19-nor-vitamin d analogs with 3,2-dihydrofuran ring

Abstract

19-nor-vitamin D analogs having an additional dihydrofuran ring connecting the 3β-oxygen and carbon-2 of the A-ring of the analog, and pharmaceutical uses therefore, are described. These compounds exhibit selective in vitro and in vivo activities, making them therapeutic agents for the treatment or prophylaxis of autoimmune diseases, some types of cancers, metabolic bone diseases, osteomalacia, osteopenia, secondary hyperparathyroidism, psoriasis, or other skin diseases.

Description

BACKGROUND OF THE INVENTION[0001]This invention relates to vitamin D compounds, and more particularly to 3,2-dihydrofuran- 19-nor-vitamin D analogs and their pharmaceutical uses.[0002]The natural hormone, 1α,25-dihydroxyvitamin D3 and its analog in ergosterol series, i.e. 1α,25-dihydroxyvitamin D2 are known to be highly potent regulators of calcium homeostasis in animals and humans, and more recently their activity in cellular differentiation has been established, Ostrem et al., Proc. Natl. Acad. Sci. USA, 84, 2610 (1987). Many structural analogs of these metabolites have been prepared and tested, including 1α-hydroxyvitamin D3, 1α-hydroxyvitamin D2, various side chain homologated vitamins and fluorinated analogs. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity may be useful in the treatment of a variety of diseases as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis, p...

AI Technical Summary

Benefits of technology

The present invention is about a new group of vitamin D compounds that have reduced biological activity in vitro but still have significant biological activity in vivo. These compounds have a unique structure with a fused dihydrofuran ring and an additional fused dihydroxy ring. These compounds can be used as slow-release drugs or local-acting drugs for the treatment or prevention of various diseases and disorders such as autoimmune diseases, cancer, secondary hyperparathyroidism, psoriasis, and bone diseases. The compounds can be administered through various routes such as topical, transdermal, oral, rectal, nasal, or parenteral. The patent text also describes the structure and biological activities of some specific examples of these compounds.

Problems solved by technology

Parallel to these studies another, closely related problem has been discussed in the literature, namely the correlation of A-ring conformation with biological activities of vitamin D compounds.

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