公开(公告)号：US20060111389A1

公开(公告)日：2006-05-25

申请号：US11157977

申请日：2005-06-22

申请人： Stephen Neidle ,  Richard Harrison ,  Lloyd Kelland ,  Sharon Gowan ,  Martin Read ,  Anthony Reszka

发明人： Stephen Neidle ,  Richard Harrison ,  Lloyd Kelland ,  Sharon Gowan ,  Martin Read ,  Anthony Reszka

IPC分类号： C07D219/04 ,  A61K31/473

CPC分类号： C07D219/08 ,  C07D219/06 ,  C07D219/10

摘要： The present invention pertains to acridone and acridine compounds of formula (I), wherein either: (a) K is ═O, L is —H, alpha is a single bond, beta is a double bond, gamma is a single bond (acridones): or, (b) K is a 9-substituent. L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond and wherein: J1 is a 2- or 3-substituent; J2 is a 6- or 7-substituent; J1 and J2 are each independently a group of the formula —NHCO(CH2)nNR1R2, wherein: n is an integer from 1 to 5; and, R1 and R2 are independently hydrogen, C1-7alkyl, C3-20heterocyclyl, or C5-20aryl, or R1 and R2, taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 3 to 8 ring atoms; and wherein, when K is a 9-substituent, K is a group of the formula —N(RN)Q, wherein: RN is an amino substituent and is hydrogen. C1-7alkyl, C3-20heterocyclyl, or C5-20aryl; and, Q is C1-7alkyl, C3-20heterocyclyl, or C5-20aryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo to inhibit telomerase, to regulate cell proliferation, and in the treatment of proliferative conditions, such as cancer.

摘要翻译： 本发明涉及式（I）的吖啶酮和吖啶化合物，其中：（a）K是-O，L是-H，α是单键，β是双键，γ是单键（吖啶酮 ）：或（b）K为9-取代基。 L不存在，α是双键，β是单键，γ是双键，并且其中：J 1是2-或3-取代基; J 2是6-或7-取代基; J 1和J 2各自各自独立地是式-NHCO（CH 2 CH 2）n NR n的基团， 其中：n为1至5的整数;其中n为1至5的整数; 且R 1和R 2独立地为氢，C 1-7烷基，C 3-20杂环基 或C 5-20-20芳基或R 1和R 2与它们所连接的氮原子一起形成一个 具有3至8个环原子的杂环; 并且其中当K是9-取代基时，K是式-N（R“N”）Q的基团，其中：R N是氨基取代基，并且是 氢。 C 1-7烷基，C 3-20杂环基或C 5-20-20芳基; 且Q为C 1-7烷基，C 3-20杂环基或C 5-20芳基，且为任选取代的; 和其药学上可接受的盐，酯，酰胺，溶剂合物，水合物及其保护形式。 本发明还涉及包含这种化合物的药物组合物，以及这些化合物和组合物在体外和体内都用于抑制端粒酶调节细胞增殖以及治疗增殖性疾病如癌症的用途。

公开(公告)号：US20050070568A1

公开(公告)日：2005-03-31

申请号：US10501474

申请日：2003-01-14

申请人： Stephen Neidle ,  Richard Harrison ,  Lloyd Kelland ,  Sharon Gowan ,  Martin Read ,  Anthony Reszka

发明人： Stephen Neidle ,  Richard Harrison ,  Lloyd Kelland ,  Sharon Gowan ,  Martin Read ,  Anthony Reszka

IPC分类号： A61K31/473 ,  A61P35/00 ,  A61P43/00 ,  C07D219/04 ,  C07D219/08 ,  C07D219/10 ,  C07D219/12

CPC分类号： C07D219/08 ,  C07D219/10

摘要： This invention pertains to certain acridine and acridine compounds of the formula (1) which inhibit telomerase, regulate cell proliteration, etc., and/or treat cancer proliferative conditions, etc.: wherein either: (a) K is ═O, L is —H, alpha single bond beta is a double bond, gamma is a single bond (acridines); or, (b) K is a 9-substituent, L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond (acridines); and wherein: J1 is a 2- or 3-substituent; J2 is a 6- or 7-substituent; J1 and J2 are each a group of the formula —N(RN)—W, wherein: RN is a nitrogen substituent and is hydrogen, C1-7alkyl, C3-20 heterocyclyl, or C5-20aryl, and is optionally substituted; and, W is C1-7alkyl, C3-20heterocyclyl, or C5-20aryl, and is optionally substitute; and wherein when K is a 9-substituent, K is a group of the formula —N(RN)-Q, wherein: RN is an amino substituent and is hydrogen, C1-7alkyl, C3-20heterocyclyl, or C5-20aryl; and, Q is C1-7alkyl, C3-20heterocyclyl, or C5-20aryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, etc., and/or in the treatment of cancer, proliferative conditions, etc.

摘要翻译： 本发明涉及抑制端粒酶，调节细胞增殖等的某些式（1）的吖啶和吖啶化合物，和/或治疗癌症增殖病症等。其中：（a）K为= O，L为 -H，α单键β是双键，γ是单键（吖啶）; 或（b）K是9取代基，L不存在，α是双键，β是单键，γ是双键（吖啶）; 并且其中：J 1是2-或3-取代基; J 2是6-或7-取代基; J 1和J 2各自为式-N（R N）-W的基团，其中：R N为氮取代基且为氢，C 1-7烷基，C 3-20杂环基， 或C 5-20芳基，并且任选被取代; 并且W是C 1-7烷基，C 3-20杂环基或C 5-20芳基，并且任选被取代; 并且其中当K是9-取代基时，K是式-N（R N）-Q的基团，其中：R N是氨基取代基并且是氢，C 1-7烷基，C 3-20杂环基， 或C5-20芳基; 且Q为C 1-7烷基，C 3-20杂环基或C 5-20芳基，并且任选被取代; 和其药学上可接受的盐，酯，酰胺，溶剂合物，水合物及其保护形式。 本发明还涉及包含这种化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途，以抑制端粒酶，调节细胞增殖等，和/或治疗癌症，增殖性 条件等