Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-05-23
1997-08-12
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142315, 5142388, 514311, 514314, 514315, 514326, 514277, 514336, 514378, 514422, 514428, 514457, 514452, 514460, 514557, 544145, 544148, 544149, 544171, 546174, 546207, 546248, 5462821, 5462824, 546341, 548240, 548517, 548527, 548572, 549 14, 549290, 549378, 549419, 549420, 562512, 562567, 562568, A61K 3138, A61K 31335, A61K 3135, A61K 3137, C07D31174, C07D30912
Patent
active
056566565
DESCRIPTION:
BRIEF SUMMARY
SUMMARY OF THE INVENTION
This application is a 371 of PCT EP93/02941 filed Oct. 25, 1993.
The present invention relates to tartronic acid derivatives of general formula (I): ##STR2## in which: Ra and Rb are independently hydrogen, an alkali or alkaline-earth metal, an ammonium or C.sub.1 -C.sub.10 alkylammonium cation, a C.sub.1 -C.sub.4 alkyl group, a C.sub.1 -C.sub.4 alkoxyethyl, allyl or p-methoxybenzyl group; formula (II): ##STR3## in which .phi. is selected from the group consisting of --CH.sub.2 --, O, S; alkoxyphenyl; 3,5-di-C.sub.1 -C.sub.4 -alkoxyphenyl; 4-hydroxy-3,5-di-C.sub.1 -C.sub.4 -alkoxyphenyl and the C.sub.1 -C.sub.7 acyloxy derivatives thereof; 4-hydroxy-3,5-di-tert-butylphenyl; 3,5-di-trifluoromethylphenyl; fur-2-yl; 5-dimethylaminomethyl-fur-2-yl; .alpha.-, .beta.- and .gamma.-pyridyl; .alpha.- and .beta.-naphthyl; .alpha.- and .beta.-naphthyloxymethyl; 2- and 3-quinolinyl; 2- and 3-(7-chloro-quinolinyl); m- and p-(2-quinolinylmethoxy)phenyl; m- and p-(7-chloro-2-quinolinylmethoxy)phenyl; 6-(2-quinolinylmethoxy)-.beta.-naphthyl and 6-(7-chloro-2-quinolinylmethoxy)-.beta.-naphthyl; pheynlthio; C.sub.1 -C.sub.4 -alkoxyphenylthio; 4-chlorophenylthio; 3,5-dimethyl-isoxazol-5-yl; 2-thienyl; 1,3-dioxolan-2-yl; 7-methoxy-cumarin-4-yl; 6,7-dimethoxy-cumarin-4-yl; a 4-oxo-thiazolidin-3-yl group substituted at the 2-position with a phenyl ring optionally having 1 to 3 substituents, which are the same or different, selected from hydroxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 acyloxy; C.sub.1 -C.sub.12 alkyl; C.sub.2 -C.sub.12 alkenyl or alkynyl; C.sub.3 -C.sub.12 cycloalkyl or cycloalkenyl; or a group of formula (III): -C.sub.4 alkyl, tert-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (FMOC), benzyloxycarbonyl, p-methoxybenzyloxycarbonyl, aminocarbonyl, C.sub.1 -C.sub.4 alkylaminocarbonyl; or R.sub.2 and R.sub.3, taken together with the nitrogen atom they are linked to, form a 5 to 7 membered nitrogen heterocycle of formula (IV): ##STR4## wherein X is a bond between 2 carbon atoms, or is selected from the group consisting of --CH.sub.2 --, O, S, N--Rc, wherein Rc can be hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, aminocarbonyl, BOC, FMOC, benzyloxycarbonyl, p-methoxy-benzyloxycarbonyl, phenyl, benzyl, benzhydryl; or when R.sub.3 is selected from hydrogen, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 acyl, aminocarbonyl, C.sub.1 -C.sub.4 alkoxycarbonyl, benzyl, p-methoxybenzyl, R.sub.1 and R.sub.2, taken together with the N and C atoms they are linked to, form a 5 to 7 membered nitrogen heterocycle;
p is the integer 2 or 3; B and R.sub.1 are H and R.sub.2 and R.sub.3 are independently hydrogen, methyl, or they form a piperidino group; mixtures, the pharmaceutically acceptable salts thereof.
The compounds specifically excluded from general formula (I) are described by Mannich and Bauroth (Berichte, 55 (1922) 3504), who, on the other hand, indicate no therapeutic uses which, on the contrary, is within the scope of the present invention together with the compounds of formula (I). These compounds of formula (I) are where: Abstr. 72 (9), 1970, N. 42684t; Bull. Chem. Soc. Jap. 48 (1), 277; Tetrahedron Lett. 30 (10), 1989, 1289; Tetrahedron Lett. 25 (20), 1969, 4976; Liebigs Ann. Chemie 2 (1990), 181.
The invention refers also to the compounds of formula (I), from which the above-mentioned compounds have been disclaimed.
The invention also relates to a process for the preparation of the compounds of formula (I) and pharmaceutical compositions containing them.
DESCRIPTION OF PREFERRED EMBODIMENTS
Examples of C.sub.1 -C.sub.4 alkyl groups are: methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, tert-butyl, preferably methyl, ethyl, tert-butyl.
Examples of C.sub.1 -C.sub.4 -alkoxyethyl groups are: methoxethyl, ethoxyethyl, propoxyethyl, iso-propoxyethyl, butoxyethyl, tert-butoxyethyl; preferably methoxyethyl.
Examples of C.sub.2 -C.sub.11 acyl groups are: acetyl, propionyl, butyryl, iso-butyryl, valeryl, pivaloyl, caprinyl, lauroyl, benzoyl, phenylacety
REFERENCES:
Chemical Abstracts, vol. 115, No. 21, 1991, Abstract No. 232008e, Jurczak, et al, "The High Pressure Reaction of 2,5-Dimethylfuran with Activated Carbonyl Compounds".
Tetrahedron Letters, vol. 25, No. 50, 1985, pp. 5747-5750, Genner, et al, "Reactions of Furans, Thiophenes and Pyrroles with Activated Carbonyl Compounds Under Thermal and High Pressure Conditions" (see pp. 5747-5748).
Chemical Abstracts, vol. 72, No. 9, 1970, Abstract No. 42684t, J. Grandjean, "Tartronic Acids", p. 352.
Bulletin of the Chemical Society of Japan, vol. 48, No. 1, 1975, pp. 277-280, Pac, et al, "Benzoyl Peroxide-And Photo-Induced Reactions of Diethyl Mesoxalate in Cyclohexane and Toluene" (see pp. 277-279).
Chemical Abstracts, vol. 51, No. 10, 1957, Abstract No. 12085g, Mikhlina, et al, "Synthesis of 3-Methyl-2-Quinclidinecarboxylic Acid".
Tetrahedron Letters, vol. 30, No. 10, 1989, pp. 1289-1292, Citterio, et al, "Oxidative Deprotonation of Carbonyl Compounds by FE(III)Salts" (see pp. 1289-1292).
Tetrahedron, (Incl. Tetrahedron Reports), vol. 25, No. 20, 1969, pp. 4967-4981, Chottard, et al, "Cyclisation Radicalaires.XII" (see pp. 4976-4981).
Liebigs Annalen Der Chemie, vol. 2, 1990, pp. 181-183, Kawabata, et al, "Electrochemical Hydroxylation of Active Methine Compounds" (see pp. 181-183).
Chemical Abstracts, vol. 85, No. 24, 1976, Abstract No. 179401m, Abe, et al, "Dibasic Acids Containing Ether Linkages" (p. 102).
Caselli Gianfranco
Clavenna Gaetano
Cotini Lorella
Gandolfi Carmelo A.
Mantovanini Marco
Dompe Farmaceutici S.p.A.
Richter Johann
Stockton Laura L.
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