Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-11-23
2002-03-26
Powers, Fiona T. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C544S130000
Reexamination Certificate
active
06362179
ABSTRACT:
BACKGROUND OF THE INVENTION
Although not very many reports have been made on a low-molecular-weight, non-peptide type compound having antagonistic activity against both substance P receptors (NK
1
receptors) and neurokinin A receptors (NK
2
receptors), for example, the below-described compounds A, B and C are known as such compounds. According to the specification of PCT publication No. WO 94/17045, the compound B has antagonistic activity against both NK
1
and NK
2
receptors. A pharmacological test of the compound B made by the present inventors, however, has revealed that the antagonistic activity of the compound B against NK
1
receptors in vitro was markedly weak. In addition, when all of these compounds are orally administered, these are accompanied by problems such as insufficient antagonistic activity against both NK
1
receptors and NK
2
receptors.
SUMMARY OF THE INVENTION
For a long time, the present inventors have carried out an extensive investigation on the synthesis of derivatives having antagonistic activity against tachykinin (particularly, antagonism against substance P, antagonistic activity against neurokinins A and B) and their pharmacological activity. As a result, it has been found that compared with the above-described known compounds, specific novel salts of an optically active substance of spiro[benzo[c]thiophene-1(3H),4′-piperidin]-2-oxide having an absolute configuration of S exhibit better oral absorption and excellent antagonistic activity against both NK
1
and NK
2
receptors to complete the present invention.
An object of the present invention is to provide the above-described compound. Another object of the present invention is to provide a medicament comprising the above-described compound as an effective ingredient, particularly, as a preventive agent or remedy (a composition for prophylaxis or treatment) for tachykinin-mediated diseases. A further object of the present invention is to provide a use of the above-described compound for the preparation of a medicament, particularly, a preventive agent or remedy (a composition for the prevention or treatment) of tachykinin-mediated diseases or is to provide a method for preventing or treating tachykinin-mediated diseases, which comprises administering a pharmacologically effective amount of the compound to a warm-blooded animal.
Examples of the preventive agent or remedy include inhibitors of an NK
1
receptor and/or NK
2
receptor. Examples of the diseases include diseases of the central nervous system such as anxiety, depression, psychosis and schizophrenia; neurodegenerative diseases such as dementia of AIDS, Alzheimer's senile dementia, Alzheimer's disease, Down's syndrome, demyelinating disease, amyotrophic lateral sclerosis, neuropathy, peripheral neuropathy and neuralgia; respiratory diseases such as chronic obstructive pulmonary disease, bronchitis, pneumonia, bronchoconstriction, asthma and cough; inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, fibrosis, arthrosteitis, degenerative arthritis and rheumatoid arthritis; eczema; allergies such as rhinitis; hypersensitivity diseases such as hypersensitivity to vines; ophthalmological diseases such as conjunctivitis, vernal conjunctivitis, vernal catarrh, destruction of the blood-aqueous humor barrier caused by various inflammatory eye diseases, elevated introcular pressure and miosis; skin diseases such as contact dermatitis, atopic dermatitis, urticaria and other eczematoid dermatitis; addictions such as alcohol dependency; somatic diseases caused by stress; sympathetic reflex dystrophy such as hand and shoulder syndrome; dysthymia; undesirable immune reactions such as rejection of grafts; diseases relating to immunopotentiation such as systemic lupus erythematosus or immunosuppression; digestive diseases such as diseases caused by abnormalities in nerves regulating the organs, colitis, ulcerative colitis and Crohn's disease; emesis such as emesis induced by adverse effects of X-ray irradiation and chemotherapy, poisons, toxins, pregnancy, vestibular disorders, postoperative illness, gastrointestinal occlusion, reduced gastrointestinal movement, visceral pain, migraine headache, increased intracranial pressure, reduced intracranial pressure or adverse reaction induced by administration of various medicaments; urinary bladder functional diseases such as cystitis and urinary incontinence; eosinophilia caused by collagen diseases, scleriasis or Fasciola hepatica infection; diseases caused by abnormal blood flow due to vasodilation or vasoconstriction such as angina pectoris, migraine headache and Reynauds's disease; and pain of pain nociceptive reception such as migraine headache, headache and toothache.
The novel salts of an optically active sulfoxide derivative according to the present invention are the hydrochloride and fumarate of 1-{2-[(2R)-(3,4 -dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}spiro[benzo(c)thiophene-1(3H),4′-piperidin]-(2S)oxide.
A novel medicament according to the present invention comprises a compound selected from the above-described ones as an active ingredient;
a novel preventive agent or remedy for tachykinin-mediated diseases according to the present invention comprises a compound selected from the above-described ones as an active ingredient,
a novel inhibitor of an NK
1
receptor and/or an NK
2
receptor according to the present invention comprises a compound selected from the above-described ones as an active ingredient,
a novel preventive agent or remedy for asthma and/or bronchitis according to the present invention comprises a compound selected from the above-described ones as an active ingredient,
a novel preventive agent or remedy for rhinitis according to the present invention comprises a compound selected from the above-described ones as an active ingredient,
a novel preventive agent or remedy for allergy according to the present invention comprises a compound selected from the above-described ones as an active ingredient, and
a novel preventive agent or remedy for urinary incontinence according to the present invention comprises a compound selected from the above-described ones as an active ingredient.
Use for the preparation of a medicament according to the present invention comprises using a compound selected from the above-described ones,
use for the preparation of a preventive agent or remedy for tachykinin-mediated diseases according to the present invention comprises using a compound selected from the above-described ones,
use for the preparation of an inhibitor of an NK
1
receptor and/or an NK
2
receptor according to the present invention comprises using a compound selected from the above-described ones,
use for the preparation of a preventive agent or remedy for asthma and/or bronchitis according to the present invention comprises using a compound selected from the above-described ones,
use for the preparation of a preventive agent or remedy for rhinitis according to the present invention comprises using a compound selected from the above-described ones,
use for the preparation of a preventive agent or remedy for allergy according to the present invention comprises using a compound selected from the above-described ones, and
use for the preparation of a preventive agent or remedy for urinary incontinence according to the present invention comprises using a compound selected from the above-described ones.
In the salts of an optically active sulfoxide derivative according to the present invention, 1-{2-[(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}spiro[benzo(c)thiophene-1(3H),4′-piperidin]-(2S)oxide is a compound represented by the following structural formula (I):
(wherein, >S*→O represents a sulfoxide group wherein the oxygen atom is attached to the sulfur atom in the S absolute configuration).
Of the hydrochloride and fumarate of 1-{2-[(2R)-(3,4-dicholorophenyl)-4-(3,4, 5-tri
Nishi Takahide
Yamaguchi Takeshi
Frishauf, Holtz Goodman, Langer & Chick, P.C.
Powers Fiona T.
Sankyo Company Limited
LandOfFree
Salts of an optically-active sulfoxide derivative does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Salts of an optically-active sulfoxide derivative, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Salts of an optically-active sulfoxide derivative will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2886151