Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-06-04
1998-12-01
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514332, 514333, 544357, 544360, 546256, 546263, C07D40112, C07D40114, A61K 31445, A61K 31495
Patent
active
058439501
DESCRIPTION:
BRIEF SUMMARY
CROSS REFERENCE
This application is a 371 of PCT/JP95/01507 filed Jul. 28, 1995
TECHNICAL FIELD
The present invention relates to a novel 1,4-dihydropyridine compound having a platelet activating factor (PAF) antagonistic action and thromboxane synthesis inhibiting action and further having an action for overcoming resistance to an anti-cancer drug or an action for reinforcing the effect of an anti-cancer drug and an anti-allergenic, antiphlogistic, a drug for overcoming resistance to an anti-cancer drug, or a drug for reinforcing the effect of an anti-cancer drug containing the said compounds or a pharmacologically acceptable salt thereof as an effective ingredient.
BACKGROUND ART
1,4-dihydropyridine derivatives have been reported to have many pharmacological activities, among which particularly the vasodilating action based on the calcium antagonistic action is widely known. Further, in addition to this vasodilating action, compounds having an action suppressing platelet aggregation are being developed with the intent of treatment of ischemic diseases (see Japanese Unexamined Patent Publication (Kokai) No. 61-197578, Japanese Unexamined Patent Publication (Kokai) No. 62-187468, and Japanese Unexamined Patent Publication (Kokai) No. 3-20271). As other actions, Japanese Unexamined Patent Publication (Kokai) No. 1-113367 reports a platelet activating factor (PAF) antagonistic action and Japanese Unexamined Patent Publication (Kokai) No. 61-167617 a thromboxane A.sub.2 (TxA.sub.2) synthesis inhibiting action, but these are considered to suppress just PAF or TxA.sub.2 alone. Further, Japanese Examined Patent Publication (Kokoku) No. 56-37225 shows compounds having a coronary vasodilating action and describes a general formula which includes the compounds of the present invention, but this publication does not describe as specific compounds the compounds included in the present invention having the 3-(3-pyridyl)propyl group etc. at the 3-position of the 1,4-dihydropyridine.
Further, Japanese Unexamined Patent Publication (Kokai) No. 61-60683 shows compounds having a thromboxane synthesis inhibiting action and describes a general formula including the compounds of the present invention, but the publication does not describe as specific compounds any compounds with an isopropyl group or other C.sub.2 -C.sub.10 alkyl group bonded at the 4-position of the 1,4-dihydropyridine. Further, the compounds described in the publication, as shown in the later test examples, have a TxA.sub.2 synthesis inhibiting action, but have no PAF antagonistic action at all.
PAF and TxA.sub.2 interact and contribute to asthma, arthritis, rhinitis, bronchitis, and rashes and other various allergenic, inflammatory, and hypersecretion type diseases and thrombosis of the circulatory system, pulmonary hypertension, and stomach ulcers, psoriasis, and other diseases. Accordingly, in the treatment of these diseases, a greater therapeutic effect can be expected by suppressing PAF and TxA.sub.2 simultaneously rather than suppressing PAF or TxA.sub.2 alone.
On the other hand, at the present time, a problem has arisen with "acquired resistance" in the chemotherapy of cancer wherein the effectiveness of the anti-cancer drug is lost during the treatment. Drug resistance to a variety of types of anti-cancer drugs is becoming a serious problem. As a method for overcoming this multi-drug resistance, it has been reported that concomitant administration of an anti-cancer drug and some calcium antagonists (nicardipine and other 1,4-dihydropyridine compounds etc.) is vol. 11, pp. 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 and Japanese Examined Patent Publication (Kokoku) No. 6-92401 describe compounds with dioxene rings or dithiene rings bonded at the 4-position of 1,4-dihydropyridine, while Japanese Unexamined Patent Publication (Kokai) No. 5-117235 and Japanese Unexamined Patent Publication
REFERENCES:
patent: 4876255 (1989-10-01), Franckowiak et al.
Fujita Masakazu
Kamakura Mie
Kiue Akira
Miura Teruhisa
Sano Tetsuro
Nikken Chemicals Co., Ltd.
Rotman Alan L.
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