Matrix metalloproteinase inhibitors

    公开(公告)号:US07601729B2

    公开(公告)日:2009-10-13

    申请号:US10571443

    申请日:2004-09-10

    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, corresponding processes for preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs).

    Inhibitors of matrix metalloproteinase

    公开(公告)号:US07375248B2

    公开(公告)日:2008-05-20

    申请号:US10561055

    申请日:2004-06-16

    CPC分类号: C07D213/42 C07C311/08

    摘要: Compounds of formula (I): wherein R1 represents optionally substituted C4-12 alkyl, optionally substituted C2-6alkylaryl, or optionally substituted 5- or 6-membered aryl or heteroaryl; Z represents a bond, CH2, O, S, SO, SO2, NR4, OCR4R5, CR4R5O, or Z, R1 and Q together form an optionally substituted fused tricyclic group; Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents COR3 or N(OR8)COR9; R2 represents SO2R10 or SO2NR10R11; R3 represents OR6, NR6R7 or NR6OH; R4 and R5 each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R6 and R7 each independently represents H, C1-6 alkyl, or C1-6 alkyl substituted with one or more heteroaryl groups, or R6 and R7 together with the nitrogen atom to which they are attached form a 5- or 6-membered ring which may optionally include 1 or more further heteroatoms selected from O, S and N; R8 and R9 each independently represents H or C1-6 alkyl; R10 and R11 each independently represents H or C1-6 alkyl; and and physiologically functional derivatives thereof, with the exception of N-(ethoxycarbonyl)-N-[4-(1H-tetrazol-1-yl)phenyl]glycine, processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metalloproteinase enzymes (MMPs) are described.

    Matrix metalloproteinase inhibitors
    7.
    发明授权
    Matrix metalloproteinase inhibitors 失效
    基质金属蛋白酶抑制剂

    公开(公告)号:US07476759B2

    公开(公告)日:2009-01-13

    申请号:US10569812

    申请日:2004-08-12

    摘要: Compounds of Formula (I): wherein: R1 is optionally substituted —C4-12 alkyl, —C2-10alkylcycloalkyl, —C2-6alkylheterocycloalkyl, —C2-6alkylaryl, optionally substituted 5- or 6-membered aryl or heteroaryl with the proviso that R2 in not pyridinyl; Z is a bond, CH2, O, S, SO, SO2, NR4, OCR4R5 or CR4R5O; or Z, R1 and Q together form an optionally substituted fused tricyclic group; Q is an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X is COR3; R2 is CONH2, CO2H, CO2R7, SO2R7 or SO2NR8R9, with the proviso that R2 is not CO2R7, when X is CONH2; R3 is OR6 or NR8R9; R4 and R5 each independently is H, C1-6 alkyl or C1-4 alkylaryl; R6 is H or C1-6 alkyl; R7 is C1-6 alkyl; and R8 and R9 each independently is H or C1-6 alkyl; or R8 and R9 together with the nitrogen atom to which they are attached form a 5- or 6-membered ring which may optionally include 1 or more further heteroatoms selected from O, S and N; or physiologically functional derivatives thereof, with the proviso that formula (I) compounds are not: [3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid and 3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid diethyl ether; butanedioic acid [3-methoxy-4-(phenylmethoxy)phenyl]; or butanedioic acid [4-(phenylmethoxy)phenyl]; and with the proviso that when R1 is C4-12alkyl, Z is other than a bond, O or CH2; 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.

    摘要翻译: 式(I)的化合物:其中:R 1是任选取代的C 1-4-12烷基,-C 2-10烷基环烷基,-C 2-6烷基杂环烷基,-C 2-6烷基芳基,任选取代的5-或6-元芳基或杂芳基,条件是R 2 非吡啶基; Z是键,CH2,O,S,SO,SO2,NR4,OCR4R5或CR4R5O; 或Z,R 1和Q一起形成任选取代的稠合三环基团; Q是任选取代的5或6元芳基或杂芳基环; X是COR3; R2是CONH2,CO2H,CO2R7,SO2R7或SO2NR8R9,条件是当X是CONH2时,R2不是CO2R7; R3是OR6或NR8R9; R 4和R 5各自独立地为H,C 1-6烷基或C 1-4烷基芳基; R6是H或C1-6烷基; R7是C1-6烷基; 且R 8和R 9各自独立地为H或C 1-6烷基; 或R 8和R 9与它们所连接的氮原子一起形成5-或6-元环,其可任选地包括1个或多个选自O,S和N的其它杂原子; 或其生理功能衍生物,条件是式(I)化合物不是:[3-(乙酰氨基)-4-环己基苯基]丁二酸和3-(乙酰氨基)-4-环己基苯基]丁二酸二乙醚; 丁二酸[3-甲氧基-4-(苯基甲氧基)苯基]; 或丁二酸[4-(苯基甲氧基)苯基]; 并且条件是当R 1为C 4-12烷基时,Z不是键O或CH 2; 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。

    Matrix metalloproteinase inhibitors
    8.
    发明授权
    Matrix metalloproteinase inhibitors 失效
    基质金属蛋白酶抑制剂

    公开(公告)号:US07250439B2

    公开(公告)日:2007-07-31

    申请号:US10559600

    申请日:2004-06-01

    摘要: Compounds of formula (I): wherein: Q represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring; X represents O, S, NR5 or CR6 R7; Y represents CHOH, CHSH, NOR8, CNR8 or CNOR8; Z represents a bond, CR10R11, O, S, SO, SO2, NR10, OCR10R11, CR10R11 O 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 CO2R8, CONR5OR9 or NR5COR9; 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 metalloproteinase enzymes (MMPs) are described.

    摘要翻译: 式(I)的化合物: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,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, 9< 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。