Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1999-11-01
2000-09-05
Stockton, Laura L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5483074, 5483097, A61K 314184, C07D23514, C07D23530
Patent
active
061143693
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to a novel benzimidazole derivative having an antiallergic activity and a drug containing it as an active ingredient.
DESCRIPTION OF THE BACKGROUND
In the treatment of type I allergy-related diseases such as pollinosis, urticaria, atopic dermatitis, allergic rhinitis and asthma, antihistamines and steroids have heretofore been frequently used. However, problems still remain with respect to the clinical usefulness thereof. The above mentioned allergy-related diseases are triggered by an immune reaction of a specific antigen with IgE antibody and progress to a chronic state via inflammation of the diseased portion or tissue damage. It has been suggested that during this process, various chemical mediators are mutually closely related to the pathologic progress. Among them, histamine is believed to be involved mainly at the initial stage of the pathologic progress from the characteristics of its pharmacological action. This is considered to be the reason why a problem remains with respect to the clinical usefulness of antihistamines. On the other hand, steroids which are used primarily in severe cases, show pharmacological activities to inhibit a series of processes of immuno-inflammatory responses in various fashions and are believed to exhibit a high level of effectiveness. However, steroids have a problem of severe side effects, and there are many restrictions in their application to oral administration or repeated administration. Thus, in the field of treatment of type I allergy-related diseases, it is very much desired to develop a drug having a new mechanism for action and having a high level of effectiveness.
In recent years, it has been reported that substance P which is a neuropeptide, acts as a mediator to promote allergic symptoms and is deeply concerned in the inflammatory symptoms particularly in the chronic phase, (TIPS, 81, 24 (1987); Am. J. Respir. Crit. Care Med., 151, 613 (1995); J. Allergy Clin. Immunol., 92, 95 (1993)). Therefore, an antagonist of substance P is considered to be capable of effectively curing the allergic symptoms in the chronic phase (particularly the chronic inflammation).
Substance P is a member of the neurokinin family, and it is known that it is widely concerned in activation of macrophages or lymphocytes, and in immunity and inflammation as a regulatory factor for production of cytokine (IL1, TNF, IL6), and it causes inflammatory symptoms such as increase in vascular permeability, plasma leakage and secretory gland stimulation. Further, it functions as a transmitter of pain from peripheral to central, and it controls the transmission system of dopamine and adrenaline in brain.
Accordingly, a substance P antagonist is considered to be effective not only as an antiallergic agent but also as analgesics or psychomimetics.
Further, a drug having not only substance P antagonistic activities but also antihistamine activities, is considered to be effective for treatment of a wide range of allergic symptoms ranging from acute phase to chronic phase and thus is expected to be a drug which has clinically high curing effects.
SUMMARY OF THE INVENTION
As a result of extensive studies, the present inventors have found that the benzimidazole derivatives of the present invention have substance P antagonistic activities, and further that among the compounds of the present invention, many also have antihistamine activities.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Benzimidazoles having antihistamine activities have already been disclosed in e.g. JP-A-59-199679, JP-A-58-79983, EP-232937B, EP144101B and U.S. Pat. No. 4,219,559. However, the compounds of the present invention are not included in such disclosed benzimidazoles. Further, such prior art references disclose nothing about substance P antagonistic activities.
Thus, it has been found that the compounds of the present invention are superior compounds as antiallergic agents, and they are not only useful as active ingredients for preventive or curing agents
REFERENCES:
patent: 5290801 (1994-03-01), Higley et al.
Fujita Yoichiro
Hirotsuka Mitsuaki
Iwama Takehisa
Kamikawaji Yoshimasa
Tanikawa Keizo
Nissan Chemical Industries Ltd.
Stockton Laura L.
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