Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Norikazu Tamura

Katsumi Itoh

Kenji Okonogi

Takashi Sohda

Hitoshi Ikeda

Takashi Ichikawa

Masayuki Ii

Hideaki Natsugari

Zen-ichi Terashita

Koichi Yoshioka

The present invention is directed to a class of cyclohexene derivatives bearing sulfamoyl and ester groups which have an inhibitory activity on nitric oxide (NO) production and cytokine production, and are useful as an agent for the prophylaxis and/or treatment of diseases such as, cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, and septic shock.

Substituted aromatic-ring compounds, process for producing the same and use

A compound of the formula: wherein Ris an aliphatic hydrocarbon group optionally having substituent(s), an aromatic hydrocarbon group optionally having substituent(s), a heterocyclic group optionally having substituent(s), a group of the formula: ORwherein Ris a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), or a group of the formula: wherein Rand Rare the same or different and each is a hydrogen atom or an aliphatic hydrocarbon group optionally having substituent(s), X is a methylene group, a nitrogen atom, a sulfur atom or an oxygen atom, Y is an optionally substituted methylene group or an optionally substituted nitrogen atom, ring A is a 5 to 8-membered ring optionally substituted further by 1 to 4 substituent(s) selected from (1) an aliphatic hydrocarbon group optionally having substituent(s), (2) an aromatic hydrocarbon group optionally having substituent(s), (3) a group of the formula: ORwherein Ris a hydrogen atom, or an aliphatic hydrocarbon group optionally having substituent(s) and (4) a halogen atom, Ar is an aromatic hydrocarbon group optionally having substituent(s), a group of the formula: is a group of the formula: or the formula: m is an integer of 0 to 2, n is an integer of 1 to 3, and the sum of m and n is not more than 4, provided that when X is a methylene group, Y is an optionally substituted methylene group, and a salt thereof have an inhibitory activity on nitric oxide (NO) production and cytokine production, and are useful as an agent for the prophylaxis and/or treatment of diseases, such as cardiac disease, autoimmune disease, inflammatory disease, central nervous system disease, infectious disease, sepsis, septic shock and the like.

Substituted aromatic-ring compounds, process for producing the same, and use

To provide a pharmaceutical composition which performs a remarkable effect with a relatively decreased dosage, and, with less side effects, a pharmaceutical composition formulated by combination of an angiotensin II-mediated compound or a salt thereof with at least one species of a compound having the activity of increasing insulin-sensitivity, a compound having the activity of improving postprandial hyperglycemia in diabetes mellitus, an indane derivative having the activity of inhibiting angiotensin converting enzyme, a pyridine derivative having the activity of inhibiting HMG-Co A reductase or salts thereof are advantageously employed.

Pharmaceutical composition

2-piperazinone-1-acetic acid derivatives and their use

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

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

Azole compounds, their production and use

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

A compound of the general formula: ##STR1## wherein X is a lower alkylene group which may optionally be substituted by a hydroxyl group, or a lower alkenylene group, Y is (1) a lower alkyl group, (2) a cycloalkyl group containing 3 to 8 carbon atoms, (3) a lower alkenyl group, (4) an aryl group, (5) an aralkyl group or (6) a 3- to 8-membered heterocyclic group, or the partial structural formula Y--SO.sub.2 --X--, with X and Y being combined with each other, represents a group of the formula: ##STR2## wherein l is an integer of 0 to 3, and m and n each is an integer of 0 to 6, provided that the sum of m and n is in the range of 2 to 6, and R is a hydrocarbon group which may optionally be substituted or a 3- to 8-membered heterocyclic group, or a pharmaceutically acceptable salt thereof a method of production thereof and use thereof. The compound (I) has antimicrobial and .beta.-lactamase inhibitory activities.

Growing community of inventors

Kobe, Japan

Norikazu Tamura