JPH02138280A - Porphyrin derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula [R2 and R2 are CH=CH2, CH(OH)CH3 or CH(O-lower alkylene-OR)CH3; R3 and R4 are OH or residue after removal of H from polufunctional compound; R is H, alkyl, alkenyl, perfluoroalkyl or residue after removal of H from cyclic compound or polyfunctional compound; M is metal]. EXAMPLE:Ga-protoporphyrinyl monoglycine. USE:A cancer orientation preparation useful for treatment, diagnosis and marker of cancer and missile therapy. PREPARATION:A porphyrin compound corresponding a compound shown by the formula containing R1 and R2 is made, then a metal is introduced into the compound and residue of polyfunctional compound (e.g. amino acid, polyamine or amino-alcohol) is bonded to R3 and R4 of the prepared metal porphyrin compound to give the compound shown by the formula.

Description

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

(b) Prior Art It has been well known that porphyrin derivatives have a selective accumulation property in cancer tissues. However, the selectivity for cancer tissue is still insufficient.
Porphyrin derivatives are toxic to light, so
When administered to humans, patients are required to remain in a dark place for a long period of time until the porphyrin derivatives that have collected in normal tissues are excreted from the body.

As a result of various studies to overcome these drawbacks, the present inventors have developed a metalloporphyrin compound (JP-A-61-83) obtained by introducing a certain metal into the porphyrin skeleton.
No. 185) and porphyrin derivatives having groups capable of forming metal chelates (Patent Publication No. 13997/1983)
It was also found that phototoxicity was reduced with respect to No. 1) while maintaining its affinity for cancer. In addition, based on these facts, porphyrin derivatives of amino acids having an iodine-labelable group and a fluorine-containing group (Japanese Unexamined Patent Publication No. 6
4-61481) was found to have a similar effect.

However, the previous patented substance (Patent Publication No. 13997/1983)
When we attempted to image tumor-bearing animals by labeling the drug with the radioactive metal ``I n+'' TC and the substance of the previous application (Japanese Patent Application Laid-open No. 64-61481) with 11111, we found that the excretion of the drug from the liver was However, it was considered difficult to diagnose and treat cancer in all parts of the body using these substances.

On the other hand, Bommer et al.
2-5924, 62-5985 and 62-598
No. 6) synthesized various amino acid derivatives of porphyrin,
We have reported the optical diagnosis of cancer using an endoscopic laser fluorescence analyzer and the phototherapy of cancer using laser beams, mainly using monoamino acid derivatives of chlorin. However, this compound is not a metalloporphyrin derivative and was developed only as a drug for laser irradiation diagnosis and treatment. In addition, the list of efficacy and effects includes descriptions of leg swelling, muscle damage, etc., and the compound appears to exhibit considerable drug toxicity.

Recently, protoporphyrin-3n and M
g complex (Japanese Patent Application Laid-Open No. 63-264524), these metal complexes of protoporphyrin derivatives do not specifically accumulate in cancer.

Paramagnetic metals such as Mn and Fe can be considered as contrast agents for nuclear magnetic resonance imaging (MHI).

Ph1lip et al. synthesized Mn-tetraphenylporphine-trisulfate (Mn-TPPS) and developed MHI.
1cancer Re5earc has announced its effectiveness
h 48, 4604 (I98811) However, this TPPS derivative is highly toxic (and has no cancer tissue selectivity, so it is difficult to put it into practical use).

For therapeutic use, mercury hemadoporphyrin sodium and protoporphyrin cobalt complexes were developed in the past as compounds that have antitumor effects by themselves and have been registered as pharmaceuticals.

However, the former was judged to be effective in 1960, and the latter in 1981, and its manufacture and sale were discontinued as it was determined that there was "no basis for determining its effectiveness."

(c) Problems to be Solved by the Invention As mentioned above, a metal porphyrin compound is obtained by introducing a certain metal into a porphyrin skeleton.

Porphyrin derivatives having a group capable of forming a metal chelate and porphyrin derivatives carrying tyrosine or the like (a group capable of being labeled with iodine) do not necessarily have sufficient selectivity and accumulation for cancer.

It is not possible to diagnose and treat all cancers in every part of the body, and there are currently no compounds that have a cell-killing effect using porphyrin compounds alone. A metalloporphyrin derivative that has a cancer cell destroying effect, and an MHI that is stronger than the previous application substance.
It became necessary to synthesize metalloporphyrin derivatives useful for diagnosis.

Among porphyrin derivatives, there are compounds that are susceptible to photosensitization and compounds that are less sensitive to photosensitization.The former suffers from the disadvantage of developing phototoxicity, but photochemotherapy (PDT) for cancer and therapy using external energy are considered. On the other hand, the latter is useful as a diagnostic and therapeutic agent for cancer because it does not exhibit phototoxicity.Therefore, it is useful as a diagnostic agent and therapeutic agent for cancer, as it does not exhibit phototoxicity.Therefore, it is possible to develop new methods for cancer treatment, diagnosis, markers, and missile therapy that utilize the characteristics of both of them individually. It is necessary to develop cancer-directed drugs for different uses.

(d) Means for solving the problem Until now, the physicochemical properties of the photoexcited cell destruction effect of porphyrin derivatives have not been fully elucidated. This destructive effect involves two mechanisms: Mechanism I, in which the dye is excited by light and turns into a triplet state, which directly destroys cancer cells; and the triplet state dye further excites oxygen to produce singlet oxygen (active oxygen), which in turn destroys cancer cells. Leading to destruction <MeChani
There are two courses: S-■I. For volufiline derivatives M
echaniss+ II is thought to be predominant. Therefore, we measured the triplet lifetime, which is an indicator of the triplet state of porphyrin (i.e., measured the fluorescence lifetime and phosphorescent lifetime), and compared the length of the phosphorescent lifetime to determine the strength or weakness of photosensitivity.1 Table 1 shows various porphyrin derivatives. From Table 1, which shows the luminescence properties of Zn, it can be seen that the phosphorescence lifetime depends on the type of coordinating metal of the metalloporphyrin derivative.

Considering that metal porphyrin derivatives such as Ga have a long phosphorescence life, while those of Mn, Fe, Cu, etc.
n complexes) are used as drugs for cancer treatment using PDT or external energy, while those with short phosphorescent lifetimes (Mn, Fe, C
We decided to develop the u-complex) for different uses: as a cancer diagnostic drug using MHI or radioisotope (RI), and as a cancer treatment drug that alone exhibits antitumor effects. Then, we calculated porphyrin derivatives for different uses that take advantage of both of these characteristics (long and short phosphorescent life). 1 PP: 10 toporphyrin, PPB:
As a result of further research on Pheomoto-Bido, it was found that when at least one polyfunctional compound is attached to the side chain of a metalloporphyrin compound, the porphyrin compound with the above characteristics maintains its affinity for cancer. It was found that it has the property of being rapidly excreted from normal tissues.

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 present invention was completed based on the above findings, and
The gist is the formula (I) (wherein R1 and R1 are each -CH=CH-CH
(OR)CH, or -CH(0-lower alkylene-
0R) CH,.

R3 and R4 are -OH or a residue obtained by removing hydrogen from a polyfunctional compound, R is -H, alkyl, alkenyl, perfluoroalkyl, a residue obtained by removing a hydroxyl group from a cyclic compound or a polyfunctional compound, and M is a residue obtained by removing a hydroxyl group from a cyclic compound or a polyfunctional compound. It exists in metal porphyrin compounds represented by metal).

The term "lower alkylene" used in connection with the meanings of the above symbols means alkylene having 5 or less carbon atoms, preferably carbon v11 to 3 (e.g., ethylene, trimethylene, propylene, etc.); [Alkenyl] means an alkyl having 20 or less carbon atoms, preferably 1 to 18 carbon atoms (e.g., methyl, ethyl, n-propyl, hexyl, octyl, decyl, dihydrocitronellyl, undecyl, dodecyl, tetradecyl, octadecyl, etc.);
The term means alkenyl having 20 or less carbon atoms, preferably 6 to 16 carbon atoms (eg, hexenyl, octenyl, geranyl, citronellyl, octadecenyl, etc.).

[ The term cyclic compound J means a cyclic compound having 7 or fewer members (eg, cyclohexyl, menthyl, etc.).

The term "polyfunctional compound" means a compound containing at least two functional groups (
For example -NHs, -OHl-〇-1-8H, -3-
5-COOH, halogen, etc.), and preferably amino acids (e.g., glycine, cysteine, glutamic acid, alanine, cystine, aspartic acid, asparagine, valinemethionine, glutamine, leucine,
(phenylalanine, isoleucine, serine, tryptophan, threonine, histidine, lysine, tyrosine, etc.)
, polyamine II (e.g. ethylenediamine, hexamethylenediamine, hydrazine, tetraethylenepentamine, etc.), polyhydric alcohols (ethylene glycol, methyl cellosolve, ethyl cellosolve, calpitol, etc.),
Heterocyclic alcohols (e.g. tetrahydrofurfuryl alcohol).

Tetrahydropyran-2-methanol, 3-pyridine-
methanol, etc.), amino alcohols (e.g., monoethanolamine, dimethylaminoethanol, hydroxyamine, hydrazinoethanol, etc.), sulfur-containing alcohols (e.g., methionol, etc.), halogenated alcohols (e.g., monobromoethanol, trichloroalcohol, etc.)
, phenethyl alcohol, taurine, hydroxyacetic acid, etc. may be used. Some of these substances have optical activity, but in that case, it does not matter whether the L-form, 0-form, or DL-form is used. Alternatively, they may be converted into DL forms during the synthesis reaction, or they may be used in the form of alkali metal salts.

The metalloporphyrin compound (I) of the present invention is a new substance and can be produced in a conventional manner.
First, a porphyrin compound corresponding to formula (I),
In step a), a compound having R1 and R2 is formed, and then in step b), a metal is introduced into the compound, and in step b), a residue of a polyfunctional compound (for example, an amino acid, etc.) is bonded to R3 and R4 of the metalloporphyrin compound obtained. (Step c), and it is not necessarily necessary to react with Steps (a), (b), and (c) sequentially, for example, Steps (b), (a), and (c) or Steps (a), (c), ( The order of the steps may be changed as in b).

The construction steps (ag and b) are described by J. E. Falk [Por
phyring and Metalloporphy
rinsl (Elsevier, 1975), etc. 1. For example, metalloporphyrin compounds having R1 and R2 corresponding to formula (I) are described in JP-A-61-1999. 7
No. 279, Japanese Patent Application Laid-Open No. 61-83185 and Patent Publication No. 63
It can be prepared according to the method described in No. 13997, that is, in step (a), R can be introduced into the R1 and R yo side chains of the porphyrin compound (I), so the polyfunctional compound can be The hydroxyl group may be reacted (or other functional groups (e.g. -NH, group) may be reacted)6 For example, when using a polyfunctional compound having a hydroxyl group, the Br of the porphyrin compound (I) may be reacted in advance. It is preferable to prepare a derivative and allow the reaction to proceed between this and the hydroxyl group of the polyfunctional compound, and for this purpose, other functional groups of the polyfunctional compound may be appropriately protected. Regarding (b), this is usually done using metal chlorides, acetates, sulfates, nitrates, etc. The types of metals include Mg, S, Tt, Mn, F.
e, Co.

Examples include Ni, Cu, Zn, Ga, Ge%In, and the like. In addition, this metal introduction step (b) may be prepared as necessary, regardless of whether before or after the step (a).6 For example, first the metal introduction step (b) is performed, then a Br derivative of the metal porphyrin compound is prepared, There is no problem in proceeding the reaction (step a) between this and a functional compound. Instead of artificially synthesizing it, it may be collected from natural sources such as plants and animals.

The metalloporphyrin compound thus constituted is then subjected to the step (C) of bonding the residues of the polyfunctional compound, that is, the metalloporphyrin compound (I) in which at least one of R3 and R4 is -OH is bonded to the polyfunctional compound (I). Compounds (mainly amino acids, polyamines, amino alcohols, etc.)
to produce a metalloporphyrin compound (I) containing a small amount of R and R4 (one of which supports a polyfunctional compound).
This can be done by the conventional method described in JP-A No. 64-6148 (published by Maruzen, 1985), etc.
This can be prepared according to the method described in No. 1.
Instead of artificially synthesizing it, it can also be obtained from natural sources such as plants and animals.

In this case, the point is to introduce the residue of the polyfunctional compound into the side chain of the porphyrin compound (I), so the amino group of the polyfunctional compound may be reacted, and other functional groups (for example - OH group) may be reacted with
For example, when using a polyfunctional compound having an amino group, R3 and R4 of the porphyrin compound (I) are generally
It is preferable to allow the reaction to proceed between the carboxyl group of the side chain and the amino group of the polyfunctional compound, and for this purpose, the former carboxyl group and/or the latter amino group may be converted into a conventional reactive group, or both may be reacted. It may be considered to appropriately protect functional groups that are present in the reaction and which are undesirable to participate in the reaction, and in both cases, the use of reaction accelerators and condensing agents such as dehydrating agents and deoxidizing agents may be considered as appropriate. It's okay to be.

The preparation of metal porphyrin compounds will be explained in more detail below by giving one representative example.

When the polyfunctional compound carries an amino group, first, a metal porphyrin compound in which at least one of R3 and R4 has an OH group (JP-A-61-7279, Sho-61-83) is used.
No. 185 or Patent Publication No. 13997/1983), a polyfunctional compound carrying an amino group (e.g., amino acid methyl ester, etc.) is mixed with a condensing agent (e.g., dicyclohexylcarbodiimide (DCC) or water-soluble carbodiimide (wS)) in a solvent.
C) 1 and the like to obtain a metalloporphyrin compound (I) in which at least one amide group-carrying polyfunctional compound is bonded to the side chains of R3 and R4. Specific examples include the following. : 111Ga-protoporphinyl monoglycine (hereinafter referred to as Ga-PP-monoGly) (21Ga-protoporphinyl diaspartic acid (hereinafter referred to as Ga-PP-
diAsp) 131Ga-protoporphinyl
Dityrosine (hereinafter referred to as Ga-PP-diTyr) +4
12-[1-(2-hydroxyethyloxy)ethyl]-4-ethynyl-Ga-deuteroporphinyl
Monoglycine (hereinafter -onoE G -Q a-[)
p -monoG ly) (512-[t-(
2-hydroxyethyloxy)ethyl]-4-ethynyl-Ga-deuteroporphinyl diglycine (hereinafter referred to as 5onoE G -Ga-DP-diGly) +612- [1-(2-hydroxyethyloxy)
ethyl]-4-ethynyl-Ga-deuteroporphinyl dileucine (hereinafter referred to as 5onoE G -G a-DP
-diLeu) (712-[1-(2-hydroxyethyloxy)ethyl]-4-ethynyl-Ga-deuteroporphinyl monoaspartic acid (hereinafter referred to as son).

E G -G a -D P -5onoA sp)+812- [1-(2-hydroxyethyloxy)ethyl J-4-ethynyl-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as -onoEG-Ga
-DP-diAsp) +9) 2-[1-(2-hydroxyethyloxy)ethyl]-4-ethynyl-Ga-deuteroporphinyl monophenylalanine (hereinafter referred to as @on).

E G -G a -D P --onoP h e) (lo12-[t-(2-hydroxyethyloxy)ethyl]-4-ethynyl-Ga-deuteroporphinyl diphenylalanine (hereinafter referred to as 5 tons).

EG-Ga-DP-diPhe) 11112-
[1-(2-hydroxyethyloxy)ethyl]-4
-ethynyl-Ga-deuteroporphinyl monotyrosine (hereinafter -onoEG-Ga -D P -s+o
say noT y r)+1212- [t-(2-
hydroxyethyloxy)ethyl]-4-ethynyl-a-deuteroporphinyl dityrosine (hereinafter -o
noE G -G a-DP-diTyr) (I312,4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monoglycine (hereinafter referred to as EG-Ga-DP-monoG 1
y) +1412.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Diglycine (hereinafter referred to as EG-Ga-DP-diG 1 y) (I512,4-bis(I-(2-hydroxyethyloxy)ethyl) -Ga-deuteroporphinyl
Monoleucine (hereinafter EG-Ga-DP-*onoL e
u) +1612.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Dileucine (hereinafter referred to as EG-Ga-DP-diLeu) +1712.4-bis[t-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monoisoleucine (hereinafter referred to as EG-Ga-D P-sono
I1e) (lδ)2.4-bis[1-(2-hydroxyethyloxy)ethyl]-Ga-deuteroporphinyl
Diisoleucine (hereinafter referred to as EG-Ga-DP-diIle) +1912.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monoserine (hereinafter referred to as EG-Ga-DP-monoS e
120) 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl monocystine (hereinafter referred to as EG-Ga-DP-5sono)
c y S) +2112.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monomethionine (hereinafter referred to as EG-Ga-DP-monoM)
e t) +2212.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monoaspartic acid (hereinafter referred to as EG-Ga-DP-ao
123) 2.4-bis[1-
(2-hydroxyethyloxy)ethyl] -Ga-
deuteroporphinyl mono-low aspartic acid (
The following EG-G a -D P -aono [D] A
(24) 2.4-bis[1-(2-hydroxyethyloxy)ethyl]-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as EG-Ga-D
P-diAsp) (2512,4-bis[1-(2-hydroxyethyloxy)ethyl]-Ga-deuteroporphinyl
Monoasparagine (hereinafter referred to as EG-Ga-DP-5on)
oA s n)+2612.4-bis[1-(2
-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl monoglutamic acid (hereinafter EG-G
a-D P--onoGlu) +2712.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Diglutamic acid (hereinafter referred to as EG-Ga-DP-diGlu) (2812,4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monolysine (hereinafter referred to as EG-Ga-DP-@onoLy
+29) 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl monophenylalanine (hereinafter referred to as EG-Ga-D P-m
onoP h e)+3012.4-bis[1-
(2-hydroxyethyloxy)ethyl] =Ga-
deuteroporfinil schifuminylalanine (hereinafter referred to as E)
G-Ga-DP-diPhe) +3112.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Monotyrosine (hereinafter referred to as EG-Ga-DP-5onoT y
r) 132+ 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl dityrosine (hereinafter referred to as EG-Ga-DP-diT yr
) (3312,4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Glycine aspartic acid (hereinafter referred to as EG-Ga-DP-Gl)
y-Asp) +3412.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Serine aspartic acid (EG-Ga-DP-3er)
-Asp) +3512.4-bis[1-(2-hydroxyethyloxy)ethyl] -Ga-deuteroporphinyl
Phenylalanine aspartate (hereinafter referred to as EG-Ga-D
P-Asp-Phe)+3612.4-bis[1
-(2-hydroxyethyloxy)ethyl] -Ga
- Deuteroporfinil Tyrosine aspartate (
(hereinafter referred to as EG-Ga-DP-Asp-Tyr) (3712,4-bis[1-(2-methoxyethyloxy)ethyl] -Ga-deuteroporphinyl monoserine (hereinafter referred to as MC-Ga-DP-sonoS e r
(38) 2.4-bis[1-(2-methoxyethyloxy)ethyl] -Ga-deuteroporphinyl monoaspartic acid (hereinafter M C-G a -D P-m
onoA sp) +3912.4-bis[1-(2-methoxyethyloxy)ethyl] -Ga-de1-teloporphinyl diaspartic acid (hereinafter referred to as M C-G a -D P-di
Asp) +4012.4-bis[1-(2-ethoxyethyloxy)ethyl] -Ga-de1-teloporphinyl monoaspartic acid (hereinafter referred to as EC-Ga-D P-mono
A sp) +4112.4-bis[1-(2-ethoxyethyloxy)ethyl]-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as EC-Ga-DP-diAsp) (4212,4 -Bis(I-methoxyethyl)Ga-
deuteroporphinyl monoserine (hereinafter C+ -G
a -D P -+5onoS e r)+4
312.4-bis(l-methoxyethyl)Ga-deuteroporphinyl monoaspartic acid (hereinafter referred to as C+
-G a -D P -monoA sp +4
412.4-bis(I-methoxyethyl)Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as Cr-G
a-DP-diAs p)+4F) 2.4-bis(I-methoxyethyl)Ga-deuteroporphinyl monotyrosine (hereinafter referred to as Cr-G a -DP-
+5onoT y r)+4612.4-bis(
I-methoxyethyl)Ga-deuteroporphinyl dityrosine (hereinafter referred to as C+-Ga-DP-diTyr) +4712.4-bis(l-ethoxyethyl)G
a-Deuteroporphinyl monoaspartic acid (hereinafter referred to as Cx -G a -D P -5onoA sp +4812.4-bis(l-ethoxyethyl)G
a-deetheroborfinyl diaspartic acid (hereinafter referred to as C5-Ga-DP-diAs p) 149) 2
．． 4-bis(l-propooxyethyl)-Ga-deuteroporfinyl diaspartic acid (hereinafter referred to as C5-Ga
-DP-diAsp)T0n) 2.4-bis(
l-isopropoxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as Cs++ms+ -
Ga D P-diAsp) +5112.4-bis(l-butoxyethyl)Ga-
Deuteroporphinyl diaspartic acid (hereinafter C4
-G a D P diA sp) +52
12.4-bis(l-pentyloxyethyl)-Ga-
deuteroporphinyl diserine (hereinafter C5-Ga-
DP-diSer) (53) 2.4-bis(I-
pentyloxyethyl) -Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as C, -Ga-DP-di
Asp (54) 2.4-bis(l-hexyloxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as C,-Ga-DP-dLAsp155) 2.4-bis(l -hebutyloxyethyl)
-Ga-deuteroporphinyl diaspartic acid (
Hereinafter referred to as Cv Ga-DPdiAsp (5612,4-bis(l-octyloxyethyl)-Ga-deuteroporphinyl diglycine (hereinafter referred to as Ca-Ga-DP-diGly) (5712
, 4-bis(l-octyloxyethyl)-Ga-deuteroporphinyl diserine (hereinafter referred to as Ca-Ga-DP
-diSer) (5al 2.4-bis(l-octyloxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as Cm-Ga-DP-dLAs)
say p+5912.4-bis(l-octyloxyethyl)-Ga-deuteroporphinyl dityrosine (
Hereinafter referred to as C*-Ga-DP-diTyr) (6012
-(I-octyloxyethyl)-4-ethynyl-Ga
- deuteroporphinyl diglycine (hereinafter Ca++
m*aol -G a -D P dlG 13') +6112- (I-octyloxyethyl)-4-ethynyl-Ga-deuteroporphinyl diserine (hereinafter referred to as Calss**l -G a -D P-diSe
+62) 2-(I-octyloxyethyl)-4-ethynyl-〇a meideuteroporphinyldiaspartic acid (hereinafter referred to as Ca III@11@l-G a-D P
diAsp) +63) 2-(I-octyloxyethyl)-4-ethynyl-Ga-deuteroporphinyl dityrosine (
Below Cal#5sal -G a D P dz
16412.4-bis(l-phenethyloxyethyl)
-Ga-deuteroporphyrin (hereinafter CIPTh*m
*tThyl -G a -D P) +651
2.4-bis(I-phenethyloxyethyl)-Ga-
deuteroporphinyl diaspartic acid (hereinafter Ca
lPhe** thyll -G a -D P -di
A s P) +6612.4-bis(l-nonyloxyethyl)-G
a-Deuteroporphinyl diaspartic acid (hereinafter referred to as Ce-GaDP-diASP) +6712.4-bis(l-decyloxyethyl)-
Ga-deuteroporphinyl diserine (hereinafter referred to as Cz+
-Ga-DP-diSer) 168) 2.4-bis(l-decyloxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as CloGa
DP-diA sp) 16912.4-bis(l-geranyloxyethyl)-Ga-deuteroporphyrin (hereinafter referred to as c1゜(.* r a , -G a
-DP) (7Ql 2.4-bis(I-geranyloxyethyl) -Ga-deuteroporphinyl
Diaspartic acid (hereinafter referred to as Cl610@ral Ga
-DP-diA Sp) +7112.4-bis(l-citronellyloxyethyl)-Ga-deuteroporphyrin (hereinafter referred to as Cl01el
tr@l -G a -D P) +7212.4
-Bis(I-citroxyloxyethyl)-Ga-deuteroporfinyl diaspartic acid (hereinafter C101
eltr@l -G a -DP -diAsp) (73) 2.4-bis(l-dihydrocitroxyloxyethyl)-Ga-deuteroporphyrin (hereinafter referred to as C1
o IIIle + trsl Ga -D
-DP-diAsp) 17512.4-bis(l-undecyloxyethyl)
-Ga-deuteroporphinyl diaspartic acid (
(hereinafter referred to as Cz-Ga-DP-diAsp) 17612.4-bis(l-dodecyloxyethyl)-
Ga-deuteroporphinyl diglycine (hereinafter referred to as C+
*-Ga-DP-diGly)+7
7) 2.4-bis(l-dodecyloxyethyl)-Ga
- deuteroporphinyl diaspartic acid (hereinafter C
1m-Ga-DP-diAs p (7812,4
-bis(l-dodecyloxyethyl)-Ga-deuteroporfinyl diglutamic acid (hereinafter Cr*-Ga
-D P -diG 1 u) (7912,4
-bis(l-tetrahydrofurfuryloxyethyl)-
Ga-deuteroporphyrin (hereinafter referred to as H4Fran-G
a-DP) (8◎) 2.4-bis(l-tetrahydrofurfuryloxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as 114F r a
n -G a -DP-diAsp) 18112.4-bis[l-(tetrahydro-2-bilanmethyloxy)ethyl] -Ga-deuteroporphyrin (hereinafter referred to as H4Pyran-Ga-DP) +8212.4- Bis[l-(tetrahydro-2-biranmethyloxy)ethyl]-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as H4Pyran-Ga
-DP-diAsp)+8312.4-bis(l
-Nicotinyloxyethyl)-Ga-deuteroporphyrin (hereinafter referred to as Nct-Ga-DP) 14412.4-bis(I-nicotinyloxyethyl)
-Ga-deuteroporphinyl diaspartic acid (
(hereinafter referred to as Net-Ga-DP-diAsp) 18512.4-bis(l-octafluoropentyloxyethyl)-Ga-deuteroporfinyl diglycine (hereinafter referred to as Cs+r+s+ Ga-DP-diG l
! 1+1612.4-bis(l-octafluoropentyloxyethyl)-Ga-deuteroporphinyl diaspartic acid (hereinafter referred to as Cs+v+a+ Ga-DP
1881M
g-protoporphinyl dityrosine (hereinafter referred to as pJig-
PP-diTyr) 18912.4-bis[1-
(2-hydroxyethyloxy)ethyl] -Mg-
Deuteroporphyrin (hereinafter referred to as EG-Mg-DP) + 9012.4-bis[1-(2-hydroxyethyloxy)ethyl] -Mg-deuteroporphyrin dityrosine (hereinafter referred to as EG-Mg-DP-diTyr
) (9112,4-bis(l-hexyloxyethyl)-
Mg-deuteroporphinyl diaspartic acid (hereinafter referred to as C*-Mg-DP-diAsp) 19212.
4-bis(I-octyloxyethyl)-Mg-deuteroporfinyl diaspartic acid (hereinafter referred to as Ca-Mg
-DP-diAs p (9312,4-bis(I)
-decyloxyethyl)-Mg-deuteroporphinyl diaspartic acid (hereinafter C1゜-Mg-DP-di
Asp) (9412,4-bis(l-dodecyloxyethyl)-Mg-deuteroporphinyl diaspartic acid (hereinafter referred to as C+m -M g -D P -di
A sp (951Mn-protoporphinyl)
Monotyrosine (hereinafter referred to as M n -P P -*onoT
y r) 1961 Mn-protoporphinyl dityrosine (hereinafter referred to as Mn-PP-diTyr) 197
12-[1-(2-hydroxyethyloxy)ethyl 1-4-ethynyl-Mn-deuteroporphyrin (hereinafter referred to as -onoE G -Mn -D P +981
2-[1-(2-hydroxyethyloxy)ethyl]-4-ethynyl-Mn-deetheroporfinyl monoglycine (hereinafter -onoE G -Mn-[) p-s
onoGly) (99) 2-(I-(2-hydroxyethyloxy)ethyl 1-4-ethynyl-M
n-thieteroporphinyl diglycine (hereinafter -on
oE G -M n-DP-diGly) 110012- [1-(2-hydroxyethyloxy)ethyl]-4-ethynyl-M n -tez-teloporphinyl diaspartic acid (hereinafter referred to as ■on).

EG-Mn-DP-diAs p)+10112
-[1-(2-hydroxyethyloxy)ethyl]-
4-ethynyl-Mn-deuteroporphinyl diphenylalanine (hereinafter referred to as -on).

EG-Mn-DP-diPhe)1102)2-
[1-(2-hydroxyethyloxy)ethyl]-
4-ethynyl-Mn-deetheroborfinyl dityrosine (hereinafter ■onoE G -Mn-DP-diTyr
(IQ312, 4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphyrin (hereinafter referred to as E G -M n -DP) f104
+ 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporfinyl monoglycine (hereinafter referred to as EG-Mn-DP-monoG l
110512, 4-bisEl-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphinyl diglycine (hereinafter referred to as EG-Mn-DP-diG 1 y
(I06) 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphinyl monoserine (hereinafter referred to as E G -M n -D P -
monoSer) (I0712,4-bis[1-(2-hydroxyethyloxy)ethyl]-Mn-deuteroporphinyl diserine (hereinafter referred to as EG-Mn-DP-diSer) (I0812, 4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphinyl monoaspartic acid (hereinafter EG-Mn-D P -5
onoA SP) (I09) 2.4-bis[
1-(2-hydroxyethyloxy)ethyl] -M
n-deuteroporphinyl diaspartic acid (hereinafter referred to as E G -M n -DP-diAsp) (I10) 2.4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphyl Nyl monophenylalanine (hereinafter referred to as EG-Mn-DP-m
onoPhe) (I1112,4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphinyl diphenylalanine (hereinafter referred to as E G -M n=DP-
diPhe) (I1212,4-bis[1-(2-hydroxyethyloxy)ethyl] -Mn-deuteroporphinyl monotyrosine (hereinafter referred to as EG-Mn-DP-monoT)
y r) tl1312.4-bis[1-(2-hydroxyethyloxy)ethyl 3-Mn-deuteroporphinyl
Dityrosine (hereinafter referred to as EG-Mn-DP-diTyr) (I14) 2.4-bis(l-pentyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as Cs-Mn-DP-diAsp) 2.4-bis(l-octyloxyethyl)-Mn-deuteroporfinyl diglycine (hereinafter referred to as Ca-Mn-DP-diGly) (tta)
2.4-bis(l-octyloxyethyl)-Mn-
Deuteroporphinyl diaspartic acid (CM
-Mn-DP-diAs p) (I1712,4-bis(l-decyloxyethyl)-
Mn-deuteroporphinyl diglycine (hereinafter referred to as Cl
oMnDP-diGly)1
118) 2.4-bis(l-decyloxyethyl)-
Mn-deuteroporphinyl dialanine (hereinafter referred to as Cl
o-M n -D P diA la) (I
1912,4-bis(I-decyloxyethyl)-Mn
-deuteroporphinyl dileucine (hereinafter C1o-
Mn-DP-diLeu)+12012.4-bis(I-decyloxyethyl)-Mn-deuteroporphinyl diserine (hereinafter referred to as CroMn-D
P-dis e r) mouth 21) 2.4-bis (
CIo M n -D
P-dicys) (I22) 2.4-bis(I-decyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as C+o-Mn DP
diAs p (I23) 2.4-bis(l
-decyloxyethyl)-Mn-deuteroporphinyl di-low aspartic acid (hereinafter referred to as C+ o-M n
-DP-di[0]Asp) (I2412,4-bis(I-decyloxyethyl)-
Mn-deuteroporphinyl diglutamic acid (hereinafter referred to as C+o-Mn-DP-diG1u)
112512, 4-bis(l-decyloxyethyl)-
Mn-deuteroporphinyl diphenylalanine (
Below, Cto M n -D P -dir"h e
) (I2612,4-bis(l-decyloxyethyl)-
Mn-deuteroporphinyl diglycyl diaspartic acid (hereinafter CIo-Mn-DP-diGly)
-diAsp) +127) 2.4-bis(I-decyloxyethyl)
-Mn-deuteroporphinyl diglycyldiaspartic acid (hereinafter C1゜-Mn-DP-diLeu-di
Asp), 112812.4-bis(l-decyloxyethyl)
-Mn-deuteroporphinyl diphenylalanyldiaspartic acid (hereinafter C1゜-Mn-DP-diPh
e-diAsp) 11291 2-(I-decyloxyethyl)-4-ethynyl-Mn-deuteroporphinyl dileucine (hereinafter referred to as C+otmsm*+-M
(I30) 2- (I-decyloxyethyl)-4-
Ethenyl-Mn-deuteroporphinyl diglutamic acid (hereinafter referred to as Clo 1m5sal -MnDP
dlGlu) +13112.4-bis(l-geranyloxyethyl)
-Mn-deuteroporphyrin (hereinafter referred to as C1゜I@, Kawa-Mn-DP) +13212.4-bis(l-geranyloxyethyl)
-Mn-deuteroporphinyl diasparagine f
IM (hereinafter C1111+1++ral -M n -D
P-diAsp) +13312, 4-bis(l-citronellyloxyethyl)-Mn-deuteroporphyrin (hereinafter referred to as Cl01
eltral -M n -D P) (I34
) 2.4-bis(l-citronellyloxyethyl)
-Mn-deuteroporphinyl monoaspartic acid (hereinafter CIo 1ellral -MnDP
-+monoA S P) +13512.4-bis(l-citronellyloxyethyl)-Mn-deuteroporfinyl diaspartic acid (hereinafter referred to as C+olclttm+ M n D P
-diA sp)
ro+H*cltt*+ M n -D
DP-diAsp) +131112- (I-dihydrocitronellyloxyethyl)-4-ethynyl-Mn-deuteroporfinyl diaspartic acid (hereinafter referred to as C1゜, □C1tt@m*
m++l -M n -D P-diA sp) 11391 2,4-bis(I-menthyloxyethyl) -Mn-deuteroporphyrin (hereinafter referred to as c1゜+11@+ntIIFll -M n D P) (I4012 ,4-bis(l-menthyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as C1llljleaak#II Mn
DP diAsp) (I4112,4-bis(l-undecyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as Cr + Mn DP diA s)
p) +1421 2.4-bis(l-dodecyloxyedyl)-Mn-deuteroporphinyl diglycine (hereinafter referred to as C order Mn-DP-diGly) +14
312.4-bis(l-dodecyloxyethyl)-Mn
- deuteroporphinyl diaspartic acid (hereinafter C
+*Mn-D P-diA sp) +144+ 2.4-bis(l-dodecyloxyethyl)-Mn-deuteroporphinyl diglutamic acid (
Below C+ m -M n -D P -di G 1
+14512.4-bis(l-dodecyloxyethyl) -Mn-deuteroporphinyl diaspartyltetraglycine (hereinafter referred to as Crm -M n -D
P-diA sp-tetra G 1 y)+14612, 4-bis(l-dodecyloxyethyl)-Mn-deuteroporphinyl diaspartyltetraaspartic acid (hereinafter referred to as Ctt-Mn-DP-
diA sp-tetra A sp) +1
4712- (I-dodecyloxyethyl)-4-ethynyl-Mn-deuteroporphinyl diaspartic acid (hereinafter C+ s 1m*asl -M n -D P
-diA sp) +14812.4-bis(l-tridecyloxyethyl) -Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as C+s-Mn-DP-diAsp) 1149) 2,4-bis( l-tetradecyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as CI4-Mn-DP-diAsp) (I6G)2,4-bis(I-tetradecyloxyethyl)-Mn- deuteroporphinyl diaspartyltetraaspartic acid (hereinafter referred to as C14-M n -D
P-diA sp-tetraA sp) (I51) 2.4-bis(l-farnesyloxyethyl)-Mn-deuteroporphyrin (hereinafter referred to as C+
s 1Far++asyll -Mn-DP) (I52) 2,4-bis(l-farnesyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as C+s Ifatm++ayll
Mn-D P-diAsP) +153+ 2.4-bis(l-hexadecyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as C+a-Mn-D P-diAs
1154) 2.4-bis(I-octadecyloxyethyl)-Mn-deuteroporphinyl diaspartyltetraaspartic acid (hereinafter referred to as CIm-Mn-DP-d
iAsp-Tetra Asp)+15512.
4-bis(l-octadecenyloxyethyl)-Mn-
Deuteroporphyrin (hereinafter referred to as C1,.+eyll
M n -D P)+15612.4-bis(
I-octadecenyloxyethyl)-Mn-deuteroporfinyl diasparagine fi (hereinafter C+1101
++yll -M n -D P-diAsp) (I5712,4-bis(l-octadecenyloxyethyl)-Mn-deuteroporphinyl diaspartyltetraaspartic acid (hereinafter referred to as C1m+6111111)
1-Mn-DP-diAs p-tetra A
1158) 2.4-bis(l-phytyloxyethyl)-Mn-deuteroporphyrin (hereinafter referred to as Cs).

1PIHajll M n -D P) (I!
19) 2,4-bis(l-tetrahydrofurfuryloxyethyl)-Mn-deuteroporfin (hereinafter referred to as N
4F r a n -M n -D P) (I6
G) 2.4-bis(I-tetrahydrofurfuryloxyethyl)-Mn-deuteroporfinyl diaspartic acid (hereinafter referred to as 114F r an -M n-DP
-diAsp) (I61) 2.4-bis[l-(tetrahydro-2-
biranmethyloxy)ethyl] -Mn-deuteroporfin (hereinafter □P y r a n-M n D
(say P)! 162) 2.4-bis[l-(tetrahydro-2-and ranmethyloxy)ethyl] -Mn-deuteroporphinyl diaspartic acid (hereinafter waPyran-M
n-DP-diAsp) (I6312,4-bis(l-nicotinyloxyethyl)-Mn-deuteroporfin (hereinafter referred to as Net-Mn-DP) (I6412,4-bis(l-nicotinyloxyethyl) -nicotinyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as NCt-Mn-DP-diAsp) +16512, 4-bis(I-(2-methylthiopropyloxy)ethyl)-Mn-de Euteroporphyrin (hereinafter referred to as Msp-Mn-DP) +166) 2.
4-bis[1-(2-methylthiopropyloxy)ethyl] -Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as Msp-Mn-DP-diAsp) (I6712,4-bis(I-octafluoropentyloxy) ethyl) -Mn-deuteroporphyrin (hereinafter referred to as C□□al-MnDP) +16812,
4-bis(l-octafluoropentyloxyethyl)
-Mn-deuteroporphinyl diglycine (hereinafter referred to as C) -Mn-DP-diGly) 116912- (I-octafluoropentyloxyethyl)-4-ethynyl-Mn-deuteroporfinyl diglycine (hereinafter referred to as C) (pl-M n-DP-di
Gly) (I7012,4-bis(l-octafluoropentyloxyethyl)-Mn-deuteroporphinyl diaspartic acid (hereinafter referred to as Cm(vral-Mn-DP-d)
iAsp) +171) 2-(I-octafluoropentyloxyethyl)-4-ethynyl-Mn-deuteroporfinyl diaspartic acid (hereinafter referred to as Cs+ra+-Mn-D
P-diAsp) +172) 2.4-bis(l-geranyloxyethyl)-Mn-deuteroporphinyl di(p-trifluoromethyl)phenylalanyldiglutamic acid (hereinafter referred to as C
+o+aera+-Mn-DP-dlPh
eIF@I-diGlu) (I7:l) 2.4-bis(l-dodecyloxyethyl)-Mn-deuteroporphinyl di(p-trifluoromethyl)phenylalanine (hereinafter referred to as CI*-Mn
-DP-diPh e tys+)117
4) 2.4-bis(l-dodecyloxyethyl)-M
n-deuteroporphinyl di(p-trifluoromethyl)phenylalanyldiglutamic acid (hereinafter C1m-
M n -D P-diP h e trs+-diG
1 u) (lys) 2- (I-dodecyloxyethyl)-4
-ethynyl-Mn-deuteroporphinyl di(p-
trifluoromethyl) phenylalanine (hereinafter C+ml
s*ma+-Mn DP-diPhe+rs+) (I76) Fe-protoporphinyl diglycine (hereinafter referred to as Fe-PP-diGly)+177) 2
- [1-(2-hydroxyethyloxy)ethyl]
-4-ethynyl-Fe-deuteroporphyrin (hereinafter referred to as -onoE G -F e -D P) +17812- [1-(2-hydroxyethyloxy)ethyl] -4-ethynyl-Fe-deuteroporphyrin diglycine (hereinafter ■anoE G -Fe-D
EG-Fe-D P
-5onoA sp) (lδ0)2.4-bis[1-(2-hydroxyethyloxy)ethyl] -
Fe-deuteroporphinyl diaspartic acid (hereinafter referred to as EG-Fe-DP-diAsp) (I8112,4-bis(l-octyloxyethyl)
-Fe-deuteroporphinyl diaspartic acid (
(hereinafter referred to as Cm-Fe-DP-diAsp) +11S212.4-bis(l-decyloxyethyl)
-Fe-deuteroporphinyl diaspartic acid (
Hereinafter referred to as C+o-Fe-DP-diA sp (I8312, 4-bis(l-dodecyloxyethyl)-Fe-deuteroporphinyl diaspartic acid (hereinafter referred to as CII-Fe-DP diA sp)
118412-(I-dodecyloxyethyl)-4-ethynyl-Fe-deuteroporfinyl diaspartic acid (hereinafter referred to as C1111111111111F e -D
P-diA sp) +18512.4-bis(l-decyloxyethyl)-
Co-deuteroporphinyl diaspartic acid (hereinafter referred to as C10-Co-DP-diAsp)
18612.4-bis(I-dodecyloxyethyl)-
Co-deuteroporphinyl diaspartic acid (hereinafter referred to as C+m-Co-D P diA sp) (I871Cu-protoporphinyl monoserine (hereinafter referred to as Cu-pp-@onoSer) (I8812-
[1-(2-hydroxyethyloxy)ethyl]-4
-ethynyl-Cu-deuteroporphyrin (hereinafter -o
118912, 4-bis(l-octyloxyethyl)
-Cu-deuteroporphinyl diaspartic acid (
(hereinafter referred to as Cm Cu -D P di A Sp) (I9012,4-bis(I-decyloxyethyl)-
Cu-deuteroporphinyl diaspartic acid (hereinafter referred to as C10-Cu-DP-diAsp)
I91) 2.4-bis(l-dodecyloxyethyl)
-Cu-deuteroporphinyl diaspartic acid (
(hereinafter referred to as C+5-Cu-DP-diAs p) (I9ZIZn-protoporphinyl monophenylalanine (hereinafter referred to as Zn-PP-■onoPhe)
19312, 4-bis[1-(2-hydroxyethyloxy)ethyl]-Zn-deuteroporphyrin (hereinafter referred to as EG-Zn-DP) (I9412, 4-bis(I-(2-hydroxyethyloxy) )ethyl]
-Zn-deuteroporphinyl dityrosine (hereinafter E
G-Zn-DP-diTyr) 419512, 4-bis(l-octyloxyethyl)
-Zn-deuteroporphinyl diasparagine M (
(hereinafter referred to as C@ZnDP-dxAsp) (I9612,4-bis(I-decyloxyethyl)
-Zn-deuteroporphinyl diaspartic acid (
+19712.4-bis(l-dodecyloxyethyl)-Zn-deuteroporphinyl diaspartic acid (hereinafter referred to as CIo-Zn-DP-diA sp)
(I98) I n-protoporphinyl monotyrosine (hereinafter referred to as In-PP-monoTyr) (I9
9) 2.4-bis[1-(2-hydroxyethyloxy)ethyl]-In-deuteroporphyrin (hereinafter referred to as EG-In-DP) 1200) 2.4-bis[
1-(2-hydroxyethyloxy)ethyl]-In
-deuteroporphinyl dityrosine (hereinafter E'G-
In-DP-diTyr) +201) 2.4-bis(I-octyloxyethyl)-In-deuteroporphinyl diaspartic acid (hereinafter referred to as Cm-In-DP-diAsp) (202 ) 2.4-bis(l-decyloxyethyl)
-In-deuteroporphinyl diaspartic acid (
Hereinafter referred to as C+a I n-DP diAs p+
20312, 4-bis(l-dodecyloxyethyl)
-In-deuteroporphinyl diaspartic acid (
(hereinafter referred to as Crs I n -D P -diA sp) (e) Effect The metalloporphyrin compound (I) according to the present invention has a scientific advantage in that it has at least one polyfunctional compound residue in the side chain of the porphyrin skeleton. They have structural characteristics that result in them exhibiting various physiological or pharmacological properties. The purpose of the present invention is to provide metal porphyrin derivatives for different uses such as treatment and diagnosis by varying the metals in the porphyrin skeleton. In the case of short phosphorescent lifetime metal porphyrin derivatives, they can be used for diagnostic purposes or as drugs that exhibit antitumor effects on their own. These porphyrin derivatives selectively accumulate in cancer cells and are slowly excreted from cancer cells, but they are rapidly excreted from normal organs and cells, so they do not damage them. Since then, most porphyrin derivatives have a strong effect on light, but by introducing a polyfunctional compound residue into the side chain of metalloporphyrin derivatives according to the present invention, excretion from normal tissues can be increased and Two types of derivatives have been made possible: derivatives designed to maximize the expression of phototoxicity while retaining selective concentration on cancer cells, and derivatives designed to suppress the expression of phototoxicity as much as possible. These properties (cancer affinity, non-phototoxicity, cancer destructive ability in combination with external energy with phototoxicity as an advantage,
The porphyrin derivatives of the present invention are particularly useful as therapeutic agents, diagnostic agents, marker missile 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 1 Laser irradiation (excitation fluorescence spectrum) of the excised organ Pancreatic cancer cells with nitrosamine carcinogenesis were transplanted subcutaneously to 14-
Test drug EG diluted with phosphate buffer was given to golden hamsters (male, 5 animals per group, weight 150 g) on the 21st day.
-Ga-DP-diGly(I4) (I0mg/
After 24 hours of intravenous injection (25 mg/kg body weight) of me), each organ containing cancer was removed, and each organ was injected with Nm-puls.
ed 1aser(N*, 337n-12ns,
The excitation fluorescence spectrum was measured, and wavelengths of 600 to 900 rho were examined based on the peak wavelength of NADH of 470 n-. (N,
-PLS measurement) Table 2 Continued from Table 2 Compounds\Cancer/organ cancer/liver cancer/lung cancer/kidney cancer/serum compounds\cancer/organ cancer/liver cancer/lung cancer/kidney cancer/serum (4) mon
oEG-Ga-DP-sonoGly(5) mnoE
G-Ga-DP-diG1y17) eonoEG-G
a-DP-1IOnoAsp(8) mnoEG-Ga
-DP-diAsp(I01mnoEG-Ga-DP-
diPhe(I2) rM3noEG-Ga-DP-d
iTyr(I3) EG-Ga-DP-sonoGly
114) EG-Ga-DP-diGly(Is) E
G-Ga-DP-eonoLeu (I9) EG-Ga
-DP-IIonoser (22) EG-Ga-DP
-sonoAsp(23) EG-Ga-DP-III
Ono[0]Asp(241EG-Ga-DP-d
iAs9(26) EG-Ga-DP-sonoGlu
(291EG-Ga-RoP-sonoPhe (30)
EG-Ga-DP-diPhe[31) EG-Ga-
DP-mnoTyr (32) EG-Ga-DP-di
Tyr133) EG-Ga-DP-G1y4sp13
4) EG-Ga-DP-3er"ASfl (35)
EG-Ga-DP-ASsrPhe (36) EG-
Ga-DP-Asp-Tyr144) C+-Ga-D
P-diAspl, 75 1.64 1.39 2.30 3.39 2.05 2.24 1.38 1.00 2.18 1.59 1.70 3.00 2.27 2.80 3.48 2.94 1.93 1.30 2.50 1.00 1.50 1.19 2.00 1.35 2, lO 1,50 3,98 2,7δ 1.56 1.42 0.81 O940 1 ,25 1,34 2,87 3,47 3,45 3,26 2,60 2,13 1,04 0,93 3,83 0,20 0,78 3,50 1,94 3,58 1,32 4,13 3,45 2,40 2,44 0,90 3,25 1,71 1,92 3,45 5,13 3,66 4,18 1,19 2,31 3,30 5,05 0, 80 2,27 2,30 1,60 1,73 1,53 0,26 1,05 1,42 2,10 2,50 145) C+-Ga-DP-monoTyr
1.26(48) C,-Ga-DP-diAsp
O,71(49)C,-Ga-DP
-diAsp 2.95 (50) Cso
mal-Ga-DP-diAsp 2.63 (
511C,-Ga-DP-diAsp
3.54(52) C,-Ga-DP-diser
2.70(53) C5-Ga-DP-di
Asp 4.07(54) C,-Ga
-DP-diAsp 5.33 (551
C,-Ga-DP-diAsp 2.96
(56) C,-Ga-DP-diGly
1.69(57) C5-Ga-DP-diser
1.64 (581C, -ra-DP-di
Asp 1.47(59) C,-Ga
-DP-diTyr 1.82 (651C
mtphsasthyu-Ga-DP-diAsp 3
．． 79(66) Co-Ga-DP-diAsp
2.07(68) C,, -Ga-DP-d
iAsp 11.54 (70) C+aua
*ra+-Ga-DP-dlAsp 3.33 (7
2) C+otc+tro+-Ga-DP-diAsp
11.37 (74) l+o+umc+tra+-
Ga-DP-diAsp 9.09 (77) C, *
-Ga-DP-diAsp 4.38 (7
8) Ctt-Ga-DP-dtGlu
2.00 (99) sonoEG-Mn-DP-diG
ly 1.031.19 1.25 3.42 2.33 4.47 1.82 3.89 5.33 2.92 2.44 1.59 2.20 2.63 2.89 3.40 23. 08 4.88 12.39 11.11 7.00 4.00 2.35 2.54 1.25 14.44 3.03 7.72 3.23 6.58 6.86 4.88 3.03 3 .85 2.12 3.23 3.79 3.54 16.44 3.82 15.6G 11.49 8.54 4.00 2.43 1.16 5.91 ! , 54 2.00 1.47 0.89 0.98 0.89 1.92 1.30 0.29 0.76 0.72 1.12 2.78 2.19 2.82 3.50 1.35 The results obtained (cancer/each organ ratio) are shown in Table 2.

Table 2 shows the values obtained by measuring the excitation fluorescence spectra of each organ extracted 24 hours after drug administration, and calculating the peak wavelength at 600 to 900n, using the peak wavelength of 470n as a reference l. Mn.

Since Fe and Cu compounds have weak fluorescence and cannot be measured by -PLS, an extraction method was used for these compound groups.

That is, each organ extracted 24 hours after drug administration is made into an acetone powder, which is extracted with an organic solvent (e.g. chloroform-methanol, etc.), and the resulting extract is exposed to UV light.
Alternatively, the cancer/each organ ratio was calculated by HPLC measurement.

As is clear from the results in Table 2, these porphyrin-related compounds have a remarkable selective affinity for cancer cells.

Example 2 In viv against pancreatic cancer derived from nitrosamines.

Hemorrhagic necrosis effect Test drug C@-Ga-DP-diAsp (54) (I0
mg/m2) administered intravenously (25 mg and 12.5 mg
As a result of blood removal and dissection 24 hours after administration, the cancer masses in the group to which this substance was administered had developed hemorrhagic necrosis, as shown in Figure 1.2.3. In addition, no changes occurred in the liver, lungs, kidneys, and other organs in the administration group, except for cancer, and in the control group (non-administration group).

Therefore, in the same manner, the antitumor effect of the test drug was divided into four stages: G, G, G1, and Gl based on the intensity of hemorrhagic necrosis 24 hours after administration of each drug and the pathological search described in Example 3. did. The results are shown in Table 3.

Example 3 Pathological search Ca-Ga-DP in the tumor-bearing hamster of Example 1
-diA sp (54) instead of Cts-M n
-DPdiA Sp+143) as in Example 2.

Each organ containing cancer (administration group and control group) was fixed with polymerin and embedded in paraffin to prepare paraffin sections, which were double stained with hematoxylin and eosin.
lll 111onoEG-Ga-DP-diAsp(
I5) εG-Ga-DP-@onoLeuf221
EG-Ga-DP-sonoAspf231 EG-G
a-DP-mno[D]Asp(261EG-Ga-D
P-1IonoGlu1331 EG-Ga-DP-G
ly-Asp+34) EG-Ga-DP-Ser・A
sp(351EG-Ga-DP-Asp・Phe(36
1EG-Ga-DP-Asp4yr+37) E-Ga
-DP-sonoserT311) E-Ga-OP-
+5onoAsp(401EC-Ga-DP-mnoA
sp(431Co-Ga-DP-mnoAsp(44
1C,-Ga-DP-diAsp+471 Cm-G
a-DP-sonoAsp14a) C5-Ga-DP
-diAsp+491 C5-Ga-DP-diAsp
(501Cm u sol -Ga-DP-diAsp
1511 C4-Ga-DP-diAsp (521C,
-Ga-DP-diSer+531 C5-Ga-DP
-diAsp+541 C, -Ga-DP-diAsp
tssl Ct-Ga-DP-dtAsp+561C
, -Ga-DP-diGly+st+ Cm-Ga-D
P-duser(581C,-Ga-DP-diAsp
(591G, -Ga-DP-diTyr(651Ca
1PIl++5etkyll-Ga-DP-diAs
p(66) Go-Ga-DP-di contact p+68) C
+5-Ga-DP-diAsp(701Coo 111
*ral-Ga-DP-diAsp1721 Ct*
+e+tyn-Ga-DP-diAgp Table 3 continued Compound hemorrhage necrosis effect (74) C+o+l1tc+tr+++-Ga-DP
-diAgp(761C11-龜-DP-diG1y+
771 C, -Ga-DP-diAsp+781 Co
o-Ga-DP-diG1u+1081 EG-Th-
DP-IIonoAap+1151 Ca-kin-D
P-diGly[1161Cs-Mn-DP-diAs
p(I171Co.-111-[1p-diGly(I
221Co. -Mn-DP-diAI! p+1231
C,,-14n-DP-d[D]Asp(I241Co
o-translation-DP-diGlu11261 Coo-Mn-
DP-diGly-diAsp(+271 Coo-M
n-DP-diLeu-diAsp(I281C,,-
ni-DP-diPhe-diAsp+132) Cto
+aatm+ -Mn-DP-diAspT1341
Ctetc+tre+-Mn-DP-wnoAsp1
1351 Co. Massage+trsl-ni-DP-diAs
p+1371 C+unctt+++-140-D
P-diAsp(I311) C+on+*c+tr+
+, aess+-Mn-DP-dtAsp(I431C
oo-1n-DP-dlAsp+14SI Coo-M
n-DP-diAsp-tetraGly (I471C
+*+m5m5+-Mn-DP-diAsp(I491
C,, -Th-DP-diAsp+154) Coo-
Mn-DP-diAsp-tetraAsp(I601
w4Fran-Mn-DP-diAgp11641 N
ct-1nn-DP-diAsp11811 Cm-F
e-DP-diAsp(I831Coo-Fe-DP-
diAsp+1851 C+5-Co-DP-diAs
p(I861Coo-Co-DP-diAsp(I91
1Ctm-Cu-DP-diAsp+1971Ctm
-Zn-DP-diAsp observation was performed.

The results are shown in Figures 4 and 5, which are photographs of tumor cell destruction in the administration group, in which many organs other than cancer and cell destruction and necrotic layers that were not seen in the control group were observed.

Example 4 In vivo proliferation inhibitory effect The test drug C1a-Mn-DP-diAsp (I221(
I0mg/ml2) intravenously administered (25mg/kg body weight)
Immediately after administration, the size of the cancer was measured from outside the skin using calipers on appropriate days.

Calculation method Volume = volume x (major axis) x (minor axis) In Figure 6, as a drug C + o - M n - D P - di
Asp(I22), C+m-Mn-DP-diA
As is clear from this curve showing tumor growth curves using sp(I431 and the control group), both drugs significantly suppressed tumors and had anticancer activity compared to the control group.

Example 5 In vLtro Photosensitivity Test Mouse leukemia cells (P2S5) 5x 10' cells in 1w
cells (24-well plate) and cultured for 2 hours. Test drug Cm-Ga-DP-diAsp (58),
Clo-Mn-DP-diAsp(I
22) and photofrinn each 1.56.3
．． 136.25.12.5.25.50 n g /
A certain amount of the test solution with a concentration of m 1 (common ratio: 2) was added to the culture solution and irradiated with light of 1 oooOLux for 1 hour.

The cells were cultured for 48 hours and the number of cells per we11 was counted. As a control, a group was provided in which light was blocked with aluminum foil during light irradiation. As an index of photosensitivity, a value (cell growth inhibition rate/%) was calculated by dividing the number of cells in each group by the number of cells in a separately provided untreated group.

As is clear from Figure 7, which shows the cell growth inhibition rate, we observed that the light-irradiated group showed a higher inhibition rate than the control group for Ga complexes.1. Expression of photosensitivity was observed after Ong/m12. On the other hand, regarding the Mnfi body, there was no obvious difference in the inhibition rate between the control and control groups, and no photosensitivity was observed.

Furthermore, an increase in the inhibition rate was observed for each drug at concentrations of 12.5 ng/mn and higher, but this seems to be due to the toxicity of the reagent itself rather than to the light.

Example 6 Phototherapy by In Vivo Yaglaser Test drug Cs-Ga-DP-diAs diluted with phosphate buffer to the tumor-bearing hamster of Example 1
p(54) and C+a-G a D P -diA
s p (6δ) (l Om g/m R) was administered intravenously (I2, 5 mg/kg body weight). 24 hours after administration, the hair above the tumor was removed, phototherapy was started, and Yag
laser (I064nm, 5w, 1osecX4)
was irradiated. After 24 hours of irradiation, the animals were exsanguinated, dissected, and observed. As shown in Figure 8.9, the cancer masses in the group to which this substance had been administered had undergone necrosis. Hey, control group (non-administered group)
The cancer mass had not undergone any changes.

Therefore, it can be seen that the substance of the present invention is effective for treatment using external energy such as Yag 1aser.

Example 7 DCHA salt of Ga-protoporphyrin (hereinafter referred to as Ga-P
DCHA salt of P) 60 mj of chloroform to Ig!
Add i5 and 10rnj2 of tetrahydrofuran and dissolve. Next, glycine ethyl hydrochloride ester (hereinafter Gly
Add 0.5 g of (OEt) ・HCI), and gradually add Wsco and Ig while stirring and allow to react for 2 hours.
After reaction (TLC [chloroform:methanol (4:1)
] 1) Wash the reaction solution with water to collect unreacted substances,
After separation, the chloroform layer was concentrated. The obtained concentrate was recrystallized from ethanol-ethyl acetate to give Ga-PP-1◎口◎Gly (OEt) (I ethyl varnish fJLt)
O,'.

2g was obtained. Yield 16.4% Example 8 1/2 NKOH alcohol solution was added to 1 g of ethyl ester O of 1 until the hydrolysis reaction was completed, and after the reaction (
(confirmed by TLC), add 10% citric acid solution, pH 5
, 5, and concentrated after extraction with chloroform. The obtained concentrate was recrystallized from methanol-ethyl acetate to give Ga-P
0.11 g of P-monoGly(I) was obtained. Yield 98
．． 0% Example 9 Chloroform 10 to 0.38 g of DCHA salt of Ga-PP
mA! Add and dissolve 3ml of acetonitrile.

Then, tyrosine methyl hydrochloride (hereinafter 7 yr
Add 0.38 g of WSCo (referred to as OM e ・HCI), gradually add 38 g of WSCo under stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare Ga-PP-diT.
Obtained 0.22 g of yr (3), yield 60.0% Example 10 2-[1-(2-hydroxyethyloxy)ethyl]
- DCHA salt of 4-ethenyl-dutete volfili (
Hereinafter referred to as DCHA salt of onoEG-Ga-DP)2
300 ml of chloroform and 150 ml of acetonitrile are added to the solution. Next, 2 g of Gly(OEt).HCl dissolved in 20 mβ of water was added, and 14 mA+ of a 10% WSC chloroform solution was gradually added while stirring.
onoEG-Ga-DP-monoGly (4
) O, l l g was obtained. Yield 7.4% Example 11 DCHA salt of sonoE G -G a -D P 1.
6g of chloroform 60mβ right and acetonitrile 30
Add mβ and dissolve. Next, Gly (OEt)・I
Add 0.75 g of Cl, gradually add 1.3 g of dicyclohexylcarbodiimide (hereinafter referred to as DCC) while stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare 5 on
oEG-Ga-DP-diGly(5)1. l1g
I got it. Yield 89.8% Example 12 1 g of DCHA salt of monoE G -G a -D P
Add 10mg of chloroform and 20mg of acetonitrile.
Add and dissolve. Next, 0.5mj of dimethylformamide (hereinafter referred to as DMF)! Hydrochloric acid aspartic acid dimethyl ester (hereinafter Asp (OMe).HC) dissolved in
2 g of 0noEG-G a-DP-mo was added, 2 mβ of 5% WSC chloroform solution was gradually added under stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain 0noEG-G a-DP-mo.
0.25 g of noAs P (7) was obtained. Yield 32.
3% Example 13 5g DCHA salt of monoE G -G a -D P
to 50 mI of chloroform and 100 mI of acetonitrile.
Add m1 and dissolve. Then, 50%Asp(QMe)
- Add 5 ml of HCI DMF solution and add WSe under stirring.
Gradually add 2.2 g and proceed in the same manner as in Example 7 and Example 8 to obtain monoE G -G a -DP-d.
3.8 g of iAsp (8) was obtained. Yield 86, 5% Example 14 DCHA salt of monoE G -G a -D P 10
g to 280 ml of chloroform and 1 ml of acetonitrile.
Add 40 ml and dissolve. Then, phenylalanine methyl hydrochloride (hereinafter Phe (OMe) .H
Add 10g of CI and stir while stirring.
8g was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain aonoE G -G a -D P -d
8.3 g of iPhe (I0) was obtained. Yield 89.8% Example 15 3 g of DCHA salt of monoE G -G a -D P
150ml of chloroform and 15ml of acetonitrile
Add 0ml and dissolve. Then, 3 g of Tyr (OMe)HHCl dissolved in 3 ml of water was added, and W was added under stirring.
SClg was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain an auto-onoE G -G a -D P.
-monoT yr (l l ) 0, 62 g
I got it. Yield 24, 9% Example 16 DCHA salt of sonoE G -G a -D P 1.
07 g to 45 ml of chloroform and 1 acetonitrile
Add 5mI2 and dissolve. Next, Tyr (OMe)
・Add 11g of IC and stir.1. 1 g of mDCC was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare 5onoEG-Ga-DP-diTyr(I2)1.
I got Olg. Yield 97.6% Example 17 Ga protoporphyrin dimethyl ester (hereinafter referred to as Ga
-P P -M e) to 150 g of 6% hydrobromic acid/acetic acid (hereinafter referred to as HB r / HOA c) 1.
Add and dissolve 512. -After standing for a day and night, concentrate under reduced pressure at 50℃ or less, add ethylene glycol to the Br form obtained after concentration, dissolve it, and leave it for a day and night. After zero reaction (confirmed by TLC)
, washed with water, hydrolyzed, and recrystallized (acetone-ethyl acetate) to give 2,4-bis[1-(2-hydroxyethyloxy)ethyl]-Ga-deetheroborphyrin c
90 g (hereinafter referred to as EG-Ga-DP) was obtained. Yield 50
．． 6% Example 18 DCHA salt 1 of EG-Ga-DP obtained in Example 17
1 OQ ml of chloroform and 100 mβ of acetonitrile are added to the solution. Then, water 10rnI2
Add Gly (OEtl・HCIIg) dissolved in
G-Ga-DP-sonoGly (I3) 0.
2g was obtained. Yield 27.2% Implementation ζ 19 20 ml 2J5 of chloroform and lOmβ of acetonitrile are added to 0.5 g of DCHA salt of EG-Ga-DP and dissolved. Next, Gly (OEtl・ICl0.25g
was added, 4 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare EG-Ga-D.
0.28 g of P-diGly (I4) was obtained. Yield 71.4% Example 20 2 g of DCHA salt of EG-Ga-DP was added with 20 g of chloroform.
Add m12 and 60 mI2 of acetonitrile to dissolve. Next, leucine methyl hydrochloride (hereinafter Leu(OMe).HCI) dissolved in DMF 5 mJ
) 1 g and gradually added 2 ml of 3% WSC chloroform solution while stirring, and the following Example 7 and Example 8 were prepared.
Operate in the same manner as EG-Ga-DP-monoLeu
15 g of (I5) O was obtained. Yield 9.6% Example 21 2 g of DCHA salt of EG-Ga-DP was added to oo form 20
Add m12 and 60mj+ of acetonitrile and dissolve. Then, L e u (OM
e)-)1cI)l g and 3% W under stirring.
Gradually add 2 ml of SC chloroform solution and proceed in the same manner as in Example 7 and Example 8 to prepare EG-Ga-DP.
-diLeu (I6) 0.21 g was obtained. Yield 1
1.9% Example 22 30 chloroform to 2 g of DCHA salt of EG-Ga-DP
Add mgJ5 and 30 mβ of acetonitrile to dissolve.

Then, serine methyl hydrochloride (hereinafter Ser (OMel・)ICI) dissolved in DMF4mjt
1 g of EG-Ga-DP-monos was added, and 6 ml of 6% WSC chloroform solution was gradually added under stirring, and the procedure was repeated in the same manner as in Example 7 and Example 8 to obtain EG-Ga-DP-monos.
0.49 g of e r (I9) was obtained. Yield 11.
8% Example 23 25g of DCHA salt of EG-Ga-DP was added with chloroform 2
Add 50 mβ and 500 mJ2 of acetonitrile to dissolve. Then, Asp(OM
e) Add 12g of HCl.

After one reaction in which 32.5 mQ of 10% WSC chloroform solution was gradually added while stirring and allowed to react for 70 minutes (confirmed by TLC), the reaction solution was washed with water, extracted and separated with 4% Na HCOs solution, and then diluted with water. Add 10% citric acid solution to the layer
(Adjust to 5.5. The pH-adjusted aqueous layer is extracted with chloroform and concentrated under reduced pressure.
Methyl ester of onoA sp (22) 6
．． 63g was obtained. On the other hand, the chloroform layer was concentrated under reduced pressure to obtain 2.3 g of the methyl ester of EG-Ga-DP-diASP (24). E
G-Ga-DP-monoAsp (22) 70mgJ
5 and EG-Ga-DP-diAsp (24) 50m
Example 24 To 5 g of DCHA salt of EG-Ga-DP was added 50 g of chloroform.
Add mε and 100 mA+ of acetonitrile to dissolve. Next, DMF2.5mj! [D]As dissolved in
Add 2.5 g of p (OMe) HCl, gradually add 18 mβ of a 5% WSC chloroform solution while stirring while cooling, and proceed in the same manner as in Example 23 to obtain E G -G a
-D P -5ono[D] A sp (23)0
．． 75g was obtained. Yield 20.1% Example 25 00 form Io per 1 g of DCHA salt of EG-Ga-DP
n! Add and dissolve 20 ml of acetonitrile.

Next, 0.5 g of hydrochloric acid glutamic acid diethyl ester (Glu (hereinafter referred to as OEtl.HCl)) dissolved in 5 mg of DMFo was added, and 4 mA of a 5% WSC chloroform solution was gradually added while stirring to prepare Examples 7 and 8. Operate in the same manner as E G -G a -D P -m
42 mg of onoG lu (26) was obtained. Yield 5.
27% Example 26 12 ml of chloroform and 20 ml of acetonitrile are added to 0.5 g of DCHA salt of EG-Ga-DP and dissolved. Then, salt-acid lysine methyl ester (hereinafter Lys (OMe)-MCI) dissolved in 10 mI2 of DMF was added.
EG-Ga-DP-son.
80 mg of oLys (28) was obtained. Yield 20.
1% Example 27 30 mJ of chloroform to 0.5 g of DCHA salt of EG-Ga-DP! 15 and 30ml of acetonitrile to dissolve. Then, Phe (OM
Add 0.5 g of el HCl and add 10% WSC while stirring.
Gradually add 5 mβ of chloroform solution and proceed in the same manner as in Example 7 and Example 8 to obtain EG-Ga-DP-mo.
0.24 g of noPhe (29) was obtained. Yield: 59. O
% Example 28 40 mg of chloroform and 13 mg of acetonitrile are added to 0.5 g of DCHA salt of EG-Ga-DP and dissolved. Then, Ph e (OM e )-HCIo,
Add 5 g of 10% WSC chloroform solution 5 while stirring.
EG-Ga-DP-diPhe (30
) 0.38g was obtained. Yield: 80.8% Example 29 150 mI of chloroform was added to 5 g of EG-Ga-DP2. Add 25 mg of acetonitrile and 15 mI2 of DMF and dissolve. Then, T dissolved in 15ml of DMF
yr (Add 5 g of OMel-HCl, gradually add 15 mβ of 5% DCC chloroform solution while stirring, and proceed in the same manner as in Example 8 to prepare EG-Ga-DP-son.
Obtained 1.4 g of oTyr (31), yield 23.2% Example 30 DCHAI of EG-Ga-DP! Chloroform 4 for Ig
Add and dissolve 0mlb and 20ml of acetonitrile.

Next, 11 g of Tyr (OMe).IC was added, and WSClg was gradually added while stirring, and the following operations were carried out in the same manner as in Examples 7 and 8 to prepare EG-Ga-DP-diTyr.
(32) Obtained 0.78 g, yield 80.5% Example 31 E G -G a -D P - obtained in Example 18
Mon.

DCHA salt of G131(I3) ethyl ester 0.2g
Add 8ml of chloroform and 4me of acetonitrile to dissolve. Next, Asp(OMet・HCI 0
．． 2 g of WSCo was added thereto, 2 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare EG-
Ga-DP-Gly・Asp (33) 0.11g
I got it. Yield 62.8% Example 32 E G -G a -D P - obtained in Example 23
Mon.

0.2 g of DCHA salt of ASP (22) methyl ester with 8rn12 chloroform and 4mI2 acetonitrile.
Add and dissolve. Then, Ser(0MeiHCI 0
．． 2 g of WSCO was added thereto, 93 g of WSCO was gradually added with stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare EG-
70 mg of Ga-DP-3er-Asp (34) was obtained. Yield 39.3% Example 33 E G -G a -D P - obtained in Example 23
Mon.

8 ml of chloroform and 4 mβ of acetonitrile are added to 0.2 g of DCHA salt of Asp(22) methyl ester and dissolved. Then, Phe (OMeiHCl 0.
2 g of WSCo was added thereto, 2 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare EG-G.
0.17 g of a-DP-Asp-Phe (35) was obtained. Yield 61.8% Example 34 E G -G a -D P - obtained in Example 29
Mon.

8 ml of chloroform and 4 ml of acetonitrile to 0.2 g of DCHA salt of Tyr(31) methyl ester
Add and dissolve. Then, Asp(OMeiHCl 0
．． 2 g of WSCO was added thereto, 12 g of WSCO was gradually added with stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare EG-
Ga-DP-As p.Tyr (3B)O,Ig was obtained. Yield 52.9% Example 35 Ga-PP-Me 10g, 6%HBr/HOA
24-bis[1-(2
MC-Ga-DP and EC-Ga -DP
2.3g and 1.63g were obtained respectively. Yield 28.1
%, 12.8%) Example 36 DCHA salt of MC-Ga-DP obtained in Example 35 0
．． 8g to 8ml of chloroform and 16ml of acetonitrile
Add m1 and dissolve. Next, 0.4 g of Asp(OMel.ICl) dissolved in 4 ml of DMFo was added, and 3 mβ of a 5% WSC chloroform solution was gradually added while stirring.
-DP-monoAsp (38) 0.13 g was obtained.

Yield 20.5% Example 37 DCHA salt of EC-Ga-DP obtained in Example 35 0
．． 8g of chloroform 8mβ and acetonitrile l
6mj! Add and dissolve. Next, 0.4 g of Asp (OMel.HCl) dissolved in 4 ml of DMFo was added, and 5% WSC was added under stirring.

Gradually add 1 ml of form solution and proceed in the same manner as in Example 7 and Example 8 to obtain EC-Ga-DP-sonoA.
0.21 g of sp (40) was obtained. Yield 33.0
% Example 38 G a - P P - M e 6 g, 10% HB r
/ HOA c60mβ was used, and methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol, and heptyl alcohol were used separately in place of ethylene glycol.

The same procedure as in Example 17 was carried out using 30 mI2 each of octyl alcohol, nonyl alcohol, decyl alcohol, and dodecyl alcohol. After hydrolysis, the former two were recrystallized (methanol-ethyl acetate), and the latter ten were After silica gel column chromatography (ethyl acetate-hexane), recrystallization was performed to obtain 2.4-bis(I-methoxyethyl)-Ga-deuteroporphyrin, 2.4-bis(I-ethoxyethyl)-Ga- Deuteroporphyrin, 2,4-bis(l-propoxyethyl)-Ga-deuteroporphyrin, 2,4-bis(I-isopropoxyethyl)-Ga-deuteroporphyrin, 2,4-bis( I-butoxyethyl)-Ga-deuteroporphyrin, 2,4-bis(
l-bentyloxyethyl)-Ga-deuteroporphyrin, 2,4-bis-hexyloxyethyl)
-Ga-deuteroporphyrin, 2,4-bis(
I-hebutyloxyethyl)-Ga-deuteroporphyrin, 2.4-bis(l-octyloxyethyl)-Ga-deuteroporphyrin, 2.4-bis(l-nonyloxyethyl)-Ga-deuteroporphyrin Porphyrin 2.4-bis(l-decyloxyethyl)-G
a-deuteroporphyrin and 2,4-bis(l-
dodecyloxyethyl)-Ga-deuteroporphyrin (hereinafter referred to as C2-Ga-DP, C,-Ga-DP, C5-
Ga-DP, Cx++s*+ -Ga-DP, C4-G
a-DPCs G a DP , Ca -G
aDP,Cy-Ga-DP,C
a-GaDP, CsGa-DP,
C+o Ga DP and C+*-Ga-DP) 1.0 g, 0.45 g, 2.7 g, 1°3 g, 2
．． 8g, 2.0g, 1.6g, 4.0g1.4g, 0.
84 g, 0.66 g and 2.0 g were obtained. Yield 15.
2%, 6.6%, 38°0%, 18.4%,
38. 1%, 26, 4%, 2084
%, 49, 9%, 16.4%, 9,
8%7,5%,21,3%) Example 39 D of C + Ga D P obtained in Example 38
Add 5 ml of chloroform 2 JS and 2 m 2 of acetonitrile to 0.5 g of CHA salt and dissolve. Then, A sp
(Add 0.5 g of OMelHCI and add WS under stirring.
After gradually adding 51 g of Co, the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain C+ -G a D P-diA.
sp (44)0. 44g was obtained. Yield: 100% Example 40 30 mg of chloroform and 30+t+Q of acetonitrile are added to 0.5 g of DCHA salt of C,-Ga-DP and dissolved. Next, 3.5 mJ of water! Tyr (O
Add 0.5 g of Me)・HCl and add 1O%W while stirring.
Gradually add 3 mQ of SC chloroform solution and proceed in the same manner as in Example 7 and Example 8 to obtain Cr - Ga -
0.14 g of D P -monoTyr (45) was obtained. Yield 34.3% Example 41 D of C*G a -D P obtained in Example 38
Chloroform 5mA to CHA salt 0.5g! Add and dissolve 2 mff of acetonitrile. Next.

Add 0.5 g of Asp (OMe)l (CI), gradually add 47 g of WSCo under stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain Cs -G a -D P-
0.42 g of diAsp (4B) was obtained. Yield 95.2
% Example 42 D of C s -G a -D P obtained in Example 38
Add 5 mI2 of chloroform and 2.5 mβ acetonitrile to 0.5 g of CHA salt and dissolve. Next, Asp
Add 0.75 g of (OMe)・HCI, and add WS under stirring.
Gradually add 52 g of Co and proceed in the same manner as in Example 7 and Example 8 to obtain Cs-Ga-DP-diAsp.
(49) 0.32 g was obtained. Yield 72.2% Example 43 C 111m++l Ga obtained in Example 38
-DP DCHA salt 0.2g and chloroform 4.5m
Add A and 1.5 mff of acetonitrile and dissolve.

Next, A sp (oMen・■ct o, 2
Add g.

While stirring, 31 g of WSCo was gradually added and the following Example 7 was prepared.
and C3°1° in the same manner as in Example 8.

-Ga-DP-diAsp (50) 0.11 g was obtained. Yield 62.2% Example 44 DCHA salt of C, -Ga-DP obtained in Example 38 0
．． 5 g of chloroform 5 mI2 and acetonitrile 2
．． Add 5mI2 and dissolve. Then, Asp (OMe
Add 0.75 g of lHCl and add WSCo, 5 g under stirring.
Gradually add 9g of C4G a-DP-diAsp (51)0 in the same manner as in Example 7 and Example 8.
．． 44g was obtained. Yield 100% Example 45 D of C s Ga -D P obtained in Example 38
Add chloroform 6rr+42 and 3 mg of acetonitrile to 0.3 g of CHA salt and dissolve. Next.

Add 0.2 g of Ser (OMelHCI), gradually add 4 ml of 5% WSC chloroform solution under stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain C5-Ga-
0.22 g of DP-diser (52) was obtained. Yield 8
6.8% Example 46 To 0.2 g of DCHA salt of Cs-G a -D P, 4.5 ml of chloroform and 1.5 m of acetonitrile were added.
Add I2 and dissolve. Next, Asp(OMel・IC
0.2 g of WSCo was added, and 25 g of WSCo was gradually added under stirring.
0.17 g of 5-Ga-DP-diAsp (53) was obtained. Yield 95.5% Example 47 DCHA salt of C, -Ga-DP obtained in Example 38 0
．． 14mj of chloroform in 75g! Add and dissolve 7ml of acetonitrile. Then, A sp (O
Add 1 g of Mel-HCl and add WSCo, 6
8 g was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain Ca-G a -D P-diAsp (
54) 0.5g was obtained. Yield 74.6% Example 48 DCHA salt of C--Ga-DP obtained in Example 38 0
．． 43g of chloroform 4mQb and acetonitrile 2
Add mA and dissolve. Then A sp (OM e
Add 44 g of IHcI 0 and add WSCo under stirring.
After gradually adding 59 g of Ct-G a -DP-diAsp (
55) 0.34g was obtained. Yield 88.3% Example 49 D of Ca-Ga-D P obtained in Example 38
45 mj2 of chloroform and 15 mρ of acetonitrile are added to 2 g of CHA salt and dissolved. Next, Gly(OE
t) Add 2 g of HCl, gradually add WSClg with stirring, and proceed in the same manner as in Example 7 and Example 8 to add C.
0.4 g of a-Ga-DP-diG I y (5B) was obtained. Yield 26.8% Example 50 Opform 15 in 1 g of DCHA salt of C,-Ga-DP
Add rr+12 and 15 mI2 of acetonitrile to dissolve. Then, 0.5 g of Ser (OMel.HCl) was added, and 10% of a 5% WSC chloroform solution was added with stirring.
m12 was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare Ca-G a -D P -diSer.
(57) 0.74 g was obtained. Yield 86.5% Example 51 1.5 g of DCHA salt of C,-Ga-DP and 80 mA of chloroform! Add and dissolve 30 mQ of acetonitrile. Then, add 2g of Asp (OMe)・HCl,
C@-Ga-DP-diAs
0.16 g of p (58) was obtained. Yield: 12.7% Example 52 45 mI2 of chloroform and 15 mβ of acetonitrile are added to 5 g of DCRAMAl of C--Ga-DP and dissolved. Then, Tyr (OMel-HCll, 5
Then, while stirring, 1 g of WSC was gradually added, and the same procedure as in Example 7 and Example 8 was repeated to obtain C,-Ga-
0.28 g of DP-diTyr (59) was obtained. Yield 2
0.3% Example 53 Ga-PP-Me6g, 3%HBr/HOAC
Using 60mI2, instead of ethylene glycol,
The same procedure as in Example 17 was carried out using 30 mβ of octyl alcohol, and after hydrolysis, recrystallization was performed using silica gel column chromatography (ethyl acetate-hexane).
G a D P and 2-(l-octyloxyethyl)
0.98 g of a mixture of -4-ethynyl-Ga-deuteroporphyrin (hereinafter referred to as C@l+++smel Ga-DP) was obtained. Yield 11.7% Example 54 C a -G a D P and C obtained in Example 53
D of mixture of 11+aane-I G a -D P
Add 45 mβ of chloroform and 45 mI2 of acetonitrile to 2 g of CHA salt and dissolve. Next, Gly(OE
Add 12 g of tl・IC, gradually add WSClg while stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare G.
Ly mixture compound. This mixture was purified by 03 (C8) medium pressure high performance preparative liquid chromatography [(eluent, MeOH-HIO (9
: 1)] C@ 1m5a*l -G a-di
0.005 g of Gly (60) was obtained. Yield 0.3% Example 55 C--Ga-DP and Ca 1111+11@l -G
120 mβ of chloroform is added to 6 g of the DCHA salt of the a-D P mixture and dissolved. Then, Asp (OMe
Add 18 g of l・IC, gradually add 2.5 g of WSe with stirring, and proceed in the same manner as in Example 7, Example 8, and Example 54 to obtain Ca 1ms++*l -G a -dx.
0.3 g of A sp (62) was obtained. Yield 6.3% Example 56 Ca-G a DP and Ca 1 mmm. )-G
a 45 m4 of chloroform and 15 mg of acetonitrile are added to 1.5 g of the DCHA salt of the D P mixture and dissolved. Then, Tyr (OM e 1-HCI
Example 7. In the same manner as in Example 8 and Example 54, Ca+s+eae+ -G a di
13 g of Tyr (63) O,O was obtained. Yield 069% Example 57 Ga-PP-Me6g, 10% HBr/HOAc60m
j! The procedure was repeated in the same manner as in Example 17 using phenethyl alcohol (30 mI2) instead of ethylene glycol, and after hydrolysis, recrystallization was performed on silica gel column chromatography (ethyl acetate-hexane) to obtain C8 N@
2.9 g of m#tRFll-G a-oP (64) was obtained. Yield: 66.1% Example 58 To 0.2 g of the DCHA salt of 64 obtained in Example 57, 4.5 mg of chloroform and 1.5 mg of acetonitrile were added and dissolved. Next, Asp (OMe)・HCI
0.2 g of WSCo was added, and 25 g of WSCo was gradually added with stirring.
1Pl+++s*Lyll -G a-DP-diAs
0.06 g of p(65) was obtained. Yield 33, 5% Example 59 DCHA salt of C, -Ga-DP obtained in Example 38 0
．． Add 10mff1J3 of chloroform and 5mβ of acetonitrile to 17g and dissolve. Then, As p (O
Add 0.2 g of Me)-HCl and add WSCo under stirring.
, 27 g was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain C*-G a -DP-diAsp.
(66) 0.15 g was obtained. Yield 98.0% Example 60 To 0.38 g of the DCHA salt of C1°-Ga-DP obtained in Example 38, 6 mρ of chloroform and 3 ml of acetonitrile were added and dissolved. Then Ser (OMe)
・Add 2g of l1clO, gradually add 4ml of 5% WSC chloroform solution while stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare Cue-Ga-DP-di.
0.29 g of Ser (67) was obtained. Yield: 88.6% Example 61 10 ml of chloroform and 5 ml of acetonitrile are added to 0.54 g of DCHA salt of Coo-Ga-DP and dissolved. Then, A sp (OM e )-ICIO
, 54 g of WSCo was added thereto, and 54 g of WSCo was gradually added under stirring.
oo Ga DP-diAsp (68) 0.48
I got g. Yield 98.4% Example 62 Ga-PP-Me4.5g, 10% HBr/HOAc4
5mJ! The procedure was repeated in the same manner as in Example 17 using 25 ml of geraniol in place of ethylene glycol, and after hydrolysis, recrystallization was performed using silica gel column chromatography (ethyl acetate-hexane).
1.0 g of ral-G a -D P (69) was obtained. Yield: 15.2% Example 63 To 0.5 g of the DCHA salt of 69, add 10 mI of chloroform and 5 mβ of acetonitrile and dissolve.
A sp (Add 0.5 g of OMel・ICI,
Example 7 was prepared by gradually adding 73 g of WSCo while stirring.
And C1゜+a*ra+-
G a-D P-diA S P (70) 0, 4
2g was obtained. Yield 93.1% Example 64 Ga-PP-Me3g, 10%HBr/HOAc30m
Example 17J5 and Example 6 using β and citronellol 18m12 instead of ethylene glycol
Operate in the same manner as 2, C6゜1cttrsl Ga-D
4 g of P (71) 1 was obtained.

Yield 31.8% Example 65 10 mβ of chloroform and 5 m12 of acetonitrile were added to 0.5 g of DCHA salt of 71 and dissolved.
0.5 g of sp (OMe).HCl was added, 72 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain Cl.

1elarsl -G a -D P-dlA Sp
(72) 0.43 g was obtained. a rate 95.3% Example 66 Ga-PP-Me3g, 10% HBr/HOAc
Using 30 mβ and 18 ml of dihydrocitronellol instead of ethylene glycol, the procedure was repeated in the same manner as in Example 17 and Example 62 to obtain CH+1□c+tr*
1-Ga-DP (73) 1, 1 g was obtained. Yield 24.8% Example 67 10 ml of chloroform and 5 mβ of acetonitrile were added to 0.5 g of DCHA salt of 73 and dissolved.
sp (OMe)-ICI O, 5 g was added, WSCo, 72 g was gradually added under stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain C1° + 11 ficltral.
-Ga-DP diAsp (74) 0.42 g was obtained. Yield 93.8% Example 68 C1. obtained in Example 38. -DCHA# of Ga-DP
! Chloroform 20mA to Ig! Add and dissolve 1 Omg of acetonitrile. Next.

Add 1 g of G 1 y(OEt)・HCl, gradually add 0.93 g of diwsC with stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain Cps-Ga-DP-diG.
0.82 g of ly (76) was obtained. Yield 100% Example 69 5 mg of chloroform and 2 mjl of acetonitrile are added to 0.5 g of DCHA salt of Cps-Ga-DP and dissolved. Next, As p (OMe)・HCl 0°5g
Add WSCo, 35. under stirring. Cps-Ga
-DP-diAsp (77) 0.44 g was obtained. Yield: 97.1% Example 70 5 ml of chloroform and 2 ml of acetonitrile are added to 0.5 g of DCHA salt of C1y-Ga-DP and dissolved. Next, 0.75 g of Glu (OE tiHcl) was added, and 44 g of WSCo was gradually added while stirring, and the same procedure as in Examples 7 and 8 was carried out to prepare Cp.
s-Ga-DP-diG 1 u (78) 046g
I got it. Yield 99.4% Example 71 Ga-PP-Me4. 5g, 10% HBr/HO
Using Ac45mI2, instead of ethylene glycol, separately 25 m each of tetrahydrofurfuryl alcohol and tetrahydrobilane-2-methanol! Operated in the same manner as Example 17i3 and Example 62 using Na
Fran-Ga-DP (79) 3.3g and H4Fy
3.2 g of r a n -G a -D P (81) was obtained. a ratio: 55.9%, 52%, 4% Example 72 Example 71t' To 0.2 g of the obtained DCHA salt of 79, 4 mJ2 of chloroform and 2 mA of acetonitrile are added and dissolved. Next, Asp(OMe)・ICl0.3g
was added, 2 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7J5 and Example 8 to prepare wnFran.
-Ga-DP-diAsp(80) 0.17g was obtained.

Yield: 95.1% Example 73 Example 71't'' 6 mA of chloroform and 3 mJ2 of acetonitrile were added to 0.3 g of the obtained DCHA salt of 81 and dissolved. Then, Asp(OMe)-ICIO,4
Then, 3 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare n4Pyra.
0.25 g of n-Ga-DP-diAsp (82) was obtained. Yield 92.9% Example 74 0.3 g of D CHA salt of Mg-protoporphyrin and 20 mj of chloroform! Add and dissolve 1 mg of lysine. Then, “ry r (OMe)-HCIo, 3
Then, while stirring, 3 g of WSCo was gradually added, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain Mg-PP-
0.1 g of diTyr (88) was obtained. Yield 34.6
% Example 75 PP-Me3g, 10%HBr/HOAc3
Example 17 and Example 6 using 18 mj+ each of ethylene glycol, octyl alcohol, decyl alcohol, undecyl alcohol, dodecyl alcohol, tetradecyl alcohol, hexadecyl alcohol and octadecyl alcohol, respectively.
2, 4-bis[1-(2-hydroxyethyloxy)ethyl]deuteroporphyrin,
2.4-bis(l-octyloxyethyl) deuteroporphyrin, 2.4-bis(l-decyloxyethyl) deuteroporphyrin, 2.4-bis(l-undecyloxyethyl) deuteroporphyrin, 2 , 4-bis(l-dodecyloxyethyl) deuteroporphyrin, 2. 4-bis(l-tetradecyloxyethyl) deuteroporphyrin, 2.
4-bis(I-hexadecyloxyethyl) deuteroporphyrin and 2,4-bis(l-octadecyloxyethyl) deuteroporphyrin (EG-DP)
C,-DP,C,. -DP, Cl1-DP, Cl-D
P, C,, -D P, C1, -D P and C
,, -D P) 3.2g, 1.78g, 1.0 each
g.

0.89g, 1.12g, 0.75g, 0.09g and o,sg were obtained. Yield 88.9%, 426%, 22.
4%, 19.1%, 23.6%.

14, 9%, 1, 7%, 14.3
% Example 76 Pyridine 1β was added to 6 g of EG-DP obtained in Example 75, 40 g of magnesium perchlorate was suspended, and the mixture was allowed to react under heating (15°C) for 3.5 hours. After concentrating the reaction solution, water was added. When added, crystals precipitate. The obtained precipitate was collected by filtration, dried, and then hydrolyzed in the same manner as in Example 8 to obtain 2.7 g of EG-Mg-DP (89). Yield 43
．． 5% Example 77 0.4 g of DCHA salt of 89 and 24 m of tetrahydrofuran
Add β and dissolve. Then, Tyr (OMe) −
Add ICIo, 4 g and wsco under stirring.

85 g was gradually added and the following procedure was repeated in the same manner as in Example 7J3 and Example 8 to obtain EG-Mg-DP-diTyr (90
) 0.12g was obtained. Yield 23.0% Example 78 Acetic acid 20ml1. , PP-Melg, manganese acetate 1
g, sodium acetate Ig was added and suspended under heating (75
After the reaction (confirmed by TLC) for 20 minutes (~78°C), water is added to the reaction solution to precipitate crystals. The obtained precipitate was collected by filtration, dried, and then hydrolyzed in the same manner as in Example 8 to obtain Mn-protoporphyrin (hereinafter referred to as Mn-P
P) 0.74 g was obtained. Yield 70.8% Example
79 0.6 g of DCHA salt of Mn-PP obtained in Example 78
Add 40 mR15 of chloroform and 2 m, g of pyridine to the solution and dissolve. Next, 0.6 g of Tyr (OMe).HCI) was added, and 6 g of WSCo was gradually added with stirring, followed by the same operation as in Example 23.
noTyr (OMe) (methyl ester of 95)
0.1 g was obtained. Yield 20.6% Example 80 0.0% to the ester obtained in Example 79. Add 1N NaOH and heat slightly to cause hydrolysis reaction. After reaction (TLC
(confirmed in Example 8), and then proceed as in Example 8 to prepare Mn-PP
0.09 g of -5onoTyr (95) was obtained. Yield 9
1.6% Example 81 0.3 g of DCHA salt of Mn-PP and 20 m of chloroform
12 and 1 ml of pyridine and dissolve.
Tyr (0.3 g of OMelHCI was added, 3 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 80 to obtain M n -PP-diTyr.
(96) 0.1 g was obtained. Yield 37.3% Example 82 2-[1-(2-hydroxyethyloxy)ethyl]-4-ethenyl deether porphyrin (hereinafter referred to as mo
1 each of i5 and EG-DP
0 g, each separately added and dissolved in 60 ml of chloroform and 20 m of methanol, then manganese acetate lo, each dissolved in 8 ml of methanol,
After 0 reaction (confirmed by TLC) in which 2 g of the mixture was added under stirring and the mixture was reacted by heating (70 to 75°C), the reaction solution was concentrated under reduced pressure. The obtained concentrate was washed with water, filtered, and the filtered material was dried.
oE G -M n -D P (97) 2, 2
g and 2.35 g of EG-Mn-DP (I03) were obtained. Yield 22.0%, 20. 8% Example 83 To 4 g of DCHA salt of 97, add 120 ml of chloroform and 60 ml of acetonitrile and dissolve. Next, add 13 g of Gly (QEtl.IC) and dissolve in WS under stirring.
After one reaction in which 4g of C was gradually added and the reaction was allowed to proceed for 80 minutes (
Confirmed by TLC) 1. The reaction solution was washed with water and diluted with 4% NaHCO-
Extract and separate the solution.

A 10% citric acid solution was added to the aqueous layer to adjust the pH to 5.5. The aqueous layer adjusted with p11 was extracted with chloroform and concentrated under reduced pressure.
The ethyl ester of ly(98) was obtained. On the other hand, the chloroform layer was concentrated under reduced pressure to produce -onoEG-Mn-DP.
-diG1y (99) ethyl ester was obtained. Hereinafter, each ester was hydrolyzed in the same manner as in Example 8 to obtain -onoEG-Mn-DP-monoG.
l y (98) 1, 2 g and horse onoE
1.5 g of G-Mn-DP-diGly (99) was obtained.

Yield 45.1%, 52. '6% Example 84 Add 50 m Q of chloroform and 0 mg of acetonitrile I to 5 g of DCHA salt of 97 and dissolve.
2.2 g of WSe was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain -onoE.
G-Mn-DP-diAsp (I00)1. Ig was obtained. Yield: 27.0% Example 85 90 mJ of chloroform and 45 mβ of acetonitrile are added to 3 g of the DCHA salt of 97 and dissolved.

Next, 3 g of Ph e (OMe)-HCl was added, 3 g of WSC was gradually added while stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain ■onoEG-Mn -
2.61 g of DP-diPhe (I01) was obtained.

Yield: 100% Example 86 To 4 g of the DCHA salt of 97, 18 ml of chloroform and 60 mJ of acetonitrile are added and dissolved. Then, T
yr (Add 4 g of OMelHCl.

Example 7 was prepared by gradually adding 2.75 g of WSe while stirring.
And by operating in the same manner as in Example 8 -◎noEG-Mn-
3.59 g of DP-diTyr (I02) was obtained. Yield 100% Example 87 Mn-protoporphyrin dimethyl ester (hereinafter referred to as Mn
-PP-Me) 10% HB r/H in 30 g
Add and dissolve 300 ml of OAc.

After standing for day and night, the B obtained after concentration was concentrated under reduced pressure at 50°C or lower.
Add 150 mQ of ethylene glycol to the r-isomer and dissolve it. After the reaction (confirmed by TLC), wash with water, carry out a hydrolysis reaction in the same manner as in Example 8, and recrystallize (acetone-
EG-Mn-DP (I03)20
20 mβ of chloroform and 40 mJ of acetonitrile were added to 2 g of the DCHA salt of Example 88 103 to dissolve it. Next, DM
Gly(OE tl・HCI l) dissolved in Flmff
gt- Add 5% WSC chloroform solution 8 under stirring
mg was gradually added and the following procedure was repeated in the same manner as in Example 23 to obtain E.
G-Mn-DP-mon.

0.13 g of Gly (I04) was obtained. Yield: 8.3% Example 89 To 2 g of DCHA salt of 103, add 20 ml of chloroform.
Add and dissolve 40 mβ of acetonitrile. Then,
Asp (QM e l. dissolved in DMF l m12)
EG-Mn-DP-son was prepared in the same manner as in Example 23 by adding 1 g of HCl and gradually adding 3 mjl of a 5% WSC chloroform solution while stirring.

0.13 g of Asp (I08) was obtained. Yield 8.9% Example 90 Ca-DP, Cra DP, Crr DP, CIo
-DP, CIo-Dp, C+5-DPJs and C+a-
5g of each DP, 30mg of chloroform separately
and 10 ml of methanol to dissolve. Next, 5.1 g of manganese acetate dissolved in 4 mβ of methanol was added to each of them under stirring, and the following procedure was repeated in the same manner as in Example 82 to convert them into C.

-M n -D P , Cre -M n -D P
, C++ -M n -D P , C1m -M
n −D P , C+ a −M n −D P
.

C1a-Mn-DPi3 and Cps-Mn-
DPPb071g, 4.75g, 4.29g, 4.56
g.

5.0g! , Ig and 5.5 g were obtained. Yield: 84.
3%, 66.4%, 58.4%, 60.5%, 63.1
%, 61.4%, 63.4% Example 91 M n -P P -Me 10% HBr in 20 g
/Add 200 mjl of HOAc and dissolve. - After standing for a day and night, concentrate under reduced pressure at 50℃ or less, add Octatool 100rnI2 to the Br body obtained after concentration, dissolve it, and leave it for a day and night.
After the reaction (confirmed by TLC), it was washed with water, followed by a hydrolysis reaction in the same manner as in Example 8, followed by recrystallization (ethyl acetate-hexane) to obtain 5 g of Ca-M n-DPi. Yield 55
．． 1% Example 92 DCHA salt 2 of C, -Mn-DP obtained in Example 90
g of chloroform 20 mJl+ and acetonitrile 4
Add 0 mε and dissolve. Next, 1 g of G 1 y (OE tl·HCI) dissolved in 1 mj2 of DMF was added, and 2 g of WS was gradually added while stirring. d
0.4 g of iG ly (I15) was obtained. Yield 2
5.0% Example 93 14 ml of chloroform and 7 mA of methanol are added to 0.7 g of DCHA salt of CM-Mn-DP and dissolved. Asp (OMel・HCl 0.
93 g of Cs-M was added, WSCl and Ig were gradually added under stirring, and the procedure was repeated in the same manner as in Example 8) and Example 8 to prepare Cs-M.
0.53 g of n-DP-diAsp (I16) was obtained.

Yield 90.0% Example 94 DCHA of C1o-Mn-DP obtained in Example 90
Add 11.4 ml of chloroform and 3.8 mQ of acetonitrile to 0.5 g of salt and dissolve.
(Add 6 g of OEtl/tlclO, and add WSC while stirring.
Example 7J3 and Example 8 below by gradually adding 6g of o.
Operate in the same manner as C1゜-Mn-DP-diGly (
I17) 0.37g was obtained. Yield: 96.7% Example 95 To 0.9 g of DCHA salt of crude Cto-Mn-DP, 18 mJs of chloroform and 8 mI2 of acetonitrile are added and dissolved. Next, 1 g of Leu (OMe).HCl was added, and 7 g of WSCl was gradually added while stirring to prepare the following Example 7. CI was prepared in the same manner as in Example 8 and Example 54.
o-Mn-DP-diLeu(+19)J and C1(I
111111111+1 M n D P di
0.36 g each of Leu (I29) and 1 g of O and O were obtained.

Yield 47.4%, 1.2% Example 96 To 0.5 g of DCHA salt of C1@-Mn-DP is added 0 mI2 of chloroform and 5 mβ of acetonitrile and dissolved. Then, Set (OMe)・HCl0.3
Add 10ml of 5% WSC chloroform solution under stirring.
I2 was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare C1°-Mre-DP-diser (I20
) 0.34g was obtained. Yield 84, 9% Example 97 5 mj of chloroform to 0.45 g of DCHA salt of Cts-Mn-DP! Add J3 and 4 ml of acetonitrile to dissolve. Next, As p (OMe)・HCI O5
Example 7. C1゜-Mn-DP-di was prepared in the same manner as in Example 8 and Example 54.
Asp (I22) 0.1 g each was obtained. Yield: 26.2% Example 98 9m12J5 of chloroform and 4mβ of acetonitrile are added to 0.45g of DCHA salt of Cts-Mn-DP and dissolved. In lie, [0] Asp (OMe)・ICl0
．． Add 59g and wsco under stirring while cooling.

7g was gradually added and the following Example 7. CI・-Mn-DP-di[D
0.15 g each of I As p (I23) was obtained.

Yield 39.4% Example 99 4.5 mε of chloroform and 1°5 m12 of acetonitrile are added to 0.2 g of DCHA salt of crude Cue-Mn-DP and dissolved. Then, Glu(OEt)・HCl0.2
9 g of WSCo was added thereto, 3 g of WSCo was gradually added under stirring, and the following procedure was repeated in the same manner as in Example 7, Example 8, and Example 54 to obtain C1°-Mn-DP-diGlu(I24)J and C.
r o 1m***l -M n -DP-diGlu
(I30) 0.06g and 0.01g were obtained, respectively. Yield 3
4.6%, 7.8% Example 100 12 m12 of chloroform and 4 m12 of acetonitrile are added to 0.5 g of DCHA salt of C1@-Mn-DP and dissolved. Then, P h e (OM e l・HC
0.7 g of WSCo was added thereto, and 75 g of WSCo was gradually added under stirring.
ts-Mn-DP-diPhe (I25) 0.44g
I got it. Yield 98.6% Example lot 117 DCHAj! obtained in Example 94! I 01
3g of chloroform and 1mρ of acetonitrile
Add and dissolve. Next, A! iP(OMel・IC
Add 10.12g and stir while stirring.
8g was gradually added and the following procedure was repeated in the same manner as in Example 7J3 and Example 8 to obtain C+o-Mn-DP-diGl.
y-diAsp (I26) 0. l l g was obtained.

Yield 93.2% Example! 02 Obtained in Example 95 119 (7) DCHAj! !
4mi of chloroform in 033g! Add and dissolve 1.5 ml of acetonitrile. Then, Asp(OM
e Add 34 g of IHcI 0 and add WSC under stirring.
Example 7 and Example 8 below by gradually adding 33 g of o.
Operate in the same manner as Cls-M low DP-diLeu-d
0.24 g of iAsp (I27) was obtained. Yield 79.5
% Example 103 0.32 g of DCHA salt of 125 obtained in Example 100
Add 7.5 ml of chloroform and 2 of acetonitrile to
．． Add 5mI2 and dissolve. Then, Asp (OMe
Add 10.3 g of 14C, gradually add 25 g of WSCo with stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain C+o M n -D P-diPhe-diA.
0.23 g of sp (I28) was obtained. Yield 78.3% Example 104 Example 17 and Example 62 using P104PP-, 10% HBr/HOAclOmg and 6 g each of geraniol, citronellol, dihydrocitronellol and menthol separately in place of ethylene glycol. In the same manner, 2.4-bis(l-geranyloxyethyl) deuteroporphyrin, 2.4-bis(I-citronellyloxyethyl) deuteroporphyrin, 2.4-bis(I-dihydrocitronellyloxy) ethyl) deuteroporphyrin and 2,4-
Bis(l-menthyloxyethyl) deuteroporphyrin (hereinafter referred to as C1゜(.erml-DP).

Cl61ci*rsl -D P + C1llllIl
*eltrel -D P and C+o1wa*tby
ll-D P) was obtained. Each of the obtained compounds was then subjected to Mn conversion in the same manner as in Example 90, and Cl6
11111tIll Mn-DP (I31),
C+o+c+tr@+ Mn DP (I33)
, Co.

1Nffieltral-Mn-DP (I3B)
J3 and C1゜Ijle++tRyll -M n
-D P (I39) 0 each. 88g0
．． Obtained 4g, 0.56g and 0.08g, yield 49
．． 3%, 22.6%, 31.5%, 4.5% Example 105 Add 0.5 g of the DCHA salt of 131 obtained in Example 104 to 10 mA of chloroform! and 5m of acetonitrile! 2
Add and dissolve. Next, Asp(OMe)・HCI
Add 0.5 g of Ct
l+1lleral M n -D P -diAs
0.4 g of p(I32) was obtained. Yield 95.2% Example 10B DCHA salt of 133 crude mixture obtained in Example 104 0
．． Add 6.6 ml of chloroform and 3.3 ml of acetonitrile to 33 g and dissolve. Next, Asp (
Add 0.33 g of OMel-HCl.

27 g of WSCo was gradually added under stirring to prepare the following example 7.
And asp body mixture compound 0 was prepared in the same manner as in Example 8.
7g was obtained. This mixture was purified by OS (C11) medium pressure high performance preparative liquid chromatography [(eluent, MeOH-H,O (I9:
1)] with C1+1c+tts+Mn-monoA
sp (I34) and C+111ettr*1-Mn
-diAsp (I35) 0.04g and 0.12 each
I got g. Yield 15.8%, 42.9% Example 107 DCHA salt of 136 crude mixture obtained in Example 104 0
．． Add 13.2 mj+ of chloroform and 6.6 mQ acetonitrile to 66 g and dissolve.

Next, 0.66 g of Asp (OMel.HCl) was added, and 54 g of WSCo was gradually added while stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain 08 g of an Asp mixture. The mixture was purified by 05 (C8) medium pressure high performance preparative liquid chromatography [(eluent, MeOH-H,O (I9:
1)] with C1olNIeltri+-Mn-diA
sp (I37)g and C111111! crte,
aasel-Mn-dtASP (I38)
0.23 g and 0.04 g of each were obtained. Yield 38.3%
8.2% Example 108 DCHA of crude C1,-Mn-DP obtained in Example 90
Add 15 m2 of chloroform and 5 m12 of acetonitrile to 0.8 g of salt and dissolve. Then As p (O
Add 0.8 g of Mel・HCI and add 10% W while stirring.
Gradually add 1 ml of SC chloroform solution and proceed in the same manner as in Examples 7, 8, and 106 to obtain C.
1* Mn-DP diAsp (I43) i3
and Ct * + m * na + M n D P-d
0.5 g and 0.15 g of iAsp (I47) were obtained. Yield 73.1%, 25.8% Example 109 0.18 g of DCHA salt of 143 obtained in Example 108
to 4.5 mβ of chloroform and 1.5 mβ of acetonitrile.
Add mI2 and dissolve. Next, Gly(OEt)・I
Add 36 g of C10, gradually add 6 g of WSCo under stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain C++-Mn-DP-diAsp-tetra Gly.
(I45) 0. 13g was obtained. Yield: 96.5% Example 110 To 0.6 g of the DCHA salt of C14-Mn-DP obtained in Example 90, 15 m2 of chloroform and 5 mJ2. Add and dissolve. Then Asp (OMel
) Add 2.25 g of IcI and add chloroform 7 with stirring.
2g of WSC dissolved in mβ was gradually added and the following example 7 was prepared.
and C+4-Mn DP by operating in the same manner as in Example 8.
-diAs p (I4-9) 0.5 g was obtained. a rate 9
7.0% Example Ill PP-Me5g, 10%HB r / HOA c 7
Example 17 and 5 mQ were used, and 30 m1 each of farnesol, oftadecenol phytol, tetrahydrofurfuryl alcohol, tetrahydrobyran-2-methanol, 3-pyridine-methanol and methionol were used separately in place of ethylene glycol. In the same manner as in Example 62, 2.4-bis(l-farnesyloxyethyl) deuteroporphyrin, 2
, 4-bis(I-octadecenyloxyethyl) deuteroporphyrin, 2.4-bis(l-phytyloxyethyl) deuteroporphyrin, 24-bis(l-tetrafurfuryloxyethyl) deuteroporphyrin Porphyrin, 2.4-bis[1-(tetrahydro-2-bilanemethyloxy)ethyl]deetheroborphyrin,
2.4-bis(l-nicotinyloxyethyl) deuteroporphyrin and 2,4-bis[1-(2-methylthiopropyloxy)ethyl] deuteroporfin (hereinafter referred to as C+@llFarm++ayll-D P *
CtslDl*FllD P, C1OIP&Ft
yllDP, 114Fran-D
P.

++4Pyran-DP, Nct-DPa and M s
p-DP) was obtained. Each of the obtained compounds was subjected to Mn conversion in the same manner as in Example 90, and each compound was converted to C+s.
+par*5syt+-Mn-DP (I51)
, CIalolei order - Mn D P (I55)
, Cma+phyty++ -Mn-D P
(I58), N4F ran −
Mn-DP (I59), ++<Pyran
-Mn-DP (I61), Net-Mn-
DP (I63) and Msp-Mn-DP (I6
5) 3.52g each, 0. 54g, 0. 3g
, 2. 25g, 2.

84g, 1.7g and 1.58g were obtained. Yield 35.
2%, 5.0%, 2.7%, 28.3%, 34.6%,
21.1%, 19.7% Example 112 To 0.06 g of the DCHA salt of Cts-Mn-DP obtained in Example 90, 9 mQj5 of chloroform and 3 ml of acetonitrile were added and dissolved. Then A sp (OMe
Add 0.5 g of l.HCI and add WSCo, 6
C1@-Mn-DP-diAsp (I53
)O,Olg was obtained. Yield 19.3% Example 113 C1. obtained in Example 90. -Mn-DP Dc)IA
! ! Add 20 ml of chloroform and 10 ml of acetonitrile to 0.84 g and dissolve. Then, A s
p (Add 0.8 g of OMeiHCI and add W while stirring.
C+a-M n -DP-diAs
63 g of po was obtained. Yield 86.3% Obtained C 1 @ -M n -D P-d iA
sp's DCHAj! ! Chloroform 12 to 0.78g
．． 4m! 2 and 6.2 mQ of acetonitrile are added and dissolved. Next, 11 g of As p (OMe).IC was added, WSClg was gradually added while stirring, and the following procedure was repeated in the same manner as in Examples 7 and 8 to obtain Cts-Mn-DP-d.
iAs p-tetra As p (I54) 0.4
3g was obtained. Yield 44.5% Example 114 0.52 g of DCHA salt of 155 obtained in Example ill
10.4 mj of chloroform! and acetonitrile 5
．． Add 2mβ and dissolve. Then Asp (OMe)・
Add 0.52 g of HCl, gradually add 6 g of WSCo under stirring, and proceed in the same manner as in Examples 7 and 8 to obtain 1 ml of C. 10. .

0.43g1k of Mn-DP-dLAsp (I56) was obtained. Yield 95.2% Example 115 0.32 g of DCHA salt of 159 obtained in Example Ill
chloroform 6.6 mβ and acetonitrile 3.3
mβ is dissolved by adding λ. Then, A sp (OM e
)-ICI 0 , 33 g and WSC under stirring.
o, 27g was gradually added to the following Example 7 and Example 8.
HaF r a n -Mn-DP-
0.28 g of diAsp(I60) was obtained. Yield 98.4
% Example 116 To 0.3 g of the DCHA salt of 161 obtained in Example 111 was added 6 m 12 of chloroform J5 and 3 m of acetonitrile.
Add mI2 and dissolve. Next, Asp (OMei
Add 0.3 g of HCl and wsco under stirring.

After gradually adding 25 g of H4Pyran-Mn-DP-diAsp, the same procedure as in Example 7 and Example 8 was carried out to obtain H4Pyran-Mn-DP-diAsp.
0.24 g of (I62) was obtained. Yield 83, 0% Example 117 0.32 g of DCHA salt of 163 obtained in Example 111
Add 6.6 mg of chloroform and 3.3 mg of acetonitrile to
mj! Add and dissolve. Next.

Add 0.33 g of A sp (OMa)・ICI, gradually add 27 g of WSCo while stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare Nct-Mn-DP.
-diAsp (I64) 0.17g was obtained. Yield 63
．． 5% Example 118 0.52 g of DCHA salt of 165 obtained in Example 111
4 ml of chloroform and acetonitrile 5.
Add 2ml and dissolve. Then Asp (OMel-
Add 0.52 g of ICI, gradually add 6 g of WSCo with stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain M sp -M n -DP-diAsp (I
66) 0.4g was obtained. Yield 92.0% Example 119 PP-Me5g, 10%HBr/HOA
c 7 using 5mI2 and replacing ethylene glycol with 25mI octafluoropentyl alcohol.
2, 2,4-bis(l-octaful to lobenthyloxyethyl) deetheroporphyrin c or less CIIF+a+
-D P) 1.6 g was obtained. The obtained compound was then subjected to Mn conversion in the same manner as in Example 90, and C@+r
1.68 g of +a+ Mn-DP (I67) was obtained.

Yield 16.7% Example 120 DCHA salt of 167 crude mixture obtained in Example 119 0
．． 3g to 6mi chloroform and 3m acetonitrile
Add and dissolve 12. Next, Gty (OEt)・HC
Add 0.3 g of Gl, gradually add 3 g of WSCo with stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare Gl.
07 g of a y-isomer mixture was obtained. This mixture was mixed with 0S(Ca
) Medium pressure high performance preparative liquid chromatography [(eluent, M e O
Cs+r+s+-M
n-DP-diGly(I68) and Cs+r
a+ M n -D P -diG ly (I6
9) 0.08g and 0.04g of each were obtained. Yield 33
．． 8% 20.9% Example 121 DCHA salt of 167 crude mixture obtained in Example 119 0
．． 3g of chloroform 6rni and acetonitrile 3
mj2 is dissolved by adding λ. Next.

Add 0.3 g of Asp (OMelMCI, gradually add 3 g of WSCo under stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain a mixture of 0.33 g of Asp body mixture.
I got it. The mixture was purified by 03 (C8) medium pressure high performance preparative liquid chromatography [(eluent, MeOH-o*O (3: t
)] attached to Ci+r+s+-Mn-D P-di
Asp(I70) and Ca+pm+ -Mn-DP
-diAsp (I71) each 0.1gjs and 0.03
．． I got it. Yield 38.6%, 14.0% Example 122 D of Clt-Mn-DP crude mixture obtained in Example 90
Add 9rnI2 of chloroform and 3mI2 of acetonitrile to 0.38g of CHA salt and dissolve. Then, hydrochloric acid p
-Trifluoromethylphenylalanine methyl ester [hereinafter referred to as Phe+vm+COMe1-HCI]0
．． 21 g of WSCo was added, and 75 g of WSCo was gradually added while stirring, and the following procedure was repeated in the same manner as in Example 7 and Example 8 to prepare P.
h e + rs + body mixture body sound compound, this mixture is 05 (
C8) Medium pressure high performance preparative liquid chromatography [(eluent, M e
OH-H*O (99:1)]
n DP-diP h e +vs+ (I73)
and C111m*@*l-Mn-DP-di
P h e +rs+ (I75) 0.12 g and 0.01 g each were obtained. Yield 41.5%, 3.0% Example
123 0.09 g of DCHA salt of 173 obtained in Example 122
Add 2.4rnJ2JS of chloroform and 0.8mg of acetonitrile to the solution and dissolve. Next, Glu (OEt
Add 12 g of l.HCto, and add WSCo, 2 with stirring.
6 g was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain Cle M n -DP-diPhe+r.
0.07 g of a+-diGlu (I74) was obtained. Yield 82.5% Example 124 C, -DP and Cll-DPP obtained in Example 75
Dimethylacetamide l0 to 25g of each separately
ml of ferric chloride, 6 g of ferric chloride 6H,Ol is suspended, and reacted under heating (I00° C.) for 3 hours. After concentrating the reaction solution, water is added to precipitate crystals. The obtained precipitate was collected by filtration and dried, and then the same operations as in Example 8 and Example 62 were carried out to obtain C.

-Fe-DP and C+s-F e -DP each 0.4
0.14 g was obtained. Yield 72.2%, 25.6% Example 125 To 0.25 g of the DCHA salt of C, -Fe-DP obtained in Example 124, 5 mj2 of chloroform and 2.5 m12 acetonitrile are added and dissolved. Then, A sp
(Add 0.25 g of OMel-HCl.

While stirring, gradually add 25 g of WSCo to Example 7 below.
13 and Example 8 to prepare C,-Fe-DP-
0.22 g of dLAsp (LSI) was obtained. Yield: 98.
0% Example 126 C +s-F e -D P obtained in Example 124
Chloroform 4 to 0.12 g of DCHA salt of Ill mixture
m12J5 and 2 mI2 of acetonitrile were added and dissolved. Next, 0.12 g of AsP (OMe).HCl was added, and 17 g of WSCO was gradually added while stirring. 09 g of a mixed compound was obtained. This mixture was purified by 03 (C8) medium pressure high performance preparative liquid chromatography [(eluent M e OH-H*O(
99: l)] C+t-Fe-diAsp
(I83) and C1111111@l1l-Fe-d
iAsp (I84) 0.04g and 0.005g each
I got it. Yield 36.7%, 5.6% Example 127 C I6-DP and C1□ obtained in Example 75
-20 chloroform separately for each DP@0.64g
mg and 10 mjl of methanol are added and dissolved. Next, 1.82 g of cobalt acetate dissolved in 10 mβ of methanol was added and reacted. The reaction solution was concentrated, and water was added to precipitate crystals. The obtained precipitate was collected by filtration and dried, and then the same operation as in Example 8 and Example 62 was carried out to obtain C.
ta-Co-.

0.53 g of each 0.6 g% of P and C-CO-D P was obtained. Yield 82.9%, 77.9% Example 128 DCHA of C1o-Co-DP obtained in Example 127
Add 15 mg J5 of chloroform and 5 mβ of acetonitrile to 0.3 g of salt and dissolve. Then Asp (OMel
Add 0.3 g of HCI, gradually add 35 g of WSCo under stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain C+aCO-DP-diAsp (I85) 0.2
6g was obtained. Yield 96.4% Example 129 Actual example t 27t'%6tt Cta-Co-DP (7
) 0.43 g of DCHA salt and 1 chloroform Omj! and 5mj of acetonitrile! Add and dissolve. Then,
Add 43 g of Asp (OMe)-HCIo, gradually add 4 g of WSCo with stirring, and proceed in the same manner as in Example 7 and Example 8 to obtain C+*C0-DP-diAs.
0.23 g of p(I86) was obtained. Yield 59.2% Example 130 To 3 g of Cta-DPo obtained in Example 75, 10 ml of chloroform and 5 mβ of methanol were added and dissolved. Next, 0.64 g of copper acetate was added and reacted. 6 The reaction solution was concentrated, and water was added to precipitate crystals. The obtained precipitate was collected by filtration and dried.

Hereinafter, the same operation as in Example 8 and Example 62 was performed to obtain Ct.
31 g of a Cu-DPo was obtained. Yield 97.0% Example 131 C + * Cu −D P obtained in Example 130
To 0.4 g of the DCHA salt, add 1 OmQ of chloroform and 3 mI of acetonitrile and dissolve. Then As
p (Add 0.4 g of OMel.HCl, gradually add 4 g of WSCo while stirring, and proceed in the same manner as in Example 7 and Example 8 to prepare Cl*-Cu-D P-di.
0.3 g of Asp (I91) was obtained. Yield 830% Example 132 EG-DP and C11-DPP obtained in Example 75
15mj of chloroform for each 25g of O! Add and dissolve 2.5 ml of methanol. Then, 5
% zinc acetate methanol solution 2.2mj! After concentrating the reaction solution, water is added to precipitate crystals. After filtering and drying the obtained precipitate, the same operations as in Example 8J3 and Example 62 were performed to obtain EG-Zn-DP (I
93) and 241 g of Cat-Zn-DPPO.

0.5g was obtained. Yield 74.5%, 93.7% Example
133 To 0.5 g of the DCHA salt of 193 obtained in Example 132, 22 ml of chloroform and 8 mJ of acetonitrile were added.
Add and dissolve. Next, Tyr (OMailICl
0.5 g of EG-Zn-DP-diTyr (
I94) 0.12g was obtained. Yield 24.7% Example 134 DCHA of C,,-Zn-DP obtained in Example 132
[Add 5 ml of chloroform and 2.5 ml of acetonitrile to 0.25 g and dissolve. Then, Asp (O
Add 0.25 g of Me)・HCl and add WSCo under stirring.
, 25g were gradually added to Example 713 and Example 8 below.
C1l-Zn-DP-diAsp (
I97) 0.21 g was obtained. Yield 92.9% Example 135 5 g of EG-DP obtained in Example 75 was added with DMFloom.
g, suspended 10 g of indium chloride, and heated (
After concentrating the reaction solution, which was allowed to react for 0.5 hours (I20℃),
Crystals precipitate when water is added. The obtained precipitate was collected by filtration and dried, followed by hydrolysis in the same manner as in Example 8.
5.4 g of G-In-DP (I99) was obtained. Yield 88
．． 9% Example 136 Add 30 mβ of chloroform to 0.5 g of DCHA salt of 199 obtained in Example 135 and dissolve it, then T y
Add 5 g of r (OM e )・HCI 0 ,
While stirring, 6 g of WSCo was gradually added and the following procedure was repeated in the same manner as in Example 7 and Example 8 to obtain EG-I n-DP-d.
0.12 g of iTyr (200) was obtained. Yield 24.6
% (G) Effects of the Invention The porphyrin derivative of the present invention has the ability to accumulate in cancer cells, has reactivity to external energy, has a destructive action on cancer cells, and does not exhibit toxicity to normal cells. , is extremely useful as a cancer treatment or cancer diagnosing agent.

[Brief explanation of the drawing]

Figure 1 shows Ca-Ga-DP-diAsp (n = odd loss, 44.49.53.55.66), Figure 2 shows C, -G
a-DP-diAsp (n=even number. 48.51.54.58.68.77) A photograph of hemorrhagic necrosis of a cancer mass 24 hours after administration. The right side of Figure 3 is Cla M n -D P -P h
eAsp (I28), inside is Cro+a*ta+ −
M n -D P-diAsp (I32), C on the left,
-Photograph of hemorrhagic necrosis of cancer mass 24 hours after administration of Fe-DP-diAsp (I81). Figure 4 shows Cat-Mn-DP-diAsp (I43).
Figure 5 is a photograph of tumor cell destruction in the administration group, Figure 5 is a photograph of tumor cells in the control group, Figure 6 is a tumor growth curve after administration of each of the following drugs, 0: control group @: Coo Mn-DP diAs p ( I
22) II: Cat-Mn-DP-diAsp
(I43) Figure 7 shows the cell proliferation inhibition rate after administration of each of the following drugs, M: Ca-Ga-DP-diAsp (58) Without light irradiation Δ: Cm-Ga-DP-diAsp (58) With light irradiation. :Cat Mn DP diAsp
(I22) No light irradiation 0: Cat Mn-DP-diAs p
(I22) With light irradiation 11: Photofrinn Without light irradiation 0: Photo
ofrinn Figure 8 with light irradiation is Cm-Ga-DP
-diAsp (54) Yag 1 24 hours after administration
A photo taken of aser phototherapy. Figure 9 is a photograph taken of the control group Yag 1aser phototherapy, Figure 10 is a photograph of EG-Ga-DP-s+onoser (I9
) methyl ester, Figure 11 shows EG-G a -D
P-monoA sp (22), Figure 12 shows C
The methyl ester of m-Ga-DP-diSer (57), Figure 13 is (,, -(, a-DP-diAs p(
58) methyl ester, Figure 14 shows the methyl ester of 58. Figure 15 shows Cs 1ms++al -G a-D P dxA
Methyl ester of sp (62), Figure 16 shows Ca
M n-DP-diAsP (I16), FIG. 17 shows C+O-Mn-DP-diAs p (I22),
Figure 18 shows Cm Ga DP, Figure 19 shows -
The mass spectra (SIMS-NOBA) of the ethyl ester of onoEG-Cu-DP-diGly are shown, respectively. Figure 20 shows C,-Ga-DP-diAsp (51),
Figure 21 shows CI-Ga-DP-diAs p (54)
, FIG. 22 shows C, -Ga-DP-diAs p (58
), Figure 23 shows Cro+lI*c+tt*I G a
D P-diAsp (74), Figure 24 is 114
F r an -Ga-DP-diAsp (80)
Nuclear magnetic resonance spectrum of methyl ester ('H-NM
R) are shown respectively. Patent Applicant Toyo Hikari Kogyo Co., Ltd. Agent Attorney Takahashi Sanbe No. 2 Strength (%) Relative strength (%) Relative strength (engineering) Relative strength i%1 Relative strength (%) Relative strength (%) Relative strength (%) Relative strength (%) Diagram diagram diagram diagram procedure amendment form (Method) November 1989

Claims (1)

[Claims] (I) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 and R_2 are each -CH=CH_2
, -CH(OR)CH_3, or -CH(O-lower alkylene-OR)CH_3, R_3 and R_4 are -OH or a residue obtained by removing hydrogen from a polyfunctional compound, R is -H, alkyl, alkenyl, per A metalloporphyrin compound represented by fluoroalkyl, a residue obtained by removing a hydroxyl group from a cyclic compound or a polyfunctional compound (M is a metal).