Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-11-05
1999-07-06
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142382, 5142372, 514255, 514331, 544124, 544162, 544360, 544398, 546193, 546232, 546338, 564256, A61K 3144, A61K 31445, C07D21134, C07D40112
Patent
active
059197960
DESCRIPTION:
BRIEF SUMMARY
The present application is a 371 of PCT/HU95/00014, filed May 4, 1995.
The invention relates to novel, biologically active hydroximic acid derivatives of the formula ##STR3## wherein X means halogen; group, and in the latter alkyl group; or R.sub.1 and R.sub.2, together with the adjacent nitrogen atom, form a 5- to 7-membered, saturated heterocyclic group optionally containing an additional nitrogen, oxygen or sulfur atom, the heterocyclic group optionally being substituted by at least one alkyl group; and
A stands for a straight or branched chain alkylene group, as well as their pharmaceutically acceptable acid addition salts and pharmaceutical compositions containing these compounds. Furthermore, the invention relates to a process for the preparation of the above compounds and to a method for the treatment of ischemic states or diseases in mammals, including men.
X as halogen means fluorine, chlorine, bromine or iodine; compounds containing chlorine as X are preferred.
Z as an aromatic group is preferably a phenyl, phenylalkyl, substituted phenyl, substituted phenylalkyl or naphthyl group. The phenyl group of the above substituted groups may be substituted by 1 to 3 identical or different group(s), which is (are) suitably halogen, haloalkyl, alkyl, hydroxy, alkoxy, nitro, amino, mono- or dialkylamino groups.
The term "Z stands for a pyridinyl group or the like" means a pyridinyl group or its homologues, e.g. picolyl or lutidyl group. Pyridinyl group is particularly preferable; whereas 3-pyridinyl group proved to be most advantageous.
Above and in the forthcoming, alkyl or alkoxy groups as R, R.sub.1 and R.sub.2 or as substituents contain preferably 1 to 8, suitably 1 to 6, most preferably 1 to 4 carbon atoms unless stated otherwise. Methyl, ethyl or n-propyl groups are most preferred.
Thus, the phenylalkyl group is in most cases a benzyl or phenylethyl group; whereas the mono- and dialkylamino groups are preferably monoC.sub.1-4 alkyl or diC.sub.1-4 alkyl groups, respectively.
The haloalkyl group may contain one or more above-mentioned halogen(s) or it may be a perfluoroalkyl group. Preferred are e.g. chloromethyl, 2-chloroethyl or trifluoromethyl groups.
The heterocyclic group formed by R.sub.1, R.sub.2 and the adjacent nitrogen together is preferably a piperidino, piperazino or morpholino group. These groups may optionally be substituted by at least one alkyl group defined above. Thus, these groups may be e.g. a 4-methylpiperazinyl or 2,2-dimethylpiperidinyl group.
The alkylene group A may contain a straight or branched chain, and suitably it contains 1 to 8, preferably 1 to 5 carbon atoms. The 1,2-ethylene, 1,3-propylene and 1,4-butylene groups are especially advantageous.
All compounds of formula (I) are novel. A part of the starting materials for their preparation is known whereas others are new. The methods of preparation of the new starting materials are described in the corresponding examples.
Insecticides being structurally similar to compounds of the formula (I) are disclosed in the Japanese patent application published under No. 60.0008253 (Kokai), and .beta.-blocking agents being structurally similar to the compounds of formula (I) are claimed in the European patent specification No. 0,147,210.
Structurally, compounds disclosed in the latter document differ from the compounds of formula (I) in that a --CH.sub.2 --CH(OH)--CH.sub.2 --(2-hydroxy-propylene) moiety is present between the terminal --NR.sup.1 R.sup.2 group and the remaining part of the molecule instead of the unsubstituted straight or branched alkylene group symbolized by A in the compounds of the formula (I). The compounds described in the European patent specification 0,417,210 are diabetes selective .beta.-antagonists and can be used especially in the therapy of diabetic angiopathy.
Beltrao, T. M. et al describe the preparative and spectroscopic investigation of O-metbylbenzamidoximes of the formula p-R.sup.1 --C.sub.6 H.sub.4 --C(NH.sub.2)--NOR (R.dbd.Me, R.sup.1 =H, Me, Cl, Br, NO.sub.2) in their article "Preparation and spectr
REFERENCES:
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Barabas Mihaly
Biro Katalin
Jaszlits Laszlo
Jednakovits Andrea
Marvanyos Ede
BIOREX Kutato es Fejleszto Rt.
Raymond Richard L.
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