Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-04-27
2000-08-15
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544281, 544362, 544368, A61K 31496, A61K 31519, C07D47104, C07D48704, C07D51304
Patent
active
061037249
DESCRIPTION:
BRIEF SUMMARY
The invention relates to novel fused heterocyclic compounds with ring junction nitrogen atom of a general formula (I) ##STR2## wherein Q stands for 2-indolizinyl, 2-imidazo[1,2-a]pyridinyl, 2-imidazo[1,2-a]-pyrimidinyl, 6-(2,3-dihydroimidazo[2,1 -b]thiazol)-yl or 6-imidazo[2,1-b]-thiazolyl group; and containing these compounds. Furthermore, the invention relates also to a process for the preparation of the compounds of formula (I) and their therapeutically useful salts in such a way that a haloalkyl ether derivative of formula (II) ##STR3## wherein Q and n are as defined above, and X means halogen is reacted with (2-methoxyphenyl)piperazine of formula (III). ##STR4##
The compounds of formula (I) according to the invention are novel and possess significant biological activity, first of all antipsychotic effects.
The invention relates also to a method of treatment, which comprises administering a therapeutically active amount of a compound of formula (I) or a therapeutically acceptable salt thereof to a patient to be treated.
Among the starting substances, some of chloroalkyl ether derivatives of formula (II) are known from the literature, such as 3-[4-(2-imidazo[1,2-a]pyridinyl) -phenoxy]propyl chlorid, 3-[4-(2-imidazo[1,2-a]pyrimidinyl)phenoxy]propyl chloride, or 3-[4-(6-imidazo[2,1-b]thiazolyl)phenoxy]propyl chloride [J. Med. Chem. 31, 2221 (1988)]. Other starting substances of formula (II) can be obtained according to the preparation process described in the above-cited literature.
(2-Methoxyphenyl)piperazine of formula (III) is a known, commercially available substance.
Compounds structurally similar to the substances of formula (I) are known from the literature. Such (substituted amino)propoxyphenylimidazo[1,2-a]pyridines, substituted amino)propoxyphenylimidazo[1,2-a]pyrimidines and (substituted amino)propoxyphenylimidazo[2,1-b]thiazoles are described in the above-cited publication [J. Med. Chem. 31, 2221 (1988)], however, unlike the compounds according to the invention, these compounds possess calcium channel-blocking and local anaesthetic effects.
In contrast to the structurally closely related compounds known from the literature, the novel compounds of formula (I) according to the invention are orally effective and are endowed of a considerable neuroleptic activitiy. Based on their biological activity, these compounds can be used as atypical antipsychotics, antidepressants, anxiolytics, neuroprotective and/or cognitive function improving agents, antiemetics or antiaddictives.
Since the 70's, antipsychotics have successfully been employed for the treatment of schizophrenia. Up to the present haloperidol has been used in the clinical practice most widely. Phenothiazines and haloperidol played a pioneering role in this therapeutic field and considerably contributed to the development of the dopamine theory of schizophrenia. Later researches confirmed also the role of serotonine and a number of other neurotransmitter systems, such as histaminerg, .alpha.-adrenerg, CCK-erg, etc. in this disorder. However, haloperidol and other typical antipsychotics improve only the positive symptoms of the disease, e. g. hallucinations, delusions, agitation and thought disturbances, whereas negative symptoms, such as emotional obtusion, autism, social isolation, neglection of personal hygiene remain unimproved. In addition, nearly 30% of the patients do not respond to the treatment and a number of undesired adverse effects cannot be excluded, either. From these, the most severe adverse effects are the appearance of extrapyramidal symptoms (EPS), because of the strong but not regionselective antagonism of D-2 dopamine receptor, deterioration of cognitive functions caused by anticholinergic effect, orthostatic hypotonia (.alpha.-adrenerg antagonism), and hyperprolactinaemia.
Nowadays, intensive research is being devoted to atypical antipsichotics, which are capable of improving both positive and negative symptoms, do not induce extrapyramidal symptoms or only in doses higher than therapeutical, only a few non-responsive p
REFERENCES:
patent: 4880824 (1989-11-01), Press et al.
patent: 5688949 (1997-11-01), Inoue et al.
patent: 6013654 (2000-01-01), TenBrink
VanTol et al. Nature, vol. 350, pp. 610-614, (1991).
Saxena, Pharmac. Ther. vol. 66, pp. 339-368, (1995).
"Discovery of Selective Dopamine D3 Ligands" by Jon Wright et al. published in Bioorganic & Medicinal Chemistry Letters, vol. 5, No. 21, 1995.
J. Med. Chem. 1988, 31, 2221-2227; P.J. Sanfilippo; Syntheses of (Aryloxy) alkylamines.
Acs Tibor
Auth Feranc
Csejtei Monika
Domany Gyorgy
Ferenczy Gyorgy
Bernhardt Emily
Dubno Herbert
Richter Gedeon Vegyeszeti Gyar Rt.
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