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US 6,545,004 B1Granted
Methods and compositions utilizing quinazolinones
AssigneeCytokinetics, Inc.
InventorsJeffrey T. Finer, Gustave Bergnes, Whitney W. Smith, John C. Chabala, Bainian Feng
Life of this patent
Estimating the term…
Abstract
Quinazolinones of formulae 1a, 1b, 1c and 1d are disclosed. They are useful for treating cellular proliferative diseases and disorders associated with KSP kinesin activity.
Claims22
A compound of a formula:
- wherein
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(isopropylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is p-chlorobenzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(dimethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is m-methoxybenzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is isopropyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is azetidin-3-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-aminoethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-aminoethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(methylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(methylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(methylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is azetidin-2-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is methylsulfinylmethyl;
- R2′ is hydrogen;
- R3 is p-toyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is piperidin-3-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is fluoro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-aminoethyl;
- R5, R6, R7 and R8 are hydrogen;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is piperidin-2-yl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 4-aminobutyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is m-chlorobenzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(piperidin-1-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(imidazol-3-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is pyrrolidin-3-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(diethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-chlorophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 4-aminobutyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is pyrrolidin-2-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(azetidin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(pyrrolidin-1-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(pyrrolidin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(dimethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is propyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(pyrrolidin-1-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(pyrrolidin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is piperidin-4-ylmethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is methylsulfinylethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(piperidin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is benzyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is (N-ethylpyrrolidin-2-yl)methyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-piperidinyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 4-piperidinyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is p-chlorobenzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2,2-dimethyl-3-(dimethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 5-aminopentyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-(dimethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is fluoro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(2-methylpiperidin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is fluoro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(N-methylpyrrolidin-2-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-trifluoromethylphenyl;
- R4 is 3-(dimethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(diethylamino)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 3-(N-methylpiperazin-1-yl)propyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is 4-(CBZ)aminobutyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is aminoethoxyethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is 2-naphthyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro
- R1 is benzyl;
- R2 is cyclohexylmethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(piperidin-1-yl)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-hydroxypropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-fluorophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 6-aminohexyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R7, and R8 are hydrogen;
- and R6 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is fluoro;
- R1 is benzyl;
- R2 is methyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-aminoethyl;
- R5, R6, R7 and R8 are hydrogen;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R7 are hydrogen;
- and R8 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R6, R7, and R8 are hydrogen;
- and R5 is chloro;
- R1 is benzyl;
- R2 is aminobutyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 2-(dimethylamino)ethyl;
- R5 and R8 are hydrogen;
- and R6 and R7 are fluoro;
- R1 is m-tolyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro;
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-(dimethylamino)ethyl;
- R5 and R8 are hydrogen;
- and R6 and R7 are fluoro;
- or
- R1 is benzyl;
- R2 is ethyl;
- R2′ is hydrogen;
- R3 is p-bromophenyl;
- R4 is 2-carboxyethyl;
- R5, R6, and R8 are hydrogen;
- and R7 is chloro,
- or a pharmaceutically acceptable salt of any of the foregoing compounds.
523 more elements
A salt of the formula
- wherein
- R1 is benzyl;
- R2 is isopropyl;
- R2′ is hydrogen;
- R3 is p-tolyl;
- R4 is 3-aminopropyl;
- R5 is hydrogen;
- R6 is hydrogen;
- R7 is chloro;
- and
- R8 is hydrogen;
- and wherein
- said salt is a mesylate.
10 more elements
A compound of formula:
- wherein:
- R1 is benzyl or halobenzyl;
- R2 ethyl or propyl;
- R2′;
- R3 is substituted phenyl;
- R4 is —(CH2)mOH or —(CH2)pR16 wherein m is two or three and p is one to three;
- R5 is hydrogen;
- R6 hydrogen;
- R7 is halo;
- R8 is hydrogen;
- and
- R16 is chosen from amino, propylamino, and azetidinyl;
- or a pharmaceutically acceptable salt thereof.
10 more elements
Dependencies are inferred from the claim text.