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|Title:||19-nor-vitamin D compounds for use in treating hyperparathyroidism|
|Abstract:||This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided.|
|Inventor(s):||DeLuca; Hector F. (Deerfield, WI), Schnoes; Heinrich K. (Madison, WI), Perlman; Kato L. (Madison, WI), Sicinski; Rafal R. (Warsaw, PL), Prahl; Jean M. (Madison, WI)|
|Assignee:||Wisconsin Alumni Research Foundation (Madison, WI)|
1. A method for treating hyperparathyroidism which comprises suppressing parathyroid activity by administering to a patient having such a disorder at least one compound having the
formula ##STR9## where X.sup.1 and X.sup.2 are each selected from the group consisting of hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where R is selected from the group consisting of alkyl, hydrogen, hydroxyalkyl, fluoroalkyl and a side chain of the
formula ##STR10## where R.sup.1 represents hydrogen, hydroxy or O-acyl, R.sup.2 and R.sup.3 are each selected from the group consisting of alkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group --(CH.sub.2).sub.m -- where m is
an integer having a value of from 2 to 5, R.sup.4 is selected from the group consisting of hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R.sup.5 is selected from the group consisting of hydrogen, fluorine, alkyl, hydroxyalkyl
and fluoroalkyl, or, R.sup.4 and R.sup.5 taken together represent double-bonded oxygen, R.sup.6 and R.sup.7 are each selected from the group consisting of hydrogen, hydroxy, O-acyl, fluorine and alkyl, or, R.sup.6 and R.sup.7 taken together form a
carbon-carbon double bond, and wherein n is an integer having a value of from 1 to 5 and wherein the carbon at any one of positions 20, 22, or 23 in the side chain may be replaced by an O, S, or N atom, with the proviso that when n is 1 then R.sup.2 and
R.sup.3 must both be methyl, said at least one compound administered by oral, topical or parenteral means in an amount from about 1 .mu.g to about 500 .mu.g per day to the patient sufficient to suppress parathyroid activity thereby treating renal
2. The method of claim 1 wherein said at least one compound is administered together with a pharmaceutically acceptable excipient.
3. The method of claim 1 wherein said at least one compound is in a solid or liquid vehicle ingestible by and non-toxic to the patient.
4. The method of claim 1 where the said at least one compound is 1.alpha.,25-dihydroxy-19-nor-vitamin D.sub.3.
5. The method of claim 1 where the said at least one compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.3.
6. The method of claim 1 where the said at least one compound is 1.alpha.,25-dihydroxy-19-nor-vitamin D.sub.2.
7. The method of claim 1 where the said at least one compound is 1.alpha.-hydroxy-19-nor-vitamin D.sub.2.
8. The method of claim 1 where the said at least one compound is 1.alpha.-hydroxy-19-nor-24 epi-vitamin D.sub.2.
9. The method of claim 1 where the said at least one compound is 1.alpha.,25-dihydroxy-19-nor-24 epi-vitamin D.sub.2.
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