Wisconsin Alumni Research Foundation

Daikin Industries, Ltd.

Other

Yoko Tanaka

Hector Floyd Deluca

Nobuo Ikekawa

Yoshiro Kobayashi

Heinrich K Schnoes

Rafal R Sicinski

Yutaka Ohira

Takeo Taguchi

Joseph K Wichmann

Joseph B Alper

Masuo Morisaki

Jun-ichi Oshida

Tadashi Eguchi

Herbert E Paaren

Katsuhiko Iseki

Tadabumi Nagai

Fluorine-containing vitamin D.sub.3 analogues of the formula [I]: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen atom, a chemically inactive hydroxy-protecting group, an acyl having 2 to 8 carbon atoms or an alkyl having 1 to 8 carbon atoms, and n is an integer of 4 to 6, which have excellent pharmacological activities, particularly anti-tumor activity owing to differentiation-inducing activity and are useful for the prophylaxis and treatment of various tumors and intermediates therefore.

Fluorine-containing vitamin D.sub.3 analogues and cell

Vitamin D.sub.3 analogues of the formula: ##STR1## wherein R.sup.1 is hydrogen atom and R.sup.2 is hydroxy, or R.sup.1 is hydroxy and R.sup.2 is hydrogen atom, X is hydrogen atom, hydroxy or a hydroxy protected by a hydroxy-protecting group, and R.sup.3 is hydrogen atom or a hydroxy-protecting group, which have vitamin D.sub.3 -like activities such as activity of controlling calcium metabolism and tumor cell differentiation-inducing activity.

Vitamin D.sub.3 analogues

Fluorine-containing vitamin D.sub.3 analogues of the formula[I]: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen atom, a chemically inactive hydroxy-protecting group, an acyl having 2 to 8 carbon atoms, or an alkyl having 1 to 8 carbon atoms, X is a straight carbon chain having 4 to 6 carbon atoms which contains at least one double or triple bond, which have excellent vitamin D.sub.3 -like activities, particularly anti-tumor activity owing to differentiation-inducing activity and are useful for the prophylaxis and treatment of various tumors, and intermediates therefor.

Fluorine-containing vitamin D3 analogues and pharmaceutical composition

Fluorine-containing vitamin D.sub.3 analogues of the formula: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen atom, a hydroxy-protecting group, having excellent pharmacological activities, such as tumor cell differentiation-inducing activity, which are useful as a medicament.

Fluorine-containing vitamin D3 analogues

The present invention provides novel derivatives of vitamin D.sub.2 and more specifically 1 alpha,25-dihydroxylated compounds of the vitamin D series. A process for the preparation of such derivatives is also provided as are certain intermediates in such process. The derivatives of this invention find ready application as substitutes for vitamin D.sub.3 or D.sub.2 or various of the known vitamin metabolites of these vitamins in their various applications to the correction of disorders involving calcium metabolism and associated bone disease.

Process for the preparation of 1 alpha,25-dihydroxylated vitamin D.sub.2

This invention is directed to new 24-homo-vitamin D compounds, to methods for preparing the same and novel intermediate compounds. The compounds are characterized by vitamin D-like activity of the order of 1.alpha.,25-dihydroxyvitamin D.sub.3, the recognized circulating hormonal form of vitamin D, or various of its derivatives and by greater antineoplastic activity than such compounds but without their attendant calcemic activity. The compounds are useful in the treatment of disease states characterized by calcium-phosphorous imbalances and where antineoplastic activity is indicated.

Hydroxylated 24-homo-vitamin D derivatives and methods for preparing same

This invention is directed to new 26-homo-vitamin D compounds, to methods for preparing the same and novel intermediate compounds.

Hydroxylated 26-homo vitamin D derivatives and methods for preparing same

The invention is directed to the preparation of hydroxylated compounds of the vitamin D.sub.2 series and specifically to a process for synthesizing 1.alpha.,25-dihydroxyvitamin D.sub.2, 1.beta.,25-dihydroxyvitamin D.sub.2, their corresponding 5,6-trans isomers and the C-24 epimers of these compounds. The hydroxylated vitamin D.sub.2 compounds obtained exhibit vitamin D-like activity and can be substituted for vitamin D.sub.3 or various of its known metabolites where such compounds are applied.

1,25-dihydroxyvitamin D.sub.2 compounds

The invention provides, as novel vitamin D derivatives, analogs of vitamin D.sub.2 compounds which lack the 24-methyl substituent and are identified as 1.alpha.-hydroxy-28-norvitamin D.sub.2 and 1.alpha.,25-dihydroxy-28-norvitamin D.sub.2. The compounds of the invention are characterized by unexpectedly high vitamin D-like activity as well as a novel activity pattern. Because of such activity they would find ready application as substitutes for vitamin D or various of the known vitamin D metabolites in their various application for the treatment of calcium disorders.

Fowl bone mineralization with 28-NOR 1.alpha.-hydroxyvitamin D.sub.2

Novel 1-hydroxylated vitamin D compounds containing a 22, 23-cis double bond in the side chain are provided. The compounds are characterized by an unexpectedly high binding affinity for the protein receptor forecasting their ready applicability as substitutes for vitamin D or various of its metabolites in their various known applications and in the treatment of various metabolic bone diseases.

Side-chain unsaturated 1-hydroxyvitamin D compounds

The invention provides a novel vitamin D derivative, 1.alpha.,25-dihydroxy-22Z-dehydrovitamin D.sub.2. The compound is characterized by unexpectedly high ability to raise serum calcium levels. The compound could therefore, find ready application as a substitute for vitamin D or its metabolites in the treatment of metabolic bone diseases or in other of their known applications.

1.alpha.,25-dihydroxy-22Z-dehydroxyvitamin D compound

The invention provides a new derivative of vitamin D.sub.3, 26,26,26,27,27-pentafluoro-1.alpha.-hydroxy-27-methoxy-cholecalciferol and a process for preparing the same. The compound is characterized by some vitamin D-like activity except that it exhibits negligible activity in mobilizing bone. This characteristic indicates that the compound would find ready application in the treatment of disease or physiological states which evince loss of bone mass and application in other situations where metabolic calcium imbalances are found.

26,26,26,27,27-pentafluoro-1.alpha.-hydroxy-27-methoxyvitamin D.sub.3

The invention provides new derivatives of vitamin D.sub.3, 2.alpha.-fluorovitamin D.sub.3 and the acylates thereof. The compounds are characterized by vitamin D-like activity in their ability to increase intestinal calcium transport and serum calcium indicating their ready application as substitutes for vitamin D.

2.alpha.-fluorovitamin D.sub.3

The invention provides new derivatives of vitamin D.sub.3 and specifically (22E,24R)-1,24-dihydroxy-.DELTA..sup.22 -vitamin D.sub.3 and (22E,24S)-1,24-dihdroxy-.DELTA..sup.22 -vitamin D.sub.3. The compounds exhibit vitamin D-like activity in their ability to stimulate intestinal calcium transport, increase serum inorganic phosphorous and mineralize bone indication ready application of the compounds in the treatment of various metabolic bone diseases. The characteristic of the compounds to not mobilize bone indicates that the compositions would find ready application in combination with vitamin D and various of its derivatives to achieve controlled bone mineralization.

1,24-dihydroxy-.DELTA..sup.22 -vitamin D.sub.3 and process for preparing

The invention provides new derivatives of vitamin D, 23,23-difluoro-25-hydroxycholecalciferol and the acylates thereof, a method for preparing said compounds and various new intermediates utilized in such process. The derivative compounds are characterized by vitamin D-like activity as evidenced by their ability to increase intestinal calcium transport and serum calcium. The compounds are further characterized by resistance to hydroxylation at C-23, which is recognized as an essential metabolic step to the inactivation of vitamin D. The compounds should, therefore, provide vitamin D-like activity of greater time duration.

Growing community of inventors

Madison, WI, United States of America

Yoko Tanaka