Shionogi Company Limited

Shionogi Seiyaku Kabushiki Kaisha

Toshiro Konoike

Yoshitaka Araki

Tsutomu Aoki

Kensuke Sakurai

Wataru Nagata

Tadahiko Yorifuji

Ken-ichi Matsumura

Takehiko Tozyo

Tetsuyoshi Hayashi

Hiroshi Harada

Mitsuaki Ohtani

Teruji Tsuji

Mitsuru Yoshioka

Nobuhiro Haga

Yasuhiro Nishitani

Susumu Kamata

Takaharu Matsuura

Sanji Hagishita

Tadatoshi Kubota

Natsuki Ishizuka

Shoji Shinomoto

Katsunori Sakai

Hiroshi Onoue

Toru Kita

Yasunobu Ishihara

Hiromi Takahashi

Hiroyuki Ishitobi

Yoshiyuki Matsuo

Teruo Sakata

Eiichi Ohsugi

Yutaka Ide

Takashi Ohya

Akira Okuyama

Yasushi Murakami

Yoshiyuki Masui

Miharu Nakamura

Shinichi Mihara

Masafumi Fujimoto

Seijiro Hara

A process for producing a compound of the formula (II): wherein Halrepresents halogen and Rand Reach independently represents halogen, alkyl, alkoxy, nitro or cyano, which comprises allowing a halogenating agent to react with a compound of the formula (I): wherein Alk represents branched alkyl and Rand Rare as defined above.

Process for producing arylsulfenyl halide

Process for preparation of sulfonamide derivatives and crystals thereof

Process for producing optically active chromene derivative

The present invention provides a compound of the formula (I):

Chromene-3-carboxylate derivatives

Carbamoylmethylurea derivatives

Triterpene derivatives of the formula (I): ##STR1## wherein R.sup.1 is hydrogen or metabolic ester residue; and R.sup.2 is hydrogen or --R.sup.3 -R.sup.4 wherein R.sup.3 is --SO.sub.3 --, --CH.sub.2 COO--, --COCOO--, or --COR.sup.5 COO-- (R.sup.5 is lower alkylene or lower alkenylene), and R.sup.4 is hydrogen or metabolic ester residue or a pharmaceutically acceptable salt thereof, which have anti-endothelin activities and are useful in prophylaxis and treatment of diseases caused by excessive secretion of endothelin.

Triterpene derivatives and endothelin-receptor antagonists containing

Triterpene derivatives of the formula (I): ##STR1## wherein R.sup.1 is hydrogen or metabolic ester residue; and R.sup.2 is hydrogen or --R.sup.3 --R.sup.4 wherein R.sup.3 is --SO.sub.3 --, --CH.sub.2 COO--, --COCOO--, or --COR.sup.5 COO-- (R.sup.5 is lower alkylene or lower alkenylene), and R.sup.4 is hydrogen or metabolic ester residue or a pharmaceutically acceptable salt thereof, which have anti-endothelin activities and are useful in prophylaxis and treatment of diseases caused by excessive secretion of endothelin.

Optically active intermediate and method for production thereof

Triterpene derivatives

Antibacterial hydroxyarylpiperazinocephalosporins of the formula: ##STR1## wherein R.sup.1 is amino or acylamino; R.sup.2 is H or methoxy; R.sup.3 is alkyl; R.sup.4 is --(P--C--Q).sub.n --, where P and Q each are H, alkyl or OH, or P and Q combine to form oxo, and n is 0 or 4; R.sup.5 is substituted or unsubstituted hydroxyaryl; R.sup.6 has a negative charge and is COO, or an anion in combination with an optionally protected carboxy; and X is O, S or S.fwdarw.O; an antibacterial preparation containing the same; a method for killing bacteria and preventing or treating bacterial infection by using the same; and syntheses of the cephalosporins are provided.

Piperaziniocephalosporins

An optically active ester of arylacetic acid of the fomula: ##STR1## wherein R.sup.1 is hydrogen or optionally substituted C.sub.1 -C.sub.2 alkyl or phenyl or taken together to from C.sub.2 -C.sub.6 alkylene, or C.sub.2 C.sub.4 -C.sub.6 alkenylene, or bicyclic-ring; R.sup.2 is hydrogen or methyl; X is single bond or Ch.sub.2, C.dbd.O, N--R.sup.4, O, S, CHNHR.sup.4, CHCH.sub.3, CH--Ar, or CHOR.sup.5 (provided that when X is single bond or CH.sub.2, C.dbd.O, N--R.sup.4, O, or S, R.sup.1 and R.sup.2 are not simultaneouly hydrogen or methyl); R.sup.3 is hydrogen, optionally substituted alkyl, or optionally substituted aralkyl; R.sup.4 is hydrogen or amino protecting group; R.sup.5 is hydrogen or hydroxy protecting group; and Ar is optionally substituted aryl; prepared by the reaction of a 94 symmetric acid anhydride with an (R)-or (S)-arylacetic acid derivative in high optical purity; useful as a intermediate for the various optically active natural products and medicines.

Monoesters of arylacetic acid and the process thereof

A 2,4,6-substituted phenol having the formula (I): ##STR1## wherein X is S or CH.sub.2 ; R.sup.1 and R.sup.2 are the same or different from each other and each is a lower alkyl group; R.sup.3 is a group of the formula: ##STR2## in which R.sup.4 is hydrogen atom or a lower alkyl group; R.sup.5 and R.sup.6 are the same or different from each other and each is hydrogen atom, a lower alkyl group, or a phenyl group which may be substituted, or a pharmaceutically acceptable salt thereof is useful as an active agent in a pharmaceutical composition. The pharmaceutical composition comprises a therapeutically effective amount of a compound having the formula (I), as an effective ingredient, in association with a pharmaceutically acceptable substantially nontoxic carrier or excipient. The pharmaceutical composition can be useful in the treatment of lipemia of mammals. Additionally the compounds can be used as antiatherosclerotic agents and antilipenic agents.

2,4,6-substituted phenol derivatives

A novel chemical, fluorochlorocyclopropane (I) of the following formula: ##STR1## is prepared by the addition of fluorochlorocarbene to the corresponding olefin (II) of the following formula:

Fluorocyclopropanes

A compound of the formula: ##STR1## wherein u represents hydrogen, carboxamido, N-hydroxycarboxamido, carboxy, azido, an aryl, an acylamino, a protected carboxy or an N-alkoxycarboxamido, or, together with v, can represent --S-- or --CH.sub.2 S--; v represents hydrogen, halogen, cyano or an alkylthio, or, together with u, can represent --S-- or --CH.sub.2 S--, or, together with w, can represent --(CH.sub.2).sub.3 CO--; w represents hydrogen, carboamoyl, cyano, carboxy, an N-alkylcarbamoyl, an alkyl, an aryl, a protected carboxy or a heterocycle, or, together with v, can represents --(CH.sub.2).sub.3 CO--; x represents halogen, trifluoromethyl, an alkylthio or an arylthio; y represents hydrogen, a light metal or a carboxylic acid protecting group; and z represents an acyloxy or a heterocycle-thio, each of the above radicals represented by the symbols u, v, w, x, y and z being optionally substituted by halogen or a carbon-, nitrogen-, oxygen- or sulfur-containing functional group, a process for preparing the compound, a pharmaceutical composition containing the compound, and a therapeutical use of the compound. A compound of the formula: ##STR2## wherein u, v, w and x are as defined above, useful as a starting compound for preparing the compound (I) is also provided.

Vinylthioacetamido oxacephalosporin derivatives

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Suita, Japan

Toshiro Konoike