Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1990-05-17
1992-10-06
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544234, 549 51, C07D49504, A61K 3150
Patent
active
051531941
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to thienocycloheptapyridazine compounds which are novel and of use as pharmaceuticals, and to their pharmaceutical use.
BACKGROUND ART
Benzodiazepine, (BZP) ,derivatives represented by diazepam have been use for a long as an antianxiety drug or a therapeutic medicine for sleep disturbance. The recent pharmacological studies have shown that there exist receptors which exhibit a specific affinity for BZP derivatives in the central nervous system [Science, vol. 198, 849 (1977)]. In the studies and researches conducted subsequently, there have been investigated and developed not only BZP derivatives but also compounds which have structures different from BZP but exhibit a high affinity for BZP receptors and a BZP-like action (BZP agonist), compounds which exhibit a high affinity for BZP receptors but exhibit a pharmacological action the reverse of BZP (BZP inverse agonist), and compounds which exhibit a high affinity for BZP receptors but nevertheless exhibit no pharmacological activity themselves and rather show an antagonistic action against the action of the agonist or the inverse-agonist (BZP antagonist) [Advance in Drug Research, vol. 14, 165 (1985)].
Since BZP derivatives which are used as an antianxiety drug have a sedative action, a muscle-relaxing action and an anticonvulsive action in addition to an antianxiety action, they often cause troubles in terms of side effects such as dizziness and sleepiness. Thus, researches of non-BZP types of compounds aiming at developing selective antianxiety drugs with less side effects are thriving. Nevertheless, there have not been found satisfactory ones yet.
Also, in recent years, amnesia-inducing actions by BZP agonists were found [Nature, vol. 321, 864 (1986)], and there have been reports suggesting the possibility that BZP-antagonists exhibiting an antagonistic action against the amnesic actions induced by BZP agonists, and BZP-inverse-agonists exhibiting an action reverse to the amnesic actions by BZP agonists, are usable as brain-function activating drugs. [Trends in Neurosciences, vol. 11, 13 (1988)].
In the meantime, in the specification of U.S. Pat. No. 4,602,019 there are disclosed compounds such as 2,4,4a,5-tetrahydro-7 -(1H-imidazol-1-yl)-3H-indeno[1,2-c]pyridazin-3-one having a cardiac action and an antihypertensive action. The Journal of Medicinal Chemistry, vol. 24, 830 (1981) discloses compounds such as 2-(4-chlorophenyl)benzothiopyrano-[4,3-c]pyrazol-3-one possessing an immune-supressing action.
DISCLOSURE OF INVENTION
The present inventors have conducted intensive studies for the purpose of developing BZP-agonists, BZP-inverse-agonists or BZP-antagonists having a non-BZP-nucleus which are useful pharmaceuticals, and providing effective compounds and pharmaceuticals.
It has been found that the above-mentioned purpose can be attained according to the present invention described hereinafter.
That is, the first invention is to provide thienocycloheptapyridazine compounds of the formula ##STR2## wherein R stands for hydrogen, a halogen or a C.sub.1-4 alkyl, Ar stands for an aryl, a heteroaryl, or an aryl or a heteroaryl having as a substituent at least a halogen, a C.sub.1-4 alkyl, a C.sub.1-4 alkoxy, nitro, amino, hydroxy, trifluoromethyl and/or a C.sub.2-5 alkanoylamino; and the bond between 4-position and 4a-position represents a single bond or a double bond.
The second invention is to provide pharmaceutical compositions comprising a thienocycloheptapyridazine compound of the above formula (I).
The symbols of the formula (I) and each of the below-mentioned formulae are defined in detail below. The halogen represents chlorine, bromine, fluorine or the like; the C.sub.1-4 alkyl represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl; the C.sub.1-4 alkoxy represents methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or tert-butoxy; the C.sub.2-5 alkanoylamino represents acetylamino, propionylamino, butyrylamino or pivaloylamino; the aryl represents phenyl, naphthyl or the like; and t
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J. Lombardino et al., J. Med. Chem. 1981, 24, 830-834.
Morimoto Yasuto
Nakao Tohru
Takehara Shuzo
Tanaka Hiroshi
Bernhardt E.
Shah Mukund J.
Yoshitomi Pharmaceutical Industries Ltd.
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