Hindered N-oxide esters of rapamycin
AssigneeAmerican Home Products Corporation
InventorsFrances C. Nelson, Guy A. Schiehser
Life of this patent
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Abstract
A compound of the structure ##STR1## wherein R and R.sup.1 are each, independently, ##STR2## or hydrogen; R.sup.2 and R.sup.3 are each, independently, alkyl, arylalkyl , or R.sup.2 and R.sup.3 may be taken together to form a cycloalkyl ring; R.sup.4 is a heterocyclic N-oxide radical, which may be optionally substituted; R.sup.5 is alkyl or arylalkyl; R.sup.6 and R.sup.7 are taken together to form a saturated N-alkyl-heterocyclic N-oxide, which may be optionally substituted; k=0-1, m=0-1; n=1-6; with the proviso that R and R.sup.1 are not both hydrogen, which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.
Claims1
A method of treating rheumatoid arthritis in a mammal in need thereof which comprises administering an antiarthritis effective amount of a compound of the structure ##STR10## wherein R and R.sup.1 are each, independently, ##STR11## or hydrogen;
- R.sup.2 and R.sup.3 are each, independently, alkyl of 1-6 carbon atoms, arylalkyl of 7-10 carbons, or R.sup.2 and R.sup.3 may be taken together to form a cycloalkyl ring of 3-8 carbon atoms;
- R.sup.4 is a heterocyclic N-oxide radical selected from the group consisting of 1-methyl-pyrazolyl-2-N-oxide, imidazolyl-3-N-oxide, 1,2,3-triazolyl 2- or 3-N-oxide, 1,2,4-triazolyl 2- or 4-N-oxide, 1,2,5-oxadiazolyl N-oxide, 1,2,3,5-oxatriazolyl N-oxide, pyridinyl N-oxide, pyridazinyl N-oxide, pyrimidinyl N-oxide, pyrazinyl N-oxide, 1,3,5-triazinyl N-oxide, 1,2,4-triazinyl N-oxide, 1,2,3-triazinyl N-oxide, 1,2,4-diazepinyl N-oxide, 2-isobenzazolyl N-oxide, 1,5-pyrindinyl N-oxide, benzpyrazolyl N-oxide, benzisoxazolyl N-oxide, benzoxazolyl N-oxide, quinolinyl N-oxide, isoquinolinyl N-oxide, cinnolinyl N-oxide, quinazolinyl N-oxide, naphthyridinyl N-oxide, pyrido[3,4-b]pyridinyl N-oxide, pyrido[4,3-b]pyridinyl N-oxide, pyrido[2,3-b]pyridinyl N-oxide, 1,4,2-benzoxazinyl N-Oxide, 2,3,1-benzoxazinyl N-oxide, carbazolyl N-oxide, and purinyl N-oxide, which may be optionally mono-, di-, or tri- substituted with a group selected from alkyl of 1-6 carbon atoms, arylalkyl of 7-10 carbon atoms, alkoxy of 1-6 carbon atoms, cyano, halo, hydroxy, nitro, carbalkoxy of 2-7 carbon atoms, trifluoromethyl, trifluoromethoxy, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-12 carbon atoms, --SO.sub. 3 H, --PO.sub.3 H.sub.2, and --CO.sub.2 H;
- R.sup.5 is alkyl of 1-6 carbon atoms or arylalkyl of 7-10 carbon atoms;
- R.sup.6 and R.sup.7 are taken together to form a saturated N-alkyl of 1-6 carbon atoms-heterocyclic N-oxide of 5-8 ring atoms, which may be optionally mono-, di-, or tri-substituted with a group selected from alkyl of 1-6 carbon atoms, aroyl of 3-11 carbon atoms, and perfluoroalkyl of 1-6 carbon atoms;
- k=0-1,
- m=0-1;
- n=1-6;
- with the proviso that R and R.sup.1 are not both hydrogen.
Dependencies are inferred from the claim text.