Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1996-01-19
1998-03-03
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540577, 514215, C07D22320, A61K 3155
Patent
active
057236062
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel aromatic and heterocyclic ring-condensed benzazepine derivatives which are useful as arginine vasopressin antagonists, to salts thereof, to pharmaceutical preparations which contain these compounds as an active ingredient and to intermediates which are useful for the synthesis of these compounds.
BACKGROUND ART
Arginine vasopressin (AVP) is a peptide which consists of 9 amino acid residues and is synthesized and secreted in the hypothalamo-neurohypophyseal system. As antagonists of the arginine vasopressin, peptide type compounds and non-peptide type compounds have been synthesized. For example, a compound disclosed in JP-A-2-32098 is known as the peptide type compound (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). On the other hand, 2,3,4,5-tetrahydro-1H-benzazepine derivatives represented by the following general formula have been disclosed in EP-A-0514667 and JP-A-5-132466 as non-peptide type vasopressin antagonists. ##STR2## (As for symbols in the above formula, see aforementioned patent publications.)
Also, International Patent Publication No. 91/05549 disclosing the compound represented by the following general formula, and 2,3,4,5-tetrahydro1H-benzodiazepine derivatives and 2,3,4,5-tetrahydro-1H-1-benzazepine derivatives disclosed in JP-A-4-154765 are known. ##STR3## (As for symbols in the above formula, see aforementioned patent publications.)
Although various studies have been made as described above, creation of novel arginine vasopressin antagonists having more excellent profiles is still now an important clinical object.
On the other hand, almost no compound is known as a compound having a nitrogen-containing aromatic 5-membered ring-condensed benzazepine skeleton, which is the basic structure of the compound of the present invention, and only processes for the synthesis of a few compounds having such a ring structure have been reported in J. Chem. Soc., Perkin Trans. 1 (1978) No. 8, 862-70 and Org. Prep. Proced. Int., 25 (5), 602-6 (1993), but their structures are clearly different from the structure of the compound of the present invention. In addition, use of these compounds as pharmaceutical preparations have not been known.
DISCLOSURE OF THE INVENTION
The inventors of the present invention have conducted extensive studies on compounds having arginine vasopressin antagonism and accomplished the present invention based on the finding that a novel aromatic and heterocyclic ring-condensed benzazepine derivative represented by the following general formula (I) shows unexpectedly excellent arginine vasopressin antagonism.
Accordingly, the present invention relates to a nitrogen-containing aromatic 5-membered ring-condensed benzazepine derivative represented by the following formula (I) and a salt thereof. ##STR4## (Symbols in the formula have the following meanings; ring B: a nitrogen-containing aromatic 5-membered ring having at least 1 nitrogen atom and optionally one oxygen or sulfur atom, which may optionally have substituent(s), R.sup.1, R.sup.2 : these may be the same or different from each other and each represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group which may optionally be substituted by lower alkyl group(s), a lower alkoxy group, A: a single bond; a group represented by the formula each represents a hydrogen atom, a lower alkyl group (provided that R.sup.3 and R.sup.4 may together form a lower alkylene group having 2 to 7 carbon atoms), and ring C: a benzene ring which may optionally have substituent(s).)
Further, the particularly preferable compound is the nitrogen-containing aromatic 5-membered ring-condensed benzazepine derivative (I) or a salt thereof wherein i) the ring B is a ring represented by the formula: ##STR5## (symbols in the formula have the following meanings; X.sup.1, X.sup.3 : one of them is a group represented by the formula .dbd.N--, and the other is a group represented by the formula --NR.sup.5 --, --O--, --S-- or .dbd.N--, or .dbd.N-
REFERENCES:
patent: 5225402 (1993-07-01), Ogawa et al.
patent: 5244898 (1993-09-01), Ogawa et al.
patent: 5258510 (1993-11-01), Ogawa et al.
patent: 5512563 (1996-04-01), Albright et al.
Koshio Hiroyuki
Matsuhisa Akira
Sakamoto Ken-ichiro
Tanaka Akihiro
Taniguchi Nobuaki
Shah Mukund J.
Wong King Lit
Yamanouchi Pharmaceutical Co. Ltd.
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