公开(公告)号：EP1353905A2

公开(公告)日：2003-10-22

申请号：EP01989111.8

申请日：2001-11-20

申请人： Scios Inc.

发明人： DUGAR, Sundeep ,  PERUMATTAM, John ,  TESTER, Richland ,  LU, Qing

IPC分类号： C07D211/18 ,  C07D513/04 ,  C07D471/04 ,  C07D207/40 ,  A61K31/445 ,  A61P29/00

CPC分类号： C07D207/416 ,  C07D211/18 ,  C07D401/06 ,  C07D471/04 ,  C07D513/04

摘要： The invention is directed to inhibition of p38-α kinase using compounds of the formula (1) and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein: Ar1 is an aryl group substituted with 0-5 non-interfering substituents, wherein two adjacent noninterfering substituents can form a fused aromatic or nonaromatic ring; L?1 and L2¿ are linkers; each R1 is independently a noninterfering substitutent; Z?1 is CR2¿ or N wherein R2 is hydrogen or a noninterfering substituent; m is 0-4; each of n and p is an integer from 0-2 wherein the some of n and p is 0-3; Ar2 is a substantially planar, monocyclic or polycyclic aromatic moiety having one or more optional ring heteroatoms, said moiety being optionally substituted with one or more optional ring heteroatoms, said moiety being optionally substituted with one or more non-interfering substituents, two or more of which may form a fused ring; Z is W¿1?-COXjY wherein Y is COR?3¿ or an isotere thereof; R3 is a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; wherein the smallest number of covalent bonds is the compound separating the atom of Ar1 bonded to L2 to the atom of Ar2 bonded to L1 is at least 6, where each of said bonds has a bond length of 1.2 to 2.0 angstroms; and/or wherein the distance in space between the atom of Ar1 bonded to L2 and the atom of Ar2 bonded to L1 is 4.5-24 angstroms; with the proviso that the protion of the compound represented by Ar2-Z is not formula (2) wherein formula (3) represents a singel or double bond; n is 0-3; one Z2 is CA or CRA and the other is CR, CR¿2?, NR or N; A is Wi-COXjY wherein Y is COR or an isostere thereof, each of W and X is a spacer of 2-6Å, and each of i and j is independently 0 ot 1; Z?3¿ is NR or O; and each R independently hydrogen or a mominterfering substituent.

公开(公告)号：EP1353905B1

公开(公告)日：2007-01-10

申请号：EP01989111.8

申请日：2001-11-20

申请人： SCIOS INC.

发明人： DUGAR, Sundeep ,  PERUMATTAM, John ,  TESTER, Richland ,  LU, Qing ,  MCENROE, Glenn

IPC分类号： C07D211/18 ,  C07D513/04 ,  C07D471/04 ,  C07D207/40 ,  A61K31/445 ,  A61P29/00

CPC分类号： C07D207/416 ,  C07D211/18 ,  C07D401/06 ,  C07D471/04 ,  C07D513/04

摘要： The invention is directed to inhibition of p38-α kinase using compounds of the formula (1) and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein: Ar1 is an aryl group substituted with 0-5 non-interfering substituents, wherein two adjacent noninterfering substituents can form a fused aromatic or nonaromatic ring; L?1 and L2¿ are linkers; each R1 is independently a noninterfering substitutent; Z?1 is CR2¿ or N wherein R2 is hydrogen or a noninterfering substituent; m is 0-4; each of n and p is an integer from 0-2 wherein the some of n and p is 0-3; Ar2 is a substantially planar, monocyclic or polycyclic aromatic moiety having one or more optional ring heteroatoms, said moiety being optionally substituted with one or more optional ring heteroatoms, said moiety being optionally substituted with one or more non-interfering substituents, two or more of which may form a fused ring; Z is W¿1?-COXjY wherein Y is COR?3¿ or an isotere thereof; R3 is a noninterfering substituent, each of W and X is a spacer of 2-6 Å, and each of i and j is independently 0 or 1; wherein the smallest number of covalent bonds is the compound separating the atom of Ar1 bonded to L2 to the atom of Ar2 bonded to L1 is at least 6, where each of said bonds has a bond length of 1.2 to 2.0 angstroms; and/or wherein the distance in space between the atom of Ar1 bonded to L2 and the atom of Ar2 bonded to L1 is 4.5-24 angstroms; with the proviso that the protion of the compound represented by Ar2-Z is not formula (2) wherein formula (3) represents a singel or double bond; n is 0-3; one Z2 is CA or CRA and the other is CR, CR¿2?, NR or N; A is Wi-COXjY wherein Y is COR or an isostere thereof, each of W and X is a spacer of 2-6Å, and each of i and j is independently 0 ot 1; Z?3¿ is NR or O; and each R independently hydrogen or a mominterfering substituent.

公开(公告)号：EP1339708A2

公开(公告)日：2003-09-03

申请号：EP01986461.0

申请日：2001-11-20

申请人： Scios Inc.

发明人： DUGAR, Sundeep ,  TAN, Xuefei ,  LUEDTKE, Gregory, R. ,  PERUMATTAM, John ,  LU, Qing ,  TESTER, Richland

IPC分类号： C07D403/12 ,  A61K31/404 ,  A61P43/00 ,  C07D487/10 ,  C07D487/04 ,  C07D209/18 ,  C07D401/12

CPC分类号： C07D401/12 ,  C07D209/18 ,  C07D403/12 ,  C07D487/04 ,  C07D487/10

摘要： The invention is directed to inhibition of p38-α kinase using compounds of formula (I) and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein Ar is an aryl group substituted with 0-5 non-interfering substituents, wherein two adjacent noninterfering substituents can form a fused aromatic or nonaromatic ring; L?1 and L2¿ are linkers; X is an aliphatic monocyclic or aliphatic polycyclic moiety optionally comprising one or more hetero ring atoms wherein the cyclic moiety may be optionally substituted with one or more noninterfering substituents and where said optional substituents may constitute a ring fused to X; n is 0-3; each R1 is hydrogen or a noninterfering substituent; (2) represents a single or double bond; one Z2 is CA or CR2A; the other Z?2 is CR3, CR3¿2, NR4 or N; and each R?2, R3 and R4¿ is independently hydrogen or a noninterfering substituent; Z?3 is NR5¿ or O; where R5 is hydrogen or a noninterfering substituent.