Title:
NOVEL CHLORIN E6 DERIVATIVE AND PHARMACEUTICALLY-ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2018/076526
Kind Code:
A1
Abstract:
Provided are a novel chlorin e6 derivative and pharmaceutically-acceptable salts thereof, a preparation method therefor, and an application thereof, relating to the technical field of pharmacy. The chlorin e6 derivative ether-based amino acid derivative comprises structural general formula I and an optical isomer of the structural general formula I. The preparation method is: etherifying 3-vinyl in chlorin e6, and producing peptide from 15-acetate carboxyl and amino acid. The chlorin e6 derivative ether-based amino acid derivative and pharmaceutically-acceptable salts thereof can be used as anti-tumor drugs of photodynamic therapy. As compared with Talaporfin which is the existing clinically-used photosensitizer, the novel chlorin e6 derivative has advantages of stronger anti-tumor activity and higher dark toxicity-phototoxicity ratio, and can be used for preparing novel anti-tumor drugs of the photodynamic therapy, including caner-treating drugs of photodynamic therapy, drugs for treating benign vascular diseases by the photodynamic therapy such as macular degeneration and nevus flammeus, as well as drugs for treating condyloma acuminate by the photodynamic therapy.
Inventors:
SHANG HUA (CN)
Application Number:
PCT/CN2016/112586
Publication Date:
May 03, 2018
Filing Date:
December 28, 2016
Export Citation:
Assignee:
LIU HUI (CN)
International Classes:
C07D487/04; A61K31/409; A61K41/00; A61P17/00; A61P27/02; A61P31/20; A61P35/00
Foreign References:
| CN1102412A | 1995-05-10 | |||
| CN105384743A | 2016-03-09 | |||
| CN104086554A | 2014-10-08 |
Other References:
FANG, YING ET AL.: "Degradation of Silkworm Excrement Crude Chlorophyll and Synthesis of Chlorin e6 Ether Derivatives", CHINESE JOURNAL OF ORGANIC CHEMISTRY, vol. 15, no. 5, 31 December 1995 (1995-12-31), pages 493 - 498, XP009511980, ISSN: 0253-2786
CHEMICAL ENGINEER, vol. 235, no. 4, 2015, pages 1 - 5
FANG YING ET AL.: "The degradation of silkworm feces chlorophyll and Synthesis of chlorin e6 ether derivatives", ORGANIC CHEMISTRY, vol. 15, no. 5, 1995, pages 493 - 498
XIUHAN GUO ET AL.: "Synthesis of new chlorin derivatives containing maleimide functional group and their photodynamic activity evaluation", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 25, no. 19, 2015, pages 4078 - 4081, XP029264276, DOI: doi:10.1016/j.bmcl.2015.08.036
GUSHCHINA, O. I. ET AL.: "Synthesis of amide derivatives of chlorine e6 and investigation of their biological activity", JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY, vol. 153, 2015, pages 76 - 81, XP029324984, DOI: doi:10.1016/j.jphotobiol.2015.09.007
KWITNIEWSKI, M. ET AL.: "Diamino acid derivatives of PpIX as potential photosensitizers for photodynamic therapy of squamous cell carcinoma and prostate cancer: in vitro studies", JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY, vol. 94, 2009, pages 214 - 222, XP025946731, DOI: doi:10.1016/j.jphotobiol.2008.11.005
SERRA, V. V.: "New porphyrin amino acid conjugates: synthesis and photodynamic effect in human epithelial cells", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18, 2010, pages 6170 - 6178, XP027192861
WANG, H. M.: "Porphyrin with amino acid moieties: a tumor photosensitizer", CHEM. BIOL. INTERACT., vol. 172, 2008, pages 154 - 158, XP022514160, DOI: doi:10.1016/j.cbi.2007.11.016
SMITH, K. M. ET AL.: "Syntheses and cellular investigations of 173-, 152-, and 131-amino acid derivatives of chlorin e6", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, 2011, pages 7464 - 7476
YAO JIANZONG ET AL.: "Synthesis and photosensitizing abilities as well as tumor photobiological activities of Chlorin F methyl ether", ACTA PHARMACEUTICA SINICA, vol. 35, no. 1, 2000, pages 63 - 66
ACTA PHARMACEUTICA SINICA, vol. 39, no. 1, 2001, pages 1 - 4
PANDEY, R. K. ET AL.: "Chlorin and porphyrin derivatives as potential photosensitizers in photodynamic therapy", PHOTOCHEMISTRY AND PHOTOBIOLOGY, vol. 53, no. 1, 1991, pages 65 - 72
MA JIAFU, YAO JIANZONG ET AL.: "Optimization of synthetic process of photosensitizer chlorin e6 by orthogonal experiments", CHINESE JOURNAL OF PHARMACEUTICALS, vol. 40, no. 20, 2005, pages 1589 - 1591
See also references of EP 3683221A4
CHEMICAL ENGINEER, vol. 235, no. 4, 2015, pages 1 - 5
FANG YING ET AL.: "The degradation of silkworm feces chlorophyll and Synthesis of chlorin e6 ether derivatives", ORGANIC CHEMISTRY, vol. 15, no. 5, 1995, pages 493 - 498
XIUHAN GUO ET AL.: "Synthesis of new chlorin derivatives containing maleimide functional group and their photodynamic activity evaluation", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 25, no. 19, 2015, pages 4078 - 4081, XP029264276, DOI: doi:10.1016/j.bmcl.2015.08.036
GUSHCHINA, O. I. ET AL.: "Synthesis of amide derivatives of chlorine e6 and investigation of their biological activity", JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY, vol. 153, 2015, pages 76 - 81, XP029324984, DOI: doi:10.1016/j.jphotobiol.2015.09.007
KWITNIEWSKI, M. ET AL.: "Diamino acid derivatives of PpIX as potential photosensitizers for photodynamic therapy of squamous cell carcinoma and prostate cancer: in vitro studies", JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY, vol. 94, 2009, pages 214 - 222, XP025946731, DOI: doi:10.1016/j.jphotobiol.2008.11.005
SERRA, V. V.: "New porphyrin amino acid conjugates: synthesis and photodynamic effect in human epithelial cells", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18, 2010, pages 6170 - 6178, XP027192861
WANG, H. M.: "Porphyrin with amino acid moieties: a tumor photosensitizer", CHEM. BIOL. INTERACT., vol. 172, 2008, pages 154 - 158, XP022514160, DOI: doi:10.1016/j.cbi.2007.11.016
SMITH, K. M. ET AL.: "Syntheses and cellular investigations of 173-, 152-, and 131-amino acid derivatives of chlorin e6", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, 2011, pages 7464 - 7476
YAO JIANZONG ET AL.: "Synthesis and photosensitizing abilities as well as tumor photobiological activities of Chlorin F methyl ether", ACTA PHARMACEUTICA SINICA, vol. 35, no. 1, 2000, pages 63 - 66
ACTA PHARMACEUTICA SINICA, vol. 39, no. 1, 2001, pages 1 - 4
PANDEY, R. K. ET AL.: "Chlorin and porphyrin derivatives as potential photosensitizers in photodynamic therapy", PHOTOCHEMISTRY AND PHOTOBIOLOGY, vol. 53, no. 1, 1991, pages 65 - 72
MA JIAFU, YAO JIANZONG ET AL.: "Optimization of synthetic process of photosensitizer chlorin e6 by orthogonal experiments", CHINESE JOURNAL OF PHARMACEUTICALS, vol. 40, no. 20, 2005, pages 1589 - 1591
See also references of EP 3683221A4
Attorney, Agent or Firm:
BEIJING AOXIANGLINGZHI PATENT AGENCY CO., LTD (CN)
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