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US 6,143,895 AGranted
Quinoline derivatives and quinoline combinatorial libraries
AssigneeTrega Biosciences, Inc.
InventorsYazhong Pei, John S. Kiely
Life of this patent
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Abstract
The present invention relates to novel tetrahydro-quinoline compounds of the following formula, libraries containing such compounds, and to the generation of such combinatorial libraries composed of such compounds: ##STR1## wherein 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 Y have the meanings provided.
Claims6
A tetrahydro-quinoline compound of the formula:
- ##STR6## wherein:
- R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.5 to C.sub.7 cycloalkenyl, C.sub.5 to C.sub.7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl or a group of the formula:
- --(CH.sub.2).sub.n --Ar--(CH.sub.2).sub.m --
- wherein n and m are independently selected from a number 0 to 6;
- and Ar is an aryl group selected from the group consisting of phenyl, substituted phenyl, heteroaryl and substituted heteroaryl;
- R.sup.2 is selected from the group consisting of hydroxy, C.sub.1 to C.sub.7 alkoxy, C.sub.1 to C.sub.7 substituted alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.7 to C.sub.12 phenylalkoxy, C.sub.7 to C.sub.12 substituted phenylalkoxy, phenoxy, substituted phenoxy, phthalimide, substituted phthalimide, amino, protected amino, (monosubstituted)amino, (disubstituted)amino, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 substituted alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, C.sub.1 to C.sub.4 substituted alkylsulfonyl, C.sub.1 to C.sub.4 alkylsulfoxide, C.sub.1 to C.sub.4 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl and substituted phenylsulfonyl;
- R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are, independently, selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.1 to C.sub.7 alkoxy, C.sub.1 to C.sub.7 substituted alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.1 to C.sub.7 acyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.5 to C.sub.7 cycloalkenyl, C.sub.5 to C.sub.7 substituted cycloalkenyl, a heterocyclic ring, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, amino, protected amino, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino, carboxamide, protected carboxamide, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 substituted alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, C.sub.1 to C.sub.4 substituted alkylsulfonyl, C.sub.1 to C.sub.4 alkylsulfoxide, C.sub.1 to C.sub.4 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl and substituted phenylsulfonyl;
- or
- one or more of adjacent position pairs R.sup.3 and R.sup.4, R.sup.4 and R.sup.5, and R.sup.5 and R.sup.6 together form a group that is, independently, selected from cyclic C.sub.2 to C.sub.7 alkylene, substituted cyclic C.sub.2 to C.sub.7 alkylene, cyclic C.sub.2 to C.sub.7 heteroalkylene and substituted cyclic C.sub.2 to C.sub.7 heteroalkylene, wherein said group is bonded to the phenyl ring depicted in Formula I;
- R.sup.7 and R.sup.8 are, independently, selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.1 to C.sub.7 acyl, C.sub.1 to C.sub.7 substituted acyl, phenylsulfonyl, substituted phenylsulfonyl, C.sub.1 to C.sub.4 alkylsulfonyl, C.sub.1 to C.sub.4 substituted alkylsulfonyl, C.sub.1 to C.sub.6 alkylaminocarbonyl, C.sub.1 to C.sub.6 substituted alkylaminocarbonyl, phenylaminocarbonyl, and substituted phenylaminocarbonyl;
- and
- Y is C(O)NHR.sup.9, wherein R.sup.9 is a hydrogen atom, C.sub.1 to C.sub.6 alkyl and C.sub.1 to C.sub.6 substituted alkyl;
- or
- a salt of the tetrahydro-quinoline compounds.
11 more elements
A tetrahydro-quinoline compound of the formula:
- ##STR7## wherein:
- R.sup.1 is selected from the group consisting of C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.2 to C.sub.7 alkenyl, C.sub.2 to C.sub.7 substituted alkenyl, C.sub.2 to C.sub.7 alkynyl, C.sub.2 to C.sub.7 substituted alkynyl, C.sub.3 to C.sub.7 cycloalkyl, C.sub.3 to C.sub.7 substituted cycloalkyl, C.sub.5 to C.sub.7 cycloalkenyl, C.sub.5 to C.sub.7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C.sub.7 to C.sub.12 phenylalkyl, C.sub.7 to C.sub.12 substituted phenylalkyl or a group of the formula:
- --(CH.sub.2).sub.n --Ar--(CH.sub.2).sub.m --
- wherein n and m are independently selected from a number 0 to 6;
- and Ar is an aryl group selected from the group consisting of phenyl, substituted phenyl, heteroaryl and substituted heteroaryl;
- R.sup.2 is selected from the group consisting of hydroxy, C.sub.1 to C.sub.7 alkoxy, C.sub.1 to C.sub.7 substituted alkoxy, C.sub.1 to C.sub.7 acyloxy, C.sub.7 to C.sub.12 phenylalkoxy, C.sub.7 to C.sub.12 substituted phenylalkoxy, phenoxy, substituted phenoxy, phthalimide, substituted phthalimide, amino, protected amino, (monosubstituted)amino, (disubstituted)amino, C.sub.1 to C.sub.4 alkylthio, C.sub.1 to C.sub.4 substituted alkylthio, C.sub.1 to C.sub.4 alkylsulfonyl, C.sub.1 to C.sub.4 substituted alkylsulfonyl, C.sub.1 to C.sub.4 alkylsulfoxide, C.sub.1 to C.sub.4 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl and substituted phenylsulfonyl;
- R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are, independently, selected from the group consisting of amino, protected amino, (monosubstituted)amino, protected (monosubstituted)amino, and (disubstituted)amino;
- R.sup.7 and R.sup.8 are, independently, selected from the group consisting of a hydrogen atom, C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 substituted alkyl, C.sub.1 to C.sub.7 acyl, C.sub.1 to C.sub.7 substituted acyl, phenylsulfonyl, substituted phenylsulfonyl, C.sub.1 to C.sub.4 alkylsulfonyl, C.sub.1 to C.sub.4 substituted alkylsulfonyl, C.sub.1 to C.sub.6 alkylaminocarbonyl, C.sub.1 to C.sub.6 substituted alkylaminocarbonyl, phenylaminocarbonyl, and substituted phenylaminocarbonyl;
- and
- Y is selected from the group consisting of CO.sub.2 H, OH, SH, NHR.sup.9, C(O)NHR.sup.9, CH.sub.2 OH, CH.sub.2 NH.sub.2, CH.sub.2 NHR.sup.9 and a functionalized resin, wherein R.sup.9 is a hydrogen atom, C.sub.1 to C.sub.6 alkyl and C.sub.1 to C.sub.6 substituted alkyl;
- or
- a salt of the tetrahydro-quinoline compounds.
9 more elements
Dependencies are inferred from the claim text.