Taiho Pharmaceutical Company Limited

Otsuka Kagaku Kabushiki Kaisha

Other

Delta-fly Pharma, Inc.

Shozo Yamada

Motoaki Tanaka

Hideo Tanaka

Sigeru Torii

Tetsuji Asao

Akira Nakai

Kazuhiko Shigeno

Hisashi Ohbayashi

Shigeo Okajima

Tomoyasu Ohno

Kazuhiro Kitagawa

Masakazu Fukushima

Makoto Kajitani

Hajime Fujimura

Takaji Honna

Shingo Yano

Yukio Tada

Yoshimitsu Suda

Yasuzo Hiramatsu

Tomohiro Yamashita

Kenji Nozaki

Tomio Yamazaki

Noriyuki Yamamoto

Nobuhiko Katsunuma

Hirofusa Ajioka

Mamoru Kiniwa

Atsuhiko Uemura

Toshiyuki Hosoya

Masayasu Kimura

Takashi Suzuki

Shin-ichi Inoue

Ryo Oyama

Kosuke Fujiwara

Yasuo Konno

Tomoyasu Ono

The present invention provides a novel antimetabolic anticancer agent that has an excellent balance between antitumor effect and toxicity. Specifically, the present invention provides a medicament containing, as an active ingredient, a 5-fluorouracil derivative represented by Formula (I) or a salt thereof: wherein Rrepresents a hydrogen atom or a protecting group of a hydroxy group, Rrepresents a lower alkoxy-lower alkyl group or a tetrahydrofuranyl group, X represents a carbon atom or a nitrogen atom, and Y represents a halogen atom or a cyano group.

5-fluorouracil derivative

A method of manufacturing substance GM-95 having general formula &lsqb;I&rsqb;, comprising (a) deprotecting a macrocyclic compound having general formula &lsqb;II&rsqb; (wherein, R 's are the same or different and each represents a lower alkyl group, and R represents a thiol protecting group) by removing acetal protecting groups (the R 's) thereof, and forming an oxazole ring through an intramolecular cyclization reaction between produced formyl group and an amide group, and (b) deprotecting a resulting macrocyclic compound having general formula &lsqb;III&rsqb; (wherein, R is as mentioned above) by removing the thiol protecting group (R ) thereof, and forming a thiazoline ring through an intramolecular cyclization reaction between a thiol group thus produced and an amide group.

Process for preparing substance GM-95

This invention provides a compound having both IL-4 production inhibitory activity and PDE (IV) inhibitory activity, represented by formula (I):

Benzimidazole derivatives and pharmacologically acceptable salts thereof

Epoxysuccinamide derivative or salt thereof

4,6-diarylpyrimidine derivatives and salts thereof

Process for preparing 1-amino-1,2,3-triazole

Benzothiadiazine derivatives

Disclosed is a process for preparing 2.beta.-substituted-methylpenicillin derivative of the formula ##STR1## wherein R is H or carboxyl protecting group, R.sub.1 is H or halo, R.sub.2 is H, lower alkyl, lower alkoxy, halogen, azido, lower alkylthio, phthalimide or a group --NHR.sub.3 (wherein R.sub.3 is H or acyl), and --N Y is an optionally substituted monocyclic or bicyclic heterocyclic group having 1 to 4 nitrogen atoms in the ring structure, the process comprising reacting a compound of the formula ##STR2## wherein X is Cl or Br, and R, R.sub.1 and R.sub.2 are as defined above with a heterocyclic compound of the formula ##STR3## wherein --N Y is as defined above.

Process for preparing 2.beta.-substituted-methylpenicillin derivatives

A process for preparing a 2.beta.-substituted-methylpenicillin compound of the formula ##STR1## wherein --N Y is an optionally substituted heterocyclic group containing 2 to 4 nitrogen atoms as the hetero atom in the ring structure, and R.sub.1 is a penicillin carboxyl protecting group, the process comprising reacting an azetidinonedisulfide compound of the formula ##STR2## wherein R.sub.1 is as defined above and R is a substituted or unsubstituted heterocyclic group with a nitrogen-containing heterocyclic compound of the formula ##STR3## wherein ##STR4## is as defined above in the presence of a metal compound.

2.alpha.-Methyl-2.beta.-(1,2,3-triazol-1-yl)methylpenam-3.alpha.-carboxylic acid derivatives are prepared by reacting a penicillanic acid sulfoxide derivative of the formula ##STR1## wherein R is a penicillin carboxyl protecting group, and R.sub.1 is hydrogen or halogen, R.sub.2 is hydrogen, lower alkyl or the like with a triazole derivative of the formula ##STR2## wherein R.sub.3 and R.sub.4 are hydrogen, trialkylsilyl, lower alkyl, lower alkoxy or the like and R.sub.5 is hydrogen or silyl substituted with 3 groups selected from the class consisting of lower alkyl, benzyl and phenyl in a solvent.

Process for preparing

Disclosed are 2.beta.-substituted-methylpenicillanic acid compounds of the formula ##STR1## wherein n is 0, 1 or 2; and ##STR2## is monocyclic or bicyclic heterocyclic ring group which has 2 to 4 nitrogen atoms as hetero atom in its ring structure and which may be optionally substituted with alkyl, alkoxycarbonyl, phenyl, formyl or benzyloxycarbonyl optionally having alkyl, nitro or a halogen atom on the benzene ring, with the proviso that said heterocyclic ring group is not 1,2,3-triazol-1-yl; or salts or esters thereof. These compounds are useful as .beta.-lactamase inhibitor.

2.beta.-Substituted-methylpenicillanic acid derivatives, and salts and

Disclosed is a penicillin derivative of the formula: ##STR1## wherein n is an integer of 0, 1 or 2; Y is a cyano group, a lower acyl group, a mono- or di-lower alkylthiocarbamoyl group, ##STR2## wherein R.sub.1 is a hydrogen atom, a lower alkyl group, a phenyl group, a group --(CH.sub.2).sub.m --OR.sub.2 or --(CH.sub.2).sub.m COOR.sub.2 (m is an integer of 1 to 6 and R.sub.2 is a hydrogen atom or a penicillin carboxyl ester-forming group which is commonly used for penicillin derivatives) or a phenyl group substituted by at least one member selected from the class consisting of lower alkyl group, halogen atom and lower alkoxy group; and R is a hydrogen atom or a penicillin carboxyl ester-forming group, or a salt thereof. They are useful as .beta.-lactamase inhibitors.

2 .beta.-substituted thiomethylpenicillin derivatives and their

An analgesic composition containing as active ingredient a piperazine derivative represented by the general formula (1) ##STR1## wherein R.sub.1 represents a cyclopropylmethyl group, an isopropyl group or an allyl group and R.sub.2 represents a phenyl group having as substituent a halogen atom or a trifluoromethyl group.

Piperazine derivative and analgesic composition containing the same

Growing community of inventors

Hanno, Japan

Shozo Yamada