Calcitriol derivatives and their uses

A method of providing for the regulated in vivo release of an active form of a vitamin D compound having a hydroxy group at carbon 25 which comprises providing a vitamin D compound, modifying the vitamin D compound by derivatizing the hydroxy group at carbon 25 with an acyl group or a hydrocarbyloxycarbonyl group to obtain a vitamin D derivative having the formula:

• ##STR12## where R.sup.5 and R.sup.6 each represent hydrogen, or taken together R.sup.5 and R.sup.6 represent a methylene group, and where R is represented by the structure:
• ##STR13## where the stereochemical center at carbon 20 in the side chain may have the R or S configuration, and where Z is selected from Y, --OY, --CH.sub.2 OY, --C.tbd.CY and --CH.dbd.CHY, where the double bond may have the cis or trans stereochemical configuration, and where Y is selected from a radical of the structure:
• ##STR14## where m and n, independently, represent the integers from 0 to 5, wherein R' is selected from the group consisting of hydrogen, OX.sup.4, fluoro, trifluoromethyl, and C.sub.1-5 -alkyl, which may be straight chain or branched and, optionally, bear a hydroxy substituent, and where R.sup.2 is selected from the group consisting of hydrogen, fluoro, tifluoromethyl and C.sub.1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy substituent, and where each of R.sup.3 and R.sup.4, is selected from trifluoromethyl and C.sub.1-5 alkyl, which may be straight chain or branched and optionally bear a hydroxy substituent, and where R.sup.1 and R.sup.2, taken together, represent an oxo group, or an aikylidene group, .dbd.CR.sup.2 R.sup.2, .dbd.CR.sup.2 R.sup.3, or the group -(CH.sub.2)p-, where p is an integer from 2 to 5, and where R.sub.3 and R.sub.4, taken together, represent the group -(CH.sub.2)q-, where q is an integer from 2 to 5, and where X.sup.1, X.sup.2, and X.sup.4 are each hydrogen, an acyl group, or a hydrocarbyloxycarbonyl group, and where X.sup.3 represents an acyl group or a hydrocarbyloxycarbonyl group, and administering an effective dose of said active form of vitamin D compound to a subject.

In a method of treating disease states resulting from calcium metabolism disorders involving the administration of an active form of a vitamin D compound having a hydroxy group at carbon 25, the improvement comprising regulating the in vivo release of said active form of vitamin D compound by derivatizing the hydroxy group at carbon 25 with an acyl group or a hydrocarbyloxycarbonyl group to obtain a vitamin D derivative having the formula:

• ##STR15## where R.sup.5 and R.sup.6 each represent hydrogen, or taken together R.sup.5 and R.sup.6 represent a methylene group, and where R is represented by the structure:
• ##STR16## where the stereochemical center at carbon 20 in the side chain may have the R or S configuration, and where Z is selected from Y, --OY, --CH.sub.2 OY, --C.tbd.CY and --CH.dbd.CHY, where the double bond may have the cis or trans stereochemical configuration, and where Y is selected from a radical of the structure:
• ##STR17## where m and n, independently, represent the integers from 0 to 5, where R.sup.1 is selected from the group consisting of hydrogen, OX.sup.4, fluoro, trifluoromethyl, and C.sub.1-5 - alkyl, which may be straight chain or branched and, optionally, bear a hydroxy substituent, and where R.sup.2 is selected from the group consisting of hydrogen, fluoro, trifluoromethyl and C.sub.1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy substituent, and where each of R.sup.3 and R.sup.4, is selected from trifluoromethyl and C.sub.1-5 alky, which may be straight chain or branched and optionally bear a hydroxy substituent, and where R.sup.1 and R.sup.2, taken together, represent an oxo group, or an alkylidene group, .dbd.CR.sup.2 R.sup.2, .dbd.CR.sup.2 R.sup.3, or the group -(CH.sub.2)p-, where p is an integer from 2 to 5, and where R.sub.3 and R.sub.4, taken together, represent the group -(CH.sub.2)q-, where q is an integer from 2 to 5, and where X.sup.1, X.sup.2, and X.sup.4 are each hydrogen, an acyl group, or a hydrocarbyloxycarbonyl group, and where X.sup.3 represents an acyl group or a hydrocarbyloxycarbonyl group, and administering an effective dose of said vitamin D derivative to a subject.