Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-09-09
1999-07-06
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514338, 514366, 546199, 546271, 548151, C07D51304, A61K 31425
Patent
active
059197994
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel imidazothiazole compound having an action in overcoming resistance to an anti-neoplastic agent or an action in enhancing the effect of an anti-neoplastic agent, more specifically relates to a tetrahydroimidazo-benzothiazole or imidazobenzothiazole compound.
BACKGROUND ART
At the present time, in chemotherapy for cancer, "acquired resistance" where the cancer suppressing effect is lost during treatment is becoming a problem. Multidrug resistance where resistance is exhibited against various types of anti-neoplastic agents is becoming an important issue. As a method for overcoming this multidrug resistance, it has been reported that co-administration of the anti-neoplastic agent and some calcium antagonists (1,4-dihydropyridine compounds such as Nicardipine) is effective. (Cancer Res., 41, 1967-1972 (1981), Cancer and Chemotherapy, vol. 11, 750-759 (1984)).
Further, Japanese Unexamined Patent Publication (Kokai) No. 2-40383, Japanese Unexamined Patent Publication (Kokai) No. 2-240081, Japanese Examined Patent Publication (Kokoku) No. 6-92391, Japanese Examined Patent Publication (Kokoku) No. 6-92401, Japanese Unexamined Patent Publication (Kokai) No. 5-117235, and Japanese Unexamined Patent Publication (Kokai) No. 2-138221 describe that a 1,4-dihydropyridine compound has an action overcoming resistance to anti-neoplastic agents. Further, recently, there are reports on quinoline or indole derivatives having a similar action in overcoming resistance to anti-neoplastic agents (see Japanese Unexamined Patent Publication (Kokai) No. 4-235983 and Japanese Unexamined Patent Publication (Kokai) No. 5-43544).
On the other hand, as imidazothiazole derivatives, action, and therefore, patent applications have been filed as an anti-allergenic, an anti-rheumatic, and an anti-asthmatic drugs (see Japanese Unexamined Patent Publication (Kokai) No. 56-138196, Japanese Unexamined Patent Publication (Kokai) No. 57-40492, and Japanese Unexamined Patent Publication (Kokai) No. 57-149288). Further, patent anti-neoplastic agent or brain enhancers (see Japanese Unexamined Patent Publication (Kokai) No. 1-319487, Japanese Unexamined Patent Publication (Kokai) No. 1-319488, Japanese Unexamined Patent Publication (Kokai) No. 2-178289, Japanese Unexamined Patent Publication (Kokai) No. 2-306918, and Japanese Unexamined Patent Publication (Kokai) No. 2-306917).
Further, as imidazothiazole derivatives, to exhibit an immunosuppressive action and an anticancer action (see U.S. Pat. No. 3,579,530 (1971)).
However, no report has been made concerning the action of a tetrahydroimidazobenzothiazole or imidazobenzothiazole compound in overcoming resistance to anti-neoplastic agents.
DISCLOSURE OF INVENTION
The present inventors synthesized large numbers of tetrahydroimidazobenzothiazole or imidazobenzothiazole compounds and screened these compounds broadly for the existence of co-acting effects thereof with anti-neoplastic agents. As a result, we discovered that imidazothiazole compounds having the following formula (A) have an action of remarkably increasing the sensitivity of cancer cells to anti-neoplastic agents, in particular the sensitivity of cancer cells having acquired resistance to anti-neoplastic agents. Further, they learned that these compounds have the effect of prolonging the period of survival of tumor bearing animals through the administration thereof in combination with anti-neoplastic agents and further are low in toxicity, whereby the present invention has been completed.
That is, in accordance with the present invention, there is provided an imidazothiazole compound having the formula (A): ##STR2## (wherein, R.sub.1 is a phenyl group or a naphthyl group which may have a substituent, R.sub.2 is an acyl group, and the bonds at two dotted line portions may or may not exist simultaneously), or a pharmacologically acceptable salt thereof and an agent for overcoming resistance to anti-neoplastic agent or an agent for enhancing the effect of anti-neoplastic agent compr
REFERENCES:
patent: 3579530 (1971-05-01), Dewar
Patent Abstracts of Japan, vol. 6, No. 257 (C-140), 16 Dec. 1982 & JP 57 149288 A (Yamanouchi Seiyaku KK), 14 Sep. 1982.
Patent Abstracts of Japan, vol. 6, No. 110 (C-109), 22 Jun. 1982 & JP 57 040492 A (Yamanouchi Pharmaceut Co Ltd), 6 Mar. 1982.
Paten Abstracts of Japan, vol. 16, No. 584 (C-1013), 24 Dec. 1992 & JP 04 235983 A (Mitssui Toatsu Chem Inc).
A.-N. El-Shorbagi et al.; Chemical and Pharmaceutical Bulletin, vol. 37, No. 11, 1989, pp. 2971-5, XP002062481.
Kiue Akira
Tasaka Shigeyuki
Gerstl Robert
Nikken Chemicals Co., Ltd.
LandOfFree
Imidazothiazole compound does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Imidazothiazole compound, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Imidazothiazole compound will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-899306