Vitamin D analogues

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 9,10-seco- cyclopentanohydrophenanthrene ring system doai

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552652, 552653, 568715, 568808, 568816, 568817, 568822, 568838, A61K 3159, C07J 900, C07C 3506

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active

052062295

ABSTRACT:
##STR1## The present invention relates to compounds of formula (I), in which formula, n is an integer from 1-7; and R.sup.1 and R.sup.2, which may be the same or different, stand for hydrogen, or lower alkyl (but with the proviso that when n=1, R.sup.1 and R.sup.2 cannot simultaneously be hydrogen, nor can R.sup.1 and R.sup.2 simultaneously be an alkyl group independently chosen from methyl, ethyl and normal-propyl, and when n=2, R.sup.1 and R.sup.2 cannot simultaneously be methyl), or lower cyclo-alkyl, or, taken together with the carbon (starred in formula I) bearing the hydroxyl group, R.sup.1 and R.sup.2 can form a saturated or unsaturated C.sub.3 -C.sub.9 carbocyclic ring; and R.sup.3 and R.sup.4 represent either simultaneously hydrogen, or when taken together constitute a bond, such that a double bond connects carbons 22 and 23; including diastereoisomeric forms (e.g. E or Z configuration of the 22,23-double bond; R or S configuration at the starred carbona atom) of the compounds of formula (I), in pure form or in mixtures. The present compounds find use in both the human and veterinary practice and show antiinflammatory and immuno-modulating effects as well as strong activity in inducing differentiation and inhibiting undesirable proliferation of certain cells, including cancer cells and skin cells.

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Lars Lind et al: "Blood Pressure is Lowered by Vitamin D (Alphacalcidol) During Long-Term Treatment of Patients with Intermittent Hypercalcaemia" Acta Med. Scand; vol. 222; (1987) pp. 423-427.
K. Muller et al: "1.alpha.,25-Dihydroxyvitamin D3 and a Novel Vitamin D Analogue MC 903 are Potent Inhibitors of Human Interleukin 1 in Vitro"; Immunology Letters, No. 17 (1988) pp. 361-366.
Lisa Binderup et al: "Effects of a Novel Vitamin D Analogue MC 903 on Cell Proliferation and Differentiation in Vitro and on Calcium Metabolism in Vivo"; Biochemical Pharmacology, vol. 37, No. 5, (1988) pp. 889-895.
Hiroshi Sai et al: "Synthesis of Some Side-Chain Homologues of 1.alpha.,25-Dihydroxyvitamin D3 and Investigation of Their Biological Activities", Chem. Pharm. Bull. vol. 34, No. 11, (1986) pp. 4508-4515.
Nobuo Ikeawa et al: "26,27-Diethyl-1A,25-Dihydroxyvitamin D3 and 24,24-Difluoro-24-Homo-1a,25-Dihydroxyvitamin D3: Highly Potent Inducer for Differentiation of Human Leukemia Cells HL-60", Chemical Pharmaceutical Bulletin; vol. 35, No. 10, (1987), pp. 4362-4365 (see particularly p. 4363).
M. J. Calverley, "Synthesis of MC 903, A Biologically Active Vitamin D Metabolite Analogue"--Tetrahedron, vol. 43, No. 20, (1987); pp. 4609-4619, (see particularly pp. 4609-4610).
Andrzej Kutner: "Novel Convergent Synthesis of Side-Chain-Modified Analogues of 1.alpha.,25-Dihydroxycholecalciferol and 1.alpha.,25-Dihydroxyergocalciferol 1", J. Org. Chem., 1988, 53, pp. 3450-3457, Chemical Abstracts, vol. 109, No. 7, (Aug. 1988); No. 55060u, Columbus, Ohio, US.

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