公开(公告)号：US5773460A

公开(公告)日：1998-06-30

申请号：US674247

申请日：1996-07-01

申请人： Louis Gaboury ,  Luc Villeneuve ,  Richard Giasson ,  Tiechao Li ,  Ajay Kumar Gupta

发明人： Louis Gaboury ,  Luc Villeneuve ,  Richard Giasson ,  Tiechao Li ,  Ajay Kumar Gupta

IPC分类号： A61K41/00 ,  C07D311/82 ,  A61K31/35

CPC分类号： C07D311/82 ,  A61K41/0057

摘要： The present invention relates to novel photoactivable rhodamine derivatives for enhancing high quantum-yield production and singlet oxygen generation upon irradiation with light while maintaining desirable differential retention of rhodamine between normal and cancer cells. Representative derivatives are 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid methyl ester hydrochloride; 2-(4, 5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid ethyl ester hydrochloride; 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid octyl ester hydrochloride; 2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride; 2-(6-ethyl amino-3-ethyl imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride; and photoactivable derivatives thereof. These derivatives are utilized in an amount to achieve appropriate intracellular levels of the derivative when irradiation of a suitable wavelength and intensity is applied to photoactivate the derivative and thereby induce cell killing.

摘要翻译： 本发明涉及用于在照射光时提高高量子产率产生和单线态氧产生的新型可光致发光罗丹明衍生物，同时保持罗丹明在正常癌细胞与癌细胞之间的期望差异保留。 代表性的衍生物是2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸甲酯盐酸盐; 2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸乙酯盐酸盐; 2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸辛酯盐酸盐; 2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸正丁酯盐酸盐; 2-（6-乙基氨基-3-乙基亚氨基-3H-呫吨-9-基） - 苯甲酸正丁酯盐酸盐; 和其可光活化的衍生物。 当照射适当的波长和强度以光激活衍生物并由此诱导细胞杀伤时，这些衍生物用量达到适当的细胞内水平的衍生物。

公开(公告)号：US5556992A

公开(公告)日：1996-09-17

申请号：US300179

申请日：1994-09-02

申请人： Louis Gaboury ,  Luc Villeneuve ,  Richard Giasson ,  Tiechao Li ,  Ajay K. Gupta

发明人： Louis Gaboury ,  Luc Villeneuve ,  Richard Giasson ,  Tiechao Li ,  Ajay K. Gupta

IPC分类号： A61K41/00 ,  C07D311/82

CPC分类号： C07D311/82 ,  A61K41/0057

摘要： The present invention relates to novel photoactivable rhodamine derivatives for enhancing high quantum-yield production and singlet oxygen generation upon irradiation with light while maintaining desirable differential retention of rhodamine between normal and cancer cells, said derivatives are selected from the group consisting of 4,5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid methyl ester hydrochloride); 4, 5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid ethyl ester hydrochloride); 4, 5-dibromorhodamine 123 (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid octhyl ester hydrochloride); 4,5-dibromorhodamine 110 n-butyl ester (2-(4,5-dibromo-6-amino-3-imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride); Rhodamine B n-butyl ester (2-(6-ethyl amino-3-ethyl imino-3H-xanthen-9-yl)-benzoic acid n-butyl ester hydrochloride); and photoactivable derivatives thereof; whereby photoactivation of the derivatives induces cell killing while unactivated derivatives are substantially non-toxic to cells. Also, the present invention relates to the use of the photoactivable derivatives of the present invention for the photodynamic therapy of a cancer patient by destroying human cancer cells, wherein appropriate intracellular levels of the derivatives are achieved and irradiation with light of a suitable wavelength is applied. The present invention also relates to a method for the photodynamic therapy of a patient suffering from leukemias, disseminated multiple myelomas or lymphomas.

摘要翻译： 本发明涉及用于在照射光时增强高量子产率产生和单线态氧的新型可光致发光罗丹明衍生物，同时保持罗丹明在正常癌细胞与癌细胞之间的期望差异保留，所述衍生物选自4,5- 二溴罗丹明123（2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸甲酯盐酸盐）; 4,5-二溴罗丹明123（2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸乙酯盐酸盐）; 4,5-二溴罗丹明123（2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸辛酯盐酸盐）; 4,5-二溴罗丹明110正丁基酯（2-（4,5-二溴-6-氨基-3-亚氨基-3H-呫吨-9-基） - 苯甲酸正丁酯盐酸盐）; 罗丹明B正丁酯（2-（6-乙基氨基-3-乙基亚氨基-3H-呫吨-9-基） - 苯甲酸正丁酯盐酸盐）; 及其可光活化衍生物; 由此衍生物的光活化诱导细胞杀伤，而未活化的衍生物对细胞基本上无毒性。 此外，本发明涉及本发明的可光反应衍生物在癌症患者的光动力治疗中的用途，其通过破坏人类癌细胞，其中实现了衍生物的适当的细胞内水平并且适用于适当波长的光的照射 。 本发明还涉及一种患有白血病，弥散性多发性骨髓瘤或淋巴瘤的患者的光动力疗法的方法。