2-yloxy)acetic acid or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 which is rapamycin 42-ester with hydroxyacetic acid or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 which is rapamycin 42-ester with 2,2-dimethyl-3-(tetrahydropyran-2-yloxy)propionic acid or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 which is rapamycin 42-ester with 3-hydroxy-2,2-dimethylpropionic acid or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 which is rapamycin 42-ester with 2,2-dimethyl[1,3]dioxalane-4-carboxylic acid or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 which is rapamycin 31,42-diester with 2,2-dimethyl[1,3]dioxalane-4-carboxylic acid or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 which is rapamycin 42-ester with 2,3-dihydroxypropionic acid or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 which is rapamycin 42-ester with 2,2-dimethyl[1,3]dioxane-5-carboxylic acid or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 which is rapamycin 42-ester with 3-hydroxy-2-hydroxymethylpropionic acid or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 which is rapamycin 42-ester with 2,2,5-trimethyl[1,3]dioxane-5-carboxylic acid or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 which is rapamycin 42-ester with 2,2-bis(hydroxymethyl)propionic acid or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 Which is rapamycin 42-ester with 2,2-dimethyl-5-(2-trimethylsilanylethoxymethyl)[1,3]-dioxane-5-carboxylic acid or a pharmaceutically acceptable salt thereof.

17. The compound of claim 1 which is rapamycin 42-ester with 3-methyl-1,5-dioxa-spiro[5.5]undecane 3-carboxylic acid or a pharmaceutically acceptable salt thereof.

18. The compound of claim 1 which is rapamycin 31,42-diester with 3-methyl-1,5-dioxa-spiro[5.5]undecane 3-carboxylic acid or a pharmaceutically acceptable salt thereof.

19. A method of treating transplantation rejection or graft vs. host disease in a mammal in need thereof, which comprises administering to said mammal an antirejection effective amount of a compound of the structure ##STR00006## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR .sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6 ; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

20. A method of treating a fungal infection in a mammal in need thereof, which comprises administering to said mammal an antifungal effective amount of a compound of the structure ##STR00007## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.1-0,--CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sub.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, or --F, --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6; and d=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

21. A method of treating rheumatoid arthritis in a mammal in need thereof, which comprises administering to said mammal an antiarthritis effective amount of a compound of the structure ##STR00008## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4)).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[.Iadd.1,.Iaddend.3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

22. A method of treating restenosis in a mammal in need thereof, which comprises administering to said mammal an antiproliferative effective amount of a compound of the structure ##STR00009## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.bCR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

23. A method of treating pulmonary inflammation in a mammal in need thereof, which comprises administering to said mammal an antiinflammatory effective amount of a compound of the structure ##STR00010## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d=0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof.

24. A pharmaceutical composition which comprises a compound of the structure ##STR00011## wherein R.sup.1 and R.sup.2 are each, independently, hydrogen or --CO(CR.sup.3R.sup.4).sub.b.Iadd.(.Iaddend.CR.sup.5R.sup.6).sub.dCR.sup.7- R.sup.8R.sup.9; R.sup.3 and R.sup.4 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or --F; R.sup.5 and R.sup.6 are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11, or R.sup.5 and R.sup.6 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.7 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3, --F, or --CO.sub.2R.sup.11; 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, --(CR.sup.3R.sup.4).sub.fOR.sup.10, --CF.sub.3--F, or --CO.sub.2R.sup.11, or R.sup.8 and R.sup.9 may be taken together to form X or a cycloalkyl ring of 3-8 carbon atoms that is optionally mono-, di-, or tri-substituted with --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.10 is hydrogen, alkyl of 1-6 carbon, atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silyl, tri-(alkyl of 1-6 carbon atoms)silylethyl, triphenylmethyl, benzyl, alkoxymethyl of 2-7 carbon atoms, tri-(alkyl of 1-6 carbon atoms)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R.sup.11 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; X is 5-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 5-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxanyl, 4-(2,2-di-(alkyl of 1-6 carbon atoms))[1,3]dioxalanyl, or 4-(2,2-di-(cycloalkyl of 3-8 carbon atoms))[1,3]dioxalanyl; b=0-6; d =0-6; and f=0-6 with the proviso that R.sup.1 and R.sup.2 are both not hydrogen and further provided that either R.sup.1 or R.sup.2 contains at least one --(CR.sup.3R.sup.4).sub.fOR.sup.10, X, or --(CR.sup.3R.sup.4).sub.fOR.sup.10 substituted cycloalkyl of 3-8 carbon atoms group, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.

.Iadd.25. The compound of claim 1, wherein said compound is: ##STR00012## .Iaddend.

.Iadd.26. The pharmaceutical composition of claim 24, wherein R.sup.1 is --CO(CR.sup.3R.sup.4).sub.b(CR.sup.5R.sup.6).sub.dCR.sup.7R.sup.8R.sup.9; b=0; d=0; R.sup.7 is methyl; R.sup.8 is --(CR.sup.3R.sup.4).sub.fOR.sup.10; R.sup.9 is --(CR.sup.3R.sup.4).sub.fOR.sup.10; each R.sup.3 is hydrogen; each R.sup.4 is hydrogen; each R.sup.10 is hydrogen; each f=1; and R.sup.2 is hydrogen. .Iaddend.
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