| abstract |
This provides pharmaceutical compositions and methods for using said compositions for the treatment of caspase mediated diseases and the processes for preparing said compounds. Claim 1: A compound of the formula (1), characterized in that: R1 is R6C (O) -, HC (O) -, R6SO2-, R6OC (O) -, (R6) 2NC (O) -, (R6) (H) NC (O) -, R6C (O) C (O) -, R6-, (R6) 2NC (O) C (O) -, (R6) (H) NC (O) C (O) - , or R6OC (O) C (O) -; R2 is hydrogen, -CF3, halo, -OR7, -NO2, -OCF3, -CN, or R8; R3 is hydrogen or aliphatic- (C1-4) -; R4 is -COOH or -COOR8; R5 is -CH2F or -CH2O-2,3,5,6-tetrafluorophenyl; R6 is aliphatic- (C1-12) -cycloaliphatic- (C3-10) -, aryl- (C6-10) -, heterocyclyl- (C3-10) -, heteroaryl- (C5-10) -, cycloaliphatic- (C3 -10) -aliphatic- (C1-12) -, aryl- (C6-10) -aliphatic- (C1-12) -, heterocyclyl- (C3-10) -aliphatic- (C1-12) -, heteroaryl- ( C5-10) -aliphatic (C1-12) -, or two R6 groups bonded to the same atom together with said atom an aromatic or non-aromatic ring of 3 to 10 members; where the ring is optionally fused to aryl- (C6-10), heteroaryl- (C5-10), cycloalkyl- (C3-10), or heterocyclyl- (C3-10); where up to 3 aliphatic carbon atoms can be replaced by a group selected from O, N (H), N (R), S, SO, and SO2; and where R6 is substituted with up to 6 substituents independently selected from R; R is halogen, -OR7, -OC (O) N (R7) 2, -NO2, -CN, -CF3, -OCF3, -R7, oxo, = NR7, = N (OR7), thioxo, 1,2- methylenedioxy, 1,2-ethylenedioxy, -N (R7) 2, -SR7, -SOR7, -SO2R7, -SO2N (R7) 2, -SO3R7, -C (O) R7, -C (O) C (O) R7, -C (O) C (O) OR7, -C (O) C (O) N (R7) 2, -C (O) CH2C (O) R7, -C (S) R7, -C (S ) OR7, -C (O) OR7, -OC (O) R7, -C (O) N (R7) 2, -OC (O) N (R7) 2, -C (S) N (R7) 2, - (CH2) 0-2NHC (O) R7, -N (R7) N (R7) COR7, -N (R7) N (R7) C (O) OR7, -N (R7) N (R7) CON (R7 ) 2, -N (R7) SO2R7, -N (R7) SO2N (R7) 2, -N (R7) C (O) OR7, -N (R7) C (O) R7, -N (R7) C ( S) R7, -N (R7) C (O) N (R7) 2, -N (R7) C (S) N (R7) 2, -N (COR7) COR7, -N (OR7) R7, -C (= NH) N (R7) 2, -C (O) N (OR7) R7, -C (= NOR7) R7, -OP (O) (OR7) 2, -P (O) (R7) 2, - P (O) (OR7) 2, or -P (O) (H) (OR7); two R7 groups together with the atoms to which they are linked form an aromatic or non-aromatic ring of 3 to 10 members having up to 3 heteroatoms independently selected from N (H), N (R), O, S, SO, or SO2 , where the ring is optionally fused to aryl (C6-10), heteroaryl (C5-10), cycloalkyl (C3-10), or heterocyclyl (C3-10), and where any ring has up to 3 substituents independently selected from J2; or each R7 is independently selected from: hydrogen-, aliphatic- (C1-12) -; cycloaliphatic- (C3-10) -; cycloaliphatic- (C3-10) -aliphatic- (C1-12) -; aryl- (C6-10) -; aryl- (C6-10) -aliphatic- (C1-12) -; heterocyclyl- (C3-10) -; heterocyclyl- (C6-10) -aliphatic- (C1-12) -; heteroaryl- (C5-10) -, or heteroaryl- (C5-10) -aliphatic- (C1-12) -; where R7 has up to 3 substituents independently selected from J2; and J2 is halogen, -OR7, -OC (O) N (R7) 2, -NO2, -CN, -CF3, -OCF3, -R7, oxo, thioxo, = NR7, = NOR7, 1,2-methylenedioxy, 1,2-ethylenedioxy, -N (R7) 2, -SR7, -SOR7, -SO2R7, -SO2N (R7) 2, -SO3R7, -C (O) R7, -C (O) C (O) R7, -C (O) C (O) OR7, -C (O) CH2C (O) R7, -C (S) R2, -C (S) OR7, -OC (O) R7, -C (O) N ( R7) 2, -OC (O) N (R7) 2, -C (S) N (R7) 2, - (CH2) 0-2NHC (O) R7, -N (R7) N (R7) COR7, - N (R7) N (R7) C (O) OR7, -N (R7) N (R7) CON (R7) 2, -N (R7) SO2R7, -N (R7) SO2N (R7) 2, -N ( R7) C (O) OR7, -N (R7) C (O) R7, -N (R7) C (S) R7, -N (R7) C (O) N (R7) 2, -N (R7) C (S) N (R7) 2, -N (COR7) COR7, -N (OR7) R7, -CN, -C (= NH) N (R7) 2, -C (O) N (OR7) R7, -C (= NOR7) R7, -OP (O) (OR7) 2, -P (O) (R7) 2, -P (O) (OR7) 2, or -P (O) (H) (OR7) ; and R8 is aliphatic- (C1-12) -cycloaliphatic (C3-10) -, (C6-10) -aryl-, heterocyclyl- (C3-10) -, heteroaryl- (C5-10) -, cycloaliphatic- (C3 -10) -aliphatic- (C1-12) -, aryl- (C6-10) -aliphatic- (C1-12) -, heterocyclyl- (C3-10) -aliphatic- (C1-12), heteroaryl- (C5 -10) -aliphatic- (C1-12) -, where up to 3 aliphatic carbon atoms can be replaced with a group selected from O, N (H), N (R), S, SO, and SO2; and where R8 is optionally substituted with up to 6 substituents independently selected from R. |