Rapamycin arylcarbonyl and alkoxycarbonyl carbamates as immunosuppressive and antifungal agents

Claim 1

A compound according to the formula: ##STR12## wherein R 1 is ##STR13## and R 2 is H or ##STR14## R 1 and R 2 are both ##STR15## R 3 is H or methyl, A is --OR 4 where R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl optionally substituted fluorine, chlorine, bromine, iodine, methoxy or ethoxy; arylalkyl or 7 to 12 atoms, aryl selected from phenyl or phenyl substituted by one or two groups selected from fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, cyano; naphthalenyl, naphthalenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, fluorine, chlorine, bromine or iodine; heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, isoquinolinyl, benzofuranyl, benzopyranyl, benzo[b]thiophenyl, benzimidazolyl, benzthiazolyl; cycloalkyl selected from cyclopentyl, cyclohexyl, adamantyl; or quinuclidinyl, or a pharmaceutically acceptable salt thereof.

Claim 8

A method of treating transplantation rejection, host vs. graft disease, and diseases of inflammation in a mammal by administering thereto an effective amount of a compound having the formula: ##STR16## wherein R 1 is ##STR17## and R 2 is H or ##STR18## R 1 and R 2 are both ##STR19## R 3 is H or methyl, A is --OR 4 where R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl optionally substituted fluorine, chlorine, bromine, iodine, methoxy or ethoxy; arylalkyl of 7 to 12 atoms, aryl selected from phenyl or phenyl substituted by one or two groups selected from fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, cyano; naphthalenyl, naphthalenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, fluorine, chlorine, bromine or iodine; heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, isoquinolinyl, benzofuranyl, benzopyranyl, benzothiophenyl, benzimidazolyl, benzthiazolyl; cycloalkyl selected from cyclopentyl, cyclohexyl, adamantyl; or quinuclidinyl, or a pharmaceutically acceptable salt thereof.

Claim 9

A method of treating transplantation rejection, host vs. graft disease, and diseases of inflammation in a mammal by administering thereto an effective amount of a compound having the formula: ##STR16## wherein R 1 is ##STR17## and R 2 is H or ##STR18## R 1 and R 2 are both ##STR19## R 3 is H or methyl, A is --OR 4 where R 4 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl optionally substituted fluorine, chlorine, bromine, iodine, methoxy or ethoxy; arylalkyl of 7 to 12 atoms, aryl selected from phenyl or phenyl substituted by one or two groups selected from fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, cyano; naphthalenyl, naphthalenyl substituted by C 1 -C 6 alkyl, C 1 -C 6 alkoxy, fluorine, chlorine, bromine or iodine; heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, isoquinolinyl, benzofuranyl, benzopyranyl, benzothiophenyl, benzimidazolyl, benzthiazolyl; cycloalkyl selected from cyclopentyl, cyclohexyl, adamantyl; or quinuclidinyl, or a pharmaceutically acceptable salt thereof.