Fujisawa Pharmaceutical Company, Ltd.

Astellas Pharma Gmbh

Fumiyuki Shirai

Toshiyuki Chiba

Masayoshi Murata

Hideo Tsutsumi

Yoshiteru Eikyu

Hiroaki Ohtake

Hisashi Takasugi

Junji Sato

Yuki Sawada

Yoshikazu Inoue

Shigeki Satoh

Kohji Hattori

Yutaka Nakajima

Naoki Ishibashi

Sunao Imada

Kazunori Kamijo

Keita Nakanishi

Takahiro Nigawara

Satoru Kuroda

Yasuharu Urano

Shohei Shirakami

Koichiro Mukoyoshi

Kaori Kubo

Naohiro Aoyama

Yuji Takasuna

Takao Takaya

Kohji Kawabata

Natsuko Kayakiri

Katsuya Nakamura

Kazuo Okumura

Hidenori Azami

Hitoshi Nakamura

Motohiro Hino

Takeshi Nakai

Takeshi Terasawa

Hirofumi Yamamoto

Kenichi Washizuka

Hiromichi Itani

Yoshihiro Kozuki

Ayako Ohki

Taro Masunaga

Yasunobu Inaba

On the basis of a cathepsin S inhibitory effect, an excellent agent for treating or preventing autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like is provided. It was found that a nitrogen-containing bicyclic heterocyclic compound has an excellent cathepsin S inhibitory effect, thereby completing the invention. The compound of the present invention has an cathepsin S inhibitory effect, and can be used as an agent for preventing and/or treating autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like.

Nitrogen-containing bicyclic aromatic heterocyclic compound

[Problem] On the basis of a cathepsin S inhibitory effect, an excellent agent for treating or preventing autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like is provided. [Means for Solution] It was found that a nitrogen-containing bicyclic heterocyclic compound has the excellent cathepsin S inhibitory effect, thereby completing the invention. The compound of the present invention has the cathepsin S inhibitory effect, and can be used as an agent for preventing and/or treating autoimmune disease, allergic disease, graft rejection of an organ, bone marrow or tissue, systemic lupus erythematosus, or the like.

This invention relates to novel N-hydroxyacrylamide compounds of formula (I) and pharmaceutically acceptable salts thereof. More particularly, it relates to novel N-hydroxyacrylamide compounds and pharmaceutically acceptable salts thereof which act as a HDAC inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of HDAC-related disease. 

Pyrazinyl hydroxyacrylamide compounds having an inhibitory effect on the activity of histone deacetylase

Compounds having the formula (I): wherein

HDAC inhibitor

A compound having the formula (I): wherein

A compound of the formula (I): wherein Ris hydrogen or lower alkyl;

Pyrazole derivatives

Cephem compounds

1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds

Preparation of optically active 3-substituted azetidinones of the formula (I) ##STR1## in which R.sup.1 is a hydroxy-protective group wherein an allylic alcohol of the formula (II) ##STR2## is acylated, then subjected to asymmetric enzymatic hydrolysis yielding the R-allylic alcohol. The hydroxyl group is protected and then stereoselectively reacted with an amine which is subsequently cyclized to yield the desired 3-substituted azetidinone. Two new species of microorganisms have been isolated, Pimelobacter sp. No. 1254 and Bacillus megaterium No. 1253 which exhibit stereoselective esterase activity.

Enzymatic process for preparing optically active 3-substituted

1-Azabicyclo[3.2.0]hept-2-ene-2-carboxyic acids having antimicrobial activity have been prepared.

The invention relates to the preparation of 3,4-disubstituted-2-azetidinone compounds of the formula: ##STR1## in which R.sup.1 is hydrogen or amido-protective group, R.sup.2 is hydroxy(lower)alkyl or protected hydroxy(lower)alkyl, R.sup.3 is lower alkyl, and R.sup.4 is 1-(lower)alkyl-1-hydroxy(C.sub.2 -C.sub.6)alkyl, 1-(lower)alkyl-1-(protected hydroxy)-(C.sub.2 -C.sub.6)alkyl or 2-thioxothiazolidin-3-yl, useful as an intermediate for the production of antimicrobial agents by reacting a compound a compound of the formula: ##STR2## in which R.sup.5 is acyl, or salts thereof, with a compound of the formula:

3,4-disubstituted-2-azetidinone derivatives and processes for

The invention relates to crystalline 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-car boxylic acid (syn isomer) useful as an antimicrobial agent.

Crystalline

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Tokyo, Japan

Fumiyuki Shirai