MX2008009901A - Vitamin d analog - rak, methods and uses thereof - Google Patents

Abstract

Compounds of formula IA or IB are provided where X1, X2 and X3 are independently selected from H or hydroxy protecting groups and R1 is selected from straight or branched chain alkyl groups having from 1 to 8 carbon atoms;straight or branched chain alkenyl groups having from 2 to 8 carbon atoms;straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms;straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms. Such compounds are used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

Description

ANALOGUE OF VITAMIN D - RAK. ITS METHODS AND USES This application claims priority of the U.S. provisional patent application. Serial No. 60 / 743,219 filed February 2, 2006. FIELD OF THE INVENTION This invention relates to vitamin D compounds, and more particularly to (20R, 25f?) - 2-methylene-l9,26-dinor-1 a, 25-dihydroxyvitamin D3 (RAK) and to pharmaceutical formulations including this compound. The invention also relates to the use of (20R, 25R) -2-methylene-l9,26-dinor-1 a, 25-dihydroxyvitamin D3 or its salts in the preparation of medicaments for use in the treatment of various diseases. BACKGROUND OF THE INVENTION The natural hormone, lo, 25-dihydroxyvitamin D3 (also referred to as 1 a, 25-dihydroxycholecalciferol and calcitriol) and its analogue in the ergosterol series, ie 1 s, 25-dihydroxyvitamin D2, are known as highly potent regulators. of calcium homeostasis in animals and humans, and its activity in cell differentiation has also been established, Ostrem et al., Proc. Nati Acad. Sci. USA, 84.2610 (1987). Many structural analogues of these metabolites have been prepared and tested, including 1s-hydroxyvitamin D3, lahydroxyvitamin D2, various approved side-chain vitamins and fluorinated analogues. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity is useful in the treatment of a variety of diseases as established in the art, such as renal osteodystrophy, vitamin D resistant rickets, osteoporosis, psoriasis and certain malignancies (see for example, Zemplar, Calcipotriol, MC-903 , Dovonex, 22-oxa-la, 25- (OH) 2D3). Renal osteodystrophy is a bone disease that occurs when the kidneys fail to maintain adequate levels of calcium and phosphorus in the blood. Renal osteodystrophy is a common problem in people with kidney disease and affects 90 percent of dialysis patients. Renal osteodystrophy is more serious in children because their bones are still growing. The condition slows the growth of bones and causes deformities. One of these deformities occurs when the legs bend inward to each other or outward to each other; This deformity is referred to as "renal rickets". Another important consequence is short stature. Symptoms can be seen in growing children with kidney disease, even after they start dialysis. Bone changes due to renal osteodystrophy may begin many years before the symptoms appear in adults with kidney disease. The symptoms of renal osteodystrophy are usually not seen in adults until they have been on dialysis for several years. Older patients and women who have gone through menopause are at increased risk of this disease because they are already vulnerable to osteoporosis, even without kidney disease. If left untreated, the bones gradually thin and weaken, and a person with renal osteodystrophy begins to experience bone and joint pain and an increased risk of broken bones. In healthy adults, the bone tissue is continuously remodeled and reconstructed. The kidneys play an important role in maintaining the mass and structure of healthy bones because they balance the levels of calcium and phosphorus in the blood. If the levels of calcium in the blood are very low, the parathyroid glands release the parathyroid hormone (PTH = parathyroid hormone). This hormone extracts calcium from the bones to raise the levels of calcium in the blood. Too much PTH in the blood causes disturbances in calcium and phosphorus homeostasis. This in turn removes too much calcium from the bones; over time, the constant removal of calcium weakens the bones. Secondary hyperparathyroidism is characterized by an elevation of PTH associated with inadequate levels of active vitamin D hormone. Typically, Vitamin D requires two sequential hydroxylations in the liver and kidney to bind and activate the Vitamin D receptor (VDR = Vitamin D receptor). The endogenous VDR activator, calcitriol [1, 25 (OH) 2 DS] is a hormone that binds to VDR that is expressed in the parathyroid gland, intestine, kidney and bones to maintain parathyroid function and homeostasis of calcium and phosphorus, and to VDR It is found in many other tissues, including prostate, endothelium and immune cells. Phosphorus also helps regulate calcium levels in bones. Healthy kidneys remove excess phosphorus in the blood. When the kidneys stop working normally, the levels of phosphorus in the blood can be very high, leading to lower levels of calcium in the blood and resulting in the loss of calcium from the bones. Healthy kidneys produce calcitriol to help the body absorb calcium from diet in the blood and bones. If calcitriol levels fall too low, PTH levels rise, and calcium is removed from the bones. Calcitriol and PTH work together to maintain normal calcium balance and healthy bones. In a patient with renal failure, the kidneys stop producing calcitriol, the calcium in the diet is not absorbed and the calcium is removed from the bones. Controlling PTH levels prevents calcium from being removed from bones. Usually, overactive or active parathyroid glands in excess are controllable with a change in diet, dialysis treatment or medication. The drug cinacalcet hydrochloride (Sensipar), approved by the Food and Drug Administration in 2004, reduces PTH levels by binding to the calcium receptor that controls the release of PTH. If PTH levels can not be controlled, the parathyroid glands may need to be removed surgically. Other treatments for the condition include taking synthetic calcitriol as a pill or in an injectable form. Renal osteodystrophy can also be treated with changes in diet. Reducing the intake of phosphorus in the diet is one of the most important stages to avoid bone disease. Often, medications such as calcium carbonate (Tums), calcium acetate (PhosLo), sevelamer hydrochloride (Renagel), or lanthanium carbonate (Fosrenoi) are prescribed with food and snacks to bind phosphorus in the intestine, which decreases the absorption of phosphorus in the blood. Other treatment selections for renal osteodystrophy include Paricalcitol, the active ingredient of Zemplar (paracalcitol injection, USP), which is a synthetic, biologically active vitamin D analogue of calcitriol with modifications to the side chain and ring A (19-nor ). Pre-clinical and in vitro studies have shown that the actions of paricalcitol are mediated through VDR binding, resulting in the selective activation of the Vitamin D response pathways. Calcitriol and paricalcitol have been shown to reduce parathyroid hormone levels to inhibit the synthesis and secretion of PTH.

The structure of the, 25-dihydroxyvitamin D3 and the numbering system employed denote the carbon atoms in this compound are shown below. 1a, 25-Dihydroxyvitamin D3 = 1a, 25-D-Hydroxycholecalciferol = Calcitriol Typically, the class of vitamin D analogs such as the 19-nor-vitamin D compounds are characterized by the absence of carbon 19 from the exocyclic methylene group of ring A , typically from the vitamin D system. Biological tests of these 19-nor analogues (eg, 1a, 25-dihydroxy-19-nor-vitamin D3) revealed a selective activity profile with high potency to induce cell differentiation, and very low activity of calcium mobilization. In this way, these compounds are potentially useful as therapeutic agents for the treatment of malignancies, or the treatment of various skin disorders. Two different methods of synthesis of these 19-nor-vitamin D analogues have been described (Perlman et al., Tetrahedron Lett., 31, 1823 (1990), Perlman et al., Tetrahedron Lett., 32, 7663 (1991), and DeLuca. et al., US patent No. 5,086,191). In the patent of the U.S.A. No. 4,666,634, 2a-hydroxyl analogs and alkoxy (e.g., ED-71) of 1o, 25-dihydroxyvitamin D3 have been described and examined by the Chugai group as potential drugs for osteoporosis and as antitumor agents. See also Okano et al., Biochem. Biophys. Res. Commun. 163, 1444 (1989). Other A 2-substituted ring analogs (with hydroxyalkyl groups, for example ED-120 and fluoroalkyl) of 1a, 25-dihydroxyvitamin D3 have also been prepared and tested (Miyamoto et al., Chem. Pharm. Bull. 41, 1111 ( 1993), Nishii et al., Osteoporosis Int. Suppl. 1, 190 (1993), Posner et al., J. Org. Chem. 59, 7855 (1994), and J. Org. Chem. 60.4617 (1995). )). Various 2-substituted analogues of 1a, 25-dihydroxy-19-nor-vitamin D3 have also been synthesized, ie compounds substituted in the 2-position with hydroxy or alkoxy groups (DeLuca et al., US Patent No. 5,536,713) , with 2-alkyl groups (DeLuca et al., U.S. Patent No. 5,945,410), and with 2-alkylidene groups (DeLuca et al., U.S. Patent No. 5,843,928), which exhibit interesting and selective activity profiles . All these studies indicate that binding sites in vitamin D receptors can accommodate different substituents on C-2 in the synthesized vitamin D analogues. In a continuing effort to explore the 19-nor class of pharmacologically important vitamin D compounds, analogs that are characterized by the presence of a methylene substituent on carbon 2 (C-2), a hydroxyl group on carbon 1 (C- 1), and a cut-off side chain connected to carbon 20 (C-20) have also been synthesized and tested. 1a-hydroxy-2-methylene-19-nor-pregnacalciferol is described in U.S. Pat. No. 6,566,352 while 1a-hydroxy-2-methylene-19-nor- (20S) -homopregnacalciferol is described in U.S. Pat. No. 6,579,861 and 1a-hydroxy- 2-methylene-19-nor-bishomopregnacalciferol is described in U.S. Pat. No. 6,627,622. All three of these compounds have relatively high binding activity with vitamin D receptors and relatively high cell differentiation activity, but little, if there is calcemic activity compared to 25-dihydroxyvitamin D3. Their biological activities make these compounds excellent candidates for a variety of pharmaceutical uses, as set forth in the '352,' 861 and '622 patents. Other 19-nor compounds are described in the U.S. patent applications. Nos. Of Series 10 / 996,642 and 10 / 997,698. Since the currently available treatments, including compounds and formulations described above have various limitations in a greater or lesser proportion, new compounds and pharmaceutical formulations are suitable which continue to decrease the caikemic effect while retaining the ability to suppress PTH. COMPENDIUM OF THE INVENTION The invention in general provides (20R, 25f?) -2-methylene-l9,26-dinor-1o, 25-dihydroxyvitamin D3 (RAK) and related compounds, pharmaceutical formulations including RAK and the use of this compound in the preparation of medications to be used in the treatment of various disease states. Therefore, in one aspect, the invention provides a compound having the formula IA or IB as shown below: IB wherein Xi, X2 and X3 are the same or different and are independently chosen from H or hydroxy-pratector groups. In some embodiments, Xi, X2 and X3 are hydroxy protecting groups such as silyl groups. In some of these embodiments, Xi, X2 and X3 are t-butyldimethylsilyl groups. In certain embodiments, R1 is chosen from straight-chain alkyl groups or branched having 1 to 8 carbon atoms, straight or branched chain alkenyl groups having 2 to 8 carbon atoms, straight or branched chain hydroxy substituted alkyl groups having 1 to 8 carbon atoms, or alkenyl hydroxy groups -substituted straight or branched chain having 2 to 8 carbon atoms. In some of these embodiments, Ri is selected from straight or branched chain alkyl groups having 2 to 7 carbon atoms, straight or branched chain alkenyl groups having from 2 to 7 carbon atoms, alkyl hydroxy-substituted chain groups straight or branched having 2 to 6 carbon atoms, or straight or branched chain hydroxy-substituted alkenyl groups having from 2 to 6 carbon atoms. In other of these embodiments, Ri is selected from straight or branched chain alkyl groups having from 2 to 7 carbon atoms, straight or branched chain alkenyl groups having from 2 to 7 carbon atoms, or hydroxy-substituted alkenyl groups straight or branched chain having 2 to 6 carbon atoms. In other embodiments, X2 and X3 are H and is CH3 such that the compound is (20f ?, 25f?) - 2-methylene-l9,26-dinor-1a, 25-dihydroxyvitamin D3 having the formula HA or (20S, 25R) -2-Methylene-l9,26-dinor-1 a, 25-dihydroxyvitamin D3 having the formula IIB as shown below: II A II B Another embodiment of the present invention provides a pharmaceutical composition, comprising an effective amount of the compound of formula IA or IB and a pharmaceutically acceptable carrier. In this pharmaceutical composition, the effective amount comprises from about 0.01 / vg to about 1 mg of the compound per gram of the composition. More preferably, the effective amount comprises from about 0.1 g to about 500 pg of the compound per gram of the composition. In certain embodiments, the present invention provides a method for treating a subject suffering from a biological condition, comprising administering an effective amount of the compound of the formula IA or IB to the subject, wherein the biological condition is chosen from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of dermal hydration adequate or insufficient secretion of sebum; renal osteodystrophy; or osteoporosis. In a preferred embodiment, the biological condition is renal osteodystrophy, vitamin D resistant rickets, osteoporosis or psoriatic arthritis. In another preferred embodiment, the biological condition is chosen from leukemia, colon cancer, breast cancer, or prostate cancer. In yet another preferred embodiment, the biological condition is chosen from multiple sclerosis, lupus, diabetes mellitus, host versus graft reaction, or rejection of organ transplants. In yet another preferred embodiment, the biological condition is chosen from rheumatoid arthritis, asthma or inflammatory bowel diseases selected from celiac disease, ulcerative colitis and Crohn's disease. In yet another preferred embodiment, the biological condition is chosen for wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration, or insufficient sebum secretion. Also preferably, in this embodiment, the effective amount of the compound is administered orally, parenterally, transdermally or topically to the subject. Even more preferably, the effective amount of the compound is administered intraperitoneally. In this embodiment, the compound is administered in a dose of 0.01 pg per day to 1 mg per day. Another aspect of the invention provides the use of the compound of the formula IA or IB in the preparation of a medicament for the treatment of a biological condition selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration, or insufficient sebum secretion; renal osteodystrophy; or osteoporosis. In still another preferred embodiment, the invention comprises a method cosmetic to maintain a certain weight, promote cosmetic weight loss or promote beneficial conditions of the skin including, inhibit wrinkles, improve the lack of adequate firmness of the skin, promote adequate dermal hydration, or insufficient secretion of sebum, in an animal subject , the method comprises using a compound of formula IA or IB. Still another preferred embodiment of the present invention provides the compound having the formula IIA or ? The invention also illustrates a pharmaceutical composition having an effective amount of the compound of the formula HA and a pharmaceutically acceptable carrier. Another aspect of the invention provides the use of the compound of formula IIA in the preparation of a medicament for the treatment of a biological condition selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration, or insufficient sebum secretion; renal osteodystrophy; or osteoporosis. Additional objects, features and advantages of the invention will be apparent from the following detailed description, drawings and appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1-5 illustrate various biological activities of (20R, 25R) -2-methylene-19,26-dinor-1a ', 25-dihydroxyvitamin D3 (referred to as "RAK" in the Figures) in comparison with those of the native hormone 1 s, 25-dihydroxyvitamin D3 (referred to as "1, 25 (OH) 2D3" in the Figures). Figure 1 is a graph comparing the relative activity of RAK and 1, 25 (OH) 2D3 to compete for binding with [3H] -1, 25- (OH) 2-D3 to the recombinant rat vitamin D receptor of integral length. Figure 2 is a bar graph comparing the calcium mobilization activity of RAK with that of 1, 25 (OH) 2D3. Figure 3 is a bar graph comparing the intestinal calcium transport activity of RAK with that of 1, 25 (OH) 2D3. Figure 4 is a graph comparing the percent cell differentiation HL-60 as a function of the concentration of NEL with that of 1, 25 (OH) 2D3. Figure 5 is a graph comparing the in vitro transcription activity of RAK with that of 1, 25 (OH) 2D3. DETAILED DESCRIPTION OF THE INVENTION In general, the invention provides a compound having the formula IA or IB as shown below: wherein Xi, X2 and X3 are identical or different and are independently chosen from H or hydroxy protecting groups. In some embodiments, X1 t X2 and X3 are hydroxy protecting groups such as silyl groups. In some of these embodiments, Xi, X2 and X3 are t-butyldimethylsilyl groups. In certain embodiments, R 1 is selected from straight or branched chain alkyl groups having 1 to 8 carbon atoms, straight or branched chain alkenyl groups having from 2 to 8 carbon atoms, straight-chain hydroxy-substituted alkyl groups or branched having 1 to 8 carbon atoms, or alkenyl groups straight or branched chain hydroxy-substituted having from 2 to 8 carbon atoms. In some of these embodiments, Ri is chosen from straight or branched chain alkyl groups having from 2 to 7 carbon atoms, straight or branched chain alkenyl groups having from 2 to 7 carbon atoms, hydroxy-substituted alkyl groups of straight or branched chain having from 2 to 6 carbon atoms, or straight or branched chain hydroxy-substituted alkenyl groups having from 2 to 6 carbon atoms. In other of these embodiments, straight or branched chain alkyl groups having 2 to 7 carbon atoms, straight or branched chain alkenyl groups having from 2 to 7 carbon atoms, or hydroxy-substituted alkenyl groups are chosen from straight or branched chain having 2 to 6 carbon atoms. As used herein, the phrase "straight or branched chain alkyl groups" refers to groups that include carbon and hydrogen atoms that only include simple carbon-carbon bonds and simple carbon-hydrogen bonds. These groups do not include any heteroatoms (atoms other than H or C). Thus, the phrase "straight or branched chain alkyl groups" includes straight chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl and octyl groups and branched chain isomers of straight chain alkyl groups , including but not limited to the following, which are provided by way of example only: -CH (CH3) 2, -CH (CH3) (CH2CH3), -CH (CH2CH3) 2, -C (CH3) 3, -C (CH2CH3) 3, -CH2CH (CH3) 2, -CH2CH (CH3) (CH2CH3), -CH2CH (CH2CH3) 2, -CH2C (CH3) 3, -CH2C (CH2CH3) 3, CH (CH3) CH ( CH3) (CH2CH3), -CH2CH2CH (CH3) 2, -CH2CH2CH (CH3) (CH2CH3), CH2CH2CH (CH2CH3) 2, -CH2CH2C (CH3) 2, -CH (CH3) CH2CH (CH3) 2, CH (CH3) ) CH (CH3) CH (CH3) 2, -CH2CH2CH2C (CH3) 2, -CH2CH2CH2CH (CH3) 2, CH2CH2CH (CH3) C (CH3) 3, -CH2CH2CH (CH3) CH (CH3) 2, and the like. As used herein, the phrase "hydroxy-substituted alkyl groups" is refers to "straight and branched chain alkyl groups" as defined above, wherein a bond to a carbon atom or a hydrogen is replaced by a bond with a hydroxyl group (-OH). As used herein, the phrase "straight and branched chain alkenyl groups" refers to "straight and branched chain alkyl groups" as defined above, except that there is at least one double bond between two of the carbon atoms. Examples include, but are not limited to the cis and trans isomers (Z and E) of -CH = CH2, -CH = C (H) (CH3), -CH = C (CH3) 2, -C (CH3) = C (H) 2, -C (CH 3) = C (H) (CH 3), -C (CH 2 CH 3) = CH 2, -C (H) = C (H) CH 2 CH (CH 3) 2, -C (H) = C (H) CH (CH3) CH (CH3) 2) C (H) = C (H) CH2C (CH3) 3, C (H) = C (H) CH (CH3) C (CH3) 3 and the like. As used herein, the phrase "hydroxy-substituted alkenyl groups" has the same meaning with respect to "straight and branched chain alkenyl groups" that "hydroxysubstituted alkyl groups" refer to "straight and branched chain alkyl groups". Thus, "hydroxy-substituted alkenyl groups" are "straight and branched chain alkenyl groups" wherein a bond to a hydrogen atom or carbon atom having no double bond with another carbon atom, is replaced by a bond with a hydroxyl group (-OH). As used herein, the term "hydroxy-protective group" means any group commonly employed for the temporary protection of the hydroxy functional group (-OH), such as but not limited to, alkoxycarbonyl, acyl, alkylsilyl or alkylarylsilyl groups (hereinafter simply referred to as "silyl" groups), and alkoxyalkyl groups. Alkoxycarbonyl protecting groups are alkyl-O-CO-groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl or allyloxycarbonyl. The term "acyl" means an alkanoyl group of 1 to 6 carbon atoms, in all its forms isomeric, or a carboxyalkanoyl group of 1 to 6 carbon atoms, such as an oxalyl, malonyl, succinyl, glutaryl, or an aromatic acyl group such as benzoyl, or a benzoyl group substituted with halo, nitro or alkyl. Alkoxyalkyl protecting groups are groupings such as methoxymethyl, ethoxymethyl, methoxyethoxymethyl or tetrahydrofuranyl and tetrahydropyranyl. Preferred silyl protecting groups are trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, dibutylmethylsilyl, diphenylmethylsilyl, phenyldimethylsilyl, diphenyl-t-butylsilyl and analogous alkylated silyl radicals. The term "aryl" specifies a phenyl-, or a phenyl group substituted with alkyl-, nitro- or halo-. An extensive list of protecting groups for hydroxy functionality is found in Protective Groups in Organic Synthesis, Greene, T.W .; Wuts, P. G. M., John Wiley & Sons, New York, NY, (3rd Edition, 1999) that can be added or removed using the procedures established therein. A "protected hydroxy" group is a hydroxy group derivatized or protected by any of the above groups commonly employed for the temporary or permanent protection of hydroxy functional groups, for example the silyl, alkoxyalkyl, acyl or alkoxy carbonyl groups, as previously defined. In other embodiments, Xi, X2 and X3 are H and P is CH3 such that the compound is (20F ?, 25R) -2-methylene-l9,26-dinor-1a, 25-dihydroxyvitamin D3 having the formula IIA or (20S, 25R) -2-Methylene-l9,26-dinor-1a, 25-dihydroxyvitamin D3 having the formula IIB as shown below: HE HAS II B The compound of the formula HA (RAK) exhibits a pattern of desired and highly advantageous biological activity. This compound is characterized by a relatively high binding to vitamin D receptors, but very low intestinal calcium transport activity, compared to that of 1ff, 25-dihydroxyvitamin D3, and has very low ability to mobilize calcium in bones, in comparison with 1, 25-dihydroxyvitamin D3. Therefore, this compound can be characterized because it has little, if there is calcemic activity. In this way, it is useful as a therapy for the suppression of secondary hyperparathyroidism or renal osteodystrophy. The compound of the invention is also especially suitable for the treatment and prophylaxis of human disorders, which is characterized by an imbalance in the immune system, for example in autoimmune diseases, including multiple sclerosis, lupus, diabetes mellitus, host versus graft reaction, and rejection of organ transplants; and additionally for the treatment of inflammatory diseases, such as rheumatoid arthritis, asthma, and intestinal inflammatory diseases such as celiac disease, ulcerative colitis and Crohn's disease.

Acne, alopecia and hypertension are other conditions that are treated with the compound of the invention. The above compound is also characterized by a relatively high cell differentiation activity. In this manner, this compound also provides a therapeutic agent and / or a cosmetic for the treatment of psoriasis, or as an anti-cancer agent, especially against leukemia, colon cancer, breast cancer and prostate cancer. In addition, due to its relatively high differentiation activity, this compound provides a therapeutic and / or cosmetic agent for the treatment of various skin conditions including wrinkles, lack of adequate dermal hydration, ie dry skin, lack of adequate skin firmness , ie loose skin and insufficient secretion of sebum. The use of this compound not only results in skin moisturization but also improves skin barrier function. The compounds of the invention are used to prepare pharmaceutical formulations or medicaments that include a compound of the invention in combination with a pharmaceutically acceptable carrier. These pharmaceutical formulations and medicaments are used to treat various biological disorders such as those described herein. Methods for the treatment of these disorders typically include administering an effective amount of the compound or an appropriate amount of a pharmaceutical formulation or a medicament that includes the compound to a subject suffering from the biological disorder. In some modalities, the subject is a mammal. In some of these embodiments, the mammal is chosen from a rodent, a primate, a bovine, an equine, a canine, a feline, a ursinus, a pig, a rabbit, or a guinea pig. In some of these embodiments, the mammal is a rat or a mouse. In some modalities, the subject is a primate such as, in some modalities, a human.

The compounds are present in a composition for treating the diseases and disorders noted above, in an amount of about O.Olpg / gm to about 1 mg / gm of the composition, preferably from about 0.1 pg / gm to about 500 pg / gm. of the composition, and is administered topically, transdermally, orally or parenterally, in doses of approximately 0.01 / vg / day to approximately 1 pg / day, preferably from approximately 0.I / g / day to approximately 500 / vg /day. In one embodiment, compounds IA or IB are HA or IIB compounds as shown below: II B In a preferred embodiment, (20, 25R) -2-methylene-l9,26-dinorcr, 25-dihydroxyvitamin D3 (RAK) was synthesized and tested and is useful for treating a variety of biological conditions as described herein. Preparation of (20F ?, 25R) -2-methylene-l9,26-dinor-1 ar, 25-dihydroxyvitamin D3 can be achieved by condensing an appropriate bicyclic Windaus-Grundmann ketone (1111) with allyl oxide phosphine IV followed by deprotection (elimination of the Yi and Y2 groups). Other compounds of the present invention are synthesized in a similar manner.

In the ketone III, Y4 is preferably a hydroxy-protective group such as silyl protecting groups. The t-butyldimethylsilyl group (TBDMS) is an example of a particularly useful hydroxy protecting group. In phosphine oxide IV, Y and Y2 are preferably hydroxy-protective groups such as silyl protecting groups. The t-butyldimethylsilyl group (TBDMS) is an example of a particularly useful hydroxy protecting group. The process described above represents an application of the concept of convergent synthesis, which has been effectively applied to the preparation of numerous vitamin compounds D (see, Lythgoe et al., J. Chem. Soc. Perkin Trans. I, 590 (1978), Lythgoe, Chem. Soc. Rev. 9,449 (1983), Toh et al., J. Org. Chem. , 1414 (1983), Baggiolini et al., J. Org. Chem. 51, 3098 (1986), Sardina et al., J. Org. Chem. 51, 1264 (1986), J. Org. Chem. 1269 (1986), DeLuca et al., U.S. Patent No. 5,086,191, DeLuca et al., U.S. Patent No. 5,536,713, and DeLuca et al., U.S. Patent No. 5,843,928. convenient reagent that can be used to prepare a large amount of 19-nor vitamin D compounds and is prepared according to the procedures described by Sicinski et al., J. Med. Chem., 41, 4662 (1998), DeLuca et al. , U.S. Patent No. 5,843,928, Perlman et al., Tetrahedron Lett., 32, 7663 (1991), and DeLuca et al., U.S. Patent No. 5,086,191, Scheme I shows the general procedure for synthesizing phosphine oxide IV. as set forth in U.S. Patent No. 5,843,928. Modification of the method The one shown in Scheme I is used to produce a large amount of vitamin D analogues as will be apparent to those skilled in the art. For example, a wide variety of phosphonium compounds is used in place of MePh3P + Br used to convert ketone B to alkene C. Examples of these compounds include EtPh3P + Br ~, PrPh3P + Br ", and compounds generally prepared by reaction of triphenylphosphine with an alkyl halide, an alkenyl halide, a protected hydroxyalkyl halide, and a protected hydroxyalkenyl halide Alkenes prepared using this procedure can then be transported to prepare phosphine oxide in a manner analogous to that used to prepare phosphine oxide H in Scheme I. Alternatively, an alkene analog to compound C of Scheme I is reduced with (Ph3P) 3RhCl and H2 to provide other vitamin D analogues. See, U.S. Patent No. 5,945,410 and Sicinski, RR et al., J. Med. Chem., 41, 4662-4674 (1998). Therefore, the process for forming phosphine oxide shown in Scheme I is used to prepare a wide variety of vitamin D analogues in addition. of the compounds of the present invention. SCHEME I ePh3P * Br rvBuLi Hydraindanones of structure III can be prepared by known methods or adapted methods as will be readily apparent to a person skilled in the art and described herein. Specific examples of some important bicyclic ketones used to synthesize vitamin D analogues are those described in Mincione et al., Synth. Commun 19, 723, (1989); and Peterson et al., J. Org. Chem. 51, 1948, (1986). In a preferred embodiment, the ketone III having the group Y4 = TBSO (12) is synthesized by Schemes II and III, as shown below: Scheme II A total process for synthesizing 2-alkylidene-19-nor-vitamin D compounds is illustrated and described in U.S. Pat. No. 5,843,928, U.S. Pat. No. 6,627,622; U.S. Patent No. 6,579,861; U.S. Patent No. 5,086,191; U.S. Patent No. 5,585,369; and US patent. No. 6,537,981. In a preferred embodiment, the compound of the Formula HA (RAK) is prepared by the following Scheme III: Scheme III NaOH EtOH Compounds of formula I, formula IA and formula IB and formula II, formula HA and formula IIB can be prepared using the methods shown in Schemes I, II and III. For the compound of the formula HA, the starting material, compound 4, is prepared using the procedure as shown below as Scheme IV. See also, Andrzej R. Daniewski and Wen Liu (J. Org. Chem. 66, 626-628 (2001). Scheme IV: L TsCI, Et3N, DMAP, The following examples illustrate the synthesis and biological activity of the compounds provided in the present invention. These examples are for illustrative purposes only and are not to be construed as limiting the scope of the invention. Example I: SYNTHESIS OF RAK Preparation of (3R) -1-p-Toluenesulfonyloxy-3-triethylsilyloxy-butane (2). To a stirred solution of (f?) - (-) - 1,3-butanediol 1 (1 g, 11.1 mmol), DMAP (30 mg, 0.25 mmol) and Et3N (4.6 mL, 3.33 g, 33 mmol) in methylene chloride Anhydrous (20 mL) is added p-toluenesulfonyl chloride (2.54 g, 13.3 mmol) at 0 degrees C. The reaction mixture is stirred at 4 degrees C for 22 h. Methylene chloride is added and the mixture is washed with water, dried (Na2SO4) and concentrated under reduced pressure. A The residue is chromatographed on silica gel with hexane / ethyl acetate (8: 2, then 1: 1) to give tosylate (2.17 g, 80% yield) as a colorless oil. To a stirred solution of tosylate (2.17 g, 8.9 mmoles) and 2,6-lutidine (1.14 mL, 1.05 g, 9.8 mmoles) in anhydrous methylene chloride (15 mL) triethylsilyl trifluoromethanesulfonate (2 mL, 2.35 g, 8.9 mmoles) it is added at -50 degrees C. The reaction mixture is allowed to warm to room temperature (4 h) and stirring is continued for an additional 20 hours. Methylene chloride is added and the mixture is washed with water, dried (Na 2 SO 4) and concentrated under reduced pressure. A residue is chromatographed on silica gel with hexane / ethyl acetate (97: 3) to give product 2 (3.16 g, 99% yield) as a colorless oil: [a] D -20.7 (c 1.62, CHCl3 ); 1 H-NMR (400 MHz, CDCl 3) d 7.77 (2H, d, J = 8.2 Hz, O-HTS), 7.33 (2H, d, J = 8.2 Hz, m-HTs), 4.10 (2H, t, J = 6.1 Hz, 1-H2), 3.90 (1 H, m, 3-H), 2.43 (3H, s, MeTs), 1.72 (2H, m, 2-H2), 1.10 (3H, d, J = 6.2Hz , 4-H3), 0.88 (9H, t, J = 7.9 Hz, 3 x SiCH2CH3), 0.50 (6H, q, J = 7.9 Hz, 3 x SiCH2CH3); 13 C NMR (100 MHz) d 144.62 (sp-Crs), 133.02 (s, -CTS), 129.72 (d, m-CTs), 127.82 (d, o-CTs), 67.78 (t, C-1), 64.45 (d, C-3), 38.46 (t, C-2), 23.81 (q, C-4), 21.51 (q, MeTs), 6.71 (q, SiCH2CH3), 4.76 (t, SiCH2CH3); MS (El) m / z 359 (0.5, MH +), 329 (59, (M + -C2H5), 285 (24), 258 (71), 229 (22), 212 (14), 199 (12), 159 (28), 145 (45), 115 (72), 91 (100), exact mass calculated for C15H2504SSi (M + -C2H5) 329.1243, found 329.1248.Preparation of (3) -1-Iodo-3-triethylsilyloxybutane ( 3) To a stirred solution of tosylate 2 (3.15 g, 8.8 mmol) in anhydrous acetone (50 mL) of potassium iodide (8 g, 48 mmol) is added and the reaction mixture is refluxed for 10 h. Water (30 mL) is added and the solution is extracted with ethyl acetate.The combined organic phases are dried (Na2SO4) and concentrated under reduced pressure.The residue is chromatographed on silica gel with hexane / ethyl acetate (97: 3) to give alcohol 3 (2.6 g, 94% yield) as a colorless oil: [s] D-39.5 (c 1.75, CHCl3); 1 H NMR (400 MHz, CDCl 3) d 3.89 (1 H, m, 3-H), 3.22 (2 H, t, J = 7.0 Hz, 1-H2), 1.91 (2 H, m, 2-H 2), 1.16 (3 H , d, J = 6.1 Hz, 4-H3), 0.96 (9H, t, J = 7.9 Hz, 3 x SiCH2CH3), 0.61 (6H, q, J = 7.9 Hz, 3 x SiCH2CH3); 13 C NMR (100 MHz) d 68.14 (d, C-3), 43.24 (t, C-2), 23.46 (q, C-4), 6.87 (q, SiCH2CH3), 5.00 (t, SiCH2CH3), 3.37 ( t, C-1); MS (El) m / z 314 (1, M +), 299 (3, M + -CH 3), 285 (100, M + -C 2 H 5), 257 (78, M + -C 4 H 9), 228 (56), 212 (99) , 184 (65), 157 (70), 129 (46), 115 (46); exact mass calculated for C8H, 8OISi (M + -C2H5) 285.0172, found 329.1248. Preparation of (3R) -Hydroxybutyltriphenylphosphonium iodide (4). To a stirred solution of iodide 3 (1.24 g, 3.9 mmol) in anhydrous acetonitrile (50 mL) triphenylphosphine (3.1 g, 11.8 mmol) is added and the reaction mixture is refluxed for 2 days. Acetonitrile was evaporated under reduced pressure, ethyl acetate (50 mL) was added and the mixture was stirred at room temperature for 4 h. After removing the solvent by filtration, the solid is washed with ethyl acetate, separated by filtration and dried. The pure phosphonium salt 4 (1.74 g, 96% yield) is obtained as white crystals: 1 H NMR (400 MHz, CD 3 OD) d 8.00 -7.70 (15H, m, HPh), 3.89 (1 H, m, 3-H) , 3.48 (2H, m, 1H2), 1.73 (2H, m, 2-H2), 1.19 (3H, d, J = 6.2 Hz, 4-H3); 13 C NMR (100 MHz) d 136.41 (d, p-Cph), 134.99 (d, Jc-P = 10.1 HZ, m-CPh), 131.70 (d, Jc-P = 12.1 HZ, 0-CPh), 120.03 ( s, Jc-P = 86.5 Hz, i-CPh), 67.94 (d, JcP = 17.1 HZ, C-3), 32.52 (t, Jc-P = 4.0 Hz, C-2), 23.38 (q, C- 4), 19.85 (t, JC-P = 54.3 Hz, C-1); Preparation of (8S, 20S) -de-A, B-20- (hydroxymethyl) pregnan-8-ol (5). Ozone is passed through a solution of vitamin D2 (3 g, 7.6 mmol) in methanol (250 mL) and pyridine (2.44 g, 2.5 mL, 31 mmol) for 50 minutes at -78 degrees C. The reaction mixture then it is washed by entrainment with oxygen for 15 minutes to remove the residual ozone and the solution is treated with NaBH 4 (0.75 g, 20 mmol). After minutes the second portion of NaBH 4 (0.75 g, 20 mmol) is added and the mixture is allowed to warm to room temperature. The third portion of NaBH (0.75 g, 20 mmol) is then added and the reaction mixture is stirred for 18 hours. The reaction is neutralized with water (40 mL) and the solution is concentrated under reduced pressure. The residue is extracted with ethyl acetate and the combined organic phases are washed with 1M aqueous HCl, saturated aqueous NaHC03l is dried (Na2SO4) and concentrated under reduced pressure. The residue is chromatographed on silica gel with hexane / ethyl acetate (75:25) to give the diol 5 1.21 g, 75% yield) as white crystals: m.p. 106-108 ° C; [] D + 30.2 ° (c 1.46, CHCI3); 1 H NMR (400 MHz, CDCl 3) d 4.08 (1 H, d, J = 2.0 Hz, 8aH), 3.63 (1 H, dd, J = 10.5, 3.1 Hz, 22-H), 3.38 (1H, dd , J = 10.5, 6.8 Hz, 22-H), 1.99 (1H, br.d, J = 13.2 Hz), 1.03 (3H, d, J = 6.6 Hz, 21-H3), 0.956 (3H, s, 18 -H3); 13 C NMR (100 MHz) d 69.16 (d, C-8), 67.74 (t, C-22), 52.90 (d), 52.33 (d), 41.83 (s, C-13), 40.19 (t), 38.20 (d), 33.53 (t), 26.62 (t), 22.54 (t), 17.36 (t), 16.59 (q, C-21), 13.54 (q, C-18); MS (El) m / z 212 (2, M +), 194 (34, M + -H20), 179 (33, M + -H20 -CH3), 163 (18, M + -CH2OH -H20), 135 (36), 125 (54), 111 (100), 95 (63), 81 (67); exact mass calculated for C13H20 (M + -H20) 194.1671, found 194.1665. Preparation of (8S, 20S) -de-A, B-8-benzoyloxy-20- (hydroxymethyl) pregnane (6). Benzoyl chloride (2.4 g, 2 mL, 17 mmol) is added to a solution of diol 5 (1.2 g, 5.7 mmol) and DMAP (30 mg, 0.2 mmol) in anhydrous pyridine (20 mL) at 0 degrees C. The reaction mixture is stirred at 4 degrees C for 24 hours, diluted with methylene chloride (100 mL), washed with 5% HCl, NaHC03 aq. saturated, dried (Na2SO) and concentrated under reduced pressure. The residue (3.39 g) is treated with a solution of KOH (1 g, 15.5 mmol) in anhydrous ethanol (30 mL) at room temperature. After stirring the reaction mixture for 3 hours, ice and HCl aq. to 5% are added until pH = 6. The solution is extracted with ethyl acetate (3 x 50 mL) and the combined organic phases are washed with NaHCO 3 aq. Saturated, dried (Na2SO4) and concentrated under reduced pressure. The residue is chromatographed on silica gel with hexane / ethyl acetate (75:25) to give alcohol 6 (1.67 g, 93% yield) as a colorless oil: [α] D +56.0 (c 0.48, CHCl 3); 1 H NMR (400 MHz, CDCl 3 + TMS) d 8.08-8.02 (2H, m, o-HBz), 7.59-7.53 (1 H, m, p-HBz), 7.50-7.40 (2H, m,? -? ^ ). 5.42 (1 H, d, J = 2.4 Hz, 8a -H), 3.65 (IH, dd, J = 10.5.3.2Hz, 22-H), 3.39 (IH, dd, J = 10.5.6.8 Hz, 22- H), 1.08 (3H, d, J = 5.3 Hz, 21-H3), 1.07 (3H, s, 18-H3); 13 C NMR (125 MHz) d 166.70 (s, C = 0), 132.93 (d.p-Cez). 131.04 (s, ¡-C &), 129.75 (d, o-CBz), 128.57 (d, m-CBz), 72.27 (d, C-8), 67.95 (t, C-22), 52.96 (d) , 51.60 (d), 42.15 (s, C-13), 39.98 (t), 38.61 (d), 30.73 (t), 26.81 (t), 22.91 (t), 18.20 (t), 16 87 (q, C-21), 13.81 (q, C-18); MS (El) m / z 316 (5, M +), 301 (3, M + -Me), 299 (1, M + -OH), 298 (2, M + -H20), 285 (10, M + -CH2OH), 257 (6), 230 (9), 194 (80), 135 (84), 105 (100); exact mass calculated for C20H28O3 316.2038, found 316.2019. Preparation of (8S, 20S) -de-A, B-8-benzoyloxy-20-formylpregnane (7). Sulfur trioxide pyridine complex (1.94 g, 12.2 mmol) is added to a solution of alcohol 6 (640 mg, 2.03 mmol), triethylamine (1.41 ml_, 1.02 g, 10.1 mmol) in anhydrous methylene chloride (10 mL) and DMSO anhydrous (2 ml_) at 0 degrees C. The reaction mixture is stirred under argon at 0 degrees C for 1 hour, and then concentrated. The residue is diluted with ethyl acetate, washed with brine, dried (Na 2 SO 4) and concentrated. The residue is purified by column chromatography on silica gel with hexane / ethyl acetate (95: 5) to give aldehyde 7 (529 mg, 83% yield) as an oil. 1 H NMR (400 MHz, CDCl 3 + TMS) d 9.60 (1H, d, J = 3.1 Hz, CHO), 8.05 (2H, m, O-HBZ), 7.57 (1 H, mp-Htt), 7.45 (2H, m, m-HBz), 5.44 (1H, s, 8 -H), 2.39 (1 H, m, 20-H), 2.03 (2H, dm, J = 11.5 Hz), 1.15 (3H, d, J = 6.9 Hz, 21-H3), 1.10 (3H, s, 18-H3); 13 C NMR (100 MHz) d 204.78 (d, CHO), 132.78 (d, p-Bz), 130.69 (s, i-Bz), 129.50 (d, o-Bz), 128.38, (d, m-Bz) , 71.66 (d, C-8), 51.30 (d), 50.95 (d), 49.20 (d), 42.38 (s, C-13), 39.62 (t), . 47 (t), 25.99 (t), 22.92 (t), 17.92 (t), 13.90 (q), 13.35 (q); MS (El) m / z 314 (1, M +), 299 (0.5, + -Me), 286 (1, M + -CO), 285 (5, M + -CHO), 257 (1, M + -C3H50), 209 (10, M + -PhCO), 192 (38), 134 (60), 105 (100), 77 (50); exact mass calculated for C20H26O3 314.1882, found 194.1665. Preparation of (8S, 20f?) - de-A, B-8-benzoyloxy-20 - [(4R) -hydroxy-pent- (1E) -en-yl] -pregnane (8). To a stirred suspension of phosphonium salt 4 (361 mg, 0.78 mmol) in anhydrous THF (5 mL) butyllithium (1.6, 980 μ?, 1.56 mmol) is added at -20 degrees C. The solution turned to orange. After 1 h a pre-cooled solution (-20 degrees C) of aldehyde 7 (81 mg, 0.26 mmol) in anhydrous THF (2 mL) is added and the reaction mixture is stirred at -20 degrees C for 3 hours and at room temperature for 18 h. The reaction is neutralized with water and the mixture is extracted with ethyl acetate. The combined organic phases were washed with brine, dried (Na 2 SO 4) and evaporated. The residue is chromatographed on silica gel with hexane / ethyl acetate (95: 5) to give product 8 (47 g, 49% yield); [a) D + 69.6 (c 1.3, CHCl3); 1 H NMR (400 MHz, CDCl 3 + TMS) d 8.05 (2H, m, o-HBZ), 7.56 (1H, m, p-HBz), 7.45 (2H, m, mH ^), 5.41 (1H, s, 8a -H), 5.40 -5.20 (2H, m, 22-H and 23-H), 3.78 (1H, m, 25-H), 1.18 (3H, d, J = 6.1 Hz, 27-H3), 1.07 ( 3H, s, 18-H3), 1.05 (3H, d, J = 6.8 Hz, 21-H3); 13c NMR (100 MHz) d 166.44 (s, C = 0), 140.80 (d, C-22), 132.66 (d, p-CBz), 130.84 (s, i-CBz), 129.51 (d, o-CBz) ), 128.32 (d, mH ^), 123.25 (d, C-23), 72.14 (d, C-8), 67.20 (d, C-25), 55.97 (d), 51.64 (d), 42.37 (t ), 41.84 (s, C-13), 39.91 (d), 39.80 (t), 30.49 (t), 27.58 (t), 22.57 (t), 22.57 (q, C-27), 20.59 (q, C) -21), 17.99 (t), 13.72 (q, C-18); MS (El) m / z 370 (12, M +), 352 (1, M + -H20), 326 (4, M + -C2H40), 284 (18, M + -C5H10O), 248 (40, M + -PhCOOH), 230 (12), 204 (31), 189 (16), 162 (97), 134 (81), 121 (61), 106 (63), 93 (66), 77 (100); exact mass calculated for C24H3403 (M +) 370.2508, found 370. 2503. Preparation of (8S, 20f?) - de-A, B-8-benzoyloxy-20 - [(4R) -hydroxypentyl] pregnane (9). A solution of compound 8 (46 mg, 0.12 mmol) in methanol (6 mL) is hydrogenated for 17 h in the presence of 10% palladium in powdered charcoal (7 mg). The reaction mixture is filtered through a pad of Celite with several methanol washes, the filtrate is concentrated and the residue is chromatographed on silica gel with hexane / ethyl acetate (95: 5) to give the product 9 (31 g. , 69% yield): [a] D +61.3 (c 0.65, CHCI3); 1 H NMR (400 MHz, CDCl 3 + TMS) d 8.06 (2H, m, O-HBZ), 7.56 (1H, m,? -? ß?), 7.45 (2H, m, m-HBz), 5.41 (1 H , d, J = 1.5 Hz, 8a -H), 3.80 (1H, m, 25-H), 2.04 (2H, m), 1.83 (2H, m), 1.19 (3H, d, J = 6.2 Hz, 27-H3), 1.04 (3H, s, 18-H3). 0.95 (3H, d, J = 6.5 Hz, 21-H3); 13 C NMR (100 MHz): 166.50 (s, C = 0), 132.66 (d, p-CBz), 130.91 (s, ¡-CBz), 129.54 (d, O-CBZ), 128.33 (d, m-CBz) ), 72.25 (d, C-8), 68.27 (d, C-25), 56.33 (d), 51.61 (d), 41.92 (s, C-13), 39.92 (t), 39.84 (t), 35.70 (t), 35.37 (d), 30.55 (t), 27.09 (t), 23.49 (q, C-27), 22.64 (t), 22.21 (t), 18.55 (q, C-21), 18.02 (t ), 13.53 (q, C-18); MS (El) m / z 372 (11, M +), 354 (2, M + -H20), 327 (0.5, M + -C2H50), 285 (1, M + -C5H11O), 267 (4, M + -PhCO), 250 (58, M + -PhCOOH), 232 (28), 217 (7), 163 (31), 135 (67), 105 (100); exact mass calculated for C24H3603 (M +) 372.2664, found 372.2672. Preparation of (8S, 20?) - de-A, B-8-benzoyloxy-20 - [(4f?) -tert-butyldimethylsilyloxy-pentylpregnano (10). ter-Butyldimethylsilyl trifluoromethanesulfonate (37 μ ?, 42 mg, 0.16 mmol) is added to a solution of alcohol 9 (30 mg, 0.08 mmol) and 2,6-lutidino (37 μL, 34 mg, 0.32 mmol) in sodium chloride. anhydrous methylene (3 mL) at -20 degrees C. The mixture is stirred under argon at 0 degrees C for 1 hour. The reaction is neutralized with water and extracted with methylene chloride. The combined organic phases were washed with brine, dried (Na 2 SO 4) and concentrated under reduced pressure. The residue is chromatographed on silica gel with hexane and hexane / ethyl acetate (97: 3) to give product 10 (39 g, 100%): [cc] D +42.7 (c 0.85, CHCl3); 1 H NMR (400 MHz, CDCl 3) d 8.06 (2H, m, o-HBZ). 7.55 (1 H, m, p-HBZ), 7.44 (2H, m, m-? ß?). 5.41 (1 H, s, 8a -H), 3.77 (1 H, m, 25-H), 2.04 (2H, m), 1.84 (2H, m), 1.1 1 (3H, d, J = 6.0 Hz, 27-H3), 1.04 (3H, s, 18-H3), 0.93 (3H, d, J = 6.5 Hz, 21-H3), 0.89 (9H, s, Si-t-Bu), 0.05 (6H, s , SiMe2); 13 C NMR (100 MHz) d 166.50 (s, C = 0), 132.65 (dp-Cez), 130.93 (s, i-CBz), 129.55 (d, o-CBz), 128.33 (d, m-Cez), 72.27 (d, C-8), 68.68 (d, C-25), 56.51 (d), 51.63 (d), 41.92 (s, C-13), 40.20 (t), 39.96 (t), 35.74 (t ), 35.40 (d), 30.57 (t), 27.09 (t), 25.91 (q, SiCMe3), 23.81 (q, C-27), 22.65 (t), 22.25 (t), 18.51 (q, C-21) ), 18.17 (s, SiCMe3), 18.04 (t), 13.54 (q, C-18), -4.37 (q, SiMe), -4.68 (q, SiMe); MS (El) m / z 485 (1, M + -H), 471 (1, M + -CH3), 307 (16, M + -PhCOOH-C4H9), 233 (40, M + -PhCOOH -t-BuSiMe20), 197 (58), 179 (55), 159 (79), 137 (64), 123 (80), 109 (100); exact mass calculated for C26H4103Si (M + -C4H9) 429.2825, found 429.2843. Preparation of (8S, 20R) -de-A, B-20 - [(4f?) - tert -butyldimethylsilyloxypentyl] pregnan-8-ol (1). A solution of sodium hydroxide in ethanol (2.5M, 2 mL) is added to a stirred solution of benzoate 10 (38 mg, 78 pmoles) in anhydrous ethanol (10 mL) and the reaction mixture is refluxed with water. h. The mixture was cooled to room temperature, neutralized with 5% aq HCl. and extract with dichloromethane. The combined organic phases were washed with NaHCO3 dried (a2SO4) and evaporated. The residue is chromatographed on silica gel with hexane / ethyl acetate (95: 5) to give the alcohol 1 1 (22 g, 74% yield): [] D +19.2 (c 0.4, CHCl3); 1 H NMR (400 MHz, CDCl 3 + TMS) d 4.07 (1 H, d, J = 1.6 Hz, 8 at -H), 3.77 (1 H, m, 25-H), 2.00 (1 H, m), 1.82 (3H, m), 1.11 (3H, d, J = 6.1 Hz, 27-H3), 0.93 (3H, s, 18-H3), 0.89 (3H, d, 21-H3) covered by 0.89 (9H, s , Si-t-Bu), 0.05 (6H, s, SiMe2); 13 C NMR (100 MHz) d 69.46 (d, C-8), 68.72 (d, C-25), 56.76 (d), 52.65 (d), 41.87 (s, C-13), 40.43 (t), 40.25 (t), 35.78 (t), 35.24 (d), 33.61 (t), 27.15 (t), 25.92 (q, SiCMe3), 23.81 (q, C-27), 22.53 (t), 22.30 (t), 18.47 (q, C-2 I), 18.16 (s, SiCMe3), 17.45 (t), 13.53 (q, C-18), -4.37 (q, SiMe), -4.68 (q, SiMe); MS (El) m / z 382 (0.5, M +), 367 (1, Ivf -CH3), 325 (3, + C4H9), 307 (3, M + -C4H9 -H20), 233 (48), 191 ( 22), 177 (38), 163 (60), 135 (79), 123 (61), 109 (76), 97 (84), 75 (100); exact mass calculated for C19H3702S¡ (M + -C4H9) 325.2563, found 325.2574. Preparation of (20R) -de-A, B-20 - [(4R) -ter-butyldimethylsilyloxypentyl] pregnan-8-one (12). Pyridinium dichromate (110 mg, 293 pmoles) is added to a solution of alcohol 11 (22 mg, 58 pmol), and pyridinium p-toluenesulfonate (3 mg, 12 pmol) in anhydrous methylene chloride (6 mL). The resulting suspension is stirred at room temperature for 3 h. The reaction mixture is filtered through a Waters silica Sep-Pak cartridge (5 g) which is further washed with hexane / ethyl acetate (8: 2). After removing the solvents, the ketone 12 (18 mg, 82% yield) is obtained as a colorless oil: [α] D -4.8 (c 1.05, CHCl 3); 1 H NMR (400 MHz, CDCl 3 + TMS) d 3.77 (1 H, m, 25-H), 2.44 (IH, dd, J = 11.5, 7.5 Hz), 1.12 (3H, d, J = 6.1 Hz, 27- H3), 0.95 (3H, d, J = 6.0 Hz, 21-H3), 0.89 (OH, s, Si-t-Bu), 0.64 (3H, s, 18-H3), 0.05 (6H, s, SiMe2 ); 13 C NMR (100 MHz) d 2 11.99 (s, GO), 68.63 (d, C-25), 62.01 (d), 56.78 (d), 49.92 (s, C-13), 40.96 (t), 40.15 ( t), 39.03 (t), 35.79 (t), 35.47 (d), 27.50 (t), 25.90 (q, SiCMe3), 24.05 (t), 23.79 (q, C-27), 22.24 (t), 19.06 (t), 18.64 (q, C-21), 18.15 (s, SiCMe3), 12.47 (q, C-18), -4.36 (q, SiMe), -4.70 (q, SiMe); MS (El) m / z 379 (3, M + -H), 365 (1 1, M + -CH 3), 323 (75, M + -C 4 H 9), 231 (46), 189 (55), 175 (78), 161 (100), 149 (90); exact mass calculated for C19H3502Si (M + -C4H9) 323.2406, found 323.2420. Preparation of (20f?, 25R) -2-Methylene-19,26-dinor-1 a, 25-dihydroxyvitamin D3 (15). To a solution of phosphine oxide 13 (105 mg, 180 pmoles) in anhydrous THF (1 mL) at -20 degrees C, PhLi is added slowly (1.8 M in di-n-butyl ether, 120 μ? _, 216 μmol) under argon with agitation. The solution turned to intense orange. After 30 minutes the mixture was cooled to -78 degrees C and a pre-cooled ketone solution (-78 degrees C) in anhydrous THF (300 + 200 μL) was added slowly. The mixture is stirred under argon at -78 degrees C for 3 hours and at 0 degrees C for 18 h. Ethyl acetate is added, and the organic phase is washed with brine, dried (Na2SO4) and evaporated. The residue is dissolved in hexane and applied in a Waters silica Sep-Pak cartridge (2 g). The cartridge is washed with hexane and hexane / ethyl acetate (99.5: 0.5) to give derivative 19-norvitamin 14 (35.5 mg, 100% yield); then the Sep-Pak was washed with ethyl acetate to recover diphenylphosphine oxide 13 (62 mg): UV (in hexane) Á max 263.2, 253.2, 244.6 nm; 1 H NMR (400 MHz, CDCl 3) d 6.22 and 5.85 (each 1 H, each d, J = 11.1 Hz, 6- and 7-H), 4.98 and 4.93 (each IH, each s, = CH2) , 4.43 (2H, m, 1 ß- and 3a -H), 3.78 (1 H, m, 25-H), 2.83 (1H, dm, J = 12.1 Hz, 9β-H), 2.52 (1H, dd, J = 13.3.6.1 HZ, 10 to -H), 2.47 (1 H, dd, J = 12.9, 4.4 Hz, 4H), 2.34 (1 H, dd, J = 13.3.2.8 Hz, 10 /? - H), 2.18 (1 H, dd, J = 12.5, 8.6 Hz, 4 /? - H), 2.00 (2H, m), 1.12 (3H, d, J = 6.0 Hz, 27-H3), 0.93 (3H , d, J = 6.4 Hz, 21-H3), 0.901 (9H, s, Si-t-Bu), 0.897 (9H, s, Si-t-Bu), 0.871 (9H, s, Si-t-Bu ), 0.551 (3H, s, 18-H3), 0.084 (3H, s, SiMe), 0.071 (3H, s, SiMe), 0.056 (9H, s, 3 x SiMe), 0.031 (3H, s, SiMe); 13 C NMR (100 MHz) d 153.03 (s, C-2), 141.24 (s, C-8), 132.70 (s, C-5), 122.45 (d, C-6), 116.13 (d, C-7) ), 106.24 (t, = CH2), 72.55 and 71.69 (each d, C-1 and C-3), 68.73 (d, C-25), 56.68 (d), 56.33 (d), 47.64 (t) , 45.70 (s, C-13), 40.66 (t), 40.24 (t), 38.61 (t), 36.11 (d), 35.94 (t), 28.78 (t), 27.72 (t), 25.94 (q, SiCMe3 ), 25.85 (q, SiCMe3), 25.80 (q, SiCMe3), 23.80 (q, C-27), 23.47 (t), 22.39 (t), 22.24 (t), 18.77 (q, C-21), 18.26 (s, SiCMe3), 18.17 (s, 2 x SiCMe3), 12.09 (q, C-18), -4.35 (q, SiMe), -4.66 (q, SiMe), -4.85 (q, 2 x SiMe), -4.88 (q, SiMe), -5.07 (q, SiMe); MS (El) m / z 497 (24, M + -t-BuMe2SiOH-t-BuMe2Si) 480 (11, M + -2t-BuMe2SiOH 366 (61), 351 (24), 271 (15), 257 (24), 234 (33), 197 (25) 147 (36), 73 (100), exact mass calculated for C44H8403S3Na (MNa +) 767.5626, found 767.5640. Protected vitamin 14 (35.4 mg, 48 pmol) is dissolved in THF ( 4 mL) and acetonitrile (4 mL) A solution of 48% acetic HF in acetonitrile (ratio 1: 9 4 mL) is added at 0 degrees C and the resulting mixture is stirred at room temperature for 2 h. NaHCO 3 Solution The saturated organic phase is added and the reaction mixture is extracted with ethyl acetate.The combined organic phases are washed with brine, dried (Na2SO4) and concentrated under reduced pressure.The residue is diluted with 2 mL of hexane / ethyl acetate (9: 1) and applied in a Waters silica Sep-Pak cartridge (2 g), an elution with hexane / ethylene acetate (9: 1, then 7: 3) gave the crude product 15 (21 mg). by reverse phase HPLC [Zorbax Eclipse XDB-C 18 column 9.4 x 250 mm, 4 mL / min, methanol / water solvent system (85: 15), Rt = 9.7 min.] To give a colorless oil (15.06 mg, 78% yield): UV (in EtOH) max 262.0, 252.5 244.3 nm; 1 H NMR (600 MHz, CDCl 3) d 6.35 and 5.88 (1 H and 1 H, each d, J = 11.2 Hz, 6-and 7-H), 5. and 5.01 (each IH, each s, = CH2) , 4.47 (2H, m, 1 ß- and 3a -H), 3.80 (1H, m, 25-H), 2.84 (1H, dd, J = 13.3, 4.5 Hz, 10? -H), 2.81 (1H , m, 9 /? - H), 2.57 (1H, dd, J = 13.3, 3.7 Hz, 4aH), 2.32 (1H, dd, J = 13.3, 6.2 Hz, 4ß-), 2.29 (1 H, dd, J = 13.3, 8.4 Hz, 10 «-H), 1.19 (3H, d, J = 6.2 Hz, 27-H3), 0.93 (3H, d, J = 6.3 Hz, 21-H3), 0.551 (3H , s, 18-H3); 13 C NMR (100 MHz) d 152.02 (s, C-2), 143.36 (s, C-8), 130.44 (s, C-5), 124.22 (d, C-6), 115.31 (d, C-7) ), 107.67 (t, = CH2), 71.80 and 70.68 (each d, C-1 and C-3), 68.29 (d, C-25), 56.49 (d), 56.33 (d), 45.80 (t) , 45.80 (s, C-13), 40.47 (t), 39.87 (t), 38.17 (t), 36.05 (d), 35.90 (t), 28.96 (t), 27.64 (t), 23.49 (q, C -27), 23.49 (t), 22.29 (2 xt), 18.78 (q, C-21), 12.08 (q, C-18); MS (El) m / z 402 (58, M +), 384 (4, M + -H20), 369 (4, M + -H20 -CH3), 351 (3.M + - 2H20 - CH3), 317 (18), 287 (21, m + - C7H150) , 269 (21), 251 (21), 233 (38), 177 (33), 163 (54), 135 (92), 105 (100); exact mass calculated for C26H 203 (M +) 402.3134, found 402.3142. Example II: BIOLOGICAL ACTIVITY (A) Linkage Vitamin D Receptor Test Material Source of Protein Whole-length recombinant rat receptor is expressed in Codon Plus RIL cells of E. coli BL21 (DE3) and purifies to homogeneity using two chromatography systems in different column. The first system was a nickel affinity resin that uses the C-terminal histidine tag in this protein. The protein that was eluted from this resin was further purified using ion exchange chromatography (S-Sepharose Fast Flow). Aliquots of the purified protein were rapidly frozen in liquid nitrogen and stored at -80 degrees C until used. For use in binding assays, the protein was diluted in TEDK50 (50 mM Tris, 1.5 mM EDTA, pH 7.4, 5 mM DTT, 150 mM KC1) with 0.1% Chaps detergent. The receptor protein and the ligand concentration are optimized such that no more than 20% of the added radiolabelled ligand binds to the receptor. Study drugs Unlabeled ligands were dissolved in ethanol and concentrations were determined using UV spectrophotometry (1, 25 (OH) 2D3: molar extinction coefficient = 18,200 and A max = 265 nm; Analogues: molar extinction coefficient = 42,000 and To max = 252 nm). Radio labeled ligand (3H-1, 25 (OH) 2D3 ~ 159 Ci / mmole) is added in ethanol to a final concentration of 1 nM. Test conditions Radiolabelled and unlabeled ligands were added to 100 mcl of the diluted protein at a final ethanol concentration < 10%, mixed and incubated overnight on ice, to reach the binding equilibrium. The next day, 100 mcl of hydroxylapatite sludge (50%) is added to each tube and mixed at 10-minute intervals for 30 minutes. The hydroxylapatite is harvested by centrifugation and then washed three t with Tris-EDTA buffer (50 mM Tris, 1.5 mM EDTA, pH 7.4) containing 0.5% Titron X-100. After the final wash, the granules were transferred to scintillation vials containing 4 ml of Biosafe II scintillation cocktail, mixed and placed in a scintillation counter. Total binding is determined from tubes containing only radiolabelling ligand. (B) Differentiation HL-60 Test Material Study Drugs The study drugs were dissolved in ethanol and the concentrations were determined using UV spectrophotometry. Serial dilutions were prepared in such a way that a range of drug concentrations could be tested without changing the final concentration of ethanol (<0.2%) present in the cell cultures. Cells Human promyelocytic leukemia cells (HL60) were developed in RPMI-1640 medium containing 10% fetal bovine serum. The cells were incubated at 37 degrees C in the presence of 5% C02. Test Conditions HL60 cells were coated at 1.2 x 10 5 cells / ml. Ten and eight hours after coating, the cells in duplicate were treated with the drug. Four days later, the cells were harvested and a nitro blue reduction assay was performed tetrazole (Collins et al., 1979; J. Exp. Med. 149: 969-974). The percent of differentiated cells is determined by counting a total of 200 cells and recording the number containing deposits of intracellular black-blue formazan. Verification of differentiation to monocytic cells is determined by measuring phagocytic activity (data not shown). (C) In vitro Transcription Assay Transcription activity is measured in ROS 1712.8 cells (bones) that were stably transfected with a 24-hydroxylase (240hase) promoter gene upstream of a luciferase reporter gene (Arbor et al., 1998). The cells were given a range of doses. Ten and seven hours after dosing, the cells were harvested and luciferase activities were measured using a luminometer. (Luciferase units relative RLU = relative luciferase units). (D) Intestinal Calcium Transport and Calcium Mobilization of Bones Male Sprague-Dawley Rats, Weanling, Underwent Diet 11 (Ca at 0.47%) + AEK for one week followed by Diet 11 (Ca at 0.02%) + AEK for 3 weeks. The rats were then fed a diet containing Ca at 0.47% for one week followed by two weeks on a diet containing 0.02% Ca. The dose administration began during the last week on the 0.02% calcium diet. Four consecutive ip doses were given approximately 24 hours apart. Twenty-four hours after the last dose, blood was taken from the severed neck and the serum calcium concentration was determined as a measure of calcium mobilization in bone. The first 10 cm of the intestine were also collected for intestinal calcium transport analysis using the inverted intestinal sac method. (E) Suppression of PTH and Hypercalcemia Species Adult female Sprague-Dawley rats are obtained from Harlan (Madison, Wl). Animal husbandry Upon receipt, the animals are identified by markings on the individual tails. The animals can then be housed in cages with a suspended stainless steel wire bottom. Each cage can contain an animal. The rooms of the animals are kept at a temperature of 20 to 22.2 degrees C (68 to 72 degrees F) and a relative humidity of 25 to 75%. The maintenance rooms are adjusted to provide 12 hours of light per day. Water and a purified rodent diet (Suda et al., Purified Rodent Diet-Diet 11) containing 0.47% and 0.3% phosphorus and fat-soluble vitamins A, D, E and K are provided ad libitum. Treatment Groups The animals were randomized to treatment groups (5 animals / group). All doses are administered intraperitoneally in 100 microliters of propylene glycol. Four to seven consecutive doses are given approximately 24 hours apart. The dose starts after the animals have been acclimatized for at least a week. Dose Preparation Control Material A. Negative Control Material Negative control material is prepared by volumetrically measuring ethanol (< 5%) and propylene glycol, mixing and then placing in storage at 2 to 8 degrees CB Positive Control Material 1 , 25 (OH) 2D3 is prepared by determining the concentration of a concentrated ethanol solution using UV spectrophotometry (extinction coefficient = 18,200, Á max = 265 nm). The required amount of 1, 25 (OH) 2D3 is measured volumetrically in propylene glycol, so that there is less than 5% ethanol in the final solution. The solution is mixed and then stored at 2 to 8 degrees C. Test Material Analogs are prepared by first determining the concentration of a concentrated ethanol solution using UV spectrophotometry (extinction coefficient = 42,000; Á max = 252 nm). The analogous solutions are then added volumetrically to propylene glycol, so that less than 5% ethanol in the final solution. The solution is mixed and stored at 2 to 8 degrees C. Method of Dosage Management Both control and test items are administered by intraperitoneal injection in 100 microliters for 4-7 consecutive days, separated by approximately 24 hours. 1, 25 (OH) 2D3 are administered for 4 consecutive days, while the test drugs are administered for 7 consecutive days. Serum PTH levels Twenty-four hours after the final dose, blood is collected from the tail artery and PTH concentration in bioactive serum is measured using the BioActive Intact PTH ELISA Kit from Immutopics, Inc. (San Clemente, CA) . Analysis of Calcium in Serum Twenty-four hours after the final dose, approximately 1 ml of blood is collected from the tail artery of each experimental animal. The blood is allowed to coagulate at room temperature and then centrifuge at 3000 x g for 15 minutes. The serum is transferred to a polypropylene tube and stored frozen at -20 degrees C. The calcium level is determined by diluting the serum in 0.1% lanthanum chloride and measuring the absorbance in an atomic absorption spectrophotometer (Perkin Elmer Model 3110 , Shelton, CT). (20R, 25) -2-Methylene-! 9,26-dinor-1? 25-dihydroxyvitamin D3 (RAK) binds the recombinant vitamin D receptor, and its binding is comparable with 1,25-dihydroxyvitamin D3 in this respect ( see Figure 1). Additionally, it is also active to stimulate the transcription of a reporter gene in stable form transfected in Ros17 / 2.8 cells (bone), indicating a higher biological activity as 1 a, 25-dihydroxyvitamin D3 (see Figure 5). It is also equally active as 1 a, 25-dihydroxyvitamin D3 to induce differentiation of HL-60 cells (see Figure 4). It has limited calcemic activity when measured either by intestinal calcium transport or bone calcium mobilization in equimolar quantities of dose 1 a, 25-dihydroxyvitamin D3 (see Figures 2 and 3). It has limited calcemic activity when measured by calcium mobilization in bones, even at 27 times the molar amount of the dose of 1 a, 25-dihydroxyvitamin D3 (See Figure 2). Accordingly, NEL is expected to possess significant activity to suppress parathyroid hormone levels in normal rats. Similarly, other similar compounds of the present invention as shown in formulas IA, IB, are expected to bind to the vitamin D receptor, stimulation in transcription of a reporter gene in stably transfected form in Ros 17 / 2.8 cells (bones), induce differentiation of HL-60 cells, have limited calcemic activity when measured either by intestinal calcium transport or calcium mobilization in bones that 1 a, 25-dihydroxyvitamin D3 and possess significant activity to suppress levels of parathyroid hormone in normal rats. Accordingly, this RAK compound and other compounds described in the invention should find their uses in the treatment of autoimmune diseases such as multiple sclerosis, type I diabetes, rheumatoid arthritis, lupus, and other similar degenerative diseases. There will also be activity significant to treat malignant growth such as colorectal, breast and prostate cancers. All these activities should be evident in the absence of raising serum calcium concentrations (see Figures 2 and 3). This compound should also be useful for treating secondary hyperparathyroidism in patients who have lost kidney function such as those on hemodialysis or peritoneal dialysis. In one embodiment, the compound of the formula IA or IB is used in a pharmaceutical composition. For example, each mi of the pharmaceutical composition can comprise 5 jug of the compound, 30% (v / v) of propylene glycol and 20% (v / v) of alcohol. The compounds of the invention are also useful for preventing or treating obesity, inhibiting adipocyte differentiation, inhibiting transcription of SCD-1 gene, and / or reducing body fat in animal subjects. Therefore, in some embodiments, a method for preventing or treating obesity, inhibiting adipocyte differentiation, inhibiting transcription of SCD-1 gene, and / or reducing body fat in an animal subject, includes administering to the animal subject, an effective amount of the compound or a pharmaceutical composition that includes the compound. The administration of the compound or the pharmaceutical composition to the subject inhibits adipocyte differentiation, inhibits gene transcription and / or reduces body fat in the animal subject. For treatment purposes, the compounds defined by formula I, ie formula IA, and formula IB, and formula II, ie formulas IIA and IIB are formulated for pharmaceutical applications as a solution in harmless solvents, or as an emulsion, suspension or dispersion in suitable solvents or carriers, or as pills, tablets or capsules, together with solid carriers, according to conventional methods known in the art. Any of these formulations may also contain other pharmaceutically acceptable and non-toxic excipients such as stabilizers, anti-oxidants, binders, coloring agents or emulsifiers or agents. taste modifiers Acceptable pharmaceutically acceptable carriers and carriers are generally known to those of skill in the art and are thus included in the present invention. These excipients and carriers are described, for example, in "Remingtons Pharmaceutical Sciences" Mack Pub. Co., New Jersey (1991). The compounds are administered orally, topically, parenterally or transdermally. The compounds are advantageously administered by injection or by intravenous infusion or suitable sterile solutions, or in the form of liquid or solid doses through the alimentary canal, or in the form of creams, ointments, patches or similar vehicles suitable for transdermal applications. In some embodiments, doses of 0.001 // g to about 1 mg per day of the compound are appropriate for treatment purposes. In some of these embodiments, an appropriate and effective dose may be in the range of 0.01 μg to 1 mg per day of the compound. In other of these embodiments an appropriate and effective dose may be in the range of 0.1 μg to 500 μg per day of the compound. These doses will be adjusted according to the type of disease or condition to be treated, the severity of the disease or condition, and the response of the subject, as is well understood in the art. The compound is conveniently administered alone, or together with another active vitamin D compound. In one embodiment, the compound of the formula NA is used in a pharmaceutical composition. For example, each mi of the pharmaceutical composition may comprise 5 μg of the compound, 30% (v / v) of propylene glycol and 20% (v / v) of alcohol. Compositions for use in the invention include an effective amount of (20f ?, 25f?) - 2-Methylene-l9,26-dinor-1 a, 25-dihydroxyvitamin D3 or (20S, 25R) -2-Methylene-l9.26 -dinor-1 a, 25-dihydroxyvitamin D3 as the active ingredient, and a convenient carrier. An effective amount of the compound to be used according to some embodiments of the invention will generally be a quantity of dose such as those described herein, and is administered topically, transdermally, orally, nasally, rectally or parenterally. In one embodiment, the dose is administered intraperitoneally. The compounds of formula IA, IB, HA or IIB are advantageously administered in amounts sufficient to effect the differentiation of promyelocytes with normal macrophages. Doses as described above are adequate, it being understood that the amounts given will have to be adjusted according to the severity of the disease, and the condition and response of the subject as well understood in the art. The compound is formulated as creams, lotions, ointments, aerosols, suppositories, topical patches, pills, capsules or tablets, or in liquid form as solutions, emulsions, dispersions or suspensions in pharmaceutically acceptable and acceptable oils or solvents, and these preparations may contain in addition other pharmaceutically harmless or beneficial components such as stabilizers, antioxidants, emulsifiers, coloring agents, binders or taste-modifying agents. The formulations of the present invention comprise an active ingredient in association with a pharmaceutically acceptable carrier thereof and optionally other therapeutic ingredients. The carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulations and not harmful to its recipient. Formulations of the present invention suitable for oral administration are in the form of discrete units such as capsules, sachets, tablets or lozenges, each containing a predetermined amount of the active ingredient; in the form of a powder or granules; in the form of a solution or suspension in an aqueous or non-aqueous liquid; or in the form of an oil-in-water emulsion or an emulsion of water-in-oil. Formulations for rectal administration are in the form of a suppository incorporating the active ingredient and carrier such as cocoa butter, or in the form of an enema. Formulations suitable for parenteral administration conveniently comprise a sterile aqueous or oily preparation of the active ingredient which is preferably isotonic with the blood of the container. Formulations suitable for topical administration include liquid or semi-liquid preparations such as liniments, lotions, application agents, oil-in-water or water-in-oil emulsions such as creams, ointments or pastes.; or solutions or suspensions such as drops; or as dews. For formulations of nasal administration, powder inhalation, self-propelling or nebulization, assorted with a spray can or nebulization, an atomizer or nebulizer may be employed. The formulations, when supplied, preferably have a particle size in the range of 10 to 100 microns. The formulations may conveniently be presented in the form of unit doses and are prepared by any of the methods well known in the pharmacy art. The term "dose unit" is understood to mean a unit dose, ie simple, that is capable of being administered to a patient as a physical and chemically stable unit dose comprising either the active ingredient as such or a mixture of diluents or carriers. solid or liquid pharmaceuticals. It is understood that the invention is not limited to the embodiments set forth herein for illustration, but encompasses all forms that fall within the scope of the following claims.

Claims (24)

1. CLAIMS 1. A compound that has the formula IA or IB wherein X1t X2 and X3 are independently chosen from H and hydroxy protecting groups; and R1 is chosen from straight or branched chain alkyl groups having from 1 to 8 carbon atoms; straight or branched chain alkenyl groups having from 2 to 8 carbon atoms; straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms; straight and branched chain hydroxy-substituted alkenyl groups which have 2 to 8 carbon atoms.
2. 2. The compound according to claim 1, characterized in that Xi, X2 and X3 are hydroxy protecting groups.
3. 3. The compound according to claim 2, characterized in that Xi, X2 and X3 are t-butyldimethylsilyl groups.
4. The compound according to claim 1, characterized in that X1 t X2 and X3 are H and R1 is CH3 and the compound has the formula IIA or IIB II B
5. 5. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
6. 6. The pharmaceutical composition according to claim 5, characterized in that the effective amount comprises from about 0.01 μ to about 1 mg of the compound per gram of the composition.
7. The pharmaceutical composition according to claim 5, characterized in that the effective amount comprises from about 0.1 ji / g to about 500 / g of the compound per gram of the composition.
8. 8. A method for treating a subject suffering from a biological condition, comprising administering an effective amount of the compound of claim 1 to the subject, wherein the biological condition is chosen from psoriasis; leukemia; colon cancer; breast cancer; Prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration, or insufficient sebum secretion; renal osteodystrophy; or osteoporosis.
9. 9. The method according to claim 8, characterized in that the biological condition is renal osteodystrophy, rickets resistant to vitamin D, osteoporosis or psoriatic arthritis.
10. The method according to claim 8, characterized in that the biological condition is chosen from leukemia, colon cancer, breast cancer, or prostate cancer. 1.
11. The method according to claim 8, characterized in that the biological condition is chosen from multiple sclerosis, lupus, diabetes mellitus, Host reaction against graft or rejection of organ transplants.
12. The method according to claim 8, characterized in that the biological condition is chosen from rheumatoid arthritis, asthma, or intestinal inflammatory diseases selected from celiac disease, ulcerative colitis and Crohn's disease.
13. 13. The method according to claim 8, characterized in that the biological condition is chosen from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration, or insufficient secretion of sebum.
14. The method according to claim 8, characterized in that the compound is administered orally, parenterally, transdermally or topically to the subject.
15. 15. The method according to claim 8, characterized in that the compound is administered intraperitoneally.
16. 16. The method according to claim 8, characterized in that the compound is administered in a dose of 0.01 // g per day to 1 mg per day.
17. 17. The use of the compound according to claim 1, in the preparation of a medicament for the treatment of a biological condition selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration, or insufficient sebum secretion; renal osteodystrophy; or osteoporosis.
18. 18. A cosmetic method to maintain a certain weight, promote cosmetic weight loss or promote beneficial skin conditions that include inhibiting wrinkles, improving the lack of adequate firmness of the skin, promoting adequate dermal hydration, or insufficient secretion of sebum, in an animal subject, the method is characterized in that it comprises using a compound of claim 1.
19. 19. The method of compliance with Claim 18, characterized in that the compound is provided in an amount equivalent to a dose range of about 0.01 μ per day to about I mg per day.
20. 20. The method according to any of claims 18-20, characterized in that the animal is a mammal.
21. 21. The method according to any of claims 18-21, characterized in that the mammal is a human.
22. 22. The compound that has the formula HA
23. 23. A pharmaceutical composition, comprising an effective amount of the compound of claim 22 and a pharmaceutically acceptable carrier.
24. 24. The use of the compound of claim 23, in the preparation of a medicament for the treatment of a biological condition selected from psoriasis; leukemia; colon cancer; breast cancer; prostate cancer; multiple sclerosis; lupus; Mellitus diabetes; host reaction against graft; rejection of organ transplants; an inflammatory disease selected from rheumatoid arthritis, asthma, or inflammatory bowel diseases; a condition of the skin selected from wrinkles, lack of adequate firmness of the skin, lack of adequate dermal hydration or insufficient sebum secretion; renal osteodystrophy; or osteoporosis.