Abstract: A method of treating metabolic bone diseases such as osteoporosis, as well as other disease states treatable with vitamin D compounds, comprises administering an effective amount of one or more modified vitamin D compound. The modified compound contains a typical vitamin D nucleus but with in vivo hydrolyzable groups at one or more of the 1, 3 and 25 carbon positions. The time of conversion of the modified compound to its active form, such as calcitriol, can be regulated to thus provide controlled release of the compound in vivo over time, by changing or modifying the hydrolyzable groups.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1c-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided.

Abstract: In vitro incubation of all-trans-retinol (atROL) with kidney homogenate from vitamin A deficient and retinoic acid supplemented (VAD-RAS) female rats produced a new retinol metabolite. The metabolite has the structure ##STR1## and is believed useful for the treatment of skin disorders such as acne, psoriasis, and ultraviolet light skin damage, as well as for promoting female fertility and the maintenance of pregnancy.

Abstract: Disclosed are 20-epi-19-nor-vitamin D compounds having the structure: ##STR1## where each of X.sub.1 and X.sub.2 independently represents hydrogen or a hydroxy-protecting group, and Z represents various known side chains.

Abstract: The invention provides new 24, 26, and/or 27 homologated vitamin D.sub.2 compounds, such as 26,27-dihomo-1.alpha.-hydroxyvitamin D.sub.2, 26,27-dihomo-1.alpha.-hydroxy-24-epivitamin D.sub.2, 26,27-dihomo-1.alpha.,25-dihydroxy-24-epi-vitamin D.sub.2 and certain hydroxy-protected derivatives thereof. The new epi compounds in particular exhibit a distinctive activity pattern comprising high potency in stimulating intestinal calcium transport and little or no activity in inducing bone calcium mobilization or the differentiation of undifferentiated cells in culture, thereby evincing utility in the treatment of diseases characterized by loss of bone mass. In contrast, the natural form exhibits no activity in either mobilizing calcium from bone or stimulating intestinal calcium transport. A process for preparing such compounds is also disclosed.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided.

Abstract: A 19-nor intermediate compound of the formula ##STR1## where R is the sidechain of a vitamin D derivative and where X.sub.1 and X.sub.2 are hydrogen or a hydroxy protecting group. The compounds are used in the preparation of 19-nor-vitamin D end products.

Abstract: Cyclohexylidene compounds of the structure: ##STR1## where X.sup.1 and X.sup.2, which may be the same or different, is hydrogen or a hydroxy-protecting group, and Y is --POPh.sub.2, or --PO (OAlkyl).sub.2, or --SO.sub.2 Ar, or --Si(Alkyl).sub.3. The compounds are used as intermediates in the preparation of 19-nor-vitamin D compounds.

Abstract: A synthesis of 1.alpha.-hydroxy-19-nor-vitamin D compounds comprises (a) the construction of a 5,8-diol-6-yne intermediate by joining ring-A and ring-C/D portions of the desired end product via the condensation of an acetylenic derivative containing the C/D-ring portion of the desired end product with a cyclic dihydroxy ketone representing the A-ring of the desired end product; (b) the partial reduction of the 6,7 acetylenic triple bond linkage between the A and C/D ring portions to obtain a 5,8-diol-6-ene intermediate; and (c) the reductive removal of the 5,8-oxygen functions to generate the required 5,7-diene end product from which the desired 7-trans(7E)-isomer is purified directly, or after optional double bond isomerization of the 7-cis(7Z)-isomer employing a novel thiophenol-promoted isomerization step.

Abstract: The invention is drawn to a compound having the following formula ##STR1## in which X.sup.1 and X.sup.2, which may be the same or different, represent hydrogen or a hydroxy-protecting group, X.sup.4 is hydrogen, A is selected from --COOAlkyl and CH.sub.2 OH, and B is a hydroxy group, or A and B, when taken together, represent an oxo group. These compounds are useful as intermediates in the production of 19-nor vitamin D derivatives.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided. The 19-nor vitamin D compounds have the formula: ##STR1## where X.sup.1 and X.sup.2 are each hydrogen or a hydroxy protecting group and R is a side chain.

Abstract: A convergent synthesis of 19-nor-vitamin D compounds, specifically 19-nor-1.alpha.,25-dihydroxyvitamin D.sub.3, is disclosed. The synthesis can also readily be utilized for preparing other 1.alpha.-hydroxylated 19-nor-vitamin D compounds. The key step in the synthesis is a suitable application of Lythgoe's procedure i.e. a Horner-Wittig reaction of the lithium anion of a phosphine oxide with a Windaus Grundmann ketone to give, after any necessary deprotection, the desired 19-nor-vitamin D compound.

Abstract: A process is disclosed for the removal of the 4-protected hydroxy group from compounds of the following formula: ##STR1## where A is --COOAlkyl and B is hydroxy, or A and B together represent either oxo or .dbd.CHCOOAlkyl, where X.sup.1 and X.sup.2 are the same or different and represent hydrogen or a hydroxy-protecting group, and where X.sup.3 is ##STR2## with a hydrogen radical source, such as tributyltin hydride or tris(trimethylsilyl)silane, and a radical initiator, such as AIBN or irradiation.

Abstract: This invention provides a novel class of vitamin D-related compounds, namely the 1.alpha.-hydroxy-19-nor-vitamin D analogs, as well as a general method for their chemical synthesis. The compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells, including malignant cells, and in inducing their differentiation, and thus represent novel therapeutic agents for the treatment of malignant and other diseases characterized by the proliferative growth of undifferentiated cells. Formulations for therapeutic use and treatment methods are also provided. The 19-nor analogs useful herein are of the general formula ##STR1## where X.sup.1 and X.sup.2 each hydrogen, acyl, alkylisilyl or alkoxyalkyl, and where R is any of the typical side chains known for vitamin D type compounds.

Abstract: The invention provides new 24, 26, and/or 27 homologated vitamin D.sub.2 compounds, such as 26,27-dihomo-1.alpha.-hydroxyvitamin D.sub.2, 26,27-dihomo-1.alpha.-hydroxy-24-epivitamin D.sub.2, 26,27-dihomo-1.alpha.,25-dihydroxy-24-epivitamin D.sub.2 and certain hydroxy-protected derivatives thereof. The new epi compounds in particular exhibit a distinctive activity pattern comprising high potency in stimulating intestinal calcium transport and little or no activity in inducing bone calcium mobilization or the differentiation of undifferentiated cells in culture, thereby evincing utility in the treatment of diseases characterized by loss of bone mass. In contrast, the natural form exhibits no activity in either mobilizing calcium from bone or stimulating intestinal calcium transport. A process for preparing such compounds is also disclosed.

Abstract: The invention describes intermediates for use in the synthesis of 1.alpha.-hydroxy-19-nor-vitamin D compounds. The intermediates have the following formula: ##STR1## The disclosed process includes (a) the construction of a 5,8-diol-6-yne intermediate by joining ring-A and ring-C/D portions of the desired end product via the condensation of an acetylenic derivative containing the C/D-ring portion of the desired end product with a cyclic dihydroxy ketone representing the A-ring of the desired end product; (b) the partial reduction of the 6,7 acetylenic triple bond linkage between the A and C/D ring portions to obtain a 5,8-diol-6-ene intermediate; and (c) the reductive removal of the 5,8-oxygen functions to generate the required 5,7-diene end product from which the desired 7-trans(7E)-isomer is purified directly, or after optional double bond isomerization of the 7-cis(7Z)-isomer employing a novel thiophenol-promoted isomerization step.

Abstract: A synthesis of 1.alpha.-hydroxy-19-nor-vitamin D compounds comprises (a) the construction of a 5,8-diol-6-yne intermediate by joining ring-A and ring-C/D portions of the desired end product via the condensation of an acetylenic derivative containing the C/D-ring portion of the desired end product with a cyclic dihydroxy ketone representing the A-ring of the desired end product; (b) the partial reduction of the 6,7 acetylenic triple bond linkage between the A and C/D ring portions to obtain a 5,8-diol-6-ene intermediate; and (c) the reductive removal of the 5,8-oxygen functions to generate the required 5,7-diene end product from which the desired 7-trans(7E)-isomer is purified directly, or after optional double bond isomerization of the 7-cis(7Z)-isomer employing a novel thiophenol-promoted isomerization step.

Abstract: New compounds of the formula ##STR1## where Y' represents hydroxy, protected-hydroxy, O-tosyl, O-mesyl, bromine, chlorine, or iodine and X.sup.1 and X.sup.2 may independently represent hydrogen or a hydroxy-protecting group are useful as intermediates for the production of 19-nor vitamin D derivatives, particularly 1.alpha.,25-dihydroxyvitamin D.sub.3, from (-)quinic acid.