Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-08-01
1997-03-04
Fan, Jane
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544336, 544406, 544407, 544408, 544409, A61K 31495, C07D24102
Patent
active
056079354
DESCRIPTION:
BRIEF SUMMARY
This invention relates to 2-heterocyclicethylamine derivatives, processes for their preparation, pharmaceutical formulations comprising them, and to their use as pharmaceuticals, in particular in the treatment of neurological disorders.
Compounds which possess anticonvulsant or N-methyl-(d)-aspartate (NMDA) blocking properties are useful in the treatment and/or prevention of neurological disorders such as stroke, cerebral ischaemia, cerebral palsy, hypoglycaemia, epilepsy, Alzheimer's disease, Huntington's chorea, Olivo-ponto-cerebellar atrophy, perinatal asphyxia, Parkinson's disease, anoxia and neuronal damage associated with substance abuse, for example, narcotics or cocaine. Undesirable side effects are associated with some neuroprotective agents and compounds with minimal psychotomimetic effects are desirable.
Certain 2-heteroarylethylamines and derivatives thereof have been described as pharmaceuticals. For example, European Patent Application No. 346791 describes 1,2-diarylethylamines in which the amine group is a cyclic amine as useful for controlling neuropathological processes and the neurodegenerative consequences thereof in mammals. U.S. Pat. No. 4,769,466 describes N-(2-aminoacetyl) -derivatives of 1,2-diarylethylamines in which one of the aryl groups is pyridine and the other is phenyl as anticonvulsants. European Patent Application No. 356035 discloses .alpha.-phenyl-2-pyridineethanamine as being useful for the treatment of neurological disorders.
Other 2-heteroarylethylamines and derivatives thereof have been described without mention of pharmaceutical utility. For example U.S. Pat. No. 4,769,466 describes 1,2-diarylethylamines in which one of the aryl groups is pyridine and the other is phenyl as intermediates. German Patents Nos. 2447258 and DE 2415063 disclose 4-methyl, 5-ethyl and 6-methyl-.alpha.-phenyl-2-pyridineethanamine, .alpha.-(2-furanyl)- and .alpha.-(2-thienyl)-2-pyridineethanamine as intermediates to the corresponding amidines. Cliffe et al, Synthesis (12), 1138-1140 (1985) describe N-(1,1-dimethylethyl)-.alpha.-phenyl-2-pyridineethanamine as an example of a highly hindered sec-alkyl-tert-alkylamine. Shuman et al, J Org Chem 27,1970-1972 (1962) describe N-[.alpha.-(2-pyridinylmethyl)benzyl] acetamide as an intermediate.
According to the invention, there is provided a compound of formula I, ##STR1## wherein A represents CH.dbd.CH, S or O; nitrogen atom in the position adjacent to the point of attachment, 0-3 further heteroatoms selected from N, O and S, and substituents R.sup.6 and R.sup.7 ; alkynyl, C.sub.3-6 cycloalkyl or NH.sub.2 CH.sub.2 CO-; alkylene chain; alkynyl. C.sub.1-6 alkyl, halogen, trifluoromethyl or NR.sup.8 R.sup.9 ; C.sub.1-6 alkyl, halogen, trifluoromethyl, C.sub.1-6 hydroxyalkyl, amidino, CONH.sub.2 or NR.sub.R.sup.9 ; substituted on N; that: represent H; and Q represents 2-pyridinyl, 4-or 6-methyl-2-pyridinyl or 5-ethyl- 2-pyridinyl; then R.sup.1 is other than H; CH.sub.2 CO--; R.sup.3, R.sup.4 and R.sup.5 each represent H; and Q represents 2-pyridinyl; then R.sup.1 is other than H; represents 2-pyridinyl; then, either R.sup.1 or one of R.sup.4 and R.sup.5 is other than H;
Specific heterocyclic rings which Q may represent include non-aromatic rings such as thiazoline, diazoline and oxazoline. However, Q preferably represents an aromatic ring, for example pyridine, pyrazine, pyrimidine, pyridazine, 1,2,4-triazine, imidazole, pyrazole, 2H-pyrrole, isoxazole, isothiazole, oxazole, thiazole, 1,2,4 -oxadiazine, 1,2,4-thiadiazine and 1,2,4-triazole.
Alkyl groups which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 may represent include methyl, ethyl, propyl, isopropyl, n-butyl, iso-butyl and s-butyl. Alkoxy groups which R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may represent include methoxy, ethoxy and propoxy. Halogen groups which R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may represent include fluorine, chlorine, bromine or iodine. Alkenyl groups which R.sup.2 and R.sup.3 may represent include 2-propenyl, 2-butenyl and 2-methyl-2-prop
REFERENCES:
patent: 4762834 (1988-08-01), Combourieu et al.
patent: 4833143 (1989-05-01), Armitage et al.
patent: 4968676 (1990-11-01), Zipperer et al.
Chemical Abstracts, #115:85433j, Griffith et al "Use of arylalkylamides in the treatment . . . " vol. 115, 1991.
I. A. Cliffe et al. "Sterically hindered lithium . . . " Synthesis, No. 12, Sep. 1985, Stuttgart De, pp. 1138-1140.
S. Fustero et al. "Synthesis and reactivity of beta-amino . . . " Tetrahedron Letters, vol. 33 No. 26, 23 Jun. 1992, Oxford GB, pp. 3801-3804.
Griffith Robert J.
Griffith Ronald C.
Schmiesing Richard J.
Fan Jane
Fisons Corporation
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