| Sonstiges: |
- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20120202821
- Publication Date: August 9, 2012
- Appl. No: 13/388891
- Application Filed: August 05, 2009
- Assignees: POLYPHOR AG (Allschwil, CH)
- Claim: 1. Compounds of the general formula I incorporating the building blocks A, B and C [chemical expression included] wherein the encircled moieties a in building block A, b in building block B and c1-C3 in building block C are derived from basic skeletons, appropriately and independently substituted as defined below, the basic skeletons of a and b corresponding to the ring systems depicted in Table 1 and Table 2, below; [table included] [table included] depending on the substitution pattern of skeletons b alternative binding modes being feasible for skeletons b3 and b4 such incorporation via the excocyclic nitrogen atom being represented by the following two structures: [chemical expression included] the encircled parts of the bridge subunits c1-c3 representing optionally substituted groups, definitions of c1-c3 being depicted in Table 3, below, each reading from the N-terminus to the C-terminus of the linker C, said linker C being, in the simplest case, constituted by one subunit c1, i.e. c1-1 to c1-6, and for the embodiments consisting of two or three subunits all possible combinations of the subunits c1-c3 and the connectivities U, V and W being possible; [table included] the substituents directly attached to building block A, B and C, i.e. R1-R17, being defined as follows: R1: H; F; Cl; Br; I; CF3; OCF3; OCHF2; NO2; CN; alkyl; alkenyl; alkynyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qSR20; —(CR18R19)qNR4R11; —(CR18R19)qOCONR4R11; —(CR18R19)qOCOOR21; —(CR18R19)qNR4COOR21; —(CR18R19)qNR4COR22; —(CR18R19)qNR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qOPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qOSO3R21; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R2: H; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qSR20; —(CR18R19)qNR4R11; —(CR18R19)qOCONR4R11; —(CR18R19)qOCOOR21; —(CR18R19)qNR4COOR21; —(CR18R19)qNR4COR22; —(CR18R19)q NR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R3: H; CF3; alkyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; R4: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or a suitable N-protecting group; R5, R7 and R9 are independently defined as: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR18R19)sOR20; —(CR18R19)sSR20; —(CR18R19)sNR4R11; —(CR18R19)sOCONR4R11; —(CR18R19)sOCOOR21; —(CR18R19)sNR4COOR21; —(CR18R19)sNR4COR22; —(CR18R19)sNR4CONR4R11; —(CR18R19)sNR4SO2R23; —(CR18R19)sNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R6, R8 and R10 are independently defined as: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; or heteroarylalkyl; R11: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; a suitable protecting group; —(CR18R19)rOR20; —(CR18R19)rSR20; —(CR18R19)rNR4R27; —(CR18R19)rOCONR4R27; —(CR18R19)rOCOOR21; —(CR18R19)rNR4COOR21; —(CR18R19)rNR4CONR4R27; —(CR18R19)rNR4SO2R23; —(CR18R19)rNR4SO2NR4R27; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R27; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qSO2NR4R27; —(CR18R19)qR24; —(CR18R19)sR25; or —(CR18R19)qR26; R12 and R13 are independently defined as H; or alkyl; R14 and R16 are independently defined as: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR18R19)sOR20; —(CR18R19)sNR4R11; —(CR18R19)sNR4COOR21; —(CR18R19)sNR4COR22; —(CR18R19)sNR4CONR4R11; —(CR18R19)sNR4SO2R23; —(CR18R19)sNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; or —(CR18R19)qCOR22; R15 and R17 are independently defined as: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; or heteroarylalkyl. substituents introduced in the sub-definitions of the radical R1-R17 being defined as follows: R18: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sSR31; —(CR29R30)sNR28R31; —(CR29R30)sOCONR28R31; —(CR29R30)sOCOOR21; —(CR29R30)sNR28COOR21; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2R23; —(CR29R30)sNR28SO2NR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qPO(OR21)2; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R19: H; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; R20: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR29R30)rOR31; —(CR29R30)rSR31; —(CR29R30)rNR28R31; —(CR29R30)rOCONR28R31; —(CR29R30)rNR28COOR21; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)rNR28SO2R23; —(CR29R30)rNR28SO2NR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R21: alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or a suitable O-protecting group. R22: alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sSR31; —(CR29R30)sNR28R31; —(CR29R30)sOCONR28R31; —(CR29R30)sNR28COOR21; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2R23; —(CR29R30)sNR28SO2NR28R31; —(CR29R30)sCOOR21; —(CR29R30)sCONR28R31; —(CR29R30)sSO2NR28R31; —(CR29R30)tCOR31; —(CR29R30)sSO2R23; —(CR29R30)tR24; —(CR29R30)tR25; or —(CR29R30)tR26; R23: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or —(CR32R33)tR24; R24: H; aryl, preferably an optionally substituted phenyl group of type C6H2R34R35R31; or a heteroaryl group, preferably one of the groups of formulae H1-H34 as shown in Table 4, below; [table included] R25: One of the groups of formulae H35-H41 as shown in Table 5, below; [table included] R26: One of the groups of formulae H42-H50 as shown in Table 6, below; [table included] R27: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; a suitable protecting group; or —(CR29R30)qR24; R28: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; a suitable N-protecting group; —(CR32R33)sOR21; —(CR32R33)sNR43R42; —(CR32R33)sNR42CONR43R42; —(CR32R33)sNR42COR21; —(CR32R33)sNR42SO2NR21; —(CR32R33)qCOOR21; —(CR32R33)qCOR23; —(CR32R33)qSO2R21; R29: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR32R33)sOR31; —(CR32R33)sSR−; —(CR32R33)sNR28R31; —(CR32R33)sOCONR28R31; —(CR32R33)sOCOOR21; —(CR32R33)sNR28COOR21; —(CR32R33)sNR28COR31; —(CR32R33)sNR28CONR28R31; —(CR32R33)sNR28SO2R23; —(CR32R33)sNR28SO2NR28R31; —(CR32R33)qCOOR21; —(CR32R33)qCONR28R31; —(CR32R33)qSO2NR28R31; —(CR32R33)qPO(OR21)2; —(CR32R33)qCOR31; —(CR32R33)qSO2R23; —(CR32R33)qR31; R30: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; R31: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or one of the groups of formulae H51-H55 as shown in Table 7 below; [table included] R32 and R33 are independently defined as H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl. R34 and R35 are independently defined as H; F; Cl; CF3; OCF3; OCHF2; NO2; CN; alkyl; alkenyl; alkynyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qSR31; —(CR29R30)qNR28R31; —(CR29R30)qOCONR28R31; —(CR29R30)qNR28COOR21; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qNR28SO2R23; —(CR29R30)qNR28SO2NR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; or —(CR29R30)qR31; R36: H; alkyl; alkenyl; alkynyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or —NR28R31; R37: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; a suitable N-protecting group; —(CR29R30)rOR31; —(CR29R30)rSR31; —(CR29R30)rNR28R31; —(CR29R30)rOCONR28R31; —(CR29R30)rNR28COOR21; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)rNR28SO2R23; —(CR29R30)rNR28SO2NR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)rSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; or —(CR29R30)qR31. R38: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qSR31; —(CR29R30)qNR28R31; —(CR29R30)qNR28COOR21; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qCOR31; or —(CR29R30)qR31; R39: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR32R33)uOR21; —(CR32R33)uNR28R43; —(CR32R33)tCOOR21; or —(CR32R33)tCONR28R43; R40: H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR32R33)uOR21; —(CR32R33)uNR28R43; —(CR32R33)tCOOR21; or —(CR32R33)tCONR28R43. R41: H; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —OR21; —NR28R43; —NR28COR23; —NR28COOR21; —NR28SO2R23; —NR28CONR28R43; —COOR21; —CONR28R43; —C(═NR43)NR28N43; —NR28C(═NR43)NR28N43; or one of the groups of formulae H56-H110 as shown in Table 8 below; [table included] R42: H; alkyl; alkenyl; cycloalkyl; cycloheteroalkyl; aryl; heteroaryl; —(CR23R33)sOR21; —(CR23R33)sNR28R43; —(CR23R33)qCOOR21; or —(CR23R33)qCONR21R43; R43: H; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; or a suitable N-protecting group; R44, R45 and R46 are independently defined as H; F; CF3; OCF3; OCHF2; NO2; CN; alkyl; alkenyl; alkynyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —OR23; —NR28R43; —NR28COR23; —NR28SO2R23; —NR28CONR28R43; —COR23; —SO2R23; R47: H; CF3; alkyl; alkenyl; alkynyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —COOR21; or —CONR28R43; R48: H; F; CF3; alkyl; alkenyl; cycloalkyl; cycloheteroalkyl; aryl; heteroaryl; —(CR23R33)tOR21; —(CR23R33)tNR28R43; —(CR23R33)tCOOR21; —(CR23R33)tCONR21R43; R49 and R50 are independently defined as H; F; CF3; alkyl; alkenyl; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; arylalkyl; heteroarylalkyl; —(CR32R33)qOR21; —(CR32R33)qNR28R43; —(CR32R33)qCOOR21; or —(CR32R33)qCONR28R43; taken together the following pairs of said substituents can define cyclic structural elements: (R4 and R11); (R4 and R27); (R5 and R6); (R5 and R7); (R5 and R9); (R5 and R14); (R5 and R16); (R7 and R8); (R7 and R9); (R7 and R16); (R9 and R10); (R14 and R15); (R16 and R17); (R18 and R19); (R27 and R28); (R28 and R31); (R28 and R43); (R29 and R30); (R32 and R33); (R34 and R35); (R37 and R38); (R39 and R40); (R39 and R41); (R39 and R49); (R42 and R43); (R44 and R45); or (R44 and R46) can form optionally substituted cycloalkyl or heterocycloalkyl moieties. in addition, the structural elements —NR4R11; —NR27R28; —NR28R31 or —NR28R43 can form one of the groups of formulae H111-H118 as shown in Table 9 below; [table included] variable heteroatoms and connector groups in the aforementioned structures being as follows: Z: O; S; S(═O); S(═O)2; or NR28; Y: O; S; or NR37; X: O; S; S(═O); or S(═O)2; Q: O; S; or NR28; U, V and W: as defined in Table 3, above; T: CR46 or N; in case T occurs several times in the same ring structure each T being defined independently of the other; and the indices being defined as follows: q=0-4; =2-4; s=1-4; t=0-2; and u=1-2; all possible stereoismers and pharmaceutical acceptable salts thereof.
- Claim: 2. Compounds according to claim 1 wherein A is a bivalent radical selected from radicals A1-A626 as depicted in Table 10, below; [table included] B is selected from the divalent building blocks B1-B21 shown in Table 11, below which are based on optionally substituted cyclic secondary amines carrying a moiety of type —CHR3-LG, wherein LG is a suitable leaving group that can be replaced by the nucleophilic groups of building blocks A thus forming an ether (—O—) or a thioether (—S—) linkage between building blocks of type A and B; [table included] R1 is H; F; Cl; Br; I; CF3; OCF3; OCHF2; NO2; CN; lower alkyl; lower alkenyl; lower alkynyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qNR4R11; —(CR18R19)qNR4COOR21; —(CR18R19)qNR4COR22; —(CR18R19)qNR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qOSO3R21; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R2 is H; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qNR4R11; —(CR18R19)qNR4COOR21; —(CR18R19)qNR4COR22; —(CR18R19)qNR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R3 is defined as in claim 1; R4 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; or a suitable N-protecting group. R5, R7 and R9 are independently defined as: H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; (CR18R19)3OR20; —(CR18R19)sNR4R11; —(CR18R19)sNR4COOR21; —(CR18R19)sNR4COR22; —(CR18R19)sNR4CONR4R11; —(CR18R19)sNR4SO2R23; —(CR18R19)sNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qPO(OR21)2; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R6, R8 and R10 are independently defined as: H; CF3; or lower alkyl; R11 is H; lower alkyl; lower alkenyl; lower cycloalkyl lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; a suitable protecting group; —(CR18R19)rOR20; —(CR18R19)rNR4R27; —(CR18R19)rNR4COOR21; —(CR18R19)rNR4CONR4R27; —(CR18R19)rNR4SO2R23; —(CR18R19)rNR4SO2NR4R27; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R27; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qSO2NR4R27; —(CR18R19)qR24; —(CR18R19)sR25; or —(CR18R19)qR26; R12 and R13 are independently defined as H; or lower alkyl. R14 and R16 are independently defined as: H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)sOR20; —(CR18R19)sNR4R11; —(CR18R19)sNR4COOR21; —(CR18R19)sNR4COR22; —(CR18R19)sNR4CONR4R11; —(CR18R19)sNR4SO2R23; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qCOR22; R15 and R17 are independently defined as: H; CF3; lower alkyl; R18 is H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sNR28R31; —(CR29R30)sNR28COOR21; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2R23; —(CR29R30)sNR28SO2NR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qPO(OR21)2; (CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R19 is H; CF3; or lower alkyl; R20 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)rOR31; —(CR29R30)rNR28R31; —(CR29R30)rNR28COOR21; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)rNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R21 and R23 are as defined in claim 1; R22 lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sNR28R31; —(CR29R30)sNR28COOR21; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2—R23; —(CR29R30)sCOOR21; —(CR29R30)sCONR28R31; —(CR29R30)sSO2NR28R31; —(CR29R30)tCOR31; —(CR29R30)sSO2R23; —(CR29R30)tR24; —(CR29R30)tR25; or —(CR18R19)tR26; R24, R25 and R26, R27 and R28 are as defined in claim 1; R29 is H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR32R33)sOR31; —(CR32R33)sNR28R31; —(CR32R33)sNR28COOR21; —(CR32R33)sNR28COR31; —(CR32R33)sNR28CONR28R31; —(CR32R33)sNR28SO2R23; —(CR32R33)qCOOR21; —(CR32R33)qCONR28R31; —(CR32R33)qSO2NR28R31; —(CR32R33)qPO(OR21)2; —(CR32R33)qCOR31; —(CR32R33)qSO2R23; —(CR32R33)qR31; R30 and R33 are H; CF3; lower alkyl. R31 and R32 are as defined in claim 1; R34 and R35 are independently defined as H; F; Cl; CF3; OCF3; OCHF2; NO2; CN; lower alkyl; lower alkenyl; lower alkynyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qNR28R31; —(CR29R30)qNR28COOR21; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; or —(CR29R30)qR31; R36 is as defined in claim 1; R37 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; a suitable N-protecting group; —(CR29R30)rOR31; —(CR29R30)rNR28R31; —(CR29R30)rNR28COOR21; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)rNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)rSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; or —(CR29R30)qR31; R38: H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qNR28R31; —(CR29R30)qNR28COOR21; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qCOR31; or —(CR29R30)qR31; R39; R40; R41; R42; R43; R44; R45; R46; R47; R48; R49 and R50 are as defined in claim 1; the variable heteroatom Z and the connector U are defined as Z being O; S(═O); or S(═O)2; and U being —C(═O)—; —NR4—C(═O)—; —C(═O)—C(═O)—; or —C(—OR20)2—C(═O)—; and substituents that can be pairwise taken together and form optionally substituted cycloalkyl or heterocycloalkyl moieties; structural elements that can form one of the groups of formulae H111-H118 (Table 9); variable heteroatoms Q, T, X and Y; and indices q-u being defined as in claim 1.
- Claim: 3. Compounds according to claim 2 wherein A is A1(a1); A2(a1); A3(a1); A4(a1); A5(a1); A6(a1); A7(a1); A9(a1); A10(a1); A73(a2); A170(a4); A209(a7); A240(a10); A272(a10); A532(a18); A609(a24); A612(a24) and A614(a24) as shown in Table 13, below; [table included] B is B4(b3); B5(b3); B6(b3); B7(b3); B8(b3); B9(b3); B10(b3); B12(b4); B13(b4); B14(b4); B15(b4); B16(b4) or B17(b5) as shown in Table 14, below; [table included] linker C is one of the groups shown in Table 15, below; [table included]
- Claim: 4. Compounds according to claim 3 wherein the building blocks of type A are A1(a1); A2(a1); A3(a1); A4(a1); A5(a1); A6(a1); A7(a1); A9(a1); A10(a1); A73(a2); A170(a4); A209(a7); A240(a10); A272(a10); A532(a18); A614(a24) as shown in Table 16, below; [table included] the building blocks of type B are B7, B8, B9 and B-17 as shown in Table 17, below; [table included] the linkers C are those listed in Table 18, below; [table included] R1 is H; F; Cl; CF3; OCF3; OCHF2; NO2; CN; lower alkyl; lower alkenyl; lower alkynyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qNR4R11; —(CR18R19)qNR4COR22; —(CR18R19)qNR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R2 is H; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)qOR20; —(CR18R19)qNR4R11; —(CR18R19)qNR4COR22; —(CR18R19)qNR4CONR4R11; —(CR18R19)qNR4SO2R23; —(CR18R19)qNR4SO2NR4R11; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26. R3 is as defined in claim 1; R4 is H; lower alkyl; lower alkenyl; or a suitable N-protecting group; R5, R7 and R9 are independently defined as: H; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)sOR20; —(CR18R19)sNR4R11; —(CR18R19)sNR4COR22; —(CR18R19)sNR4CONR4R11; —(CR18R19)sNR4SO2R23; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R11; —(CR18R19)qSO2NR4R11; —(CR18R19)qCOR22; —(CR18R19)qSO2R23; —(CR18R19)qR24; —(CR18R19)qR25; or —(CR18R19)qR26; R6, R8 and R10 are independently defined as: H; CF3; or CH3; R11 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; a suitable protecting group; —(CR18R19)rOR20; —(CR18R19)rNR4R27; —(CR18R19)rNR4CONR4R27; —(CR18R19)rNR4SO2R23; —(CR18R19)qCOOR21; —(CR18R19)qCONR4R27; —(CR18R19)qCOR22; —(CR18R19)qR24; —(CR18R19)sR25; or —(CR18R19)qR26; R12 and R13 are independently defined as H; or lower alkyl; R14 and R16 are independently defined as: H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR18R19)sOR20; —(CR18R19)sNR4R11; —(CR18R19)sNR4COR22; —(CR18R19)qCOOR21; or —(CR18R19)qCONR4R11; R15 and R17 are independently defined as: H; CF3; or CH3; R18 is H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sNR28R31; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R19 is H; CF3; or CH3; R20 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)rOR31; —(CR29R30)rNR28R31; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)rNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)qSO2R23; —(CR29R30)qR24; —(CR29R30)qR25; or —(CR29R30)qR26; R21 and R23 are as defined in claim 1; R22 is lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)sOR31; —(CR29R30)sNR28R31; —(CR29R30)sNR28COR31; —(CR29R30)sNR28CONR28R31; —(CR29R30)sNR28SO2R23; —(CR29R30)sCOOR21; —(CR29R30)sCONR28R31; —(CR29R30)sSO2NR28R31; —(CR29R30)tCOR31; —(CR29R30)sSO2R23; —(CR29R30)tR24; —(CR29R30)tR25; or —(CR29R30)tR26; R24, R25, R26, R27 and R28 are as defined in claim 1; R29 is H; F; CF3; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR32R33)sOR31; —(CR32R33)sNR28R31; —(CR32R33)sNR28COR31; —(CR32R33)sNR28CONR28R31; —(CR32R33)qCOOR21; —(CR32R33)qCONR28R31; —(CR32R33)qCOR31; or —(CR32R33)qR31; R30 and R33 are H; CF3; or CH3; R31 and R32 are as defined in claim 1; R34 and R35 are independently defined as H; F; Cl; CF3; OCF3; OCHF2; lower alkyl; lower alkenyl; lower alkynyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qNR28R31; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qNR28SO2R23; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)gSO2NR28R31; —(CR29R30)qCOR31; —(CR29R30)gSO2R23; or —(CR29R30)qR31; R36 is as defined in claim 1; R37 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; a suitable N-protecting group; —(CR29R30)rOR31; —(CR29R30)rNR28R31; —(CR29R30)1NR28COOR21; —(CR29R30)rNR28COR31; —(CR29R30)rNR28CONR28R31; —(CR29R30)qCOOR21; —(CR29R30)qCONR28R31; —(CR29R30)qCOR31; or —(CR29R30)qR31; R38 is H; lower alkyl; lower alkenyl; lower cycloalkyl; lower heterocycloalkyl; aryl; heteroaryl; lower arylalkyl; lower heteroarylalkyl; —(CR29R30)qOR31; —(CR29R30)qNR28R31; —(CR29R30)qNR28COR31; —(CR29R30)qNR28CONR28R31; —(CR29R30)qCOOR21; —(CR29R30)9CONR28R31; —(CR29R30)qCOR31; or —(CR29R30)qR31; R39; R40; R41; R42; R43; R44; R45; R46; R47; R48; R49; and R50 are as defined in claim 1; the variable heteroatom Z and the connector U are defined as: Z: O; or S(═O)2. U: —C(═O)—; —NR4—C(═O)—; or —C(═O)—C(═O)—; and substituents that can be pairwise taken together and form optionally substituted cycloalkyl or heterocycloalkyl moieties; structural elements that can form one of the groups of formulae H111-H118 as shown in Table 9; and variable heteroatoms Q, T, X and Y; indices q-u; are as defined in claim 1.
- Claim: 5. Compounds according to claim 1 wherein readily accessible substances that define possible subunits of the linker C are those listed in Table 19, below; [table included]
- Claim: 6. Compounds according to claim 1, selected from: (2S,11S,19aS)-2-(acetylamino)-15-fluoro-N-[2-(1H-indol-3-yl)ethyl]-7,12-dimethyl-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecine-11-carboxamide, (2S,11S,19aS)—N-[2-(dimethylamino)ethyl]-15-fluoro-2-{[2-(1H-indol-3-yl)acetyl]amino}-7,12-dimethyl-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecine-11-carboxamide; (2 S,11S,19aS)-15-fluoro-2-{[2-(1H-indol-3-yl)acetyl]amino}-N-[2-(1H-indol-3-yl)ethyl]-7,12-dimethyl-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecine-11-carboxamide; (2S,11S,19aS)-2-{[2-(dimethylamino)acetyl]amino}-15-fluoro-N-[2-(1H-indol-3-yl)ethyl]-7,12-dimethyl-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecine-11-carboxamide; tert-butyl N-[(2S,11S,19aS)-15-fluoro-11-({[2-(1H-indol-3-yl)ethyl]amino}carbonyl)-7,12-dimethyl-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecin-2-yl]carbamate; (2S,11S,19aS)—N-[2-(dimethylamino)ethyl]-15-fluoro-7,12-dimethyl-2-{[2-(1-naphthyl)acetyl]amino}-5,8,13-trioxo-2,3,6,7,8,9,10,11,12,13,19,19a-dodecahydro-1H,5H-pyrrolo[2,1-c][1,4,7,12]benzoxatriazacyclopentadecine-11-carboxamide; benzyl N-[(4S,6S,10S)-14-methyl-6-{[2-(2-naphthyl)acetyl]amino}-9,15-dioxo-2-oxa-8,14-diazatricyclo[14.3.1.0˜4,8˜]icosa-1(20),16,18-trien-10-yl]carbamate; benzyl N-[(4S,6S,13S)-6-{[2-(1H-indol-3-yl)acetyl]amino}-11,15-dimethyl-9,12,16-trioxo-2-oxa-8,11,15-triazatricyclo[15.3.1.0˜4,8˜]henicosa-[(21),17,19-trien-13-yl]carbamat; N-[(4S,6S,13S)-6-{[2-(1H-indol-3-yl)acetyl]amino}-11,15-dimethyl-9,12,16-trioxo-2-oxa-8,11,15-triazatricyclo[15.3.1.0˜4,8˜]henicosa-[(21),17,19-trien-13-yl]decanamide.
- Claim: 7. (canceled)
- Claim: 8. A composition having the compound according to any one of claims 1-6 in a therapeutically active amount and having agonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2α receptor (FP receptor).
- Claim: 9. A pharmaceutical composition containing a compound according to any one of claims 1-6 and a therapeutically inert carrier.
- Claim: 10. The composition according to claim 9 having agonistic or antagonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2α receptor (FP receptor).
- Claim: 11. The composition according to claim 9 or 10 in a form suitable for oral, topical, transdermal, injection, buccal, transmucosal, pulmonary or inhalation administration.
- Claim: 12. The composition according to claim 11 in form of tablet, degree, capsule, solution, liquid, gel, plaster, scream, ointment, syrup, slurry, suspension, spray, nebuliser or suppository.
- Claim: 13. A medicament comprising the compound according to claim 1 having agonistic or antagonistic activity on the motilin receptor (MR receptor), on the serotonin receptor of subtype 5-HT2B (5-HT2B receptor), and on the prostaglandin F2α receptor (FP receptor).
- Claim: 14. A method of treating hypomotility disorders of the gastrointestinal tract such as diabetic gastroparesis and constipation type irritable bowl syndrome; for the treatment of CNS related diseases like migraine, schizophrenia, psychosis or depression; for the treatment of ocular hypertension such as associated with glaucoma and preterm labour; said method comprising administering the compound of claim 1 to a patient in need thereof.
- Claim: 15. (canceled)
- Current U.S. Class: 514/250
- Current International Class: 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 07; 61
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