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US 5,859,190 AGranted
Combinatorial libraries of hydantoin and thiohydantoin derivatives, methods of making the libraries and compounds therein
AssigneeTrega Biosciences, Inc.
InventorsJean-Philippe Meyer, John M. Ostresh, Richard A. Houghten
Life of this patent
Estimating the term…
Abstract
The invention provides a rapid approach for combinatorial synthesis and screening of libraries of hydantoin and thiohydantoin compounds. The present invention further provides the compounds made by the combinatorial synthesis.
Claims25
A composition of matter, comprising a combinatorial library of two or more hydantoin compounds comprising the structure:
- ##STR19## wherein:
- R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, amino, (monosubstituted) amino, (disubstituted)amino, (trisubstituted)amino, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
- R.sup.2 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.3 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
- R.sup.4 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.5 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- X is selected from the group consisting of an oxygen atom(O) and a sulfur atom(S);
- Y is selected from the group consisting of a nitrogen atom (N) and an oxygen atom (O);
- Z is selected from the group consisting of hydrogen, an amino resin, and a hydroxy resin;
- m is zero to five;
- n is zero to four;
- and
- p is zero or one,
- provided that when Y is nitrogen, p is one and Z is hydrogen or an amino resin and further provided that when Y is oxygen p is zero and Z is hydrogen or a hydroxy resin.
11 more elements
A single hydantoin compound comprising the structure:
- ##STR20## R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, amino, (monosubstituted) amino, (disubstituted)amino, (trisubstituted)amino, carboxy, substituted carboxy, carbamoyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
- R.sup.2 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.3 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl, provided that, where C.sub.1 to C.sub.10 substituted alkyl is selected and the substitution is with a protected carboxy, the carboxy-protecting group is selected from the group consisting of 4-nitrobenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 2,4-dimethoxybenzyl, 2,4,6-trimethoxybenzyl, 2,4,6-trimethylbenzyl, pentamethylbenzyl, 3,4-methylenedioxybenzyl, benzhydryl, 4,4'-dimethoxytrityl, 4,4', 4"-trimethoxytrityl, 2-phenylprop-2-yl, trimethylsilyl, t-butyldimethylsilyl, 2,2,2-trichloroethyl, .beta.-(trimethylsilyl)ethyl, .beta.-(di(n-butyl)methylsilyl)ethyl, p-toluenesulfonylethyl, 4-nitrobenzyl-sulfonylethyl, allyl, cinnamyl, and 1-(trimethylsilylmethyl)-prop-1-en-3-yl;
- R.sup.4 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.5 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- X is selected from the group consisting of an oxygen atom(O) and a sulfur atom(S);
- Y is a nitrogen atom (N);
- Z is a hydrogen atom;
- m is zero to five;
- n is zero to four;
- and
- p is one,
- or a pharmaceutically-acceptable salt thereof.
10 more elements
A single thiohydantoin compound comprising the structure:
- ##STR21## wherein:
- R.sup.1 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl;
- C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, amino, (monosubstituted) amino, (disubstituted)amino, (trisubstituted)amino, carboxy, substituted carboxy, carbamoyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
- R.sup.2 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.3 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl;
- C.sub.1 to C.sub.10 substituted alkyl, C.sub.7 to C.sub.16 phenylalkyl, C.sub.7 to C.sub.16 substituted phenylalkyl, phenyl, substituted phenyl, C.sub.3 to C.sub.7 cycloalkyl, and C.sub.3 to C.sub.7 substituted cycloalkyl;
- R.sup.4 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- R.sup.5 is selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.10 alkyl, C.sub.2 to C.sub.10 alkenyl, benzyl, substituted benzyl, naphthylmethyl, and substituted naphthylmethyl;
- X is a sulfur atom(S);
- Y is selected from the group consisting of a nitrogen atom (N) and an oxygen atom (O);
- Z is a hydrogen atom;
- m is zero to five;
- n is zero to four;
- and
- p is zero or one, provided that when Y is nitrogen, p is one and further provided that when Y is oxygen p is zero and Z is hydrogen, or a pharmaceutically-acceptable salt thereof.
12 more elements
Dependencies are inferred from the claim text.