Eisai R&d Management Co., Ltd.

Shuji Shirotori

Keigo Tanaka

Norio Murai

Satoshi Inoue

Shinya Abe

Masayuki Matsukura

Tomohiro Matsushima

Kazutaka Nakamoto

Keiko Takahashi

Atsushi Kamada

Takahisa Sakaguchi

Setsuo Funasaka

Kazunori Wakasugi

Mitsuo Nagai

Hiroshi Obaishi

Kazumasa Nara

Yoshiaki Ohashi

Shuichi Suzuki

Satoshi Nagao

Yuzo Watanabe

Daisuke Ito

Yosuke Kaburagi

An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein R, R, X, Y, ring A, Z, Rand Rare as defined in the specification.

Heterocycles substituted pyridine derivatives and antifungal agent containing thereof

The invention provides acid addition salts of the compounds represented by formula (1) or (2), or crystals thereof, and processes for preparing the same. The salts or crystals have HGFR inhibitory activity and excellent physical properties (solubility, safety, etc.) and are therefore useful as anti-tumor agents, angiogenesis inhibitors and inhibitors for metastasis for a various types of tumor. 

Phenoxypyridine derivative salts and crystals thereof, and process for preparing the same

A compound represented by the following formula, or a salt thereof or a hydrate of the foregoing, has excellent hepatocyte growth factor receptor (HGFR) inhibitory activity, and exhibits anti-tumor activity, angiogenesis inhibitory activity, and cancer metastasis inhibitory activity. Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; Rand Rrepresent hydrogen; R, R, R, and Rmay be the same or different and each represents hydrogen, halogen, Calkyl or the like; Rrepresents hydrogen or the like; Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; n represents an integer of 1 or 2; X represents &#x2014;CH&#x2550;, nitrogen or the like.

Pyridine derivatives and pyrimidine derivatives (3)

Provided is a fluoroboron compound which is highly safe and stable and is capable of forming a cyclic ether-fused ring by the intramolecular alkoxymethylation reaction, or a salt thereof. The compound can be synthesized by the intramolecular alkoxymethylation reaction of a fluoroboron compound represented by the formula (I) or a salt thereof in the presence of a metal catalyst.  represents an aromatic ring; L represents a substituent such as a halogen atom; R represents a substituted or unsubstituted alkylene group having 1 or 2 carbon atoms; and M represents an alkali metal cation or the like, with the proviso that L and &#x2014;R&#x2014;OCHBFM are respectively located on contiguous carbon atoms on the aromatic ring, or in the case of a fused aromatic ring, on two carbon atoms adjacent to one carbon at the fused position).

Fluoroboron compound having aromatic ring or salt thereof, and method for producing compound having cyclic ether-fused aromatic ring using the same

The present invention provides an antifungal agent that has excellent antifungal action, and is also excellent in terms of its properties, safety, and metabolic stability. The present invention discloses a compound represented by the following formula I or a salt thereof, and an antifungal agent comprising the compound or the salt: wherein Rrepresents a hydrogen atom, a halogen atom, an amino group, a Calkyl group, a Calkoxy group, or a C-alkoxy-C-alkyl group; Rrepresents a hydrogen atom or an amino group; X, Y, Z, and W independently represent a nitrogen atom, an oxygen atom, a sulfur atom, or &#x2014;CH&#x2014;, provided that at least two among X, Y, and W are nitrogen atoms; the ring A represents a 5- or 6-membered heteroaryl ring or a benzene ring; Q represents a methylene group, an oxygen atom, &#x2014;CHO&#x2014;, &#x2014;OCH&#x2014;, &#x2014;NH&#x2014;, &#x2014;NHCH&#x2014;, or &#x2014;CHNH&#x2014;; and Rrepresents a Calkyl group, a Ccycloalkyl group, a Caryl group, or a 5- or 6-membered heteroaryl group, each of which may have one or two substituents.

Pyridine derivative substituted by heteroaryl ring, and antifungal agent comprising the same

An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein Rrepresents a hydrogen atom, a halogen atom, an amino group, a Calkyl group, a Calkoxy group or a Calkoxy Calkyl group; Rrepresents a hydrogen atom, a Calkyl group, an amino group or a di Calkylamino group; one of X and Y is a nitrogen atom while the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom, or 1 or 2 Calkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, &#x2014;CHO&#x2014;, &#x2014;OCH&#x2014;, &#x2014;NH&#x2014;, &#x2014;CHNH&#x2014;, &#x2014;NHCH&#x2014;, &#x2014;CHS&#x2014;, or &#x2014;SCH&#x2014;; Rrepresents a hydrogen atom, a halogen atom, a Calkyl group, a Ccycloalkyl group, a Caryl group, a 5- or 6-member heteroaryl group, or 5- or 6-member non-aromatic heterocyclic group which may have 1 or 2 substituents; and Rrepresents a hydrogen atom or a halogen atom.

A compound represented by the following formula, a salt thereof or a hydrate of the foregoing has an excellent hepatocyte growth factor receptor (HGFR) inhibitory activity, and exhibits anti-tumor activity, angiogenesis inhibitory activity and cancer metastasis inhibitory activity. [Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; Rand Rrepresent hydrogen; R, R, R, and Rmay be the same or different and each represents hydrogen, halogen, Calkyl or the like; Rrepresents hydrogen or the like; Rrepresents a 3- to 10-membered non-aromatic heterocyclic group or the like; n represents an integer of 1 or 2; X represents &#x2014;CH&#x2550;, nitrogen or the like.]

A process for preparing a compound represented by the formula (I): comprising reacting a compound represented by the formula (II) or salt thereof: with a compound represented by the formula (III): in the presence of a condensation reagent,wherein Rrepresents 1) optionally substituted azetidin-1-yl, 2) optionally substituted pyrrolidin-1-yl, 3) optionally substituted piperidin-1-yl, etc.; R, R, Rand Rmay be the same or different and each represents hydrogen or fluorine; and Rrepresents hydrogen or fluorine.

Process for preparing phenoxypyridine derivatives

The present invention provides compounds which are useful as safe substitutes for the organotin reagent used in coupling reaction for the oxymethylation of aromatic rings, such as alkoxymethylation or hydroxymethylation, with a palladium catalyst and which can dispense with chromatographic purification with silica gel in the production and are suitable for mass production; and compounds applicable even to the oxymethylation of aromatic ring substrates which do not permit coupling reaction by conventional technique or have low reactivity.

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Tsukuba, Japan

Shuji Shirotori