Phenylethylamines and condensed rings variants as prodrugs...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C514S297000, C514S212010, C514S411000, C546S101000, C548S427000

Reexamination Certificate

active

06998405

ABSTRACT:
Compounds of the general formula Iwherein rings B, C, D and E may be present or not and, when present, are combined with A as A+C, A+E, A+B+C, A+B+D, A+B+E, A+C+E, A+B+C+D or A+B+C+D+E, rings B, C and E being aliphatic whereas ring D may be aliphatic or aromatic/heteroaromatic, and wherein X is —(CH2)m—, in which m is an integer 1–3, to form a ring E or, when E is absent, a group R1bound to the nitrogen atom, wherein R1is selected from the group consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to 3 carbon atoms, cycloalkyl(alkyl) groups of 3 to 5 carbon atoms (i.e. including cyclopropyl, cyclopropylmethyl, cyclobutyl and cyclobutylmethyl) and wherein Y is —(CH2)n—, in which n is an integer 1–3, to form a ring C or when C is absent, a group R2bound to the nitrogen atom, wherein R2is selected from the group consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to 7 carbon atoms, cycloalkyl(alkyl) groups of 3 to 7 carbon atoms, alkenyl or alkylnyl groups of 3 to 6 carbon atoms, arylalkyl, heteroarylalkyl having 1 to 3 carbon atoms in the alkyl moiety, whilst the aryl/heteroaryl nucleus may be substituted, provided that when rings B, C, D and E are absent NR1R2is different from dimethylamino, N-methyl-N-ethylamino, N-methyl-N-propynyl-amino, N-methyl-N-propylamino and N-hydroxipropyl-N-methylamino, and salts thereof with pharmaceutically acceptable acids or bases are disclosed as well as the use of such compounds for the manufacturing of pharmaceutical compositions for the treatment of Parkinson's disease, psychoses, Huntington's disease, impotence, renal failure, heart failure or hypertension, such pharmaceutical compositions and methods of treating Parkinson's disease and schizophrenia.

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Tommy Litjefors et al., “Pre-and Postsynaptic Dopaminergic Activities of Indolizidine and Quinolizidine Derivatives of 3-(3-Hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP) Further Developments of a Dopamine Receptor Model”, J. Med Chem., vol. 33, 1990, pp. 1015-1022, Chart I.
Klaus P. Bogeso et al., “Indolizidine and Quinolizidine Derivatives of the Dopamine Autoreceptor Agonist 3-(3-Hydroxyphenyl)-N-n-propylpideridine (3-PPP)”, J. Med. Chem., vol. 30, 1987, pp. 142-150, Figure 1.
Cor J. Grol et al., “Resolution of 5,6-Dihydroxy-2-(N,N-di-n-propylamino)tetralin in Relation to the Structural and Stereochemical Requirements for Centrally Acting Dopamine Agonists”, J. Med. Chem., vol. 28, 1985, pp. 679-683, scheme 1.

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