Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Yu Momose

Takashi Sohda

Hiroyuki Odaka

Hitoshi Ikeda

Hiroyuki Kimura

Tsuyoshi Maekawa

Hiroshi Imoto

Sachiko Imai

Junichi Sakamoto

Naoki Tarui

Nozomu Sakai

Ken-ichi Naruo

Junji Matsui

Etsuya Matsutani

Katsuhito Murase

Nobuyuki Takakura

Masatoshi Hazama

Mitsuru Kawada

Yukio Fujisawa

Yasuo Sugiyama

Zen-ichi Terashita

Iwao Yamazaki

Junji Mizoguchi

Tatsuya Ito

Tomoko Asakawa

Katsuhiro Murase

Toru Kawamura

A neurotrophin production/secretion promoting agent which comprises an azole derivative of the formula: wherein Rrepresents a halogen atom, a heterocyclic group which may optionally be substituted, a hydroxy group which may optionally be substituted, a thiol group which may optionally be substituted, or an amino group which may optionally be substituted; A represents an acyl group which may optionally be substituted, a heterocyclic group which may optionally be substituted, a hydroxy group which may optionally be substituted, or a carboxyl group which may optionally be esterified or amidated; B represents an aromatic group which may optionally be substituted; X represents oxygen atom, sulfur atom, or nitrogen atom which may optionally be substituted; and Y represents a divalent hydrocarbon group or heterocyclic group, or a salt thereof; which is useful as an agent for preventing or treating neuropathy.

Neurotrophin production/secretion promoting agent

The present invention provides an agent for preventing or treating neuropathy having superior action and low toxicity. This agent comprises a compound represented by the formula: wherein ring A is a 5-membered aromatic heterocycle containing 2 or more nitrogen atoms, which may further have substituent(s); B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a divalent acyclic hydrocarbon group; Z is &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;NR&#x2014;, &#x2014;CONR&#x2014; or &#x2014;NRCO&#x2014; (Ris a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; Ris an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, provided that when the 5-membered aromatic heterocycle represented by ring A is imidazole, then Z should not be &#x2014;O&#x2014;, or a salt thereof.

Agent for preventing or treating neuropathy

The present invention provides a compound represented by the formula: wherein Ris an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is &#x2014;(CH)-Z- or -Z-(CH)&#x2014; (n is an integer of 0 to 8, Zis a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; Ris a hydrogen atom, a cyano group, &#x2014;PO(OR)(OR) (Rand Rare the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and Rand Rare optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

Five-membered heterocyclic compounds

The present invention relates to a compound represented by the formula wherein Ris an optionally substituted 5-membered heterocyclic group; X is a bond etc.; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; Y is a bond etc.; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is &#x2014;(CH)&#x2014;Z&#x2014; (n is an integer of 0 to 8 and Zis a bond etc.) and the like; ring B is a 5-membered heterocycle optionally further having 1 to 3 substituents; W is a divalent saturated hydrocarbon group having 1 to 20 carbon atoms; Ris &#x2014;OH etc., or a salt thereof. A pharmaceutical composition containing this compound is useful as a prophylactic or therapeutic agent of diseases such as diabetes mellitus and the like.

Five-membered heterocyclic alkanoic acid derivative

An alkanoic acid derivative useful as a prophylactic or therapeutic agent of diabetes mellitus, hyperlipidemia, impaired glucose tolerance and the like can be provided by a compound represented by the formula wherein Ris an optionally substituted 5-membered aromatic heterocyclic group; X is a bond and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; Y is a bond and the like; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is &#x2014;(CH)-Z-(n is an integer of 1 to 8 and Zis an oxygen atom and the like) and the like; ring B is a pyridine ring optionally further having 1 to 3 substituents, and the like; U is a bond and the like; W is a divalent hydrocarbon group having 1 to 20 carbon atoms; and Ris &#x2014;OH and the like, provided that, when ring B is a benzene ring optionally further having 1 to 3 substituents, U should be a bond, or a salt thereof.

Alkanoic acid derivatives process for their production and use thereof

The present invention provides a compound represented by the formula (I) wherein Ris a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group, an optionally substituted thiol group or an optionally substituted amino group,

Azole compounds

A compound of formula (I) F wherein Rrepresents a hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; x represents a bond, an oxygen atom, a sulfur atom, or a group of the formula: &#x2014;CO&#x2014;, &#x2014;CS&#x2014;, &#x2014;CR(OR)&#x2014; or &#x2014;NR&#x2014; wherein each of Rand Rrepresents a hydrogen atom or a hydrocarbon group which may be stubstituted, Rrepresents a hydrogen atom or a protective group for a hydroxyl group; m represents an integer of 0 to 3; Y represents an oxygen atom, a sulfur atom, or a group of the formula: &#x2014;SO&#x2014;, &#x2014;SO&#x2014;, &#x2014;NR&#x2014;, &#x2014;CONR&#x2014; or &#x2014;NRCO&#x2014; wherein Rrepresents a hydrogen atom or a hydrocarbon group which may be substituted; ring A represents an aromatic ring which may further have 1 to 3 substituents; n represents an integer of 1 to 8; ring B represents a nitrogen-containing 5-membered hetero ring which may further be substituted by an alkyl group.

5-membered n-heterocyclic compounds with hypoglycemic and hypolipidemic activity

A compound represented by the formula (I)wherein one of Rand Ris a hydrogen atom or a substituent and the other is an optionally substituted cyclic group; W is a bond or a divalent aliphatic hydrocarbon group; Y is a group of the formula: &#x2014;OR(wherein Ris a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group) or an optionally esterified or amidated carboxyl group, or a salt thereof or a prodrug thereof has a superior insulin secretion promoting action and a hypoglycemic action and shows low toxicity. Therefore, the compound is useful as a pharmaceutical agent, particularly as an agent for the prophylaxis or treatment of diabetes and diabetic complications, and the like.

Isoxazole derivatives

To provide a novel oxyiminoalkanoic acid derivative which has excellent hypoglycemic and hypolipidemic actions and which is used for the prevention or treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance and impaired glucose tolerance. A compound represented by the formula: wherein Ris an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a bond, &#x2014;CO&#x2014;, &#x2014;CH(OH)&#x2014; or a group represented by &#x2014;NR&#x2014; wherein Ris a hydrogen atom or an optionally substituted alkyl group; n is an integer of 1 to 3; Y is an oxygen atom, a sulfur atom, &#x2014;SO&#x2014;, &#x2014;SO&#x2014; or a group represented by &#x2014;NR&#x2014; wherein Ris a hydrogen atom or an optionally alkyl group; ring A is a benzene ring optionally having additional one to three substituents; p is an integer of 1 to 8; Ris a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; q is an integer of 0 to 6; m is 0 or 1; Ris a hydroxy group, OR(Ris an optionally substituted hydrocarbon group.) or NRR(Rand Rare the same or different groups which are selected from a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted acyl group or Rand Rcombine together to form a ring); Rand Rare the same or different groups which are selected from a hydrogen atom or an optionally substituted hydrocarbon group wherein Rmay form a ring with R; provided that when Ris a ethoxymethyl, a Calkyl, phenyl or p-methoxyphenyl and q=m=0, Ris NRR; and provided that O-[2-chloro-4-(2-quinolylmethoxy)phenylmethyl]oxime and a methyl pyruvate of [2-chloro-4-(2-quinolylmethoxy)phenylmethyl]-2-iminoxypropionic acid are excluded; or a salt thereof.

Oxyiminoalkanoic acid derivatives

Crystals of (E)-4-&lsqb;4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino&rsqb;-4-phenylbutyric acid (provided that crystals having a melting point of 126&deg; C. to 127&deg; C. are excluded), which have an excellent anti-diabetic action.

Crystals of an oxyiminoalkanoic acid derivative and their use as antidiabetics

Neurotrophin production secretion promoting agent

Apoptosis inhibitor

Oxazolidinedione derivatives and their use

1,3-Azole derivatives, pharmaceutical compositions thereof and methods for regulating the function of retinoid-related receptors with 1,3-azole derivatives are disclosed. Such regulation may be useful for preventing or treating diabetes, preventing or treating hyperlipidemia, preventing or treating impaired glucose tolerance (IGT) or for preventing transition from impaired glucose tolerance to diabetes.

Growing community of inventors

Takarazuka, Japan

Yu Momose