Back to results
US 6,388,081 B1Granted
4-substituted-quinoline derivatives and 4-substituted-quinoline combinatorial libraries
AssigneeLion Bioscience AG
InventorsThomas K. Hayes, Behrouz Forood, John S. Kiely
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel 4-substituted quinoline compounds of the following formula, libraries containing such compounds, and to the generation of such combinatorial libraries composed of such compounds: wherein R1, R2, R3, R4, R5, R6, R7, R9, and Y, have the meanings provided.
Claims9
A combinatorial library of two or more compounds of the formula:
- wherein in the above Formula I, the dashed lines (—————) means fully saturated or fully unsaturated and further wherein:
- R1 is absent or present and, when present, is selected from the group consisting of C1 to C10 alkylene, C1 to C10 substituted alkylene, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C2 to C10 alkenylene, C2 to C10 substituted alkenylene, C2 to C10 alkynyl, C2 to C10 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenylene, substituted phenylene, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, heterocyclic ring, substituted heterocyclic ring, heteroaryl ring, substituted heteroaryl ring, amino, (monosubstituted)amino, a group of the formula:
- —CH2CONH— and a group of the formula:
- —(CH2)p—Ar—(CH2)q—
- wherein p and q are independently selected from a number 0 to 6, wherein both p and q are not both 0;
- and Ar is an aryl group selected from the group consisting of phenyl, substituted phenyl, heteroaryl ring and substituted heteroaryl ring;
- R2, R3, and R4 are, independently, selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C1 to C10 alkyl, C2 to C10 alkenyl, C2 to C10 alkynyl, C1 to C10 substituted alkyl, C2 to C10 substituted alkenyl, C2 to C10 substituted alkynyl, C1 to C7 alkoxy, C1 to C7 substituted alkoxy, C1 to C7 acyloxy, C1 to C7 acyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, amino, protected amino, (monosubstituted) amino, protected (monosubstituted) amino, (disubstituted)amino, carboxamide, protected carboxamide, C1 to C4 alkylthio, C1 to C4 substituted alkylthio, C1 to C4 alkylsulfonyl, C1 to C4 substituted alkylsulfonyl, C1 to C4 alkylsulfoxide, C1 to C4 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl and substituted phenylsulfonyl;
- R5 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C2 to C10 alkynyl, C2 to C10 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, carboxy, protected carboxy, C1 to C7 acyl, C1 to C7 substituted acyl, heterocyclic ring, substituted heterocyclic ring, heteroaryl ring and substituted heteroaryl ring;
- R6 is selected from the group consisting of phenyl, substituted phenyl, napthyl, substituted naphphyl, a group of the formula:
- wherein n is from 1 to 4, and a group of the formula:
- wherein R10 and R11 are, independently, selected from the group consisting of hydrogen, C1 to C10 alkyl, C1 to C10 substituted alkyl, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, C1 to C7 acyl, C1 to C7 substituted acyl, C1 to C4 alkyl sulfoxide, phenylsulfoxide, substituted phenylsulfoxide, C1 to C4 alkylsulfonyl, phenylsulfonyl, and substituted phenylsulfonyl;
- R7 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, phenyl, and substituted phenyl;
- R9 is absent or present and, when present, is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, C1 to C7 acyl, C1 to C7 substituted acyl, phenylsulfonyl, substituted phenylsulfonyl, C1 to C4 alkylsulfonyl, C1 to C4 substituted alkylsulfonyl, C1 to C6 alkylaminocarbonyl, C1 to C6 substituted alkylaminocarbonyl, phenylaminocarbonyl, and substituted phenylaminocarbonyl, provided that when the ring is unsaturated, R9 is absent;
- and
- Y is C(O)NHR12, wherein R12 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, and a functionalized resin,
- or a salt of the 4-substituted quinoline.
13 more elements
A combinatorial library of two or more compounds of the formula:
- wherein in the above Formula I, the dashed lines (— — — — —) means fully saturated or fully unsaturated and further wherein:
- R1 is absent or present and, when present, is selected from the group consisting of C1 to C10 alkylene, C1 to C10 substituted alkylene, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C2 to C10 alkenylene, C2 to C10 substituted alkenylene, C2 to C10 alkynyl, C2 to C10 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenylene, substituted phenylene, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, heterocyclic ring, substituted heterocyclic ring, heteroaryl ring, substituted heteroaryl ring, amino, (monosubstituted)amino, a group of the formula:
- —CH2CONH— and a group of the formula:
- —(CH2)p—Ar—(CH2)q—
- wherein p and q are independently selected from a number 0 to 6, wherein both p and q are not both 0;
- and Ar is an aryl group selected from the group consisting of phenyl, substituted phenyl, heteroaryl ring and substituted heteroaryl ring;
- R2, R3, and R4 are, independently, selected from the group consisting of a hydrogen atom, halo, hydroxy, protected hydroxy, cyano, nitro, C1 to C10 alkyl, C2 to C10 alkenyl, C2 to C10 alkynyl, C1 to C10 substituted alkyl, C2 to C10 substituted alkenyl, C2 to C10 substituted alkynyl, C1 to C7 alkoxy, C1 to C7 substituted alkoxy, C1 to C7 acyloxy, C1 to C7 acyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, heterocyclic ring, substituted heterocyclic ring, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclic C2 to C7 alkylene, substituted cyclic C2 to C7 alkylene, cyclic C2 to C7 heteroalkylene, substituted cyclic C2 to C7 heteroalkylene, carboxy, protected carboxy, hydroxymethyl, protected hydroxymethyl, amino, protected amino, (monosubstituted)amino, protected (monosubstituted)amino, (disubstituted)amino, carboxamide, protected carboxamide, C1 to C4 alkylthio, C1 to C4 substituted alkylthio, C1 to C4 alkylsulfonyl, C1 to C4 substituted alkylsulfonyl, C1 to C4 alkylsulfoxide, C1 to C4 substituted alkylsulfoxide, phenylthio, substituted phenylthio, phenylsulfoxide, substituted phenylsulfoxide, phenylsulfonyl and substituted phenylsulfonyl;
- R5 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C2 to C10 alkynyl, C2 to C10 substituted alkynyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, carboxy, protected carboxy, C1 to C7 acyl, C1 to C7 substituted acyl, heterocyclic ring, substituted heterocyclic ring, heteroaryl ring and substituted heteroaryl ring;
- R6 is selected from the group consisting of phenyl, substituted phenyl, napthyl, substituted naphphyl, a group of the formula:
- wherein n is from 1 to 4, and a group of the formula:
- wherein R10 and R11 are, independently, selected from the group consisting of hydrogen, C1 to C10 alkyl, C1 to C10 substituted alkyl, C2 to C10 alkenyl, C2 to C10 substituted alkenyl, C3 to C7 cycloalkyl, C3 to C7 substituted cycloalkyl, C5 to C7 cycloalkenyl, C5 to C7 substituted cycloalkenyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, C1 to C7 acyl, C1 to C7 substituted acyl, C1 to C4 alkyl sulfoxide, phenylsulfoxide, substituted phenylsulfoxide, C1 to C4 alkylsulfonyl, phenylsulfonyl, and substituted phenylsulfonyl;
- R7 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, C7 to C12 phenylalkyl, C7 to C12 substituted phenylalkyl, phenyl, and substituted phenyl;
- R9 is absent or present and, when present, is a hydrogen atom;
- and
- Y is selected from the group consisting of CO2H, OH, SH, NHR12, C(O)NHR12, CH2OH, CH2NH2, and CH2NHR12, wherein R12 is selected from the group consisting of a hydrogen atom, C1 to C10 alkyl, C1 to C10 substituted alkyl, and a functionalized resin,
- or a salt of the 4-substituted quinoline.
13 more elements
Dependencies are inferred from the claim text.