JPH03101662A - Novel heterocyclic compound and anticancer effect-enhancing agent containing the same compound as active ingredient - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [A is O, S, CH2, etc.; B is (CH2)n ((n) is 1-10), formula II (R<4> is OH, alkoxy, etc.), etc.; C is formula III, formula IV (R<5> and R<6> are H, alkyl, etc.), etc.; D is CR<7>R<8>R<9>, formula V, NR<7>R<8> (R<4> to R<9> are H, OH, phenyl, etc.; J is O, CH2-CH2, CH=CH, etc.), etc.; C and D form formulae VI and VII, etc.; E, F, G and H are C or N and at least one thereof is N; R<1> and R<2> are halogen, alkyl, amino, alkoxy, alkylthio, CN, NO2, etc.] and salt thereof. EXAMPLE:5-[3-{4-(dibenzosberan-5-yl)piperazine-1-yl}-2-hydroxy-propoxy ]quinoline. USE:An anticancer agent effect-enhancing agent capable of inhibiting the flow-out of anticancer agent from cancer cell. PREPARATION:A heterocyclic compound expressed by formula VIII is reacted with epihaliogenohydrin and the resultant epoxy compound expressed by formula IX is reacted with an amine expressed by the formula H-C-D to provide the compound expressed by formula I [B is formula II (R<4> is OH)].

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel compound and an anticancer drug effect enhancer containing the same as an active ingredient.

[Prior Art and Problems] The number of cancer patients is increasing year by year, and the mortality rate due to cancer ranks first in Japan, and there is a high social interest in cancer treatment.

Research and development of anticancer drugs for the treatment of cancer has been actively carried out, and various anticancer drugs are used clinically for the treatment of cancer. Although its effectiveness is steadily improving year by year, in many cases it is not always satisfactory to completely suppress cancer growth and maintain long-term survival of cancer patients. In addition, many attempts are currently being made clinically to enhance the effects of anticancer drugs by combining multiple anticancer drugs (multidrug combination therapy). However, this case is also unsatisfactory as a chemotherapy method for cancer, and there is a strong need for the development of new cancer therapeutics from a new perspective.

Under these circumstances, one possible method would be to develop a more powerful anticancer drug or a method for more selectively transporting the anticancer drug to the target organ. These studies are currently being carried out all over the world, but the current situation is that they are becoming increasingly difficult. On the other hand, another important method is to try to enhance the effects of existing anticancer drugs.

In particular, the development of agents that enhance the effects of existing anticancer drugs against drug-resistant cancer, which is a serious clinical problem in cancer chemotherapy, is considered to be a very important new cancer treatment method. The background to this shift toward anticancer drugs in clinical practice is not necessarily simple. Resistance in clinical practice can be broadly divided into two aspects. The first is when the cause is sought in the individual cancer patient, and the second is when the cause is sought in the cancer cells themselves. In recent years, the mechanism of resistance in this second case is being elucidated at the molecular level, and treatment methods for this are also being investigated. That is, a gene responsible for multidrug resistance has recently been isolated, and this gene is a membrane protein expressed in multidrug-resistant cells, pm protein (P-glyco
It was revealed that the gene was derived from the gene pratern. P-glycoprotein is presumed to be a protein that has the function of excreting anticancer drugs from cells, and is considered to be a protein that plays a central role in the multidrug resistance mechanism. In addition, some mechanisms have been suggested to be common to cancers that are inherently difficult to respond to anticancer drugs, such as solid cancers.

In other words, many anticancer drugs pass through the cell membrane and exert their effects within the cell, but in resistant cancer cells, the injected anticancer drug is excreted outside the cell by the action of this P-glycoprotein, and the drug inside the cancer cell is released. Concentrations are kept low. As a result, it is thought that the effects of anticancer drugs are less likely to be expressed. Therefore, the present inventors believe that, for example, a substance that suppresses the action of P-glycoprotein and inhibits the outflow of anticancer drugs from cancer cells has an effect of enhancing the effect of anticancer drugs, and is particularly effective in overcoming resistance.
We believe that it can be used as a new cancer chemotherapeutic agent.

In fact, Tsuruo et al. have shown that calcium antagonists such as verapamil block the outflow of anticancer drugs from cancer cells, and can therefore be used in combination against resistant cancers in vitro and in vivo.
It has been found that it has the effect of enhancing the effects of anticancer drugs such as adriamycin and pincristin. but,
When these calcium antagonists are used clinically in cancer patients, side effects such as a decrease in blood pressure and induction of arrhythmia appear, which poses a major problem as a cancer treatment agent. Therefore, there has been a desire for a drug that has a stronger effect of enhancing anticancer drug effects against resistant cancers and has fewer side effects.

[Means for Solving the Problems] In view of the above viewpoints, the inventors of the present invention have conducted extensive studies and have found that:
The present invention was completed based on the discovery that a specific compound exhibits a strong effect of enhancing anticancer drug effects against resistant cancers, and has low toxicity and low side effects.

That is, the present invention is based on the general formula (I) (wherein A is an oxygen atom, a sulfur atom, a methylene group, an amine group, or -NR'
-, and its bonding position shall be at all possible positions on the condensed ring, or N-(CHz+T 1. Indicates an atom or a nitrogen atom, provided that at least one of them is a nitrogen atom.

R' and R'' each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, an amino group, a substituted amino group, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfone group, a trifluoromethyl group, a cyano group, a nitro group , represents an amide group or a hydroxy group, and all possible positions on the condensed ring are substituted, one each on each of the two rings constituting the condensed ring, or two on one ring at the same time. R3 is a hydrogen atom, a lower alkyl group, or an acyl group; R4 is a hydroxyl group, a lower alkylamino group, a lower alkoxy group, or a lower acyloxy group; RS.R8 is each independently a hydrogen atom, a lower an alkyl group or a hydroxyalkyl group, R7, R8. C or nitrogen atom, J is −+ CHz+=. − CH feces C}I−. −
OCHx- or an oxygen atom, n represents an integer from 1 to 10, and m represents an integer from O to 2. ) and its salts (hereinafter referred to as compounds of the present invention) and anticancer drug effect enhancers containing them as active ingredients. The halogen atoms mentioned here include fluorine atoms,
It means chlorine atom, bromine atom, and iodine atom. Moreover, the lower alkyl group means a methyl group, an ethyl group, a proyl group, a butyl group, and the like.

In addition, the substituted amino group means a methylamino group, a dimethylamino group, an ethylamino group, a diethylamino group, a probylamine group, a butylamino group, and the like. In addition, lower alkoxy group means methoxy group, ethoxy group, proboxy group, butoxy group, etc. Moreover, the amide group means a formamide group, an acetamide group, a penzamide group, and the like.

Moreover, the acyl group means a formyl group, an acetyl group, a probanoyl group, a benzoyl group, and the like.

Further, the acyloxy group means a formyloxy group, an acetoxy group, etc.

Furthermore, the term hydroxyalkyl group refers to 2-hydroxyethyl group, 2-hydroxybrobyl group, 3-hydroxybrobyl group, and the like. Furthermore, the term "substituted phenyl group" refers to a halogenophenyl group, an alkoxyphenyl group, an aminophenyl group, an alkylaminophenyl group, an acylaminophenyl group, a hydroxyphenyl group, etc. substituted at the 2-position, 3-position, or 4-position. Examples of the partial structure of general formula (I) include 2-methylquinoline, 3-methylquinoline,
4-methylquinoline, 6-methylquinoline, 7-methylquinoline, 8-methylquinoline, 2-ethylquinoline,
3-ethylquinoline, 4-ethylquinoline, 6-ethylquinoline, 7-ethylquinoline, 8-ethylquinoline,
2.4-dimethylquinoline, 2.4-diethylquinoline, 7-nitroquinoline, 8-nitroquinoline, 2-
Methoxyquinoline, 3-methoxyquinoline, 4-methoxyquinoline, 6-methoxyquinoline, 7-methoxyquinoline, 8-methoxyquinoline, 2-chloroquinoline, 3
-chloroquinoline, 4-chloroquinoline, 6-chloroquinoline, 7-chloroquinoline, 8-chloroquinoline, 2
- Trifluoromethylquinoline, 3-trifluoromethylquinoline, 4-trifluoromethylquinoline, 6-trifluoromethylquinoline, 7-trifluoromethylquinoline, 8-trifluoromethylquinoline, 2.4-bis(trifluoromethylquinoline) fluoromethyl)quinoline, 2-fluoroquinoline, 3-fluoroquinoline, 4-fluoroquinoline,
6-fluoroquinoline, 7-fluoroquinoline, 8-fluoroquinoline, 2-promoquinoline, 3-promoquinoline, 4-promoquinoline, 6-promoquinoline, 7-
Promoquinoline, 8-promoquinoline, 2-iodoquinoline, 8-iodoquinoline, 2-probylquinoline, 3
-probylquinoline, 2,4-dibrobylquinoline,
8-propylquinoline, 2-butylquinoline, 8-butylquinoline, 2.4-dibutylquinoline, 2-aminoquinoline, 7-aminoquinoline, 8-aminoquinoline,
2-methylaminoquinoline, 7-methylaminoquinoline, 8-methylaminoquinoline, 2-dimethylaminoquinoline, 7-dimethylaminoquinoline, 8-dimethylaminoquinoline, 2-ethylaminoquinoline, 8-ethylaminoquinoline, 2- Diethylaminoquinoline, 8-diethylaminoquinoline, 2-propylaminoquinoline, 8
-Propylaminoquinoline, 2-ethoxyquinoline, 7
-Ethoxyquinoline, 8-ethquinquinoline, 2-proboxyquinoline, 7-proboxyquinoline, 2-butoxyquinoline, 8-butoxyquinoline, 2-cyanoquinoline, 2-formamidequinoline, 2-acetamidoquinoline, 7-acetamide Examples include quinoline, 8-acetamidoquinoline, 3-hydroxyquinoline, 7-hydroxyquinoline, 8-hydroxyquinoline, isoquinoline, quinoxaline, quinazoline, and cinnoline.

Further, A, which is a partial structure of general formula (I), includes 101 oxygen atoms, 1 S- sulfur atom, methylene group -Cth-,
Amino group-N}I-methylamino group-N (CHa)
-, ethylamino group -N (CH2CH,) -propylamino group -N (CHIC}12CH.) -, butylamino group -N (CHaCHiCHzCHs)-, acetylamino group -N (COC}I,)-, formylamino Group -N (CHO) -, propanoylamino group -
N (COCH2CH3) -, penzoylamino group-N (COPh), and the like.

In addition, B, which is a partial structure in general formula (1), is -CH
zCL-, -C}IzCHzCHs-, -CHz
CHzCHzCHz-,-CHzCH (OH) CH
z-, -CHiCH (OCOCHs) CHi-
-CHzCH (OCHO) CHi-. -CHZC
H (NL) CHg-,-CHzCH (NHCH3
)CH2-, -CHzCH (NMez) CHz
-, -C1{2C}I(NHCH2C}I,)CH2-
, -CH2CH(OCH3)C}12-, -CHz
CH(OCLCL)CL-, -COCHaCHa-
．． COCHzCH2CHz-, -COCH2CH*C
Examples include H2CHz-.

In addition, as C which is a partial structure of general formula (I), a biverazine ring, a homobiverazine ring, N,N'-dimethylethylenediamine, N. N'-diethylethylenediamine,
Examples include ethylamine, probylamine, N-methylprobylamine, biperidine ring, and the like.

Further, as D, which is a partial structure of -1'lR formula (I), diphenylmethyl group, benzyl group, (4-pyridyl)
Methyl group, (3-biridyl)methyl group, (2-biridyl)methyl group, phenyl-(2-biridyl)methyl group, phenyl-(3-biridyl)methyl group, phenyl-(4-
(pyridyl)methyl group, di(2-biridyl)methyl group, di(4-biridyl)methyl group, diphenyl-hydroxymethyl group, triphenylmethyl group, (4-chlorophenyl)monophenylmethyl group, bis(4-chlorophenyl) ) methyl group, (4-fluorophenyl)-phenylmethyl group, bis(4-fluorophenyl)methyl group, (4-methoxyphenyl)-phenylmethyl group, bis(4-methoxyphenyl)methyl group, (4- Hydroxyphenyl)-phenylmethyl group, bis(4-hydroxyphenyl)methyl group, (4-dimethylaminophenyl)-phenylmethyl group, (2.3-dimethoxyphenyl)-(3.4-
dimethoxyphenyl)methyl group, bis(4-dimethylaminophenyl)methyl group, 5-fluorenyl group, 9,I
O-dihydro-9-anthracenyl group, 5-dibenzosuberanyl group, 6.11-dihydrodibenz [b, el
xebin-11-yl group, 5-dibenzosuberenyl group, 5-xanthenyl group, diphenylmethoxy group, 5-dibenzosuberanyloxy group, phenyl-(2-biridyl)methoxy group, phenyl-(3-biridyl)methoxy group group, phenyl-(4-biridyl>methoxy group, di(2-biridyl)methoxy group, di(3-pyridyl)methoxy group,
Di(4-biridyl)methoxy group, bis(4-methoxyphenyl)methoxy group, bis(4-hydroxyphenyl)
Methoxy group, bis(4-dimethylaminophenyl)methoxy group, (2,3-dimethoxyphenyl)-(3.4-
dimethoxyphenyl)methoxy group, 6. 11-dihydrodibenz[b,e]oxebin-11-yloxy group, 5-dibenzosuberenyloxy group, 5-xanthenyloxy group, 2.2-diphenylethyl group, 2.2-di(2- pyridyl)ethyl group, 2.2-di(4-bilidyl)ethyl group, 2-phenyl-2-(2-bilidyl)ethyl group, 2-phenyl-2-(3-bilidyl)ethyl group,
2-phenyl-2-(4-pyridyl)ethyl group, 2.2
-diphenyl-2-hydroxyethyl group, 2- (4-
chlorophenyl)-2-phenylethyl group, 2.2-bis(4-chlorophenyl)ethyl group, 2-(4-methoxyphenyl)-2-phenylethyl group, 2.2-bis(
4-methoxyphenyl)ethyl group, 2-(4-hydroxyphenyl)-2-phenylethyl group, 2.2-bis(
4-hydroxyphenyl)ethyl group, 2-(4-dimethylaminophenyl)-2-phenylethyl group, 2-(2
．． 3-dimethoxyphenyl)-2-(3.4-dimethoxyphenyl)ethyl group, (5-dibenzosuberanyl)methyl group, 2.2-diphenylacetyl group, 2-phenylacetyl group, 2-(4 -Biridyl)acetyl group, 2-(
3-Biridyl) acetyl group, 2-(2-biridyl) acetyl group, 2-phenyl-2-(2-biridyl) acetyl group, 2-phenyl-2-(3-biridyl) acetyl group,
2-phenyl-2-(4-pyridyl)acetyl group, 2.
2-di(2-biridyl)acetyl group, 2.2-di(4
-Biridyl)acetyl group, 2,2.2-triphenylacetyl group, 2-(4-chlorophenyl)-2-phenylacetyl group, 2.2-bis(4-chlorophenyl)acetyl group, 2-(4-fluoro phenyl)-2-phenylacetyl group, 2.2-bis(4-fluorophenyl)acetyl group, 2-(4-methoxyphenyl)-2-phenylacetyl group, 2.2-bis(4- methoxyphenyl)
Acetyl group, 2-(4-hydroxyphenyl)-2-phenylacetyl group, 2.2-bis(4-hydroxyphenyl)acetyl group, 2-(4-dimethylaminophenyl)-2-phenylacetyl group, 2 .2-bis(4-dimethylaminophenyl)acetyl group, 2-(2.3-dimethoxyphenyl)-2-(3.4-dimethoxyphenyl)acetyl group, dibenzosuberane-5-carbonyl group,
Fluorene-5-carbonyl group, 6. 11-dihydrodibenz[b,e]oxebine-11-carbonyl group,
Dibenzosuberene-5-carbonyl group, 5-xanthenecarbonyl group, 3.3-diphenylbrobyl group, 3-(
dibenzosuberan-5-yl)ethyl group, (diphenylmethyl)amino group, 5-dibenzosuberanylamino group,
N,N-diphenylamino group, N-phenyl-N- (
2-Biridyl)amine group, N-phenyl-N-(3-biridyl)amino group, N-phenyl-N-(4-bilidyl)amine group, N,N-bis(4-chlorophenyl)amino group, N,N- bis(4-fluorophenyl)amino group,
N,N-bis(4-methoxyphenyl)amino group, N.
N-bis(4-hydroxyphenyl)amino group, 9,I
O-dihydroacridin-10-yl group, 10.11
-dihydrodibenzo[b,fl azebin-5-yl group, dibenzo[b,f] azebin-5-yl group, N,
N-diphenylcarbamoyl group, N-phenyl-N-(
2-Biridyl)carbamoyl group, N-phenyl-N-
(3-Biridyl)carpamoyl group, N-phenyl-N-(4-biridyl)carpamoyl group, N,N-bis(4-
chlorophenyl)carbamoyl group, N,N-bis(4-
fluorophenyl)carbamoyl group, N,N-bis(4
-methoxyphenyl)carbamoyl group, N,N-bis(
4-hydroxyphenyl)carbamoyl group, 9. lO
-dihydroacridine-10-carbonyl group, 10.
11-dihydrodibenzo[b,fl azevin-5-
Examples thereof include a carbonyl group, a dibenzo[b,fl azevin-5-carbonyl group, and a diphenylmethylene group.

Further, as a compound of general formula (I), 5- {3- (4-diphenylmethylbiperazine-1
-yl)-2-hydroxybroboxy}quinoline, 5-
[3-{4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-diphenylmethylbiverazin-1)
-yl)-2-hydroxybroboxy}-2-methylquinoline, 5- {3- (4-diphenylmethylbiperazine-1
-yl)-2-hydroxybroboxy}-3-methylquinoline, 5- {3- (4-diphenylmethylbiverazine-1
-yl)-2-hydroxybroboxy}-4-methylquinoline, 5-{3-(4-diphenylmethylbiperazine-1
-yl)-2-hydroxybroboxy}-6-methylquinoline, 5- {3-(4-diphenylmethylbiperazine-1-
yl)-2-hydroxybroboxy}-7-methylquinoline, 5- {3- (4-diphenylmethylbiperazine-1
-yl)-2-hydroxybroboxy}-8-methylquinoline, 5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl)-2-hydroxybroboxy)-2-methylquinoline , 5- [3- (4- (dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxy]-3-methylquinoline, 5- [3- {4- (dibenzosuberan-5-yl) yl) biverazin-1-yl}-2-hydroxybroboxy]-4-methylquinoline, 5- (3- (4- (dibenzosuberan-5-yl) biverazin-1-yl)-2-hydroxybroboxy] -6-methylquinoline, 5-(3-(4-(dibenzosuberan-5-yl)biperazin-1-yl)-2-hydroxybroboxy]-7-methylquinoline, 5-[3-(4-( dibenzosuberan-5-yl) biverazin-1-yl}-2-hydroxybroboxy]-8-methylquinoline, 5- (3- (4-diphenylmethyl biverazine-1)
-yl)-2-hydroxybroboxy}-2-methoxyquinoline, 5-(3-(4-diphenylmethylbiverazine-1)
-yl)-2-hydroxyproboxy}-3-methoxyquinoline, 5-{3-(4-diphenylmethylbiperazine-l)
-inole-2-hydroxybroboxy}-4-methoxyquinoline, 5- (3- (4-diphenylmethylbiverazine-1)
-yl)-2-hydroxybroboxy}-6-methoxyquinoline, 5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}-7-methoxyquinoline, 5-(3 -(4-diphenylmethylbiperazine-■-
yl)-2-hydroxybroboxy}-8-methoxyquinoline, 5-[3-{4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxyproboxy]-2-methoxyquinoline, 5 - (3- (4- (dibenzosuberan-5-yl) biverazin-1-yl)-2-hydroxybroboxyco-3-methoxyquinoline, 5-[3-{4-(dibenzosuberan-5-yl) biverazin-1-yl}-2-hydroxybroboxy]-4
-methoxyquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]101 methoxyquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy), 5-[3-(4-(dibenzosuberan-5-yl) -5-yl)biverazin-1-yl}-2-hydroxyproboxy]-7-methoxyquinoline, 5-[3- {4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxy broboxy]-8-methoxyquinoline, 2-ethyl-5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}quinoline, 2-ethyl-5-[3-{4 − (Dibenzosuberane −
5-yl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-{3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxyproboxy}-2-proyl Quinoline, 5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl)-2-hydroxybroboxy}-
2-probylquinoline, 2-butyl-5-(3-(4-diphenylmethylpiverazin-1-yl)-2-hydroxybroboxy}quinoline, 2-butyl-5-[3-{4-(dibenzosuberan) −
5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 2,4-dimethyl-5-(3-(4-diphenylmethylpiverazin-1-yl)-2-hydroxybroboxy} Quinoline, 2,4-dimethyl-5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl)-2-hydroxybroboxy)quinoline, 5-(3-(4-diphenylmethylbiverazine) -1
-yl)-2-hydroxybroboxy}-7-nitroquinoline, 5-(3-(4-diphenylmethylbeverazin-1-yl)-2-hydroxybroboxy}-8-nitroquinoline, 5-[3 -(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxyproboxyJ-7-nitroquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biperazin-1) -yl}-2-hydroxybroboxy]-8
-nitroquinoline, 2-chloro5- {3- (4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline, 3-chloro5- (3- (4-diphenylmethylbiperazin- ■-yl)-2-hydroxybroboxy}quinoline, 4-chloro5- {3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline, 6-chloro5- (3 -(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline, 7-chloro5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy} Quinoline, 8-chloro5-(3-(4-diphenylmethylpiverazin-1-yl)-2-hydroxybroboxy}quinoline, 2-chloro5-[3-(4-(dibenzosuberan-5-yl) ) biperazin-l-yl}-2-hydroxybroboxy]quinoline, 3-chloro5-[3-(4-(dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 4 -chloro5- [3- (4-(dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 6-chloro5- [3- {4- (dibenzosuberan-5-yl) yl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 7-chloro5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline , 8-chloro-5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl)-2-hydroxybroboxycoquinoline, 5-{3-(4-diphenylmethylbiverazin-1- yl)-2-hydroxybroboxy}-2-}lifluoromethylquinoline, 5-{3- (4-diphenylmethylbiperazine-1-
yl)-2-hydroxybroboxy}-4-trifluoromethylquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxyco-
2-trifluoromethylquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxyco-
4-trifluoromethylquinoline, 2,4-bis(trifluoromethyl)-5-(3-(
4-diphenylmethylpiperazin-1-yl)-2-hydroxybroboxy)quinoline, 2,4-bis(trifluoromethyl)-5-[3-{
4-(dibenzosuberan-5-yl)biperazine-1-
yl}-2-hydroxybroboxy]quinoline, 5-(
3-(4-diphenylmethylbiperazin-1-yl)-
2-hydroxybroboxy}-2-fluoroquinoline, 5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxyproboxy}-4-fluoroquinoline, 5-[3-(4 -(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]-
2-fluoroquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]-
4-Fluoroquinoline, 2-bromo5-{3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}quinoline, 3-bromo5-(3-(4-diphenylmethylbiverazin- 1-yl)-2-hydroxybroboxy}quinoline, 4-bromo5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline, 2-bromo5-(3 - (4- (dibenzosuberan-5-yl) biverazin-1-yl) -2-hydroxybroboxy]quinoline, 3-bromo5- [3- {4- (dibenzosuberan-5-yl) biverazin-l-yl }-2-hydroxybroboxy]quinoline, 4-bromo5-[3-(4-(dibenzosuberan-5-yl)biverazin-l-yl}-2-hydroxyproboxy]quinoline, 2-amino-5- {3 - (4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}quinoline, 2-amino-5- [3- {4- (dibenzosuberan-5-yl)biperazin-1-yl}-2- hydroxybroboxy]quinoline, 5-(3-(4-diphenylmethylpiperazine-1)
-yl)-2-hydroxybroboxy}-2-methylaminoquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]-2
-Methylaminoquinoline, 2-dimethylamino-5- (3- (4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}quinoline, 2-dimethylamino-5- [3- (4- ( dibenzosuberan-5-yl)biperazin-1-yl}-2-
hydroxybroboxy]quinoline, 2-ethoxy5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}
Quinoline, 2-ethoxy5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 2-cyano5-(3-(4-diphenylmethyl) biperazin-1-yl)-2-hydroxybroboxy}quinoline, 2-cyano5-(3-(4-(dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxy)quinoline , 5- {3- (4-diphenylmethylpiperazine-1
-yl)-2-hydroxybroboxy}-8-hydroxyquinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]-8
-hydroxyquinoline, 5- {3- (4-diphenylmethylbiperazine-l
-yl)-2-hydroxybropylthio}quinoline, 5
- (3- (4- (dibenzosuberan-5-yl)
biverazin-1-yl}-2-hydroxybropylthio]quinoline, 5- {4- (4-diphenylmethyl biverazin-1
-yl)butyl}quinoline, 5-[3-{4-(dibenzosuberan-5-yl)piperazin-1-yl}butylcoquinoline, 5-(3-(4-diphenylmethylbiverazine-1)
-yl)-2-hydroxybrobylamino}quinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-l-yl}-2-hydroxybrobylaminocoquinoline, N- {3- 4-diphenylmethylbiperazine-1
-yl)-2-hydroxybutyl)-N-methyl-5
-Quinolineamine, N- [3- (4- (Dibenzosuberan-5-yl) biverazin-1-yl}-2-hydroxybrovir]
1N-methyl-5-quinolineamine, N-(3-(4-diphenylmethylbiverazine-1)
-yl)-2-hydroxybrobyl}-N-acetyl-5-quinolineamine, N-(3-{4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybrobyl}-N −
Acetyl-5-quinolineamine, 5-{2-(4-diphenylmethylbiperazin-1-yl)ethoxy}quinoline, 5-[2-(4-(dibenzosuberan-5-yl)biperazin-l-yl}) ethoxy]quinoline, 5-
{4-(4-diphenylmethylbiverazin-1-yl)butoxy}quinoline, 5-(4-(4-(dibenzosuberan-5-yl)biverazin-1-yl)butoxy]quinoline, 5-(
3- (4-diphenylmethylbiperazin-1-yl)
broboxy}quinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}broboxy]quinoline, 5-
{2-acetoxy 3-(4-diphenylmethylbiverazin-1-yl)proboxy}quinoline, 5-12-acetoxy 3-(4-(dibenzosuberan-5-yl)
biperazin-1-yl}proboxycoquinoline, 5-(2-amino-3-(4-diphenylmethylbiperazin-l-yl)broboxy}quinoline, 5-[2-amino-3-{4-(dibenzosuberan) -5-yl)biverazin-1-yl}broboxy]quinoline, 5-(3-(4-diphenylmethylbiverazin-1)
-yl)-2-methylaminobroboxy}quinoline, 5
- [3- {4- (dibenzosuberan-5-yl)
biperazin-1-yl}-2-methylaminobroboxycoquinoline, 5-{3-(4-diphenylmethylbiperazin-1-yl)-2-methoxybroboxy}quinoline, 5-[3
- {4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-methoxybroboxyquinoline, 5-(3-(4-diphenylmethylbiperazine-1)
-yl)probionamido}quinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}brobionamido]quinoline, 5-{3-(4-diphenylmethylbiperazine) -1
-yl)-N-methyl-probionamide}quinoline, 5-[3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-N-methylprobionamide]quinoline, 5-(3-( 4-diphenylmethylhomobiverazin-1-yl)-2-hydroxybroboxy}quinoline,
5-[3- (4- (dibenzosuberan-5-yl)
homobeverazin-l-yl}-2-hydroxybroboxy]quinoline, 5- (3- [N- {2- (N-diphenylmethyl-N-methylamino)ethyl}-N-methylamino]
-2-hydroxybroboxy)quinoline, 5-{3-(N-[2-{N-(dibenzosuberane-
5-yl)-1N-methylamino}ethyl]-N-methylamino)-2-hydroxyproboxy}quinoline, 5-
[3-(4-(diphenylhydroxymethyl)biveridin-1-yl}-2-hydroxyproboxy]quinoline, 5-(3-(4-(diphenylmethylene)biveridin-1-yl}-2-hydroxybrobo oxy]quinoline, 5-{3-(4-diphenylmethylbiveridin-1-yl)-2-hydroxybroboxy}quinoline, 5-[
3-(4-(diphenylhydroxymethyl)biveridin-1-yl}-2-hydroxybroboxy]-2
-Chloroquinoline, 5-(3-(4-(phenyl-2-biridylmethyl)biverazin-1-yl)-2-hydroxybroboxy]quinoline, 5-[3-(4-fphenyl-3-biridylmethyl)biverazin-1 -yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(phenyl-4-biridylmethyl)biperazin-l-yl}-2-hydroxybutboxy]quinoline, 5-[3-(4- (di(2-biridyl)methyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- (4-(di(3-biridyl)methyl)biperazin-1-yl}-2- hydroxyproboxy]quinoline, 5-[3-{4-(di(4-biridyl)methyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4- chlorophenyl)
methyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4-fluorophenyl))
methyl)biverazin-1-yl}-2-hydroxyproboxy]quinoline, 5-[3-{4-((4-chlorophenyl)monophenylmethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4-methoxyphenyl)methyl)biperazin-1-yl}-2-hydroxybutboxy]quinoline, 5-[3-{4-(bis(4-hydroxyphenyl)methyl) ) biperazin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4-dimethylaminophenyl)methyl)piverazin-1-yl}-2-hydroxybroboxycoquinoline, 5- [3-{4-((2,3-dimethoxyphenyl)-
(3.4-dimethoxyphenyl)methyl)viverazine-
1-yl}-2-hydroxybroboxy]quinoline, 5
- [3- {4- (fluoren-5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3-(4- (9, 10-dihydro 9-anthracenyl) viperazine-1- yl}-2-hydroxybroboxy]quinoline, 5-[3-44-(6,Il-dihydrodibenz[b,el-xebin-11-yl)biperazine-
l-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(dibenzosuberen-5-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- {4-(xanthen-5-yl)piverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(diphenylmethoxy)viveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(dibenzosuberan-5-yloxy)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(phenyl-2-biridylmethoxy)biperidine-1) -yl}-2-hydroxyproboxy]quinoline, 5-[3-(4-(phenyl-3-biridylmethoxy)biveridin-1-yl)-2-hydroxybroboxy]quinoline, 5-[3-( 4- (phenyl-4-biridylmethoxy)biveridin-1-yl}-2-hydroxypoxy]quinoline, 5- [3- (4- (di(2-biridyl)methoxy)biveridin-1-yl} -2-hydroxybroboxy]quinoline, 5-[3-{4-(di(3-pyridyl)methoxy)biperidin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(di(3-pyridyl)methoxy)biperidin-l-yl}-2-hydroxybroboxy]quinoline, (4-Biridyl)methoxy)biperidin-aleyl}-2-hydroxybroboxy]quinoline, 5-[3- {4-(bis(4-chlorophenyl)
methoxy)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(bis(4-fluorophenyl)methoxy)biveridin-1-yl}-2-hydroxybroboxy]quinoline , 5-[3-{4-((4-chlorophenyl)monophenylmethoxy)biveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4-methoxyphenyl) methoxy)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-(bis(4-hydroxyphenyl)methoxy)biperidin-1-yl)-2-hydroxybroboxy] Quinoline, 5-[3- {4- (bis(4-dimethylaminophenyl)methoxy)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- (4- ((2.3 -dimethoxyphenyl)-(3.4-dimethoxyphenyl)methoxy)biperidin-1-yl}-2-hydroxybutboxy]quinoline, 5-[3-{4-(9,IO-dihydro-9-anthra) cenyloxy)piveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(6, t+-dihydrodibenz[b
, e]xebin-11-yloxy)viveridin-
1-yl}-2-hydroxybroboxycoquinoline, 5
-[3- {4- (dibenzosuberen-5-(luoxy)biveridin-1-yl}-2-hydroxybuboxy)quinoline, 5- [3- {4- (xanthene-5-yloxy)biperidin-1 -yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2. 2-diphenylethyl)biverazin-1-yl}-2-hydroxybroboxycoquinoline, 5- [3- {4- (dibenzosuberan-5-yl)methylbiverazin-1-yl}-2-hydroxybroboxycoquinoline, 5- [3- {4- (2-phenyl-2-(2-biridyl)ethyl)biverazin-1-yl }-2-hydroxyproboxy]quinoline, 5-[3-{4-(2-phenyl-2-(3-biridyl)ethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3 - {4- (2-phenyl-2-(4-biridyl)ethyl)biverazin-■-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2. 2-di(2- biridyl)ethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- {4- (2. 2-di(3-pyridyl)
ethyl)piperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- (4- (2. 2-di(4-biridyl)ethyl)piverazin-1-yl}-2-hydroxybroboxy ]quinoline, 5-[3- {4- (2. 2-bis(4-chlorophenyl)ethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2. 2-bis(4-chlorophenyl)ethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(2.2-(4-chlorophenyl)monophenylethyl)biverazine- 1-yl}-
2-hydroxybroboxy]quinoline, 5-[3-{4-(2,2-bis(4-methoxyphenyl)ethyl)piperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{ 4- (2.2-bis(4-hydroxyphenyl)ethyl)piverazin-1-yl}-2-
hydroxybroboxy]quinoline, 5-[3- {4- (2. 2-bis(4-dimethylaminophenyl)ethyl)biverazin-1-yl}-
2-hydroxybroboxy]quinoline, 5-[3-{4-(2-(2.3-dimethoxyphenyl)-2-(3.4-dimethoxyphenyl)ethyl)biverazin-1-yl}-2-hydroxy Broboxycoquinoline, 5-[3-{4- (fluorene-5
-yl) methylbiverazin-1-yl}-2-hydroxyproboxy]quinoline, 5- [3- {4- (9, l O-dihydro 9
-anthracenyl)methylbiverazin-1-yl}-2
-hydroxybroboxy]quinoline, 5-[3-{4-(6, 11-dihydrodibenz(b
,eloxebin-11-yl)methylbiperazine-1
-yl}-2-hydroxybroboxyJ quinoline, 5-
(3-{4-(dibenzosuberen-5-yl)methylbiverazin-1-yl)-2-hydroxybroboxy]
Quinoline, 5-(3-(4-(xanthen-5-yl)methylbiperazin-1-yl)-2-hydroxybroboxy]quinoline, 5-[3-(4-(diphenylacetyl)biperidin-1-yl}- 2-hydroxybroboxy]quinoline, 5-[3-(4-(dibenzosuberane-5-carbonyl)biperidin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(phenyl- 2-Biridylacetyl)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(phenyl-3-biridylacetyl)biperidin-1-yl}-2-hydroxybroboxy) ]quinoline, 5-[3-(4-(phenyl-4-bilidylacetyl)biveridin-1-yl}-2-hydroxybuboxycoquinoline, 5-[3-(4-(di(2-bilidyl)acetyl) )
biveridin-l-yl}-2-hydroxybroboxy]
Quinoline, 5-[3-(4-(di(3-biridyl)acetyl)
biverizin-l-yl}-2-hydroxybroboxy]
Quinoline, 5-43-<4- (di(4-biridyl)acetyl)
biveridin-1-yl}-2-hydroxybroboxy]
Quinoline, 5-[3-(4-(bis(4-chlorophenyl)acetyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-(bis(4-fluorophenyl)) acetyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- (4- ((4-chlorophenyl)monophenylacetyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline , 5-[3-{4-(bis(4-methoxyphenyl)acetyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(bis(4-hydroxyphenyl)acetyl) )
acetyl)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-(bis(4-dimethylaminophenyl)acetyl)biperidin-1-yl}-2-hydroxybroboxy) Quinoline, 5-[3-{4-((2.3-dimethoxyphenyl)-(3.4-dimethoxyphenyl)acetyl)viveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3- (4-(9,IO-dihydroanthracenyl-9-carbonyl)viveridin-
1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-(6.11-dihydrodibenz[b,e]oxebin-11-carbonyl)biveridin-1-yl)-2-hydroxy bropoxy]quinoline, 5-[3-{4-(dibenzosuberene-5-carbonyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(xanthene-5-carbonyl) ) biverizin-1-yl}-2-hydroxyproboxy]quinoline, 5-[3-{4- (2.2-diphenylacetyl)biverazin-1-yl}-2-hydroxybroboxycoquinoline, 5-[3 -{4- (dibenzosuberane-5-carbonyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3- (4- (2-phenyl-2-(2-biridyl)acetyl)biperazine -1-yl)-2-hydroxybroboxy]quinoline, 5-(3-(4-(2-phenyl-2-(3-pyridyl)acetyl)biperazin-l-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2-phenyl-2-(4-biridyl)acetyl)piperazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2. 2- di(2-biridyl)acetyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (2.2-di(3-biridyl)acetyl)biperazin-1-yl} -2-hydroxybroboxy]quinoline, 5-[3-{4-(2.2-di(4-biridyl)acetyl)biperazin-l-yl}-2-hydroxybutboxy]quinoline, 5-[3 - {4-(2. 2-bis(4-chlorophenyl)acetyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3- {4-(2. 2-bis(4-fluoro phenyl)acetyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4-(2- (4-chlorophenyl)
-2-phenylacetyl)biperazin-l-yl}-2
-hydroxybroboxy]quinoline, 5-[3-{4- (2. 2-bis(4-methoxyphenyl)acetyl)biverazin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3- ( 4- (2.2-bis(4-hydroxyphenyl)acetyl)biperazin-1-yl}-2
-hydroxybroboxy]quinoline, 5-[3- (4- (2. 2-bis(4-dimethylaminophenyl)acetyl)biperazin-1-yl}
-2-hydroxypoxy]quinoline, 5- [3- {4- (2- (2. 3-dimethoxyphenyl)-2- (3.4-dimethoxyphenyl) acetyl) biverazin-1-yl}- 2-Hydroxybroboxy]quinoline, 5-[3-(4-(Flyene-5-carbonyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(9 .10-dihydroanthracenyl-9-carbonyl)biverazin-1-yl}-2
-hydroxybroboxy]quinoline, 5-[3-{4-(6. 11-dihydrodibenz[b
, e]oxebine-11-carbonyl)biperazine-
1-yl}-2-hydroxybroboxy]quinoline, 5
-(3-(4-(dibenzosuberen-5-carbonyl)biperazin-1-yl)-2-hydroxybroboxy]quinoline, 5-[3-(4-(xanthene-5-carbonyl)biperazin-1-yl) }-2-hydroxybroboxy]quinoline, 5- (3- (4- (3. 3-diphenylpropyl)piperazin-1-yl)-2-hydroxybroboxy]quinoline, 5-[3- {4 - (2-(5-dibenzosuberanyl)ethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(diphenylmethylamino)piveridin-1-yl}-2 -hydroxybroboxy]quinoline, 5-[3-{4-((5-dibenzosuberanyl)amino)viveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4- N. N-diphenylamino)
Piveridin-1-yl)-2-hydroxybroboxy]
Quinoline, 5-[3-(4-(N-phenyl-N-(2-biridyl)amino)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-(4-(N-phenyl- N-(3-biridyl)amino)biperidin-l-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(N-phenyl-N-(4-biridyl)amino)biperidin-l-yl}- 2-hydroxybroboxy]quinoline, 5-[3-{4-(N,N-bis(4-chlorophenyl)amino)piveridin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3- 4-(N,N-bis(4-fluorophenyl)amino)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(N,N-bis(4-methoxyph) enyl)amino)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5- (3- (4- (N, N-bis(4-hydroxyphenyl)amino)biperidin-1-yl)-2-
hydroxybroboxy]quinoline, 5-[3-(4-(9.IO-dihydroacridin-IO-yl)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4- (10. 11-dihydrodibenzo[b.fl azebin-5-yl)biveridin-l-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4- (dibenzo[b,f] azebin-
5-yl)biperidin-l-yl)-2-hydroxybroboxy]quinoline, 5-[3-(4-(N,N-diphenylcarbamoyl)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5 -[3-{4- (N-phenyl-N-(2-biridyl)carbamoyl)biveridin-1-yl}-2-hydroxybroboxycoquinoline, 5-[3-{4- (N-phenyl-N-(3 -Biridyl)carbamoyl)piperidin-1-yl}-2-hydroxybroboxycoquinoline, 5-[3-(4- (N-phenyl-N-(4-pyridyl)carbamoyl)biveridin-1-yl}-2-hydroxy broboxy]quinoline, 5-[3-(4-(N,N-bis(4-chlorophenyl)carpamoyl)biperidin-1-yl}-2
-hydroxybroboxy]quinoline, 5- [3- (4- (N.N-bis(4-fluorophenyl)carbamoyl)biveridin-1-yl)-
2-hydroxybroboxy]quinoline, 5- [3- {4- (N, N-bis(4-methoxyphenyl)carbamoyl) biveridin-1-yl}-
2-hydroxybroboxy]quinoline, 5-[3-{4-(N,N-bis(4-hydroxyphenyl)carbamoyl)biveridin-l-yl}
-2-hydroxybutboxy]quinoline, 5- [3- {4- (9. 10-dihydroacridine-l-carbonyl)biperidin-1-yl}-2
-hydroxybroboxy]quinoline, 5-[3-{4-(10, l I-dihydrodibenzo(b, fl azevin-5-carbonyl)biveridin-1-yl}-2-hydroxybroboxy]quinoline, 5 -[3-{4- (dibenzo(b,fl azebin-5-carbonyl)biperidin-1-yl}-2
-hydroxyboxy]quinoline, 5-[3-(4-(diphenylmethylene)biperidin-1-yl}-2-hydroxybroboxy]quinoline, 5-(3-(4-(diphenylmethylbiverazine-1)
-yl)-2-hydroxybroboxy}isoquinoline, 5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy)isoquinoline, 5-(3-(4 - (diphenylmethylhomobiverazin-l-yl)-2-hydroxybroboxy}isoquinoline, 8- {3- (4-diphenylmethylbiverazine-l)
-yl)-2-hydroxybroboxy}isoquinoline, 8-[3-(4-(diphenylmethylbiverazine-1)
-yl)-2-hydroxybroboxy}quinoline, 5-
{3-(4-diphenylmethylbiverazin-l-yl)-2-hydroxybroboxy}quinoxaline, 5- {3-(4-diphenylmethylbiverazin-1)
-yl)-2-hydroxybromeroxy}quinazoline, 5
-[3-(4-((4-pyridyl)monophenylmethyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 2,4-dimethyl-5-[3-{(α.α-diphenyl) Acetyl) biverazin-1-yl}-2-hydroxybroboxy]quinoline, 2-trifluoromethyl-4-methyl-5-[3-
{4-(dibenzosuberan-5-yl)piverazine-1
-yl}-2-hydroxybroboxy]quinoline, 2-trifluoromethyl-4-methyl-5-[3-
{4-(α.α-diphenylacetyl)biverazine-1
-yl}-2-hydroxybroboxy]quinoline, 2-trifluoromethyl-4-methyl-5-{3-
(4-diphenylmethylbiverazin-l-yl)-2
monohydroxybroboxy}quinoline, 5-[3-(4- (bis-(4-fluorophenyl)
methyl)biverazin-1-yl}-2-hydroxybroboxy]isoquinoline, 5-[3-{4-((4-chlorophenyl)monophenylmethyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5 -[3-{4- (bis-(4-methoxyphenyl)
methyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{4-(iminobenzyl-5-carbonyl)piperazin-1-yl}-2-hydroxybroboxy]quinoline, 2.4 -dimethyl-5-[3-(4- (iminobenzyl-5-carbonyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5-[3-{N'- (dibenzosuberan-5-yl)ethylenediamine} -2-hydroxybroboxy]quinoline, 5-[3-{N.N'-dimethyl-N゜-(dibenzosuberan-5-yl)ethylenediamine}-2-hydroxybroboxy]quinoline, 2-methylthio-5-[ 3- (4- (dibenzosuberan-5-yl) biverazin-1-yl}-2-hydroxybroboxy] quinoline, 2-methylthio-5- [3- {4-(α.α-diphenylacetyl) piperazine- 1-yl}-2-hydroxybroboxy]quinoline, 2,4-dimethyl-5-[3- {N,N'-dimethyl-N'- (dibenzosuberan-5-yl)ethylenediamino}-2-hydroxybrobo xycoquinoline, 2,4-dimethyl-5-[3(4-diphenylmethylenebiveridin-1-yl)-2-hydroxybroboxy]quinoline, 5-(3-(10.11-dihydroN-methyl-
5H-dibenzo[a,d] monocyclohebutene-Δ6・
'brobylamino)-2-hydroxybroboxy}quinoline, 5- {3- (3.3-diphenylbrobylamino)
-2-hydroxybroboxy}quinoline, 5- {3-
(2.2-diphenylethylamino)-2-hydroxybroboxy}quinoline, 2-methylsulfonyl-5-
[3- {4- (Dibenzosuberan-5-yl) biverazin-1-yl}-2-hydroxybroboxy]quinoline, 5- [3- {4- (xanthen-9-yl) biverazin-1-yl}- 2-hydroxybroboxy]quinoline, 5-[3- {N-methyl-3-(5-iminodibenzyl)probylamino}-2-hydroxybroboxy]
Quinoline, 5- {3- (4-diphenylmethylbiverazine-1
-yl)-2-hydroxybrobylthio}quinoline, 5-(3- (4- (dibenzosuberan-5-yl)
Biperazin-1-yl)-2-hydroxybrovir quinoline, and the like. Examples of the salts of the compounds of the present invention include salts with inorganic acids such as hydrochloric acid and sulfuric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, and tartaric acid. Furthermore, since the compound of the present invention has an asymmetric carbon in its structure, optical isomers exist, and the compound of the present invention is assumed to contain all of these. Next, regarding the synthesis method of the compound of the present invention, the first method is to react a heterocyclic compound represented by the following formula with a halide such as shrimp chlorohydrin or shrimp bromohydrin in the presence of a base. This leads to an epoxy compound. The base herein refers to inorganic bases such as sodium hydroxide, sodium hydride, potassium t-butoxy, and sodium carbonate, and organic bases such as triethylamine, pyridine, and DBU. As a solvent, water solvent or alcohol,
Acetone, THF. An organic solvent such as DMF can be used, and the reaction temperature is preferably in the range of 0 to 100°C.

(In the formula, R', R'', A, E, F, G, H are the same as above,
X represents a halogen atom. ) Furthermore, by thermally reacting the synthesized epoxy compound and the corresponding amine derivative, the general formula CI) of the present invention is obtained.
The compound can be obtained.

(In the formula, R', R'', A, E, F, G, H. C and D have the same meanings as above.) Here, thermal means from room temperature to the boiling point of the solvent used, and As a method, an organic solvent such as alcohol, acetone, chloroform, or DMF is used.A second method is to thermally combine a halide such as shrimp chlorohydrin or shrimp bromohydrin with a corresponding amine derivative. reaction or in the presence of a base to induce corresponding epoxy compounds and hydroxyhalogen compounds. D has the same meaning as above.) Furthermore, the heterocyclic compound shown below and the synthesized epoxy compound or hydroxyhalogen compound are reacted in the presence of a base or acid or thermally to obtain a compound of general formula (I). (In the formula, R'.R".A.C.D, E, F, G, H have the same meanings as above, and X represents a halogen atom.) Here, the base means sodium hydroxide, Represents an inorganic base such as sodium hydride, potassium t-butoxy, potassium carbonate, etc., or an organic base such as triethylamine, pyridine.DBU.

In addition, acids include organic acids such as tosylic acid and camphorsulfonic acid, or inorganic acids such as hydrochloric acid and sulfuric acid, or
Represents Lewis acids such as titanium tetrachloride, tin tetrachloride, and trimethylsilyltrifluoromethanesulfonic acid. Solvents include methylene chloride, acetone, alcohol,
Organic solvents such as tetrahydrofuran and dimethylformamide can be used. Thermal refers to the range from room temperature to the boiling point of the solvent used. In addition, as a third method, a heterocyclic compound represented by the following formula and 1,2-dibromoethane,
A dihalogenoalkyl compound such as 1.3-dibromopropane, 1.3-dichloropropane, or 1.4-dibromobutane is reacted in the presence of a base to yield the corresponding halogenoalkyl compound.

The base here refers to inorganic bases such as sodium hydroxide, sodium hydride, potassium t-butoxy, and sodium carbonate, and organic bases such as triethylamine, pyridine, and DBU.

As a solvent, water solvent, alcohol, acetone,
Organic solvents such as THF and DMF can be used, and the reaction temperature ranges from room temperature to the boiling point of the solvent used.

(In the formula, R'.R'', A, E, F, G.H have the same meanings as above. By the reaction, a compound of the general formula (1) of the present invention in which B is -{Cllrh- can be obtained.

(In the formula, R'.R2, A, C.D.F.F, G, H represent the same meanings as above. X represents a halogen atom6) Thermal here means This means up to the boiling point, and organic solvents such as alcohol, acetone, chloroform, and DMF are used as the solvent.

As a fourth method, a heterocyclic compound represented by the following formula is reacted with an acid halide such as 3-chlorobrobionic acid chloride or an acid anhydride thermally or in the presence of a base to form the corresponding halide.

Here, thermal means from room temperature to the boiling point of the solvent used.

Bases include sodium hydroxide, sodium hydride,
It represents an inorganic base such as t-butoxypotassium, an organic base such as triethylamine, pyridine, DBU, etc. As the solvent, organic solvents such as methylene chloride, chloroform, and toluene are used.

(In the formula, R', R'', A, E.F.G, H, and X have the same meanings as above.) Furthermore, by thermally reacting the synthesized halide with the corresponding amine derivative, B is -CO (CL) 7
It is possible to obtain a compound of the general formula (I) of the present invention which is -. 0 (in the formula R', R", A, .C, D.E, F, G, H.X
has the same meaning as above. ) Thermal here means from room temperature to the boiling point of the solvent used, and the solvent used is an organic solvent such as acetone, chloroform, alcohol, or DMF. Further, as a fifth method, the hydroxyl group of the compound obtained in the first and second methods can be used to obtain the corresponding compound of the acylchlora general formula (I). Further, the compound of general formula (1) can be obtained by reacting with p-toluenesulfonyl chloride, methanesulfonyl chloride, etc., and then reacting with an alkali metal alkoxide, an alkylamine, etc.

(In the formula, R', R'', A, CD, E, F, G, H have the same meanings as above, R3 is a hydrogen atom or lower alkyl group, R
4 represents a lower alkoxy group, a lower acyloxy group, or a lower alkylamino group, and Y represents an alkali metal atom or a hydrogen atom. ) The effect of enhancing the anticancer drug effect on resistant cancer of the compound of the present invention is as follows:
Adriamycin-resistant human ovarian cancer cell line 2780A
D or, using the adriamycin-resistant human myeloid leukemia cell line K562/ADM, it is proven by the effect of enhancing the uptake of the anticancer drug into the cells and the effect of enhancing the action of the anticancer drug. That is, as will be described in detail in the Examples, all of the compounds of the present invention exhibited significant anticancer drug uptake enhancement effects and anticancer drug action enhancement effects. Furthermore, the anticancer agent to be used in combination with the compound of the present invention or its salt is not particularly limited, but preferable ones are non-antimetabolite anthracycline antibiotics, such as adriamycin, daunomycin, aclacinomycin A; actinomycin antibiotics such as actinomycin C, actinomycin D; chromomycin antibiotics such as mithramycin, toyomycin; vinca alkaloids such as pincristine, vinblastine; maytansines; bodophyllotoxin derivatives such as VP 1 6-2 1
3. Homohalintonin; anguwidene; bruceantin; neocarzinostatin: anthramycin; mitomycin C; cisplatin derivatives and the like.

The compounds of the present invention and their salts can be administered at the same time, before or after the anticancer drug, in combination with the anticancer drug, or separately. In other words, the compound of the present invention and its salt can be prepared alone in preparations according to various administration methods, and can be administered separately with various anticancer drugs. It can also be administered after making a preparation according to the administration method.

The administration method varies depending on the symptoms of the subject, the properties of the anticancer drug, etc., but for adults, 1000 mg per day is recommended.
tablets, granules, powders, suspensions,
It can be administered orally, such as capsules and syrups, or parenterally, such as injections, suppositories, and isotonic solutions for infusion. For example, in the case of tablets, crystalline cellulose, light anhydrous silicic acid, etc. are used as adsorbents, and corn starch, lactose, calcium phosphate, magnesium stearate, etc. are used as excipients. In addition, when used as an injection,
It is used as an aqueous solution of the compound, a suspension aqueous solution using cottonseed oil, corn oil, peanut oil, olive oil, etc., or an emulsion using a surfactant such as 1{CO-60. Furthermore, as for the administration method of anticancer drugs, various administration methods selected for each anticancer drug can be used as they are. [Effects of the Invention] The compounds of the present invention have the characteristics of strongly interfering with the outflow of anticancer drugs from cancer cells, having low toxicity, and having very few side effects such as lowering of blood pressure. Therefore, the compound of the present invention is effective against cancer cells that are less sensitive to anticancer drugs and cancer cells that have acquired resistance to anticancer drugs, and can provide a new treatment method for cancer chemotherapy, which is currently at a dead end. [Examples] The present invention will be illustrated below with examples, but the present invention is not limited thereto. Example 1 5-(3-(4-diphenylmethylbiverazine-1)
-yl)-2-hydroxybroboxy}quinoline a)5
- 1 g of hydroxyquinoline was dissolved in 20 ml of dry DMF, 0.28 g of sodium hydride (containing 60%) was added, and the mixture was heated and stirred at 50° C. for 30 minutes. Add shrimp chlorohydrin I. to the reaction solution. After adding 92 g and stirring at 90°C for 3 hours, the solvent was distilled off under reduced pressure. Water was added to the residue and extracted with chloroform. The chloroform extract was decolorized and purified using activated carbon, dried over anhydrous sodium sulfate, and then distilled off. The residue was purified using silica gel column chromatography.

When effluent is carried out with chloroform:methanol=100:1, the target product, 5-(2.3-epoxybroboxy)quinoline, is released as an oily substance with 0. 88 g was obtained.

b) The epoxy body obtained above 0. 88 g and N
1.1 g of monodiphenylmethylbiperazine was dissolved in 20 ml of ethanol and heated under reflux for 3 hours. After the reaction, ethanol was distilled off, and the residue was purified using silica gel column chromatography. It flows out with chloroform:methanol=50:1, and both parts of the target product are combined and the solvent is distilled off.The residue is crystallized by adding a small amount of ether, then filtered and dried to obtain 5-{3- 1.5 g of (4-diphenylmethylbiverazin-l-yl)-2-hydroxybroboxy}quinoline was obtained. mp. 16] ~163℃ IR vcm-' (KBr): 3400 (br
). 2790,1580.1265,1092. 78
8 NMR δt)l)m(CDCIs): 2.3 to 2.
9 (m.10H), 3.55 (br, s, I}1),
4.05-4.25 (m, 4H). 6.82 (d, d,
IH), 7. I ~7.8 (m, 13H) 8.54
(d, d, IH), 8.84 (d, d, IH) Example 2 5- (3-(4-(dibenzosuberan-5-yl) biverazin-1-yl)-2-hydroxybroboxy) Quinoline a) 11.3 g of anhydrous biperazine was mixed with 80 ml of dioxane, and after adding 5.0 g of 5-chlorobenzosuberane, the reaction solution was heated under reflux for 7 hours. After cooling, insoluble materials were removed by filtration, and the solvent was distilled off under reduced pressure. A small amount of petroleum ether was added to the residue to crystallize it, filtered, and dried to obtain 5.1 g of N-(dibenzosuberan-5-yl)viverazine. mp. 110 to 111.5°C IR vcm-' (κBr): 3420, 32
50, 2920, 2800. 1B30,1490
, 1450, 1330. 1140b) Example 1,
0.88 g of the epoxy compound obtained in a) and 1.2 g of N-(dibenzosuberan-5-yl)biperazine were dissolved in 20 ml of ethanol and heated under reflux for 3 hours. After the reaction,
The solvent was distilled off, and the residue was purified using silica gel chromatography. Chloroform:methanol=50:1 was flowed out, and 1.4 g of the target product, 5-[3-(4-dibenzosuberan-5-yl)piperazin-1-yl}-2-hydroxybroboxy]quinoline, was obtained. .

IR v cm-' (KBr): 2900, 2
800, 1620, 1590, 1570, 145
0, 1260, 1140. 1100NMRδI)
l)m(CDCh) +2. 1-3. 0(m, 1
21{), 3. 1-3. 6 (br, s, IH),
3.7 ~ 4.4 (m, 6H), 6.8 (d, IH)
, 6.9 ~ 7.9 (m, IIH), 8.5 (d,
II{), 8.8 (d, IH) Example 3 5- (3-[N- (2- (N-diphenylmethyl-N-methylamino)ethyl)-N-methylamino]-
2-Hydroxybroboxy)quinoline a) 25 g of N,N'-dimethylethylenediamine and 6 g of diphenylmethyl chloride in 100 ml of dioxane
The mixture was dissolved in water and heated under reflux for 4 hours. The solvent was distilled off, water was added to the residue, and the mixture was extracted with chloroform.

The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off.

The residue was purified by silica gel column chromatography using a solvent of chloroform:methanol = 25:1 to obtain N-diphenylmethyl-N,N'-dimethylethylenediamine (4.6%).
g was obtained as an oil.

IR v am” ' 2960. 2860, 2800, 1600, 1
500, 1460. 1030NMR δppm (C
DCIs) :l. 8 (s, IH). 2.1 (s.3
H) 2.35 (s, 3H). 2.4 ~ 2.8 (m, 4
H), 4.35 (s, Ill). 7. 1-7. 6
(m, IOH) b) 1.06 g of the amine compound obtained above and Example 1-1 (
0.84 g of the epoxy compound obtained in a) was dissolved in 20 ml of ethanol and heated under reflux for 3 hours. The solvent was distilled off under reduced pressure, and the residue was diluted with chloroform:methanol==100:
The effluent from step 1 was purified by silica gel column chromatography to give 5-(3-[N-{2-(N-diphenylmethyl-N-methylamino)ethyl}-N-methylamino]-2-hydroxybrobo 1.3 g of xy)quinoline was obtained.

IR v cm-' 2960, 2800, 1
620, 1590. 15B0, 1490,145
0. 1280 NMR δppm (CDCIs): 2.2 (s,
3}1), 2.3 (s, 3H), 2.4 ~ 3.0 (m
, 3H), 3.9 ~ 4.25 (m, 4} 1), 4
．． 3(s, IH). 6.9 (d, IH). 7.0～
7.8 (m, 138), 8.5 {d, I}l), 8.
85(d, I}I) Example 4 5-{ 3-(4-diphenylmethyl homoviperazine-
1-yl)-2-hydroxybroboxy}quinoline 0.88 g of the epoxy compound obtained in Example 1-a) and N
-diphenylmethylhomobiverazine (1.2 g) was dissolved in 20 ml of ethanol and heated under reflux for 3 hours. After the reaction, the solvent was distilled off, and the residue was purified using silica gel chromatography. When eluted with chloroform:methanol=50:1, the target 5-{3-(4-diphenylmethylhomobiperazin-■-yl)-2-hydroxybroboxy}
1.6 g of quinoline was obtained.

IR Vcm-' (KBr): 3040, 3000,
2920, 2820, 1610.1580. 1570
．． 1460, 1260. 1170NMR δp
pm(CDCIs): 1.8(t,2}1),
2.4-3.2 (m, 108), 3. 65 (s
, 1}1) , 4. 15 (s, 3H),
4. 6 (s, IH), 6.8 (d, IH), 7
．． 0 to 7.9 (m, 13N), 8.5 (d.IH).
8. 8 (d, IH) Example 5 2.4-dimethyl-5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy)quinoline a) 3-amino-2-cyclohexyl 2.8 g of cenone and 5.0 g of acetylacetone were mixed and heated and stirred at 70° C. for 1 hour.

The mixture was further heated and stirred at 160' to 170°C for 9 hours.

Excess acetylacetone and water were distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using the effluent of chloroform:methanol=:50:1. 2,4-dimethyl-5. as colorless crystals. 6, 7. 8-tetrahydro-5-oxoquinoline 1. 85 g was obtained.

mp 54-57°C b) 1.6 g of the above synthesized tetrahydroquinoline compound and 10
%Pd-C 0.2g was added to 15ml of diethylene glycol butyl ether acetate at 200°C under nitrogen stream.
The mixture was heated and stirred for 6 hours. After cooling, the precipitate and Pd-C were filtered out. The filtrate was purified by silica gel column chromatography after distilling off the solvent to obtain the desired product. Further, the precipitated crystals were dissolved in methanol, Pd-C was filtered off, and then dried under reduced pressure to obtain the desired 2,4-dimethyl-5-hydroxyquinoline.

Total yield 0. 82 g mp 222-224°C NMR δppm (DMSO-do): 2.
50 (s, 3H), 2. 82 (s, 3H
), 6.7 ~7. 1 (m, 2H), 7.20 ~
7.50 (m, 2H), 10.0 (s, IH) C) Hydroxyquinoline synthesized as above 0.
72 g of shrimp and shrimp chlorohydrin were reacted and treated according to Example 1-(a) to obtain an epoxy compound. Further, the reaction treatment with diphenylbiperazine compound according to 1-(b) is carried out to obtain 2.4
1.13 g of -dimethyl-5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxyproboxy}quinoline was obtained.IR vcm-' (KBr):
3400, 2800, 1600, 1450, 1260.
1050 NMRδppm (CDCIs): 2.5-2.8
5 (m.16}1), 3.65 (br.s, IH), 4
．． 0 ~ 4.3 (m, 4H), 6.75 (d, IN),
7. 0 (s, IH), 7. 15-7.
6 (m, 12}1) Example 6 5-[3-{4-(6, 1+-dihydrodibenzo(b
LiAI
This was added dropwise to a solution of L suspended in 70 ml of dry ether under water cooling.

After heating under reflux for 4 and a half hours, the mixture was cooled and saturated sodium sulfate solution was added.

After filtering off insoluble matter, drying and evaporating the solvent, the residue was purified by silica gel column chromatography using chloroform:methanol=100:1 as the eluent solvent to obtain 11-hydroxy-6.1
1-dihydrodibenzo [b. e] Oxepin 4.0
I got g. IR v cm-' (KBr): 3260,
1600, 1570, 1480, 1440.12
80. 1250 NMR δppm (CDCIs): l. 55(s,
1}1), 4.75 to 4.95 (m, IH),
5, 3 (s, IH), 5.8-6.3 (m, IH),
6.5 ~7. 6 (m, 8H) b) 3.6 g of the 11-hydroxydibenzo-isolated xebine obtained above was dissolved in 70 ml of dry methylene chloride, and 3.0 g of thionyl chloride was added dropwise under water cooling.

After stirring at room temperature for 1 hour, the solvent and excess thionyl chloride were distilled off under reduced pressure.

Further, the residue was dissolved in 40 ml of methylene chloride, and added to a solution of 8.8 g of anhydrous biverazine dissolved in 90 ml of methylene chloride, followed by stirring at room temperature for 1 hour. Filter out insoluble matter,
The filtrate was washed with water and then dried.

After distilling off the solvent, purification was performed using silica gel force column chromatography using chloroform:methanol=20+1 as the eluent solvent, and 1
l-biperazino-6.11-dihydrodibenzo[b,
e] 3.2 g of oxevin was obtained.

NMR δppm (CDCIs): 2.1 (s,
IH), 2.2 to 3.0 (m8H), 3. 8
(s, II{), 4. 6 (d, IH).
6. 7 (s, 18) ,6. 8-7. 3
(m, 8H)C) 2.5 g of the dibenzoxebine compound synthesized above and 1.1 g of the epoxy compound synthesized in Example 1-(a) were added to Example 1-(b)
5-[3-{4-(6, 11-
2.6 g of dihydrodibenzo(b,eloxebin-11-yl)biperazin-1-yl}-2-hydroxybroboxy]quinoline was obtained.

IR vcm-' (KBr): 3400, 2930,
2800, +615.15901570.1480,1
450.1270NMR δppm (CDCIs)
: 2.1 to 3.0 (m, 10B), 3.9 (s.
IH), 4.05 to 4.3 (m, 3H), 4.7 (d
, IH). 6.8 (t, 4} 1), 7.0 ~ 7.4 (
m, 8H), 7.55 (t, IH), 7.7 (d, I
H), 8.55 (d, IH). 8.55 (d, IH
) Example 7 5-(3-(4-(diphenylhydroxymethyl)biveridin-1-yl)-2-hydroxyproboxy}quinoline Example 1 - Eboxy compound 0 synthesized by (a)
．． 4g and 0.6g of 4-(diphenylhydroxymethyl)viveridin were reacted and treated according to Example I-1(b) to produce 5-(3-(4-(diphenylhydroxymethyl)viveridin-1-yl). 0.75g of -2-hydroxybroboxy}quinoline was obtained.IR
v cm-' (KBr): 3380. 2925
, 1610, +580. 1568,1265,1
095, 790,740,695NMRδp1)m(
CDCIs): 1.55 (m, 4H), 2.09 (m
, IH), 2.3 ~ 2.5 (m, 2} 1), 2.5
~2.7 (m, 2H), 2.95 (m, IH)
, 3.09 (m, l}1), 3.6 (br, 2H)
．． 4.0-4.25 (m, 3H). 6.80 (d, I
H), 7. 15 (m, 2} 1), 7.2 ~ 7.35
(m, 5H), 7.4 ~ 7.6 (m, 5B), 7.6
6(d, IH), 8.53(dd, I}I),
8. 81 (dd, IH) Example 8 5-[3-{4-(2,2-diphenylacetyl)biverazin-1-yl}-2-hydroxybroboxyJ-
2-Methoxyquinoline a) 1.6 g of 5-hydroxy-2-methoxyquinoline was reacted and treated according to Example 1-(a) to yield 5-(2.3-epoxybroboxy)-2-methoxyquinoline. 1.4g was obtained.

NMR δppm (CDCIs): 2.82 (dd,
IH), 2.95 (t, IH), 3.4 to 3.5 (m
, IH), 4.0-4.2 (m, IH), 4.06
．． (a, 3H), 4.38 (dd, l}l), 6.
71 (dd.I}I), 6.86 (d, ltl), 7.
4 ~ 7.55 (m, 2} 1), 8.42 (d, IH
) b) 0.7 g of the epoxy compound synthesized above and N
-(2,2-diphenylacetyl)piperazine 1.0g
Example 1 - (Reaction and treatment according to bl) to obtain 5-[3-{4-(2.2-diphenylacetyl)biverazin-1-yl}-2-hydroxybroboxy]-2-methoxyquinoline 1.39 g of was obtained. IR v cm-' (KBr): 1630, 1
610, 1590, 1570, 1430, 139
5,1310. 1240 NMR δppm (CDCIs): 2.2-2.8 (m
,6}1),3.4 ~3.6(m,2!{),3.6
~3.9(m,2}1),3.9 ~4.3(m,6
H), 5.19 (s, IH), 6.6-6.75 (m,
1}1). 6.85 (d, 1N), 7.0 ~ 7.6
(m, 14H). 8.34(d,IH) Example 9 5-[3-{4-(dibenzosuberan-5-yl)biverazin-1-yl}-2-hydroxybroboxy]-2
-Methoxyquinoline Example 8 - Eboxy compound 0 synthesized by (a)
．． 7g and the dibenzosuberanyl biverazine compound synthesized according to Example 2-(a). Using 92 g, the reaction and treatment were carried out according to Example 1-(b), and the above compound was converted into 1. I got 22g. IR v cm-' (KBr): 3040, 30
00, 2920, 2800, 1610, 1595
,+570.1430,1395,1310.1200
NMR δppm (CDCIs): 2.2~
2.9 (m, 12H), 3.9-4. 2 (m, 6
M), 4. 05 (s, 38), 6. 7
1 (dd, It{), 6. 84 (d, IH)
, 7.0 ~ 7.3 (m, 8H), 7.4 ~ 7.5
Hm, 21 {). 8. 37 (d. IH) Example 10 5-(3-[N-(2-(N-diphenylmethyl-N-ditylamino)ethynole)-N-ethynoleamino]-2-hydroxybroboxy}quinoline a) N, Example 3 using 21 g of N'-diethylethylenediamine and 7.3 g of diphenylmethyl chloride.
Perform the reaction and treatment according to (a) to obtain 4.2% of N-diphenylmethyl-N,N'-diethylethylenediamine.
I got g. NMR δppm (CDCIs): 0.9-1.
4 (m, 6N), 2.4 ~ 3.2 (m, 8} 1), 4
．． 8 (s, 1} 1), 7.1 ~ 7.8 (m, 108 l
b) 1.52 g of the diamine compound synthesized above and the epoxy compound 1 synthesized according to Example 1-(a).
08 g was reacted and treated according to Example 1-(b) to give 5-(3-[N-{2-(N-diphenylmethyl-N-ditylamino)ethyl)-N-ethylaminoco-2-hydroxybrobo xy}quinoline (
1.5g was obtained.

IR v cm-' (KBr): 3400.16
30, 1590, 1450. 14+0.1280
．． 1100 NMR δppm (CDCIs): 1. O(m, 6
H), 2.3-2.9 (m108), 3.95-4
．． 2 (m, 4H), 6.85 (d, 18). 7.0～
7.85 (m, IIH), 8.55 (d.IH), 8.
9(d,IH) Example 1l 5- {3- (4- (2, 3, 3°, 4°-tetramethoxydiphenylmethyl)piverazin-l-yl)-2-hydroxybroboxy}quinoline a) 2, 3.3°. 4′-Tetramethoxybenzhydrol 3. 45 g of N-(2,3,3°.4°-tetramethoxydiphenylmethyl)biperazine 3.1 was reacted and treated according to Example 6-(b).
I got g.

NMR δppm (CDCIs): 1.9 (s, I
H), 2.35 (s, 4H), 2. 85 (t, 4
H), 3. 8 Is, 128). 4. 7
(s, 1}1), 6. 75 (m. 2H)
, 7. 0 (m. 3H), 7. 25 (s
, IN) b) 3.1 g of the biverazine derivative synthesized above and 0.1 g of the epoxy compound synthesized according to Example 1-(a). 86 g was reacted and treated according to Example 1-(b) to give 5-(3-(4-(2,3
, 3°,4°-tetramethoxydiphenylmethyl)biperazin-1-yl)-2-hydroxybroboxy)quinoline in 1. I got 82g. IR vcm-'(κBr): 3400, 292
0, 1640. 1595, 1520, +480.
1420.1280 NMR δppm (CDCI3): 1.8~
2.3 (m, IH), 2.3 ~ 2.9 (m. IOH
), 3.5 to 4.0 (s, 12H). 4.05
~4.4 (m, 3}1), 4.7 (s, 1}1), 6
．． 75 (q.2H), 6.85 (d, 18), 6.95
~7. 1(m, 3}1), 7.25(s, It{
), 7.35 (q, 1} 1), 7.55 (t, IH),
7.7 (d, IH), 8.55 (d.1}1), 8.
9 (q, IH) Example 12 3-Ethyl-5-{3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxyproboxy}quinoline 750 mg of 3-ethyl-5-hydroxyquinoline in DM
Dissolve in 10 ml of F, 60% sodium hydride 180
mg was added. After stirring at 50°C for 30 minutes, 1.25g of epichlorohydrin was added, and the mixture was stirred at 90°C for 3 hours. The solvent was distilled off, and the residue was dissolved in chloroform and washed with water. The chloroform layer was dried and concentrated, and the residue was dissolved in 10 ml of ethanol. Furthermore, 750 mg of N-diphenylmethylbiperazine was added, and the mixture was heated under reflux for 3 hours. The solvent was distilled off, and the residue was dissolved in chloroform:methanol=
The product was purified by silica gel column chromatography using 50:1 as an eluent solvent to obtain 800 mg of 3-ethyl-5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline).

IR 1/cm-' (KBr): 3450, 2805
, 1600, 1578, 1450, 1262. 109
0,742,705NMRδppm (CDCIs)
:l. 32 (t, 3H). 2.3 to 2.85 (m,
12H). 4.0 to 4.25 (m, 4H). 6.80
(d, l}I), 7.1 ~7, 28 (m.6}1)
, 7.37-7.5 (m, 5H). 7.64 (dIH
), 8.28 (d, IH), 8.73 (d, IH) Example 13 5-(3-(4-(diphenylmethylene)biperidin-1-yl}-2-hydroxybroboxy)quinoline 4- (diphenylmethylene)viveridin 1.25 g
The above compound was reacted and treated according to Example 1-(b) using I got 96g. NMRδpp
m (CDCIs): 2.3-3.0 (m, 10}1),
4.1 ~4.4(m, 3}11.6.87(d, I
H), 7.0 to 7.5 (m, IIH), 7.5 to 7.
8 (m, 2H), 8. 5 ~ 8.75 (m, II {
), 8, 75-9.0 (m.IH) Example 14 5-[3-(4-(diphenylmethyl)biperidin-1-yl)-2-hydroxybroboxycoquinoline 4-(diphenylmethyl)viveridin 1 ．． Using 0.09 g, the reaction and treatment were carried out according to Example 1-(b) to obtain 0.14 g of the above compound. NMRδl)I)m (CDCIs”DMsO-da
): 1. 6-1. 9 (m, 4}1). 2
, 3 ~ 2.5 (m, IH), 2.5 ~ 2.7 (m
, 3H), 2.7 to 3.0 (m, 18). 3.0 ~
3.3 (m, IH), 3.3 ~ 3.7 (m, 3}1)
,4. 1-4.3 (m, 2H), 4.55-4.7
5 (m, IH)6. 83 ~6. 94 (m,
1}1) , 7. 68-7. 70 (m, 1
3}1) ,8.6 ~8.7(m, IH),8.8
4 - 8.92 (m, IH) Example 15 5-12-hydroxy-3- (4- (phenyl-2
Using 0.93 g of 1-pyridylmethyl)biverazin-1-yl}proboxy]quinoline N-(phenyl-2-pyridylmethyl)viverazine, the reaction and treatment were carried out according to Example 1-(b) to obtain 1.22 g of the above compound. Ta. NMR
δppm (CDCIs): 1.5? (s,l}l).
2.3-2.9 (m, 10}1), 4.05-4
．． 30 (m.3H). 4.45 (s, IH). 6.8
7 (d, IH), 7.05 ~ 7.72 (m.12H
), 8, 52 (d, IH). 8.58 (d.1}1
). 8.90(dd,1}1) Example 16 5-[3-{4-(2.2-diphenylacetyl)
biverazin-1-yl}-2-hydroxybroboxy]
Quinoline Example 1 - Eboxy form 0 synthesized by (a)
．． Example 1 - (b
), and 1.2 g of the above compound was obtained.
Obtained. NMRδppm (CDCIs): 2. 1-2
．． 3 (m, IH), 2.3 ~ 2.75 (m, 5H)
, 3.3 ~ 3.6 (m, 3} 1), 3.6 ~ 3.8
(m, :)H), 4.05 to 4.25 (m, 3N).
5.18 (s, IH). 6.83 (d, IH). 7.
1 ~ 7.45 (m, 11N), 7.57 (t, IH)
, 7.69 (d, 18), 8. 4-8. 5
5 (m, IH) Example 17 5-[3-{4-(2,2-diphenylethyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline Eboxy synthesized by Example 1-(a) body 0
．． 85 g and N-(2.2-diphenylethyl)viverazine 1. Example 1-(
The above compound was reacted and treated according to 1.b).
I got 2g. NMRδppm (CDCIs): 2.3-2
．． 75 (m, 10} 1), 2.97 (d, 2} 1), 4
．． 0 ~ 4.25 (m, 4H), 6.85 (d, IH)
,7. 10-7.70 (m, 138), 8.45
~8.55 (m. IH), 8.80 ~8. 92
(m, 1}1) Example 18 5-[3-{4-(5-dibenzosuberanyl)biverazin-1-yl}-2-hydroxybroboxy]-2
-Chloroquinoline a) Using 0.8 g of 2-chloro-5-hydroxyquinoline, the reaction and treatment according to Example 1-(a) resulted in 2-
Chloro-5-(2,3-epoxybroboxy)quinoline at 0. I got 62g. IR vcm-' (KBr): 3040, 2980,
2820.16+0.1580, 1490, 1460
, +395. 1370. 1290, 1260,
1200, 1170, 1140, 1130, 1
075, 1060, 900, 860, 8207
90. 740 b) 0.32 g of the epoxy compound synthesized above and 0.32 g of the N-(dibenzosuberanyl) biverazine compound synthesized in Example 2-(a). Using 37 g, reaction and treatment were carried out according to Example 1-(b) to produce 5-[3
-{4-(dibenzosuberanyl)biperazin-1-yl}-2-hydroxybroboxyco-2-chloroquinoline at 0. I got 63g. NMRδppm (CDCIs): 2.15 ~ 2.9 (
m. 12H), 3.9 to 4.25 (m, 6H). 6
．． 75 ~ 6.95 (m, IH), 6.95 ~ 7
．． 40 (m, 98), 7. 58 (d,
IH), 8. 47 (d, 18) Example 19 5-[3-(4-(diphenylhydroxymethyl)biveridin-1-yl}-2-hydroxybroboxy]-2-chloroquinoline Example 1 8-By (a) Example 1 using 0.31 g of the synthesized epoxy compound and 0.35 g of 4-(diphenylhydroxymethyl)viveridine.
The reaction and treatment according to (b) were carried out to obtain 0.0% of the above compound.
I got 52g. NMR δppm (CDCIs): 1.35 ~ 1.6
(m, 48), 1.95 to 2.7 (m, 6H), 2.
8 ~ 3.0 (m, 1} 1), 3.0 ~ 3.2 (m,
1}1), 4.0 to 4.25 (m, 3}1), 6.8
~6.9 (m, IH), 7. 1 ~ 7.65 (m,
13}1), 8.48 (d, IH) Example 20 5-(3-(4-(5-dibenzosuberenyl)biverazin-■-yl)-2-hydroxybroboxy]quinoline Example 1- Eboxy compound 0 synthesized by (a)
．． 4g and N-(dibenzosuberenyl)biperazine 0.6
Using g, the reaction and treatment were carried out according to Example i-(b) to obtain 0.85 g of the above compound. NMRδpp
m (CDCIs): 1.9 ~ 2.7 (m, 101 {
), 4.0 to 4.25 (m, 3H), 4. 2
9 (s, I8), 6. 82 (d, IH)
, 6. 96 (s, 2H), 7. 15-7.
80 (m, IIH), 8.40 ~ 8.50 (m,
18), 8. 80-8. 90 (m, IH)
Example 21 2.4-dimethyl-5-[3-(4-(6,.11
-dihydrodibenzo[b,e]oxebin-11-yl)biverazin-1-yl}-2-hydroxybroboxy}quinoline Example 5 - 2,4-dimethyl-5-hydroxyquinoline obtained by (b) 0. 8g and Example 6-1 (b
Using 1.04 g of 11-piperazino-6,+1-dihydrodibenzo[b,e]oxebine obtained in Example 5-(c), 1.6 g of the above compound was obtained. .

IR vcm-'(κBr): 3400, 163
0, 1595, 1440. 1380, l260 NMR δppm (CDCIs) +2.25 ~2.
6 (m, IOH). 2.6 (s, 3H), 2.85 (s
, 3H), 3.9(s, IH). 4.05 ~ 4.25
(m, 3}1) , 4. 7 (d, IH),
6. 8 (m, 4H), 6. 95 (s,
IH), 7.05-7.35 (m, 6HJ.7.5
(t, 1B), 7.6 (d, IH) Example 22 5-[3-{4-(dibenzosuberan-5-yl)
biverazin-1-yl}-2-hydroxybroboxy]
-2.4-Dimethylquinoline Example 5 - 0.8 g of 2,4-dimethyl-5-hydroxyquinoline synthesized by (b) and Example 2-(
Using 1.04 g of dibenzosuberanylbiverazine synthesized in a), the reaction and treatment were carried out according to Example 5-(c) to obtain 1.6 g of the above compound. NMR
δppm (CDCIs): 2.2 ~ 2.9 (m,
+2t{). 2.62(s, 3}1), 2.83(s,
3H). 3.9 ~ 4.25 (m, 6H), 6.75 (
d, 1} 1), 6.95-7.25 (m.9) {), 7
．． 48 (t, IH), 7.59 (d, IN} Example 23 5- (3-(4-diphenylmethylbiverazine-1-
yl)-2-hydroxybroboxy}-6-methylquinolinea) 3-amino-6-methylphenol3. 48g
5.5 ml of glycerol and 7 g of sodium m-nitrobenzenesulfonate were dissolved in 20 ml of an 80% aqueous sulfuric acid solution, and the mixture was heated and stirred at 150°C for 1 hour. After cooling, it was neutralized with an aqueous sodium hydroxide solution to a pH of 8 to 9. The aqueous layer was removed by filtration, the residue was dissolved in methanol, and insoluble materials were filtered off.

Concentrate the methanol solution and make chloroform:methanol=
25:1 was purified by silica gel column chromatography using 5-hydroxy-6-methylquinoline as the effluent solvent.
7 g and 1.6 g of 7-hydroxy-6-methylquinoline were obtained. 5-hydroxy-6-methylquinoline IR vcm-' (KBr): 1578.1255,
1178.1082,915.800 NMRδppm (DMSO-d6): 2.4(s, 3H
), 7.42 (dd, E), 7. 5 (s, 2}
1), 8. 62 (dd, IH), 8.
78 (dd, 1N), 9. 3(br, IH
) 7-Hydroxy-6-methylquinoline NMRδppm (DMSO-da): 2. 38
(S, 3H), 7. 31 (dd, IH)
7. 4 (s, IH), 7. 7 (s,
IH), 8. 20 (dd, IH). 8.
72 (dd, IH) b) Dissolve 5.04 g of diphenylmethyl biverazine and 5.5 g of shrimp chlorohydrin in 50 ml of acetone and add 4.0 g of triethylamine. 2ml was added.

After heating under reflux for 2 hours, the solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to obtain 4-(3-chloro-2-hydroxybrobyl)-1-diphenylmethylbiverazine.
．． 9g and 4- (2. 3-Eboxyprovir)-1-
2.8 g of diphenylmethylbiperazine was obtained.

4-(3-chloro2-hydroxybrobyl)-1-diphenylmethylbiverazine NMRδppm (CDCIs) +2. :7~2.
9 (m, 1(IH), 3.5~4.0(
m, 3H), 4.20 (s, 18), 7.0 ~ 7.5
(m,IOH)4- (2.3-Eboxybrovir)
-1-diphenylmethylbiverazine NMRδppm (CDCJs): 2. 1-2.
8 (m, 12H), 2. 9-3. 1 (m
, I}I), 4. 20(s, IN), 7.
0 to 7. 5(m, 1(l}IJC) 170 mg of 5-hydroxy-6-methylquinoline synthesized by (a) above and 4-(3
395 mg of -chloro-2-hydroxybrobyl)-1-diphenylmethylbiverazine were dissolved in 10 ml of dry THF and 143 mg of t-BuOK were added.

After heating under reflux for 10 hours, the mixture was poured into an aqueous ammonium chloride solution and extracted with chloroform. It was dried over anhydrous magnesium sulfate and concentrated.

The residue was purified by silica gel column chromatography using chloroform:methanol 50:1 as the eluent solvent to obtain 5-(
3-(4-diphenylmethylbiverazin-1-yl)
100 mg of -2-hydroxybroboxy}-6-methylquinoline was obtained. NMR δppm (CDCIs): 3.46 (s,
3}1), 2.2 to 3.0 (m, 10H). 3.7(
br. s. IH), 3.8 ~ 4.1 (m, 2} 1),
4.0-4.2 (m, IH), 4.23 (s, IH),
7.7 ~7.0 (m, 12H),? ．． 88(d,1}
1), 8.60(dd, 1}1), 8.8fl+(dd
,2}1) Example 24 5- (3-(4-diphenylmethylbiverazine-1-
Example 2 Using 3.9 g of 3-amino-4-methylphenol, 7 ml of glycerol, and 8.7 g of sodium m-nitrobenzenesulfonate in 29 ml of an 80% aqueous sulfuric acid solution 3-(a) to obtain 290 mg of 5-hydroxy-8-methylquinoline. 6 NMR δppm (flMsO-da): 6. 8(d
, l}I), 7. 3(d, IH), 7. 3(
dd, IH), 8.5 (dd, II), 7.8 (dd,
II). IO. 0(br,s,1}1) b) 360 mg of 5-hydroxy-8-methylquinoline synthesized above and 4-(3-chloro-2-hydroxybrovir) synthesized according to Example 2 3-(b) -1-diphenylmethylbiperazine]. Example 23 using 39g and t-BuOK300mg
5-(3-(4-
120 mg of diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}-8-methylquinoline was obtained. IR vcm-' (KBr): 3350.2900,
1610, +580.1540.1430. 1360
, 1270, 1230. +200. 1080.
900, 800.740,690 NMR δppm (CDCI3): 2.4 ~ 2.7
(m, 10N), 3.79 (brs, IH). 4
．． 0 ~ 4.2 (m, 3} 1), 4.2 (s, 18)
, 6.7 (d, IH), 7.1 ~ 7.4 (m, 12H
), 8.5 (dd, IH), 8, 9 (dd, IH) Example 25 5- (3-(4-diphenylmethylbiperazine-1-
a) 2.25 g of 3-amino-4-methoxyphenol and 3. 7 ml and sodium m-nitrobenzenesulfonate were reacted and treated according to Example 2 3-(a) to obtain 180 mg of 5-hydroxy-8-methoxyquinoline. NMRδppm (CDCIs+DMSO-ds): 4
．． 0(s, 3}1). 6. 90 (s.2H1,
7.41 (dd. II{). 8. 58(dd,
I}l), 8.90(dd1}!), 9. 30
(br, IH) b) Using 180 mg of 5-hydroxy-8-methoxyquinoline synthesized above, the reaction and treatment were carried out according to Example 23-(c) to give 5-{3-
(4-diphenylmethylbiverazin-1-yl)-2-
Humanoxybroboxy}-8-methoxyquinoline 140
I got mg. IR vcm-' (KBr): 3360, 2500,
1620.1580, 1540, 1470, 1440
, 1400, +370. 1280, 1100,
900, 800,730 NMR δppm (CDCIs): 2.5 ~ 2.8 (m
,10}1),3.28 (br.s, IH),4.
03 (s, 3H), 4.11-4.2 (m, 2H), 4
．． 24(s, 18), 6.77<d, I}1), 6.9
0 (di}l), 7.15 ~ 7.45 (m, III
), 8.54 (dd, IH), 8.93 (dd, I
t{) Example 26 5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}-8-nitroquinoline Example 2 using 180 mg of 5-hydroxy-8-nitroquinoline 3-(c) to obtain 15 mg of the above compound. IR Vcm-' (KBr): 3350, 2900,
2400, +610.1570.1510, 1420
．． 13+0. 1270. 1180, 1080.
1000900, 730 NMRδppm (CDCI3):2. 5-2. 9
(m, IOH), 4. 2-4. 3(m,
4H), 6. 7 (d, IH), 7.1
~7.4 (m, IIH), 8.2 (d, IN), 8
．． 7(dd, I}I), 9. 1(dd, l}I
) Example 27 5-(3-(4-diphenylmethylbiverazine-1-
yl)-2-hydroxybrobylamino}quinoline 1.11 g of 5-aminoquinoline and Example 23-(b)
4-(3-chloro-2-hydroxybrobyl)-1-diphenylmethylbiperazine 1.19
g was dissolved in 20 ml of chloroform and heated at 180°C to 200°C for 4 hours using an autoclave.

The reaction solution was concentrated, and the residue was purified by silica gel column chromatography using ethyl acetate as the eluent solvent to obtain 460 mg of 5-(3-(4-diphenylbiperazin-1-yl)-2-hydroxybrobylamino)quinoline. Obtained. IR v cm-' (KBr): 3220, 2
500, 1620, 1570, 1510.14+
0. 1330, 1290, +010, NMR δ
ppm (CDCIs): 2.2-2.8 (m, IOH)
, 3.1-3.5 (m.2H), 3.6 (br, IH)
, 4.0 ~ 4.2 (m, IH), 4.21 (s, If
f). 5.1 (br, IH), 6.57 (d, IH),
7.1-7.5 (m. 12H), 8.25 (d, ]
}I), 8.84 (d, IH) Example 28 5- {3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybrobylamino}-8-methoxyquinoline 5-amino 8 - Reaction according to Example 27 using 1.81 g of methoxyquinoline and 1.23 g of 4-(3-chloro-2-hydroxybrobyl)-1-diphenylmethylbiverazine synthesized according to Example 2 3-(b), 5-(3-(4-diphenylmethylpiverazin-1-yl)-2-hydroxybrobylamino}
200 mg of -8-methoxyquinoline was obtained.

IR 1/cm-' (KBr): 3350, 2900
,2780,1600.1580.1470, 144
0, +390. 1270, 1090, 990,
730, 690NMR δppm (CDCIs
) :2. 4-2. 7 (m, IOH),
3. 09 (dd, 1} 1), 3.30 (dd, 1}
1), 4.0 (s, 3} 1), 4.0 ~ 4.2 (m,
IH). 4. 22 (s, 1}1) , 4
．． 5 (br, IH), 6. 54 (d, 1
}1), 6.92 (d, IH), 7. 1 to 7.4
(m, IIH), 8.25 (dd, IH), 8
．． 90 (dd, IH) Example 29 5-(3-(4-diphenylmethylbiverazine-1-
yl)-2-hydroxybroboxy}-8-chloroquinoline 0.64 g of 8-chloro5-hydroxyquinoline and 4-chloro(2-hydroxybrobyl)-1-diphenyl synthesized according to Example 2 3-(b) Using 1.48 g of methylbiperazine, the reaction and treatment were carried out according to Example 2 3-(c) to give 5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}- 0.68 g of 8-chloroquinoline was obtained.

IR ycm-'(KBr)+3400.2920.
2800,1600.1580!300. 1250.
1!50. 1080. 1000NMR δppm
(CDCIs): 2.1-3.3 (m, 10}1), 4
．． 0 ~ 4.2 (m, 4H), 4.22 (s, 1} 1)
, 6.70 (d, l}l), 7.07 ~ 7.45 (m
, IIH), 7.67 (d, IH), 8.58 (d
d, IH). 9. 02 (dd, IH) Example 30 N-(3-(4-diphenylmethylbiverazin-l-yl)-2-hydroxybutyvir}-N-methyl-5-
Quinoline amine a) 762 g of 5-aminoquinoline and 4 ethyl rutoformate
0ml were mixed and heated under reflux for 5 hours. After distilling off excess ethyl orthoformate, the residue was dissolved in 250 ml of absolute ethanol.
3.8 g of sodium borohydride was added under water cooling. It was left at room temperature overnight and then heated to 40-50°C for 2 hours. After the solvent was distilled off under reduced pressure, water was added. It was extracted with methylene chloride and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was washed with ether to obtain 3.3 g of 5-(methylamine)quinoline. NMRδppm (CDCIs): 3.05 (d, 3
H), 4.4 (dr. IH), 6.6 (dd, IH)
, 7.1 ~ 7.7 (m, 3N), 8.2 (dd, IH
), 8. 8 (dd, IH) b) 5-(methylamino)quinoline 0.8 (dd, IH) b) 5-(methylamino)quinoline synthesized as above. 59 g was dissolved in 15 ml of THF, and a 1.6 M n-BuLi hexane solution was added under water cooling. 36m
Added l. Next, 1.42 g of 4-(3-chloro-2-hydroxybrobyl)-1-diphenylmethylpiperazine synthesized in Example 2 3-(b) was added to T
A solution dissolved in 8 ml of HF was added. Furthermore, 1.6
M n-BuLi hexane solution 2. Add 36ml,
It was left at room temperature overnight. The reaction solution was added to an aqueous ammonium chloride solution and extracted with methylene chloride. After drying over anhydrous magnesium sulfate, it was concentrated, and the residue was mixed with methylene chloride:methanol=20:1 as the effluent solvent.
Purified by silica gel column chromatography, N-3-(4-diphenylmethylbeverazin-1-yl)-2-hydroxybrobyl)-N-methyl-5-quinolineamine
I got 0mg. IR v cm-' (KBr): 3
400, 2600, 1630, 1590. 14
501410 NMR δppm (CDCl3):2. 1-2
．． 6 (m. 6H). 2. 90 (s, 3H
), 3. 00 (dd, Ill), 3.
19 (dd, E), 3. 59 (br, s
, 18), 3.95 ~ 4.03 (m, IH), 4, 2
0 (s, 1}1) . 7. 0 to 7. 5 (
m, 12H). 7. 58 (dd, IH)
, 7. 85 (d. IH), 8. 69(d
, IH), 8.86 (d, IH) Example 3l 5-(3-(4-diphenylmethylbiverazin-1yl)-2-hydroxybrobylthio}quinoline 5-quinothiol 220 mg and Example 23- (b)
4-(3-chloro-2-hydroxybrobyl)-1-(diphenylmethyl)biperazine synthesized by 1.
React according to Example 2 3-(c) using 2 g,
The treatment yielded 130 mg of 5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxyprobylthio}quinoline. NMR δppm (CD
CIs): 2.2~2,7 (m, 10}1),
3. 0 to 3. 1 (m, 2} 1), 3.9 (m,
1}1). 4.20 (s.1}1), 7.1 to 7.8
(m. 13H), 8. 00 (d. 01)
．． 8. 75 (d. IH), 8. 93 (
d, IH) Example 32 5-(3-(4-diphenylmethylbiberazin-1-yl)broboxy}quinoline a) Using 1.0 g of 5-hydroxyquinoline and 2.1 g of 1,3-dibromobroban, t -BuOK 0.78
Reaction according to Example 1-(a) with g as a base,
After treatment, 0.65 g of 5-(3-bromobroboxy)quinoline was obtained. b) The bromo compound CI. 65g and N
-diphenylmethylbiverazine 0. Using 62 g, the reaction and treatment were carried out according to Example 1-(b), and 5-3
-0.65 g of (4-diphenylmethylbiverazin-1-yl)broboxy}quinoline was obtained. IR v c
m-' (KBr) +3400. 1600, 14
50, +420. 13801280. 11 (10 NMRδppm (CDCIs): 2.O ~ 2.
15(t, 2H), 2. 3 ~2. 7(m, I
OH), 4. 15 (t, 2B). 4.
23 (s, 1}1), 6. 81 (d, 1N
). 7. 16 ~7.7 (m, 13}1), 8.5
5(d,IH), 8.88(d,1}1) Example 33 5-{4-(4-diphenylmethylpiverazin-1-yl)butoxy}quinoline 5-hydroxyquinoline l. Using Og and 2.3 g of 1,4-dibromobutane, reaction and treatment were carried out according to Example 3 2-(a) to produce 5-(4-promobutoxy).
Quinoline 0. 78 g was obtained. Additionally, 0.0% of N-diphenylmethylbiperazine. 78 g of Example 3 2-
The reaction and treatment according to (b) were carried out to obtain 0.0% of the above compound.
I got 8g.

IR v cm-' (KBr): 3420, 1
635, 1595. 1415, 1280NMRδ
ppm (CDCIs) +1.7 ~ 2.1 (m, 4H)
, 2.3 to 2.8 (m, 10}1), 4. 1 ~
4.3 (m, 3H). 6.8(d, IH), 7. 1
~7.8 (m, 13H), 8.55 (d, l}I). 8
．． 9(d,l}I) Example 34 5-(2-(4-diphenylmethylbiverazin-1-yl)ethoxy}quinoline Using 1.05 g of 5-hydroxyquinoline and 2.04 g of 1,2-dibromoethane Example 3 2-(a)
The reaction and treatment were carried out according to the procedure described above to obtain 0.2 g of 5-(2-promoethoxy)quinoline. Furthermore, using 0.2 g of N-diphenylmethylbiverazine, the reaction and treatment were carried out according to Example 3 2-(b) to obtain 0.1 g of the above compound.

NMR δppm (CDCIs): 2.4 ~ 3.2 (m
, IOHI, 4.2 to 4.5 (m.3}1). 6.8
5 (d, IH), 7.1 to 7.8 (m.13}1),
8.5(d, IH), 8. 9 (d, 1}1
) Example 35 5- {3-(4-diphenylmethylbiperazine-1-
a) 4.5 g of 5-aminoquinoline and 60 m of methylene chloride
3-chlorobrobionic acid chloride dissolved in lO,
5g and 9g of triethylamine were added. After standing overnight at room temperature, IN aqueous sodium hydroxide solution was added and extracted with methylene chloride. After washing twice with sodium bicarbonate solution, drying and concentration gave crystals. The crystals were washed with methylene chloride and collected by filtration to give 5-(3
- Chlorobrobinamide) quinoline as a crystal 2.
I got 2g. NMR δppm (CDCIg): 2.
9 (t, 28), 3.3 (s, 18), 3.9 (t.
2H), 7, 0-8. 5 (m. 5}1),
8. 9 (dd, 1}1) b) 1.1 g of the chloro compound synthesized above and N-diphenylmethylbiverazine synthesized according to Example 1-(b) 1.
2 g of 5-(3-(4-diphenylmethylbeverazin-1-yl)probionamide)}quinoline was reacted and treated according to Example 1-(b) in an ethanol solvent.
．． I got 0g. TR v cm-' (KBr): 3420, 2
580, 1690, +630. 1600, +55
0. 1420, 1370. 1280NMR δp
pm (CDCIs): 2. 4-3. 9 (m,
12H). 4. 29 (s, 1} 1), 7.1
~7.5 (m, IIH), 7.69 (t, It{),
7.88Cd, IH), 8.21 (d, IH),
8.35 (d, IH), 8.92 (d, 18),
If. 09 (s, IH) Example 36 5-(3-(4-(dibenzosuberan-5-yl)biverazin-1-yl)propionamide}quinoline Example 3 Chloro compound 1 synthesized by 5-(a) N synthesized by .1g and Example 2-(a)
-(dibenzosuberan-5-yl)biverazine 1.32
5-(3-(4-(dibenzosuberane-
5-yl)biperazin-1-yl)propionamide}
1.6 g of quinoline was obtained.

IR v cm-' (KBr): 3400, 2
620, 1690, 1630, 1590, 153
0, 1410. 1280 NMRδppm (CDCIs): 2. 2-3.
0 (m, 14H), 3. 9-4. 1(
m, 3H), 7.0-7.2 (m, 8H), 7.50 (
dd, 1}1), 7.73 (t, IH). 7.92 (
d, IH), 8.20 (d, 1} 1), 8.46 (d,
IH). 9. 01 (d, II{) , 11
．． 1 (s, IH) Example 37 5-{N-methyl-(3-(4-diphenylmethylbiverazin-1-yl)probionamide)}quinoline Example 3 0 - Synthesized by (a) 474 mg of 5-(methylamino)quinoline and 30 ml of methylene chloride
850 mg of 3-chlorobrobionic acid chloride and 0.5 ml of triethylamine were added at room temperature. After standing overnight at room temperature, a 1N aqueous sodium hydroxide solution was added to make it alkaline. It was extracted with methylene chloride, washed twice with aqueous sodium bicarbonate, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, 756 mg of the remaining 8N-(diphenylmethyl)viverazine was added, and Examples 1 to (b) were dissolved in ethanol solvent.
) to form 5-{N-methyl-(3-(
880 mg of 4-diphenylmethylbiverazin-1-yl)probionamide}quinoline was obtained. IR v cm-' (KBr): 3400, 2
520, 1650. 1500. 1410.112
0 NMR 5ppm (CDCI,): 1.9-2.50 (
m, IOH), 2.64 (br, t, 2}1), 3.3
4 (s, 3H), 4. 13(s, IH), 7.0
~7.5 (m, 128), 7.72 (dd, IH)
,8. 1 to 8.2 (m, 2} 1). 8. 97 (d
d, IH) Example 38 5-{N-methyl-(3-(4-(dibenzosuberane-
5-yl) biverazin-l-yl) propionamide)
}-Quinoline According to Example 37, 5-(methylamino)quinoline 47
4mg and 850mg of 3-chloroprobionic acid chloride
was reacted. Further, 834 mg of N-(dibenzosuberan-5-yl)viverazine synthesized according to Example 2-(a) was added to Example 1-(b) in an ethanol solvent.
5-{N-methyl-(3-(4-
1.02 g of dibenzosuberanylbiverazin-1-yl)probionamide)}-quinoline was obtained.

IR vcm-' (KBr): 3400, 2900,
2500, +650.1590.1410. 1120 NMRδppm (C[lCfs): l. 7(br,
IN), L. S ~2. 4 (m, 12H), 2.
5 ~ 2.6 (m, 2} 1), 2.6 ~ 2.9 (m, 2
H). 3.34 (s, 3H). 3.86 (s, IN),
3.8 ~ 4.0 (m, 2tl), 7.0 ~ 7.7 (
m, +3}1). 8.1-8.15 (m, 2fl) 8
．． 98(ad.1}1) Example 39 5-[N-acetyl{2-acetoxy3-{4-diphenylmethylbiverazin-1-yl)brobylamino}]quinoline 5-{3 synthesized by Example 27 -(4-diphenylmethylpiverazin-1-yl)-2-hydroxybrobylaminotoquinoline1. Og was dissolved in 4.5 g of acetic anhydride and left overnight. It was poured into aqueous sodium bicarbonate solution and extracted with methylene chloride. After drying over anhydrous magnesium sulfate and concentration, the residue was purified by silica gel column chromatography using ethyl acetate as the eluent to obtain 1.05 g of the above compound. NMRδppm (CDCIs): 1.69 (s, 3
H). 1.77 (a, 3H), 2.1 ~ 2.7 (m
, 88), 3.37 (dd.IH), 3.69 (dd,
IH). 4. 10 (s, IH), 3.
34 (dd, 18), 3. 61 (dd, 1
}1), 4. 6 1 (dd, IH) Example 40 5-[N-acetyl{3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybrobylamino}]quinoline Synthesized by Example 39 5-[N-acetyl{
2-acetoxy3-(4-diphenylmethylbiperazin-1-yl)probylamino}]quinoline 0.55 g
and 0.5 g of potassium carbonate in 10 ml of methanol and 5 ml of water.
1 of a mixed solvent and left at room temperature overnight. The extract was extracted with methylene chloride, dried over anhydrous magnesium sulfate, and concentrated to obtain 0.5 g of the above compound.

NMR δppm (CDCIs): 1.74 (s
, 3H), 2.1 ~ 2.9 (m, 108), 3
．． 4 ~ 3.6 (m, IH), 3.8 ~ 4.2 (m
, 3H). 7. 1 ~ 7.8 (m, 13}
1), 8. 1 to 8.3 (m, 2H), 8. 96
~8. 99 (m. IH) Example 4l 2-chloro5-(3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}quinoline 2-chloro5-hydroxyquinoline 1g and Example 2
4-(3-chloro2-hydroxybrobyl)-1-diphenylmethylpiperazine synthesized by 3-(b)2. Example 2 3-(c
), the reaction and treatment were carried out according to 2-chloro5-(3
-(4-diphenylmethylbiperazin-1-yl)-2
-Hydroxybroboxy}quinoline (1.39 g) was obtained.

NMI? δ9pm (DMSO-ds):2. 2～
2. 4 (m, 4H), 2. 4 ~ 2.7 (
m, 6} 1), 3.9 to 4.3 (m, 4H), 4.91
(s, 1) {). 6. 9-7. 7 (m, 14
H), 8. 64 (d, IH) Example 42 5-(3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}-2-methoxyquinoline 0.6 g of 5-hydroxy-2-methoxyquinoline Example 23-(C)
The reaction and treatment were carried out according to the procedure to obtain 1.2 g of 5-{3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}-2-methoxyquinoline.

NMRδppm (DMSO-do): 2. 2 ~
2. 7 (m. 4H), 2. 4 ~ 2.7 (
m, 6H), 3.9 to 4.15 (m.6H), 4.1
9(s, IH). 4.83 (s. 18), 6.75~
6.9 (m.2H), 7.05 ~ 7.55 (m, 1
2}1), 8. 46 (d, IJI) Example 4
3 5- (3-(4-diphenylmethylbiverazine-1-
yl)-2-hydroxybroboxy}isoquinoline a) 3.55 g of 5-hydroxyisoquinoline, 3.4 g of shrimp chlorohydrin and 5.0 g of potassium carbonate were mixed with 40 ml of acetone and heated under reflux for 6 hours.

After removing the insoluble matter by filtration, the solvent was distilled off, and the residue was purified by silica gel column chromatography. The target product, 5-(
1.6 g of 2.3-epoxyproboxy)isoquinoline
Obtained as an oil.

IR 1Jcm-' (liq.fi1m): 3480
, 2920, 1670, 1580, 1490, 139
0, 1280. 1250b) 0.8 g of the epoxy compound obtained above and 1.0 g of N-diphenylmethylbiverazine
g was dissolved in 20 mβ of ethanol and heated under reflux for 2 hours. After the reaction, the solvent was distilled off, and the residue was purified by silica gel column chromatography. When chloroform:methanol=50:1 flows out, the target product 5-{
3-(4-diphenylmethylbiperazin-1-yl)-
0.7 g of 2-hydroxy}isoquinoline was obtained as a powder.

IR vcrn-'(κB'冫:3420.2
820, 1620, +580. 1490,l4
50 NMR δppm (CDCIs): 2. 2 to 3
．． 0 (m, IOH), 3. 8(s,I}I
), 4.15 (s, 2H), 4.25 (s, 2
H), 6.9 to 7.8 (m, 13H), 8.0 (d,
IH), 8.5(d, II-1), 9. 2 (d
, ]}I) Example 44 5-(3-(4-(dibenzosuberan-5-yl)
biperazin-1-yl)-2-hydroxybuboxy]
0.93 g of the epoxy compound obtained in Isoquinoline Example 43, a) and 1.29 g of the biperazine compound obtained in Example 2, a)
was dissolved in 20 ml of ethanol and heated under reflux for 2 hours. After the reaction, the solvent was distilled off, and the residue was purified by silica gel column chromatography. When chloroform:methanol=50:1 flows out, the target product 5-
1.14 g of [3-{4-(dibenzosuberan-5-yl)biperazin-1-yl}-2-hydroxybroboxy]isoquinoline was obtained as a powder. IR vcm-' (KBr): 3400. '2920
, 2800, 1580, 1490, 1450, 139
0. 1280. 1110NMR δppm (CD
CIs): 3.6 ~ 4.4 (m, 7H), 6.9 ~
7.6 (m, 118), 8.0 (d, IH), 8.5 (
m, IH). 9.15 (s, IH) Example 45 5-{3-(4-diphenylmethylhomobiverazin-1-yl)-2-hydroxybroboxy}inquinoline obtained in Example 43, a) 0.74g of epoxy compound and 0.74g of N-diphenylmethylhomobiverazine. 97 g was dissolved in 20 mI2 of ethanol and heated under reflux for 2 hours. After the reaction, the solvent was distilled off, and the residue was purified using silica gel column chromatography. Chloroform: methanol = 50
: When it flows out at l, the target product 5- (3- (
4-diphenylmethylhomobiperazin-1-yl)-2
-Hydroxybroboxy}isoquinoline was obtained as 1.04 g powder.

NMRδppm (CDCIs): 1.8 (t, 21{), 2.3 ~ 3.3 (m, 108
), 4.0 (s, IH), 4.15 (s, 3H), 4.
55 (s, 1} 1), 6.8 ~ 7.7 (m, 13H)
8. 0 (d, IH), 8. 5 (dd,
11{) ． 9. 15 (s, IH) Example 46 4-3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxyproboxy}quinoline 3.55 g of 4-hydroxyquinoline, 3.4 g of shrimp chlorohydrin and Mix 5 g of potassium carbonate with 50 ml of acetone,
The mixture was heated under reflux for an hour. After filtering off the insoluble matter, the solvent was distilled off, and the residue was purified by silica gel column chromatography. Chloroform: Methanol = 100 + 1 and 4-(2.3
2.1 g of -epoxybroboxy)quinoline were obtained as an oil. Furthermore, 1.6 g of this epoxy compound and 2.0 g of N-diphenylmethylbiverazine were added in 40 mJ2 of ethanol.
and heated under reflux for 2 hours. After the reaction, the solvent was distilled off, and the residue was purified using silica gel column chromatography. When effluent with chloroform:methanol=50:l, the target product 4-{3-(4-diphenylmethylbiverazine-1)
1.5 g of quinoline (-yl)-2-hydroxybroboxy was obtained as a powder.

IR v cm-' (KBr): 3400, 2
800, 1630, 1580, 1490, 145
0.1230.1010 NMR δppm (CDCIs): 2.0 ~ 3.
0 (m, IOH), 3.5 ~ 3.9 (m, IH), 3
．． 9 ~ 4.6 (m, 3} 1), 5.85 (d, IH
), 6. 9-7. 8 (m, 14H). 8
．． 1 (d, IH) Example 47 8-(3- (4-diphenylmethylbiperazine-1-
yl)-2-hydroxybroboxy}isoquinoline 80 mg of 8-hydroxyisoquinoline and Example 23-(
204 mg of 4-(3-chloro-2-hydroxypropyl)-1-diphenylmethylbiverazine obtained in step b) was dissolved in 15 mI2 of dry THF, and after adding 68 mg of t-butoxypotassium, the mixture was stirred at room temperature for 20 hours. The reaction solution was poured into 15 m4 of a saturated aqueous ammonium chloride solution, and extracted with 150 mβ of methylene chloride. After drying with anhydrous sodium sulfate, the solvent was distilled off, and the residue was purified using silica gel thin layer chromatography. The mixture was developed with chloroform:methanol=25:1 and separated and purified to obtain 70 mg of 8-{3-(4-diphenylmethylbiverazin-1-yl)-2-hydroxybroboxy}isoquinoline as a powder. IR v cm-' (KBr) +3400. 2
800, 1570, 1450. 1390,128
0. 1120 NMR δI)pm (CDCl3): 2.4-3.
0 (m, 108), 3.7 (br, s.1}1), 4.
0 ~ 4.5 (m, 4H), 6.96 (d, IH),
7. 1-7.8 (m, 13H), 8.56 (d,
18), 9.60 (s, IH) Example 48 1-(3-(4-diphenylmethylbiperazine-1)
-yl)-2-hydroxybroboxy}isoquinoline 1 g of 1-hydroxyisoquinoline was dried in DMF at 20 m℃.
Dissolved in potassium t-butoxy 0. 77 g was added, and the mixture was heated and stirred at 50°C for 30 minutes. 1.91 g of shrimp chlorohydrin was added to the reaction solution, and the mixture was heated and stirred at 90°C for 2 hours. The solvent was distilled off under reduced pressure, ethanol was added to the residue, the precipitated salt was filtered off, and activated carbon was added to the ethanol solution for purification. The ethanol solution was adjusted to 30+nI2, and after adding 1 g of diphenylmethylbiperazine, it was heated under reflux for 2.5 hours. The solvent was distilled off and the residue was purified by silica gel column chromatography, chloroform:methanol=50:1
When the solution was discharged, 1.94 g of the target product, 1-{3-(4-diphenylmethylbiperazin-1-yl)-2-hydroxybroboxy}isoquinoline, was obtained as a powder. NMRδppm (CDCIs): 2.0-2.8 (m, 8H), 2.9 (d.2H).
3.4 ~ 4.5 (m, 5H), 6.5 (dd, IH
), 6.8-7.9 (m, 14H) 8.4 (dd,
II{) Example 49 8-(3-(4-diphenylmethylbiverazine-1)
-yl)-2-hydroxybroboxy}monoquinoline 8-hydroxyquinoline 200 mg and Example 23-(
319 mg of biverazine obtained in b) was added to dry THF.
Dissolved in 5 mβ and further added t-butoxypotassium 120
ng was added. After stirring at room temperature for 5 days, the mixture was poured into 20 ml of 1N aqueous sodium hydroxide solution and extracted with 100 mβ of methylene chloride. The methylene chloride solution was washed with dilute sodium hydroxide and dried over anhydrous sodium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography using chloroform:methanol=50:1 to obtain the target product, 8-(3-(4-diphenylmethylbiperazin-1-yl)). 45 mg of -2-hydroxybroboxy}quinoline was obtained as a powder.IR
vcm-' (KBr): 3350, 2800, 1500
, 1450, 1320.1110 NMR δppm (CDC13): 2.2 ~ 3.
0 (m, 10H). 4.1 to 4.8 (m, 4H). 4
．． 9 (br, S, IH), 7.0 ~ 7.8 (m.14
H), 8.15 (dd.1}1), 8.85 (dd, I
H) Example 50 5-{3- (4-diphenylmethylbiperazine-1-
yl)-2-hydroxybroboxy}quinoline 5-hydroxyquinoxaline Ig and dry DMF 20mI
2, 0.78 g of t-butoxypotassium was added thereto, and the mixture was heated and stirred at 50° C. for 30 minutes. 1.9 g of shrimp chlorohydrin was added to the reaction solution, and the mixture was heated and stirred at 90'C for 3 hours. The solvent was distilled off under reduced pressure, water was added to the residue, and the mixture was extracted with 50ml of chloroform.

The chloroform solution was dried over anhydrous sodium sulfate, then distilled off, and the residue was purified using silica gel column chromatography.

When flowing out with chloroform: methanol = 100:1,
5-(2,3-Evoxybroboxy)quinoxaline as an oily substance. 28 g was obtained. This epoxy body 0
．． 28 g and N-diphenylmethylbiverazine 0.
35 g was dissolved in 10 ml of ethanol and heated under reflux for 3 hours. After the reaction, the solvent was distilled off, and the residue was purified using silica gel column chromatography. When chloroform:methanol=50:1 flows out, the target product 5-(3-
(4-diphenylmethylpiperazin-1-yl)-2-
Hydroxybroboxy}-quinoxaline as powder 0
．． 12g was obtained.

IR vcm-'(κBr): 3360, 298
0.1600. 156G, 1480, 1460.
1440. 1290. 1100NMR δpp
m(CDCIs): 2.2-3.2(n+, IOH). 3.8(s,
IH), 4. 1 ~ 4.6 (m, 4} 1), 7.0 ~
8.0 (m.13H), 8.7 - 9.1 (m, 28) Example 51 5- {3- (4-diphenylmethylbiverazine-1
-yl)-2-hydroxybroboxy}quinazoline 2 g of 5-hydroxyquinazoline was dissolved in 30 mβ of dry DMF, and potassium t-butoxy i. Add s g, 5
The mixture was heated and stirred at 0°C for 1 hour. 4 g of shrimp chlorohydrin was added to the reaction solution, and the mixture was heated and stirred at 90° C. for 3 hours. The solvent was distilled off under reduced pressure, and the residue was purified using silica gel column chromatography. When chloroform:methanol=100:1 is discharged, 0.0. 84 g was obtained. This epoxy body 0. 84 g of N-diphenylmethylbiverazine and 1.05 g of N-diphenylmethylbiverazine were dissolved in 20+nβ ethanol and heated under reflux for 3 hours. After the reaction, the solvent was distilled off, and the residue was purified using silica gel column chromatography. When flowing out with chloroform:methanol=50:1, the target product 5- (3-
(4-diphenylmethylpiverazin-1-yl)-2-
hydroxybroboxy}-quinazoline as a powder.
48 g was obtained. IR Vcm-' (KBr):
3400.2800, 1610, 1580.1130N
MR δppm (CDCI,): 2.2 to 3.0 (
m, IOH), 3.4 (br, s, Hl), 2.0
~2.3 (m, 4H). 6.9 ~ 7.9 (m, 13H
), 9. 28 (s, Hl), 9. 70 (
s, 1N) Example 52 5 [3- {4- ((4-Biridyl)monophenylmethyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline N-{(4-biridyl)monophenylmethyl}biperazine The above compound was obtained by carrying out the reaction and treatment according to Example 1-(b).

NMRδppm: (CDCl3) 2. 3 ~3. 9 (m. IOH), 4. 05
~4.20(m, 3}1). 4. 25 (s,
IH), 6. 85 (d, IH). 7. 2
~7. 4 (m, 8}1), 7. 58 (
t, 18), 7.70 (d, IH), 8.50 (
d, IH), 8.55 (d, IH), 8. 89 (
d, IH) IR v cm-' (KBr): 3350,1
620, 1590, 1410, 1370, 1270, 1
100.780 Example 53 2.4-Dimethyl-5-[3-((α.α-diphenylacetyl)biverazin-1-yl}-2-hydroxybroboxy]quinoline obtained by Example 5-(b) Example 1-(a) using 2.4-dimethyl-5-hydroxyquinoline and N-(α.α-diphenylacetyl)biperazine
, (b) to obtain the above compound.

IR v cm-' (KBr) (HCI salt): 3
350 (br.). 1630, 1595, 1
430, 1380, 1260, 1090. 102
5, 735, 690NMR 270MHZ (CDC
l3) δppm: 2. 10 ~ 2.72 (m, 5
H), 2.63 (s.3H), 2. 83 (s, 3
H), 3. 30 ~3. 60 (m, 3}1
), 3.60 to 3.80 (m.2}1), 4.
00~4.20 (m, 28). 5. 19(s, IH
), 6.75 (d, IH), 6.99 (s, IH)
, 7.20 ~ 7.40 (m, IOH), 7.47 (
tr, Hl), 7. 60 (d, IH) Example 54 2-trifluoromethyl-4-methyl-5-[3- {
4-(dibenzosuberan-5-yl)-biperazine-1
-yl}-2-hydroxybroboxy]quinoline In Example 5-a), b), α. A similar reaction and treatment was carried out using α,α-trifluoroacetone to obtain 2-trifluoromethyl-4-methyl-5-hydroxyquinoline. Furthermore, using N-(dibenzosuberan-5-yl)biperazine, Example 1
- The above compound was obtained by carrying out the reaction and treatment according to (a) and (b).

NMR (CDCI3) δppm: 2. 20
~2. 90 (m, 12H). 2. 76 (
s, 3H) 3.92 to 4.25 (m, 6H), 6.
95 to 7.20 (m, 91-1), 7. 55 ~7
．． 75 (m, 3H)IR (KBr) v
cm-': 2920, 2800, 1590,
1370, 1350, 1330, 1270, 11
80,1140.750 Example 55 2-trifluoromethyl-4-methyl-5-[3-{4
- (α.α-diphenylacetyl)viverazine-1-
yl}-2-hydroxybroboxy]quinoline Example 1 using 2-trifluoromethyl-4-methyl-5-hydroxyquinoline obtained in Example 54 and N-(α,α-diphenylacetyl)biverazine -(a)
, (b) to obtain the above compound.

NMR (CDC13) δppm: 2. 15-2
．． 70 (m, 6H), 2. 77 (s,
3H). 3. 40-3. 55 (m, 28)
．． 3. 65-3. 80 (m, 2H), 4.
00-4. 35 (m, 3H), 5. 20
(s, IH) ,? ．． 00(d, IH, J←7.
41), 7. 10-7.50 (m, 10}1), 7
．． 60-7. 80 (m, 3H)IR (KB
r) v cm-': 1630, 1595, 145
0,1430,+380.1350,1270,116
0.1140 Example 56 2-trifluoromethyl-4-methyl-5-{3-(4
- (diphenylmethylbiperazin-1-yl)-2-
Hydroxybroboxy}quinoline Example 11(a) was prepared using 2-trifluoromethyl-4-methyl-5-hydroxyquinoline obtained in Example 54 and N-diphenylmethylbiverazine. (The above compound was obtained by performing reaction treatment according to bl. NMR (CDCI.) δppm: 2. 20-
2. 90 (m. IOH). 2. 77 (s
, 3H)4. 00-4. 35 (m, 4H)
, 7. 02 (d, IH, J-7. 92Hz
)． 7. 10-7. 55 (m, 108),
7. 55 ~7. 80 (m, 3H)IR
(KBr) v cm-': 2800, 159
5, 1450, 1380, 1350, 1330
, 1270, 1180. 1140 Example 57 5-[3-(4-(bis-(4-fluorophenyl)methyl)biverazin-1-yl}-2-hydroxybroboxy}quinoline Eboxy compound obtained by Example 1-(a) and N
-{Bis-(4-fluorophenyl)methyl}viverazine was used to react and treat according to Example 1-(b) to obtain the above compound.

IRv""cm-' (l {Cl salt): max 3400. +630. 1590. 1510. 1
410, 1280. 1230NMR (CDCIs
) δppm: 2. 1-2.9 (1011, bm), 4. 1-4.
3 (3H, m), 6.85 ~ 7.75 (12H, m)
, 8.55 (IH, dd). 8. 9 (1}1, d
d) Example 58 5-[3-{4-((4-chlorophenyl)-phenylmethyl)biverazin-1-yl}-2-hydroxybroboxy}quinoline Example 1-Eboxy compound obtained by (a) and N
- Reaction according to Example 1 - (b) using ((4-chlorophenyl)monophenylmethyl}biperazine,
The above compound was obtained by processing. IRνK"cm-' (MCI salt): max 3400, 1630, 1590, 1410, 1380.
1280NMR (CDCIs) δppm: 2.
17-2.93 (10}1, bm). 4. 1-4.
3 (41{.m), 6. 85 (IH.d),
7. 16-7. 74 (12H, m), 8.
55 (IH, dd), 8. 9 (IH. d
d) Example 59 5-[3-(4-(bis-(4-methoxyphenyl)methyl)biperazin-1-yl}-2-hydroxybroboxy}quinoline Example 1 - Eboxy compound obtained by (a) and N
-{4-bis(4-methoxyphenyl)methylbiperazine was used to react and treat according to Example 1-(b) to obtain the above compound. IRV KB'cm-' (MCI): max 3400, 1635, 1610, 1595, 1
510, 1410, 1280, l250 NMR (CDCI!) δppm: 2. 34-
2. 76 (IOH, bm). 3. 75 (
6H. s) ,4. 11-4. 24 (4H,
m), 6. 80-6. 87 (5H.m)
,7. 26-7. 39 (5H, m), 7.
55-7. 71 (2H, m), 8. 57
(ILd), 8. 89 (IH, dd) Example 60 5-[3-(4-(Iminodibenzyl-5-carbonyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline obtained by Example 1 - (a) Eboxy body and N
Using -(iminodibenzyl-5-carbonyl)viverazine, the reaction and treatment were carried out according to Example 1-(b) to obtain the above compound.

IR v KBrcm-' (HCI): maX 3400, 1640, 2600, 1490, 1
415, 1380, 1280NMR (CDCI3
1 δppm: 2. 3-2. 4 (2N, m), 2. 53
-2. 61 (4H, m), 3. 1 5 (4
H, s), 3. 40 (4H, m) ,4.
10-4. 22 (3H, m), 6. 85
(IH, d), 7. 09-7. 71 (11
}1, m), 8. 52 (1}1, dd)
．． 8. 90 (IH, dd) Example 61 2.4-dimethyl-5- [3- (4- (iminodibenzyl-5-carbonyl)biperazin-1-yl}-
Using the epoxy form of 2-hydroxybroboxy]quinoline obtained in Example 5 and N-(iminodibenzyl-5-carbonyl)viverazine, the reaction and treatment were carried out according to Example 1-(b) to obtain the above compound. ．． NMR (CDCIs) δppm: 1. 8-2.
1 5 (IH, m), 2. 26-2. 4
0 (2}1. m) ,2. 50-2. 60 (
4H, m), 2. 64 (3H, s) ,2
．． 84 (3H, a), 3. 16 (4}1
．． s), 3. 40 (4}1, s) ,4.
10-4. 20 (3H, m), 6. 77
(IH, d) ,6. 99 (l}l, a)
, 7. 09-7. 62 (IOH, m)IRv
""cm-' (HCI salt): max 3400, 3240, 1640, 1600. 1
4B0, 1440, +390.1270. 126
0 Example 62 5-[3-(N'-(dibenzosuberane-5-
yl) ethylenedi7mino}-2-hydroxybroboxycoquinoline Example 1 - The epoxy compound obtained by (a) and N
-(Dibenzosuberan-5-yl)ethylenediamine was reacted and treated according to Example 1-(b) to obtain the above compound. NMR (CDCIs) δppm: 2. 20-2
．． 59 (2}1, bs), 2. 60-3.
0 (8H, m) ,3. 56-3. 72 (
2H, m). 4. 04-4. 25 (3}1
, m) ,4. 77 (IH, s), 8.
82 (IH, d), 7. OS-7. 75 (
1 1}1. m), 8. 53 (l}l, d
d) ,8. 87 (l}l, dd) IRv KB'cm-' (HCI): max 3400. 2920, 1630, 1590, 1
410, 1380, 1280, 1l00 Example 63 5-[3-{N,N'-dimethyl-N'-(dibenzosuberan-5-yl)ethylenediamino}-2-hydroxybroboxy]quinoline Example 1 - (a ) and N
, N'-dimethyl-N°-(dibenzosuberan-5-yl)ethylenediamine was reacted and treated according to Example 1-(b) to obtain the above compound. NMR (CDCI3) δppm: 2. 13
(6}1, d), 2. 4-2. 55 (5H
, m). 2. 56-2. 90 (3H, m)
, 3. 90-4. 20 (6H, m) ,6
．． 85 (IH, d), 6. 98-7. 7
5 (1 1H, m) ,8. 57 (IH, d
d), 8. 92 (IH, dd)rRv",'
,',crn-' (HCI salt): 3400, 292
0, 1630, 1590, 1470, 1410
, 1370, 1280. 1100 Example 64 2-Methylthio-5-[3-(4-(dibenzosuberan-5-yl)piverazin-1-yl}-2-hydroxybroboxy]quinoline 2-methylthio-5-hydroxyquinoline in Example 1 - According to (a), the epoxy compound was reacted and treated with N-(dibenzosuberan-5-yl)piverazine to obtain the above compound.

NMR (CDCI3) δppm: 2. 20-2
．． 85 (m, 12H), 2. 67 (s,
3H) ,3. 85-4. 20 (m, 6H)
, 6. 74 (d, IH, J=8.9)
,6. 95-7. 30 (m, 9H), 7.
40-7. 55 (m, 2H), 8. 26
(d, IH, J=8.9)IR v KBrcm
-' (HCI salt): max 1615 1600. 1575, 1480, 14
40, 1390, 1335, +285. 1250
．． 1125 Example 65 2-Methylthio-5-[3- {4- (α.α-diphenylacetyl)biperazin-1-yl}-2-hydroxybroboxy]quinoline 2-methylthio-5-hydroxyquinoline in Example 1 - According to (a), the epoxy compound was reacted and treated with N-(α.α-diphenylacetyl)biperazine to obtain the above compound. NMR (CDCh) δppm: 2.15-2.25 (m, IH), 2.35-2.7
0 (m, 58). 2.68(s,3}1). 3.40
-3.55 (m, 2H), 3.65-3.80 (m, 2H)
H), 4.05-4.20 (m, 3}1), 6.75
(d, It{, JII8. 4), 7. 15
-7. 35 (m, IIH). 7.45-7.5
5 (m.2H), 8.38 (d, IH, J=8.91
) IRVκBrcm-' (}ICI salt): max 1630. 1580. +440. 1420, 1
390, 1250. 1+30.1070. 102
0 Example 66 2.4-Dimethyl-5-[3-{N,N'-dimethyl-N'-(dibenzosuberan-5-yl)ethylenediamino}-2-hydroxybroboxy]quinoline obtained according to Example 5 Reaction according to Example 1-(b) using the obtained epoxy compound and N,N'-dimethyl-N'-(dibenzosuberan-5-yl)ethylenediamine,
The above compound was obtained by processing.

NMR (CDCI3) δppm: 2. 1 2
(6H, d), 2. 40-2. 6 (5}
1, m) ,2. 65 (:E, s), 2.
70-2. 90 (5H, m), 3. 93-
4. 10 (6H.m). 6. 77 (IH
, d) ,7. 00-7. 20 (9}1, m
), 7. 45-7. 65 (2H, m) Example 67 2.4-dimethyl-5-(3-(4-diphenylmethylenebiperidin-1-yl)2-hydroxybroboxy)quinoline Eboxy compound obtained by Example 5 and Using 4-diphenylmethylenebiveridine, the reaction and treatment were carried out according to Example 1-(b) to obtain the above compound.

NMR (CDCIs) δppm: 1. 74-
1. 97 (IH. bm) 2. 35-2. 6
0 (6H, m) ,2. 62-2. 95 (1
0}1. m). 4. 05-4. 30 (3
H, m). 6. 80- (IH, d), ?
．． 00 (IH, s)7. 10-7. 35 (
IOH, m), 7. 45-7. 65 (2H
, m) rR v KBrcm-' (}ICI salt)
:max 3380, 2900, 2640, 1630, 1
600, +470. 1440,1380.1270 Example 68 5-(3-[N-((3-(dibenzosuberane-5-indeli)probyl)-N-methylamino]-
2-Hydroxybroboxy)quinoline Example 1-(a)
The epoxy compound obtained by the above reaction and N-(3-(dibenzosuberane-5-indene)probyl)-N-methylamine were reacted and treated according to Example 1-(b) to obtain the above compound. NMR (CDCIs) δppm: 1. 45-2
．． 05 (5}1, bm). 2. 28 (3
}1, s). 2. 31-2. 85 (6H,
m), 3. 2-3. 5 (IH, bm).
4. 05-4. 35 (3H, m), 6.
8-7. 76 (12H, m). 8. 52-8
．． 58- (II. m), 8. 89-8.
93 (IH, m)IRνK"'cm-' (HCI
salt): max 3360, 2640, 1630, 1590, 1
475, 1410, 13701270. 1100 Example 69 5-{3- (3.3-diphenylbrobylamino)-
2-Hydroxybroboxy}quinoline Example 1 - (
The epoxy compound obtained in a) and 3,3-diphenylbrobylamine were reacted and treated according to Example 1-(b) to obtain the above compound.

NMR (C[]CI,) δppm: 2.43-
2.60 (m, 2}1), 2.80-3.15 (m, 3
11), 4. 90-5. 20 (m, 5H),
6. 67 (d, 1}1, J=7.42)
,7. 05-7. 45 (m, IIH), 7
．． 45-7, 80 (m, 2H), 8.53 (d
, LH, J=8.4), 8.80-8.95 (IH,
m) IR (κBr) v cm-': 1610,
1580, 1490, 1460, 1400,
1360, 13151270, 1200. 117
0. 1140 Example 70 5-(3-(2.2-diphenylethylamine)-2
-hydroxybroboxy}quinoline Example 1 - (a
) and 2,2-diphenylethylamine were reacted and treated according to Example 1-(b) to obtain the above compound.

NMR (CDCIs) δppm: 2. 85-
3. 40 (m, 38), 4. 00-4.
28 (m, 5H), 6.82 (d, IH, J=7
．． 42), 7.05-7.40 (m, l1t+), 7.
52-7. 72 (m, 2}1), 8. 4
5-8. 55 (m, IH), 8. 85-8.
90 (IH, m)IR (KBr) v cm
-' (HCI salt): +620.1580.1480.
1440.1400. +370.12701200,1
170.1140 Example 71 2-Methylsulfonyl-5-[3-(4-(dibenzosuberan-5-yl)biperazin-lyl}-2-
Hydroxybroboxy]quinoline 2-methylsulfonyl-5-hydroxyquinoline was made into an epoxy form according to Example 1-(a), and reacted and treated with N-(dibenzosuberan-5-yl)viverazine to obtain the above compound.

NMR (CDCI,) δppm: 2. 20-2
．． 90 (m. 12H), 3. 35 (s.
3H) ,3. 90-4. 30 (m, 6H)
, 6. 95-7, 25 (m, 9H)7. 6
6-7. 82 (m. 2}1), 8. 07
(d, l}I, J=8.4) ,8. 83 (
d, IH, J=8. 911IR (KBr)
v cm-': 1640, 1610, +575.
1465, 1450, 1300, 1270.1160.
1140.1120 Example 72 5-[3-(4-(xanthen-9-yl)biverazin-1-yl}-2-hydroxybroboxy]quinoline Example 1 - Eboxy compound obtained by (a) and N-
Example 1 using (xaten-9-yl)biperazine
- The above compound was obtained by carrying out the reaction and treatment according to (b).

NMRδppm (CDCIs): 2. 3-2. 7 (m, IOH). 4. 0
-4. 15 (m, 3H), 4, 83 (s, IH
), 6. 81 (d, IH), 7. l-
7. 4 (m, 9ftl, 7.56(t, IH)
,7.67(d,1}1),8.52(d,IH),8
．． 88 (d, 1}1) IR (KBr) v cm-': 3400,
2800, 1580, 1460, 1440, 1240.
980740 Example 73 5- [3- {N-methyl-3-(5-iminodibenzyl)probylamine}-2-hydroxybroboxy]
The epoxy compound obtained in Example 1-(a) of quinoline and desipramine were reacted and treated according to Example 1-(b) to obtain the above compound.

NMR (CDCIs) δppm: 1. 65-1. 76 (2H, m). 2.
18 (3H, s), 2. 37-2. 58 (
4}1. m, 3. 11 (48, s) ,3
．． 67-3. 86 (2}1, m, 3.9
8-4. 10 (3}1, m)6.74-6.86
(3H,m,6.97-7.08(6}1.m),7
．． 27-7. 32 (IH. m), 7. 4
8-7. 67 (2}1, m). 8. 42-8
．． 50 (IH, m, 8.81-8.84
(1}1, dd)IRv""cm-' (HCI salt): max 33B0, 2640, +630. 1590. 1
485, 1470. 1410, 1380, 1280
．． 1110 Example 74 5- {3- (4-diphenylmethylbiperazine=1
-yl)-2-hydroxypropylthio}quinoline Example 2 3-(b) prepared by 4-(3
1.2 g of monochloro-2-hydroxybrobyl-1-diphenylmethylbiperazine and 2 of 5-mercabutoquinoline.
Dissolve 20mg of DBU in 10mf2 of chloroform,
After adding 311 mg of, the mixture was left to stand at room temperature for 12 days. The reaction solution was poured into 20 mβ of water and extracted twice with methylene chloride. The organic layer was separated, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure. The residue was subjected to silica gel chromatography (AcOE
t effluent) to obtain 130 mg of the above compound. IRvm8W, (KBr): Cm 3300.2520, 1620, 1580, +420.
1390.1360,1290,1070.910 NMR δppm (CDCIs):2. 3-2
．． 7 (m, 12B), 3. 8-3. 9
(m, IH). 4. 21 (s, IH),
7. 1-7. 7 (m, 13H). 8. 00
(dd. 1}1), 8.75 (dd, 181, 8.
94 (dd, IH) Example 75 5- {3-[4-(Dibenzosuberan-5-yl)biperazin-l-yl}-2-hydroxybrobylti]quinoline Example 2 3- In (b), 4-(3-chloro2-hydroxybrobyl)-1-(dibenzosuberan-5-yl) prepared by using 4-(dibenzosuberan-5-yl)viverazine in place of diphenylmethylrubiverazine. The reaction and treatment were carried out according to Example 74 using 932 mg of viperazine and 270 mg of 5-mercabutoquinoline to obtain 220 mg of the above compound.

IR v ""'+ (KBr): Cm 3300, 2500, 15130. +390.1360
,1300,1070,860,760,650,62
0 NMR δppm (CDCl3): 2. 1-2.
7 (m, 12H), 2. 7-2. 9 (
m, 2H). 3. 8-4. 1 (m, 4H)
, 7. 0-7. 8 (m, 11N) ,8.
1) Q(d, IH), 8. 75 (dd, IH)
, 8.93 (dd, +8) Example 76 5- [3- (4- (5-dibenzosuberanyl)biperazin-l-yl}-2-hydroxybroboxy]-
2.4-ditrifluoromethylquinoline a) 0.38 g of 2.4-ditrifluoromethyl-5-hydroxyquinoline was reacted and treated according to Example 1-(a) to give 2.4-ditrifluoromethyl-5-(
0.18 g of 2.3-epoxybroboxy)quinoline was obtained.

NMRδppm (CDCI3): 2.7-2.8 (m, II{). 2.9-3.0 (m
, IN), 3. 4-3. 5 (m, lfl)
, 4. 1-4. 4 (m, 2H) ,7.19
(d, IH), 7.81 (t, IH), 7.96 (d,
1}1). 8. 08 (s, E) b) 0.18 g of the epoxy compound synthesized above and 5
5-
[3- {4-(5-dibenzosuberanyl)biverazin-1-yl}-2-hydroxyproboxy]-2.4
-0.3g of ditrifluoromethylquinoline was obtained.

NMRδppm (CDCIs): 2. 16-2.90 (m, 12H). 3.9-4.
3 (m, 6H). 7. 0-7. 3 (m, 108
), 7. 80 (t, IH). 7. 94
(d, IH), 8. 05 (s, 18) Example 77 5-[3-(4-(Dibenzosuberen-5-ylidene)biperidin-l-yl}-2-hydroxybutboxy]quinoline synthesized by Example 1 - (a) Eboxy body 1
．． 65 g and 4-(dibenzosuberen-5-ylidene)biperidine 1. 66 g of 5-[3-{4-(dibenzosuberen-5-ylidene)biperidine}-2-hydroxybroboxy]quinoline was reacted and treated according to Example 1-(b). I got 32g. IR v cm-' (KBr): 3400.
2700, 1645, 1590, 1410,
1105. 790NMR δppm (CDCIs)
: 2. 1-2.9(m, 10}1). 3.9-4.2
(m, 3H), 6. 78 (d, I}I), 6
．． 86 (s, 2H), 7. 1-7. 3
(m. 8H), 7.50 (t.I}l冫, 7.63
(d.I}I), 8.47 (d,l}l), 8.
81 (d, IH) Example 78 5-[2-Hydroxy-3-(4-(5-hydroxydibenzosuberan-5-yl)biveridin-1-yl}proboxy]quinoline Example 1 - Synthesized by (a) Eboxy body 0
．． 80g and 4-(5-hydroxydibenzosuberane-5
Example 1-(
b) and react according to 5-[2-hydroxy-3-
4- (5-hydroxydibenzosuberan-5-yl)
biperidinylbroboxy}]quinoline to 0. 99g
Obtained.

IR v cm-' (KBr): 3400.
2700, +630. 1590, 1410, 1
280. 1105790 NMR δppm (CDCIs): 1. 2-2.
6 (m, 12H), 2. 9-3. 05
(m, 2H) ,3. 43-3. 52 (m,
2H), 4. 0-4. 1 (m, 1}1)
,4. 1 5 (d, 2H), 6. 82 (
d, E), 7. 0-7. 2 (m, 6}1
), 7.33 (dd, IH), 7. ss(t,
IH), 7.65 (d. IH), 7. 80 (d,
2}1), 8.51 (d, I11). 8.66(
dd,1}1) Example 79 5-[2-hydroxy-3-(4-(5-hydroxydibenzosuberen-5-yl)biperidin-1-yl}
broboxy]quinoline Example 1 - Eboxy compound 1 synthesized by (a)
．． 08g and 4-(5-hydroxydibenzosuberene-5
Example 1-(b) using 1.6 g of viveridin (-yl)
5-[2-hydroxy-3-(
4- (5-hydroxydibenzosuberen-5-yl)
biveridinyl}proboxy]quinoline 1. 41g
Obtained.

IR v cm-' (KBr): 3350, 2
700, 1630, 1590, 1410, 12
80. 1105790 NMR δppm (CDCI!): 1.4 (t,
2N), 1.7(t.l}I), 2.0(t,l}I)
,2. 4-3. 0 (m, 8N). 4. 0
-4. 2 (m, 3}1). 6. 79 (d.
IH), 6. 92 (s, 2H), 7.
1-7. 4 (m. 7H) , 7.52 (t, I
H), 7.65 (dd, IH), 7.87 (dd, 2}
1), 8. 45 (dd, 1N), 8. 83
(dd, 18) Example 80 5-[3-(4-(Dibenzosuberan-5-ylidene)biperidin-1-yl}-2-hydroxybroboxy]quinoline Eboxy synthesized by Example 1-(a) body 0
．． 4g and 0.41g of 4-(dibenzosuberan-5-ylidene)viveridine were reacted and treated according to Example 1-(b) to give 5-[3-{4-(dibenzosuberan-5-ylidene)viveridine}- 0.4 g of 2-hydroxybroboxy]quinoline was obtained.

IR v cm-' (KBr): 3400,
2920, 1630, 1590, 1410, 1
280. 1 100790 NMR δI)l)m (CDCI 3):2.
3-3. 0 (m, 12H), 3. 3-3.
5 (m, 2H) ,4. 0-4.3 (m.
3H), 6. 82 (d, l}I). 6.
9-7. 2 (m, 8H), 7. 32 (d
d. IH). 7.54 (t, IH), 7.66 (
d, l}l), 8.52 (dd, IH)8. 85
(dd, IH) Example 81 5-[3-(4-(Dibenzosuberan-5-yl)biveridin-l-yl}-2-hydroxybroboxy]quinoline Eboxy compound synthesized by Example 1-(a) 1
．． 45 g of 4-(dibenzosuberan-5-yl)viveridine were reacted and treated according to Example 1-(b) using 1.6 g of 4-(dibenzosuberan-5-yl)viveridine.
5-yl)biveridin}-2-hydroxybroboxy]
quinoline 0. I got 97g. IR v am-'
(KBr) :3400, 2700, 1630,
1590, 1410, 1280. 110579
0 NMRδppm (CDCIs): 2. 1-3. 0 (m, 12}1) , 3, 3
-3. 5 (m. 2H). 4. 0-4. 3
(m. 3}1), 6. 83 (d, IH)
,7. 0-7. 1 (m, 8H), 7. 3
3 (dd, IH), 7. 54(t, l}I)
,7.66(d,l}l),8. 52(d, IH
). 8. 86 (del, II{) Example 82 5- [3- [N-methyl-N- {3- (5H-
10, I+-dihydrodibenzo[b,f]azebin-5-yl)proyl}amino]-2-hydroxybroboxy]quinoline Example 1 - Eboxy compound 0 synthesized by (a)
．． 67g and 5H-10.11-dihydro-5- {3-
(Methylamino)propyl}-dibenzo(b,fl) Using 1.0 g of azebin, reaction and treatment were performed according to Example 1-(b) to give 5-[3-[N-methyl-N- {3-
(5H-10,ll-dihydrodibenzo[b,fl
1.07 g of azevinyl)propyl}amine]-2-hydroxybroboxycoquinoline was obtained. fR v cm
-' (KBr) :3380. 2660, +63
0. 1590. 1485, 1410. 1280
1110 NMR δI)pm (CDCIs): 1. 70
(m, 2H), 2. 20 (s, 3H),
2. 35-2. 61 (m. 4H), 3.
10 (s, 4H). 3, 65-3. 80 (m
．． 2H). 3. 95-4. 15 (m, 3
H). 4. 20-4. 35 (m. I}I),
6. 7-6. 9 (m, 3H), 6. 95-7.
15 (m, 6H), 7. 30 (m, 1
}1) ,7. 45-7. 70 (m, 2H)
．． 8. 45 (n+, IH), 8. 85
(m, IH) Example 83 5-[3-(4-(Dibenzosuberan-5-yl)biverazin-1-yl}proboxy]quinoline Example 3 2-Quinoline compound synthesized by (a) 0.6 5-(3-(4-(dibenzosuberan-5-yl)viverazine-1- 0.7 g of il)broboxy]quinoline was obtained. IR vcm-'(κB'): 3420, 164[), 1600, 1420,
1380, 1285. 1110NMR δppm
(CDCa) :2. 0-2. 95 (m, +
4}1) , 3. 8-4. 10 (m, 3H
), 4. 13-4. 25 (m. 2H).
6. 83 (d, IH), 7. 0-7. 2
(m, 88), 7. 35 (m, IH),
7. 51-7.70 (m, 2H), 8. 5
5 (dd, 1}1) ,8. 9 (dd, IH
) Example 84 5-[3-(4-(diphenylmethylene)biveridin-1-yl}broboxy]quinoline Example 3 2-
0.55 g of quinoline compound synthesized by (a) and 4
-(diphenylmethylene)viveridine 0. 68 g was reacted and treated according to Example 1-(b).
0.59 g of [3-(4-(diphenylmethylene)biverizinin-1-yl}propoxy]quinoline was obtained. IR v am-' (KBr): 3400, 2
920, 1630, 1590, 1460, 14
10. 13751280 NMR δppm (CDCIs): 2. 1-2.
7 (m. 12H), 4. 27 (t, 2
H) ,6. 85 (d. IH), 7. 1-
7. 4 (m, IIH) ,7. 56-7. 7
(m. 2H), 8. 59 (dd, IH)
．． 8. 9 (dd, IH) Test Example 1 Effect of enhancing anticancer drug uptake into drug-resistant cancer cells Adriamycin-resistant strain 2 of human ovarian cancer cell A2780
780AD (A. M. Logan et al., Scie
nce, vol. 224, pp. 994-996. 1984) were suspended in RPMI-1640 culture solution containing 5% fetal bovine serum at IXIO' cells/ml, and 1ml of cancer cell suspension per well was seeded in a 24-well multi-well culture plate with a diameter of 16 cm. , 5% CO2, and cultured at 37°C. 24
After hours, the culture solution was mixed with 20 nM'}I-pincristin (
RPMI-1640 culture medium containing 5% fetal bovine serum, 10mM Heves buffer (0. After dissolving in DMSO, exchanged with 5 ml,
Add 5 μl of the test compound diluted with physiological phosphate buffer (
The concentration in the reaction solution is 1.0 or 10.0 μg/ml), 5
%C (h, After 2 hours of incubation at 37°C, the cells were washed with chilled physiological phosphate buffer. This was added to 0.5 ml of
? 0. Add 2N NaOH, transfer to vial, and heat at 56°C.
The cells were lysed by taking a hot bath for 30 to 60 minutes. 4 ml of Acid Aquasol 2 was added, and the amount of 3H-pincristin taken into the cells was measured using a liquid scintillation counter. The effect was expressed as a percentage (%) of the amount of pincristin taken up by the drug-treated group, with the amount of pincristin taken up by the drug-untreated control group being taken as 100. The results are shown in Table 1.

Test Example 2 Effect of enhancing the action of anticancer drugs Adriamycin-resistant strain K562/ADM of human myeloid leukemia cell K562 was treated with RPMI-containing 5% fetal bovine serum.
The cancer cell suspension was suspended in 1640 culture solution at 2 x 10' cells/ml, and 2 ml of cancer cell suspension per tube was seeded in 12 x 75 mm tubes, and cultured at 37°C in 5% CO₂.

6 hours later pincristin (O~3000ng/ml)
and the concentration of the test compound in the reaction was 0.3, 1.3 ng.
/ml and 5% Co. The culture was continued for 72 hours at 37°C. 9. Cell suspension. 5ml ISOT
In addition to ON II, after counting the number of cells with a Coulter counter, the 50% growth inhibitory concentration of pincristin, IC,
. (ng/ml) was determined. Table 2 shows the results of tests conducted on the compounds listed in Table 1.
C.S. Value and effect enhancement degree (multiples are shown in parentheses in Table 2)
It is shown as. Other compounds also showed similar action-enhancing effects.

Test Example 3 Enhancement effect of anticancer drugs in vincristine-resistant mouse leukemia-bearing mice 10' mouse leukemia cells P3 in female CDFI mice
88 pincristin-resistant strain P388/VCR was implanted intraperitoneally, and pincristin and the test compound were simultaneously administered intraperitoneally once a day for 5 days.

Observe the number of days of survival, and set the number of survival days of the control group as 100,
The survival days of the drug-treated group were expressed as a percentage (%) (T/
C). The results are shown in Tables 3(a) to (f).

Other compounds also showed similar survival effects.

Table 1 Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 2 *1 Umbrella 2 Adriamycin-resistant human myeloid leukemia K562 cells (
Concentration of pincristin that inhibits the proliferation of K562/ADM) by 50%. Effect of pincristin enhancement (~ times) by the test compound.

K562/AD) ICs of a cell pincristin alone
. It was calculated by dividing the value of (655 ng/ml) by each value in the table.

table 3-(b) 3-(a) 3-(c) table 3-(d) table 3-(e)

Claims (1)

[Claims] 1. A compound represented by the following general formula (I) and a salt thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A represents an oxygen atom, a sulfur atom, a methylene group, an amino group, or -NR^3-, and the bonding position can be any possible on the condensed ring. B is ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and C is ▲Mathematical formulas, chemical formulas, etc. There are tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ D is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ , ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ▲There are mathematical formulas, chemical formulas, tables, etc.▼, or ▲There are mathematical formulas, chemical formulas, tables, etc.▼, C and D. can form ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼ or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ E, F, G or H each independently represents a carbon atom or nitrogen atom.However, at least one of them shall represent a nitrogen atom.R^1, R^2 each independently represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group, a substituted amino group, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfone group, a trifluoromethyl group, a cyano group, a nitro group, an amide group, or a hydroxy group. , substitution positions take all possible positions on the condensed ring, and the 2 constituting the condensed ring
R^3 is a hydrogen atom, a lower alkyl group, or an acyl group, and R^4 is a hydroxyl group or a lower alkylamino group. , a lower alkoxy group or a lower acyloxy group, R^5 and R^6 each independently represent a hydrogen atom, a lower alkyl group or a hydroxyalkyl group, and R^7, R^8 and R^9 each Independently hydrogen atom, hydroxyl group, phenyl group, pyridyl group or substituted phenyl group, I is oxygen atom, ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ or nitrogen atom, J is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, -CH=CH
-, -OCH_2- or an oxygen atom, n represents an integer of 1 to 10, and m represents an integer of 0 to 2. 2. The compound according to claim 1, represented by the following general formula (II), and a salt thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, C' is piperazine or piperidine, and D' is ▲
There are mathematical formulas, chemical formulas, tables, etc.▼, ▲There are mathematical formulas, chemical formulas, tables, etc.▼, or, H, G, R1, R^2, I and J represent the same meaning as in general formula (1). ) 3. In general formula (II), G is a carbon atom, H is a nitrogen atom, R
^1, R^2 are each independently a hydrogen atom, halogen atom, lower alkyl, J is ▲ there is a mathematical formula, chemical formula, table, etc. ▼ or -CH=CH-, I is ▲ there is a mathematical formula, chemical formula, table, etc. 3. The compound according to claim 2, which is ▼ and a salt thereof. 4. The compound and its salt according to claim 3, wherein in the general formula (II), ▲, which is a mathematical formula, a chemical formula, a table, etc., is substituted at the 5-position of the condensed ring. 5. The compound represented by general formula (II) is 5-[3-{4
-dibenzosuberan-5-yl)piperazin-1-yl}-2-hydroxypropoxy]quinoline. 6. The compound represented by general formula (II) is 5-[3-{4
-diphenylmethylene)piperidin-1-yl}-2-
5. The compound according to claim 4, which is hydroxypropoxyquinoline. 7. The compound represented by general formula (II) is 5-[3-{4
-dibenzosuberane-5-ylidene)piperidine-1-
5. The compound according to claim 4, which is 2-hydroxypropoxy]quinoline. 8. A heterocyclic compound represented by the following formula and epihalogenohydrin are reacted in the presence of a base to form the corresponding epoxy compound. ^2, A, E, F, G, H are general formulas (
Same as I), X represents a halogen atom. ) Furthermore, a method of synthesizing the compound of general formula (I) by thermally reacting the synthesized epoxy compound with the corresponding amine derivative. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ 9. Epihalogenohydrin and the corresponding amine derivative are reacted thermally or in the presence of a base to form the corresponding epoxy compound and hydroxyl. ▲There are mathematical formulas, chemical formulas, and tables. A method for synthesizing a compound of general formula (I) by reacting a synthesized epoxy compound or hydroxyhalogen compound in the presence of a base or acid or thermally. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (or ▲There are mathematical formulas, chemical formulas, tables, etc.▼) (In the formula, R^1, R^2, A, C, D, E, F, G, H are general formulas Same meaning as (I), X represents a halogen atom.
) 10. A heterocyclic compound represented by the following formula and a dihalogenoalkyl are reacted in the presence of a base to form the corresponding halogenoalkyl compound. ▼ (In the formula, R^1, R^2, A, E, F, G, H, and n have the same meanings as in general formula (I), and X represents a halogen atom.) Further synthesized halogenoalkyl General formula (I) is obtained by thermally reacting the compound with the corresponding amine derivative.
How to synthesize compounds of. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1, R^2, A, C, D, E, F, G, H,
n represents the same meaning as in general formula (I). X represents a halogen atom. ) 11. A heterocyclic compound represented by the following formula, an acid halide, or an acid anhydride is reacted thermally or in the presence of a base to form the corresponding halide. R^1, R^2, A, E, F, G, H, X, and n have the same meanings as in general formula (I).) Furthermore, the synthesized halide and the corresponding amine derivative were thermally reacted A method of synthesizing the compound of general formula (I) by ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1, R^2, A, C, D, E, F, G, H,
n and X represent the same meanings as in general formula (I). ) A 12,5-hydroxyquinoline derivative and epichlorohydrin are reacted in a solvent in the presence of a base, and after the reaction, the solvent is distilled off, the residue is extracted with chloroform, and further purified by silica gel column chromatography to obtain an epoxy compound. Further, the epoxy compound and the amine derivative H-C'-D'(C' and D' represent the same meanings as in general formula (II)) are melted in a solvent and reacted under heating under reflux. 9. The synthesis method according to claim 8, wherein the compound of general formula (II) is synthesized by distilling off and purifying the residue using silica gel column chromatography. 13. An anticancer drug effect enhancer comprising a compound represented by the general formula (I) according to claim 1 and a salt thereof as an active ingredient. 14. The effect enhancer according to claim 2, wherein the anticancer drug is a non-antimetabolite. 15. The effect enhancer according to claim 14, wherein the non-antimetabolite is vincristine or adriamycin. 16. The effect according to claim 13, wherein the anticancer drug effect enhancer is an orally administered tablet, granule, powder, suspension, capsule, or syrup, or an injection, suppository, or isotonic solution for infusion. Enhancer.