Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-03-23
1998-11-10
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142245, 5142248, 5142298, 514250, 514297, 540547, 540495, 544 56, 544582, 544108, 544348, 546102, 546103, 546104, C07D20988, C07D21908, A61K 3140, A61K 3147
Patent
active
058344624
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INDUSTRIAL APPLITCATION
This invention relates to a novel sulfonamide or sulfonic ester derivative, a process for producing the same and a medicinal composition comprising this compound as an active ingredient.
PRIOR ART
There have been a number of chemotherapeutic agents used for cancer, for example, alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, vincristine and etoposide originating in plants and metal complexes such as cisplatin. However each of these agents exerts an insufficient antitumor effect. Thus there has been an urgent need to develop a novel antitumor agent.
Further, there have been reported antitumor compounds of aromatic sulfonamide type such as 4-aminobenzenesulfonamide derivatives (Japanese Patent Publication No. 3093/1968), 2-sulfanilamide-quinoxaline derivatives (Japanese Patent Laid-Open No. 429/1987) and N-(2-anilino-3-pyridyl)benzenesulfonamide derivatives (Japanese Patent Laid-Open No. 39256/1993). No antitumor compound of aromatic sulfonic ester type has been reported so far.
DISCLOSURE OF THE INVENTION
The present invention aims at providing novel sulfonamide derivatives and novel sulfonic ester derivatives each having excellent antitumor activity and differing in the basic skeleton from the conventional antitumor compounds. It further aims at providing processes for producing these compounds and medicinal compositions comprising these compounds as an active ingredient.
In view of these aims, the present inventors have conducted extensive studies to seek excellent antitumor compounds. As a result, they have found that a novel sulfonamide derivative and a novel sulfonic ester derivative with a tricyclic structure have each excellent antitumor activity and a low toxicity, thus completing the present invention.
Accordingly, the present invention relates to a sulfonamide derivative or a sulfonic ester derivative represented by the following general formula (I) or a pharmacologically acceptable salt thereof: ##STR3## wherein G represents an aromatic 5- or 6-membered ring having 1 or 2 substituents; alkyl or oxygen; and following formulae (a), (b), (c), (d), (e) and (f); ##STR4## wherein rings A and B each represent each an optionally substituted unsaturated 5- or 6-membered ring; alkyl, or --NHCO--; --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)--, --C(O)N(R.sup.10)--, --N.dbd.C(R.sup.11)--, --C(R.sup.11).dbd.N--, --OCH(R.sup.12)--, --CH(R.sup.12)O--, --S(O).sub.n CH(R.sup.13)--, --CH(R.sup.13)S(O).sub.n --, --N(R.sup.14)CH(R.sup.15)-- or --CH(R.sup.15)N(R.sup.14)--, wherein n represents 0, 1 or 2, R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are the same or different from one another and each represents hydrogen or lower alkyl, R.sup.5, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.15 each represents hydrogen or lower alkyl, and R.sup.14 represents hydrogen, lower alkyl or lower acyl; and hydrogen or lower alkyl; 4-methoxycarbonylaminophenyl, X in the tricyclic structure (a) of M is --N(R.sup.2)--and Y is oxygen or --S(O).sub.n --, wherein n is 0, is excluded therefrom.
The present invention involves the following modes.
A sulfonamide derivative or a sulfonic ester derivative represented by the following general formula (I-a) or a pharmacologically acceptable salt thereof: ##STR5## wherein R.sup.31 represents hydrogen, halogen, lower alkyl, lower alkoxy, nitro, cyano or amino optionally substituted by lower alkyl; represents hydrogen, lower alkyl, lower alkoxy or halogen; hydrogen or lower alkyl; and following formulae (a), (b), (c), (d), (e) and (f): ##STR6## wherein rings A and B represent each an optionally substituted unsaturated 5- or 6-membered ring; (R.sup.37)--, --C(O)--, --N(R.sup.38)--, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NHCO--, --CONH--, --CH.dbd.N--, --N.dbd.CH--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 S--, --SCH.sub.2 --, --CH.sub.2 N(R.sup.39)--, --N(R.sup.40)CH.sub.2 --, --CH.sub
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Haneda Toru
Kitoh Kyosuke
Kotake Yoshihiko
Koyanagi Nozomu
Nagasu Takeshi
Berch Mark L.
Eisai Co. Ltd.
Kifle Bruck
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