JPH03284681A - Porphyrin derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula [R1 is -CH=CH2 or-CH2-CH2-OR (R is H or -COCH3); R2 is -CHO, CH3, NO2 or halogen; M is 2H or metal]. USE:The compound has activities such as accumulation to cancer cell, reactivity stimulated by external energy, destruction of cancer cell, etc., and is free from toxicity to normal cell. Accordingly, it is useful as a remedy and diagnostic for cancer. PREPARATION:The objective compound can be produced by using methyl pheophorbide as a starting raw material, producing a chlorin trimethyl ester having R1 group, introducing CHO group, NO2 group or halogen to the meso site of the ester compound, modifying the resultant formyl porphyrin compound to methyl group, partially hydrolyzing the obtained trimehyl ester derivative of the meso-modified porphyrin, subjecting the resultant meso-modified porphyrin dimethyl ester to the substitution reaction at delta-meso site and partially hydrolyzing the product with an acid.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application The present invention relates to a novel cancer-directing preparation containing a porphyrin derivative as an active ingredient and used for cancer treatment, diagnosing, marker, and missile therapy.

(b) Prior Art In 1924, P. Oliard reported that porphyrin derivatives selectively accumulate in cancer tissues and emit fluorescence. Since then, many researchers have attempted to develop new therapeutic agents for cancer using the properties of this compound.

Porphyrin is a general term for compounds whose basic skeleton is porphine (I), which is a cyclic compound in which four virol rings are bonded by a methine group, and which are obtained by substituting surrounding hydrogen atoms.

(I) Porphine (I) forms the basic skeleton of hemin in hemoglobin. Among the four virol rings, chlorin (2), in which one bond at the 3° and 4-positions is saturated, is the basic skeleton of chlorophyll in chlorophyll. Bacteriochlorin (3), in which two saturated reduced virols face each other, is the basic skeleton of bacteriochlorophyll present in photosynthetic bacteria.

(2) (3) Synthetic porphyrins include tetraphenylporphyrin (TPP) substituted with phenyl groups at four meso positions and eight virol β
Octaethylporphyrin substituted with an ethyl group (
OEP), TPP and OE, P are easy to synthesize, dissolve well in organic solvents, have a simple structure and good symmetry, are close to natural porphyrins, and are classified as phthalocyanines (PC) (4), which are classified as azaporphyrins. ) is also easy to synthesize and has been known for a long time.

(4) Metal porphyrins, which are metal complexes of these porphyrins, also exist.

For blood-derived porphyrin derivatives, HPD (pho
tofrin I■1. D HE (photofr
inll■), quaternary ammonium salt-supported porphyrin derivatives (JP-A-62-167783, 62-20508
No. 2, No. 63-145283), etc. are disclosed.

As a result of various researches, we have discovered metal porphyrin compounds (Japanese Patent Laid-Open No. 61-83185) and porphyrin compounds with groups capable of forming metal chelates (Patent Publication No. 63-83).
-13997), porphyrin amino acid derivatives with iodine-labelable groups and fluorine-containing groups (JP-A-64-61481), which can be used for o and photochemical therapy, cause specific hemorrhagic necrosis, and can be used for NMR imaging. Alkoxy metal porphyrin amino acids that can be used as agents! A derivative (Special II Hei 0X-146615) was discovered.

On the other hand, regarding chlorophyll-derived porphyrin derivatives, pheophobite derivatives (Japanese Patent Application Laid-Open No. 57-185220)
, Burpurin derivatives (JP-A-63-290881) and chlorin derivatives (JP-A-62-5912, 62-
No. 5924, No. 62-5985, No. 62-5986), etc. are disclosed.

As a result of various studies on pheophobite derivatives, we found that hydroxyl group-carrying pheophobite derivatives
92287), hydroxyl group-carrying dimeric pheophobite derivatives (JP-A No. 61-7279), metal pheophobite derivatives' (JP-A No. 61-83185), pheophorite derivatives with groups capable of forming metal chelates. We have discovered a batate derivative (Japanese Patent Publication No. 13997/1982) and a batateryophobide derivative (Japanese Patent Application Laid-open No. 196586/1986).

In addition, for synthetically derived porphyrin derivatives, one ego-tetrakis (
4-sulfonatophenylporphyr
in (TPPS), meso-tetrak
is (4-N-methylpyridyl po
Men-substituted porphyrin derivatives such as rphyrin (TMPyP) have been disclosed.

On the other hand, although the purpose is different from the above, Collman et al. [JA
C.S.,,103. lS&(I9δ1)] synthesizes a dimer compound by introducing a substituent at the men's position. Also,
KM, Smlth et al. [J, Org, Che-,
45, 2218 (I9801) synthesizes δ-meso-substituted chlorin ea trimethyl ester from methylpheophobite.The purpose of this study is the partial synthesis of methylbacteriopheophobite C and d.

(c) Problems to be Solved by the Invention As mentioned above, the affinity of porphine and chlorin derivatives to cancer has been extensively studied. However, the meso-substituted porphyrin derivatives whose relationship with cancer is currently being studied are compounds with a phenyl group or pyridyl group introduced at the meso position, and no other substituents have been found. There is a need to develop novel men-substituted porphyrin compounds for missile therapy.

(d) Means for solving the problem Chlorin compounds, which are pheophobite derivatives, are more water-soluble than the starting material pheophobite, and can be converted into various substituents, leading to more active derivatives. can. Then, the vinyl group at position 2 is converted into an alcohol form (primary alcohol), eliminating the asymmetric center, and lI! By avoiding the compound to become a mixture of stereoisomers and introducing various functional groups such as CHOCl and NOl at the δ meso position, the absorption wavelength can be made longer and the affinity for cancer is increased. I also found out that it can be done.

Also, the trimethyl ester form of chlorin e is not water-soluble, while chlorin e itself, which is a hydrolyzate of this trimethyl ester form, is highly water-soluble! ! One of the applicants, which has poor affinity, is chlorin e substituted at the δ meso position.
, a derivative, water-soluble, and 1! As a result of further research in search of a compound with high affinity, the 2-position of chlorin e substituted at the δ-meso position was changed to Of(!), and the 7-position obtained by partial hydrolysis of one of the trimethyl esters became an M-free carboxylic acid. , 6.γ
It has been found that the porphyrin having the above-mentioned properties can be obtained if the position is a dimethyl ester chlorin derivative.

The properties of the present porphyrin derivatives do not essentially change even when combined with other active substances or when combined with other external energies.

The gist is formula (I) (In the formula, R4 is =CH=CH* or CH* -CHx OR.

R1 is =CHO, -CHl-No, or halogen.

R is -H or -COCH.

M exists in a porphyrin compound represented by 2H or a metal).

The word "metal" used in connection with the meanings of the above symbols includes atomic numbers of 12 or higher, preferably atomic numbers of 23 to 85 (eg, Mn, Fe, Co, Ni).

Cu, Zn, Ga, Ge, In).

The porphyrin compound (I) of the present invention is a new substance,
It can be produced in a conventional manner, usually by first constructing a chlorine trimethyl ester having R using methylpheophobite as a starting material, and then introducing a COO group, NO1 group or a halogen into the men position. (Step B), and further modify the obtained formylporphyrin compound with a methyl group (Step C), and partially hydrolyze the trimethyl esters of these men-position-modified porphyrin compounds to obtain men-position-modified porphyrin. obtaining a dimethyl ester compound (step d), and
It is not necessarily necessary to react steps (a), (b), (c), and (d) sequentially, and the order of the steps may be changed depending on the case.

Configuration step (a) Hani, M, Sm1th, etc. CBiorg,
Cbes, 9.1 (I980): J, Org, Ch.
es+, 45.2218 (I9801] and J.E.
Fa1. Written by [Porphyrins and Meta
This can be done by conventional methods, such as those described in J.D. lloporphyrins] (Elsevier, 1975). That is, for step (a), it is sufficient to introduce R into the R1 side chain of the porphyrin compound (I), and to obtain the primary alcohol (-CH=C)l,OH), TI(NO,) must be introduced in advance. It is preferable to prepare an acetal derivative of the porphyrin compound (I) using the above-described method, and to proceed with the reaction using a reducing agent such as sodium borohydride (NaBH).

The chlorin e a trimethyl ester compound thus constituted is then subjected to a substitution reaction at the δ meso position (step b), that is, a CuO group, NOs group, or a halogen is introduced at this meso position to form a chlorin e a substituted at the δ meso position. , to produce trimethyl ester. Furthermore, a compound obtained by converting the obtained formylporphyrin compound into a methyl group is synthesized (step C).These substances are synthesized according to the method described in the literature mentioned in step a! The obtained meso-substituted chlorin e, trimethyl ester is partially acid-hydrolyzed in step d to produce meso-modified chlorin e, dimethyl ester compound (I), which is the substance of the present application.
) instead of artificially synthesizing them, they may be harvested from natural sources such as plants and animals.

Specific examples include the following compounds.

(I) Chlorin e, trimethyl ester [hereinafter referred to as Chlo
rir+ (OMe)s] (2) 2-(2-hydroxyethyl)-2-devinylchlorin ea trimethyl ester [hereinafter referred to as 20H-Ch l or in (
312-(2-acetoxyethyl)-2-devinylchlorin es trimethyl ester [hereinafter referred to as 20AC-Chlorin (OMe)s] (4) Cυ δ-formyl-2-(2- hydroxyethyl)-2-devinylchlorin es) dimethyl ester below Cu 8CHO-20H-Ch l or
i in (OMe)s] (5) δ-formyl-
2-(2-hydroxyethyl)-2-devinylchlorin e a trimethyl ester [hereinafter δCHO-20H
-Chlorin(OMe)s] (6) δ-Methyl-2-(2-hydroxyethyl)
-2-Devinyl chlorin e11 trimedel ester E or less δMe-20H-Chlorin (OMe)
(7) δ-chloro-2-(2-hydroxyethyl)-
2-Devinylchlorin ea trimethyl' ester [hereinafter referred to as δC1-C1-20H-Chlorfn (Oj)] (8) δ-nitro-2-(2-hydroxybutyl)-
2-devinylchlorin es trimethyl ester [hereinafter referred to as δNow-20H-Chlorirn(OMe)s] (9) Chlorin ea [hereinafter referred to as Chlorin]! 1012-(2-hydroxyethyl)-2-devinylchlorin e, 6. γ-dimethyl ester [hereinafter 20
B-Ch 1 or in (OMe)x] (I1) δ-formyl-2-(2-hydroxyethyl)-2-devinylchlorin e, 6. γ-dimethyl ester [hereinafter δCHO-20H-Chlorin (OM
e) x] (I2) δ-methyl-2-(2-hydroxyethyl)-2-devinylchlorin e, 6. γ-
Dimethyl ester L or less δMe-20H- Ch l O! -i n (OMe)*] (I3
) δ-chloro-2-(2-hydroxyethyl)-2-
Devinylchlorin e, 6. γ-dimethylgostyl [hereinafter referred to as δC1-20H-Chlorin (OMe)*] (I4) δ-nitro-2-(2-hydroxyethyl)-2-devinylchlorin e a 6 , γ-dimethyl ester [ Hereinafter, δNO, -20H-Ch l or in (OMe
)z] (e) Effect The porphyrin compound (I) according to the present invention has -C)(O group, NO8 group, CH,
group, halogen, avoiding complete hydrolysis of the trimethyl ester and partially hydrolyzing only the methyl ester at the 7-position; 6. Because it has a chemical structure characterized by the fact that dimethyl ester remains at the γ-position, it exhibits various physiological and pharmacological properties. Based on these properties (cancer affinity and cancer destruction through a combination of external energy), the porphyrin derivatives of the present invention are particularly useful as therapeutic agents, diagnostic agents, markers, mizyle therapeutic agents, etc. for cancer and malignant tumors.

(f) Examples The pharmacological effects and manufacturing method of the substance of the present application will be explained below using examples.

Example l Determination of cell killing effect by light irradiation (iri vitro
) 1X10' HGC-27 cells (Irn 1 ) were placed in a Vetri dish (3.5 cm) and cultured for 2 days. Each drug was prepared at various concentrations, added to the Vetri dish, incubated for 30 minutes, and washed with phosphate buffer. After leaving it for 2-3 minutes c
old 5pot PICL-5X (halolHe
5 minutes ago (5, δmW/as
s") was irradiated with light.2 The light irradiation was performed by cutting off wavelengths of 600 nm or less.2 Afterwards, the cells were cultured for 48 hours and the number of viable cells was counted. As a control, a sample was prepared in which the light was blocked with aluminum foil during the light irradiation. The photocell destruction effect was ID.

(50% cell proliferation brightness rate).

Table 1 shows the log 1/ID5o value (log
1/M+, the graphs of which are shown in Figures 1-6.

As is clear from the table and figure, the inhibition rate was higher than that of the control group, especially 20H- Ch I or i rr (OMe) (I0).
8 and δMe-Chlorin (OMe) (I
2) had a strong effect.

Table 1 Compound light irradiation No light irradiation +91 5.88 4
．． 97 (I0) 7.28
6.24+111 5.85
5.69 (I2)
F, 14 6. X9f13)
6.36 6.10 (I
416,645,98 Example 2 Chlorin (OMe) (I)+5 and 20
H-Chiorin (OMe) (2) was synthesized by the method of Sm1th et al. described above for methylpheophobite.

Example 3 2 obtained in Example 2 was acetylated with pyridine-acetic anhydride according to a conventional method, and 20AC-Ch 1 or
i in (OMe) (3) was obtained.

Nuclear magnetic resonance spectrum (CDCI, ) 15 pp-: 1.71f3H,t), 1.73
(3B, dl, 1.75-2.56 f4Hml, 2
．． 06 (31(, s, 2-0^c1.3.31fH1
,s), 3.39(3+(,sl, 3.57(3H,s
), 3.63 (3F1.sl, 3.7643H, sl.

3.78(2)1. ql, 4.20 (2F1.tl, 4
．． 25 (3B, sl, 4.37-4.45i211.m
), 4.77i2)1. tl, 5.22 (IH, d),
5.34(I11, dl, 8.69(I1(, s, δ-
1(I,9,44i1F(,sl,9.69(eye 1.s
) Mass spectrum (E I-MS) ψ: 698 (M”).

Elemental analysis (as Cs5H4J-Oa) Theoretical value: C,
67, (+3+ 8,6.63; N, 8. (I1%.

Actual value: C, 66, 68+ 1+, 6.65. N,
7. ! 14% 4 Example 4 3 (575 mg1) obtained in Example 3 was dissolved in dichloromethane, and Cu(OAc) was made into a copper complex with a saturated methanol solution. After purifying this tR complex with an alumina column, it was purified with dimethylformamide and POC1. Perform the Wilmsmeier reaction using Cu δCHO-20H-Chlo
rin(OMe) (4) was obtained.

After demetalizing the obtained 4 with concentrated HgSO4,
%Hm SO4 Make methyl ester with methanol solution and recrystallize with dichloromethane-methanol.
δ CHO-20H-Ch 1 or i
n(OM e ) (5) (87 mg) was obtained. mp, 119°C.

Yield 15%.

Nuclear magnetic resonance spectrum (CDC1,) δ ppm: 1.46f3H, dl, 1.63f3H
, t, 1.1.58-2.64 (411, ml, 3.
+5 (3H, sl, 3.22 (3H, s), 3.38 (
31'1. s).

3.65 (3H, sl, 3.50-4.70 (511!)
, m), 3.74f2H, ql.

3,81 (3H,s), 4.21 (31i,s)
, 4.90 (IH, d), 5.05flLd1.
5.2[1(I11,s+1.9.30(lH,sl,
9.33flH,sl, 11.66(IH,s, δ
-CI (01.

Visible absorption maximum (CMC1,) n* (t, l: 414 (I12,0001,51
0(9,4001°547f12.8003G94(3
8□aOO).

Mass spectrum (EI-MS) L: 61!14 (kl”).

Elemental analysis (CmmH-48-Da) Theoretical value: C
,66,22,H,6,45,N,IS,13%.

Actual value: C, 65, 94: ■, 6.33. N.7.
96%.

Example 5 5 (390-g) obtained in Example 4 was dissolved in acetic acid, a NaBHa vinegar solution was added, and the mixture was allowed to react for 10 minutes.

After the reaction, the mixture was poured into saturated brine, extracted with chloroform, and concentrated. The residue was treated with trifluoroacetic acid and BISO4, converted into a methyl ester with 5% BISO4 methanol solution, and subjected to silica gel column chromatography to obtain δMe.
-208-Ch 1 or in (OMe) (
6) (33s+g) was obtained. Yield 21%.

Nuclear magnetic resonance spectrum (CDC1*) δ pp-
: 1.54 (3B, d), 1.60 (3B, t),
1.60~2.57 (4H41,3,29(3H,s
), 3.45f3B,s), 3.53(3f1.s).

3,61 (3H,s), 3.76 (2Lq)
, 3.83 f3H,s), 3': 84(3
B, s), 4.13-4.31 (5H, s+], 4.2
4(3)1. sl, 4.57f1. H, ql, 4.98
(lH, d), 5.27flt1. dl, 9.43 (I
H, sl, 9.54 (lB, sl.

Visible absorption maximum (CHCI Hatake) nm (E): 406ft32.0 [101
510l50.0001゜531Sf6.700J, 6
66137.800).

Mass spectrum (EI-MS) ψ: 670FIII”).

Elemental analysis (as C15H4, N40.) Theoretical value: C
, 68,04: H, 6,918N, 8.35% Actual value: C, 67,93: H, 7,01: N, 8.17
%.

Example 6 To the chloroform solution of 3 (I00sig) obtained in Example 3, add concentrated CI and 5% HO, and stir vigorously for 5 hours to react. After treating the 0 reaction solution, 5% H ，
It was made into a methyl ester with S04 methanol solution and subjected to silica gel column chromatography to obtain δ(I-20H-Ch
lorin (OMe) (7)f44mg) was obtained. Yield 40%.

Nuclear magnetic resonance spectrum (CDC1,) δ ppm: 1.65f3H,d), 1.69(3H
,t), 1.59-2.59 (4) 1, ml, 3
．． 28 (3)1. sl, 3.54 (31(,
s), 3.56 (3H, s).

3.63 (3H, sl, 3.73 (2H, Ql, 3.8
3 (3R, sl, 4.16-4.32 (5B4), 4.
25 (3H, s), 4.87flH, ql, 5.09:
2H,aj,S,3XiXR,di,9.52i)H,
sl, 9.60 (IW,,s) Visible absorption maximum (CHC
1s ) nm It, ): 4O4(I34,0001,5
07 (I3, δOO).

536fIO, 2001, 612 (6,00O1,66
7+51.0001° mass spectrum (EI-MS) ψ: 690 fM”).

Elemental analysis (CS TeB,,N,0C1) Theoretical value: C, 64, 29: B, 6.27: N, g, 1
1%.

Actual measurement value: C, 64, 29: t'1.6.28: N
, 7.89%.

Example 7 3 (330 mg) obtained in Example 3 and Tl(NO
, ) s tetrahydrofuran droplet was heated for 5 minutes,
After cooling, the reaction solution was treated with SO and gas. After the treatment, the 0 reaction solution was converted into a methyl ester with 5% HwSOa methanol solution, and subjected to silica gel column chromatography to obtain 6Now-20.
H-Chforir+ (OMe) (8) [45mg
I got 1. Yield 13%.

Nuclear magnetic resonance spectrum (CDC1,) δ ppm: 1.54f31'1. dl, 1.6
9 (3B, t), 1°75~2.61 (4fls),
3.17f3H,sl,3.27(31(,sl,3.
54f3R,s).

3.62 (3R, sl, 3.73 (2H, q), 3.8
3 (3H, s), 4.14-4.39 (5B, -), 4
．． 26 (3B, sl, 4.63 (I11, ql, 5.1
0HH, d), 5.31 (]H, d), 9.64f
lH, sl, 9.56 (I11, s) visible absorption maximum (
CHCli nm (εl: 398 (I20,000), 500 (I
0,9001°531 (6,000), 66B+46.
6001° Mass spectrum (E I-MS) ψ: 7 (N (M”) Elemental analysis (as C5yH4sNios) Theory @: C
, 63,33: H, 6,18: N, 9.98%.

Actual value: C, 63, 13+ ++, 6.19: N, 9
．． 75% Example 8 200 mg of 1 obtained in Example 2) was dissolved in tetrahydrofuran and HNKO+ (hydrolyzed with alcohol solution, Chl o r i n (9)
I got 83 wgl. Yield 42%.

Nuclear magnetic resonance spectrum [+CD, lOCO]b pp
m: 1.70 (3H, t), 1.77 (3B, d),
1.78-3.1Of411, ml, 3.2'8 (3H
, sl, 3.52 (3H, sl, 3.65 (3H, sl
.

3.90 (2H, ql, 4.38-4.76 (2H, a
), S, 45 (lIl, d).

5.64 fllll, d), 6.13-6.44 f2
H,ml, 11.22 flH,sl.

9.10 (I[1, g), 9.65 (IR, sl, 9.
84 (LH, sl.

Visible absorption maximum [(CH, lOCO] nm (c l: 400 (I27,0001,499
f9.100).

528 (4,6001,608+4.5001.664
(41,1001° mass spectrum (FAB-MS) O: 597 (approval H4).

Example 9 50% FlI of each trimethyl ester 2.5.6.7J3 and 8 obtained in Examples 2.4.5.6 and 7
20H-Chlorin (OMe
) (I0), δCHO20H-Chlorin
(OMe) (I1)δMe-20H-Ch l
or in (OMe)*(I2), δC1-20
H-Ch 1 or in (OMe) (I3)
and δNO, -20H-Ch 1 or i n (
OMe) (I4) were obtained. Each yield 85
%.

0 Nuclear magnetic resonance spectrum (CD C1m) δ ppm:
f, 69 (3H, t), 1.72 (3H, d), 1.
73-2.57 (4R, m), 3. Z7 (3H,s)
, 3.36 f3H,s), 3.56(3H,s).

3,72 (3L sl, 3.76 (2B, q
), 4.09 (2B, t), 4.22 (3
H, sl, 4.31 (2H, tl, 4.41 (2H, m
), 5.23 (IH, d), S, 29 (IB, dl, 8
．． 68(IH,s), 9.38flH,s), 9.68
(Ill, sl.

Visible absorption maximum (CHCIm) nm (E): 399 (I35,0O01,498
(I1,200!

526f3.2001.601 (4,6001,655
(40,100+.

Mass spectrum (FAB-MS) ψ: 64N praise■0).

1 Nuclear magnetic resonance spectrum (CDCi,) δ ppm+ 1.43 (3H, dl, 1.62 (
3B, t), 1.90-2.75 (4H, ml, 3°1
5 (3H, sl, 3.18 (311, s), 3.38f
3H1fl.

3.55 (2H, m), 3.78 (3B, s), 3.9
5 (2B, ssl, 4.19f3H, s), 4.23 (
2H, ql, 4.28 (lH, ml, 4.83 (IR,
d), 5.20 (LH, m), 5.23 (lH, dl,
9.28 flH, sl, 9.32 (I11, s),! ,
1.6OflH,sl.

Visible absorption maximum (CHCl8) nwa (t l: 41N11δ, 000], 512
F6.9001゜547 f9.5001 ,641
i5°8001.694 (33,000).

Mass spectrum (FA, B-MS) ψ: 6
70FM Fl”l.

2 Nuclear magnetic resonance spectrum (CDC1,) δpp+m: 1.52f3H, dl, 1.64 (3B
, tl, 1.70-2.51f4H, -), 3.28
f3H,s), 3.42 f3H,sl, 3.52
(3H, s).

3.74 (2H, q), 3.78 (3H, sl, 3.8
2 (3H, s), 4.10-4.38 (5H, m), 4
．． 21f3H, S), 4.55 (IB, ml, 5.00
flH, d), 5.24 (IH, d), 9.43 flH
, s), 9.53 (lH, sl visible absorption maximum (CHC
l,) nm (ε): 406 (I32,0001,5
08 (I0,000+.

538 (6,700), 666 (37,800
1.

Mass spectrum (FAB-MS) ψ: 657 (MW’).

3 Nuclear magnetic resonance spectrum (CDC1,) δ ppm: 1.64131'1. d), 1.68
(3H, t). l, 54-2.63 (411, m), 3
．． 2F (3H, s), 3.53 (3H, s), 3.5
5 (3H, s).

3.73 (2H, ql, 3.78f3H, sl, 4.1
5 (2B, tl, 4.22 (3H, s), 4.29 (2
H, tl, 4.55 (LH, s), 4.89 (IH, q
)5°09flt1. d), 5.27 (IH, d), 9
．． 52 (IH, s), 9.60 (IH, s) Visible absorption maximum (CHCl,) ns (t, l: 404 (I57,0001,50
7f11.70[]1゜535f8.300+, 613
(4,300), 666 (4g, 700+.

Mass spectrum (FAB-M3) (677 (MH”).

4 Nuclear magnetic resonance spectrum (CDCI) δ pp: 1.53 (3B, dl, 1.68 (3H
,t), 1.74-2.65f4H,m), 3.14(
3H, s), 3.24 (3H, s), 3.52 (3H,
s).

3.70 (28, ql, 3.77 (3H, sl, 4.1
1(2[1, tl, 4.22f3)1. s), 4.2
9 (2H, t), 4.38 (IH, m), 4.62 ('
IH, m), 5.09 (IH, d), 5.24flH,
dl, 9.62flH,s), 9.65(l)1. sl Visible absorption maximum (CHCl, ) nm (E l: 399 (I25,000), 5
0G (I1,000>.

531(6,0+70), 66&(46,500)-Mass spectrum (FAB-MS) 111: 682ftMll"l- (g) Effects of the invention The porphyrin derivative of the present invention has a tendency to accumulate in cancer cells and respond to external energy. It is extremely useful as a cancer therapeutic agent or cancer diagnostic agent because it has a destructive effect on cancer cells and cancer cells, and is not toxic to normal cells.

[Brief explanation of drawings]

1st r! 4 is Chlorirh (9), Figure 2 is 20H
-Chlorin (OMe) (I0), Figure 3 shows δCHO-20H-Ch 1 or in (OMe)
(I1), 41st! ! ! I is δMe-20H-C
hlorin(OMe) (I2), Fig. 5 δCヱ-20H-Chlorin (OMe)s(I3)t5 and Fig. 6 δN0I-20H-Chlorin (OM
e) * indicates the cell inhibition rate of the treatment group, O indicates the light irradiation group, or / indicates the control group without light irradiation.

Claims (1)

[Claims] (I) General formula (wherein R_1 is -CH=CH_2 or -CH_2-CH_2-OR, R_2 is -CHO, -CH_2, -NO_2 or halogen, R is -H or -COCH_2, A porphyrin compound represented by M (2H or metal).