Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1995-06-27
1997-03-25
Grumbling, Matthew V.
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C07D40304, A61K 3147
Patent
active
056146272
DESCRIPTION:
BRIEF SUMMARY
This is a national stage application filed under 35 USC 371 of PCT/JP94/01504, filed Sep. 12, 1994.
FIELD OF THE INVENTION
The present invention relates to a quinazoline compound exhibiting an excellent activity as a medicine.
BACKGROUND OF THE INVENTION AND PRIOR ART
Angina pectoris which is one of ischemic heart diseases has been known as a disease which frequently attacks the aged. Although nitrate compounds, nitrite compounds, calcium antagonists, .beta.-blockers and so forth have been used as therapeutic agents for the disease, they are still insufficiently effective in treating angina pectoris or in preventing the evolution thereof into myocardial infarction. Further, lowering in the age of a patient with an ischemic heart disease and complication of the condition thereof have recently occurred owing to, e.g., increasing the stress by change in life style and complication of society. Therefore, a new type of more excellent medicine has been eagerly expected.
Among the above-mentioned medicines which are now in use, those which are each one of medicines which have been used most frequently and which have been used for the longest time are nitrate compounds and nitrite compounds. And it is presumed that cyclic GMP (hereinafter abbreviated to cGMP), which is one of the cyclic nucleotides known as intracellular second messengers, participates in the action of these medicines. The cGMP is well known to have relaxing activities on vascular smooth muscle and bronchial smooth muscle. Although the action mechanism of these medicines is not always apparent, it is generally believed that these medicines activate guanylate cyclase to thereby accelerate the synthesis of cGMP, thus increasing the activity of cGMP. However, these medicines exhibit poor biological availability and a relatively short reaction time. Further, it has been reported that tolerance occurs, which becomes a clinical problem.
Under these circumstances, the present inventors have started searching and studying to develop a new type of more excellent medicine.
Namely, the present inventors have directed their attention to a cGMP phosphodiesterase (hereinafter abbreviated to cGMP-PDE) inhibiting activity and have extensively studied on compounds exhibiting such an activity for a long time. As the result, they have found that a nitrogen-containing condensed heterocyclic compound which will be described below exhibits such an activity and hence is efficacious against various ischemic heart diseases and the like. Thus, the present invention has been accomplished.
Although literatures disclosing quinazoline derivatives useful as medicines include, e.g., Toku-hyo Hei. 2-502462 and WO9307124, the compounds disclosed therein are different from the compound of the present invention in both structure and function.
DISCLOSURE OF THE INVENTION
The present invention relates to a quinazoline compound represented by the general formula (I) or a pharmacologically acceptable salt thereof: ##STR2## (wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 may be the same or different from each other and each represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; and represents a hydrogen atom, a lower alkyl group, a hydroxyalkyl group, a lower alkoxyalkyl group, a cyanoalkyl group, a heteroarylalkyl group, a cycloalkyl group, a cycloalkylalkyl group or a carboxyl alkyl group which may be protected, or alternatively R.sup.6 and R.sup.7 may form a ring together with the nitrogen atom to which they are bonded, this ring optionally having a substituent).
In the general formula (I), the lower alkyl group in the definitions of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 means a linear or branched alkyl group having 1 to 6 carbon atoms, for examples, methyl, ethyl, n-propyl, n-butyl, isopropyl, isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, 1-ethylpropyl, isoamyl and n-hexyl. The most desirable examples include methyl group and ethyl group.
The lower alkoxy group in the definitions of R.sup.1, R.sup.2, R.su
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Adachi Hideyuki
Ishihara Hiroki
Kodama Kohtaro
Saeki Takao
Souda Shigeru
Eisai Co. Ltd.
Grumbling Matthew V.
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