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    S1P AND/OR ATX MODULATING AGENTS
    81.
    发明申请
    S1P AND/OR ATX MODULATING AGENTS 审中-公开
    S1P和/或ATX调节剂

    公开(公告)号：WO2014081752A1

    公开(公告)日：2014-05-30

    申请号：PCT/US2013/070878

    申请日：2013-11-20

    申请人： BIOGEN IDEC MA INC.

    发明人： PENG, Hairuo ,  LIN, Edward, Yin-shiang ,  CHAO, Jianhua ,  XIN, Zhili ,  MA, Bin ,  GUCKIAN, Kevin ,  CHAN, Timothy ,  KUMARAVEL, Gnanasambandam ,  TAVERAS, Arthur, G.

    IPC分类号： C07D207/08 ,  C07D211/22 ,  C07D211/56 ,  C07D211/62 ,  C07D211/70 ,  C07D213/74 ,  C07D237/22 ,  C07D239/47 ,  C07D295/15 ,  C07D295/155 ,  C07D401/12 ,  A61K31/40 ,  A61K31/451 ,  A61K31/4545 ,  A61K31/495

    CPC分类号： C07D211/22 ,  A61K31/451 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D207/08 ,  C07D211/56 ,  C07D211/62 ,  C07D211/70 ,  C07D213/74 ,  C07D237/22 ,  C07D239/47 ,  C07D295/15 ,  C07D295/155 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04

    摘要： Compounds of formula (I) wherein: X is -0-, -S(0) r -, -CH 2 -, or -NR-, wherein r is 0, 1, or 2; X 1 , X 2 , and X 5 are each independently CR 7 or N; one of X 3 or X 4 is C and is attached by a single bond to -L-, and the other is CR 7 or N, provided that no more than three of X 1 , X 2 , X 3 , X or X 5 are N; Ring A is monocyclic C 5-6 scycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or 0; wherein Ring A is further optionally substituted with from 1 to 3 R 4 ; provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl; L is a bond, -0-, -NR-, -S(0) n -, -CH 2 -,or -C(O)-, wherein n is 0, 1, or 2; 1 2 L 1 is an C 1-8 alkylene, C 3-s cycloalkylene, -CH 2 -L 2 -, or a 3- to 8- membered heterocyclylene comprising 1 to 5; R 1 is C 6-20 alkyl or a monocyclic C 3-8 cycloalkyl; wherein said C 3-8 cycloalkyl is substituted with at least one R 6 and may be optionally substituted with from 1 to 5 additional R 6 substituents, wherein R 6 for each occurrence is independently selected; and R 2 is -C(0)OR 3 , -C(0)N(R 3 )-S(0) 2 R 3 , -S(0) 2 OR 3 , -C(0)NHC(0) R 3 , -Si(0)OH, - B(OH) 2 , -N(R 3 )S(0) 2 R 3 , -S(0) 2 N(R 3 ) 2 , -O-P(O) (OR 3 ) 2 , or -P(0)(OR 3 ) 2 , -CN, - S(0) 2 NHC(0)R 3 , -C(0)NHS(0) 2 R3, - C(0)NHOH, -C(0)NHCN, -CH(CF 3 )OH, -C(CF 3 ) 2 OH, or a selected heteroaryl or heterocyclyl; and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).

    摘要翻译： 式（I）化合物其中：X为-O - ， - S（O）r - ， - CH 2 - 或 - NR-，其中r为0,1或2; X 1，X 2和X 5各自独立地为CR 7或N; X 3或X 4中的一个为C并且通过单键连接至-L-，另一个为CR 7或N，条件是X 1，X 2，X 3，X或X 5中不超过3个为N; 环A是单环C 5-6环烷基或包含1至5个独立地选自N，S或0的杂原子的5至6元单环杂环基; 其中环A进一步任选被1至3个R 4取代; 环A不是吗啉基，硫代吗啉基或四氢-2H-吡喃基; L是键，-O - ， - NR - ， - S（O）n - ， - CH 2 - 或-C（O） - ，其中n是0,1或2; 1 2 L 1是C 1-8亚烷基，C 3 - 亚环亚烷基，-CH 2 -L 2 - 或包含1至5的3-至8-元亚杂环基; R1是C6-20烷基或单环C3-8环烷基; 其中所述C 3-8环烷基被至少一个R 6取代，并且可以任选被1至5个另外的R 6取代基取代，其中每次出现的R 6是独立选择的; 并且R 2是-C（O）OR 3，-C（O）N（R 3）-S（O）2 R 3，-S（O）2 OR 3，-C（O）NHC（O）R 3，-Si ， - B（OH）2，-N（R3）S（O）2R3，-S（O）2N（R3）2，-OP（O）（OR3）2或-P（0）（OR3）2 ，-CN，-S（O）2 NHC（O）R 3，-C（O）NHS（O）2 R 3，-C（O）NHOH，-C（O）NHCN，-CH（CF 3）OH，-C CF 3）2 OH，或选择的杂芳基或杂环基; 和其药学上可接受的盐可调节一种或多种SIP受体的活性和/或自分泌素（ATX）的活性。

    LIGANDS FOR ANTIBODY PURIFICATION BY AFFINITY CHROMATOGRAPHY
    82.
    发明申请
    LIGANDS FOR ANTIBODY PURIFICATION BY AFFINITY CHROMATOGRAPHY 审中-公开
    通过亲和色谱法进行抗体纯化的配体

    公开(公告)号：WO2011104307A2

    公开(公告)日：2011-09-01

    申请号：PCT/EP2011/052758

    申请日：2011-02-24

    申请人： GRAFFINITY PHARMACEUTICALS GMBH ,  BITTERMANN, Holger ,  BURKERT, Klaus ,  KALBFUSS-ZIMMERMANN, Bernd ,  KEIL, Oliver ,  NEUMANN, Thomas ,  OTT, Inge ,  SCHMIDT, Kristina ,  SEKUL, Renate

    发明人： BITTERMANN, Holger ,  BURKERT, Klaus ,  KALBFUSS-ZIMMERMANN, Bernd ,  KEIL, Oliver ,  NEUMANN, Thomas ,  OTT, Inge ,  SCHMIDT, Kristina ,  SEKUL, Renate

    IPC分类号： C07K1/22 ,  B01D15/08 ,  C07K16/06 ,  C07C237/10 ,  C07D207/16 ,  C07D211/62

    CPC分类号： C07C237/22 ,  B01D15/3804 ,  B01J20/286 ,  B01J20/289 ,  B01J20/3253 ,  C07B2200/11 ,  C07D207/16 ,  C07D211/62 ,  C07D243/08 ,  C07D295/104 ,  C07K1/22 ,  C07K16/065 ,  C07K16/22

    摘要： The present invention relates to the use, for affinity purification of a protein, of a compound according to the general formula (I), wherein A is selected from the group: -O-;-S-; >CR 7 R 8 ; and NR 9 ; D is a linear or branched Ci to C6 alkyl group, which may comprise a cycloalkyl unit, wherein 1 or more C-atoms which are not connected to each other may be replaced by O or S, and wherein one or more C-atoms in the alkyl group may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; L is the linking point via which the compound is attached to a support matrix, L optionally comprising a spacer group -Z-; R 1 , R 2 are identical or different and are independently of each other selected from the group: H; -OH; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit; wherein in the alkyl 1 C-atom may be replaced by -O-, or a terminal C-atom may be replaced by -OH; wherein N may be part of a heterocycle having 3 to 7 members; and wherein one or more C- atoms in the alkyl may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; R 3 , R 4 , R 5 and R 6 are identical or different and are independently of each other selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein in the alkyl 1 C-atom may be replaced by -0-, or a terminal C-atom may be replaced by -OH; and wherein one or more C-atoms in each R 3 , R 4 , R 5 and R 6 may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; and - NR 10 R 11 ; R 7 , R 8 are identical or different and are selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, wherein the alkyl group may optionally be substituted; R 9 is selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein the alkyl group may optionally be substituted; R 10 , R 11 can be identical or different and are independently of each other selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein the alkyl group may optionally be substituted. Preferably, the entity to be separated of purified is an antibody, in particular an antibody of the Bevacizumab type or the Ranibizumab type.

    摘要翻译： 本发明涉及用于亲和纯化蛋白质的根据通式（I）的化合物，其中A选自：-O - ; - S-; > CR7R8; 和NR9; D是直链或支链的C 1 -C 6烷基，其可以包含环烷基单元，其中不彼此连接的一个或多个C原子可以被O或S替代，并且其中一个或多个C原子在 烷基可以被一个或多个彼此独立地选自F，C 1，Br，I; L是化合物连接到载体基质上的连接点，L任选地包含间隔基团-Z-; R1，R2相同或不同，彼此独立地选自H： -哦; 直链和支链的C 1 -C 4烷基，其可以包含环烷基单元; 其中在烷基中，C原子可以被-O-取代，或者C末端可被-OH取代; 其中N可以是具有3至7个成员的杂环的一部分; 并且其中所述烷基中的一个或多个C原子可以被一个或多个彼此独立地选自F，C 1，Br，I; R3，R4，R5和R6相同或不同，彼此独立地选自H： 直链和支链的C 1 -C 4烷基，其可以包含环烷基单元，并且其中在烷基C 1可以被-O-取代，或者C末端可被-OH取代; 并且其中每个R 3，R 4，R 5和R 6中的一个或多个C原子可以被一个或多个彼此独立地选自F，C 1，Br，I， 和 - NR10R11; R 7，R 8相同或不同，选自H; 直链和支链C1至C4烷基，其可以包含环烷基单元，其中烷基可以任选被取代; R9选自H： 直链和支链C1至C4烷基，其可以包含环烷基单元，并且其中烷基可以任选被取代; R 10，R 11可以相同或不同，彼此独立地选自H; 直链和支链C 1 -C 4烷基，其可以包含环烷基单元，并且其中烷基可以任选地被取代。 优选地，待分离纯化的实体是抗体，特别是贝伐单抗型或拉唑珠单抗型的抗体。

    INHIBITORS OF 17BETA-HYDROXYSTEROID DEHYDROGENASE
    87.
    发明申请
    INHIBITORS OF 17BETA-HYDROXYSTEROID DEHYDROGENASE 审中-公开
    17BA-羟基脱氢酶抑制剂的抑制剂

    公开(公告)号：WO2009066072A3

    公开(公告)日：2009-10-15

    申请号：PCT/GB2008003889

    申请日：2008-11-19

    申请人： STERIX LTD ,  VICKER NIGEL ,  BAILEY HELEN VICTORIA ,  HEATON WESLEY ,  DAY JOANNA MARY ,  PUROHIT ATUL ,  POTTER BARRY VICTOR LLOYD

    发明人： VICKER NIGEL ,  BAILEY HELEN VICTORIA ,  HEATON WESLEY ,  DAY JOANNA MARY ,  PUROHIT ATUL ,  POTTER BARRY VICTOR LLOYD

    IPC分类号： C07C209/14 ,  A61K31/167 ,  A61K31/36 ,  A61K31/4409 ,  A61P5/24 ,  A61P35/00 ,  C07C211/50 ,  C07C233/43 ,  C07C237/42 ,  C07D207/26 ,  C07D211/58 ,  C07D211/62 ,  C07D317/66

    CPC分类号： C07D207/26 ,  C07C217/90 ,  C07C233/43 ,  C07C237/42 ,  C07D211/58 ,  C07D211/62 ,  C07D317/66

    摘要： There is provided a compound having Formula (I), wherein each of R1, R2, R3, R4, R5, R6, R7, R8 and R9 are independently selected from (a) H, (b) R13, -OC(R13)3, -OCH(R13)2, -OCH2R13, -C(R13)3, -CH(R13)2, or -CH2R13 wherein R13 is a halogen; (c) -CN; (d) optionally substituted alkyl, (e) optionally substituted heteroalkyl; (f) optionally substituted aryl; (g) optionally substituted heteroaryl; (h) optionally substituted arylalkyl; (i) optionally substituted heteroarylalkyl; (j) hydroxy; (k) alkoxy; (I) aryloxy; (m) -SO2-alkyl; and (n) -N(R14)C(O)R15, wherein R14 and R15 are independently selected from H and hydrocarbyl, wherein the optional substituents of (d) (e) (T) (h) and (i) are selected from the group consisting of: C1-6 alkyl, halo, cyano, nitro, haloalkyl, hydroxy, C1-6 alkoxy, carboxy, carboxyalkyl, carboxamide, mercapto, amino, alkylamino, dialkylamino, sulfonyl, sulfonamido, aryl and heteroaryl; wherein n and p are independently selected from 0 and 1; X is an optional group selected from O, S, S=O, S(=O)2, C=O, S(=O)2NR16, C=ONR17, NR18, in which R16, R17, and R18 are independently selected from H and hydrocarbyl, R10 is selected from H and hydrocarbyl, R11 is selected from CR19R20 and C=O, in which R19 and R20 are independently selected from H and hydrocarbyl, R12 is selected from a substituted five or six membered carbon rings optionally containing one or more hetero atoms selected from N, S, and O and optionally having fused thereto a further ring, and wherein the one or more substituents are selected from hydrocarbyl groups.

    摘要翻译： 提供具有式（I）的化合物，其中R1，R2，R3，R4，R5，R6，R7，R8和R9各自独立地选自（a）H，（b）R13，-OC（R13） 3，-OCH（R 13）2，-OCH 2 R 13，-C（R 13）3，-CH（R 13）2或-CH 2 R 13，其中R 13是卤素; （c）-CN; （d）任选取代的烷基，（e）任选取代的杂烷基; （f）任选取代的芳基; （g）任选取代的杂芳基; （h）任选取代的芳基烷基; （i）任选取代的杂芳基烷基; （j）羟基; （k）烷氧基; （I）芳氧基; （m）-SO 2 - 烷基; 和（n）-N（R 14）C（O）R 15，其中R 14和R 15独立地选自H和烃基，其中选择（d）（e）（T）（h）和（i） 羟基，C 1-6烷氧基，羧基，羧基烷基，羧酰胺，巯基，氨基，烷基氨基，二烷基氨基，磺酰基，亚磺酰氨基，芳基和杂芳基; 其中n和p独立地选自0和1; X是选自O，S，S = O，S（= O）2，C = O，S（= O）2NR16，C = ONR17，NR18的任选基团，其中R 16，R 17和R 18独立地选自 R 10选自H和烃基，R 11选自CR 19 R 20和C = O，其中R 19和R 20独立地选自H和烃基，R 12选自取代的五或六元碳环，任选含有 一个或多个选自N，S和O的杂原子，并且任选地与另一个环稠合，并且其中一个或多个取代基选自烃基。

    COMPOUND
    88.
    发明申请
    COMPOUND 审中-公开
    复合

    公开(公告)号：WO2009066072A2

    公开(公告)日：2009-05-28

    申请号：PCT/GB2008/003889

    申请日：2008-11-19

    申请人： STERIX LIMITED ,  VICKER, Nigel ,  BAILEY, Helen, Victoria ,  HEATON, Wesley ,  DAY, Joanna, Mary ,  PUROHIT, Atul ,  POTTER, Barry, Victor, Lloyd

    发明人： VICKER, Nigel ,  BAILEY, Helen, Victoria ,  HEATON, Wesley ,  DAY, Joanna, Mary ,  PUROHIT, Atul ,  POTTER, Barry, Victor, Lloyd

    IPC分类号： C07C209/14 ,  C07C211/50 ,  C07C233/43 ,  C07C237/42 ,  C07D207/26 ,  C07D211/58 ,  C07D211/62 ,  C07D317/66 ,  A61K31/167 ,  A61K31/4409 ,  A61K31/36

    CPC分类号： C07D207/26 ,  C07C217/90 ,  C07C233/43 ,  C07C237/42 ,  C07D211/58 ,  C07D211/62 ,  C07D317/66

    摘要： There is provided a compound having Formula (I), wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from (a) H, (b) R13, -OC(R 13 ) 3 , -OCH(R 13 ) 2 , -OCH 2 R 13 , -C(R 13 ) 3 , -CH(R 13 ) 2 , or -CH 2 R 13 wherein R 13 is a halogen; (c) -CN; (d) optionally substituted alkyl, (e) optionally substituted heteroalkyl; (f) optionally substituted aryl; (g) optionally substituted heteroaryl; (h) optionally substituted arylalkyl; (i) optionally substituted heteroarylalkyl; (j) hydroxy; (k) alkoxy; (I) aryloxy; (m) -SO 2 -alkyl; and (n) -N(R 14 )C(O)R 15 , wherein R 14 and R 15 are independently selected from H and hydrocarbyl, wherein the optional substituents of (d) (e) (T) (h) and (i) are selected from the group consisting of: C 1-6 alkyl, halo, cyano, nitro, haloalkyl, hydroxy, C 1-6 alkoxy, carboxy, carboxyalkyl, carboxamide, mercapto, amino, alkylamino, dialkylamino, sulfonyl, sulfonamido, aryl and heteroaryl; wherein n and p are independently selected from 0 and 1; X is an optional group selected from O, S, S=O, S(=O) 2 , C=O, S(=O) 2 NR 16 , C=ONR 17 , NR 18 , in which R 16 , R 17 , and R 18 are independently selected from H and hydrocarbyl, R 10 is selected from H and hydrocarbyl, R 11 is selected from CR 19 R 20 and C=O, in which R 19 and R 20 are independently selected from H and hydrocarbyl, R 12 is selected from a substituted five or six membered carbon rings optionally containing one or more hetero atoms selected from N, S, and O and optionally having fused thereto a further ring, and wherein the one or more substituents are selected from hydrocarbyl groups.

    摘要翻译： 提供具有式（I）的化合物，其中R1，R2，R3，R4，R5，R6，R7，R8和R9各自独立地选自（a）H，（b）R13，-OC（R13） 3，-OCH（R 13）2，-OCH 2 R 13，-C（R 13）3，-CH（R 13）2或-CH 2 R 13，其中R 13是卤素; （c）-CN; （d）任选取代的烷基，（e）任选取代的杂烷基; （f）任选取代的芳基; （g）任选取代的杂芳基; （h）任选取代的芳基烷基; （i）任选取代的杂芳基烷基; （j）羟基; （k）烷氧基; （I）芳氧基; （m）-SO 2 - 烷基; 和（n）-N（R 14）C（O）R 15，其中R 14和R 15独立地选自H和烃基，其中选择（d）（e）（T）（h）和（i） 羟基，C 1-6烷氧基，羧基，羧基烷基，羧酰胺，巯基，氨基，烷基氨基，二烷基氨基，磺酰基，亚磺酰氨基，芳基和杂芳基; 其中n和p独立地选自0和1; X是选自O，S，S = O，S（= O）2，C = O，S（= O）2NR16，C = ONR17，NR18的任选基团，其中R 16，R 17和R 18独立地选自 R 10选自H和烃基，R 11选自CR 19 R 20和C = O，其中R 19和R 20独立地选自H和烃基，R 12选自取代的五或六元碳环，任选含有 一个或多个选自N，S和O的杂原子，并且任选地与另一个环稠合，并且其中一个或多个取代基选自烃基。