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1. 发明授权

EP1663970B1 MATRIX METALLOPROTEINASE INHIBITORS 有权
标题翻译：基质金属蛋白酶
公开(公告)号：EP1663970B1
公开(公告)日：2008-11-05
申请号：EP04765231.8
申请日：2004-09-10
申请人： GLAXO GROUP LIMITED
发明人： GAINES, Simon, GlaxoSmithKline , HOLMES, Ian, Peter, GlaxoSmithKline , MARTIN, Stephen, Lewis, GlaxoSmithKline , WATSON, Stephen, Paul, GlaxoSmithKline
IPC分类号： C07D209/48 , C07D239/54 , C07D405/10 , C07D403/10 , A61K31/505 , A61K31/4035 , A61K31/506 , A61P29/00
CPC分类号： C07D209/48 , C07D239/54 , C07D403/10 , C07D405/10
摘要： Compounds of Formula (I): Wherein: A represents bond, C1-6alkyl or CH=CH-C1-4alkyl; B represents bond, O, S, SO, SO2, CO, CR7R8, CO2R14, CONR14R15, N(COR14)(COR15), N(SO2R14)(COR15) or NR14R15; D represents bond, or C1-6alkyl; E represents substituted aryl or substituted or unsubstituted heteroaryl; Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, SO, SO2, CO, CNR5, CNOR5, CNNR5R6, NR11 or CR7R8; Y represents CR5OR11, CR5SR11, NOR5, CR5NR6R11, SO, SO2, CO, CNR5, CNOR5 or CS; R1 and R1' each independently represents H, C1-6alkyl or C1-4alkylaryl; R2 represents CO2R12, CH2OR12 or CONR12R13, CONR12OR13, NR12COR13, SR12, PO(OH)2, PONHR12 or SONHR12; R3 represents H, C1-6alkyl or C1-4alkylaryl; R4 represents optionally substituted aryl or heteroaryl; Z represents a bond, CH2, O, S, SO, SO2, NR5, OCR5R6, CR9R10O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl; R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl; R9 and R10 each independently represents H, C1-6 alkyl optionally substituted by halo, cyano, OR11 or NR6R11 , C1-4 alkylaryl optionally substituted by halo, cyano, OR11 or NR6R11, OR11 or, together with the N to which they are attached, R9 and R10 form a heterocyclic group: R11 represents H, C1-6 alkyl, C1-4 alkylaryl or COR5; R12 and R13 each independently represent H, C1-3 alkyl, C1-3 alkylaryl or C1-3 alkylheteroaryl or, together with the functionality to which they are attached, R12 and R13 form a heterocyclic group: R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group: and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.

2. 发明公开

EP1654213A1 MATRIX METALLOPROTEINASE INHIBITORS 有权
标题翻译： MATRIX METALLOPROTEASE INHIBITOREN
公开(公告)号：EP1654213A1
公开(公告)日：2006-05-10
申请号：EP04739544.7
申请日：2004-06-01
申请人： GLAXO GROUP LIMITED
发明人： GAINES, Simon, GlaxoSmithKline , HOLMES, Ian, Peter, GlaxoSmithKline , WATSON, Stephen, Paul, GlaxoSmithKline
IPC分类号： C07C59/48 , C07C59/52 , C07C59/56 , C07C59/58 , C07C59/68 , C07C59/86 , C07C233/33 , C07C255/57 , C07C291/14 , C07C321/26 , C07C323/33
CPC分类号： C07D307/91 , C07C17/16 , C07C59/48 , C07C59/54 , C07C59/56 , C07C59/68 , C07C59/90 , C07C205/56 , C07C233/54 , C07C255/57 , C07C323/62 , C07C2603/18 , C07D277/04 , C07C22/04
摘要： Compounds of formula (1): Wherein: Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents 0, S, NR5 or CR6 R7; Y represents CHOH, CHSH, NOR8, CNR8 or CNOR8; Z represents a bond, CR10 R11, 0,S,S0,S02, NR10, OCR10R11, CR10R11O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R1, R1’, R3 and R3 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R2 represents C02 R8, CONR5OR9 or NR5 COR9; R4 represents optionally substituted 5- or 6-membered aryl or heteroaryl; R5 represents H or C1-3 alkyl; R6 and R7 each independently represents H, C1-3 alkyl or halo; R8 represents H or C1-2 alkyl; R9 represents H or C1-3 alkyl; R10 and R11 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metal loproteinase enzymes (MMPs) are described.
摘要翻译：式（I）化合物：其中：Q表示任选取代的5或6元芳基或杂芳基环; X表示O，S，NR 5或CR 6 R 7; Y代表CHOH，CHSH，NOR 8，CNR 8或CNOR 8; Z表示键，CR 10，O，S，SO，SO 2，NR 10， OCR 10，10，11，10，10，10或10，其中R 4，R 4，和Q一起形成任选取代的稠合三环基团; R 1，R 1，R 3，R 3和R 3'各自独立地表示H，C 1， 1-6烷基或C 1-4烷基芳基; R 2表示CO 2 R 8，CONR 5或9或NR 9， SUP> 5 COR ^{9 ; R 4表示任选取代的5或6元芳基或杂芳基; R 5表示H或C 1-3烷基; R 6和R 7各自独立地表示H，C 1-3烷基或卤素; R 8表示H或C 1-12烷基; R 9表示H或C 1-3烷基; R 10和R 11各自独立地表示H，C 1-6烷基或C 1-4烷基芳基; 和其生理功能衍生物，其制备方法，含有它们的药物制剂及其作为基质金属蛋白酶（MMP）抑制剂的用途。}

3. 发明公开

EP1663970A1 MATRIX METALLOPROTEINASE INHIBITORS 有权
标题翻译： MATRIXMETALLOPROTEINASEINHIBITOREN
公开(公告)号：EP1663970A1
公开(公告)日：2006-06-07
申请号：EP04765231.8
申请日：2004-09-10
申请人： GLAXO GROUP LIMITED
发明人： GAINES, Simon, GlaxoSmithKline , HOLMES, Ian, Peter, GlaxoSmithKline , MARTIN, Stephen, Lewis, GlaxoSmithKline , WATSON, Stephen, Paul, GlaxoSmithKline
IPC分类号： C07D209/48 , C07D239/54 , C07D405/10 , C07D403/10 , A61K31/505 , A61K31/4035 , A61K31/506 , A61P29/00
CPC分类号： C07D209/48 , C07D239/54 , C07D403/10 , C07D405/10
摘要： Compounds of Formula (I): Wherein: A represents bond, C1-6alkyl or CH=CH-C1-4alkyl; B represents bond, O, S, SO, SO2, CO, CR7R8, CO2R14, CONR14R15, N(COR14)(COR15), N(SO2R14)(COR15) or NR14R15; D represents bond, or C1-6alkyl; E represents substituted aryl or substituted or unsubstituted heteroaryl; Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, SO, SO2, CO, CNR5, CNOR5, CNNR5R6, NR11 or CR7R8; Y represents CR5OR11, CR5SR11, NOR5, CR5NR6R11, SO, SO2, CO, CNR5, CNOR5 or CS; R1 and R1' each independently represents H, C1-6alkyl or C1-4alkylaryl; R2 represents CO2R12, CH2OR12 or CONR12R13, CONR12OR13, NR12COR13, SR12, PO(OH)2, PONHR12 or SONHR12; R3 represents H, C1-6alkyl or C1-4alkylaryl; R4 represents optionally substituted aryl or heteroaryl; Z represents a bond, CH2, O, S, SO, SO2, NR5, OCR5R6, CR9R10O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R5 and R6 each independently represent H, C1-6 alkyl or C1-4 alkylaryl; R7 and R8 each independently represent H, halo, C1-6 alkyl or C1-4 alkylaryl; R9 and R10 each independently represents H, C1-6 alkyl optionally substituted by halo, cyano, OR11 or NR6R11 , C1-4 alkylaryl optionally substituted by halo, cyano, OR11 or NR6R11, OR11 or, together with the N to which they are attached, R9 and R10 form a heterocyclic group: R11 represents H, C1-6 alkyl, C1-4 alkylaryl or COR5; R12 and R13 each independently represent H, C1-3 alkyl, C1-3 alkylaryl or C1-3 alkylheteroaryl or, together with the functionality to which they are attached, R12 and R13 form a heterocyclic group: R14 and R15 each independently represent H, C1-6 alkyl, C1-4 alkylaryl or C1-4 alkylheteroaryl or together with the functionality to which they are attached R14 and R15 form a heterocyclic or fused heterocyclic group: and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.

4. 发明授权

EP1654213B1 MATRIX METALLOPROTEINASE INHIBITORS 有权
标题翻译：基质金属蛋白酶抑制剂
公开(公告)号：EP1654213B1
公开(公告)日：2007-05-23
申请号：EP04739544.7
申请日：2004-06-01
申请人： GLAXO GROUP LIMITED
发明人： GAINES, Simon, GlaxoSmithKline , HOLMES, Ian, Peter, GlaxoSmithKline , WATSON, Stephen, Paul, GlaxoSmithKline
IPC分类号： C07C59/48 , C07C59/52 , C07C59/56 , C07C59/58 , C07C59/68 , C07C59/86 , C07C233/33 , C07C255/57 , C07C291/14 , C07C321/26 , C07C323/33
CPC分类号： C07D307/91 , C07C17/16 , C07C59/48 , C07C59/54 , C07C59/56 , C07C59/68 , C07C59/90 , C07C205/56 , C07C233/54 , C07C255/57 , C07C323/62 , C07C2603/18 , C07D277/04 , C07C22/04
摘要： Compounds of formula (1): Wherein: Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents 0, S, NR5 or CR6 R7; Y represents CHOH, CHSH, NOR8, CNR8 or CNOR8; Z represents a bond, CR10 R11, 0,S,S0,S02, NR10, OCR10R11, CR10R11O or Z, R4 and Q together form an optionally substituted fused tricyclic group; R1, R1’, R3 and R3 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R2 represents C02 R8, CONR5OR9 or NR5 COR9; R4 represents optionally substituted 5- or 6-membered aryl or heteroaryl; R5 represents H or C1-3 alkyl; R6 and R7 each independently represents H, C1-3 alkyl or halo; R8 represents H or C1-2 alkyl; R9 represents H or C1-3 alkyl; R10 and R11 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; and physiologically functional derivatives thereof, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metal loproteinase enzymes (MMPs) are described.

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