Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-04-27
1998-04-14
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514212, 514289, 240597, 546 44, 546741, A61K 3147, A61K 31485, C07D22128, C07D48900
Patent
active
057391459
DESCRIPTION:
BRIEF SUMMARY
This application is the National phase of PCT/JP94/10477 filed on Jun. 28, 1994.
1. Technical Field
The present invention relates to antitussive agents whose effective components are morphinan derivatives or pharmacologically acceptable acid-addition salts thereof. The compounds to be used according to the present invention have strong antitussive activity, and thus suppress coughing which accompanies bronchography, bronchoscopy, and a host of respiratory diseases including colds, acute bronchities, chronic bronchitis, bronchiectasis, pneumonia, lung tuberculosis, silicosis, silicotuberculosis, pulmonary cancer, upper respiratory inflammations (pharyngitis, laryngitis, nasal catarrh), asthmatic bronchitis, bronchial asthma, infantile asthma, (chronic) pulmonary emphysema, pneumoconiosis, pulmonary fibrosis, pulmonary silicosis, pulmonary suppuration, pleuritis, tonsillitis, coughing hives and whooping cough.
2. Related Art
Codeine, dextromethorphan and the like are known as high-strength antitussive agents acting on central nervous system. These drugs are used not only by doctors, but also as single components in combination cold medicines; however, they inherently have side effects serious enough to be clinically problematic, including drug dependence, respiratory depression, smooth muscle depressomotor effects (constipation) and psychotomimetic effects. Of particular seriousness is the overuse of antitussive agents containing codeine, and the psychotomimetic effects of dextromethorphan, for which reasons safer centrically acting high-strength antitussive agents have been desired.
The existence of opioid receptors as receptors which contribute to a variety of pharmacological effects, mainly analgesic, has been demonstrated, and they are known to be further classified into three types, .mu., .delta., and .kappa.. .sigma.-receptors are also known which exhibit a psychotomimetic effect. The antitussive effects of morphine and codeine which act on the .mu.-type receptors and dextromethorphan which acts on the .sigma.-type have long been known, but it has not been possible to avoid the serious side effects such as drug dependence, respiratory depression, smooth muscle depressomotor effects (constipation) and psychotomimetic effects.
Incidentally, agonists with affinity to the .kappa.-receptor, one of the four types mentioned above, are said not to exhibit the serious side effects which are clinically problematic, such as drug dependence, respiratory depression, smooth muscle depressomotor effects, etc. experienced with .mu.-receptor agonists such as morphine. Furthermore, the psychotomimetic effects experienced with existing .kappa.-receptor agonists are said to be caused by their affinity to .sigma.-receptors. Consequently, it is an object of the present invention to provide antitussive agents whose effective components are .kappa.-receptor agonists which do not exhibit the serious side effects associated with .mu.-agonists and .sigma.-agonists.
DISCLOSURE OF THE INVENTION
The present inventors, as a result of diligent research aimed at overcoming the aforementioned problems, have found that morphinan derivatives represented by general formula (I) are antitussive compounds with the above-mentioned excellent characteristics, and the present invention has been completed upon this finding.
Namely, the present invention relates to the use as antitussive agent of a morphinan derivative represented with general formula (I) below or pharmacologically acceptable acid salt thereof: ##STR2## alkyl group having 1-5 carbon atoms, a cycloalkylalkyl group having 4-7 carbon atoms, a cycloalkenylalkyl group having 5-7 carbon atoms, an aryl group having 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, an alkenyl group having 4-7 carbon atoms, an allyl group, a furan-2-ylalkyl group having 1-5 carbon atoms, or a thiophen-2-ylalkyl group having 1-5 carbon atoms; R.sup.2 represents a hydrogen atoms, a hydroxy group, a nitro group, an alkanoyloxy group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon ato
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Endoh Takashi
Kawai Koji
Nagase Hiroshi
Negishi Yuji
Ueno Shinya
Huang Evelyn
Ivy C. Warren
Toray Industries Inc.
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