Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1994-05-12
1995-04-18
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514259, 514311, 514312, 514418, 514456, 514469, 514470, 514603, 514620, 514639, 514640, 514653, 544287, 546153, 546176, 548512, 549283, 549302, 549398, 549401, 549462, 549466, 558408, 564 74, 564164, 564251, 564257, 564265, 564342, 564345, 564355, 564366, 564389, 564384, A61K 31135, A61K 31311, C07C23720, C07D30779
Patent
active
054079616
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is based upon PCT Application No. PCT/EP 92/02995, filed Dec. 22, 1992, which claims priority from EPO application Ser. No. 91.203,430.3, filed Dec. 30, 1991.
BACKGROUND OF THE INVENTION
In U.S. Pat. No. 4,246,429 there are described a number of benzeneacetamides and thioamides being useful as intermediates in the preparation of phytopharmaceutical compounds. Unexpectedly, it has now been found that some analogous intermediates effectively inhibit the replication of HIV and consequently may be useful for the treatment of individuals infected by HIV, in particular HIV-1.
DESCRIPTION OF THE INVENTION
The present invention is concerned with compounds having the formula ##STR2## the pharmaceutically acceptable acid addition salts thereof and the stereochemically isomers forms thereof, wherein R.sup.16 and R.sup.17 each independently are hydrogen or C.sub.1-4 alkyl; or R.sup.18 is hydrogen or hydroxy; nitro, aminocarbonyl, or a radical C.sub.1-6 alkyl-(C.dbd.Z)--, wherein Z represents O, N--OH, N--OCH.sub.3, N--NH.sub.2 or N--N(CH.sub.3).sub.2 ; together form a bivalent radical of formula (CH.sub.2).sub.m wherein m is 3 or 4, --(C.dbd.O)--O--CH.sub.2 --, --(C.dbd.O)--O--(CH.sub.2).sub.2 --, --(C.dbd.O)--(CH.sub.2).sub.2 --, --(C.dbd.O)--(CH.sub.2).sub.3 --, --(C.dbd.O)--CH.sub.2 --O--, --(C.dbd.O)--CH.sub.2 --NH--, --(C.gradient.O)--(CH.sub.2).sub.2 --O--, --O--(CH.sub.2).sub.2 --, --O--(CH.sub.2).sub.3 --, --N.dbd.CH--CH.dbd.CH--, --(N.fwdarw.O).dbd.CH--CH.dbd.CH-- or --(C.dbd.O)--NH--CH.dbd.N--, wherein one or two hydrogen atoms can optionally be replaced with C.sub.1-4 alkyl; or --(CH.sub.2).sub.m -- wherein m is 3 or 4 and wherein one or two hydrogen atoms can optionally be replaced with C.sub.1-4 alkyl, in which case R.sup.5 represents hydrogen, C.sub.1-6 alkyloxy, C.sub.1-6 alkyl, halo, nitro, aminocarbonyl, or a radical C.sub.1-6 alkyl-(C.dbd.Z), wherein Z is as defined hereinabove; R.sup.19 is hydrogen or hydroxy; 2,2,2-trifluoroethoxy, (trifluoromethyl)carbonyl, aminocarbonyl, (cyclopropyl)carbonyl or a radical C.sub.1-6 alkyl--C(.dbd.Z)-- wherein Z is defined as hereinabove; and alkyl, nitro, C.sub.1-4 alkyloxy or trifluoromethyl.
The compounds of formula (I) wherein at least one of R.sup.16 and R.sup.17 is hydrogen may also exist in their tautomeric form. Said form although not explicitly indicated hereinabove is intended to be included within the scope of the present invention.
In the foregoing definitions halo defines fluoro, chloro, bromo and iodo; C.sub.1-4 alkyl defines straight and branch chained saturated hydrocarbon radicals having from 1 to 4 carbon atoms, such as, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, and 1,1-dimethylethyl; C.sub.1-6 alkyl defines C.sub.1-4 alkyl and the higher homologs thereof having 5 or 6 carbon atoms, such as, for example, pentyl, hexyl and the like; C.sub.1-4 alkanediyl defines bivalent straight or branch chained hydrocarbon radicals containing from 1 to 4 atoms, such as, for example, 1,2-ethanediyl, 1,3-propanediyl, 1,4-butanediyl and the branched isomers thereof; C.sub.3-6 cycloalkyl defines cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The pharmaceutically acceptable acid addition salts as mentioned hereinabove comprise the therapeutically active non-toxic acid addition salt forms which the compounds of formula (I-a) or (I-b) are able to form. Said salts can conveniently be obtained by treating the base form of the compounds of formula (I-a) or (I-b) with appropriate acids such as inorganic acids, for example, hydrohalic acid, e.g. hydrochloric, hydrobromic and the like acids, sulfuric acid, nitric acid, phosphoric acid and the like; or organic acids, such as, for example, acetic, hydroxyacetic, propanoic, 2-hydroxypropanoic, 2-oxo-propanoic, ethanedioic, propanedioic, butanedioic, (Z)-2-butenedioic, (E)-2-butenedioic, 2-hydroxybutanedioic, 2,3-dihydroxybutanedioic, 2-hydroxy-1,2,3-propane-tricarboxylic, methanesulfonic, ethanesulfonic, benzenesu
REFERENCES:
patent: 4246429 (1981-01-01), Van Daele
Bosmans Jean-Paul R. M. A.
Janssen Marcel A. C.
Janssen Paul A. J.
Nuyens Karin J. M. M.
Van Daele Georges H. P.
Janssen Pharmaceutica N.V.
Metz Charles J.
Raymond Richard L.
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