Sumitomo Chemical Company, Limited

Taisho Pharmaceutical Co., Ltd.

Sumitomo Pharmaceuticals Company Limited

Noritaka Hamma

Masayoshi Minai

Shunji Aono

Yoshio Suzuki

Eiichi Murayama

Takashi Katsumata

Toshio Nishizawa

Yoshikazu Saito

Takenari Nakagome

Toshitsugu Fukumaru

Kaoru Maeshima

Masataka Fukumura

Katsuyuki Toki

Hideaki Fukushima

Itsuro Sugata

Hiroshi Nakatani

There are disclosed herein novel derivatives of 26,26,26,27,27,27-hexafluorovitamin D.sub.3 providing excellent pharmacological effects, and a process for the preparation thereof. These novel compounds are represented by the general formula ##STR1## wherein R.sub.1 and R.sub.2 each denotes a hydrogen atom or a protecting group for the hydroxyl group; R.sub.3 and R.sub.4 each denotes a hydrogen atom, a hydroxyl group or a protected hydroxyl group and R.sub.4 ' and R.sub.5 ' each denotes a hydrogen atom, or alternatively R.sub.3 and R.sub.3 ' together or R.sub.4 and R.sub.4 ' together denote an oxo group; provided that R.sub.3, R.sub.3 ', R.sub.4 and R.sub.4 ' cannot denote hydrogen atoms simultaneously. The process for the preparation comprises subjecting a previtamin D.sub.3 derivative represented by the formula ##STR2## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.3 ', R.sub.4 and R.sub.4 ' are as defined above, to thermal isomerization to give a vitamin D.sub.3 derivative represented by the general formula ##STR3## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.3 ', R.sub.4 and R.sub.4 ' are as defined above, and optionally subjecting it to a deprotection reaction.

Fluorine derivatives of vitamin D.sub.3 and process for producing the

There are disclosed novel derivatives of 26,26,26,27,27,27-hexafluorovitamin D.sub.3 having fluorine atom at the 23- and/or 24-position which have an excellent pharmacological activity and a process for production thereof. The novel compounds are represented by the general formula: ##STR1## wherein R.sub.1 ' denotes a hydrogen atom, a hydroxyl group or a protected hydroxyl group, R.sub.2 denotes a hydrogen atom or a protecting group for hydroxyl group, R.sub.3 denotes a hydrogen atom, a fluorine atom, a hydroxyl group or a protected hydroxyl group and R.sub.4 and R.sub.4 ' each denotes a hydrogen atom, or one of them denotes a hydrogen atom and the other denotes a fluorine atom, hydroxyl group or a protected hydroxyl group or R.sub.4 and R.sub.4 ' are combined to denote an oxo group, with a proviso that at least one of R.sub.3, R.sub.4 and R.sub.4 ' denote a fluorine atom. The process for production thereof comprises subjecting to thermal isomerization a compound represented by the general formula: ##STR2## wherein R.sub.1 ', R.sub.2, R.sub.3, R.sub.4 and R.sub.4 ' are the same as defined above, to thermal isomerization and optionally further to deprotection reaction.

Bisphenoxy carboxylic acid derivatives useful as an antiarteriosclerosis agent with good absorbability and low toxicity, which are novel compounds represented by the general formula, ##STR1## wherein R.sub.1 and R.sub.2 represent hydrogen atoms or lower alkyl groups and A preresents ##STR2## (wherein in case R.sub.3 is a hydrogen atom, R.sub.4 represents an amino-lower-alkyl group, an N-lower-alkylaminoalkyl group, a heterocyclic group, or a heterocyclic group-substituted alkyl group; or R.sub.3 and R.sub.4 may join through an intermediary hetero atom to form a heterocyclic group and if said hetero atom is a nitrogen atom, this nitrogen atom can bear a lower alkyl group as a substituent) or ##STR3## (wherein R.sub.5 represents a hydrogen atom, a hydroxyalkyl group or a derivative thereof, and R.sub.6 represents a hydroxyalkyl group or a heterocyclic group; or R.sub.5 and R.sub.6 may join to form a cyclic group, or may join through another intermediary hetero atom to form a heterocyclic group and if said hetero atom is a nitrogen atom, this nitrogen atom can bear a lower alkyl group as a substituent).

Diheterocyclic esters of 4-(1,1-bis-(phenoxy-propionic or -butoyric

Novel anti-atherosclerosis agents having the formula, ##STR1## wherein R is hydrogen or lower alkyl, n and m each signify an integer of 4 - 6, and A is hydrogen or a group of the formula, ##STR2## WHEREIN R and m have the same meanings as defined above. These compounds are produced, for example, by reacting a bisphenolic compound of the formula, ##STR3## with chloroform and a ketone compound of the formula, ##STR4## in the presence of an alkali. Alternatively, they are produced by reacting the bisphenolic compound with .alpha.-halogeno- or .alpha.-hydroxycarboxylic acid derivative of the formula, ##STR5## wherein R and m have the same meanings as defined above, and X is halogen or hydroxyl.

Phenoxyalicyclic carboxylic acid derivatives

An improved process for producing a peptide and a cephalosporin which comprises treating a phosphoramide derivative of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are each an alkyl group, a cycloalkyl group, an aryl group or an aralkyl group, and A.sub.1 is a peptide residue or a cephalosporin residue, with a phosphorus acid to produce a peptide or a cephalosporin of the formula A.sub.1 --NH.sub.2 wherein A.sub.1 is as hereinbefore defined.

Preparation of peptides and cephalosporins

Bisphenoxy carboxylic acid derivatives useful as an antiarteriosclerosis agent with good absorbability and low toxicity, which are novel compounds represented by the general formula, ##STR1## wherein R.sub.1 and R.sub.2 represent hydrogen atoms or lower alkyl groups and A represents ##STR2## (wherein in case R.sub.3 is a hydrogen atom, R.sub.4 represents an amino-lower-alkyl group, an N-lower-alkylaminoalkyl group, a heterocyclic group, or a heterocyclic group-substituted alkyl group; or R.sub.3 and R.sub.4 may join through an intermediary hetero atom to form a heterocyclic group and if said hetero atom is a nitrogen atom, this nitrogen atom can bear a lower alkyl group as a substituent) or ##STR3## (wherein R.sub.5 represents a hydrogen atom, a hydroxyalkyl group or a derivative thereof, and R.sub.6 represents a hydroxyalkyl group or a heterocyclic group; or R.sub.5 and R.sub.6 may join to form a cyclic group, or may join through another intermediary hetero atom to form a heterocyclic group and if said hetero atom is a nitrogen atom, this nitrogen atom can bear a lower alkyl group as a substituent), are prepared by reacting a bisphenoxy acid represented by the general formula, ##STR4## wherein R.sub.1 and R.sub.2 have the same meanings as defined above, or a reactive derivative thereof with a hetero atom-containing alcohol compound represented by the general formula, ##STR5## wherein R.sub.3 and R.sub.4 have the same meanings as defined above, an amine derivative represented by the general formula, ##STR6## wherein R.sub.5 and R.sub.6 have the same meanings as defined above, or a salt thereof. Alternatively, the bisphenoxy carboxylic acid derivatives represented by the said general formula (I), wherein A is ##STR7## R.sub.5 is hydrogen and R.sub.6 is a hydroxyalkyl group, are prepared by heating a bisphenoxy acid derivative represented by the general formula, ##STR8## wherein R.sub.1 and R.sub.2 have the same meanings as defined above and X represents an alkylene chain.

Novel bisphenoxy carboxylic acid derivatives and their salts

A pharmaceutical composition consisting essentially of pharmaceutically effective amount of an N-substituted fatty acid amide of the formula, ##EQU1## wherein R is a C.sub.13 - C.sub.25 aliphatic hydrocarbon chain or a C.sub.13 - C.sub.25 hydroxylated aliphatic hydrocarbon chain and RCO-- is other than isostearoyl; R' is d- or l-.alpha.-C.sub.1 - C.sub.4 alkylbenzyl, racemic-, d- or l-.alpha.-C.sub.1 - C.sub.4 alkylbenzyl substituted in the benzene ring with one or two substituents selected from the group consisting of C.sub.1 - C.sub.4 alkyl, C.sub.1 - C.sub.4 alkoxy, halogen and nitro, or racemic-, d- or l-.alpha.-benzylbenzyl; R' is hydrogen; or R' and R' together are cyclohexyl; and when RCO-- is isotearoyl R' is alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, hydroxycycloalkyl, alkoxycycloalkyl, alkylphenyl, hydroxyphenyl, alkoxyphenyl, halogenophenyl, halogen-alkyl-substituted phenyl, halogenoalkyl- and halogen-substituted phenyl, alkoxy- and halogen-substituted phenyl, benzyl, racemic-, d- or l-.alpha.-C.sub.1 - C.sub.4 alkylbenzyl, benzyl substituted in the benzene ring with lower alkyl or lower alkoxy, racemic-, d- or l-.alpha.-benzylbenzyl or hydroxybenzyl, and R' is hydrogen or any one of the groups represented by R', and a pharmaceutically acceptable carrier, which is useful for lowering elevated levels of cholesterol in the blood.

Pharmaceutical compositions containing fatty acid amide derivatives

Novel compounds having the formula, ##SPC1## Wherein R.sub.1, R.sub.2 and R.sub.3 are each independently hydrogen or a C.sub.1 -C.sub.4 alkyl; n is an integer of 4-6; and Y is hydrogen or a group of the formula ##EQU1## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined above. These compounds are produced, for example, by reacting a bisphenolic compound of the formula, ##SPC2## With chloroform and a ketone compound of the formula,

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Sakai, Japan

Noritaka Hamma