Acylated hetero-alicyclic derivatives

Details Acylated hetero-alicyclic derivatives Acylated hetero-alicyclic derivatives

2000-06-05

2001-09-11

Ramsuer, Robert W. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C540S543000, C540S544000, C540S598000, C544S070000, C544S087000, C544S058500, C544S121000, C544S130000

Reexamination Certificate

active

06288059

ABSTRACT:

The present invention relates to compounds having selective antagonistic activity against NK
2
receptors.
BACKGROUND OF THE INVENTION
NK
1
receptors, NK
2
receptors and NK
3
receptors are known to act as tachykinin receptors. With respect to tachykinin antagonists, compounds that demonstrate selective antagonistic activity on one of NK
1
, NK
2
and NK
3
receptors, and compounds that demonstrate antagonistic activity on more than one of the sub-types of receptors (e.g. Against both NK
1
) and NK
2
receptors) have been found in recent years. In the case of intending to inhibit comprehensively the action of tachykinin, it is important to use a compound that demonstrates antagonistic action against more than one of the types of receptors.
However, since it is generally predicted that the frequency of occurrence of effects other than the desired pharmacological effect increases when inhibiting the action of more than one of the types of receptors, a compound which demonstrate selective and potent antagonistic action against a specific receptor is also important.
Compounds considered to be structurally similar to the compounds of the present invention are disclosed in EP-776893, but these compounds demonstrate antagonistic action against both NK
1
, and NK
2
receptors and, therefore, they should be considered to be completely different from the compounds of the present invention that selectively demonstrate antagonistic action against NK
2
receptors.
With respect to selective antagonistic action against NK
2
receptors, clinical studies on SR48968 (a compound having structural formula A shown below) have begun at present. Moreover, SR144190 (a compound having structural formula B shown below) is reported to have NK
2
receptor-selective antagonistic activity that is more potent than that of SR.48968 (X. Edmonds-Salt. Et al., Tachykinin in Health and Disease, Sep. 7-11, 1997 in Cairns, Australia, Abstract p. 5).
DISCLOSURE OF THE INVENTION
As a result of conducting extensive research on tachykinin antagonists, the inventors of the present invention found that novel acylated hetero-alicyclic deliveries have excellent NK
2
-selective antagonistic activity, thereby leading to completion of the present invention.
Moreover, another object of the present invention is to provide a novel medicament containing an above-mentioned compound as an active ingredient. Examples of diseases for which this medicament can be applied 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 coughs; inflammatory diseases such as inflammatory bowel disease (IBD), psoriasis, fibrosis, arthrosteitis, degenerative arthritis and rheumatoid arthritis; eczema; allergic diseases such as rhinitis; hypersensitivity diseases such as hypersensitivity to vines; ophthalmological diseases such as conjunctivitis, vernal conjunctivitis, vernal cetarrh, 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 dermnatitis, 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 headaches, increased intracranial pressure, reduced intracranial pressure or adverse reactions 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 headaches, headaches and toothache; and sleep apnea. The novel medicament of the present invention can particularly be used as a preventive agent or therapeutic agent for asthma and/or bronchitis, rhinitis, allergic diseases and urinary incontinence.
(1) This invention relates to a compound of the formula (I):
{wherein
R
1
represents a (C
3
-C
7
)cycloalkyl group, a 3- to 7-membered saturated heterocyclic group, a (C
3
-C
7
)cycloalkyl group substituted with 1 to 3 substituents selected from Substituent group A and Substituent group B, or a 3- to 7-membered saturated heterocyclic group substituted with 1 or 2 substituents selected from Substituent group A and Substituent group B,
R
2
represents an aryl group, a heteroaryl group, an aryl group substituted with 1 to 3 substituents selected from Substituent group A, or a heteroaryl group substituted with 1 to 3 substituents selected from Substituent group A,
A represents a methylene group, a carbonyl group or a sulfonyl group,
B represents a single bond, a (C
1
-C
4
)alkylene group or a (C
2
-C
4
)alkenylene group,
D represents an oxygen atom or a sulfur atom,
G represents a (C
1
-C
4
)alkylene group or a (C
2
-C
4
)alkenylene group.
L represents a group of formula —N(R
3
)—or —C(R
4
)(R
5
)—
[wherein R
3
represents an aryl group, a heteroaryl group, an aryl group substituted with 1 to 3 substituents selected from Substituent group A, or a heteroaryl group substituted with 1 to 3 substituents selected from Substituent group A,
R
4
represents a hydrogen atom, an aryl group, a heteroaryl group, an aryl group substituted with 1 to 3 of substituents selected from Substituent group A, or a heteroaryl group substituted with 1 to 3 substituents selected from Substituent group A, a (C
3
-C
7
) cycloalkyl group, a 3- to 7-membered saturated heterocyclic group, a (C
3
-C
7
) cycloalkyl group substituted with 1 to 3 substituents selected from Substituent group A and Substituent group B, or a 3- to 7-membered saturated heterocyclic group substituted with 1 or 2 substituents selected from Substituent group A and Substituent group B,
R
5
represents a lower alkyl group, an amino group, an acylamino group, an acylamino lower alkyl group, an acylamino group wherein the nitrogen atom is substituted with a lower alkyl group, a hydroxy group, a hydroxy lower alkyl group wherein the oxygen atom is optionally substituted with an aralkyl group, a lower alkoxy group or a group of formula —CO—R
6
(wherein R
6
represents a lower alkyl group, a lower alkoxy group, an amine residue, an aryl group substituted with 1 to 3 substituents selected from Substituent group A, or a heteroaryl group substituted with 1 to 3 substituents selected from Substituent group A) or
R
4
and R
5
, together with the carbon atom to which they are attached, form a (C
5
-C
8
) cycloalkane ring, a (C
5
-C
8
)cycloalkene ring, or a 5- to 8-membered saturated heterocyclic ring (any of these rings may be optionally substituted with 1 or 2 substituents selected from Substituent group A and Substituent group B and may be optionally fused with an aryl ring, a heteroaryl ring, an aryl ring substituted with 1 to 3 substituents selected from Substituent group A or a heteroaryl ring substituted with 1 to 3 substituents selected from Substituent group A),
R
7
represents a lower alkyl group,
Z represents two hydrogen atoms or an oxygen

Affiliated with

Also associated with

Rating

Acylated hetero-alicyclic derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Acylated hetero-alicyclic derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Acylated hetero-alicyclic derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2478254