Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 9,10-seco- cyclopentanohydrophenanthrene ring system doai
Patent
1998-01-14
1999-08-03
Dees, Jose' G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
9,10-seco- cyclopentanohydrophenanthrene ring system doai
552653, A61K 3159, C07C40100
Patent
active
059325658
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a hitherto unknown class of compounds which shows antiinflammatory and immunomodulating effects as well as strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells, including cancer cells and skin cells, to pharmaceutical preparations containing these compounds, to dosage units of such preparations, and to their use in the treatment and prophylaxis of hyperparathyroidism, particularly secondary hyperparathyroidism associated with renal failure, for promoting osteogenesis and treating osteoporosis, for treating neurological dysfunctions such as Alzheimer's disease and a number of disease states including diabetes mellitus, hypertension, acne, alopecia, skin ageing, imbalance in the immune system, inflammatory diseases such as rheumatoid arthritis and asthma as well as diseases characterized by abnormal cell differentiation and/or cell proliferation, such as psoriasis and cancer.
The compounds of the present invention are represented by the general formula I ##STR2## in which Q stands for a C.sub.1 -C.sub.8 hydrocarbylene diradical, R stands for hydrogen or C.sub.1 -C.sub.6 hydrocarbyl, or two R groups, taken together with the carbon atom bearing the hydroxy group can form a C.sub.3 -C.sub.8 carbocyclic ring.
Preferred compounds of formula I are those in which Q stands for a C.sub.3 -C.sub.5 hydrocarbylene diradical.
More preferred compounds are those in which Q stands for (CH.sub.2).sub.n, C.tbd.C--(CH.sub.2).sub.n-1, where n is 3, 4 or 5 and R stand for methyl or ethyl.
In the context of this invention, the expression hydrocarbyl (hydrocarbylene) indicates the radical (diradical) obtained after removal of 1 (2) hydrogen atom(s) from a straight, branched or cyclic, saturated or unsaturated hydrocarbon.
Examples of R include, but are not limited to, hydrogen, methyl, trifluoromethyl, ethyl, vinyl, normal-, iso- and cyclopropyl, and propen-2-yl.
Examples of two R groups when taken together include di-, tri-, tetra-, and pentamethylene.
Examples of Q include, but are not limited to di-, tri-, tetra-, penta-, and hexamethylene, --CH.dbd.CH--CH.sub.2 --, CH.sub.2 --CH.dbd.CH--CH.sub.2 --, --CH.dbd.CH--CH.sub.2 CH.sub.2 - --, --C.tbd.C--CH.sub.2 --, --CH.sub.2 --C.tbd.C--CH.sub.2 --, --C.tbd.C--CH.sub.2 --CH.sub.2 -, and o-, m- and p-(C.sub.6 H.sub.4)--CH.sub.2 --.
Particularly preferred groups are: R=methyl or ethyl and Q=methylene, ethylene, tri-, tetra-methylene, --C.tbd.C--CH.sub.2 --.
It has been shown that 1.alpha., 25-dihydroxy-vitamin D.sub.3 (1,25(OH).sub.2 D.sub.3) influences the effects and/or production of interleukins (K. Muller et al., Immunol. Lett., 17, (1988), 361-366), indicating the potential use of this compound in the treatment of diseases characterized by a dysfunction of the immune system, e.g. autoimmune diseases, AIDS, host versus graft reactions, and rejection of transplants or other conditions characterized by an abnormal interleukin-1 production, e.g. inflammatory diseases such as rheumatoid arthritis and asthma. Promising immunological properties of vitamin D analogues have been described (L. Binderup, Biochem. Pharmacol., 43, (1992), 1885-1892).
It has also been shown that 1,25(OH).sub.2 D.sub.3 is able to stimulate the differentiation of cells and inhibit excessive cell proliferation (E. Abe et al., Proc. Natl. Acad. Sci., U.S.A., 78, (1981), 4990-4994), and it has been suggested that this compound might be useful in the treatment of diseases characterized by abnormal cell proliferation and/or cell differentiation such as leukemia, myelofibrosis and psoriasis.
Also, the use of 1,25(OH).sub.2 D.sub.3, or its pro-drug 1.alpha.-OH-D.sub.3, for the treatment of hypertension (L. Lind et al., Acta Med. Scand., 222, (1987), 423-427) and diabetes mellitus (S. Inomata et al., Bone Mineral., 1, (1986), 187-192) has been suggested. Another indication for 1,25(OH).sub.2 D.sub.3 is suggested by the recent observation of an association between hereditary vitamin D resistance and alopecia: treatment with 1,25(OH).sub.2 D.sub.3
REFERENCES:
Brown, et al: "New active analogues of vitamin D with low calcemic activity", Kidney International, vol. 38, No. 29, (1990), pp. 22-27, XP000373974.
Maynard et al: "18-Substituted Derivatives of Vitamin D: 18-Acetoxy-1.alpha.,25-dihydroxyvitamin D.sub.3 and Related Analgues", J. Org. Chem. 1992, vol. 57, pp. 3214-3217, XP002035173.
Badio Barbara
Dees Jos,e G.
Leo Pharmaceutical Products Ltd. A/S (L.o slashed.vens kemiske F
LandOfFree
Vitamin D analogues does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vitamin D analogues, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vitamin D analogues will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-849604