Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-12-06
1997-08-12
Chang, Ceila
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514309, 514316, 514322, 514323, 514324, 514329, 5142358, 5142362, 5142365, 5142368, 544124, 544129, 546139, 546187, 546193, 546198, 546199, 546201, 546202, 546207, 546208, 546209, 546210, 546211, A61K 31445, C07D40114, C07D40506, C07D40914
Patent
active
056566425
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP 94/00549 filed Apr. 4, 1994.
1. Industrial Field of Utilization
The present invention relates to novel peripheral vasodilating agents each containing, as an active ingredient, a piperidine derivative having an excellent peripheral vasodilating activity.
2. Prior Art and Problems to Be Solved by the Invention
Various compounds having a peripheral vasodilating activity have been used for the treatment of various disturbances in peripheral circulations. As such compounds, there are known, for example, nicotinic acid derivatives such as Inositol Nicotinate, Ecofrol, Nicametate, Nicotinyl Alcohol Tartarate and the like; norephedrin derivatives such as Nylidrin hydrochloride, Isoxsuprine hydrochloride and the like; Bamethan sulfate and compounds similar thereto; imidazoline derivatives such as Tolazoline hydrochloride and the like; and Trimethylcyclohexyl mandelate.
Some of these known peripheral vasodilating compounds, however, have effects to the heart such as effect to heart rate, hypotensive effect, myocardinal contraction effect and the like, and other adverse effects. Therefore, development of new peripheral vasodilating compound is still desired.
In addition to the above, various compounds, each of which having chemical structural formula similar to that of the piperidine derivative represented by the below-mentioned general formula (1), have been known in some prior art references for example: (Otsuka Pharmaceutical Co., Ltd.): Publication No. Sho 64-9313 (1989)]; Publication No. Sho 64-53248 (1989)]; (1977); other than the present applicant's company: (Laid-open) No. Hei 2-169569; EP-A-0296560A2; U.S. Pat. Nos. 5,100,901; & 4,895,841)]; 207384f]; Abstr., 109, (15): 128570x, DE-A-3740383]; 46341c]; Abstr., 117, (9): 90151m; EP-A-457686, (Chem. Abstr., 116, (11): 106097r]; Abstr., 104, (15): 129918a]; (Laid-open) Nos. Sho 56-92884; 56-125385; 56-161386; 56-164183; 56-164184, 56-166188, 57-40482; Chem. Pharm. Bull., 1985, 33, (3), pp. 1116-1128; J. Heterocyclic Chem., 20, pp. 565-573 (1983); Abstr., 104, (9): 68856e]; Japanese Patent Kokai (Laid-open) No. Sho 59-21680 [EP-A-99139, Chem. Abstr., 101, (3): 23473z]; formulae similar to those of piperidine compounds of the present invention, but the former do not overlapped with the latter: Kokai (Laid-open) No., Sho 54-36259]; Chem. Abstr., 91, (7): 56817t [Japanese Patent Kokai (Laid-open) No. Sho 54-8589]; 62-89679]: 61-161262]; 2-138161]; 206799y [Japanese Patent Kokai (Laid-open) No. Hei 2-306951]; Sho 44-17387 & 43-29585] 162500x];
These compounds being disclosed in the above-mentioned prior art references indeed possess certain pharma-cological activities, for example myocardial contraction increasing activity (positive inotropic activity), coronary blood flow increasing activity, hypotensive activity and antiinflammatory activity, etc. However, such known compounds do not possess any peripheral vasodilating activities at all.
The present inventors made an extensive study in order to develop a peripheral vasodilating agent of new type and, as a result, found that the piperidine derivatives of the general formula (1) shown below or salts thereof have an excellent peripheral vasodilating activity.
Each of the piperidine derivatives of the present invention, when contained in and used as a peripheral vasodilating agent, is useful as an agent for improving peripheral circulatory disturbances caused by arterial diseases (e.g. Berger disease, obstructive arteriosclerosis, Raynaud disease and Raynaud syndrome), venous diseases (e.g. venous thrombosis and thrombophlebites) and other diseases (e.g. congelation, frostbite, feeling of cold and decubitus), and is effective for the preventions and treatments of feeling of coldness accompanied by oversensitivity to the cold and hypnagogic disturbance, etc.
The piperidine derivatives of general formula (1) and their salts according to the present invention are characterized particularly in that while they have an excellent peripheral vasodilating activity, they show low pharmacologi
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Fujioka Takafumi
Shimizu Hiroshi
Tabusa Fujio
Tanaka Michinori
Teramoto Shuji
Chang Ceila
Otsuka Pharmaceutical Co. Ltd.
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