Ono Pharmaceutical Co., Ltd.

Tomoyuki Hasegawa

Yasufumi Kawanaka

Eiji Kasamatsu

Toshiaki Matsui

Kaoru Kobayashi

Kazuhiko Torisu

Fumio Nambu

Tetsuji Saito

Shigeru Sakuyama

Tetsuo Obitsu

Haruo Imawaka

Yasumasa Hamada

Masamitsu Hoshikawa

Masaki Okamoto

Tsutomu Akiyama

Saiko Matsuda

Hiroshi Araki

Yuichi Gemba

Yutaka Mikami

According to the present invention, crystals comprising (2R)-2-propyloctanoic acid and an amine, which can be used as bulk drugs for safely orally administrable solid preparations with keeping the pharmacological effect, are provided. Among these crystals, the crystal with dibenzylamine per se is particularly useful as bulk drug for pharmaceuticals and can be used as an intermediate to produce (2R)-2-propyloctanoic acid having an optical purity of more than 99.5% e.e. which has not been obtained.

Crystal comprising (2R)-2-propyloctanoic acid and amine

8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine methanesulfonate of the structural formula (I) has Corticotropin Releasing Factor (CRF) antagonist activity and is useful in treating neuropsychiatric and digestive system diseases.

8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d] pyrazolo[1,5-a]pyrimidine methanesulfonate as a CRF antagonist

Crystals comprising (2R)-2-propyloctoic acid and an amine which retain the pharmacological effect of (2R)-2-propyloctoic acid and can be safely used as a medicinal raw drug for peroral solid preparations. Of these crystals, the crystals especially with dibenzylamine are advantageous because not only the crystals themselves are useful as a medicinal raw drug but also use of the crystals as an intermediate can yield (2R)-2-propyloctoic acid having an optical purity exceeding 99.5% e.e., which has not been obtained hitherto.

The present invention relates to a process for producing (2R)-2-propyloctanoic acid, which comprises subjecting (2R)-2-hexyloxirane to a two-carbon adding reaction with ring-opening reaction, followed by a protecting reaction of a hydroxyl group to convert it to a compound represented by formula (I): (wherein X represents an optionally protected hydroxyl group) and then subjecting the compound to a one-carbon adding reaction to convert it to (2R)-2-propyloctanamide, followed by recrystallization and hydrolysis. According to the process of the present invention, (2R)-2-propyloctanoic acid can be produced by less steps as compared with the conventional method without a dangerous reaction.

Process for producing (2R)-2-propyloctanoic acid and intermediate therefor

The present invention relates to a compound represented by formula (I) wherein Rrepresents optionally protected hydroxy or oxo,indicates &#x3b1;-configuration, &#x3b2;-configuration or a mixture of these in an arbitrary proportion, n represents an integer of 1 to 3, and m represents 0 or an integer of 1 to 10; and wherein two or more R's are not bound to the same carbon atom other than the terminal carbon atom, a salt thereof or a prodrug thereof. The compounds represented by formula (I) have an ability to improve astrocyte function, and they are useful as a preventive and/or therapeutic agent for a brain infarction, neuronal dysfunction by brain infarction, Parkinson's disease, Parkinson's syndrome, amyotrophic lateral sclerosis or Alzheimer's disease.

Branched carboxylic acid compound and use thereof

Indole derivatives represented by formula (I)  wherein all symbols represent the same as that in specification), production methods thereof, and DP receptor antagonist comprising them as active ingredients. Since the compounds of formula (I) binds and antagonizes to DP receptor, they are useful for the prevention and/or treatment against allergic diseases, diseases accompanied with itching, secondary diseases generated by behaviors caused by itching, inflammation, chronic obstructive pulmonary disease, ischemic reperfusion disorder, cerebrovascular disorder, pleuritis complicated by rheumatoid arthritis, ulcerative colitis.

Indole compounds, process for producing the same and drugs containing the same as the active ingredient

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Sakai-gun, Japan

Tomoyuki Hasegawa