19-nor-vitamin D compounds
DC
First Claim
1. A compound having the formula ##STR10## where X1 and X2 are each selected from hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where R is selected from alkyl, hydrogen, hydroxyalkyl, said hydroxyalkyl having from 4 to 5 carbon atoms, fluoroalkyl and a side chain of the formula ##STR11## wherein R1 represents hydrogen, hydroxy or O-acyl, R2 and R3 are each selected from alkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group --(CH2)m --where m is an integer having a value of from 2 to 5, R4 is selected from hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R5 is selected from hydrogen, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or R4 and R5 taken together represent double-bonded oxygen, R6 and R7 are each selected from hydrogen, hydroxy, O-acyl, fluorine and alkyl, or, R6 and R7 taken together form a carbon-carbon double bond, and wherein n is an integer having a value of from 1 to 5 and wherein any of the groups -CH(CH3)-, -CH(R7)-, or -CH(R6)- at positions 20, 22 and 23, respectively, may be replaced by an oxygen atom, with the proviso that when n is 2 to 5 each R4 is independently selected from hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, and each R5 is independently selected from hydrogen, fluorine, alkyl, hydroxyalkyl and fluoroalkyl.
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Abstract
This invention provides a novel class of vitamin D-related compounds, namely the 1α-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. The 19-nor vitamin D compounds have the formula: ##STR1## where X1 and X2 are each hydrogen or a hydroxy protecting group and R is a side chain.
113 Citations
12 Claims
- 1. A compound having the formula ##STR10## where X1 and X2 are each selected from hydrogen, acyl, alkylsilyl and alkoxyalkyl, and where R is selected from alkyl, hydrogen, hydroxyalkyl, said hydroxyalkyl having from 4 to 5 carbon atoms, fluoroalkyl and a side chain of the formula ##STR11## wherein R1 represents hydrogen, hydroxy or O-acyl, R2 and R3 are each selected from alkyl, hydroxyalkyl and fluoroalkyl, or, when taken together represent the group --(CH2)m --where m is an integer having a value of from 2 to 5, R4 is selected from hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, R5 is selected from hydrogen, fluorine, alkyl, hydroxyalkyl and fluoroalkyl, or R4 and R5 taken together represent double-bonded oxygen, R6 and R7 are each selected from hydrogen, hydroxy, O-acyl, fluorine and alkyl, or, R6 and R7 taken together form a carbon-carbon double bond, and wherein n is an integer having a value of from 1 to 5 and wherein any of the groups -CH(CH3)-, -CH(R7)-, or -CH(R6)- at positions 20, 22 and 23, respectively, may be replaced by an oxygen atom, with the proviso that when n is 2 to 5 each R4 is independently selected from hydrogen, hydroxy, fluorine, O-acyl, alkyl, hydroxyalkyl and fluoroalkyl, and each R5 is independently selected from hydrogen, fluorine, alkyl, hydroxyalkyl and fluoroalkyl.
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7. 1α
- ,25-dihydroxy-19-nor-vitamin D3.
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8. 1α
- -hydroxy-19-nor-vitamin D3.
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9. 1α
- ,25-dihydroxy-19-nor-vitamin D2 .
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10. 1α
- -hydroxy-19-nor-vitamin D2.
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11. 1α
- -hydroxy-19-nor-24 epi-vitamin D2.
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12. 1α
- ,25-dihydroxy-19-nor-24 epi-vitamin D2.
Specification
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- Resources
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Current AssigneeWisconsin Alumni Research Foundation (University of Wisconsin System)
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Original AssigneeWisconsin Alumni Research Foundation (University of Wisconsin System)
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InventorsDeLuca, Hector F., Sicinski, Rafal R., Prahl, Jean M., Schnoes, Heinrich K., Perlman, Kato L.
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Primary Examiner(s)PRIOR, KIMBERLY
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Application NumberUS08/442,492Time in Patent Office588 DaysField of Search552/653, 514/167US Class Current552/653CPC Class CodesA61P 17/00 Drugs for dermatological di...A61P 35/00 Antineoplastic agentsA61P 35/02 specific for leukemiaA61P 5/12 for decreasing, blocking or...C07C 401/00 Irradiation products of cho...Y02P 20/55 Design of synthesis routes,...
