Shionogi Company Limited

Shionogi Seiyaku Kabushiki Kaisha

Saichi Matsumoto

Hirokuni Jyoyama

Masami Doteuchi

Nobuhiro Haga

Susumu Kamata

Takuji Mizui

Kentaro Hirai

Masanao Inagaki

Kohji Hanasaki

Ryuji Suzuki

Tsuneaki Sakata

Toshihiko Okada

Takeshi Shiota

Kenzo Koizumi

Shinji Kakudo

Masayuki Narisada

Fumihiko Watanabe

Tatsuo Tsuri

Shuh Narumiya

Toru Kita

Antirheumatic agent

Antirheumatic

A selective and high-yield method is described for producing stereoisomeric benzylidene derivatives of the formula III: ##STR1## wherein R.sup.1 and R.sup.2 each independently is lower alkyl, lower alkoxy or halogen; Y is SO.sub.2, SO or CO; --A-- is optionally substituted lower alkylene; --B-- is --CH.sub.2 -- or --O--; or --A-- and --B-- taken together may form optionally substituted phenylene or optionally substituted lower alkenylene; and R is hydrogen, optionally substituted lower alkyl, cycloalkyl, lower alkoxy, hydroxy, optionally substituted aryl, optionally substituted arylalkyl; optionally substituted arylalkyloxy, heterocyclic ring or N-protecting groups, which comprises reacting a compound of the formula I: ##STR2## wherein R.sup.1 and R.sup.2 are as defined above and X is lower alkoxy or halogen with a compound of the formula II: ##STR3## wherein Y, --A--, --B-- and R are as defined above in the presence of a base.

Method for producing benzylidene derivatives

Benzylidene derivatives having anti-inflammatory activities, are shown by the following formula I: ##STR1## wherein A is -CH.sub.2 - or -CH.sub.2 CH.sub.2 -; B is a bond or -CH.sub.2 -, -CHOH-, -CO-, -O-, or A and B may taken together form -CH=CH-; D is &gt;N- or &gt;CH-; R.sup.1 and R.sup.2 each independently is hydrogen, lower alkyl or lower alkoxy; R.sup.3 is hydrogen, lower alkyl, cycloalkyl, lower alkoxy, arylalkyloxy, heteroarylalkyloxy, lower alkylcarbonyl, arylcarbonyl, substituted or unsubstituted carbamoyl, or a group of the formula:

Benzylidene derivatives

The present invention relates to novel 3-benzylidene-1-carbamoyl-2-pyrroridone analogues having advantage anti-inflammatory activities, which is represented by the formula: ##STR1## wherein R.sup.1 and R.sup.2 each is independently hydrogen, alkyl, alkoxy, or halogen; R.sup.3 is hydrogen or acyl; R.sup.4 is hydrogen, alkyl, hydroxy, alkoxy, cyano, or halogen; R.sup.5 and R.sup.6 each is independently hydrogen, alkyl, aryl, aralkyl, heterocyclic group, substituted or unsubstituted amino, or OR.sup.7 wherein R.sup.7 is hydrogen, alkyl, aryl, acyl, or aralkyl, or taken together with the adjacent nitrogen atom may form heterocyclic group which may contain N, O, and/or S, and X and Y each is independently O, S, substituted or unsubstituted imino, or substituted or unsubstituted methylene. In more detail, the present invention provides an anti-inflammatory agent which is useful for the treatment of chronic inflammation and has little side effect, e.g., stomach disease.

3-benzylidene-1-carbamoyl-2-pyrrolidone analogues

3-benzylidene-1-carbamoyl-2-pyrrolidone compounds useful as

(Di-tert-butylhydroxyphenyl)thio substituted hydroxamic acid derivatives of the formula: ##STR1## wherein X is straight or branched C.sub.1 to C.sub.15 alkylene which may be attached to Y through phenylene, provided that X is not n-butylmethylene; Y is CO--N(OH) or N(OH)--CO; and R is hydrogen or straight or branched C.sub.1 to C.sub.9 alkyl, C.sub.3 to C.sub.9 cycloalkyl, aryl, or aralkyl, provided that R is not hydrogen when Y--R is N(OH)--CO--R; or a pharmaceutically acceptable salt thereof; useful in treating arteriosclerosis, ulcer, inflammation, allergy, or the like.

Di-tert-butyl(hydroxy)phenylthio substituted hydroxamic acid derivatives

Phenolic thioethers of the formula: ##STR1## wherein R is a hydrogen atom or a protective group for carboxyl, X is a straight or branched C.sub.4 -C.sub.15 alkylene group, a straight or branched C.sub.1 -C.sub.15 alkylene group having a phenylene group or a straight or branched C.sub.2 -C.sub.15 alkenylene group, and their salts, which inhibit the denaturation of low density lipoproteins (LDL) and the incorporation of LDL by macrophages and are useful as anti-arteriosclerosis agents.

Phenolic thioethers, and their production and use

Novel isoprenoidamine compounds (I) which show antiulcer activity are provided. ##STR1##

Isoprenoidamine compounds which are useful antiulcer agents

Isoprenoidamine compounds useful as antiulcer agents

Growing community of inventors

Ikeda, Japan

Saichi Matsumoto