Takeda Chemical Industries, Inc.

Takeda Chemical Industries, Co., Ltd.

Katsumi Itoh

Kenji Okonogi

Akihiro Tasaka

Norikazu Tamura

Yoshikazu Oka

Kohei Nishikawa

Akio Miyake

Hirosada Sugihara

Minoru Hirata

Tomoyuki Kitazaki

Shinji Terao

Setsuo Harada

Akinobu Nagaoka

Yuzo Ichimori

Masayuki Ii

Junji Yamada

Norio Tada

Hiroshi Hosono

Cycloalkene derivatives, process for producing the same, and use

A quaternized nitrogen-containing imidazol-1-yl or 1,2,4-triazol-1-yl compound wherein one of the nitrogen atoms constituting an azole ring is quaternized with a substituent capable of being eliminated in vivo and the substituent can be eliminated in vivo to be converted into an antifungal azole compound, has an improved solubility in water, can advantageously be applied to injection, has an improved internal absorption and can be expected to have a good effect for the treatment or prevention of disease.

Azole compounds, their production and their use

Azole compounds, their production and use

The present invention provides an azole compound represented by the formula (I): ##STR1## , wherein Ar is an optionally-substituted phenyl group; R.sup.1 and R.sup.2 are, the same or different, a hydrogen atom or a lower alkyl group, or R.sup.1 and R.sup.2 may combine together to form a lower alkylene group; R.sup.3 is a hydrogen atom or an acyl group; Y is a nitrogen atom or a methine group; and A is an optionally-substituted saturated cyclic amide group bonded through a first nitrogen atom, or a salt thereof, which is useful for prevention and therapy of fungal infections of mammals as antifungal agent.

A compound of the formula (V): ##STR1## wherein Ar' is a halogenated phenyl group, R is a hydrocarbon residue having a functional group at the .alpha.-carbon, R.sup.3' is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, Y and Z are, the same or different, a nitrogen atom or a methine group optionally substituted with a lower alkyl group, and (R) and (S) represent configurations, which is an optically active intermediate for production of optically active triazole compounds (I): ##STR2## wherein the symbols have the same meanings as defined above, and methods of preparing the compounds (V) and (I).

Production of optically active triazole compounds and their intermediates

The present invention provides an azole compound represented by the formula (I): ##STR1## wherein Ar is an optionally-substituted phenyl group; R.sup.1 and R.sup.2 are, the same or different, a hydrogen atom or a lower alkyl group, or R.sup.1 and R.sup.2 may combine together to form a lower alkylene group; R.sup.3 is a hydrogen atom or an acyl group; Y is a nitrogen atom or a methine group; and A is an optionally-substituted saturated cyclic amide group bonded through a first nitrogen atom, or a salt thereof, which is useful for prevention and therapy of fungal infections of mammals as antifungal agent.

Triazole and imidazole compounds and their use as antifungal therapeutic

An optically active azole compound of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are independently a hydrogen atom, a halogen atom, a haloalkyl group, a haloalkoxy group or an optionally substituted nitrogen-containing heterocyclic group; R.sup.3 is a hydrogen atom or an acyl group; Q is CH or N; ##STR2## is a nitrogen-containing aromatic five-membered heterocyclic group having at least two adjacent nitrogen atoms as the ring-constituting atoms which may be substituted, or an aromatic condensed heterocyclic group having two or more nitrogen atoms as the ring-constituting atoms which may be substituted; and (R) shows that the carbon atom marked with (R) has R-configuration; provided that either of R.sup.1 and R.sup.2 is an optionally substituted nitrogen-containing heterocyclic group when ##STR3## is an 1H-1,2,4-triazol-1-yl group, or a salt thereof, which is useful as an antifungal agent.

Optically active azole compounds and their production

An azole compound represented by the formula (I): ##STR1## wherein Ar is a substituted phenyl group; R.sup.1 and R.sup.2 independently are a hydrogen atom or a lower alkyl group, or R.sup.1 and R.sup.2 may combine together to form a lower alkylene group; R.sup.3 is a group bonded through a carbon atom; R.sup.4 is a hydrogen atom or an acyl group; X is a nitrogen atom or a methine group; and Y and Z independently are a nitrogen atom or a methine group which may optionally be substituted with a lower alkyl group, or a salt thereof, which is useful for prevention and therapy of fungal infections of mammals as antifungal agent.

Production of Di or tri-azolyl substituted 5-keto azole compounds

The novel 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-propanol derivertives of the formula (I): ##STR1## wherein, R.sup.0, R.sup.1 and R.sup.2 are the same or different and represent a hydrogen atom or a lower alkyl group; A represents a formula: ##STR2## wherein, X stands for a chemical bond or a formula: ##STR3## (wherein, X' stands for a chemical bond or an alkylene group having 1 to 5 carbon atoms which may contain sulfur or oxygen atom as the constituent atoms, R.sup.5 and R.sup.6 are the same or different and stand for a hydrogen atom or a lower alkyl group), R.sup.3 stands for an aromatic heterocyclic group which may be substituted, n denotes 0, 1 or 2), and R.sup.4 stands for a hydrogen atom or an alkanoyl group, or a physiologically acceptable salt thereof have antifungal activities, and they are used for preventing or treating infectious diseases caused by fungi.

Triazole compounds and antifungal compositions thereof

An azole compound represented by the formula (I): ##STR1## wherein X is a nitrogen atom; Ar is a phenyl group substituted by halogen or a halogenated C.sub.1-4 alkyl group; R.sup.1 and R.sup.2 independently are a hydrogen atom or a lower alkyl group, or R.sup.1 and R.sup.2 may combine together to form a lower alkylene group; n denotes an integer of 0 to 2; and R.sup.7 is a hydrogen atom, a hydroxyl group which may be optionally acylated by an acyl group selected from acetyl, propionyl, butyryl, isobutyryl, phenylacetyl and benzoyl, or may form a bond together with R.sup.1 ; or a salt thereof.

1-(1h-1,2,4-triazole-yl)-2-propanol compounds

A triazole compound of the-formula (I): ##STR1## wherein Ar is a substituted phenyl group, R.sup.1, R.sup.2 and R.sup.3 each represents, the same or different, a hydrogen atom or a lower alkyl, R.sup.4 and R.sup.5 each represents, the same or different, a hydrogen atom, an alkyl group, an aralkyl group, an aryl group or an aromatic heterocyclic group or R.sup.4 and R.sup.5 together with the nitrogen atom to which they are attached may form a heterocyclic ring, or its salt, which is useful as antifungal agents.

Triazoles, their production and use

An azole compound represented by the formula (I): ##STR1## wherein Ar is a substituted phenyl group;

An optically active azole compound of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are independently a hydrogen atom, a halogen atom, a haloalkyl group, a haloalkoxy group or an optionally substituted nitrogen-containing heterocyclic group; R.sup.3 is a hydrogen atom or an acyl group; Q is CH or N; --NA is a nitrogen-containing aromatic five-membered heterocyclic group having at least two adjacent nitrogen atoms as the ring-constituting atoms which may be substituted, or an aromatic condensed heterocyclic group having two or more nitrogen atoms as the ring-constituting atoms which may be substituted; and (R) shows that the carbon atom marked with (R) has R-configuration; provided that either of R.sup.1 and R.sup.2 is an optionally substituted nitrogen-containing heterocyclic group when --NA is an 1H-1,2,4-triazol-1-yl group, or a salt thereof, which is useful as an antifungal agent.

Optically active tetrazole compounds, and fungicidal compositions thereof

The novel azole compounds of the formula: ##STR1## wherein Ar stands for substituted phenyl; R.sup.1, R.sup.2 and R.sup.3 independently stand for a hydrogen atom or a lower alkyl group; B stands for a hydroxyl group or an organic residue bonded through a carbon atom; X stands for a CH group or a nitrogen atom; m denotes an integer of 1 to 4; n denotes an integer of 0 to 2, provided that, when B is a hydroxyl group, n is 2, or a physiologically acceptable salt thereof have antifungal activities, and they are used preventing or treating infectious diseases caused by fungi.

Growing community of inventors

Osaka, Japan

Katsumi Itoh