Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-11-19
2001-07-10
Aulakh, C. S. (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S199000, C546S194000, C514S318000
Reexamination Certificate
active
06258825
ABSTRACT:
FIELD OF THE INVENTION
The present invention is useful in the medicinal field. More specifically, the 2-oxoimidazole derivative of the present invention has an action to inhibit nociceptin from binding to a nociceptin receptor ORL1 and is useful as an analgesic, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension.
BACKGROUND ART
Nociceptin (the same substance as orphanin FQ) is peptide comprising 17 amino acids and having a similar structure to that of opioid peptide. Nociceptin has an augmenting activity on reaction against nociceptive stimulation, an appetite stimulating activity, an activity for reducing a space learning ability, an antagonism against an analgesic action of a classic opiate agonist, a dopamine release inhibitory action, a water diuresis action, a vasodilative action, and a systemic blood pressure-lowering action, and it is considered to take part in controlling pain, appetite and memory learning through a nociceptin receptor ORL1 [refer to Nature, vol. 377, pp. 532 (1995); Society for Neuroscience, vol. 22, pp. 455 (1996);
NeuroReport, vol. 8, pp. 423 (1997); Eur. J. Neuroscience, vol. 9, pp. 194 (1997); Neuroscience, vol. 75, pp. 1 and 333 (1996); and Life Science, vol. 60, pp. PL15 and PL141 (1997)]. Further, it is known that morphine tolerance is reduced in a knockout mouse in which a nociceptin receptor ORL1 is deficient [Neuroscience Letters, vol. 237, pp. 136 (1997)].
Accordingly, it can be expected that a substance which specifically prevents nociceptin from binding to a nociceptin receptor ORL1 is useful as an analgesic against diseases accompanied with pains such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension.
A compound which is structurally similar to the compound of the present invention is disclosed in International Publication WO96 /13262 and the like. However, the compound of the present invention is neither specifically disclosed nor indicated, and an action to prevent nociceptin from binding to a nociceptin receptor ORL1 is not entirely described as well.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide an analgesic, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension, which are novel and have an action to prevent nociceptin from binding to a nociceptin acceptor ORL1.
The present inventors have found that a compound represented by Formula [I] has a high affinity to a nociceptin receptor and prevents the action of nociceptin, whereby it is useful as an analgesic against diseases accompanied with pains such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia, a reliever against tolerance to a narcotic analgesic represented by morphine, a reliever against dependence on a narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a remedy for schizophrenia, a remedy for Parkinsonism, a remedy for chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension, and thus, they have completed the present invention:
[wherein
represents an aromatic carbo- or heterocyclic ring which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a hydroxyl group, a lower alkoxy group and a carboxyl group; Ar
2
represents an aromatic carbo- or heterocyclic group which may have a substituent selected from the group consisting of a halogen atom, a lower alkyl group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a hydroxyl group, a lower alkoxy group and a carboxyl group; Cy represents a mono-, bi- or tricyclic aliphatic carbocyclic group having 3 to 20 carbon atoms, which may have a substituent selected from the group consisting of a halogen atom, a lower alkylidene group, a lower alkenyl group, a lower alkynyl group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a lower alkoxy group and a group represented by —R
4
;
represents a mono- or bicyclic aliphatic nitrogen-containing heterocyclic group having 3 to 14 carbon atoms, which may have a substituent selected from the group consisting of a halogen atom, a lower alkylidene group, a lower alkenyl group, a lower alkynyl group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a hydroxyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group, a di(lower alkyl)carbamoyl group and a group represented by —R
3
; R
1
represents a hydrogen atom, a lower alkenyl group, a lower alkynyl group, a cyclo(lower alkyl) group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a hydroxyl group, a lower alkoxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group or a di(lower alkyl)carbamoyl group, or a lower alkyl group which may have a substituent selected from the group consisting of a halogen atom, a cyclo(ower alkyl) group, an amino group, a lower alkylamino group, a di(lower alkyl)amino group, a (lower alkyl)sulfonylamino group, an aminosulfonylamino group, a (lower alkylamino)sulfonylamino group, a (di-lower alkylamino)sulfonylamino group, a carbamoylamino group, a (lower alkylcarbamoyl)amino group, a (di-lower alkylcarbamoyl)amino group, a hydroxyl group, a lower alkoxy group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di(lower alkyl)carbamoyloxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group, a di(lower alkyl)carbamoyl group and a group represented by Ar
2
; R
2
represents a hydrogen atom or a lower alkyl group; R
3
represents a lower alkyl group which may have a substituent selected from the group consisting of an amino group, a lower alkylsulfonylamino group, an aminosulfonylamino group, a (lower alkylamino)sulfonylamino group, a (di-lower alkylamino)sulfonylamino group, a carbamoylamino group, a (lower alkylcarbamoyl)amino group, a (di-lower alkylcarbamoyl)amino group, a hydroxyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di(lower alkyl)carbamoyloxy group, a carboxyl group, a lower alkoxycarbonyl group, a carbamoyl group, a lower alkylcarbamoyl group, a di(oower alkyl)carbamoyl group, an aromatic heterocyclic group and a group represented by —R
5
; R
4
represents a lower alkyl group which may have a substituent selected from the group consisting of a cycloalkyl group having 3 to 10 carbon atoms and an aromatic carbo- or heterocyclic group; and R
5
represents a lower alkylamino group, a di(lower alkyl)amino group or a lower alkoxy group, which may have an aromatic carbo- or heterocyclic group].
The present invention relates to the compound represented by Formula [I], salts or esters there
Hayashi Kyoko
Hirano Kaori
Ito Yoshiki
Iwasawa Yoshikazu
Kawamoto Hiroshi
Aulakh C. S.
Banyu Pharmaceutical Co. Ltd.
Wenderoth , Lind & Ponack, L.L.P.
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