Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1989-08-09
1991-02-12
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514221, 540497, 540499, 540503, A61K 3155, C07D48704, C07D49500
Patent
active
049924370
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to thienodiazepine compounds and their salts which are novel and useful as medicaments, and to their pharmaceutical use.
BACKGROUND OF THE ART
In the specification of U.S. Pat. No. 3,849,405, it is disclosed that some kinds of thieno[2,3-e]-1,4-diazepine compounds possess central nervous actions such as an antidepressive action and an anticonvulsive action. In the specification of U.S. Pat. No. 3,904,641, it is disclosed that a certain kind of s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine compound has a useful pharmacological activity on the central nervous system such as an antidepressive activity and an anticonvulsive activity.
Meanwhile, as the substances which exist in the gastro-intestinal tissues and central nervous system and which are concerned with the control of the secretion of pancreatic enzymes and gastric acid, known are cholecystokinin (referred to also as CCK) which is a neuropeptide consisting of 33 amino acids and gastrin consisting of 34 amino acids. In connection with CCK, CCK-8 which consists of the 8 amino acids at the C terminus of CCK also possesses the same actions. Also, pentagastrin which consists of the 5 amino acids at the C terminus of gastrin possesses the same actions. The amino acid sequence of pentagastrin is identical with that at the C terminus of CCK.
Since the substances which exhibit an antagonistic action to these CCK and gastrin are effective in the prophylaxis and therapy of such diseases as pancreatic disorders and gastrointestinal ulcers, a number of such antagonistic substances have been studied so far. As an antagonistic substance to CCK, benzotripto is known [Proc. Natl. Acad. Sci. U.S.A., vol. 78, p. 6304 (1981)], and progulmide is known as an antagonistic substance to gastrin, [J. Med. Chem., vol. 27, p. 1597 (1984)]. Their actions are, however, relatively weak, and therefore, compounds having higher activities have been desired.
Besides, peptide antagonistic substances are not altogether satisfactory in that the durability of their actions is short and in that they are unstable and are not absorbed fully.
DISCLOSURE OF THE INVENTION
After the present inventors had conducted intensive studies for the purpose of creating substances which displayed effective antagonistic actions to CCK and gastrin and were useful as medicaments, they found a certain kind of thienodiazepine compound attained the purpose, which culminated in the completion of the present invention.
That is, this invention is to provide thienodiazepine compounds of the general formula ##STR2## wherein R.sup.1 and R.sup.2 are the same or different and respectively stand for a hydrogen atom, a halogen, an alkyl or an aralkyl, or mean a group wherein R.sup.1 and R.sup.2 combinedly together form a ring; R.sup.3 stands for an oxygen atom, R.sup.4 stands for a hydrogen atom, an alkyl, an alkenyl or a group of the formula --(CH.sub.2).sub.m COOR.sup.6 (wherein R.sup.6 stands for a hydrogen atom, an alkyl, an alkenyl or an aralkyl and m stands for an integer of 1-6), or R.sup.3 and R.sup.4 stand for a group wherein R.sup.3 and R.sup.4 combinedly together form a group of the formula .dbd.N--N.dbd.C(R.sup.5)-- [wherein R.sup.5 stands for a hydrogen atom, an alkyl, an alkenyl, an aralkyl or a group of the formula --(CH.sub.2).sub.n COOR.sup.7 (wherein R.sup.7 stands for a hydrogen atom, an alkyl, an alkenyl or an aralkyl and n stands for an integer of 1-6)]; Ar and X are the same or different and respectively stand for an aryl or a heteroaryl; and p stands for an integer of 1-6, or their salts.
Also, the present invention is to provide pharmaceutical compositions containing a thienodiazepine compound of the above-mentioned general formula (I) or a salt thereof.
In the foregoing definition and the present specification, the halogen means chlorine, bromine, fluorine or iodine; the alkyl means an alkyl having 1-20 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertbutyl, pentyl, isopentyl, tert-pentyl, hexyl, octyl, 2-ethylhexyl, 1,1,3,3-tet
REFERENCES:
patent: 3849405 (1974-11-01), Nakanishi et al.
patent: 3904641 (1975-09-01), Nakanishi et al.
Evans et al., J. Med. Chem., 31, 1988, pp. 2235-2246.
Haga Kei-ichiro
Hitotsuyanagi Yukio
Hosoya Masahiro
Naka Yoichi
Shah Mukund J.
Ward E. C.
Yoshitomi Pharmaceutical Industries Ltd.
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