1. A compound of the following formula, or a pharmaceutically acceptable salt or N oxide thereof:
wherein:
W is CRW, X is CRX, Y is CRY, and Z is CRZ; or
W is N, X is CRX, Y is CRY, and Z is CRZ; or
W is CRW, X is N, Y is CRY, and Z is CRZ; or
W is N, X is CRX, Y is CRY, and Z is N; or
W is CRW, X is N, Y is N, and Z is CRZ; or
W is N, X is CRX, Y is N, and Z is CRZ; or
W is N, X is N, Y is CRY, and Z is CRZ;
wherein:
\u2014RW is independently \u2014H or \u2014RWW;
\u2014RX is independently \u2014H or \u2014RXX;
\u2014RY is independently \u2014H or \u2014RYY; and
\u2014RZ is independently \u2014H or \u2014RZZ;
wherein:
\u2014RWW is independently \u2014X1, \u2014R1, \u2014OH, \u2014CF3, or \u2014OCF3;
\u2014RXX is independently \u2014X1, \u2014R1, \u2014OH, \u2014CF3, or \u2014OCF3;
\u2014RYY is independently \u2014X1, \u2014R1, \u2014OH, \u2014CF3, or \u2014OCF3; and
\u2014RZZ is independently \u2014X1, \u2014R1, \u2014OH, \u2014CF3, or \u2014OCF3;
wherein:
each \u2014X1 is independently \u2014F, \u2014CI, \u2014Br, or \u2014I; and
each \u2014R1 is independently linear or branched saturated C1-4alkyl;
and wherein:
-L3P- is independently a single covalent bond or -L3PL-;
wherein:
-L3PL- is independently -L3PR1-, \u2014C(\u2550O)\u2014, -L3PR2-C(\u2550O)\u2014, \u2014S(\u2550O)2\u2014, -L3PR3-S(\u2550O)2\u2014, or \u2014O-L3PR4-;
wherein:
each -L3PR1- is linear or branched saturated C1-4alkylene;
each -L3PR2- is linear or branched saturated C1-4alkylene;
each -L3PR3- is linear or branched saturated C1-4alkylene;
each -L3PR4- is linear or branched saturated C1-4alkylene;
and wherein:
\u2014R3N is independently \u2014NH2, NHRA, NRARB, or \u2014NRCRD;
wherein:
each \u2014RA is independently:
\u2014RA1, \u2014RA2, \u2014RA3, \u2014RA4, \u2014RA5, -LA-RA2, -LA\u2014RA3, -LA\u2014RA4, or -LA\u2014RA5;
each \u2014RA1 is linear or branched saturated C1-6alkyl,
and is optionally substituted with one or more groups \u2014RS1;
each \u2014RA2 is saturated C3-6cycloalkyl,
and is optionally substituted with one or more groups \u2014RS2C;
each \u2014RA3 is non-aromatic C3-7heterocyclyl,
and is optionally substituted on carbon with one or more groups \u2014RS2C,
and is optionally substituted on secondary nitrogen, if present, with a group \u2014RSN;
each \u2014RA4 is independently phenyl or naphthyl,
and is optionally substituted with one or more groups \u2014RS3C;
each \u2014RA5 is C5-10heteroaryl,
and is optionally substituted on carbon with one or more groups \u2014RS3C,
and is optionally substituted on secondary nitrogen, if present, with a group \u2014RSN;
each -LA- is linear or branched saturated C1-4alkylene;
and wherein:
each \u2014RS1 is independently:
\u2014F, \u2014Cl, \u2014Br, \u2014I,
\u2014OH, \u2014ORTT,
\u2014OCF3,
\u2014NH2, \u2014NHRTT, \u2014NRTT2, \u2014RTM,
\u2014C(\u2550O)OH, \u2014C(\u2550O)ORTT, \u2014OC(\u2550O)RTT,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRTT, \u2014C(\u2550O)NRTT2, \u2014C(\u2550O)RTM,
\u2014NHC(\u2550O)RTT, \u2014NRTNC(\u2550O)RTT,
\u2014NHC(\u2550O)NH2, \u2014NHC(\u2550O)NHRTT, \u2014NHC(\u2550O)NRTT2, \u2014NHC(\u2550O)RTM,
\u2014NRTNC(\u2550O)NH2, \u2014NRTNC(\u2550O)NHRTT, \u2014NRTNC(\u2550O)NRIT2, \u2014NRTNC(\u2550O)RTM,
\u2014NHC(\u2550O)ORTT, \u2014NRTNC(\u2550O)ORTT,
\u2014OC(\u2550O)NH2, \u2014OC(\u2550O)NHRTT, \u2014OC(\u2550O)NRTT2, \u2014OC(\u2550O)RTM,
\u2014C(\u2550O)RTT,
\u2014S(\u2550O)2NH2, \u2014S(\u2550O)2NHRTT, \u2014S(\u2550O)2NRTT2, \u2014S(\u2550O)2RTM,
\u2014NHS(\u2550O)2RTT, \u2014NRTNS(\u2550O)2RTT,
\u2014S(\u2550O)2RTT,
\u2014CN, \u2014NO2, \u2014SRTT, or \u2550O;
each \u2014RS2C is independently:
\u2014RTT,
\u2014F, \u2014Cl, \u2014Br, \u2014I,
\u2014OH, \u2014ORTT,
-LT-OH, -LT-ORTT,
\u2014CF3, \u2014OCF3,
\u2014NH2, \u2014NHRTT, \u2014NRTT2, \u2014RTM,
-LT-NH2, -LT-NHRTT, -LT-NRTT2, -LT-RTM,
\u2014C(\u2550O)OH, \u2014C(\u2550O)ORTT, \u2014OC(\u2550O)RTT,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRTT, \u2014C(\u2550O)NRTT2, \u2014C(\u2550O)RTM,
\u2014NHC(\u2550O)RTT, \u2014NRTNC(\u2550O)RTT,
\u2014NHC(\u2550O)NH2, \u2014NHC(\u2550O)NHRTT, \u2014NHC(\u2550O)NRTT2, \u2014NHC(\u2550O)RTM,
\u2014NRTNC(\u2550O)NH2, \u2014NRTNC(\u2550O)NHRTT, \u2014NRTNC(\u2550O)NRIT2, \u2014NRTNC(\u2550O)RTM,
\u2014NHC(\u2550O)ORTT, \u2014NRTNC(\u2550O)ORTT,
\u2014OC(\u2550O)NH2, \u2014OC(\u2550O)NHRTT, \u2014OC(\u2550O)NRTT2, \u2014OC(\u2550O)RTM,
\u2014C(\u2550O)RTT,
\u2014S(\u2550O)2NH2, \u2014S(\u2550O)2NHRTT, \u2014S(\u2550O)2NRTT2, \u2014S(\u2550O)2RTM,
\u2014NHS(\u2550O)2RTT, \u2014NRTNS(\u2550O)2RTT,
\u2014S(\u2550O)2RTT,
\u2014CN, \u2014NO2, \u2014SRTT, or \u2550O;
each \u2014RS3C is independently:
\u2014RTT,
\u2014F, \u2014Cl, \u2014Br, \u2014I,
\u2014OH, \u2014ORTT,
-LT-OH, -LT-ORTT,
\u2014CF3, \u2014OCF3,
\u2014NH2, \u2014NHRTT, \u2014NRTT2, \u2014RTM,
-LT-NH2, -LT-NHRTT, -LT-NRTT2, -LT-RTM,
\u2014C(\u2550O)OH, \u2014C(\u2550O)ORTT, \u2014OC(\u2550O)RTT,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRTT, \u2014C(\u2550O)NRTT2, \u2014C(\u2550O)RTM,
\u2014NHC(\u2550O)RTT, \u2014NRTNC(\u2550O)RTT,
\u2014NHC(\u2550O)NH2, \u2014NHC(\u2550O)NHRTT, \u2014NHC(\u2550O)NRTT2, \u2014NHC(\u2550O)RTM,
\u2014NRTNC(\u2550O)NH2, \u2014NRTNC(\u2550O)NHRTT, \u2014NRTNC(\u2550O)NRIT2, \u2014NRTNC(\u2550O)RTM,
\u2014NHC(\u2550O)ORTT, \u2014NRTNC(\u2550O)ORTT,
\u2014OC(\u2550O)NH2, \u2014OC(\u2550O)NHRTT, \u2014OC(\u2550O)NRTT2, \u2014OC(\u2550O)RTM,
\u2014C(\u2550O)RTT,
\u2014S(\u2550O)2NH2, \u2014S(\u2550O)2NHRTT, \u2014S(\u2550O)2NRTT2, \u2014S(\u2550O)2RTM,
\u2014NHS(\u2550O)2RTT, \u2014NRTNS(\u2550O)2RTT,
\u2014S(\u2550O)2RTT,
\u2014CN, \u2014NO2, or \u2014SRTT;
and additionally, two adjacent groups \u2014RS3C, if present, may together form:
\u2014O\u2014CH2\u2014O\u2014 or \u2014O\u2014CH2CH2\u2014O\u2014;
each \u2014RSN is independently:
\u2014RTT,
-LT-OH, -LT-ORTT,
-LT-NH2, -LT-NHRTT, -LT-NRTT2, -LT-RTM,
\u2014C(\u2550O)RTT,
\u2014C(\u2550O)ORTT,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRTT, \u2014C(\u2550O)NRTT2, \u2014C(\u2550O)RTM, or
\u2014S(\u2550O)2RTT;
wherein:
each -LT- is linear or branched saturated C1-4alkylene;
each \u2014RTT is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl, or benzyl; wherein said linear or branched saturated C1-4alkyl is optionally substituted with \u2014OH or \u2014ORTTT, wherein \u2014RTTT is linear or branched saturated C1-4alkyl;
each \u2014RTN is linear or branched saturated C1-4alkyl;
each \u2014RTM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
optionally substituted on carbon with one or more groups selected from: \u2014RTMM, \u2014C(\u2550O)RTMM, \u2014S(\u2550O)2RTMM, \u2014F, \u2014NH2, \u2014NHRTMM, \u2014NRTMM2, \u2014OH, and \u2014ORTMM; and
optionally substituted on secondary nitrogen, if present, with a group selected from: \u2014RTMM, \u2014C(\u2550O)RTMM, \u2014C(\u2550O)ORTMM, and \u2014S(\u2550O)2RTMM;
wherein each \u2014RTMM is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl, or benzyl;
and wherein:
\u2014RB is independently \u2014RB1, \u2014RB2, or -LB-RB2;
\u2014RB1 is linear or branched saturated C1-6alkyl, and is optionally substituted with \u2014OH or \u2014ORBB,
wherein \u2014RBB is linear or branched saturated C1-4alkyl;
\u2014RB2 is saturated C3-6cycloalkyl; and
-LB- is linear or branched saturated C1-4alkylene;
and wherein:
\u2014NRCRD is independently \u2014NRC1RD1, \u2014NRC2RD2, \u2014NRC3RD3, \u2014NRC4RD4, or \u2014NRC5RD5;
wherein:
\u2014NRC1RD1 is a monocyclic non-aromatic heterocyclyl group having from 4 to 8 ring atoms, wherein exactly 1 of said ring atoms is a ring heteroatom, and is N, or exactly 2 of said ring atoms are ring heteroatoms, and are both N, or exactly 2 of said ring atoms are ring heteroatoms, and are N and O, or exactly 2 of said ring atoms are ring heteroatoms, and are N and S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2;
and wherein said monocyclic non-aromatic heterocyclyl group is:
optionally substituted on carbon with one or more groups \u2014RNC, and
optionally substituted on secondary nitrogen, if present, with a group \u2014RNN;
\u2014NRC2RD2 is a fused bicyclic non-aromatic heterocyclyl group having from 7 to 12 ring atoms, wherein exactly 1 of said ring atoms is a ring heteroatom, and is N, or exactly 2 of said ring atoms are ring heteroatoms, and are both N, or exactly 2 of said ring atoms are ring heteroatoms, and are N and O, or exactly 2 of said ring atoms are ring heteroatoms, and are N and S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2, or exactly 3 of said ring atoms are ring heteroatoms, one of which is N, and each of the other two is independently N, O, or S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2;
and wherein said fused bicyclic non-aromatic heterocyclyl group is:
optionally substituted on carbon with one or more groups \u2014RNC, and
optionally substituted on secondary nitrogen, if present, with a group \u2014RNN;
\u2014NRC3RD3 is a bridged non-aromatic heterocyclyl group having from 7 to 11 ring atoms, wherein exactly 1 of said ring atoms is a ring heteroatom, and is N, or exactly 2 of said ring atoms are ring heteroatoms, and are both N, or exactly 2 of said ring atoms are ring heteroatoms, and are N and O, or exactly 2 of said ring atoms are ring heteroatoms, and are N and S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2, or exactly 3 of said ring atoms are ring heteroatoms, one of which is N, and each of the other two is independently N, O, or S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2;
and wherein said bridged non-aromatic heterocyclyl group is:
optionally substituted on carbon with one or more groups \u2014RNC, and
optionally substituted on secondary nitrogen, if present, with a group \u2014RNN;
\u2014NRC4RD4 is a spiro non-aromatic heterocyclyl group having from 6 to 12 ring atoms, wherein exactly 1 of said ring atoms is a ring heteroatom, and is N, or exactly 2 of said ring atoms are ring heteroatoms, and are both N, or exactly 2 of said ring atoms are ring heteroatoms, and are N and O, or exactly 2 of said ring atoms are ring heteroatoms, and are N and S, or exactly 3 of said ring atoms are ring heteroatoms, one of which is N, and each of the other two is independently N, O, or S, wherein said S is optionally in the form of S(\u2550O) or S(\u2550O)2;
and wherein said spiro non-aromatic heterocyclyl group is:
optionally substituted on carbon with one or more groups \u2014RNC, and
optionally substituted on secondary nitrogen, if present, with a group \u2014RNN;
wherein:
each \u2014RNC is independently:
\u2014RQQ,
\u2014F, \u2014Cl, \u2014Br, \u2014I,
\u2014OH, \u2014ORQQ,
-LQ-OH, -LQ-ORQQ,
\u2014CF3, \u2014OCF3,
\u2014NH2, \u2014NHRQQ, \u2014NRQQ2, \u2014RQM,
-LQ-NH2, -LQ-NHRQQ, -LQQ-NRQQ2, -LQ-RQM,
\u2014C(\u2550O)OH, \u2014C(\u2550O)ORQQ, \u2014OC(\u2550O)RQQ,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRQQ, \u2014C(\u2550O)NRQQ2, \u2014C(\u2550O)RQM,
\u2014NHC(\u2550O)RQQ, \u2014NRQNC(\u2550O)RQQ,
\u2014NHC(\u2550O)NH2, \u2014NHC(\u2550O)NHRQQ, \u2014NHC(\u2550O)NRQQ2, \u2014NHC(\u2550O)RQM,
\u2014NRQNC(\u2550O)NH2, \u2014NRQNC(\u2550O)NHRQQ,
\u2014NRQNC(\u2550O)NRQQ2, \u2014NRQNC(\u2550O)RQM,
\u2014NHC(\u2550O)ORQQ, \u2014NRQNC(\u2550O)ORQQ,
\u2014OC(\u2550O)NH2, \u2014OC(\u2550O)NHRQQ, \u2014OC(\u2550O)NRQQ2, \u2014OC(\u2550O)RQM,
\u2014C(\u2550O)RQQ,
\u2014S(\u2550O)2NH2, \u2014S(\u2550O)2NHRQQ, \u2014S(\u2550O)2NRQQ2, \u2014S(\u2550O)2RQM,
\u2014NHS(\u2550O)2RQQ, \u2014NRQNS(\u2550O)2RQQ,
\u2014S(\u2550O)2RQQ,
\u2014CN, \u2014NO2, \u2014SRQQ, or \u2550O;
each \u2014RNN is independently:
\u2014RQQ,
-LQ-OH, -LQ-ORQQ,
-LQ-NH2, -LQ-NHRQQ, -LQ-NRQQ2, -LQ-RQM,
\u2014C(\u2550O)RQQ,
\u2014C(\u2550O)ORQQ,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRQQ, \u2014C(\u2550O)NRQQ2, \u2014C(\u2550O)RQM, or
\u2014S(\u2550O)2RQQ;
wherein:
each -LQ- is linear or branched saturated C1-4alkylene;
each \u2014RQQ is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl or benzyl; wherein said linear or branched saturated C1-4alkyl is optionally substituted with \u2014OH or \u2014ORQQQ, and said phenyl and benzyl are optionally substituted with \u2014RQQQ, wherein each \u2014RQQQ is linear or branched saturated C1-4alkyl;
each \u2014RQN is linear or branched saturated C1-4alkyl;
each \u2014RQM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
optionally substituted on carbon with one or more groups selected from: \u2014RQMM, \u2014C(\u2550O)RQMM, \u2014S(\u2550O)2RQMM, \u2014F, \u2014NH2, \u2014NHRQMM, \u2014NRQMM2, \u2014OH, and \u2014ORQMM; and
optionally substituted on secondary nitrogen, if present, with a group selected from: \u2014RQMM, \u2014C(\u2550O)RQMM, \u2014C(\u2550O)ORQMM, and \u2014S(\u2550O)2RQMM;
wherein each \u2014RQMM is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl, or benzyl;
and wherein:
\u2014NRC5RD5 is independently: 1H-pyrrol-1-yl; 2H-isoindol-2-yl; 1H-indol-1-yl; 1H-pyrazol-1-yl; 1H-benzoimidazol-1-yl; 1H-imidazol-1-yl; 2H-indazol-2-yl; 1H-indazol-1-yl; 4H-1,2,4triazol-4-yl; 1H-1,2,3triazol-1-yl; 1H-1,2,4triazol-1-yl; 1H-benzotriazol-1-yl; or 1H-tetrazol-1-yl; and is optionally substituted with one or more groups \u2014RH;
wherein each \u2014RH is independently:
\u2014RHH,
\u2014F, \u2014Cl, \u2014Br, \u2014I,
\u2014OH, \u2014ORHH,
-LH-OH, -LH-ORHH,
\u2014CF3, \u2014OCF3,
\u2014NH2, \u2014NHRHH, \u2014NRHH2, \u2014RHM,
-LH-NH2, -LH-NHRHH, -LH-NRHH2, -LH-RHM,
\u2014C(\u2550O)OH, \u2014C(\u2550O)ORHH, \u2014OC(\u2550O)RHH,
\u2014C(\u2550O)NH2, \u2014C(\u2550O)NHRHH, \u2014C(\u2550O)NRHH2, \u2014C(\u2550O)RHM,
\u2014NHC(\u2550O)RHH, \u2014NRHHC(\u2550O)RHH,
\u2014NHC(\u2550O)NH2, \u2014NHC(\u2550O)NHRHH, \u2014NHC(\u2550O)NRHH2, \u2014NHC(\u2550O)RHM,
\u2014NRHNC(\u2550O)NH2, \u2014NRHNC(\u2550O)NHRHH, \u2014NRHNC(\u2550O)NRHH2, \u2014NRHNC(\u2550O)RHM,
\u2014NHC(\u2550O)ORHH, \u2014NRHNC(\u2550O)ORHH,
\u2014OC(\u2550O)NH2, \u2014OC(\u2550O)NHRHH, \u2014OC(\u2550O)NRHH2, \u2014OC(\u2550O)RHM,
\u2014C(\u2550O)RHH,
\u2014S(\u2550O)2NH2, \u2014S(\u2550O)2NHRHH, \u2014S(\u2550O)2NRHH2, \u2014S(\u2550O)2RHM,
\u2014NHS(\u2550O)2RHH, \u2014NRHNS(\u2550O)2RHH,
\u2014S(\u2550O)2RHH,
\u2014CN, \u2014NO2, or \u2014SRHH;
wherein:
each -LH- is linear or branched saturated C1-4alkylene;
each \u2014RHH is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl, or benzyl; wherein said linear or branched saturated C1-4alkyl is optionally substituted with \u2014OH or \u2014ORHHH, wherein \u2014RHHH is linear or branched saturated C1-4alkyl;
each \u2014RHN is linear or branched saturated C1-4alkyl;
each \u2014RHM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
optionally substituted on carbon with one or more groups selected from: \u2014RHMM, \u2014C(\u2550O)RHMM, \u2014S(\u2550O)2RHMM, \u2014F, \u2014NH2, \u2014NHRHMM, \u2014NRHMM2, \u2014OH, and \u2014ORHMM; and
optionally substituted on secondary nitrogen, if present, with a group selected from: \u2014RHMM, \u2014C(\u2550O)RHMM, \u2014C(\u2550O)ORHMM, and \u2014S(\u2550O)2RHMM;
wherein each \u2014RHMM is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, saturated C3-6cycloalkyl-methyl, phenyl, or benzyl;
and wherein:
\u2014R5 is independently \u2014R5A, \u2014R5B, \u2014R5C, \u2014R5D, or \u2014R5E;
\u2014R5A is linear or branched saturated C1-4alkyl;
\u2014R5B is saturated C3-6cycloalkyl;
\u2014R5C is independently \u2014F, \u2014CI, \u2014Br, or \u2014I;
\u2014R5D is \u2014CF3; and
\u2014R5E is independently \u2014C\u2261CH or C3-6alkynyl optionally substituted with one or more groups \u2014REE; wherein each \u2014REE is independently selected from \u2014OH, \u2014OREEE, \u2014NH2, \u2014NHREEE, and \u2014NREEE2;
wherein each \u2014REEE is linear or branched saturated C1-4alkyl;
and wherein:
\u2014R4 is \u2014H;
\u2014R6 is independently \u2014H or \u2014F; and
\u2014R7 is independently \u2014H or \u2014F; and
\u2014R8 is independently \u2014H or \u2014F.
2. A compound according to claim 1, wherein:
W is CRW, X is CRX, Y is CRY, and Z is CRZ.
3. A compound according to claim 1, wherein:
W is CRW, X is N, Y is CRY, and Z is CRZ.
4. A compound according to claim 1, wherein:
\u2014RW, if present, is \u2014H;
\u2014RX, if present, is \u2014H;
\u2014RY, if present, is \u2014H; and
\u2014RZ, if present, is \u2014H.
5. A compound according to claim 1, wherein -L3P- is a single covalent bond.
6. A compound according to claim 1, wherein -L3P- is -L3PL-.
7. A compound according to claim 1, wherein -L3PL-, if present, is -L3PR1-.
8. A compound according to claim 1, wherein -L3PL-, if present, is \u2014C(\u2550O)\u2014.
9. A compound according to claim 1, wherein -L3PL-, if present, is -L3PR2-C(\u2550O)\u2014.
10. A compound according to claim 1, wherein:
each -L3PR1-, if present, is independently \u2014CH2\u2014, \u2014CH(Me)-, or \u2014C(Me)2-; and
each -L3PR2-, if present, is independently \u2014CH2\u2014, \u2014CH(Me)-, or \u2014C(Me)2-.
11. A compound according to claim 1, wherein \u2014R3N is \u2014NRARB.
12. A compound according to claim 1, wherein \u2014R3N is \u2014NRCRD.
13. A compound according to claim 1, wherein each \u2014RA, if present, is independently: \u2014RA1, \u2014RA3, or -LA-RA3.
14. A compound according to claim 1, wherein:
each \u2014RA1, if present, is independently linear or branched saturated C1-4alkyl, and is optionally substituted with one or more groups \u2014RS1; and
each \u2014RA3, if present, is piperidinyl,
and is optionally substituted on carbon with one or more groups \u2014RS2C,
and is optionally substituted on secondary nitrogen with a group \u2014RSN.
15. A compound according to claim 1, wherein each \u2014RSN, if present, is independently:
\u2014RTT,
\u2014C(\u2550O)RTT, or
\u2014C(\u2550O)ORTT.
16. A compound according to claim 1, wherein each \u2014RTT, if present, is -Me.
17. A compound according to claim 1, wherein \u2014NRCRD, if present, is \u2014NRC1RD1, wherein, \u2014NRC1RD1 is independently selected from the following groups, and is:
optionally substituted on carbon with one or more groups \u2014RNC, and
optionally substituted on secondary nitrogen, if present, with a group \u2014RNN:
18. A compound according to claim 1, wherein:
each \u2014RNC, if present, is independently:
\u2014RQQ,
\u2014OH, \u2014ORQQ,
\u2014NH2, \u2014NHRQQ, \u2014NRQQ2, \u2014RQM, or
\u2550O;
each \u2014RNN, if present, is independently:
\u2014RQQ,
-LQ-OH, -LQ-ORQQ,
-LQNH2, -LQ-NHRQQ, -LQ-NRQQ2, -LQ-RQM,
\u2014C(\u2550O)RQQ, or
\u2014C(\u2550O)ORQQ; and
each \u2014RQQ is independently linear or branched saturated C1-4alkyl, saturated C3-6cycloalkyl, or saturated C3-6cycloalkyl-methyl.
19. A compound according to claim 1, wherein each \u2014RQQ, if present, is -Me.
20. A compound according to claim 1, wherein \u2014NRCRD, if present, is \u2014NRC5RD5, wherein \u2014NRC5RD5 is: 1H-pyrazol-1-yl; and is optionally substituted with one or more groups \u2014RH.
21. A compound according to claim 1, wherein \u2014NRCRD, if present, is \u2014NRC5RD5, wherein \u2014NRC5RD5 is: 1H-imidazol-1-yl; and is optionally substituted with one or more groups \u2014RH.
22. A compound according to claim 1, wherein each \u2014RH, if present, is independently \u2014RHH.
23. A compound according to claim 1, wherein \u2014R5 is \u2014R5A, wherein \u2014R5A is -Me.
24. A compound according to claim 1, wherein \u2014R5 is \u2014R5C, wherein \u2014R5C is \u2014Cl.
25. A compound according to claim 1, wherein \u2014R6 is \u2014H.
26. A compound according to claim 1, selected from IQ-001 through IQ-238 or a pharmaceutically acceptable salt or a N-oxide thereof.
27. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier or diluent.
28. A method of preparing a pharmaceutical composition comprising the step of mixing a compound according to claim 1, and a pharmaceutically acceptable carrier or diluent.
29. A method of inhibiting PARP function, TNKS1 andor TNKS2 function, or Wnt signalling in a cell, in vitro or in vivo, comprising contacting the cell with an effective amount of a compound according to claim 1.
30. A method of treatment of colorectal cancer, comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound according to claim 1.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A saddle-straddling type motor vehicle, comprising:
an air-cooled engine attached to a body frame and having a cylinder block located on a rear side in a direction in which said motor vehicle runs and a cylinder head located on a front side in the direction in which said motor vehicle runs;
a primary passage that guides air into a combustion chamber of said air-cooled engine;
a fuel injection device having an injection nozzle that injects fuel in said primary passage; and
a secondary passage that branches off from upstream of said primary passage and that guides air to a vicinity of said injection nozzle of said fuel injection device at least when said air-cooled engine is idling,
said fuel injection device being located further forward than said cylinder block in the direction in which said motor vehicle runs.
2. The saddle-straddling type motor vehicle according to claim 1, wherein said air-cooled engine further comprises an intake valve located at a border between said primary passage and said combustion chamber, and
said fuel injection device is situated at an incline between said primary passage and said intake valve.
3. The saddle-straddling type motor vehicle according to claim 1, wherein said body frame includes:
a head pipe disposed approximately uprightly in a front part of said motor vehicle; and
a main frame extending rearward and obliquely downward from said head pipe.
4. A saddle-straddling type motor vehicle, comprising:
a body frame situated from a front part to a rear part of said motor vehicle; and
an air-cooled engine attached to said body frame,
said body frame including
a head pipe disposed approximately uprightly in the front part of said motor vehicle; and
a main frame extending rearward and obliquely downward from said head pipe, and
said air-cooled engine including
a cylinder block forming a cylinder that reciprocatably accommodates a piston;
a cylinder head forming a combustion chamber together with said cylinder block and having a primary passage communicating with said combustion chamber through an intake valve opening;
an intake valve provided to open and close said intake valve opening;
a fuel injection device having an injection nozzle that injects fuel; and
a secondary passage that branches off from upstream of said primary passage and that guides air to a vicinity of said injection nozzle of said fuel injection device at least when said air-cooled engine is idling;
said cylinder head being located in a front part under said main frame and said cylinder block being located in a rear part under said main frame such that a center axis of said cylinder extends approximately horizontally in a front-to-rear direction of said motor vehicle and so that said cylinder head is hit by a wind when said motor vehicle runs, and
said fuel injection device being provided in said cylinder head so that said fuel injection device injects the fuel toward said intake valve opening from an injection passage in a side wall of said primary passage.
5. The saddle-straddling type motor vehicle according to claim 4, wherein said primary passage extends approximately uprightly from said intake valve opening, said intake valve is located so that its axis extends approximately in the front-to-rear direction, and said fuel injection device is located at an incline between said primary passage and said intake valve.
6. The saddle-straddling type motor vehicle according to claim 4, wherein said primary passage extends approximately uprightly from said intake valve opening, said intake valve is located so that its axis extends approximately in the front-to-rear direction, and said fuel injection device is located at an incline on a side of said primary passage.
7. The saddle-straddling type motor vehicle according to claim 4, wherein said air-cooled engine further comprises:
a throttle body extending upward from said primary passage; and
a first openingclosing mechanism capable of opening and closing in said throttle body,
and wherein said secondary passage branches off from a part of said throttle body that is upstream of said first openingclosing mechanism.
8. The saddle-straddling type motor vehicle according to claim 7, wherein said engine further comprises a second openingclosing mechanism capable of opening and closing and located, in said throttle body, upstream of the part from which said secondary passage branches off.
9. The saddle-straddling type motor vehicle according to claim 8, wherein, when no load is placed on said engine and when a load equal to or smaller than a first value is placed on said engine, said first openingclosing mechanism is approximately full closed and an open degree of said second openingclosing mechanism is controlled by an operation by a rider.
10. The saddle-straddling type motor vehicle according to claim 9, wherein, when a load larger than said first value is placed on said engine, an open degree of said first openingclosing mechanism is controlled by an operation by the rider, and the open degree of said second openingclosing mechanism is controlled in association with said first openingclosing mechanism.
11. The saddle-straddling type motor vehicle according to claim 10, wherein, when the load placed on said engine is equal to or smaller than a second value that is larger than said first value, an air flow rate in said secondary passage increases as the load placed on said engine increases, and when the load placed on said engine exceeds said second value, the air flow rate in said secondary passage decreases.
12. The saddle-straddling type motor vehicle according to claim 11, wherein, while the load placed on said engine is larger than said second value, the air flow rate in said secondary passage remains approximately constant.
13. The saddle-straddling type motor vehicle according to claim 12, wherein, when the load placed on said engine is larger than said first value, an air flow rate in said primary passage increases as the load placed on said engine increases.
14. The saddle-straddling type motor vehicle according to claim 4, wherein a distance from a tip of said injection nozzle of said fuel injection device to said intake valve opening is 4 cm or less.
15. The saddle-straddling type motor vehicle according to claim 4, wherein said fuel injection device is situated so that at least part of said fuel injection device is exposed outside from said cylinder head.
16. The saddle-straddling type motor vehicle according to claim 4, wherein said fuel injection device is situated to incline obliquely upward toward a front with respect to a horizontal direction.
17. The saddle-straddling type motor vehicle according to claim 4, wherein said intake valve is located so that its axis is inclined obliquely upward toward a front at an angle larger than 0 degree and smaller than 45 degrees with respect to a horizontal direction.
18. The saddle-straddling type motor vehicle according to claim 17, wherein said cylinder head has an exhaust passage that guides burned gas outside from said combustion chamber through an exhaust valve opening,
said engine further comprises an exhaust valve provided to open and close said exhaust valve opening, and
said exhaust valve is situated so that its axis is inclined obliquely downward toward the front at an angle larger than 0 degree and smaller than 45 degrees with respect to the horizontal direction.