Diastereomers of 2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin D
Compounds of formula I are provided where X 1 , X 2 , and X 3 are independently selected from H or hydroxy protecting groups. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.
1. A compound according to formula I
wherein X 1 , X 2 , and X 3 are independently selected from H and hydroxy protecting groups.
2. The compound of claim 1 , wherein X 1 , X 2 , and X 3 are hydroxy protecting groups.
3. The compound of claim 2 , wherein X 1 and X 2 are both t-butyldimethylsilyl groups and X 3 is a triethylsilyl group.
4. A compound according to formula II
5. The compound of claim 4 , according to formula IIA
6. The compound of claim 4 , according to formula IIB
7. The compound of claim 4 , according to formula IIC
8. The compound of claim 4 , according to formula IID
9. The compound of claim 4 , according to formula IIE, IIF, IIG, or IIH
10. The compound of claim 4 , according to formula IIG or IIH
11. A pharmaceutical composition, comprising an effective amount of the compound of claim 4 and a pharmaceutically acceptable carrier.
12. A method of treating a subject suffering from a biological condition, comprising administering an effective amount of the compound of claim 4 to the subject, wherein the biological condition is selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; diabetes mellitus; host versus graft reaction; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases; a skin condition selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion; renal osteodystrophy; or osteoporosis.
13. The method of claim 12 , wherein the biological condition is psoriasis.
14. The method of claim 12 , wherein the biological condition is selected from leukemia, colon cancer, breast cancer, or prostate cancer.
15. The method of claim 12 , wherein the biological condition is selected from multiple sclerosis, lupus, diabetes mellitus, host versus graft reaction, or rejection of organ transplants.
16. The method of claim 12 , wherein the biological condition is selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases selected from celiac disease, ulcerative colitis and Crohn's disease.
17. The method of claim 12 , wherein the biological condition is selected from wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion.
18. The method of claim 12 , wherein the compound is administered in a dosage of from 0.01 μg per day to 1 mg per day.
19. A compound according to Formula IIIC or IIID, wherein X 3 is H:
where
Formula IIIC is (20R,22S)-Des-A,B-22-methyl-cholestan-8,25-diol; and
Formula IIID is (20R,22R)-Des-A,B-22-methyl-cholestan-8,25-diol.
20. The compound of claim 19 , wherein the compound is in crystalline form.
21. The crystalline compound of claim 20 wherein the compound is of Formula IIIC and has a molecular packing arrangement defined by monoclinic space group C2 and unit cell dimensions a=26.4 Å, α=90°, b=6.08 Å, β=118°, c=12.7 Å, γ=90°.
22. The crystalline compound of claim 20 wherein the compound is of Formula IIID and has a molecular packing arrangement defined by monoclinic space group P2 and unit cell dimensions a=11.4 Å, α=90°, b=16.5 Å, β=119°, c=11.5 Å, γ=90°.