Wisconsin Alumni Research Foundation

Kureha Kagaku Kogyo Kabushiki Kaisha

Daikin Industries, Ltd.

Taisho Pharmaceutical Co., Ltd.

Nihon Nohyaku Co., Ltd.

Cac Corporation

Yoshiro Kobayashi

Nobuo Ikekawa

Yoko Tanaka

Hector Floyd Deluca

Takahiro Suzuki

Takashi Yamauchi

Itsumaro Kumadaki

Masaaki Takahashi

Takeo Taguchi

Heinrich K Schnoes

Yutaka Ohira

Tadashi Eguchi

Hitoshi Kurono

Katsuhiko Iseki

Akira Iizuka

Tsumoru Kodaira

Tadabumi Nagai

Yoshinori Inagaki

Iori Sakai

Yoshinori Kume

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

A fluorine-containing vitamin D.sub.2 derivative represented by the following formula ##STR1## wherein R.sup.1 represents a methyl or trifluoromethyl group, and R.sup.2 represents a trifluoromethyl group when R.sup.1 is a methyl group, and a hydrogen atom or a methyl group when R.sup.1 is a trifluoromethyl group. This compound is useful for the prevention or treatment of calcium pathobolism or osteoporosis.

Fluorine-containing vitamin D.sub.2 derivatives

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

A novel compound of 2-[para-(2-substituted or unsubstituted-3,3,3-trifluoropropyl)phenyl]propionic acid or a salt thereof which has a specific pharmacological activity and a pharmaceutical composition comprising the novel compound as an active ingredient are disclosed.

2-[Para-(2-substituted or

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.

23,23-Difluoro-25-hydroxy-vitamin D.sub.3 and process for preparing same

The invention provides new derivatives of vitamin D, 23,23-difluoro-1,25-dihydroxycholecalciferol and the acylates thereof. The derivative compounds are characterized by vitamin D-like activity.

23,23-Difluoro-1.alpha.,25-dihydroxy-vitamin D.sub.3

The invention provides a new derivative of vitamin D, 23,23-difluoro-1,25-dihydroxycholecalciferol. The compound is characterized by vitamin D-like activity as evidenced by its ability to increase intestinal calcium transport. It is further characterized by its resistance to hydroxylation at C-23, which is recognized as an essential metabolic step to the inactivation of vitamin D, and therefore should provide vitamin D-like activity of greater time duration.

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

A novel trifluoropropyl derivative of mono-substituted benzene represented by the general formula: ##STR1## wherein R is halogen atom, hydroxy, trifluoromethyl, n-octyl, n-dodecyl, or phenoxy group not substituted or mono-substituted by 3,3,3-trifluoropropyl group, and n is an integer of 1, 2 or 3, with the proviso that the total number of 3,3,3-trifluoropropyl group of the derivative of mono-substituted benzene is at most 3, and a process for producing the derivative of mono-substituted benzene.

Process for producing 3,3,3-trifluoropropyl substituted phenol

A novel trifluoropropyl derivative of mono-substituted benzene represented by the general formula: ##STR1## wherein R is halogen atom, trifluoromethyl, n-octyl, n-dodecyl, or phenoxy group not substituted or mono-substituted by 3,3,3-trifluoropropyl group, and n is an integer of 1, 2 or 3, with the proviso that the total number of 3,3,3-trifluoropropyl group of the derivative of mono-substituted benzene is at most 3, and a process for producing the derivative of mono-substituted benzene.

Substituted benzene derivatives having at least one benzene ring

Novel trifluoropropyl-substituted aryl- or aralkylbenzene of the formula: ##STR1## wherein R is a not-substituted or ring-substituted phenyl-, benzyl-, phenethyl- or alpha-methylbenzyl group by one 3,3,3-trifluoropropyl group, and n is an integer of 1,2 or 3, provided that the total number of 3,3,3-trifluoropropyl group of the above-mentioned trifluoropropyl-substituted aryl- or aralkylbenzene is at most 3, and a process for producing thereof are disclosed.

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Tokyo, Japan

Yoshiro Kobayashi