Banyu Pharmaceutical Co. Ltd

Dainippon Sumitomo Pharma Co., Ltd.

Sumitomo Chemical Company, Limited

Sumitomo Dainippon Pharma Co., Ltd.

Astrazeneca Aktiebolag

Kazuhiko Takahashi

Hidehito Kotani

Hiraku Itadani

Katsuya Uchiyama

Kento Senami

Shoji Watanabe

Koji Fujimoto

Yasuko Yamauchi

Hiroaki Suwa

Kenji Saito

Akio Kanatani

Kazuki Hashimoto

Shigeru Tokita

Akane Ishihara

Ayumu Kurimoto

Shinzaburo Masaki

Masahito Sekiguchi

Hiroshi Yoshihara

Kazuya Minamisaka

Satoshi Mashiko

Takanori Okahashi

Wataru Katoda

Hiromitsu Araki

Hiromits Araki

Nao Odagiri

Tsutomu Kobayashi

Takashi Kawai

Provided is a method for producing a 2-alkylcarbonylnaphtho[2,3-b]furan-4,9-dione-related substance, which is suitable for the production on an industrial scale. The present invention provides: a method for producing an intermediate for the production of a 2-alkylcarbonyl[2,3-b]furan-4,9-dione, which comprises reacting a 1-butyne derivative in which a ketone or an alcohol is protected with a 2-hydroxy-1,4-naphthoquinone derivative having a leaving group at position-3 in a solvent in the presence of a metal or a metal compound and a base; and a substance relating to the intermediate.

Method for producing 2-alkylcarbonylnaphtho[2,3-b]furan-4,9-dione-related substance, and said related substance

A method for producing adenine compound (1): wherein m and n are independently an integer of 2 to 5, Ris Calkyl group, Rand Rare the same or different, and hydrogen atom, or Calkyl group, or Rand Rare combined with an adjacent nitrogen atom to form pyrrolidine, morpholine, piperidine, piperazine, etc., and Ris Calkyl group,which comprises a step of reacting compound (2): and compound (3): in the presence of a boron-containing reducing agent.

Method for preparing adenine compound

A stabilized amrubicin hydrochloride composition which comprises 3 to 8 wt. % water and 92 to 97 wt. % amrubicin hydrochloride; and a method of storing amrubicin hydrochloride.

Stabilization of amrubicin hydrochloride

To clarify histamine receptor H3 protein function in vivo, the present inventors constructed a nonhuman higher animal in which the expression of a histamine receptor H3 gene was artificially inhibited. As a result, the present inventors found that this nonhuman higher animal showed increased body weight, food intake, blood insulin level, or blood leptin level compared with a control. Thus, the present inventors found that abnormalities in the histamine receptor H3 protein relate to diseases characterized by changes in body weight or food intake, and this has made it possible to screen drugs for treatment or prevention of these diseases, and to examine these diseases.

Utilization of histamine receptor h3 gene participating in body weight or food intake control

In the examination of obesity or leanness, the examination is based on the expression level of the MCP-1 gene or the MCP-1 protein in a tissue or cell analyte, or on the polymorphism in the gene. In the evaluation of compounds, including screening for therapeutic agents for obesity or leanness, the properties of the MCP-1 gene or the MCP-1 protein are utilized to carry out the evaluation.

Method for examining obesity or leanness

Examination of obesity or emaciation is performed based on expression levels of LCE gene or protein in a test tissue or a test cell or a polymorphism of the gene. Evaluation of compounds including screening of therapeutic agents for obesity or emaciation is performed utilizing the nature of LCE gene or protein.

Method of evaluating compound efficacious in treating obesity

Internal domain 3 of seven transmembrane G protein-coupled receptors is important for G protein binding or receptor activity, and is well conserved. In H3 receptors, which are a type of G protein-coupled receptor, this region is also conserved in the same way. Therefore, as a result of using PCR to introduce point mutations into sequences encoding the region in H3 receptor cDNA, H3 receptor mutants comprising extremely strong constitutive activity could be successfully produced. The present inventors further found that by using constitutively active H3 receptor mutants, drug candidate compounds such as H3 receptor inverse agonists can be screened more easily and efficiently.

Constitutively active histamine H3 receptor mutants and uses thereof

Process for producing 5-amino-3-methylpyrazole

Growing community of inventors

Osaka, Japan

Kazuhiko Takahashi