13903
2011 2012
23659052
High Energy Materials for Cancer Drugs: A Novel Mechanism of Action
SHIBATA NORIO
40293302
Designed and synthesis of a novel anti-cancer agent,
trifluoroethoxyphthalocyanine-aminotetrazole conjugate (TFEO-Pc-AT) is described. The
target compound was synthesized nicely by the use of copper-catalyzed Click-reaction of
1-(2-azidoethyl)-5-aminotetrazole and phthalocyanine containing terminal alkyne as a key
step. TFEO-Pc-AT showed excellent photodynamic activities against B16-F10 murine
melanoma upon illumination with a 660 nm laser, while no cytotoxicity of TFEO-Pc-AT was
observed without illumination.
2,900,000
1981
PDT
870,000
3,770,000
Angew. Chem.
2006, 45 8163
Int. Ed
Eur. J. Org. Chem.
2010, 15, 2878
F3 CH 2 CO
OCH2 CF 3
F 3 CH2 CO
OCH2 CF3
OCH 2CF3
N
F 3CH2 CO
N
F 3CH2 CO
N
F 3 CH2 CO
PDT
N
M
N
N
N
O
N
F 3 CH2 CO
NH
OCH2 CF 3
F3 CH 2 CO
OCH2 CF3
1a
OCH2 CF3
OCH2 CF 3
F3CH 2CO
F 3CH2 CO
1000
N
N
F 3CH2 CO
40
N
N
F3CH2 CO
60
OCH2 CF 3
N
N
F3 CH 2CO
OR
OCH2CF 3
N
M
O
O
OCH2 CF 3
N
F 3 CH2 CO
N
RO
OCH2 CF3
RO
M: Zn, Vo
R=H, TBDMS, p-Tol
NHAc
N
O
OR
N
N
N
1b
PDT
II
7-800nm
5Shreeve
PDT
Klapötke
Shreeve, J. M. et al. Angew. Chem. Int.
Ed. 2010, 49, 7320.; Klapötke et al Helv.
Chim. Acta 2007, 90, 2132.
Shreeve
N
NH
N N
Drug
Ener get ic mater ials
tetrazole ring
H2 N
H
N
F3 CH 2CO
N
n-Bu
N
N
HN
N
N N
Cl
N N
5-Aminotetrazole
Losartan
F3 CH 2CO
NH 2
N
N NO2
OH
OCH2 CF 3
OCH2 CF3
N
Zn
F3CH 2CO
HN
NH
N N
Nitoroimino-tetrazole
N
N
N
F3 CH2 CO
N
N
N
N 3 CuI
DMF, 80 C
OCH 2CF3
F3CH 2CO
OCH2 CF 3
F 3CH2 CO
F3 CH 2CO
OCH 2CF3
OCH 2CF3
OCH2 CF 3
OCH2 CF3
N N
N
F3 CH 2CO
N
F3CH 2CO
N
Zn
N
N
F3 CH2 CO
F3CH 2CO
NH2
N
N
N N
OCH 2CF3
OCH2 CF 3
F 3CH2 CO
OCH 2CF3
OCH 2CF3
PDT
in vitro
2.0×104
B16F10
DMSO
40
1000
MTT
660 nm
40
60
PDT
50
700nm
30
2.00
2013
M&D
19
21
650nm
720nm
0.15
http://www.ach.nitech.ac.jp/~organic/sh
ibata/index.html
(1)
SHIBATA NORIO
40293302
92
(2012) 2012
25 28
(2)
(3)
58
2012
Satoru Mori, Etsuko Tokunaga, Norio
Shibata, Synthesis and Bioactivity of
Trifluoroethoxy-coated
Phthalocyanine
Linked with 5-Aminotetrazole, 20th
International Symposium on Fluorine
Chemistry, 2012 July 22-27, Kyoto
Satoru Mori, Etsuko Tokunaga, Norio
Shibata,
Synthesis
and
Biological
Activity of 5-Aminotetrazole derivative,
the 6th Takeda Science Foundation
symposium
on
pharmascience,
2012
September 13-14, Osaka
2012
38
11
11
28
30
2012
30