DC-89 derivatives represented by the formula: ##STR1## wherein X represents hydrogen or CO.sub.2 CH.sub.3 ; and ##STR2## wherein Z represents Cl or Br; R represents hydrogen, CONR.sup.1 R.sup.2 (in which R.sup.1 and R.sup.2 independently represent hydrogen, a straight-chain or branched alkyl group having 1 to 4 carbon atoms or phenyl) or ##STR3## (in which n represents an integer of 0 to 4; R.sup.3 represents CH.sub.2, ##STR4## oxygen, N--CH.sub.3, or N--CH.sub.2 CONR.sup.1 R.sup.2 in which R.sup.1 and R.sup.2 have the same significances as defined above); and W represents hydrogen or ##STR5## (in which W.sup.1 and W.sup.2 independently represent hydrogen or OR.sup.2 in which R.sup.4 represents a straight-chain or branched alkyl group having 1 to 4 carbon atoms or a straight-chain or branched alkenyl group having 2 to 4 carbon atoms, and pharmaceutically acceptable salts thereof have an excellent anti-tumor and antibacterial activity and are expected to be useful as anti-tumor compositions and antibacterial compositions.

BACKGROUND OF THE INVENTION 
The present invention relates to DC-89 derivatives. The compounds exhibit 
an excellent anti-tumor and antibacterial activity and are expected to be 
useful as anti-tumor agents and antibacterial agents. 
As compounds similar to the DC-89 derivatives of the present invention, 
DC-89Al, DC-89A2, DC-89B1 and DC-89B2 represented by the following 
structural formula are known. These compounds exhibit an antibacterial 
activity against various bacteria and also show an antitumor activity 
against melanoma B-16, etc. 
##STR6## 
DC-89Al is disclosed in WO 87/06265 (EP-A-0271581); and DC-89A2, DC-89Bl 
and DC-89B2 are disclosed in Japanese Published Unexamined Patent 
Application No. 119787/90 (EP-A-0351865). SF2582A and SF2582B which are 
the same compounds as DC-89A2 and DC-89Al respectively are disclosed 
inJapanese Published Unexamined Patent Application No. 139590/89 
(EP-A-0318056). DC-88A and DC113 having the following structures are 
disclosed in WO 87/06265 and Japanese Published Unexamined Patent 
Application No. 177890/90 (EP-A-0376300), respectively. DC-88A and DC113 
not only show an antibacterial activity against a variety of bacteria but 
also exhibit an anti-tumor activity against melanoma B-16, etc. 
##STR7## 
DC-88A derivatives and DC-89 derivatives are disclosed in Japanese 
Published Unexamined Patent Application No. 288879/90 (EP-A-0354583), 
Japanese Published Unexamined Patent Application No. 7287/91 
(EP-A-0365041) and Japanese Published Unexamined Patent Application No. 
128379/91 (EP-A-0406749). These derivatives are also disclosed in 
EP-A-0461603 and EP-A-0468400, and a patent application directed to DC-89 
derivatives has been filed as Japanese Patent Application No. 21243/91. 
Further, derivatives of SF2582C are disclosed in Japanese Published 
Unexamined Patent Application No. 275581/89 (EP-A-0339681) and CC-1065 and 
its derivatives are disclosed in Japanese Published Unexamined Patent 
Application No. 64695/79 (U.S. Pat. No. 4,169,888), Japanese Published 
Unexamined Patent Application No. 193989/85 (EP-A-0154445), WO 88/04659 
and EP-A-0359454. 
SUMMARY OF THE INVENTION 
The present invention relates to DC-89 derivatives represented by formula 
(I): 
##STR8## 
wherein X represents hydrogen or CO.sub.2 CH.sub.3 ; and 
##STR9## 
wherein Z represents Cl or Br: R represents hydrogen, CONR.sup.1 R.sup.2 
(in which R.sup.1 and R.sup.2 independently represent hydrogen, a 
straight-chain or branched alkyl group having 1 to 4 carbon atoms or 
phenyl) or 
##STR10## 
(in which n represents an integer of 0 to 4; R.sup.3 represents CH.sub.2, 
##STR11## 
oxygen, N--CH.sub.3, or N--CH.sub.2 CONR.sup.1 R.sup.2 in which R.sup.1 
and R.sup.2 have the same significances as defined above); and W 
represents hydrogen or 
##STR12## 
(in which W.sup.1 and W.sup.2 independently represent hydrogen or OR.sup.4 
in which R.sup.4 represents a straight-chain or branched alkyl group 
having 1 to 4 carbon atoms or a straight-chain or branched alkenyl gropu 
having 2 to 4 carbon atoms), and pharmaceutically acceptable salts 
thereof. 
DETAILED DESCRIPTION OF THE INVENTION 
The compounds represented by formula (I) are hereinafter referred to as 
Compounds (I). Similarly, the compounds represented by formulae (II) 
through (IV) are referred to as Compounds (II) through (IV). Compounds 
(I)a, (I)b, etc. are intended to be included in Compounds (I). In the 
definitions of R.sup.1 and R.sup.4 in formula (I), the straight-chain or 
branched alkyl having 1 to 4 carbon atoms include, for example, methyl, 
ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl. 
As the pharmaceutically acceptable salts of Compounds (I), inorganic 
acid-addition salts such as hydrochloride, hydrobromide, hydroiodide, 
sulfate, phosphate and nitrate, and organic acid-addition salts such as 
acetate, benzoate, maleate, fumarate, succinate, tartrate, citrate, 
oxalate, glyoxylate, aspartate and methanesulfonate may be mentioned.

The processes for preparing Compounds (I) are described below. 
Process 1 
Compound (I)a [Compound (I) wherein 
##STR13## 
and W is hydrogen) can be prepared by treating Compound (A) shown by the 
formula: 
##STR14## 
or Compound (B) shown by the formula: 
##STR15## 
which are described in Japanese Published Unexamined Patent Application 
No. 128379/91 (EP-A-0406749), with a base in an inert solvent. 
##STR16## 
As the base, sodium methoxide, sodium hydroxide, potassium hydroxide, 
potassium t-butoxide, triethylamine, 1,8-diazabicycloundecene (DBU), 
potassium carbonate, etc. may be used. The base is usually used in an 
amount of 1 to 3 equivalents based on Compound (A) or Compound (B). As the 
inert solvent, water, methanol, tetrahydrofuran (THF), dioxane, 
acetonitrile, etc. may be used singly or in combination. The reaction is 
generally carried out at -20.degree. C. to 50.degree. C. and is completed 
in 30 minutes to 5 hours. 
Process 2 
Compound (I)b [Compound (I) wherein 
##STR17## 
and W is a group other than hydrogen] can be prepared by allowing Compound 
(I)a to react with a reactive derivative of the corresponding carboxylic 
acid in an inert solvent in the presence of a base. 
##STR18## 
In these formulae, W.sup.a represents W as defined above with the exception 
of hydrogen and X has the same significance as defined above. 
As the base, sodium hydride, lithium diisopropylamide, potassium 
t-butoxide, triethylamine, 4-dimethylaminopyridine, etc. may be used. The 
base is usually used in an amount of 1 to 2 equivalents based on Compound 
(I)a. As the inert solvent, dimethylformamide, THF, toluene, 
dimethylsulfoxide, etc. may be used singly or in combination. Examples of 
the reactive derivatives of carboxylic acids include acyl halides such as 
acid chlorides and acid bromides; activated esters such as p-nitrophenyl 
esters, 2,4,5-trichlorophenyl esters and N-oxysuccinimide esters, etc. The 
reactive derivative is usually used in an amount of 1 to 3 equivalents 
based on Compound (I)a. The reaction is generally carried out at 
-50.degree. C. to 30.degree. C. and is completed in 30 minutes to one day. 
Process 3 
##STR19## 
Compound (I)c [Compound (I) wherein 
and R is hydrogen] can be prepared by allowing Compound (I)a or Compound 
(I)b to react with hydrochloric acid or hydrobromic acid in an inert 
solvent. 
##STR20## 
In these formulae, X, W and Z have the same significances as defined above. 
Hydrochloric acid or hydrobromic acid is usually used in an amount of 1to 
20 equivalents based on Compound (I)a or Compound (I)b. As the inert 
solvent, water, dimethylformamide, THF, toluene, dioxane, acetonitrile, 
etc. may be used singly or in combination. The reaction is generally 
carried out at -20.degree. C. to 50.degree. C. and is completed in 10 
minutes to one hour. 
Process 4-1 
Compound (I)d [Compound (I) wherein 
##STR21## 
and R is CONR.sup.1 R.sup.2 or 
##STR22## 
can be prepared by allowing Compound (I)c to react with Compound (II)a 
represented by the formula: 
EQU R.sup.1 R.sup.2 NCOCl (II)a 
(wherein R.sup.1 and R.sup.2 have the same significances as defined above) 
or Compound (II)b represented by the formula: 
##STR23## 
(wherein R.sup.3 and n have the same significances as defined above) in an 
inert solvent in the presence of a base. 
##STR24## 
In these formulae, R.sup.a represents CONR.sup.1 R.sup.2 or 
##STR25## 
in the definition of R; and X, W and Z have the same significances as 
defined above. 
As the base, triethylamine, pyridine, 4-dimethylaminopyridine, etc. may be 
used. The base is usually used in an amount of 1 to 5 equivalents based on 
Compound (I)c, but when the base serves also as a solvent, it may be used 
in large excess of Compound (I)c. As the inert solvent, pyridine, 
methylene chloride, dimethylformamide, THF, toluene, etc. may be used 
singly or in combination. Compound (II) is usually used in an amount of 1 
to 10 equivalents based on Compound (I)c. The reaction is generally 
carried out at -50.degree. C. to 50.degree. C. and is completed in 30 
minutes to one day. 
Process 4-2 
Compound (I)d can also be prepared according to the following steps. 
(Step 1) 
Compound (III) can be prepared by allowing Compound (I)c to react with 
p-nitrophenyl chloroformate in an inert solvent in the presence of a base. 
##STR26## 
In these formulae, X, Z and W have the same significances as defined 
above. 
p-Nitrophenyl chloroformate is usually used in an amount of 1 to 5 
equivalents based on Compound (I)c. As the inert solvent, pyridine, 
methylene chloride, dimethylformamide, THF, toluene, etc. may be used 
singly or in combination. The reaction is generally carried out at 
-80.degree. C. to 50.degree. C. and is completed in 30 minutes to one day. 
(Step 2) 
Compound (I)d can be prepared by allowing Compound (III) to react with 
Compound (IV)a represented by the formula: 
EQU R.sup.1 R.sup.2 NH (IV)a 
(wherein R.sup.1 and R.sup.2 have the same significances as defined above) 
or Compound (IV)b represented by the formula: 
##STR27## 
(wherein R.sup.3 and n have the same significances as defined above) in an 
inert solvent in the presence of a base. 
##STR28## 
In these formulae, R.sup.a, X, Z and W have the same significances as 
defined above. 
As the base, triethylamine, pyridine, 4-dimethylaminopyridine, etc. may be 
used. The base is usually used in an amount of 1 to 5 equivalents based on 
Compound (III), but when the base serves also as a solvent, it may be used 
in large excess of Compound (III). As the inert solvent, pyridine, 
methylene chloride, dimethylformamide, THF, toluene, etc. may be used 
singly or in combination. Compound (IV) is usually used in an amount of 1 
to 5 equivalents based on Compound (III). The reaction is generally 
carried out at -80.degree. C. to 50.degree. C. and is completed in 30 
minutes to one day. 
After completion of the reaction in each step, water, an acid or a buffer 
solution may be added to the reaction mixture, if necessary, followed by 
extraction with a water-immiscible solvent such as ethyl acetate, 
chloroform or ether. The extract is washed with water, an aqueous solution 
of sodium chloride, or the like, and dried over anhydrous sodium sulfate, 
or the like. Then, the solvent is distilled off, and the residue is 
subjected to silica gel column chromatography, thin layer chromatography, 
high performance liquid preparative chromatography, recrystallization, or 
the like to effect purification. 
In the case where a salt of Compound (I) is desired and it is produced in 
the form of the desired salt, it can be subjected to purification as such. 
In the case where Compound (I) is produced in the free state and its salt 
is desired, Compound (I) can be converted into its salt by dissolving or 
suspending the compound in an appropriate solvent and adding a suitable 
acid to the solution or suspension. 
Intermediates may be directly used in the subsequent reaction without being 
isolated or purified. Compounds (I) and pharmaceutically acceptable salts 
thereof may be in the form of adducts with water or various solvents, 
which are also within the scope of the present invention. Furthermore, all 
possible stereoisomers of Compounds (I) including optical isomers and 
mixtures thereof also fall within the scope of the present invention. 
The structures and compound numbers of representative compounds which fall 
under Compounds (I) are shown in Table 1. 
TABLE 1 
__________________________________________________________________________ 
##STR29## 
Compound 
No. Type 
X Z R W.sup.3 W 
__________________________________________________________________________ 
1 A CO.sub.2 CH.sub.3 
-- -- -- H 
2 A CO.sub.2 CH.sub.3 
-- -- CH.sub.3 MEC 
3 B CO.sub.2 CH.sub.3 
Br CON(CH.sub.3).sub.2 CH.sub.3 MEC 
4 B CO.sub.2 CH.sub.3 
Br 
##STR30## CH.sub.3 MEC 
5 B CO.sub.2 CH.sub.3 
Br 
##STR31## CH.sub.3 MEC 
6 B CO.sub.2 CH.sub.3 
Br 
##STR32## CH.sub.3 MEC 
7 B CO.sub.2 CH.sub.3 
Br 
##STR33## CH.sub.3 MEC 
8 B CO.sub.2 CH.sub.3 
Br 
##STR34## CH.sub.3 MEC 
9 B CO.sub.2 CH.sub.3 
Br 
##STR35## CH.sub.3 MEC 
10 B CO.sub.2 CH.sub.3 
Br 
##STR36## CH.sub.3 MEC 
11 B CO.sub.2 CH.sub.3 
Br 
##STR37## CH.sub.3 MEC 
12 B CO.sub.2 CH.sub.3 
Br 
##STR38## CH.sub.3 MEC 
13 A CO.sub.2 CH.sub.3 
-- -- n-C.sub.3 H.sub.7 
MEC 
14 A CO.sub.2 CH.sub.3 
-- -- 
##STR39## 
MEC 
15 A CO.sub.2 CH.sub.3 
-- -- n-C.sub.5 H.sub.11 
MEC 
__________________________________________________________________________ 
The pharmacological activity of representative Compounds (I) is shown 
below. 
Growth Inhibitory Effect against HeLaS.sub.3 Cells 
HeLaS.sub.3 cells were suspended in a medium comprising MEM medium, 10% 
fetal calf serum and 2 mM glutamine (hereinafter referred to as medium A) 
to a concentration of 3.times.10.sup.4 cells/ml. The cell suspension thus 
prepared was put into wells of a 96-well microtiter plate in an amount of 
0.1 ml per well. After incubation at 37.degree. C. for 20 hours in a 
CO.sub.2 incubator, Compound (I) appropriately diluted with medium A was 
added to each well in an amount of 0.05 ml. 
The cells were further cultured at 37.degree. C. for 72 hours in the 
CO.sub.2 -incubator and the culture supernatant was removed. After the 
residue was washed once with phosphate buffer saline (PBS), a medium 
comprising medium A and 0.02% Neutral Red was added in an amount of 0.1 ml 
per well. Then, the cells were cultured at 37.degree. C. for one hour in 
the CO.sub.2 -incubator, whereby the cells were stained. After removal of 
the culture supernatant, the residue was washed once with physiological 
saline. The pigment was extracted with 0.001N hydrochloric acid/30% 
ethanol and the absorbance of the extract was measured at 550 nm using a 
microplate reader. The concentration of the test compound at which the 
growth of the cells is inhibited by 50% (IC.sub.50) was calculated by 
comparing the absorbance of untreated cells with those of the cells 
treated with the test compound at known concentrations. The result is 
shown in Table 2. 
Therapeutic Effect against Sarcoma 180 Tumor 
Five male ddY-strain mice each weighing 18 to 20 g were used for each group 
as test animals, and 5.times.10.sup.5 Sarcoma 180 tumor cells were 
implanted subcutaneously into the animals at the axilla. One day after the 
implantation, 0.2 ml of physiological saline containing Compound (I) at 
the concentration indicated in Table 2 was intravenously administered to 
each mouse. T/C [T: average tumor volume (mm.sup.3) of the group treated 
with the test compound, C: average tumor volume (mm.sup.3) of the control 
group which received an intravenous administration of 0.2 ml of 
physiological saline]was determined seven days after the implant 
The result is shown in Table 2. 
TABLE 2 
______________________________________ 
Compound Dose 
No. IC.sub.50 (nM) 
(mg/kg) T/C 
______________________________________ 
2 0.18 
3 11 8.0 0.027 
4 &lt;0.24 
7 4.0 0.20 
9 4.0 0.17 
11 8.0 0.12 
12 2.0 0.25 
______________________________________ 
Acute Toxicity Test 
A test compound was intravenously administered to ddY-strain male mice each 
weighing 20.+-.1 g. MLD (the minimum lethal dose) was determined by 
observing the mortality for 14 days after the administration. 
The result is shown in Table 3. 
TABLE 3 
______________________________________ 
Acute Toxicity 
Compound No. (MLD) mg/kg 
______________________________________ 
2 2.0 
3 &gt;8.0 
4 &gt;8.0 
5 &gt;8.0 
7 8.0 
9 4.0 
11 &gt;8.0 
12 2.0 
______________________________________ 
Compounds (I) and pharmaceutically acceptable salts thereof may be used as 
anti-tumor agents and antibacterial agents, singly or in combination with 
at least one pharmaceutically acceptable carrier. For example, Compounds 
(I) or salts thereof are dissolved in a physiological saline or in an 
aqueous solution of glucose, lactose, mannitol, or the like to prepare a 
pharmaceutical composition suitable for injection. Alternatively, 
Compounds (I) or salts thereof are freeze-dried in a conventional manner 
and mixed with sodium chloride to prepare a powder injection. 
If necessary, the pharmaceutical composition may contain additives well 
known in the art of medical preparation, for example, pharmaceutically 
acceptable salts. Although the dose of the composition may vary depending 
upon the age, condition, etc. of the patient, it is suitable to administer 
Compound (I) in a dose of 0.01 to 20 mg/kg/day for mammals including human 
beings. Administration may be made, for example, once a day (single 
administration or consecutive administrations) or intermittently 1 to 3 
times a week or once every 2 to 3 weeks, intravenously. If desired, 
intraarterial administration, intraperitoneal administration, 
intrathoracical administration, etc. are also possible in a similar dose 
and in a similar manner. Further, if desired, the composition may also be 
administered orally, in a similar dose and in a similar manner. Forms for 
oral administration include tablets, capsules, powders, granules and 
ampoules, which contain pharmaceutical auxiliaries well known in the art 
of medical preparation. 
Certain specific embodiments of the present invention are illustrated by 
the following examples. 
The physicochemical properties of the compounds shown in the following 
examples were determined with the following equipments. 
______________________________________ 
NMR JEOL, Ltd. FX-100 (100 MHz) 
Bruker AM-400 (400 MHz) 
JEOL, Ltd. GX-270 (270 MHz) 
JEOL, Ltd. EX-270 (270 MHz) 
MS Hitachi Ltd. M-80B 
JEOL, Ltd. SX-102 
IR Japan Spectral Co., Ltd. IR-810 
______________________________________ 
As the silica gel, Wakogel C-200.RTM. manufactured by Wako Pure Chemical 
Industries, Ltd. was used. 
EXAMPLE 1 
Synthesis of Compound 1 
In 2 ml of methanol was dissolved 14 mg [0.029 mmol) of Compound (A), and 
0.03 ml of methanol containing 28 wt% sodium methoxide (0.16 mmol) was 
added to the solution. The mixture was stirred at room temperature for one 
hour. To the reaction mixture was added 0.2 M phosphate buffer of pH 7, 
followed by extraction with chloroform. The chloroform layer was washed 
with a saturated aqueous solution of sodium chloride, dried over anhydrous 
sodium sulfate, and then concentrated under reduced pressure. The 
resulting crude product was purified by silica gel column chromatography 
(20 ml of silica gel, chloroform : methanol =25 : 1) to give 7.4 mg (yield 
99%) of Compound 1. 
The physicochemical properties of Compound 1 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3 +DMSO-d.sub.6) .delta.(ppm); 11.72(1H, br 
s), 6.92(1H, br s), 5.34(1H, s), 3.72(3H, s), 3.67(1H, dd, J=10.6, 5.3Hz), 
3.51(1H, dd, J=10.6, 10.6Hz), 3.39(1H, m), 2.46(3H, s), 1.98(1H, dd, 
J=7.7, 2.4Hz), 0.98(1H, dd, J=4.6, 2.9Hz), 
SIMS (m/z); 259(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 1682, 1607, 1573, 1458, 1379, 1305, 1273, 1229, 
1194, 1156, 1108 
EXAMPLE 2 
Synthesis of Compound 2 
To 2 ml of N,N-dimethylformamide was added 23 mg (0.57 mmol) of 60% sodium 
hydride, and 2 ml of N,N-dimethylformamide containing 95.6 mg (0.37 mmol) 
of Compound 1 obtained in Example 1 was added to the mixture, followed by 
stirring at 0.degree. C. for two hours in an argon atmosphere. The 
reaction mixture was cooled to -50.degree. C. and 2 ml of 
N,N-dimethylformamide containing 166 mg [0.56 mmol) of 4-nitrophenyl 
4-methoxycinnamate was added thereto. The mixture was stirred at 
-50.degree. C. to room temperature for one hour. After 0.2M phosphate 
buffer of pH 7 was added to the reaction mixture, extraction was carried 
out with ethyl acetate. The ethyl acetate layer was washed with a 
saturated aqueous solution of sodium chloride, dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was purified by silica gel column chromatography (20 ml of silica 
gel, chloroform : methanol = 50 : 1) to give 132 mg (yield 85%) of 
Compound 2. 
The physicochemical properties of Compound 2 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 11.14(1H, br), 7.79 (1H, d, 
J=15.4Hz), 7.52(2H, d, J=8.7Hz), 7.26 (1H, s), 6.91(2H, d, J=8.8Hz), 
6.75(1H, d, J=15.4Hz), 4.24(1H, dd, J=10.9, 10.9Hz), 4.15(1H, dd, J=10.9, 
4.8Hz), 3.85(3H, s), 3.82(3H, s), 3.56(1H, m), 2.62(3H, s), 2.39(1H, dd, 
J=7.6, 3.5Hz), 1.31(1H, dd, J=4.9, 3.5Hz) 
EIMS (m/z); 419(M).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 1702, 1601, 1512, 1390, 1292, 1241, 1225, 1173, 
1110, 1072 
EXAMPLE 3 
Synthesis of Compound 3 
In 3 ml of acetonitrile was dissolved 30 mg (0.072 mmol) of Compound 2 
obtained in Example 2, and 1.5 ml of 48% hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 3 ml of methylene chloride, and 3 ml of methylene 
chloride containing 36 mg (0.179 mmol) of p-nitrophenyl chloroformate was 
added to the solution at -78.degree. C. Then, 0.025 ml (0.180 mmol) of 
triethylamine was added to the mixture, followed by stirring for 0.5 hour. 
After 0.032 ml (0.356 mmol) of a 50% aqueous solution of dimethylamine was 
added to the reaction mixture, the mixture was stirred at -78.degree. C. 
to room temperature for 0.5 hour. Then, 0.2M phosphate buffer of pH 7 was 
added to the reaction mixture, followed by extraction with chloroform. The 
chloroform layer was washed with a saturated aqueous solution of sodium 
chloride, dried over anhydrous sodium sulfate, and then concentrated under 
reduced pressure. The resulting crude product was purified by silica gel 
column chromatography (30 ml of silica gel, chloroform : methanol =100 : 
1) to give 36 mg (yield 90%) of Compound 3. 
The physicochemical properties of Compound 3 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 8.98(1H, br), 8.25(1H, s), 
7.80(1H, d, J=15.5Hz), 7.56(2H, d, J=8.7Hz), 6.93(2H, d, J=8.8Hz), 
6.81(1H, d, J=15.5Hz), 4.56 (1H, m), 4.48(1H, br d, J=10.6Hz), 4.30(1H, 
dd, J=9.1, 2.4Hz), 3.94(3H, s), 3.86(3H, s), 3.81(1H, dd, J=10.4, 1.7Hz), 
3.34(1H, dd, J=10.5, 10.4Hz), 3.18(3H, s), 3.06(3H, s), 2.60(3H, s) 
SIMS (m/z); 572, 570(M+H).sup.30 
IR (KBr) .nu.(cm.sup.-1); 2364, 1701, 1686, 1637, 1601, 1511, 1399, 1250, 
1173, 1109, 1091 
EXAMPLE 4 
Synthesis of Compound 4 
In 5 ml of acetonitrile was dissolved 20 mg (0.048 mmol) of Compound 2 
obtained in Example 2, and 2.2 ml of 1N hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 3 ml of methylene chloride, and 19.3 mg [0.096 
mmol) of p-nitrophenyl chloroformate was added to the solution at 
-10.degree. C. Then, 0.013 ml (0.096 mmol) of triethylamine was added to 
the mixture, followed by stirring for 0.5 hour. After 0.014 ml (0.14 mmol) 
of piperidine was added to the reaction mixture, the mixture was stirred 
at -10.degree. C to room temperature for 0.5 hour. Then, 0.2 M phosphate 
buffer of pH 7 was added to the reaction mixture, followed by extraction 
with chloroform. The chloroform layer was washed with a saturated aqueous 
solution of sodium chloride, dried over anhydrous sodium sulfate, and then 
concentrated under reduced pressure. The resulting crude product was 
purified by silica gel column chromatography [30 ml of silica gel, 
n-hexane ethyl acetate =1 : 1) to give 22 mg (yield 75%) of Compound 4. 
The physicochemical properties of Compound 4 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 9.21(1H, br), 8.22(1H, s), 
7.80(1H, d, J=15.2Hz), 7.57(2H, d, J=8.7Hz), 6.94(2H, d, J=8.8Hz), 
6.81(1H, d, J=15.1Hz), 4.54 (1H, m), 4.47(1H, br d, J=10.5Hz), 4.31(1H, 
dd, J=9.2, 9.2Hz), 3.95(3H, s), 3.86(3H, s), 3.80(1H, dd, J=10.2, 2.2Hz), 
3.68(2H, br), 3.55(2H, br), 3.21(1H, dd, J=10.2, 10.2Hz), 2.53(3H, s), 
1.68 (6H, br) 
SIMS (m/z); 612, 610(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 2930, 2364, 1694, 1649, 1599, 1511, 1431, 1408, 
1244, 1215, 1092, 1025 
EXAMPLE 5 
Synthesis of Compound 5 
In 5 ml of acetonitrile was dissolved 20 mg (0.048 mmol) of Compound 2 
obtained in Example 2, and 2.2 ml of 1 N hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1 N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 3 ml of methylene chloride, and 19.3 mg (0.096 
mmol) of p-nitrophenyl chloroformate was added to the solution at 
-10.degree. C. Then, 0.013 ml (0.096 mmol) of triethylamine was added to 
the mixture, followed by stirring for 0.5 hour. After 0.012 ml (0.14 mmol) 
of pyrrolidine was added to the reaction mixture, the mixture was stirred 
at -10.degree. C. to room temperature for 0.5 hour. Then, 0.2M phosphate 
buffer of pH 7 was added to the reaction mixture, followed by extraction 
with chloroform. The chloroform layer was washed with a saturated aqueous 
solution of sodium chloride, dried over anhydrous sodium sulfate, and then 
concentrated under reduced pressure. The resulting crude product was 
purified by silica gel column chromatography (30 ml of silica gel, 
chloroform : methanol =100 : 1) to give 22 mg (yield 76%) of Compound 5. 
The physicochemical properties of Compound 5 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 8.92(1H, br), 8.26(1H, s), 
7.80(1H, d, J=15.2Hz), 7.57(2H, d, J=8.7Hz), 6.94(2H, d, J=8.8Hz), 
6.80(1H, d, J=15.1Hz), 4.57(1H, m), 4.47(1H, br d, J=10.3Hz), 4.30(1H, dd, 
J=9.0, 9.0Hz), 3.96(3H, s), 3.86(3H, s), 3.81 (1H, dd, J=10.2, 2.1Hz), 
3.65(2H, t, J=6.6Hz), 3.51(2H, t, J=6.6Hz), 3.22(1H, dd, J=10.2, 10.2 Hz), 
2.69(3H, s), 2.00(4H, br) 
SIMS (m/z); 598, 596(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 2944, 1697, 1637, 1491, 1412, 1313, 1218, 1109, 
1087 
EXAMPLE 6 
Synthesis of Compound 6 
In 5 ml of acetonitrile was dissolved 50 mg [0.12 mmol) of Compound 2 
obtained in Example 2, and 2.5 ml of 48% hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1 N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 5 ml of methylene chloride, and ml of methylene 
chloride containing 61 mg (0.30 mmol) of p-nitrophenyl chloroformate was 
added to the solution at -78.degree. C. Then, 0.042 ml (0.30 mmol) of 
triethylamine was added to the mixture, followed by stirring for 0.5 hour. 
After 0.040 ml (0.36 mmol) of N-methylpiperazine was added to the reaction 
mixture, the mixture was stirred at -78.degree. C. to room temperature for 
0.5 hour. Then, 0.2M phosphate buffer of pH 7 was added to the reaction 
mixture, followed by extraction with chloroform. The chloroform layer was 
washed with a saturated aqueous solution of sodium chloride, dried over 
anhydrous sodium sulfate, and then concentrated under reduced pressure. 
The resulting crude product was purified by silica gel column 
chromatography (30 ml of silica gel, chloroform : methanol =20 : 1) to 
give 67 mg (yield 89%) of Compound 6. 
The physicochemical properties of Compound 6 are as follows. 
huH-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 9.79(1H, br), 8.21(1H, s), 
7.77(1H, d, J=15.2Hz), 7.57(2H, d, J=8.8Hz), 6.93(2H, d, J=8.8Hz), 
6.78(1H, d, J=15.3Hz), 4.53(1H, m), 4.41(1H, br d, J=10.5Hz), 4.25(1H, dd, 
J=9.3, 9.3Hz), 3.95(2H, br), 3.93(3H, s), 3.86(3H, s), 3.84(2H, br), 
3.79(1H, dd, J=9.7, 2.6Hz), 3.22(1H, dd, J=10.2, 10.2Hz), 2.94(4H, br), 
2.67(3H, s), 2.62(3H, s) 
SIMS (m/z); 627, 625(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 2360, 1692, 1647, 1602, 1507, 1400, 1291, 1217, 
1173, 1094 
EXAMPLE 7 
Synthesis of Compound 7 
In a mixture of 2 ml of ethanol and 4 ml of methanol was dissolved 45 mg 
(0.072 mmol) of Compound 6 obtained in Example 6, and 0.025 ml of 5.8 N 
hydrogen chloride-ethanol was added to the solution, followed by stirring 
at 0.degree. C. for one hour. The reaction mixture was concentrated under 
reduced pressure to give 47 mg (yield of Compound 7. 
The physicochemical properties of Compound 7 are as follows. 
.sup.1 H-NMR (400MHz, DMSO-d.sub.6) .delta.(ppm); 12.07(1H, br), 10.57 (1H, 
br), 8.10(1H, s), 7.74(2H, d, J=8.8Hz), 7.58(1H, d, J=15.3Hz), 7.06(1H, d, 
J=15.3Hz), 7.00(2H, d, J=8.8Hz), 4.50(1H, m), 4.42(3H, br), 4.17(1H, br), 
3.85(3H, s), 3.82(3H, s), 3.79(1H, br), 3.58(3H, br), 3.50(4H, br), 
2.86(3H, s), 2.68(3H, s) 
IR (KBr) .nu.(cm.sup.-1); 2364, 1740, 1705, 1648, 1599, 1511, 1405, 1251, 
1218, 1173, 1095, 1023 
EXAMPLE 8 
Synthesis of Compound 8 
In 1.5 ml of acetonitrile was dissolved 25 mg (0.06 mmol) of Compound 2 
obtained in Example 2, and 1.5 ml of 48% hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 2 ml of dichloromethane, and 37 mg (0.18 mmol) of 
p-nitrophenyl chloroformate was added to the solution at -78.degree. C. 
Then, 0.025 ml (0.18 mmol) of triethylamine was added to the mixture, 
followed by stirring for 0.5 hour. After 35 mg (0.21 mmol) of 
piperidinopiperidine was added to the reaction mixture, the mixture was 
stirred at -78.degree. C. to 0.degree. C. for 0.5 hour. Then, 0.2M 
phosphate buffer of pH 7 was added to the reaction mixture, followed by 
extraction with chloroform. The chloroform layer was washed with a 
saturated aqueous solution of sodium chloride, dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was purified by silica gel column chromatography (20 ml of silica 
gel, chloroform : methanol =10 : 1) to give 38 mg (yield 91%) of Compound 
8. 
The physicochemical properties of Compound 8 are as follows: 
.sup.1 H-NMR (270MHz, CDCl.sub.3) .delta.(ppm); 9.14(1H, br), 8.23(1H, s), 
7.79(1H, d, J=15.2Hz), 7.58(2H, d, J=8.6Hz), 6.94(2H, d, J=8.6Hz), 
6.80(1H, d, J=15.2Hz), 4.57 (1H, m), 4.45(2H, m), 4.33(2H, m), 3.96(3H, 
s), 3.86(3H, s), 3.79(1H, br d, J=9.7Hz), 3.22(1H, dd, J=10.0, 10.0Hz), 
3.03(1H, m), 2.88(1H, m), 2.66(3H, s), 2.62(5H, br), 1.92(2H, br), 
1.67(6H, br), 1.49(2H, br) 
FABMS (m/z); 695, 693(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 1701, 1642, 1599, 1560, 1542, 1515, 1409, 1253, 
1208, 1092 
EXAMPLE 9 
Synthesis of Compound 9 
In a mixture of 1 ml of ethanol and 0.5 ml of methanol was dissolved 26 mg 
(0.037 mmol) of Compound 8 obtained in Example 8, and 0.008 ml of 6.86 N 
hydrogen chloride-ethanol was added to the solution, followed by stirring 
at room temperature for one hour. The reaction mixture was concentrated 
under reduced pressure to give mg (yield 96%) of Compound 9. 
The physicochemical properties of Compound 9 are as follows: 
.sup.1 H-NMR (270MHz, DMSO-d.sub.6) .delta.(ppm); 12.02(1H, s), 9.96 (1H, 
br), 8.05(1H, s), 7.74(2H, d, J=8.9Hz), 7.57(1H, d, J=15.3Hz), 7.05(1H, d, 
J=15.4Hz), 6.99(1H, d, J=8.9Hz), 4.46(2H, m), 4.41(2H, br), 4.19(1H, br d, 
J=13.3Hz), 3.84(3H, s), 3.80(3H, s), 3.77(1H, br), 3.47(5H, br), 3.13(1H, 
br d, J=12.9Hz), 2.95(2H, br), 2.66(3H, s), 2.15(2H, br), 1.82(6H, br), 
1.70(2H, br) 
IR(KRr) .nu.(cm.sup.-1); 1688, 1646, 1598, 1514, 1407, 1252, 1213, 1093, 
1023 
EXAMPLE 10 
Synthesis of Compound 10 
In 1.5 ml of acetonitrile was dissolved 25 mg (0.06 mmol) of Compound 2 
obtained in Example 2, and 1.5 ml of 48% hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 2 ml of dichloromethane, and 37 mg (0.18 mmol) of 
p-nitrophenyl chloroformate was added to the solution at -78.degree. C. 
Then, 0.025 ml (0.18 mmol) of triethylamine was added to the mixture, 
followed by stirring for 0.5 hour. After 39 mg (0.21 mmol) of 
N-isopropyl-1-piperazineacetamide was added to the reaction mixture, the 
mixture was stirred at -78.degree. C. to 0.degree. C. for 0.5 hour. Then, 
0.2M phosphate buffer of pH 7 was added to the reaction mixture, followed 
by extraction with chloroform. The chloroform layer was washed with a 
saturated aqueous solution of sodium chloride, dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was purified by silica gel column chromatography (20 ml of silica 
gel, chloroform : methanol =20 : 1) to give 31 mg (yield 73%) of Compound 
10. 
The physicochemical properties of Compound 10 are as follows. 
.sup.1 H-NMR (270MHz, CDCl.sub.3) .delta.(ppm); 8.96(1H, br s), 8.25 (1H, 
s), 7.80(1H, d, J=15.5Hz), 7.57(2H, d, J=8.5Hz), 6.94(2H, d, J=8.5Hz), 
6.80(1H, d, J=15.5Hz), 6.80(1H, m), 4.58(1H, m), 4.47(1H, br d, J=10.9Hz), 
4.31(1H, dd, J=8.9, 8.9Hz), 3.96(3H, s), 3.86(3H, s), 3.79(2H, m), 
3.63(2H, br), 3.23 (1H, dd, J=10.0, 10.0Hz), 3.05(2H, s), 2.67(3H, s), 
2.61(4H, br), 1.27(1H, m), 1.19(6H, d, J=6.3Hz) 
FABMS (m/z); 712, 710(M+H).sup.+ 
IR (KBr) .nu.(cm.sup.-1); 1701, 1646, 1602, 1561, 1514, 1409, 1305, 1249, 
1219, 1189, 1093 
EXAMPLE 11 
Synthesis of Compound 11 
In a mixture of 1 ml of ethanol and 1 ml of methanol was dissolved 18 mg 
(0.025 mmol) of Compound 10 obtained in Example 10, and 0.006 ml of 6.86 N 
hydrogen chloride-ethanol was added to the solution, followed by stirring 
at room temperature for three hours. The reaction mixture was concentrated 
under reduced pressure to give 18 mg (yield 96%) of Compound 11. 
The physicochemical properties of Compound 11 are as follows. 
.sup.1 H-NMR (270MHz, DMSO-d.sub.6) .delta.(ppm); 12.21(1H, s), 10.39 (1H, 
br), 8.60(1H, br s), 8.09(1H, s), 7.75(2H, d, J=8.4Hz), 7.57(1H, d, 
J=14.3Hz), 7.06(1H, d, J=14.3Hz), 6.99(1H, d, J=8.4Hz), 4.41(3H, m), 
4.12(1H, m), 3.91(4H, m), 3.84(3H, s), 3.81(3H, s), 3.77(1H, m), 3.69(6H, 
m), 2.68(3H, s), 1.22 (1H, m), 1.11(6H, d, J=6.4Hz) 
IR (KBr) .nu.(cm.sup.-1); 1678, 1643, 1599, 1515, 1409, 1251, 1212, 1095, 
1032 
EXAMPLE 12 
Synthesis of Compound 12 
In 1.5 ml of acetonitrile was dissolved 25 mg (0.06 mmol) of Compound 2 
obtained in Example 2, and 1.5 ml of 48% hydrobromic acid was added to the 
solution. The mixture was stirred at room temperature for one hour. To the 
reaction mixture was added 1N hydrobromic acid, followed by extraction 
with chloroform. The chloroform layer was dried over anhydrous sodium 
sulfate, and then concentrated under reduced pressure. The resulting crude 
product was dissolved in 2 ml of dichloromethane. To the solution were 
added 0.033 ml (0.30 mmol) of phenyl isocyanate and 0.042 ml (0.30 mmol) 
of triethylamine at 0.degree. C., and the mixture was subjected to 
reaction at 0.degree. C. for three hours. Then, 0.2 M acetate buffer of pH 
4 was added to the reaction mixture, followed by extraction with 
chloroform. The chloroform layer was washed with a saturated aqueous 
solution of sodium chloride, dried over anhydrous sodium sulfate, and then 
concentrated under reduced pressure. The resulting crude product was 
purified by silica gel column chromatography (20 ml of silica gel, 
chloroform : methanol =30 : 1) to give 18 mg (yield 48%) of Compound 12. 
The physicochemical properties of Compound 12 are as follows. 
.sup.1 H-NMR (270MHz, CDCl.sub.3) .delta.(ppm); 9.69(1H, s), 8.35(1H, s), 
7.78(1H, d, J=15.5Hz), 7.71(1H, br s), 7.53 (2H, d, J=8.9Hz), 
7.29-6.99(5H, m), 6.91(2H, d, J=8.8Hz), 6.75(1H, d, J=15.6Hz), 4.44(1H, 
m), 4.35(1H, br d, J=11.2Hz), 4.14(1H, dd, J=10.2, 8.9Hz), 3.91(3H, s), 
3.85(3H, s), 3.69(1H, br d, J=10.2Hz), 3.09(1H, dd, J=9.8, 9.8Hz), 
2.52(3H, s) 
FABMS (m/z); 620, 618(M+H).sup.+ 
IR (KBr) .nu.[cm.sup.-1); 1733, 1699, 1642, 1603, 1514, 1444, 1412, 1305, 
1253, 1204, 1092 
EXAMPLE 13 
Synthesis of Compound 13 
In 0.1 ml of N,N-dimethylformamide was dissolved 3 mg (0.075 mmol) of 60% 
sodium hydride, and 0.3 ml of N,Ndimethylformamide containing 16 mg (0.062 
mmol) of Compound 1 obtained in Example 1 was added to the solution. The 
mixture was stirred at -20.degree. C. for three hours in an argon 
atmosphere. To the reaction mixture was added 0.5 ml of 
N,N-dimethylformamide containing 25 mg (0.076 mmol) of 4-nitrophenyl 
4-propyloxycinnamate, followed by stirring at -20.degree. C. to 0.degree. 
C. for one hour. After 0.2M phosphate buffer of pH 7 was added to the 
reaction mixture, extraction was carried out with ethyl acetate. The ethyl 
acetate layer was washed with a saturated aqueous solution of sodium 
chloride, dried over anhydrous sodium sulfate, and then concentrated under 
reduced pressure. The resulting crude product was purified by silica gel 
column chromatography (20 ml of silica gel, chloroform : methanol =100 : 
1) to give 22 mg (yield 80%) of Compound 13. 
The physicochemical properties of Compound 13 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 10.01(1H, br), 7.77 (1H, d, 
J=15.4Hz), 7.32-6.93(4H, m), 6.84(1H, d, J=15.7Hz), 6.67(1H, br), 4.24(1H, 
dd, J=11.0,l 11.0Hz), 4.15(1H, dd, J=11.0, 4.7Hz), 3.94(2H, t, J=6.3Hz), 
3.82(3H, s), 3.55(1H, m), 2.59(3H, s), 2.39(1H, dd, J=7.5, 3.2Hz), 
1.82(2H, m), 1.31 (1H, dd, J=4.9, 3.7Hz), 1.05(3H, t, J=7.4Hz) 
SIMS (m/z); 447(M+H).sup.+, 259 
IR (KBr) .nu.(cm.sup.-1); 1697, 1654, 1596, 1437, 1388, 1292, 1246, 1213, 
1110 
EXAMPLE 14 
Synthesis of Compound 14 
In 0.1 ml of N,N-dimethylformamide was dissolved 3 mg (0.075 mmol) of 60% 
sodium hydride, and 0.3 ml of N,N-dimethylformamide containing 16 mg 
(0.062 mmol) of Compound 1 obtained in Example 1 was added to the 
solution. The mixture was stirred at -20.degree. C. for three hours in an 
argon atmosphere. To the reaction mixture was added 0.5 ml of 
N,N-dimethylformamide containing 25 mg (0.077 mmol) of 4-nitrophenyl 
4-propenyloxycinnamate, followed by stirring at -20.degree. C. to 
0.degree. C. for one hour. After 0.2M phosphate buffer of pH 7 was added 
to the reaction mixture, extraction was carried out with ethyl acetate. 
The ethyl acetate layer was washed with a saturated aqueous solution of 
sodium chloride, dried over anhydrous sodium sulfate, and then 
concentrated under reduced pressure. The resulting crude product was 
purified by silica gel column chromatography (20 ml of silica gel, 
chloroform : methanol =100 : 1) to give 24 mg (yield 87%) of Compound 14. 
The physicochemical properties of Compound 14 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 10.51(1H, br), 7.77 (1H, d, 
J=15.6Hz), 7.33-6.95(4H, m), 6.84(1H, d, J=15.6Hz), 6.77(1H, br), 6.07(1H, 
m), 5.43(1H, dd, J=17.4, 1.8Hz), 5.31(1H, dd, J=10.5, 1.2Hz), 4.57(2H, dt, 
J=5.1, 1.5Hz), 4.25(1H, dd, J=10.9, 10.9Hz), 4.15(1H, dd, J=11.0, 4.6Hz), 
3.82(3H, s), 3.57(1H, m), 2.60(3H, s), 2.40(1H, dd, J=7.6, 3.5Hz), 
1.32(1H, dd, J=4.7, 3.7Hz) 
SIMS (m/z); 445(M+H).sup.+, 259 
IR (KBr) .nu.(cm.sup.-1); 1701, 1603, 1486, 1445, 1388, 1292, 1246, 1215, 
1109 
EXAMPLE 15 
Synthesis of Compound 15 
In 0.1 ml of N,N-dimethylformamide was dissolved 3 mg (0.075 mmol) of 60% 
sodium hydride, and 0.3 ml of N,N-dimethylformamide containing 16 mg 
(0.062 mmol) of Compound 1 obtained in Example 1 was added to the 
solution. The mixture was stirred at -20.degree. C. for three hours in an 
argon atmosphere. To the reaction mixture was added 0.5 ml of 
N,N-dimethylformamide containing 27 mg (0.076 mmol) of 4-nitrophenyl 
4-pentyloxycinnamate, followed by stirring at -20.degree. C. to 0.degree. 
C. for one hour. After 0.2M phosphate buffer of pH 7 was added to the 
reaction mixture, extraction was carried out with ethyl acetate. The ethyl 
acetate layer was washed with a saturated aqueous solution of sodium 
chloride, dried over anhydrous sodium sulfate, and then concentrated under 
reduced pressure. The resulting crude product was purified by silica gel 
column chromatography (20 ml of silica gel, chloroform : methanol =100 : 
1) to give 24 mg (yield 82%) of Compound 15. The physicochemical 
properties of Compound 15 are as follows. 
.sup.1 H-NMR (400MHz, CDCl.sub.3) .delta.(ppm); 10.34(1H, br), 7.78 (1H, d, 
J=15.4Hz), 7.52-6.93(4H, m), 6.85(1H, d, J=15.4Hz), 6.67(1H, br), 4.24(1H, 
dd, J=11.0, 1.0Hz), 4.15(1H, dd, J=11.0, 4.6Hz), 3.99(2H, t, J=6.6Hz), 
3.82(3H, s), 3.55(1H, m), 2.61(3H, s), 2.39(1H, dd, J=7.6, 3.4Hz), 
1.81(2H, m), 1.44(4H, m), 1.31(1H, dd, J=4.9, 3.7Hz), 0.94(3H, t, J=7.0Hz) 
SIMS (m/z); 475(M+H).sup.+, 259 
IR (KBr) .nu.(cm.sup.-1); 1701, 1628, 1599, 1457, 1389, 1255, 216, 1109