Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-07-01
1999-03-30
Mach, Margaret M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514311, 546160, 546161, 546168, A61K 3147, C07D21538, C07D21544, C07D21514
Patent
active
058890211
DESCRIPTION:
BRIEF SUMMARY
THIS APPLICATION IS A 371 OF PCT/SE94/00552, FILED JUN. 8, 1994.
TECHNICAL FIELD
The present invention relates to novel compounds, and therapeutically acceptable salts thereof, which inhibit exogenously or endogenously stimulated gastric acid secretion and thus can be used in the prevention and treatment of gastrointestinal inflammatory diseases. In further aspects, the invention relates to compounds of the invention for use in therapy; to processes for preparation of such new compounds; to pharmaceutical compositions containing at least one compound of the invention, or a therapeutically acceptable salt thereof, as active ingredient; and to the use of the active compounds in the manufacture of medicaments for the medical use indicated above.
BACKGROUND ART
Substituted quinoline derivatives that inhibit gastric acid secretion are known in the art, for example from EP-A1-259,174 and EP-A1-330,485.
DISCLOSURE OF THE INVENTION
It has surprisingly been found that compounds of the formula I, which are 4-amino-3-acylquinoline derivatives in which the quinoline is substituted in the 8-position by alkylthioethoxy, alkylthiopropoxy, alkylsulfinylethoxy, alkylsulfinylpropoxy, alkylsulfonylethoxy or alkylsulfonylpropoxy, are effective as inhibitors of gastric acid secretion, and that they exert this effect by inhibiting the gastrointestinal H.sup.+,K.sup.+ -ATPase.
In one aspect, the invention thus relates to compounds of the general formula I: ##STR2## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is
Throughout the specification and the appended claims, a given chemical formula or name shall encompass all stereo and optical isomers and racemates thereof where such isomers exist, as well as pharmaceutically acceptable acid addition salts thereof and solvates thereof such as for instance hydrates.
The following definitions shall apply throughout the specification and the appended claims.
Unless otherwise stated or indicated, the term "C.sub.1 -C.sub.6 alkyl" denotes a straight or branched alkyl group having from 1 to 6 carbon atoms. Examples of said lower alkyl include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl and straight- and branched-chain pentyl and hexyl.
Unless otherwise stated or indicated, the term "cycloalkyl" denotes a cyclic alkyl group having a ring size from C.sub.3 to C.sub.6, optionally additionally substituted by lower alkyl. Examples of said cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl and cydoheptyl.
Unless otherwise stated or indicated, the term "C.sub.1 -C.sub.6 alkoxy" denotes a straight or branched alkoxy group having from 1 to 6 carbon atoms. Examples of said lower alkoxy include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, t-butoxy and straight- and branched-chain pentoxy and hexoxy.
Unless otherwise stated or indicated, the term "halogen" shall mean fluorine, chlorine, bromine or iodine.
Depending on the process conditions and the starting materials, the end products of the formula I are obtained either in neutral or salt form. Both the free base and the salts of these end products are within the scope of the invention.
Acid addition salts of the new compounds may in a manner known per se be transformed into the free base using basic agents such as alkali or by ion exchange. The free base obtained may also form salts with organic or inorganic acids.
In the preparation of acid addition salts, preferably such acids are used which form suitably therapeutically acceptable salts. Examples of such acids are hydrohalogen acids, sulfonic acids, phosphoric acid, nitric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxyl or sulfonic acids, such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, pyruvic acid, p-hydroxybensoic acid, embonic acid, methanesulfonic acid, ethanesulfonic acid, hydroxyethanesulfonic acid, halogenbensenesulfonic acid
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Astra Aktiebolag
Mach Margaret M.
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