US 2012/0059016 A1Published application

Piperidine and piperazine derivatives as autotaxin inhibitors

AssigneeMerck Patent GmbH

InventorsKai Schiemann, Melanie Schultz, Wolfgang Staehle

Life of this patent

Estimating the term…

Abstract

The present invention relates to piperidine and pyrazine derivatives according to formulae (Ia), (Ib) and (II) as autotaxin inhibitors and the use of such compounds for the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by increased lysophosphatic acid levels and/or the activation of autotaxin, in particular of different cancers.

Claims19

Dependent claims

A compound according to formula (Ia)

wherein:
W1, W2 together independently form “—N═N—, —C(O)—O—, —C(O)—S—, —C(O)—N(R5)-, —C(S)—N(R5a)-, —C(O)—C(R6)(R7)-, —N═C[N(R8)(R9)]-”;
Y1 is independently selected from the group consisting of “—C(O)—, —C(S)—, —S(O)2—, —N(R10)-C(O)—, —C(O)—N(R11)-, —OC(O)—, single bond”;
Y2 is independently selected from the group consisting of “—C(R12)(R13)-, —O—, —N(R14)-, —C(O)—, —C(O)—NH—, single bond”;
Y3 is independently selected from the group consisting of “—O —, —C(O)—, single bond”;
Z1 is independently selected from the group consisting of “O, S, N(R15)”;
L is independently selected from the group consisting of the group consisting of:
B is independently selected from the group consisting of “cycloalkyl, heterocyclyl, aryl, heteroaryl”, wherein “cycloalkyl, heterocyclyl, aryl, heteroaryl” can be independently substituted with one or more identical or different substituents selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —SF3, —N3, —NH2, —NHX1, —NX2X3, —NO2, —OH, ═O, —OCF3, —SCF3, —OCHF2, —SCHF2, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2, —SO3H, —P(O)(OH)2, —C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7X8, —O—X9, —O(—X10-O)a—H (a=1, 2, 3, 4, 5), —O(—X11-O)b—X12 (b=1, 2, 3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15, —O—C(O)—NX16X17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22), —OS(O2)—X23, —NHC(O)—NH2, —NHC(O)—X24, —NX25C(O)—X26, —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29X30, —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36X37, —NHS(O2)—X38, —NX39S(O2)—X40, —S—X41, —S(O)—X42, —S(O2)—X43, —S(O2)NH—X44, —S(O2)NX45X46, —S(O2)O—X47, —P(O)(OX48)(OX49), —Si(X50)(X51)(X52), —C(NH)—NH2, —C(NX53)-NH2, —C(NH)—NHX54, —C(NH)—NX55X56, —C(NX57)-NHX58, —C(NX59)-NX60X61, —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67, —N(—C(O)—NH—O—X68)2, —N(—C(O)—NX69-O—X70)2, —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75, —C(S)—NH—X76, —C(S)—NX77X78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81, —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85, —C(O)—NH—NX86X87, —C(O)—NX88-NX89X90, —C(S)—NH—NH—X91, —C(S)—NH—NX92X93, —C(S)—NX94-NX95X96, —C(O)—C(O)—O—X97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99X100, —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111X112”;
wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48, X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60, X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72, X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84, X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96, X97, X98, X99, X100, X101, X102, X103, X104, X105, X106, X107, X108, X109, X110, X111, X112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively X7, X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78 and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95, X96 and/or X99, X100 and/or X105, X106 and/or X108, X109 and/or X111, X112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
R1, R2, R3, R3a, R3b, R4, R4a, R4b, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 are independently from each other selected from the group consisting of:
“V”;
alternatively, R3a and R4a, R3b and R4b as well as R3 and R4 together can form “cycloalkyl” or “heterocyclyl”;
V is independently selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —SF3, —N3, —NH2, —NHA1, —NA2A3, —NO2, —OH, ═O, —OCF3, —SCF3, —OCHF2, —SCHF2, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2, —SO3H, —P(O)(OH)2, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6, —C(O)NA7A8, —O-A9, —O(-A10-O)a—H (a=1, 2, 3, 4, 5), —O(-A11-O)b-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14, —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19), —OSi(A20)(A21)(A22), —OS(O2)-A23, —NHC(O)—NH2, —NHC(O)-A24, —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30, —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37, —NHS(O2)-A38, —NA39S(O2)-A40, —S-A41, —S(O)-A42, —S(O2)-A43, —S(O2)NH-A44, —S(O2)NA45A46, —S(O2)O-A47, —P(O)(OA48)(OA49), —Si(A50)(A51)(A52), —C(NH)—NH2, —C(NA53)-NH2, —C(NH)—NHA54, —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62, —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)2, —N(—C(O)—NA69-O-A70)2, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73), —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79, —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85, —C(O)—NH-NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91, —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100, —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;
wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A106, A107, A108, A109, A110, A111, A112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36, A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77, A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95, A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or A111, A112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
m is independently 0, 1, 2, or 3;
n is independently 0, 1, 2, or 3;
o is independently 0, 1, 2, or 3;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios;
or
a compound according to formula (Ib)
wherein:
W1, W2 together independently form “—N═N—, —C(O)—O—, —C(O)—S—, —C(O)—N(R5)-, —C(O)—C(R6)(R7)-, —N═C[N(R8)(R9)]-”;
Y1 is independently selected from the group consisting of “—C(O)—, —C(S)—, —N(R10)-C(O)—, —C(O)—N(R11)-, —OC(O)—, single bond”;
Y2 is independently selected from the group consisting of “—C(R12)(R13)-, —O—, —N(R14)-, —C(O)—NH—, single bond”;
Z1 is independently selected from the group consisting of “O, S, N(R15)”;
L is independently selected from the group consisting of the group consisting of:
B is independently selected from the group consisting of “cycloalkyl, heterocyclyl, aryl, heteroaryl”, wherein “cycloalkyl, heterocyclyl, aryl, heteroaryl” can be independently substituted with one or more identical or different substituents selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —N3, —NH2, —NHX1, —NX2X3, —NO2, —OH, —OCF3, —SCF3, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2—SO3H, —P(O)(OH)2, C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7X8, —O—X9, —O(—X10-O)a—H (a=1, 2, 3, 4, 5), —O(—X11-O)b—X12 (b=1, 2, 3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15, —O—C(O)—NX16X17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22), —OS(O2)—X23, —NHC(O)—NH2, —NHC(O)—X24, —NX25C(O)—X26, —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29X30, —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36X37, —NHS(O2)—X38, —NX39S(O2)—X40, —S—X41, —S(O)—X42, —S(O2)—X43, —S(O2)NH—X44, —S(O2)NX45X46, —S(O2)O—X47, —P(O)(OX48)(OX49), —Si(X50)(X51)(X52), —C(NH)—NH2, —C(NX53)-NH2, —C(NH)—NHX54, —C(NH)—NX55X56, —C(NX57)-NHX58, —C(NX59)-NX60X61, —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67, —N(—C(O)—NH—O—X68)2, —N(—C(O)—NX69-O—X70)2, —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75, —C(S)—NH—X76, —C(S)—NX77X78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81, —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85, —C(O)—NH—NX86X87, —C(O)—NX88-NX89X90, —C(S)—NH—NH—X91, —C(S)—NH—NX92X93, —C(S)—NX94-NX95X96, —C(O)—C(O)—O—X97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99X100, —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111X112”;
wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48, X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60, X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72, X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84, X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96, X97, X98, X99, X100, X101, X102, X103, X104, X105, X106, X107, X108, X109, X110, X111, X112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively X7, X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78 and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95, X96 and/or X99, X100 and/or X105, X106 and/or X108, X109 and/or X111, X112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 are independently from each other selected from the group consisting of:
“V”.
V is independently selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —N3—NH2, —NHA1, —NA2A3, —NO2, —OH, —OCF3—SCF3, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2—SO3H, —P(O)(OH)2, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6, —C(O)NA7A8, —O-A9, —O(-A10-O)a—H (a=1, 2, 3, 4, 5), —O(-A11-O)b-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14, —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19), —OSi(A20)(A21)(A22), —OS(O2)-A23, —NHC(O)—NH2, —NHC(O)-A24, —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30, —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37, —NHS(O2)-A38, —NA39S(O2)-A40, —S-A41, —S(O)-A42, —S(O2)-A43, —S(O2)NH-A44, —S(O2)NA45A46, —S(O2)O-A47, —P(O)(OA48)(OA49), —Si(A50)(A51)(A52), —C(NH)—NH2, —C(NA53)-NH2, —C(NH)—NHA54, —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62, —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)2, —N(—C(O)—NA69-O-A70)2, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73), —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79, —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85, —C(O)—NH—NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91, —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100, —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;
wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A106, A107, A108, A109, A110, A111, A112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36, A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77, A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95, A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or A111, A112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
n is independently 0, 1, 2, or 3;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios, or
a compound according to formula (II)
wherein according to formulae (Ia) or (Ib) as claimed in claim 1:
Y2 independently is a single bond;
n independently is 2;
W1, W2, Y1, Y3, L, Z1, B, R1, R2, R3, R4 have the meanings according to formulae (Ia) or (Ib) as claimed in claim 1;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

49 more elements

A compound selected from the group consisting of:

Compound 1
3-(2-Hydroxy-phenyl)-1-[1′-(3′- trifluoromethyl-biphenyl-2-carbonyl)- [4,4′]bipiperidinyl-1-yl]propan-1- one
Compound 2
4-[4-(1H-Benzotriazol-5- ylcarbamoyl)-2-oxo-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 4- chloro-benzyl ester
Compound 3
5-Oxo-1-[1-[3-(4-trifluoromethyl- phenyl)-propionyl]-piperidin-4-yl]- pyrrolidine-3-carboxylic acid (1H- benzotriazol-5-yl)-amide
Compound 4
4-[4-(1H-Benzotriazol-5- ylcarbamoyl)-2-oxo-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 5
4-[5-(2-Oxo-2,3-dihydro- benzooxazol-6-ylcarbamoyl)-pyridin- 3-yl]-piperazine-1-carboxylic acid 4- chloro-benzyl ester
Compound 6
4-[5-(1H-Benzotriazol-5- ylcarbamoyl)-pyridin-3-yl]- piperazine-1-carboxylic acid 4- chloro-benzyl ester
Compound 7
4-{3-[(1H-Benzotriazole-5- carbonyl)-amino]-pyrrolidin-1-yl}- piperidine-1-carboxylic acid 4- chloro-benzyl ester
Compound 8
1H-Benzotriazole-5-carboxylic acid (1-{1-[3-(4-trifluoromethyl-phenyl)- propionyl]-piperidin-4-yl-pyrrolidin- 3-yl)-amide
Compound 9
4-{3-[(1H-Benzotriazole-5- carbonyl)-amino]-pyrrolidin-1-yl}- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 10
4-[3-(1H-Benzotriazol-5- ylcarbamoyl)-phenyl]-piperazine-1- carboxylic acid 4-chloro-benzyl ester
Compound 11
[1′-(1H-Benzotriazole-5-carbonyl)- [4,4′]bipiperidinyl-1-yl]-(4′-methyl- biphenyl-2-yl)-methanone
Compound 12
1′-(1H-Benzotriazole-5-carbonyl)- [4,4′]bipiperidinyl-1-carboxylic acid 3,5-dichloro-benzyl ester
Compound 13
[1′-(1H-Benzotriazole-5-carbonyl)- [4,4′]bipiperidinyl-1-yl]-(4′-methyl- biphenyl-3-yl)-methanone
Compound 15
4-[2-Oxo-4-(2-oxo-2,3-dihydro- benzooxazol-6-ylcarbamoyl)- pyrrolidin-1-yl]-piperidine-1- carboxylic acid 3,5-dichloro-benzyl ester
Compound 16
4-[2-Oxo-4-(2-oxo-2,3-dihydro- benzooxazol-6-ylcarbamoyl)- pyrrolidin-1-yl]-piperidine-1- carboxylic acid 4-chloro-benzyl ester
Compound 17
4-[2-Oxo-4-(2-pyridin-2-yl- ethylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 19
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3,5-dichloro-benzyl ester
Compound 20
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3,5-dichloro-benzyl ester
Compound 21
3-(2-Hydroxy-phenyl)-1-{4-[4-(3′- trifluoromethyl-biphenyl-2-carbonyl)- piperazin-1-yl]-piperidin-1-yl}- propan-1-one
Compound 22
1-[1′-(1H-Benzotriazole-5-carbonyl)- [4,4′]bipiperidinyl-1-yl]-3-(4- trifluoromethyl-phenyl)-propan-1-one
Compound 23
1-[1′-1H-Benzotriazole-5-carbonyl)- [4,4’]bipiperidinyl-1-yl]-2-(4-chloro- phenyl)-ethanone
Compound 24
1-{1-[4-Methyl-2-(4-trifluoromethyl- phenyl)-thiazole-5-carbonyl]- piperidin-4-yl}-5-oxo-pyrrolidine-3- carboxylic acid (1H-benzotriazol-5- yl)-amide
Compound 25
4-[4-(2-Oxo-2,3-dihydro- benzooxazole-6-carbonyl)-piperazin- 1-yl]-piperidine-1-carboxylic acid 3,5-dichloro-benzyl ester
Compound 27
4-[4-(1H-Benzotriazol-5- ylcarbamoyl)-2-oxo-pyrrolidin-1-yl]- piperidine-1-carboxylic acid tetrahydro-furan-2-ylmethyl ester
Compound 28
4-[2-Oxo-4-(2-pyridin-4-yl- ethylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 29
9-(1H-Benzotriazole-5-carbonyl)-3,9- diaza-spiro[5.5]undecane-3- carboxylic acid 3,5-dichloro-benzyl ester
Compound 30
4-[2-Oxo-4-(2-pyridin-3-yl- ethylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 31
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid (3,5-dichioro- phenyl)-amide
Compound 32
1-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl-3-(4-trifluoromethyl-phenyl)- propan-1-one
Compound 33
6-(4-{4-[3-(4-Trifluoromethyl- phenyl)-propionyl]-piperazin-1-yl]- piperidine-1-carbonyl)-3H- benzooxazol-2-one
Compound 34
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-trifluoromethyl- benzyl ester
Compound 35
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3,5-bis- trifluoromethyl-benzyl ester
Compound 36
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-chloro-2-fluoro- benzyl ester
Compound 37
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4- trifluoromethylsulfanyl-benzyl ester
Compound 38
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 5-chloro-2-methoxy- benzyl ester
Compound 39
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 2-chloro-benzyl ester
Compound 40
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-methyl-benzyl ester
Compound 41
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3-chloro-benzyl ester
Compound 42
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-chloro-benzyl ester
Compound 43
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-isopropyl-benzyl ester
Compound 45
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3,4-dichloro-benzyl ester
Compound 46
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 2,4-dichloro-benzyl ester
Compound 47
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-trifluoromethoxy- benzyl ester
Compound 48
(1H-Benzotriazol-5-yl)-(4-{4-[4- methyl-2-(4-trifluoromethyl-phenyl)- thiazole-5-carbonyl]-piperazin-1-yl- piperidin-1-yl)-methanone
Compound 49
6-(4-{1-[3-(4-Trifluoromethyl- phenyl)-propionyl]-piperidin-4-yl- piperazine-1-carbonyl)-3H- benzooxazol-2-one
Compound 50
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-trifluoromethyl-phenyl)- propan-1-one
Compound 51
3-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-ylamino]-pyrrolidine-1- carboxylic acid 3,5-dichloro-benzyl ester
Compound 52
(1H-Benzotriazol-5-yl)-{4-[4-(5- trifluoromethyl-1H-benzoimidazole- 2-carbonyl)-piperazin-1-yl]- piperidin-1-yl-methanone
Compound 53
4-{4-[2-(1H-Imidazol-4-yl)- ethylcarbamoyl]-2-oxo-pyrrolidin-1- yl}-piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 54
4-[2-Oxo-4-(4-[1,2,4]triazol-1-yl- phenylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 55
4-[2-Oxo-4-(4-pyrazol-1-yl- phenylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 56
4-{4-[4-(3-Methyl-5-oxo-4,5- dihydro-pyrazol-1-yl)- phenylcarbamoyl]-2-oxo-pyrrolidin- 1-yl}-piperidine-1-carboxylic acid 3,5-dichloro-benzyl ester
Compound 57
4-[2-Oxo-4-(4-[1,2,3]thiadiazol-4-yl- phenylcarbamoyl)-pyrrolidin-1-yl]- piperidine-1-carboxylic acid 3,5- dichloro-benzyl ester
Compound 58
(E)-3-(3H-Imidazol-4-yl)-1-(4-{1-[3- (4-trifluoromethyl-phenyl)- propionyl]-piperidin-4-yl-piperazin- 1-yl)-propenone
Compound 59
N-[4-(4-{1-[3-(4-Trifluoromethyl- phenyl)-propionyl]-piperidin-4-yl}- piperazine-1-carbonyl)-phenyl]- methanesulfonamide
Compound 60
1-(4-{4-[3-(1H-Imidazol-2-yl)- benzoyl]-piperazin-1-yl-piperidin-1- yl)-3-(4-trifluoromethyl-phenyl)- propan-1-one
Compound 61
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-chloro-2-fluoro-phenyl)- propan-1-one
Compound 62
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4-chloro-2-fluoro- benzyl ester
Compound 63
3-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-ylamino]-pyrrolidine-1- carboxylic acid 4-chloro-2-fluoro- benzyl ester
Compound 64
6-(4-{4-[3-(4-Chloro-2-fluoro- phenyl)-propionyl]-piperazin-1-yl- piperidine-1-carbonyl)-3H- benzooxazol-2-one
Compound 65
4-[1-(2-Oxo-2,3-dihydro- benzooxazole-6-carbonyl)-piperidin- 4-yl]-piperazine-1-carboxylic acid 4- chloro-2-fluoro-benzyl ester
Compound 66
1-{3-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-ylamino]- pyrrolidin-1-yl}-3-(4-chloro-2-fluoro- phenyl)-propan-1-one
Compound 67
1-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl}-3-(4-chloro-2-fluoro-phenyl)- propan-1-one
Compound 68
3-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-ylamino]-pyrrolidine-1- carboxylic acid 4-trifluoromethyl- benzyl ester
Compound 69
1-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl}-3-(3,5-dichloro-phenyl)- propan-1-one
Compound 70
4-[1-(1H-Benzotriazole-5-carbonyl)- pyrrolidin-3-ylamino]-piperidine-1- carboxylic acid 4-trifluoromethyl- benzyl ester
Compound 71
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4-trifluoromethyl- benzyl ester
Compound 72
2-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl-N-(4-chloro-3-trifluoromethyl- phenyl)-2-oxo-acetamide
Compound 73
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 2-fluoro-4- trifluoromethyl-benzyl ester
Compound 74
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 2-fluoro-5- trifluoromethyl-benzyl ester
Compound 75
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3-fluoro-5- trifluoromethyl-benzyl ester
Compound 76
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4-trifluoromethoxy- benzyl ester
Compound 77
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3-chloro-5- trifluoromethyl-benzyl ester
Compound 78
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3-chloro-4-fluoro- benzyl ester
Compound 79
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3,4,5-trifluoro-benzyl ester
Compound 80
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4-bromo-benzyl ester
Compound 81
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-nitro-phenyl)-propan-1- one
Compound 82
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(2,4-dichloro-phenyl)- propan-1-one
Compound 83
(E)-1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-bromo-2-fluoro-phenyl)- propenone
Compound 84
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-isopropyl-phenyl)-propan- 1-one
Compound 85
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3,4-dichloro-benzyl ester
Compound 86
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4- trifluoromethylsulfanyl-benzyl ester
Compound 87
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 4-isopropyl-benzyl ester
Compound 88
1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl}-3-(4-methanesulfonyl-phenyl)- propan-1-one
Compound 89
4-{4-[(S)-2-Amino-3-(1H-imidazol- 4-yl)-propionyl]-piperazin-1-yl- piperidine-1-carboxylic acid 4- trifluoromethyl-benzyl ester
Compound 90
(E)-1-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl-3-(3,5-dichloro-phenyl)- propenone
Compound 91
(1H-Benzotriazol-5-yl)-{4-[1-(3,5- dichloro-4-fluoro-benzoyl)-piperidin- 4-yl]-piperazin-1-yl}-methanone
Compound 92
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3-chloro-4- trifluoromethyl-benzyl ester
Compound 93
4-[4-(1H-Benzotriazole-5-carbonyl)- piperazin-1-yl]-piperidine-1- carboxylic acid 3,5-dichloro-4- fluoro-benzyl ester
Compound 94
4-(3-{4-[4-(1H-Benzotriazole-5- carbonyl)-piperazin-1-yl]-piperidin- 1-yl-3-oxo-propyl)-benzonitrile
Compound 95
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3-chloro-5- trifluoromethyl-benzyl ester
Compound 96
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3-chloro-4- trifluoromethyl-benzyl ester
Compound 97
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3,5-dichloro-4- fluoro-benzyl ester
Compound 98
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3,5-dibromo-4- methyl-benzyl ester
Compound 99
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 5-chloro-2-fluoro-3- trifluoromethyl-benzyl ester
Compound 100
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 4-fluoro-3- trifluoromethyl-benzyl ester
Compound 101
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-piperazine-1- carboxylic acid 3-chloro-4- trifluoromethoxy-benzyl ester
Compound 102
1-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl}-2-(3-fluoro-4-trifluoromethyl- phenyl)-ethanone
Compound 103
1-{4-[1-(1H-Benzotriazole-5- carbonyl)-piperidin-4-yl]-piperazin- 1-yl}-2-(2-fluoro-4-trifluoromethyl- phenyl)-ethanone
Compound 104
Compound 105
Compound 106
Compound 107
Compound 108
Compound 109
Compound 110
Compound 111
Compound 112
Compound 113
Compound 114
Compound 115
Compound 116
Compound 117
Compound 118
Compound 119
Compound 120
Compound 121
Compound 122
Compound 123
Compound 124
Compound 125
Compound 126
Compound 127
Compound 128
Compound 129
Compound 130
Compound 131
Compound 132
Compound 133
Compound 134
Compound 135
Compound 136
Compound 137
Compound 138
Compound 139
Compound 140
Compound 141
Compound 142
Compound 143
Compound 144
Compound 145
Compound 146
Compound 147
Compound 148
Compound 149
Compound 150
Compound 151
Compound 152
Compound 153
Compound 154
Compound 155
Compound 156
Compound 157
Compound 158
Compound 159
Compound 160
Compound 161
Compound 162
Compound 163
Compound 164
Compound 165
Compound 166
Compound 167
Compound 168
Compound 169
Compound 170
Compound 171
Compound 172
Compound 173
Compound 174
Compound 175
Compound 176
Compound 177
Compound 178
Compound 179
Compound 180
Compound 181
Compound 182
Compound 183
Compound 184
4-[1-(1H-Benzotriazole-5-carbonyl)- piperidin-4-yl]-3-oxo-piperazine-1- carboxylic acid 3,5-bis- trifluoromethyl-benzyl ester
Compound 185
4-{4-[(1H-Benzotriazole-5- carbonyl)-amino]-cyclohexyl}- piperazine-1-carboxylic acid benzyl ester
Compound 186
4-{4-[(1H-Benzotriazole-5- carbonyl)-amino]-cyclohexyl}- piperazine-1-carboxylic acid 3,5-bis- trifluoromethyl-benzyl ester
Compound 187
4-{4-[(1H-Benzotriazole-5- carbonyl)-amino]-cyclohexyl}- piperazine-1-carboxylic acid 3- chloro-5-trifluoromethyl-benzyl ester
Compound 188
4-{4-[(1H-Benzotriazole-5- carbonyl)-amino]-cyclohexyl}- piperazine-1-carboxylic acid 4- trifluoromethylsulfanyl-benzyl ester
Compound 189
4-{4-[(1H-Benzotriazole-5- carbonyl)-amino]-cyclohexyl}- piperazine-1-carboxylic acid 3- fluoro-4-trifluoromethyl-benzyl ester.

287 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/258,068Filed 3 Mar 2010
Priority: EP 09 004 856.22 Apr 2009
Published: 8 Mar 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification42 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/496
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: non-condensed piperazines…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system

Family

US 8,822,476 B2Related patent
US 2012/0059016 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound according to formula (Ia)

wherein:
W1, W2 together independently form “—N═N—, —C(O)—O—, —C(O)—S—, —C(O)—N(R5)-, —C(S)—N(R5a)-, —C(O)—C(R6)(R7)-, —N═C[N(R8)(R9)]-”;
Y1 is independently selected from the group consisting of “—C(O)—, —C(S)—, —S(O)2—, —N(R10)-C(O)—, —C(O)—N(R11)-, —OC(O)—, single bond”;
Y2 is independently selected from the group consisting of “—C(R12)(R13)-, —O—, —N(R14)-, —C(O)—, —C(O)—NH—, single bond”;
Y3 is independently selected from the group consisting of “—O —, —C(O)—, single bond”;
Z1 is independently selected from the group consisting of “O, S, N(R15)”;
L is independently selected from the group consisting of the group consisting of:
B is independently selected from the group consisting of “cycloalkyl, heterocyclyl, aryl, heteroaryl”, wherein “cycloalkyl, heterocyclyl, aryl, heteroaryl” can be independently substituted with one or more identical or different substituents selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —SF3, —N3, —NH2, —NHX1, —NX2X3, —NO2, —OH, ═O, —OCF3, —SCF3, —OCHF2, —SCHF2, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2, —SO3H, —P(O)(OH)2, —C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7X8, —O—X9, —O(—X10-O)a—H (a=1, 2, 3, 4, 5), —O(—X11-O)b—X12 (b=1, 2, 3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15, —O—C(O)—NX16X17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22), —OS(O2)—X23, —NHC(O)—NH2, —NHC(O)—X24, —NX25C(O)—X26, —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29X30, —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36X37, —NHS(O2)—X38, —NX39S(O2)—X40, —S—X41, —S(O)—X42, —S(O2)—X43, —S(O2)NH—X44, —S(O2)NX45X46, —S(O2)O—X47, —P(O)(OX48)(OX49), —Si(X50)(X51)(X52), —C(NH)—NH2, —C(NX53)-NH2, —C(NH)—NHX54, —C(NH)—NX55X56, —C(NX57)-NHX58, —C(NX59)-NX60X61, —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67, —N(—C(O)—NH—O—X68)2, —N(—C(O)—NX69-O—X70)2, —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75, —C(S)—NH—X76, —C(S)—NX77X78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81, —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85, —C(O)—NH—NX86X87, —C(O)—NX88-NX89X90, —C(S)—NH—NH—X91, —C(S)—NH—NX92X93, —C(S)—NX94-NX95X96, —C(O)—C(O)—O—X97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99X100, —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111X112”;
wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48, X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60, X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72, X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84, X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96, X97, X98, X99, X100, X101, X102, X103, X104, X105, X106, X107, X108, X109, X110, X111, X112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively X7, X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78 and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95, X96 and/or X99, X100 and/or X105, X106 and/or X108, X109 and/or X111, X112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
R1, R2, R3, R3a, R3b, R4, R4a, R4b, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 are independently from each other selected from the group consisting of:
“V”;
alternatively, R3a and R4a, R3b and R4b as well as R3 and R4 together can form “cycloalkyl” or “heterocyclyl”;
V is independently selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —SF3, —N3, —NH2, —NHA1, —NA2A3, —NO2, —OH, ═O, —OCF3, —SCF3, —OCHF2, —SCHF2, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2, —SO3H, —P(O)(OH)2, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6, —C(O)NA7A8, —O-A9, —O(-A10-O)a—H (a=1, 2, 3, 4, 5), —O(-A11-O)b-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14, —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19), —OSi(A20)(A21)(A22), —OS(O2)-A23, —NHC(O)—NH2, —NHC(O)-A24, —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30, —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37, —NHS(O2)-A38, —NA39S(O2)-A40, —S-A41, —S(O)-A42, —S(O2)-A43, —S(O2)NH-A44, —S(O2)NA45A46, —S(O2)O-A47, —P(O)(OA48)(OA49), —Si(A50)(A51)(A52), —C(NH)—NH2, —C(NA53)-NH2, —C(NH)—NHA54, —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62, —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)2, —N(—C(O)—NA69-O-A70)2, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73), —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79, —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85, —C(O)—NH-NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91, —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100, —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;
wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A106, A107, A108, A109, A110, A111, A112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36, A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77, A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95, A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or A111, A112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
m is independently 0, 1, 2, or 3;
n is independently 0, 1, 2, or 3;
o is independently 0, 1, 2, or 3;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios;
or
a compound according to formula (Ib)
wherein:
W1, W2 together independently form “—N═N—, —C(O)—O—, —C(O)—S—, —C(O)—N(R5)-, —C(O)—C(R6)(R7)-, —N═C[N(R8)(R9)]-”;
Y1 is independently selected from the group consisting of “—C(O)—, —C(S)—, —N(R10)-C(O)—, —C(O)—N(R11)-, —OC(O)—, single bond”;
Y2 is independently selected from the group consisting of “—C(R12)(R13)-, —O—, —N(R14)-, —C(O)—NH—, single bond”;
Z1 is independently selected from the group consisting of “O, S, N(R15)”;
L is independently selected from the group consisting of the group consisting of:
B is independently selected from the group consisting of “cycloalkyl, heterocyclyl, aryl, heteroaryl”, wherein “cycloalkyl, heterocyclyl, aryl, heteroaryl” can be independently substituted with one or more identical or different substituents selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —N3, —NH2, —NHX1, —NX2X3, —NO2, —OH, —OCF3, —SCF3, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2—SO3H, —P(O)(OH)2, C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7X8, —O—X9, —O(—X10-O)a—H (a=1, 2, 3, 4, 5), —O(—X11-O)b—X12 (b=1, 2, 3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15, —O—C(O)—NX16X17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22), —OS(O2)—X23, —NHC(O)—NH2, —NHC(O)—X24, —NX25C(O)—X26, —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29X30, —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36X37, —NHS(O2)—X38, —NX39S(O2)—X40, —S—X41, —S(O)—X42, —S(O2)—X43, —S(O2)NH—X44, —S(O2)NX45X46, —S(O2)O—X47, —P(O)(OX48)(OX49), —Si(X50)(X51)(X52), —C(NH)—NH2, —C(NX53)-NH2, —C(NH)—NHX54, —C(NH)—NX55X56, —C(NX57)-NHX58, —C(NX59)-NX60X61, —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67, —N(—C(O)—NH—O—X68)2, —N(—C(O)—NX69-O—X70)2, —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75, —C(S)—NH—X76, —C(S)—NX77X78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81, —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85, —C(O)—NH—NX86X87, —C(O)—NX88-NX89X90, —C(S)—NH—NH—X91, —C(S)—NH—NX92X93, —C(S)—NX94-NX95X96, —C(O)—C(O)—O—X97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99X100, —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111X112”;
wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36, X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48, X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60, X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72, X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84, X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96, X97, X98, X99, X100, X101, X102, X103, X104, X105, X106, X107, X108, X109, X110, X111, X112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively X7, X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78 and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95, X96 and/or X99, X100 and/or X105, X106 and/or X108, X109 and/or X111, X112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15 are independently from each other selected from the group consisting of:
“V”.
V is independently selected from the group consisting of:
“(i) “hydrogen, alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, —F, —Cl, —Br, —I, —CN, —CF3, —N3—NH2, —NHA1, —NA2A3, —NO2, —OH, —OCF3—SCF3, —SH, —O—SO3H, —OP(O)(OH)2, —CHO, —COOH, —C(O)NH2—SO3H, —P(O)(OH)2, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6, —C(O)NA7A8, —O-A9, —O(-A10-O)a—H (a=1, 2, 3, 4, 5), —O(-A11-O)b-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14, —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19), —OSi(A20)(A21)(A22), —OS(O2)-A23, —NHC(O)—NH2, —NHC(O)-A24, —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30, —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37, —NHS(O2)-A38, —NA39S(O2)-A40, —S-A41, —S(O)-A42, —S(O2)-A43, —S(O2)NH-A44, —S(O2)NA45A46, —S(O2)O-A47, —P(O)(OA48)(OA49), —Si(A50)(A51)(A52), —C(NH)—NH2, —C(NA53)-NH2, —C(NH)—NHA54, —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62, —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)2, —N(—C(O)—NA69-O-A70)2, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73), —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79, —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85, —C(O)—NH—NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91, —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97, —C(O)—C(O)—NH2, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100, —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103, —C(S)—C(O)—NH2, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106, —C(S)—C(S)—NH2, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109, —C(O)—C(S)—NH2, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;
wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13, A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65, A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78, A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91, A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103, A104, A105, A106, A107, A108, A109, A110, A111, A112 are independently from each other selected from the group consisting of:
“alkyl, (C9-C30)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36, A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77, A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95, A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or A111, A112 respectively together can also form “heterocyclyl”;
wherein optionally above substituents of substituents group (i) can in turn independently from each other be substituted with one or more identical or different substituents V;
n is independently 0, 1, 2, or 3;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios, or
a compound according to formula (II)
wherein according to formulae (Ia) or (Ib) as claimed in claim 1:
Y2 independently is a single bond;
n independently is 2;
W1, W2, Y1, Y3, L, Z1, B, R1, R2, R3, R4 have the meanings according to formulae (Ia) or (Ib) as claimed in claim 1;
and the physiologically acceptable salts, derivatives, prodrugs, solvates and stereoisomers thereof, including mixtures thereof in all ratios.

49 more elements

Facts

Application

13/258,068Filed 3 Mar 2010

Priority

EP 09 004 856.22 Apr 2009

Published

8 Mar 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification42 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/496
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: non-condensed piperazines…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system