Arylidene-heterocyclic derivatives and process for their preparation
    1.
    发明授权
    Arylidene-heterocyclic derivatives and process for their preparation 失效
    亚芳基杂环衍生物及其制备方法

    公开(公告)号:US5587385A

    公开(公告)日:1996-12-24

    申请号:US452288

    申请日:1995-05-26

    摘要: The invention relates to compounds of formula ##STR1## wherein Ar is mono- or bicyclic ring system chosen from benzene, naphthalene, tetrahydronaphthalene, quinoline and indole;Het is ##STR2## R is hydrogen, halogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 acyloxy, cyano, nitro, amino or --COOR.sub.3 in which R.sub.3 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.1 is hydrogen, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 acyloxy, cyano, nitro, amino or --COOR.sub.3 in which R.sub.3 is as defined above;R.sub.2 is hydrogen, halogen, hydroxy or C.sub.1 -C.sub.6 alkyl; and the pharmaceutically acceptable salts thereof, and wherein when at the same time the (Ar) R.sub.1 R.sub.2 group represents unsubstituted phenyl or 4-chloro-, 4-cyano-, 4-amino- or 3,4-dimethoxy-phenyl and Het is a 4-homophthalimide group, then R is other than hydrogen, which are useful as anti-proliferative agents.

    摘要翻译: 本发明涉及式(I)的化合物,其中Ar是选自苯,萘,四氢萘,喹啉和吲哚的单环或双环体系; Het是R 3是氢或C 1 -C 6烷基的氢,卤素,羟基,C 1 -C 6烷氧基,C 2 -C 6酰氧基,氰基,硝基,氨基或-COOR 3; R 1是氢,羟基,C 1 -C 6烷基,C 1 -C 6烷氧基,C 2 -C 6酰氧基,氰基,硝基,氨基或-COOR 3,其中R 3如上所定义; R2是氢,卤素,羟基或C1-C6烷基; 并且其中当同时(Ar)R 1 R 2基团表示未取代的苯基或4-氯 - ,4-氰基 - ,4-氨基 - 或3,4-二甲氧基 - 苯基且Het为 4-高邻苯二甲酰亚胺基,则R不是氢,其可用作抗增殖剂。

    3-aryl-glycidic ester derivatives
    2.
    发明授权
    3-aryl-glycidic ester derivatives 失效
    3-芳基 - 缩水甘油酯衍生物

    公开(公告)号:US5436235A

    公开(公告)日:1995-07-25

    申请号:US16980

    申请日:1993-02-12

    CPC分类号: C07D405/04 C07D303/48

    摘要: The present invention relates to 3-aryl-oxirane derivatives of the formula ##STR1## wherein Ar is 4'-quinoline or 5'-quinoline; each of R and R.sub.1 independently is hydrogen or C.sub.1 -C.sub.6 alkoxy; one of X and Y is hydrogen, cyano, --COOR.sub.2 or --CONR.sub.3 R.sub.4, and the other of X and Y is cyano, --COOR.sub.2 or --CONR.sub.3 R.sub.4, wherein R.sub.2 is C.sub.1 -C.sub.6 alkyl and each of R.sub.3 and R.sub.4 independently is hydrogen or C.sub.1 -C.sub.6 alkyl, and pharmaceutically acceptable salts thereof, which are useful in therapy as tyrosine kinase inhibitors, in particular as anti-proliferative agents, typically as anti-cancer agents, in the treatment of psoriasis and in inhibiting the development of atheromatous plaque.

    摘要翻译: 本发明涉及式为“IMAGE”的3-芳基 - 环氧乙烷衍生物,其中Ar为4'-喹啉或5'-喹啉; R和R 1各自独立地是氢或C 1 -C 6烷氧基; X和Y中的一个是氢,氰基,-COOR 2或-CONR 3 R 4,X和Y中的另一个是氰基,-COOR 2或-CONR 3 R 4,其中R 2是C 1 -C 6烷基,R 3和R 4各自独立地是氢或C 1 -C6烷基和其药学上可接受的盐,其可用于治疗作为酪氨酸激酶抑制剂,特别是作为抗增殖剂(通常作为抗癌剂)用于治疗牛皮癣和抑制动脉粥样硬化斑块发展。

    Arylidene-heterocyclic derivatives and process for their preparation
    3.
    发明授权
    Arylidene-heterocyclic derivatives and process for their preparation 失效
    亚芳基杂环衍生物及其制备方法

    公开(公告)号:US5639884A

    公开(公告)日:1997-06-17

    申请号:US400113

    申请日:1995-03-06

    摘要: The invention relates to compounds of formula ##STR1## wherein Ar is mono- or bicyclic ring system chosen from benzene, naphthalene, tetrahydronaphthalene, quinoline and indole;Het is ##STR2## R is hydrogen, halogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 acyloxy, cyano, nitro, amino or --COOR.sub.3 in which R.sub.3 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.1 is hydrogen, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 acyloxy, cyano, nitro, amino or --COOR.sub.3 in which R.sub.3 is as defined above;R.sub.2 is hydrogen, halogen, hydroxy or C.sub.1 -C.sub.6 alkyl; and the pharmaceutically acceptable salts thereof, and wherein when at the same time the (Ar)R.sub.1 R.sub.2 group represents unsubstituted phenyl or 4-chloro-, 4-cyano-, 4-amino- or 3,4-dimethoxy-phenyl and Het is a 4-homophthalimide group, then R is other than hydrogen, which are useful as anti-proliferative agents.

    摘要翻译: 本发明涉及式(I)的化合物,其中Ar是选自苯,萘,四氢萘,喹啉和吲哚的单环或双环体系; Het是R 1是氢或C 1 -C 6烷基的氢,卤素,羟基,C 1 -C 6烷氧基,C 2 -C 6酰氧基,氰基,硝基,氨基或-COOR 3; R 1是氢,羟基,C 1 -C 6烷基,C 1 -C 6烷氧基,C 2 -C 6酰氧基,氰基,硝基,氨基或-COOR 3,其中R 3如上所定义; R2是氢,卤素,羟基或C1-C6烷基; 其中当(Ar)R 1 R 2基团同时表示未取代的苯基或4-氯 - ,4-氰基 - ,4-氨基 - 或3,4-二甲氧基 - 苯基且Het为 4-高邻苯二甲酰亚胺基,则R不是氢,它们可用作抗增殖剂。

    Biologically active 3-substituted oxindole derivatives useful as
anti-angiogenic agents
    4.
    发明授权
    Biologically active 3-substituted oxindole derivatives useful as anti-angiogenic agents 失效
    用作抗血管生成剂的生物活性3-取代羟吲哚衍生物

    公开(公告)号:US5576330A

    公开(公告)日:1996-11-19

    申请号:US354215

    申请日:1994-12-12

    摘要: The new use of a compound of formula (I) ##STR1## wherein Y is a bicyclic ring selected from naphthalene, tetralin, quinoline, isoquinoline and indole;n is zero or an integer of 1 to 3;R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkanoyl;R.sub.2 is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, cyano, carboxy, nitro, or NHR, wherein R is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.3 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.4 is hydrogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.6 alkanoyloxy, carboxy, nitro or NHR, wherein R is as defined above;R.sub.5 is hydrogen, C.sub.1 -C.sub.6 alkyl or halogen; or a pharmaceutically acceptable salt thereof;and wherein when Y is naphthalene then n is zero or an integer of 1 to 3, whereas when Y is tetralin, quinoline, isoquinoline or indole then n is zero, 1 or 2; and wherein when the bicyclic ring Y is naphthalene, quinoline, isoquinoline or indole, then each of the substituents OR.sub.1, R.sub.2 and oxindolylidene may be independently on either of the aryl or heteroaryl moieties of said bicyclic ring, whereas only the benzene moiety is substituted when Y is tetralin;and wherein when Y is naphthalene, tetralin, quinoline or isoquinoline, then R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl and R.sub.3, R.sub.4 and R.sub.5 are hydrogen; whereas when Y is indole, then R.sub.2 is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, cyano, carboxy, nitro or --NHR, in which R is as defined above, R.sub.3 is hydrogen or C.sub.1 -C.sub.6 alkyl, R.sub.4 is hydrogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, carboxy, nitro or --NHR, wherein R is as defined above, and R.sub.5 is hydrogen, halogen or C.sub.1 -C.sub.6 alkyl;as anti-angiogenic agent is disclosed.

    摘要翻译: 式(I)化合物(I)的新用途其中Y是选自萘,四氢化萘,喹啉,异喹啉和吲哚的双环; n为0或1〜3的整数, R1是氢,C1-C6烷基或C2-C6烷酰基; R2是氢,卤素,C1-C6烷基,氰基,羧基,硝基或NHR,其中R是氢或C1-C6烷基; R3是氢或C1-C6烷基; R 4是氢,羟基,C 1 -C 6烷氧基,C 2 -C 6烷酰氧基,羧基,硝基或NHR,其中R如上定义; R5是氢,C1-C6烷基或卤素; 或其药学上可接受的盐; 当Y为萘时,n为0或1〜3的整数,Y为四氢化萘,喹啉,异喹啉或吲哚时,n为0,1或2。 并且其中当双环Y为萘,喹啉,异喹啉或吲哚时,则所述取代基OR 1,R 2和羟吲哚基中的每一个可以独立地表示在所述二环的芳基或杂芳基部分上,而只有苯部分被取代, Y是四氢化萘; 其中当Y为萘,四氢化萘,喹啉或异喹啉时,则R2为氢,卤素,氰基或C1-C6烷基,R3,R4和R5为氢; 而当Y为吲哚时,R 2为氢,卤素,C 1 -C 6烷基,氰基,羧基,硝基或-NHR,其中R如上定义,R 3为氢或C 1 -C 6烷基,R 4为氢,羟基, C 1 -C 6烷氧基,C 1 -C 6烷酰氧基,羧基,硝基或-NHR,其中R如上所定义,R 5是氢,卤素或C 1 -C 6烷基; 作为抗血管生成剂被公开。

    Method and intermediates for preparing 2-alkoxy and 2-aryloxy estrogen compounds
    5.
    发明申请
    Method and intermediates for preparing 2-alkoxy and 2-aryloxy estrogen compounds 有权
    制备2-烷氧基和2-芳氧基雌激素化合物的方法和中间体

    公开(公告)号:US20100099141A1

    公开(公告)日:2010-04-22

    申请号:US12285901

    申请日:2008-10-16

    IPC分类号: C12P33/00 C07J51/00

    摘要: The present invention relates to a method for preparing 2-alkoxy and 2-aryloxyestrogen compounds, and the intermediate compounds prepared during the use of this method, which intermediate compounds are useful intermediates in the preparation of certain physiologically active compounds.

    摘要翻译: 本发明涉及一种制备2-烷氧基和2-芳氧基雌激素化合物的方法,以及在该方法的使用中制备的中间体化合物,该中间体化合物是制备某些生理活性化合物的有用中间体。

    Substituted tetralymethylen-Oxindoles analogues as tyrosine kinase
inhibitors
    8.
    发明授权
    Substituted tetralymethylen-Oxindoles analogues as tyrosine kinase inhibitors 失效
    取代的四氢甲基 - 羟吲哚类似物作为酪氨酸激酶抑制剂

    公开(公告)号:US6147073A

    公开(公告)日:2000-11-14

    申请号:US981473

    申请日:1998-01-12

    CPC分类号: C07D209/34

    摘要: A tetralylmethylene-2-oxindole derivative having the following formula (I) ##STR1## wherein one or two of R, R.sub.1, R.sub.2 and R.sub.3 the said two being the same or different, are selected from:a) --X--(CH.sub.2).sub.m --NH.sub.2, --X--(CH.sub.2).sub.m --NR.sub.4 R.sub.5 or --X--(CH.sub.2).sub.m --NHR.sub.6, in which X is --O--, --S-- or --NH--, m is an integer of 2 to 4, one of R.sub.4 and R.sub.5 is hydrogen or C.sub.1 -C.sub.6 alkyl and the other is C.sub.1 -C.sub.6 alkyl or R.sub.4 and R.sub.5 taken together with the N atom to which they are linked form a 5 to 7 membered saturated heteromonocycle, and R.sub.6 is C.sub.2 -C.sub.6 alkanoyl or a C-terminally linked peptidyl residue containing from 1 to 3 aminoacids wherein the terminal amino group is either free or protected or in an alkylated form to provide a --NR.sub.4 R.sub.5 group in which R.sub.4 and R.sub.5 are as defined above.

    摘要翻译: PCT No.PCT / EP97 / 02672 Sec。 371日期:1998年1月12日 102(e)日期1998年1月12日PCT提交1997年5月15日PCT公布。 公开号WO97 / 45409 日期1997年12月4日具有下式(I)的四亚甲基-2-羟基吲哚衍生物,其中所述两个相同或不同的R 1,R 2,R 2和R 3中的一个或两个选自:a)-X-( CH2)m-NH2,-X-(CH2)m-NR4R5或-X-(CH2)m-NHR6,其中X是-O - , - S-或-NH-,m是2〜4的整数 R 4和R 5中的一个是氢或C 1 -C 6烷基,另一个是C 1 -C 6烷基或R 4和R 5与它们所连接的N原子一起形成5至7元饱和杂单环,并且R 6是C 2 - C6链烷酰基或含有1至3个氨基酸的C末端连接的肽基残基,其中末端氨基是游离的或被保护的或以烷基化形式提供,其中R4和R5如上所定义的-NR4R5基团。

    Substituted quinolymethylen-oxindole analogues as tyrosine kinase
inhibitors
    9.
    发明授权
    Substituted quinolymethylen-oxindole analogues as tyrosine kinase inhibitors 失效
    取代的喹喔啉甲氧基吲哚类似物作为酪氨酸激酶抑制剂

    公开(公告)号:US5905149A

    公开(公告)日:1999-05-18

    申请号:US983516

    申请日:1998-01-29

    摘要: Quinolylmethylen-oxindole derivatives having general formula (I), wherein R is H or --(CH.sub.2).sub.n --COR.sub.7 group in which n is an integer of 1 to 4 and R.sub.7 is hydroxy, amino, C.sub.1 -C.sub.6 alkoxy or --NR.sub.5 R.sub.6 in which one of R.sub.5 and R.sub.6 is hydrogen or C.sub.1 -C.sub.6 alkyl and the other is C.sub.1 -C.sub.6 alkyl or R.sub.5 and R.sub.6 taken together with the N atom to which they are linked form a 5 to 7 membered saturated heteromonocycle or R.sub.7 is a N-terminally linked peptidyl residue containing from 1 to 3 aminoacids in which the terminal carboxyl group may be present as such, as amide, as alkali metal salt or as a C.sub.1 -C.sub.4 alkyl ester, one or two of R.sub.1, R.sub.2, R.sub.3 and R.sub.4, which may be the same or different, are selected from: a) --X--(CH.sub.2).sub.m --NH.sub.2, --X--(CH.sub.2).sub.m --NR.sub.5 R.sub.6 or --X--(CH.sub.2).sub.m --NHR.sub.8 group; b) --NH--C(.dbd.NH)--NR.sub.5 R.sub.6, --NH--C(.dbd.NH)--NHR.sub.8, --N.dbd.CH--NH.sub.2, --N.dbd.CH--NR.sub.5 R.sub.6 or --N.dbd.CH--NHR.sub.8 group; c) --X--(C.sub.2).sub.n --COR.sub.7 group; d) --COR.sub.a or --COR.sub.9 group; e) --Y--CO--Y'--R.sub.10 group; and f) --NHR.sub.8 or --NHR.sub.11 group and the pharmaceutically acceptable salts thereof, are tyrosine kinase inhibitors.

    摘要翻译: PCT No.PCT / EP97 / 02673。 371日期1998年1月29日 102(e)日期1998年1月29日PCT提交1997年5月15日PCT公布。 公开号WO97 / 46551 日本1997年12月11日具有通式(I)的喔苯基亚甲基 - 羟基吲哚衍生物,其中R为H或 - (CH 2)n -COR 7基,其中n为1〜4的整数,R 7为羟基,氨基,C 1 -C 6烷氧基 或-NR 5 R 6,其中R 5和R 6中的一个为氢或C 1 -C 6烷基,另一个为C 1 -C 6烷基或R 5和R 6与它们所连接的N原子一起形成5至7元饱和杂单环或R7 是含有1至3个氨基酸的N-末端连接的肽基残基,其中末端羧基可以原样存在,作为酰胺,作为碱金属盐或作为C 1 -C 4烷基酯,R 1,R 2, R 3和R 4可以相同或不同,选自:a)-X-(CH 2)m -NH 2,-X-(CH 2)m -NR 5 R 6或-X-(CH 2)m -NHR 8基团; b)-NH-C(= NH)-NR 5 R 6,-NH-C(= NH)-NHR 8,-N = CH-NH 2,-N = CH-NR 5 R 6或-N = CH-NHR 8基团; c)-X-(C2)n-COR7基团; d)-COR a或-COR 9基团; e)-Y-CO-Y'-R10基团; 和f)-NHR 8或-NHR 11基团及其药学上可接受的盐是酪氨酸激酶抑制剂。

    Substituted 3-arylidene-7-azaoxindole compounds and process for their
preparation
    10.
    发明授权
    Substituted 3-arylidene-7-azaoxindole compounds and process for their preparation 失效
    取代的3-亚芳基-7-氮杂羟基吲哚化合物及其制备方法

    公开(公告)号:US5719135A

    公开(公告)日:1998-02-17

    申请号:US669315

    申请日:1996-07-09

    CPC分类号: C07D471/04

    摘要: The present invention relates to compound of formula (I) ##STR1## wherein A is benzene, naphthalene, 5,6,7,8,-tetrahydronaphthalene, quinoline, isoquinoline, indole or 7-azaindole; R.sub.1 is --H, --CN, --SO.sub.3 R.sub.4 --, --SO.sub.2 NHR.sub.5, ##STR2## --COOR.sub.6, --CONHCH.sub.2 (CHOH).sub.n CH.sub.2 OH, ##STR3## --NR.sub.7 R.sub.8, --N(CH.sub.2 CH.sub.2 OH).sub.2, --NHCH.sub.2 (CHOH).sub.n CH.sub.2 OH, --NHCONH.sub.2, --NH--C(NH.sub.2).dbd.NH, --NHCO(CHOH).sub.n CH.sub.2 OH, ##STR4## --NHSO.sub.2 R.sub.9, --OR.sub.10, --OCH.sub.2 (CHOH).sub.n CH.sub.2 OH, --OOC(CHOH).sub.n CH.sub.2 OH, --OPO(OH).sub.2, --CH.sub.2 NH.sub.2, --C(NH.sub.2).dbd.NH, --CH.sub.2 NHC(NH.sub.2).dbd.NH, ##STR5## --CH.sub.2 OH, --CH.sub.2 OOC(CHOH).sub.n CH.sub.2 OH, --CH.sub.2 OPO(OH).sub.2 or --PO(OH).sub.2 ; R.sub.2 is C.sub.1 -C.sub.6 alkyl, halogen, or hydroxy; R.sub.3 is --H or C.sub.1 -C.sub.6 alkyl; R.sub.4 is --H, C.sub.1 -C.sub.6 alkyl or --CH.sub.2 (CHOH).sub.n CH.sub.2 OH; R.sub.5 is --H, C.sub.1 -C.sub.6 alkyl, --CH.sub.2 (CHOH).sub.n CH.sub.2 OH or --(CH.sub.2).sub.m NMe.sub.2 ; R.sub.6 is --H, C.sub.1 -C.sub.6 alkyl or --CH.sub.2 (CHOH).sub.n CH.sub.2 OH; each of R.sub.7 and R.sub.8 independently is --H or C.sub.1 -C.sub.6 alkyl;R.sub.9 is methyl or tolyl; R.sub.10 is --H, C.sub.1 -C.sub.6 alkyl, or C.sub.2 -C.sub.6 alkanoyl; Z is >CH.sub.2, >O, >NH, or >NCH.sub.2 CH.sub.2 OH; n is zero or 1; m is 2 or 3; p is 1, 2 or 3; q is zero, 1 or 2; and the pharmaceutically acceptable salt thereof, for use as tyrosine kinase inhibitors.

    摘要翻译: PCT No.PCT / EP95 / 04247 Sec。 371日期:1996年7月9日 102(e)日期1996年7月9日PCT提交1995年10月30日PCT公布。 公开号WO96 / 16964 日本时间1996年6月6日本发明涉及式(I)化合物其中A为苯,萘,5,6,7,8, - 四氢萘,喹啉,异喹啉,吲哚或7-氮杂吲哚; R1是-H,-CN,-SO3R4-,-SO2NHR5,-COOR6,-CONHCH2(CHOH)nCH2OH,图示-NR7R8,-N(CH2CH2OH)2,-NHCH2(CHOH)nCH2OH,-NHCONH2 ,-NH-C(NH 2)= NH,-NHCO(CHOH)n CH 2 OH,-NCO 2 -NH 9,-OR 10,-OCH 2(CHOH)n CH 2 OH,-OOC(CHOH)n CH 2 OH,-OPO(OH)2,-CH 2 NH ,-C(NH 2)= NH,-CH 2 NHC(NH 2)= NH,-CH 2 OH,-CH 2 OOC(CHOH)n CH 2 OH,-CH 2 OPO(OH)2或-PO(OH) R2是C1-C6烷基,卤素或羟基; R3是-H或C1-C6烷基; R4是-H,C1-C6烷基或-CH2(CHOH)nCH2OH; R5是-H,C1-C6烷基,-CH2(CHOH)nCH2OH或 - (CH2)mNMe2; R6是-H,C1-C6烷基或-CH2(CHOH)nCH2OH; R 7和R 8各自独立地为-H或C 1 -C 6烷基; R9为甲基或甲苯基; R 10是-H,C 1 -C 6烷基或C 2 -C 6烷酰基; Z是> CH2,> O,> NH或> NCH2CH2OH; n为零或1; m为2或3; p为1,2或3; q为零,1或2; 及其药学上可接受的盐,用作酪氨酸激酶抑制剂。