公开(公告)号：US07557215B2

公开(公告)日：2009-07-07

申请号：US10596783

申请日：2004-12-22

申请人： Laurence Hylton Patterson ,  Klaus Pors ,  Paul Henry Teesdale-Spittle

发明人： Laurence Hylton Patterson ,  Klaus Pors ,  Paul Henry Teesdale-Spittle

IPC分类号： C07D211/00 ,  C07D207/04

CPC分类号： C07D207/08 ,  C07D207/06 ,  C07D207/10 ,  C07D207/12 ,  C07D207/46 ,  C07D211/18 ,  C07D211/22 ,  C07D211/38 ,  C07D211/46 ,  C07D211/94

摘要： Anthraquinone compounds of the general formula (I) or a salt thereof (Formula I) in which R1 to R4 are each selected from the group consisting of H, C1-4 alkyl, X1, —NHR0N (R5)2 in which R0 is a C1-12 alkanediyl and each R5 is H or optionally substituted C1-4 alkyl, and a group of formula (II) in which at least one of R6, R7 and R8 is selected from X2, and X2 substituted C1-4 alkyl and any others are H or C1-4 alkyl; R9 is selected from H, C1-4 alkyl, X2 and X2 substituted C1-4 alkyl; m is 0 or 1; n is 1 or 2; X1 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; and X2 is a halogen atom, a hydroxyl group, a C1-6 alkoxyl group, an aryloxy group or an acyloxy group; provided that at least one of R1 to R4 is a group of formula (II). The N-oxides are useful prodrugs which are selectively bioreduced in hypoxic tumours to the corresponding cyclic amine derivatives. The amine compounds are cytotoxic and may be used as alkylating agents having topoisomerase II inhibiting activities in cancer therapy.

摘要翻译： 通式（I）的蒽醌化合物或其盐（式I）其中R 1至R 4各自选自H，C 1-4烷基，X 1，-NHRO N（R 5）2，其中R 0为 C 1-12烷二基，每个R 5为H或任选取代的C 1-4烷基，以及其中R 6，R 7和R 8中的至少一个选自X 2，以及X 2取代的C 1-4烷基和任何 其余为H或C 1-4烷基; R 9选自H，C 1-4烷基，X 2和X 2取代的C 1-4烷基; m为0或1; n为1或2; X1是卤素原子，羟基，C1-6烷氧基，芳氧基或酰氧基; X2是卤素原子，羟基，C1-6烷氧基，芳氧基或酰氧基; 条件是R 1至R 4中的至少一个为式（II）的基团。 N-氧化物是有用的前药，其在缺氧肿瘤中选择性地生物还原成相应的环胺衍生物。 胺化合物是细胞毒性的，并且可以用作在癌症治疗中具有拓扑异构酶II抑制活性的烷化剂。

公开(公告)号：US20070208085A1

公开(公告)日：2007-09-06

申请号：US11655043

申请日：2007-01-17

申请人： Agamemnon Epenetos ,  Klaus Pors ,  Paul Smith ,  Laurence Patterson

发明人： Agamemnon Epenetos ,  Klaus Pors ,  Paul Smith ,  Laurence Patterson

IPC分类号： A61K31/137

CPC分类号： A61K31/137

摘要： The present invention generally relates to chemotherapeutic treatment of proliferative disorders, such as cancer. The invention more specifically relates to inhibition of pan-cell cycle progression with alkylating anthraquinones, which may inhibit mitotic commitment, lead to limited expression of G2 arrest and force cells to enter polyploidy via an aberrant mitosis. The methods of the invention are particularly useful in the treatment of chemotherapy-resistant cancers.

摘要翻译： 本发明一般涉及增生性疾病如癌症的化学治疗。 本发明更具体地涉及用烷基化蒽醌抑制泛细胞周期进程，其可抑制有丝分裂承诺，导致G2阻滞的有限表达，并且通过异常有丝分裂使强制细胞进入多倍体。 本发明的方法在化疗耐药性癌症的治疗中特别有用。