Eisai Company, Limited

Kyosuke Kitoh

Yoshimasa Machida

Shigeto Negi

Norihiro Ueda

Seiichiro Nomoto

Yoshihiko Kotake

Takeshi Nagasu

Tatsuo Watanabe

Jun Niijima

Nozomu Koyanagi

Kentaro Yoshimatsu

Hiroshi Yoshino

Isao Saito

Makoto Asada

Kappei Tsukahara

Kanemasa Katsu

Takashi Kamiya

Toshimi Okada

Atsumi Iijima

Isao Sugiyama

Hiroshi Yamauchi

Toru Haneda

Hiroyuki Sugumi

Hironori Ikuta

Takaharu Nakamura

Toshihiko Naito

Yuuki Komatu

Yasunobu Kai

Naoko Tsukahara

Hiroaki Nomura

Yukio Ohya

Yoshihiro Kubota

Takeshi Suzuki

Motosuke Yamanaka

Seiichi Araki

Kenji Koga

Takeo Kanai

Noritoshi Koyama

Katsumi Ida

Takayuki Ikeuchi

Hirovuki Sugumi

Kyoko Koizumi

Kiyoshi Tomioka

Novel tricyclic heterocyclic sulfonamide derivatives and sulfonic ester derivatives which have excellent antitumor activity and are represented by the following general formula (I) and processes for producing the same are provided. The present sulfonamide derivatives or a sulfonic ester derivatives are represented by the following general formula (I): ##STR1## wherein G represents an aromatic 5- or 6-membered ring; L represents 0 or --N(R.sup.1)-- and --R.sup.1 represents hydrogen or lower alkyl; and M represents a tricyclic structure selected from among the following; ##STR2## rings A and B each represent an unsaturated 5- or 5 -membered ring; X represents N(R.sup.2) wherein R.sup.2 represents hydrogen or lower alkyl, or NHCO; Y represents 0, S(O).sub.n, C(R.sup.3) (R.sup.4), C(O), N(R.sup.5), CH(R.sup.6)CH(R.sup.7), C(R.sup.8).dbd.C(R.sup.9), N(R.sup.10) C(O), N.dbd.CR.sup.11), OCH(R.sup.12), S(O).sub.n CH(R.sup.13) or N(R.sup.14)CH(R.sup.15); Z represents nitrogen or C(R.sup.16); and n represents 0, 1 or 2, R.sup.3 to R.sub.13, R.sup.15 and R.sup.16 each represent hydrogen or lower alkyl, and R.sup.14 represents hydrogen, lower alkyl or lower acyl.

Tricyclic heterocyclic sulfonamide and sulfonic ester derivatives

A sulfonamide derivative or a sulfonic ester derivative represented by the following general formula (I): ##STR1## {G represents an aromatic 5- or 6-membered ring; L represents O or --N(R.sup.1)-- (R.sup.1 represents hydrogen or lower alkyl); and M represents ##STR2## rings A and B represent each an unsaturated 5- or 6-membered ring; Y represents O, S(O).sub.n, C(R.sup.3)(R.sup.4), C(O), N(R.sup.5), CH(R.sup.6)CH(R.sup.7), C(R.sup.8).dbd.C(R.sup.9), N(R.sup.10)C(O), N.dbd.C(R.sup.11), OCH(R.sup.12), S(O).sub.n CH(R.sup.13) or N(R.sup.14)CH(R.sup.15).

A novel pyrimidine derivative having an excellent antitumor activity, which is represented by the following general formula (I) or a pharmacologically acceptable salt thereof: ##STR1## wherein R.sup.1 represents a hydroxyl or amino group;

Condensed pyrimidine derivative

Sulfonamide compounds of formula (I) or a pharmacologically acceptable salt thereof: ##STR1## exhibit excellent antitumor activity and low toxicity.

Pyrimidinyl or pyridinyl sulfonamide substituted compounds

Sulfonamide compounds of the formula or pharmacologically acceptable salts thereof: ##STR1## wherein: R.sup.1 is a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, nitro group, phenoxy group, cyano group, acetyl group, amino group or a protected amino group; R.sup.2 and R.sup.3 may be the same or different from each other and each is a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group; R.sup.4 and R.sup.7 may be the same or different from each other and each is a hydrogen atom or a lower alkyl group; R.sup.5 and R.sup.6 may be the same or different from each other and each is a hydrogen atom, halogen atom, lower alkoxy group, amino group or amino group substituted with a lower alkyl or a phenyl group; A is .dbd.CH--; B is .dbd.CH--; and E is selected from the group consisting of ##STR2## in which Q is an oxygen atom or a sulfur atom; and R.sup.11 is a hydrogen atom, a lower alkyl group, an amino group which may be substituted with a lower alkyl group, a lower alkoxy group, a 2-thienyl group, a 2-furyl group, phenyl group or a phenyl group having from 1 to 3 substituents, said substituents being the same or different from one another and selected from the group consisting of a halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, carboxyl group, esterified carboxyl group, amidated carboxyl group, lower alkylthio group and phenoxy group; and (b) a phenyl group or a phenyl group having from 1 to 3 substituents.

Sulfonamide phenyl substituted compounds

A novel pyrimidine derivative having an excellent antitumor activity, which is represented by the following general formula (I) or a pharmacologically acceptable salt thereof: ##STR1## wherein R.sup.1 represents a hydroxyl or amino group; R.sup.2 represents a phenylene, pyridinediyl, thiendiyl, furandiyl or thiazoldiyl group, --CO.sub.2 R.sup.5 and --CO.sub.2 R.sup.6 may be the same or different from each other and each represents a carboxyl group or a carboxylic acid ester, the part ##STR2## A represents an oxygen atom, a group represented by the formula: ##STR3## (wherein R.sup.3 and R.sup.4 may be the same or different from each other and each represents a hydrogen or halogen atom or a hydrocarbon group which may be substituted, or alternatively R.sup.3 and R.sup.4 may be united to form an alkylidene group which may be substituted) or a group represented by the formula: ##STR4## (wherein R.sup.70 represents a hydrogen atom or a hydrocarbon group), and n is an integer of 1 to 3, provided that the compound in which R.sup.1 represents oxygen, and hydrogen is attached to nitrogen at 3-position is included in the above shown definition, a process for preparation the same, and an antitumor drug containing the same.

Sulfonamide derivatives of the general formula (I): ##STR1## wherein preferably R.sup.1 represents a lower alkoxy group, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may be the same or different from one another and each represent a hydrogen atom, halogen atom or lower alkyl group, A and B may be the same or different from each other and each represent .dbd.N-- or .dbd.CH--, E represents an aromatic 6-membered cyclic group, which may have 1 or 2 nitrogen atoms in the ring, and be substituted with 1 to 3 substituents which may be the same or different from one another with the proviso that a combination of R.sup.1 which is a hydrogen atom, lower alkyl group, nitro group or amino group which may be protected, R.sup.2 and R.sup.3 which are each a hydrogen atom, A and B which are each .dbd.CH-- and E which is a phenyl group which may be substituted with 1 to 3 substituents G which may be the same or different from one another is excluded, or pharmacologically acceptance salts of them, have an excellent antitumo-activity.

Sulfonamide derivatives

Sulfonamide derivatives of the general formula (I): ##STR1## wherein preferably R.sup.1 represents a lower alkoxy group, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may be the same or different from one another and each represent a hydrogen atom, halogen atom or lower alkyl group, A and B may be the same or different from each other and each represent .dbd.N-- or .dbd.CH--, E represents an aromatic 6-membered cyclic group, which may have 1 or 2 nitrogen atoms in the ring, and be substituted with 1 to 3 substituents which may be the same or different from one another with the proviso that a combination of R.sup.1 which is a hydrogen atom, lower alkyl group, nitro group or amino group which may be protected, R.sup.2 and R.sup.3 which are each a hydrogen atom, A and B which are each .dbd.CH-- and E which is a phenyl group which may be substituted with 1 to 3 substituents G which may be the same or different from one another is excluded, or pharmacologically acceptable salts of them, have an excellent antitumor activity.

Pyridine carboxamide compounds which have useful as pharmaceutical

Sulfonamide derivatives of the general formula (I): ##STR1## wherein preferably R.sup.1 represents a lower alkoxy group, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may be the same or different from one another and each represent a hydrogen atom, halogen atom or lower alkyl group, A and B may be the same or different from each other and each represent .dbd.N-- or .dbd.CH--, E represents an aromatic 6-membered cyclic group, which may have 1 or 2 nitrogen atoms in the ring, and be substituted with 1 to 3 substituents which may be the same or different from one another with the proviso that a combination of R.sup.1 which is a hydrogen atom, lower alkyl group, nitro group or amino group which may be protected, R.sup.2 and R.sup.3 which are each a hydrogen atom, A and B which are each .dbd.CH-- and E which is a phenyl group which may be substituted with 1 to 3 substituents G which may be the same or different from one another is excluded, or pharmacologically acceptance salts of them, have an excellent antitumor activity.

Sulfonamide derivatives of the general formula (I): ##STR1## wherein preferably R.sup.1 represents a lower alkoxy group, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are as defined in the specification, A and B may be the same or different from each other and each represents .dbd.N-- or .dbd.CH--, E represents an aromatic 6-membered cyclic group, which may have 1 or 2 nitrogen atoms in the ring, and may be substituted with 1 to 3 substituents which may be the same or different from one another with the proviso that a combination of R.sup.1 which is a hydrogen atom, lower alkyl group, nitro group or amino group which may be protected, R.sup.2 and R.sup.3 which are each a hydrogen atom, A and B which are each .dbd.CH-- and E which is a phenyl group which may be substituted with 1 to 3 substituents G which may be the same or different from one another is excluded, or pharmacologically acceptance salts of them.

A 3-propenylcephem derivative of the following formula: ##STR1## wherein R.sub.1 represents a fluoro-substituted lower alkyl group or a cyano-substituted lower alkyl group, and A represents a cyclic or an acylic ammonio group, or a pharmaceutically acceptable salt thereof, exhibiting excellent anti-bacterial activities against both Gram-positive bacteria and Gram-negative bacteria; Process for the preparation thereof; Anti-bacterial composition; Intermediate for the 3-propenylcephem derivative; and Process for the preparation of the intermediate.

3-propenylcephem derivative

An azacyclooctadiene compound having the formula (1) or a pharmacologically acceptable salt thereof is novel and useful as an anti-tumor agent. ##STR1## in which R1 is --CH2R, R being hydrogen, --COCH3, --OH, --NH2, --COOH or --OCOCH3, or may form --CH2--X--Y-- together with R2; R2 is hydrogen, an alkyl having 1 to 4 carbon atoms or --COR10, R10 being hydrogen, an alkyl having 1 to 4 carbon atoms, --OR11 or --NHR11, R11 being an alkyl having 1 to 4 carbon atoms, or may form --CH2--X--Y-- together with R1; R3, R4 and R5 each are hydrogen or methyl; R6 and R7 each are hydrogen or may form the direct bond to each other; R8 is hydrogen or may form the direct bond to R7; and R9 is hydrogen, --N3, --NH2, --OCH3 or .dbd.0; X being oxygen or --NZ--, Z being hydrogen, methyl, --COCH3, --CH2COOH, --CO--CH.dbd.CH2, --CO--CH.dbd.CH--CH3, --CH2C6H5, --CH2OH, --CH2OCOCH3 or --CH2--COOC(CH3)3, Y being --SC--, --CO-- or --CH2--.

Azacyclooctadiene compound and pharmaceutical use

Novel thiadiazolylacetamide cephem derivatives of the following formula are described. ##STR1## wherein A represents a quaternary ammonio group; or a pharmaceutically acceptable salt thereof. These novel compounds are useful as antibacterial agents, because they have a broad antibacterial spectrum ranging from gram-negative bacteria to gram-positive bacteria. Processes for the preparation of these novel compounds are also described.

Thiadiazolylacetamide cephem derivatives

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Ibaraki, Japan

Kyosuke Kitoh