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    SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME
    2.
    发明申请
    SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME 审中-公开
    磺酰脲类化合物及相关化合物及其用途

    公开(公告)号：WO2017140778A1

    公开(公告)日：2017-08-24

    申请号：PCT/EP2017/053498

    申请日：2017-02-16

    Applicant: THE UNIVERSITY OF QUEENSLAND ,  THE PROVOST, FELLOWS, FOUNDATION SCHOLARS, AND THE OTHER MEMBERS OF BOARD, OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

    Inventor： O'NEILL, Luke ,  COLL, Rebecca ,  COOPER, Matthew ,  ROBERTSON, Avril ,  SCHRODER, Kate ,  MACLEOD, Angus Murray ,  MILLER, David John

    IPC: C07D231/18 ,  C07C307/06 ,  C07C307/08 ,  C07C307/10 ,  C07D295/26 ,  A61P29/00

    CPC classification number: C07D295/26 ,  C07C307/06 ,  C07C307/10 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2603/10 ,  C07D231/18

    Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, solvates and prodrugs thereof: Formula (I) wherein Q is selected from O, S and Se; J is S or Se; W 1 and W 2 , when present, are independently selected from N and C; R 1 and R 2 are independently selected from the group consisting of hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, cycloalkenyl, amino, amido, alkylthio, acyl, arylalkyl and acylamido, all of which may be optionally substituted; and wherein at least one of W 1 and W 2 is present and is a nitrogen atom and when R 1 and R 2 are cyclic then the respective W 1 or W 2 may form part of the ring structure. The present invention also relates to pharmaceutical compositions including such compounds, to methods of treatment using such compounds, in particular in relation to NLRP3 inflammasome mediated disorders, and to associated diagnostic uses.

    Abstract translation: 本发明涉及式（I）化合物及其药学上可接受的盐，溶剂化物和前药：其中Q选自O，S和Se的式（I） J是S或Se; 当存在时，W 1和W 2独立地选自N和C; R 1和R 2独立地选自氢，C 1 -C 12烷基，C 1 -C 12烷基，C 1 -C 12烷氧基， C12-C12低级链烯基，C2-C12炔基，芳基，杂环基，杂芳基，环烷基， 环烯基，氨基，酰氨基，烷硫基，酰基，芳基烷基和酰基酰氨基，它们都可以被任意取代; 并且其中W 1和W 2中的至少一个存在并且是氮原子，并且当R 1和R 2如上所述时， / sup>是循环的，那么相应的W 1或W 2可以形成环结构的一部分。 本发明还涉及包含此类化合物的药物组合物，涉及使用此类化合物的治疗方法，特别是涉及NLRP3炎性体介导的疾病，以及相关的诊断用途。

    COLCHINOL DERIVATIVES AS VASCULAR DAMAGING AGENTS
    7.
    发明申请
    COLCHINOL DERIVATIVES AS VASCULAR DAMAGING AGENTS 审中-公开
    COLCHINOL衍生物作为血管破坏剂

    公开(公告)号：WO00040529A1

    公开(公告)日：2000-07-13

    申请号：PCT/GB1999/004436

    申请日：1999-12-24

    IPC: C07D295/08 ,  A61K31/165 ,  A61K31/167 ,  A61K31/192 ,  A61K31/197 ,  A61K31/198 ,  A61K31/225 ,  A61K31/255 ,  A61K31/265 ,  A61K31/27 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/5375 ,  A61K31/661 ,  A61K31/704 ,  A61P9/00 ,  A61P35/00 ,  C07B53/00 ,  C07C68/02 ,  C07C69/96 ,  C07C213/00 ,  C07C217/74 ,  C07C231/02 ,  C07C231/12 ,  C07C233/23 ,  C07C233/43 ,  C07C237/04 ,  C07C237/48 ,  C07C249/12 ,  C07C251/44 ,  C07C253/20 ,  C07C255/60 ,  C07C257/14 ,  C07C269/04 ,  C07C269/06 ,  C07C271/22 ,  C07C271/24 ,  C07C271/52 ,  C07C273/18 ,  C07C275/42 ,  C07C301/02 ,  C07C303/28 ,  C07C303/40 ,  C07C305/24 ,  C07C307/08 ,  C07C309/15 ,  C07F9/09 ,  C07F9/40 ,  C07H15/248 ,  C07C13/547 ,  A61K31/19 ,  A61K31/22

    CPC classification number: A61K31/165

    Abstract: The invention relates to the use of compounds of formula (I): wherein X is -C(O)-, -C(S)-, -C=NOH, or -CH(R )- wherein R is hydrogen, hydroxy, C1-7alkoxy, -OR or -NR R (wherein R is a group -Y R (wherein Y is a direct bond, -C(O)-, -C(S)-, -S-, -C(O)O, -C(O)NR -, -SO2- or -SO2NR - (wherein R and R , which may be the same or different, each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R is as defined herein, and R includes hydrogen; R , R and R are as defined herein and are preferably methyl; R , R and R are as defined herein with the proviso that R is not hydroxy, alkoxy, substituted alkoxy, -OPO3H2, -O-C1-7alkanoyl or benzyloxy; and salts thereof in the manufacture of a medicament for use in the production of a vascular damaging effect in warm-blooded animals such as humans. The present invention further relates to compounds of the formula (I), pharmaceutical compositions containing them, processes for their preparation and to a method of treatment using the compounds to produce a vascular damaging effect in a warm-blooded animal such as a human. The compounds of formula (I) and the pharmaceutically acceptable salts thereof may be useful in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    Abstract translation: 本发明涉及式（I）化合物的用途：其中X是-C（O） - ， - C（S） - ， - C = NOH或-CH（R 7） - ，其中R 7 >是氢，羟基，C 1-7烷氧基，-OR 8或-NR 8 R 9（其中R 8是基团-Y 1 R 10（其中Y 1是 -C（O） - ， - C（O）O，-C（O）NR 11 - ， - SO 2 - 或-SO 2 NR 12 - （其中R 11和R 12可以相同或不同，各自独立地表示氢，C 1-3烷基或C 1-3烷氧基C 2-3 - 烷基），R 10如本文所定义，R 9， 包括氢; R 1，R 2和R 3如本文所定义，并且优选为甲基; R 4，R 5和R 6如本文所定义，条件是R“ 5>不是羟基，烷氧基，取代的烷氧基，-OPO 3 H 2，-O-C 1-7烷酰基或苄氧基;及其盐在制备用于在温血动物如人中产生血管损伤作用的药物 本发明还涉及式（I）的化合物，含有它们的药物组合物， 以及使用该化合物在温血动物如人中产生血管损伤作用的治疗方法。 式（I）化合物及其药学上可接受的盐可用于治疗许多疾病状态，包括癌症和类风湿性关节炎。

    USE OF COLCHINOL DERIVATIVES AS VASCULAR DAMAGING AGENTS
    8.
    发明申请
    USE OF COLCHINOL DERIVATIVES AS VASCULAR DAMAGING AGENTS 审中-公开
    将胆碱衍生物用作血管破坏剂

    公开(公告)号：WO99002166A1

    公开(公告)日：1999-01-21

    申请号：PCT/GB1998/001977

    申请日：1998-07-06

    IPC: A61K31/66 ,  A61K31/09 ,  A61K31/135 ,  A61K31/165 ,  A61K31/17 ,  A61K31/18 ,  A61K31/196 ,  A61K31/216 ,  A61K31/27 ,  A61K31/661 ,  A61K31/662 ,  A61P17/06 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07C13/547 ,  C07C217/74 ,  C07C233/23 ,  C07C271/24 ,  C07C275/28 ,  C07C307/02 ,  C07C307/04 ,  C07C307/08 ,  C07C311/07 ,  C07F9/12

    CPC classification number: A61K31/661 ,  A61K31/135 ,  A61K31/165 ,  A61K31/17 ,  A61K31/18 ,  A61K31/196 ,  A61K31/216 ,  A61K31/27 ,  C07C217/74 ,  C07C233/23 ,  C07C271/24 ,  C07C275/28 ,  C07C307/08 ,  C07C311/07 ,  C07C2601/08 ,  C07C2603/32 ,  C07F9/12

    Abstract: Colchinol derivatives of formula (I) wherein R1, R2, R3 and R6 are each independently H, optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, alkanoyl, PO3H2; X is carbonyl (CO), thiocarbonyl (CS), methylene (CH2) or a group CHR4; R4 is OH, O-alkyl or NR8R9; R5 and R7 are each independently H, alkyl, halogen, hydroxy, alkoxy, nitro or amino; R8 is H, optionally substituted alkyl, cycloalkyl, alkanoyl, thioalkanoyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl or arylaminosulfonyl; and R9 is H, alkyl or cycloalkyl and the pharmaceutically acceptable salts, solvates, and hydrates thereof have been found to be useful for treatment of diseases involving angiogenesis. Some of these compounds are novel. Particularly preferred are those compounds in which R6 is PO3H2.

    Abstract translation: 其中R 1，R 2，R 3和R 6各自独立地为H，任选取代的烷基，环烷基，烯基，炔基，芳烷基，烷酰基，PO 3 H 2; X是羰基（CO），硫代羰基（CS），亚甲基（CH 2）或CHR 4基团; R4是OH，O-烷基或NR8R9; R 5和R 7各自独立地为H，烷基，卤素，羟基，烷氧基，硝基或氨基; R 8是H，任选取代的烷基，环烷基，烷酰基，硫代烷酰基，芳基，杂芳基，芳基羰基，杂芳基羰基，烷氧基羰基，芳氧基羰基，氨基羰基，烷基氨基羰基，二烷基氨基羰基，芳基氨基羰基，烷基磺酰基，芳基磺酰基，氨基磺酰基，烷基氨基磺酰基，二烷基氨基磺酰基或芳基氨基磺酰基。 已经发现R9是H，烷基或环烷基，其药学上可接受的盐，溶剂合物和水合物可用于治疗涉及血管生成的疾病。 这些化合物中的一些是新的。 特别优选的是其中R 6是PO 3 H 2的那些化合物。

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