TROPOLONE DERIVATIVES AND PHARMACEUTICAL COMPOSITION THEREOF FOR PREVENTING AND TREATING ISCHEMIC DISEASES

Abstract: The present invention provides novel tropolone derivatives of formula (I), wherein R10 is a substituted or unsubstituted piperazinyl or benzothiazolidinyl group, and pharmaceutical compositions thereof. These compounds are useful for the prevention and treatment of ischemic diseases, including cerebrovascular diseases and cardiovascular diseases.

Description: TROPOLONE DERIVATIVES AND PHARMACEUTICAL COMPOSITION THEREOF FOR PREVENTING AND TREATING ISCHEMIC DISEASES Field of the Invention The present invention relates to novel compounds and novel pharmaceutical compositions containing them for preventing or treating ischemic diseases. Particularly, the present invention provides tropolone derivatives or a pharmaceutically acceptable esters or salts thereof and compositions containing them as an active ingredient. More particularly, it relates to a preventive or a remedy for cerebrovascular diseases such as cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attacks (TIA), trauma, the sequelae associated with brain surgery, or cardiovascular diseases such as variant angina pectoris, unstable angina, myocardial infarction, arrhythmia caused upon re lowing of coronary blood stream after procedures such as Percutaneous Transluminal Coronary Angioplasty/Percutaneous Transluminal Coronary Recanalization/Coronary Artery Bypass Grafting (PTCA PTCR/CABG) and the like. Background of the Invention Cellular disorders due to ischemia mainly comprise two disorder stages, that is, (1) a stage which proceeds under anoxic/hypoxic conditions and (2) a process of injury by active oxygen inevitably generated in the course of ischemia/reperfusion [see Nishida et al., Metabolism, vol. 24, 379 (1987)]. The typical ischemic diseases include, for example, cerebrovascular diseases such as cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attacks (TIA), trauma, the sequelae associated with brain surgery, or cardiovascular diseases such as variant angina pectoris, unstable angina, myocardial infarction, arrhythmia caused upon reflowing of coronary blood stream by PTCA/PTCR/CABG and the like. Further, disorders of transplanted organs upon organ transplantation, disorders of organs caused by decreased bloodflow after shock, temporary devascularization of an organ during a surgical operation and the like. These diseases are difficult to be explained with a single mechanism, and it is considered to be caused by complicatedly related factors. In clinical practice, various medicines are selected for the particular causes and conditions. For example, as a preventive and a remedy for cerebrovascular diseases, Glyceol, Ozagrel, Nizofenone, Ticlopidine, AVS and the like are used and studied for the acute stage from the viewpoint of prevention of brain edema and cerebrovascular contraction. On the other hand, in the chronic stage, cerebral circulation improvers such a nicardipine, cinnarizine, flunarizine, dilazep; cerebrai circulation metabolism improvers such as vinpocetine, Nicergoline, pentoxifylline, and ifenprodil; and cerebral metabolism improvers such as Idebenone, GABA, and calcium hopatenate have been used. For variant angina pectoris and unstable angina, vasodilators such as nitro compound, and calcium (Ca) antagonists have been used. For myocardial infarction, cardiac disorder upon reflowing of coronary blood by PTCA/PTCR/CABG and the like, 5- lipoxygenase inhibitors and radical scavengers have been investigated, but, no medicines with a clinically satisfactory result have been found. Problems to be Solved bv the Invention The present inventors have thought that such ischemic diseases are caused by disorder of cell membrane or tissue by active oxygen and excessive and sudden flow of extracellular calcium ion into the cell, said two causes being closely related to each other. That is, when a disorder of cell membrane is caused by active oxygen, extracellular calcium flows into the cell. Accordingly, an amplification reaction may proceed, wherein protease in the cell is activated, resulting in deactivation of function as a cell, or phospholipase is activated to decompose the ingredients of the cell membrane, resulting in further inflow of calcium. Arachidonic acid separated out from ingredients of a cell membrane by activation of phospholipase may be metabolized and converted into a material which derives phagocytes (e.g., leukotrienes) or a material which coagulates blood plates to produce thrombus (e.g., thromboxane A 2 ). Further, it produces active oxygen again in this conversion step. Accordingly, the diseases may become worse. From such a point of view, the present inventors have studied intensively medicines which are effective for prevention and cure of ischemic diseases. As the result, we have found that a certain kind of novel tropolone derivative is effective. Thus, we have attained the present invention. Means to Solve the Problems The present invention particularly provides: (1.) A tropolone derivative of the formula: wherein R 10 is a moiety of the formula II or III wherein R j and R 2 are die same or different and are: (a) hydrogen, (b) C r C 5 alkyl, (c) substituted or non-substituted aryl, or (d) a substituted or non-substituted heterocyclic group; wherein R 3 and R 4 are the same or different and are: (a) hydrogen, (b) C--C 5 alkyl, (c) C r C 5 alkyl substituted by -OH, -COOR 5 , or -CN, (d) C 7 -C 20 arylalkyl, (e) C 7 -C 20 arylalkyl containing O, S or N as heteroatoms, (f) halogen, (g) -OH, (h) C r C 5 alkoxy, (i) -CN, 0) -CO 2 R 5 , or (k) -NO 2 ; wherein R 41 is (a) -OR 3 , (b) -ORe, (c) -NR 7 R 8 , (d) -N^MCH^-R,--, or (e) a group represented by the formula IV wherein R 5 is (a) hydrogen, or (b) C r C 5 alkyl; wherein Rg is (a) hydrogen, (b) C r C 5 alkyl, (c) C r C 5 alkyl substituted by OH, COOR 5 , or CN, (d) C 7 -C 20 aralkyl, or (e) C 7 -C 20 aralkyi substituted by O, S or N; wherein R 7 and Rg are the same or different and are: (a) hydrogen, (b) C r C 5 alkyl, (c) C r C 5 alkyl substituted by -OH, -COOR 5 , or -CN, or containing O, S, or N as heteroatoms, (d) C 7 -C 20 aralkyl, (e) C 7 -C 20 aralkyl containing O, S or N as heteroatoms, or (f) R 7 and Rg together form a 5 to 7 membered ring may contain 1-3 of the following ring substituents; (0 -CH 2 -, (ii) -O-, or (iii) -NR9-; wherein Rg is (a) hydrogen, (b) C r C 5 alkyl, or (c) C 7 -C 20 aralkyl, or (d) C 7 -C 20 aralkyl containing O, S or N as heteroatoms; wherein R^ is (a) hydrogen, (b) C r C 3 alkyl, (c) substituted or unsubstituted aryl, or (d) substituted or unsbustituted heterocycle; wherein R 21 and R 31 are the same or different and are (a) hydrogen, or (b) C r C 3 alkyl; wherein g i is (a) substituted or unsubstituted aryl, (b) substituted or unsubstituted heterocycle, (c) -OR 71 , (d) -CO 2 R 81 , or (e) -NRr RiOi; wherein R 51 , R 71 , and R gl are the same or different and are (a) hydrogen, or (b) C r C 3 alkyl; wherein R<- j and R 10 ι are the same or different and are (a) hydrogen, (b) C r C 3 alkyl, (c) a substituted or unsubstituted aryl group, or (d) a substituted or unsubstituted heterocycle; wherein 2Q I is (a) hydrogen, (b) C r C 5 alkyl, (c) C 2 -C 20 aralkyl, (d) C 6 -CJO arylsulfonyl, or (e) C 6 -C 10 arylsulfonyl containing O, S, or N as additional heteroatoms; wherein Ar j and Ar 2 are the same or different aryl group optionally substituted by (a) halogen, (b) trihalomethyl, (c) C 6 -C 10 aryl, or (d) Cg-C 10 aryl substituted by C j -C 3 alkoxy; wherein X is (a) -O-, (b) -CH 2 -, or (c) -N-(CH 2 ) p -R π ; wherein m is 1, 2, 3, or 4; wherein n is 0, 1, or 2; wherein p is 0, 1, or 2; and wherein q is 1 or 2; or a pharmaceutically acceptable ester or salt thereof; (2.) A tropolone derivative as described in (1) wherein R 41 is OR 3 (wherein R 3 is definitions (a) to (e)), R 10 is a moiety of the Formula II, R 21 and R 31 are hydrogen and q is 1, represented by die formula: or a pharmaceutically acceptable ester or salt thereof; (3.) A tropolone derivative as described in (1), wherein < 4l is -ORg or -NR 7 R 8 , R 10 * s a moiety of Formula III, R j is definitions (a) to (c), R 3 and R 4 are definitions (a), (b), and (f) to (k), represented by the formula: or a pharmaceutically acceptable ester or salt thereof; (4.) A tropolone derivative as described in (1), wherein R 1 is -N ( 5i)-(CH2) m -Rgι or a group of the Formula IV; R 10 is a group of the Formula II, represented by d e formula: or a pharmaceutically acceptable ester or salt thereof; and (5.) A pharmaceutical composition for preventing or treating ischemic diseases which is characterized by containing a tropolone derivative described above or a pharmaceutically acceptable ester or salt thereof as an active ingredient. The carbon atom content of the various hydrocarbon containing moieties is indicated by, e.g., "C j -C j ," wherein i is die minimum number of carbon atoms and j is the maximum number of carbon atoms. In the compound of the present invention represented by die general formula [I], a lower alkyl group represented by R 1 and R 2 includes, for example, C^ alkyl group such as ediyl, ediyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isoamyl. An aryl group includes, for example, Cg.jQ -t-T- which may contain 1 to 7 substitutents selected from a group consisting of the aforementioned lower alkyl group, halogen, nitro, cyano, lower alkoxy group. Such halogen includes chloro, fluoro, bromo and iodo; and lower alkoxy group includes a C j ,5 alkoxy group. The example of these aryl groups includes, for example, phenyl, p-chlorophenyl, m-chlorophenyl, o-chlorophenyl, o,m-dichloropheπyl, p-fluorophenyl, p-trifluorσphenyl, p-nitrophenyl, m- nitrophenyl, o-nitrophenyl, p-cyanophenyl, m-cyanophenyl, o-cyanophenyl, p-methoxyphenyl, m- medioxyphenyl, o-methoxyphenyl, m,p-dimethoxyphenyl. A heterocyclic group includes a 5-10 membered heterocyclic group containing at least one hetero atom. These may be substituted widi substitutents similar to those in the above aryl group. Examples of such heterocyclic group includes 2-pyridyl, 3-pyridyl, and 4-pyridyl. A lower alkyl group represented by R which may be substituted by hetero atoms includes C j ^ Q alkyl group substituted by a ino, mono- or di-substituted amino group substituted by substituted or non-substituted aralkyl, lower alkyl group or substituted/non-substituted aralkyl group, or hydroxyl group. A lower alkyl group as a substitutent includes C j . 5 alkyl, and an aralkyl group includes C 7 _ 2u aralkyl group which may be substituted by die substitutent similar to those in the above aryl group. The example of such lower alkyl group which may be substituted by hetero atom includes, for example, mediyl, ethyl, n-propyl, n-butyl, 2-[N,N- dimethylaminojethyl, 3-[N,N-dimethylamino]propyl, 2-[N-methyl-N-phenethyIamino]ethyl, 3-[N-methyl-N-phenethylamino]propyl,2-[N-methyl-N-2,3-dimedιoxyphenethylamino]edιyl,3-[N- medιyl-N-2,3-dimethoxyphenethylamino]propyl, 2-hydroxyethyl, 3-amino-2-hydroxypropyl, 3- dimedιylamino-2-hydroxypropyl, 3-diisopropylamino-2-hydroxypropyl. An aralkyl group includes C 7 _2o aralkyl group which may be substituted by a substitutent similar to those in the above aryl group, (e.g., containing O, S, or N as heteroatoms) for example, benzyl, phenethyl, 3,4- dimethoxyphenethyl, 2,3,4-trimethoxyphenethyl. Aryl groups represented by Ar 1 and Ar 2 include those similar to the aryl groups represented by R 1 and R 2 , for example, phenyl, p-chlorphenyl, m-chlorphenyl, o-chlorphenyl, o,m-dichlorphenyl, o,p-dichlorphenyl, m,p-dichlorphenyI, p-fluorophenyl, m-fluorophenyl, o- fluorophenyl, p-trifluorophenyl, m-trifluorophenyl, o-trifluorophenyl, p-medioxyphenyl, m- methoxyphenyl, o-methoxyphenyl. An arylsulfonyl group in which a constituent may be substituted by a heteroatom includes C 6 -C 10 arylsulfonyl containing at least one heteroatom selected from the group consisting of N, S and O. These may be subjected to nuclear substitution by substituents similar to those in die above aromatic group. Examples thereof include, for example, phenylsulfonyl, naphthylsulfonyl, quinolylsulfonyl, and isoquinolylsulfonyl. A pharmaceutically acceptable salt of the tropolone derivative of the present invention represented by d e general formula [I] includes a salt widi a mineral acid such as hydrochloric acid, sulfuric acid; a salt widi an organic sulfonic acid such as methanesulfonic acid, p-toluenesulfonic acid; a salt widi an organic carboxylic acid such as acetic acid, propionic acid, succinic acid, lactic acid, tartaric acid, malic acid, citric acid and die like. An ester thereof includes. an ester widi an organic carboxylic acid such as acetic acid, propionic acid, oxalic acid and die like. The embodiments of die compound of die present invention represented by die general formula [IA] are shown below: 1A) 7-[4-(4-chloroberιzhydryl)piperazii-C-l-meώyl]-2-hydroxy-4-isopropyl-2,4,6-cyclohφtatrien- 1-one; 2A) 7-[4-(4-chlorober___hyd_yl)piperazino-l-mediyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien- 1-one; 3A) 7-{ l-[4-(4-chlorobenzhydryl)piperazinomethyl]-c--phenyl}-4-isopropyl-2-methoxy-2,4,6- cy cloheptatrien- 1 -one; 4A) 7-{l-[4-(4-chlorobenzhydryl)]piperazinomethyl-o.-methyl}-4-isopropyl-2-methoxy-2,4,6- cy cloheptatrien- 1 -one; 5A) 7-{l-[4-(4-chlorobenzhydryl)]piperazinomethyl]-a-butyl}-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one; 6A) 7-(4-benzhydrylpiperazino-l-methyl)-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one; 7A) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one; 8A) 7-{4-[4,4 i(trifluoromeΛyl)ben__hydιyl]pirj€razino-l-medιyl}^-isopropyl-2-me-hoxy-2,4,6- cycloheptatrien-1-one; 9A) 4-isopropyl-2-methoxy-7-[4-(4-trifluoromethylbenzhydryl)piperazino-l-methyl]-2,4,6- cy cloheptatrien- 1 -one; 10A) 7-[4-(4-chloro-4'-methoxybenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one; 11 A) 7-[4-(4-fluoro-3',4'-dimethoxybenzhydryl)piperazino-l-methyl]-4-isopropyl-2-medioxy- 2,4,6-cycloheptatrien-l-one; 12A) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-ethoxy-4-isopropyl-2,4,6- cy cloheptatrien- 1 -one; 13A) 2-butoxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2,4,6- cycloheptatrien-1-one; 14A) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-phenoxy-2,4,6- cycloheptatrien-1-one; 15A) 2-benzyloxy-7-[4-(4,4'-difluorobenzhydryI)piperazino-l-methyl]-4-isopropyl-2,4,6- cy cloheptatrien- 1 -one; 16A) 7-[4-(4,4'-difluorobenzhydryl)piperazino- 1 -methy_]-2-[2-(3 ,4-dimethoxyphenyl)ethoxy]-4- isopropyl-2,4,6-cycloheptatrien-l-one; 17A) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-[3-(dimethylamino)propoxy]-4- isopropyl-2,4,6-cycloheptatrien-l-one; . 18A) 7-[4-(4,4 , -difluorobenzhydryl)piperazino- l -methyl]-2-[3-(N-methyl-N- phenethyiamino)propoxy]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 19A) 7-[4-(4-chloroben__hydryl)piperazino-l-methyl]-2-methoxy-2,4,6-cycloheptatrien-l-one; and 20A) 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-2-methoxy-4-phenyl-2,4,6-cycloheptatrien-l- one. The tropolone derivative of die present invention represented by die general formula (IA) can be produced, for example, according to die following reaction scheme. -10- Reaction Scheme A (wherein R-, R 2 , R 3 , Ar- and Ar 2 are as defined above, halo is a halogen atom such as chloro, bromo, iodo). That is, tropolone represented by the general formula [All] is subjected to an aminomethylation reaction with formaldehyde and a piperazine derivative to synthesize tropolone derivative [Ala]. This reaction is carried out in the presence or absence of inert solvent, for example, acetone, dimethylsulfoxide, dimethylformaldehyde, alcohols such as methanol, eth nol, ethers such as tetrahydrofuran. a solvent containing halogen such as dichloromethane, chloroform,' using formaldehyde and a piperazine derivative (1-3 equivalent of the compound [All], each) and acetic acid (0.5-3 equivalent) by heating at room temperature to 100°C. A particularly preferable process is a process wherein formaldehyde and a piperazine derivative (e.g., 1-1.2 equivalent of the compound [All]) and acetic acid are heated at room temperature to 65°C. As for the alkylation reaction of tropolone derivative [Ala], the methods which are generally employed for the alkylation reaction of phenois can be employed. For example, as an aikylating agent, alkyl halide or aryl halide such as methyl iodide, benzyl chloride and sulfate esters such as dimethyl sulfate may be used, and as a base, sodium hydride, amine such as triethylamine, an alkali such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium bicarbonate or the like may be used. The above aikylating agent (1-3 equivalent of the compound [Ala]) and die base (catalytic amount to 5 eq.) are used, which are heated with die compound [Ala] in the aforementioned inert solvent at 0-100°C to give tropolone derivative [Alb]. On die odier hand, tropolone [All] is allowed to react widi formaldehyde according to a method disclosed in the literature [Proc. Japan Acad.,27, 561 (1951)] to give the compound [AIII] wherein a hydroxymethyl group is introduced into the position 7, then converted to die compound [AIV] by the aforementioned alkylation. The compound [AIV] may be halogenated widi amine such as pyridine or triediylamine and medianesulfonyl chloride (1-3 eq.) in die presence or absence of an inert solvent, for example, acetone, dimediylsulfoxide, dimethylformaldehyde, ether such as tetrahydrofuran, a solvent containing halogen such as dichloromethane, chloroform at 0-100°C to give the tropolone derivative [AV]. Conversion of the tropolone derivative [AV] to die tropolone derivative [Alb] can be readily conducted by heating at room temperature to 100°C with piperazine compound (1-3 eq.) and amine such as pyridine, triethylamine, or alkali such as sodium carbonate, sodium bicarbonate in die presence or absence of an inert solvent, for example, acetone, dimediylsulfoxide, demediylformaldehyde, alcohols such as methanol, ethanol, ether such as tetrahydrofuran, a solvent containing halogen such as dichloromediane, chloroform. The compound [Ale] which is tropolone derivative [AI] having substitutent R 2 can be synthesized as follows: The compound [AIV] is oxidized using manganese dioxide (5-20 equivalent of the compound [AIV]) in a halogenated hydrocarbon solvent such as mediylene chloride, chloroform at 0-50°C, preferably at room temperature to prepare the compound [A Via]. The compound [A Via] is hydrolyzed with an aqueous solution or an alcoholic solution of sodium hydroxide, potassium hydroxide or the like (1-5 eq.) at room temperature according to the conventional method to give the compound [AVIb]. The compound [AVIb] can be converted to die compound [A Vila] wherein a substitutent R 2 is introduced by a reaction widi organic lidiium reagent R 2 -Li such as methyllithium, n-butylliuiium, phenyllithium in a solvent such as tetrahydrofuran in an inert gas atmosphere. The compound [A Vila] can be converted to die compound [AVIIb] according to the same procedure as that of die aforementioned alkylation. Conversion of the compound [AVIIb] to the tropolone derivative [Ale] can be conducted in one-step by heating with 4-substituted piperazine (1-5 equivalent of the compound [AVIIb]) in an aromatic hydrocarbon solvent such as toluene, xylene. Alternatively, it may be prepared by two-step reaction, that is, it is halogenated in the same manner as described above to give the compound [A VIII], then reacted widi 4- substituted piperazine. Thus obtained compound of die present invention represented by the general formula [IA] can be isolated and purified by die conventional mediod such as recrystallization, and chromatography. Additional embodiments of the compounds of the present invention represented by the general formula [IB] are: IB) 2-(2 ' -oxo-3 ' -methoxy-5 ' -isopropyl-3 ' ,5 , ,7 ' -cycloheptatrienyl)-3-(2- phenediylbenzod iazoline; 2B) 2-(2'-oxo-3'-me-hoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-methylbenzothiazoline; 3B) 2-(2 * -oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-benzylbenzothiazoline; 4B) 2-(2'_oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(2-picolyl)benzothiazoline; 5B) 2-(2'-oxo-3 , -me-hoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(3-picolyl)benzothiazoline; 6B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(4-picolyl)benzothiazoline; 7B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3' ,5' ,7'-cycloheptatrienyl)-3-[2-(2- pyridyl)edιyl]ben_-θthiazoline; 8B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3 ' ,5' ,7'-cycloheptatrienyl)-3-[2-(3,4- dimedιoxyphenyl)edιyl]benzothiazoline; 9B) 2-(2 ' -oxo-3 ' -methoxy-5 ' -isopropyl-3 ' ,5 , ,7 , -cycloheptatrienyl)-3-(2- quinolyl)medιylbenzothiazoline; 10B) 2-(2 , -oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-[3-(N-methyl-N- phenethylamino)propyl]benzothiazoline; 11B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3\5' ,7'-cycloheptatrienyl)-3-[2-(N,N- dimedιylamino)ethyl]benzodιiazoline; 12B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3' ,5\7'-cycloheptatrienyl)-3-[3-(N,N- dimedιylamino)propyl]benzothiazoline; 13B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3 , ,5',7'-cycloheptatrienyl)-3-{3-[4-(4',4'- difluorobenzhydryl)piperazin-l-yl)propyl}benzothiazoline; 14B) 2-(2'-oxo-3'-medioxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-methylbenzothia-_oline; 15B) 2-(2'-oxo-3 '-(l-piperadinyl)-5'-isopropyl-3\5' ,7 , -cycloheptatrienyl)-3- phenethylbenzothiazoline; 16B) 2-(2'-oxo-3'-(2-(N,N-dimethyl)aminoethyl)amino-5 , -isopropyl-3',5',7'-cyclohq)tatrienyl)-3- (2-phenethylbenzothiazoline; 17B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7 , -cycloheptatrienyl)-3-(2-phenethyl-l,l- dioxobenzothiazoline; and 18B) 2-(2'-oxo-3'-methoxy-5'-isopropyl-3\5',7'-cycloheptatrienyl)-3-(2-phenethyl-l- oxobenzoth iazol ine . The tropolone derivative of the present invention represented by die general formula [IB] can be produced, for example, according to the following reaction scheme: Reaction Scheme B (wherein R ls R 2υ ι- R3, R4, » R 6> R 7- R 8- n ^ R 41 are ^ define above) That is, a tropolone represented by die general formula [BVI] is allowed to react widi formaldehyde according to die method disclosed in die literature [Proc. Japan Acad.,27, 561 (1951)] to give die compound [BV] wherein a hydroxymethyl group is introduced into the position 7, then converted to the compound [BlVa] by the aforementioned alkylation reaction. As the alkylation reaction, die methods which are generally employed for alkylation reaction of phenols can be employed. For example, die reaction can be conducted in die presence of a base using an aikylating agent corresponding to die objective alkyl group such as mediyl iodide, benzyl chloride, or sulfate derivatives of the objective alkyl group such as dimethyl sulfate. Examples of the base include sodium hydride, amines such as triediylamine, sodium hydroxide, potassium hydroxide, potassium carbonate, sodium bicarbonate or die like. The above aikylating agent (1-3 equivalent amounts of the compound [BV]) is used. The amount of a base varies according to the kind of reagent, for example, sodium hydride (1-1.2 equivalent amounts) and amines and potassium carbonate (2-5 equivalent amounts) are normally used. The reaction solvent may be any inert solvent, preferably ethers such as tetrahydrofuran, solvents containing halogen such as dichlormed ane, chloroform, or polar solvents such as dimediylsulfoxide, dimediylfor amide. The reaction temperature varies according to a kind of a base and aikylating agent and, die range between 0-100°C is normally preferred. The compound [BlVa] can be converted to die compound [BlVb] only by heating in the presence of the objective amine and an aromatic hydrocarbon such as benzene, toluene, xylene, or a solvent containing halogen such as carbon tetrachloride, tetrachlorethylene. The amount of amine to be used may be normally 1 to 2 equivalent amounts, particularly 1.2 to 1.5 equivalent amounts based on die compound [BlVa] and they may be used in an excessive amount. The oxidation reaction of the compounds [BlVa] and [BlVb] can be conducted by using manganese dioxide (5-20 equimolar of the compounds [BlVa] and [BlVb]) at 0-50°C, preferably at room temperature to convert to the compounds [Blla] and [Bllb], respectively. The compounds [BHIa] and [Blllb] are condensed with 2-Aminodιiophenols to give the compounds [Bla] and [Bib], respectively. The condensation reaction can be conducted using a solvent containing halogen such as dichlormediane, chloroform, an aromatic hydrocarbon such as benzene, toluene, xylene, an aromatic hydrocarbon containing nitrogen such as pyridine quinoline and the like, preferably at room temperature to 100°C. 2-aminothiophenols [BII] may be used in an excessive or small amount based on die compound [Bill], but it is preferred diat diey are used in almost the same equivalent as mat of die compound [Bill] in view of die reaction yield and isolation and purification process of the product. Further, die condensation reaction may be conducted using its oxidized dimer, compound [BII'] instead of the compound [BII] under a reduction condition. That is, diose containing an SH group such as the compound [BII] sometimes oxidized by air during storage or during treatment for reaction to convert to the compound [BII']. In that case, the compound [BII'] is retreated widi a reducing agent such as sodium borohydride to return to the compound [BII], or the compounds [Bla] and [Bib] can be synthesized by reacting the compound [Bill] and [BII'] in die presence of trivalent phosphorous compound (1/3 to die same moles of the compound [Bill]) such as triethyl phosphate, triphenyl phosphine, tricyclohexyl phosphine and the like. The compound [Bla] can also be converted to d e compound [Bib] by reacting with various amines in the aforementioned reaction condition. The compound wherein R 2 contains an arylsulfonyl group can be easily synthesized by using die corresponding compound [IB] wherein R 2 is H and reacting it widi the corresponding arylsulfonyl chloride in die presence of an organic amine such as pyridine, triediylamine. The obtained compound of d e present invention represented by die general formula [IB] can be isolated and purified by conventional mediod such as recrystallization, column chromatography. The embodiments of die compound of die present invention represented by die general formula [IC] will be shown below: 1C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 2C) 7-[4-(4,4'-difluorobei-zhydryl)piperazino-l-methyl]-2-(N-3-dimedιylaminopropylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 3C) 7-[4-(4,4' -difluorobenzhydryl)piperazino- l -methyl]-4-isopropyl-2-(N-2- methylaminoethylamino)-2,4,6-cycloheptatrien-l-one; 4C) 2-(N-2-aminoethylamino)-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl- 2,4,6-cycloheptatrien-l-one; 5C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 6C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- ethylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7C) 2-(N-2-diethyaminoethylamino)-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4- isopropyl-2,4,6-cycloheptatrien-l-one; 8C) 2-[N-2-(N * -2-aminoethylamino)ethylamino]-7-[4-(4,4'-difluorobenzhydryl)piperazino-l- methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 9C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2- pyridylamino)ethylamino]-2,4,6-cycloheptatrien-l-one; 10C) 7-[4-(4,4'-difluorobenzhydryl)piperazino- l -methyl] -4-isopropyl-2-[N-2-(2- pyrimidylamino)edιylamino]-2,4,6-cycloheptatrien-l-one; 11C) 7-[4-(4,4'-difluorobenzhydryl)piperazino- l -methyl] -4-isopropyl-2-[(N-2-(2- pyridyl)edιylamino]-2,4,6-cycloheptatrien-l-one; 12C) 7-[4-(4,4'-difluorobenzhydryl)piperazino- l -methyl]-4-isopropyl-2-(N-2- pyridylmedιylamino)edιylamino)-2,4,6-cycloheptatrien-l-one; 13C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-2-(N-2-hydroxyethylamino)-4-isopropyl- 2,4,6-cycloheptatrien-l-one; 14C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]^Φ-isopropyl-2-(N-2-medιoxyedιylamino)- 2,4,6-cycloheptatrien-l-one; 15C) mediyl 2-{N-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-l-oxo-2,4,6- cycloheptatrien-2-ylamino}acetate; 16C) ethyl 3-{N-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-4-isopropyl-l-oxo-2,4,6- cycloheptatrien-2-ylamino}propionate; 17C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-piperidino-2,4,6- cycloheptatrien-1- ne; 18C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-4-isopropyl-2-mo holino-2,4,6- cycloheptatrien-1-one; 19C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(l-piperazino)-2,4,6- cycloheptatrien- i -one; 20C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-[4-(3-ethylamino-2- pyridyl)piperazino]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 21C) 7-[4-(4,4'-difluorobenzhydryl)-2,6-dimediylpiperazino-l-methyl]-4-isopropyl-2-methoxy- 2 ,4,6-cy cloheptatrien- 1 -one; 22C) 7-[4-(4,4'-difluorobenzhydryl)-2-me-hylpiperazino-l-methyl]-4-isopropyl-2-medioxy-2,4,6- cy cloheptatrien- 1 -one; 23C) 7-[4-(4,4'-difluorobenzhydryl)hexahydro-lH-l,4-diazepin-l-ylmethyl]-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one; 24C) 7-[4-(4,4'-difluorobenzhydryl)-2,6-dimethylpiperazino-l-methyl]-2-(N-2- dimedιylaminoethyl-N-medιylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 25C) 7-[4-(4,4'-difluorobenzhydi7l)-2-memylpiDer-E_no-l-methyl]-2-(N-2-dimeώyl__miι_oethyl-N- methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 26C) 7-[4-(4,4'-difluorobenzhydryl)hexahydro-lH-l,4-diazepin-l-ylmethyl]-2-(N-2- dimediylaminoediyl-N-mediylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 27C) 7-[4-(4-chlorobenzhydryl)piperaziικ)-l-memyl]-2-(N-2-dimedιylaminoethyl-N-methylam_no)- 4-isopropyl-2,4,6-cycloheptatrien-l-one; 28C) 7-(4-benzhydrylpiperazino-l-methyl)-2-(N-2-dimethylaminoethyl-N-methylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 29C) 2 -(N -2 -dim ethyl amino ethyl -N-m ethyl amino)-4-i sop ropy 1 -7 - [4-(4- trifluoromethylbeιιzhydryl)piperazino-l-methyl]-2,4,6-cycloheptatrien-l-one; 30C) 7-[4-(4-chloro-4'-methoxybenzhydryl)piperazino-l-methyl]-2-(N-2-dimedιylaminoedιyl-N- methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 31C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- methylamino)-2,4,6-cycloheptatrien-l-one; and 32C) 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethyIaminoethyl-N- methylamino)-4-phenyl-2,4,6-cycloheptatrien-l-one. The tropolone derivative of die present invention represented by die general formula [Tj can be produced, for example, according to die following reaction scheme: Reaction Scheme C [C III] [C I] (wherein R j , R 2 , R 3 , R 4 , Ar 1 ? Ar 2 , are as defined above, and Hal is a halogen atom such as chloro, bromo, iodo) That is, the compound [CII] is heated widi a piperazine compound (1-3 mole equivalent) and amines such as pyridine, triediylamine or alkalis such as sodium hydroxide, cesium carbonate, sodium bicarbonate in die presence or absence of inert solvent, for example, hexamethylphospholictriamide, dimediylsulfoxide, dimediylformamide, acetone, benzene, alcohols such as methanol, ethanol, ethers such as ethyl ether, tetrahydrofuran, a solvent containing halogen such as dichloromediane, chloroform, at room temperature to 100°C to obtain the compound [CIII]. The conversion of die compound [CIII] into [CI] can easily be conducted in die presence or absence of the aforementioned inert solvent except for alcohols by heating widi an amine compound (1-10 equivalent amounts of the compound [CII]) at room temperature to solvent refluxing temperature. If the amine used for the reaction with [CIII] is the salt form such as hydrochloride, the co-use of amines such as pyridine, thriediylamine, diisopropyl amine will be recommended. The compound can also be produced, for example, according to die processes described above for compounds of die formula IA. The pharmacological utility of the compounds of the present application is seen by the following tests (both in vitro and in vivo) using die compounds of die present invention and a control agent, and die results are shown. 1. in vitro Anti-lipid peroxidation effect Protocol A Brain microsomal fractions were prepared from male rats of SD strain, and a portion (0.2 mg protein) was incubated at 37°C for 15 minutes with a mixture of Fe 3 + (0.1 mM) - ADP (0.5 mM) in the presence or absence of die test compound, in final volume of 1 ml of 10 mM HEPES, 150 mM KCl, 0.2 mM NADPH, pH 7.4. After incubation, 1.5 ml of TCA-TBA-HCl reagent (16.7% trichloroacetic acid, 0.4% thiobarbituric acid, 0.278 N hydrochloric acid) was added and d e reaction mixture was heated in a boiling water for 15 minutes. After cooling in ice-bath, die reaction mixture was centrifuged, and die absorbance of the supernatant at 535 nm was measured. The amount of thiobarbituric acid reactive substance (TBAR) was obtained by calculation using an extinction coefficient of 1.56 x 10 5 M "5 cm "1 . The test compound was allowed to react at die concentration of 10 μM and 50 μM, and die inhibition ratio of TBAR production at each concentration showed die antiperoxidation activity of die drug. The results are shown in Table 1A for compounds of die formulas IA, IB, and IC, respectively. The compounds widi highest inhibition rate have the greatest anti-lipid peroxidation effect. Table 1A Anti-Lipid Peroxidation Effect Compound Anti-Lipid Peroxidation (% inhibition) No. 10 μM 50 μM 1A 6.7 < 21.3 2A 28.8 84.7 3A 13.8 16.3 4A 25.8 75.1 5A 30.5 38.7 6A 15.9 63.2 7A 27.2 59.2 8A 32.3 51.8 9A 29.2 88.1 10A 24.0 81.6 12A 21.4 50.4 13A 23.1 27.4 15A 22.4 29.0 16A 19.1 19.1 18A 37.0 93.1 Table IB Anti-Lipid Peroxidation Effect Table 1C Anti-Lipid Peroxidation Effect Compound Anti-Lipid Peroxidation ( " % inhibition) No. 10 μM 50 μM 1C 59.4 95.3 2C 29.6 90.8 3C 88.0 91.6 4C 45.2 92.9 5C 32.2 90.6 6C 35.9 91.5 7C 21.3 90.4 8C 33.1 92.2 9C 88.1 91.6 10C 46.3 92.5 11C 32.2 89.8 12C 86.4 89.3 13C 36.9 89.5 14C 27.0 90.4 15C 38.6 79.8 16C 29.1 58.0 17C 32.4 44.1 18C 26.7 41.2 19C 30.1 89.1 20C 91.6 93.8 21C 47.8 89.9 22C 32.8 88.7 23C 21.6 90.7 2. in vitro Ca-antagonism A strip of pig right coronary artery was depolarized widi high K + (75 mM) for 30 minutes to induce voltage dependent 45 Ca-influx. The extracellular 5 Ca was chelated by adding EGTA and removed by washing, then the strip was lysed at ICXrC. " "Ca in this lysate was measured as intracellular 5 Ca by a scintillation counter. The concentration of the test compound was 10 "7 , 10 " 6 , 10" 5 M, and applied until depolarization by K + was completed. Ratio of inhibition at various concentrations of the test compounds for increasing die intracellular 45 Ca by K + was determined. The results are shown in Table 2. The compound with high inhibition ratio has strong Ca- antagonism. Table 2A Ca-Antagonism to © O X 3. in vitro Coronary vasodilation effect Protocol C The right portion of a porcine coronary artery was isolated, and cut into 3 mm wide strip which was suspended in a organ badi filled wid 20 ml of Krebs - Henseleit solution (37°C). During the experiment the bath solution was aerated with 95% O2 + 5% Co 2 . The change in tension was measured using an isometric transducer. After load tension was stabilized, die preparation was contracted widi PGF 2α (10 -3 x 1- M). After the contract level had stabilized the test compound was cumulatively applied from 10 " to 10 M. Papaverine (10 M) was used to obtain maximal relaxation at the end of die experiment. The result was expressed as die percentage of papverine-induced relaxation, and die concentration of die test compound which gave 25% relaxation of papaverine-induced relaxation was defined as ED25. If ED25 was less than 10 "5 M, die compound was estimated as "active." The results are shown in Table 3. The compound widi low ED 2 5 value has great coronary vasodilation effect. Table 3 Coronary Vasodilation Compound Coronary Vasodilation No. (ED^μM) 1A > 10 2A 1.8 7A 1.9 4. in vivo Ischemic heart/reperfusion test Protocol D Experiment was carried out using rats anesthetized wid pentobarbital under artificial respiration. After the forth rib was excised, heart was exposed by dioracoto y, and die diread was placed under die left coronary artery at it origin. Then, die heart was returned and a diread was passed in a tube. Compounds were applied d rough tail vein. After 10 minutes, die thread in die tube was pulled to occlude coronary artery. Five minutes after occlusion, die diread was loosened again for reperfusion. Then, ventricular arrhy imia was recorded on electrocardiogram (lead II), by sticking needle electrodes into a right fore-limb and a left hind-limb. Duration time of ventricular tachycardia and occurrence of ventricular fibrillation caused after reperfusion were compared between a group receiving die test compounds and a similarly treated vehicle group. If eidier of two parameters of the group diat received die test compound became less than half of that of die group diat received the vehicle, the test compound was estimated as "active". The results are shown in Table 4. Table 4 Ischemic Heart/Repeifusion Test Compound Minimal Effective Dose No. (mg/kg, i.v.) 2A 0.3# 7A <5 10B <5 11B <5 5. in vivo Behavior test Protocol E Bilateral common carotid arteries of both sides of ICR strain male mice (about 8 weeks old) were occluded for 5 minutes while lightly anesthetized, then blood was reperftiged. The test compounds were intraperitoneally administered 10 minutes before occlusion and within 3 hours after reperfusion. Since a day after reperfusion, behavior disorder was evaluated by spontaneous motor activity of exploratory behavior, traction test and passive avoidance test. That is, spontaneous motor activity was evaluated as follows. Motor activity was measured by tilting cage mediod for 30 minutes since immediately after a mouse was placed in a measurement cage. If die motor activity was at least more than (average of spontaneous motion of the group received solvent) + 2 x SD, die compound was evaluated as "active." In traction test, bodi fore limbs of the mouse were placed on the horizontally stretched wire. If the mouse put its hind limb widiin 2 seconds, the compound was estimated as "active.". In passive avoidance test, a step-through type apparatus was used, and as acquisition trial of blood reperfusion, electrical shock (about 0.5 mA, 3 seconds) was given to the mice as soon as the whole body of mice entered die black room and on d e next day test trial was carried out. The mouse which stayed in a light room for at least 300 seconds was estimated as an active example. In all tests, the test compound which provided at least 50% of active animals was determined as "active." The results are shown in Table 5. 11B i.p. 1.0 12B i.p. 1.0 #: methanesulfonate 6. Normal cerebral flow stream test Protocol D B Experiment was carried out using rats anesthetized widi urethane. After a cannulas for blood pressure monitoring and diat for drug administration were inserted into femoral artery and vein, respectively. Temporal bone was cut away on a brain stereotaxis apparatus and a probe for measurement of cerebral blood flow was placed on dura mater. The cerebral blood flow was measured using a laser Dopplar blood flow meter. Firstly, a solvent of die test compound was administered intravenously and then three doses of the compound were administered in order of dose every fifteen-minute intervals. When an average of increase in cerebral blood flow due to die test compound minus 2xSE was larger than diat of change in cerebral blood flow due to the solvent, die dose was estimated as "active" . The compound (IB) was active in the dose of not less than 3 mg/kg i.v. 7. in vivo Anti-anoxia effect Protocol C C A group (5 mice) of ICR strain male mice (about 8-week-old) were used. One or two hours after the test compounds were orally administered, a ledial dose (3.0 mg/kg) of KCN was administered into tail vein. A period of time to respiratory arrest and a survival rate were measured. The test compound which provided at least 50% of active example was determined as "active". The results are shown in Table 3. Table 3 Anti-anoxia effect Compound Minimal Effective Dose No. (mg/kg, p.o.) 1C 100" *: methanesulfonate As is obvious from die above pharmacological experiments, the compound of the present invention represented by the general formula [I] is useful as a pharmaceutical composition for preventive and treating cerebrovascular diseases such as cerbral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attacks, cerebral injury, sequelae accompanied widi brain surgery, or cardiovascular diseases such as variant angina pectoris, unstable angina, myocardial infarction, arrhythmia caused upon reflowing of coronary blood stream by PTCA/PTCR/CABG and the like. When it is used as such a composition, the compound represented by die general formula [I] can be combined with pharmaceutically acceptable carrier, vehicle, diluent and formulated into an oral or parenteral dosage form such as powder, granulate, tablet, capsule, injection and the like. The dosage varies depending on the administration route, age, weight of the patient, conditions to be treated or the like. For example, when it is orally administered to an adult patient, die dosage may be 10-50 mg, preferably 10-25 mg a day and it can be administered once or divided into several times a day, although greater or lesser amounts may be used, depending on the criteria described above. Widiin die preferred dosage range, the compound of the present invention represented by die general formula [I] never shows any toxicity. Examples The present invention will be further explained in detail in die following examples, but it is not construed to be limited to diem. Example 1 Production of 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-2-hydroxy-4-isopropyl- 2,4,6-cycloheptatrien-l-one Hinokitiol (500 mg, 3.5 mmol), l-(4-chlorobenzhydryl)piperazine (1.05 g, 3.66 mmol) and acetic acid (0.21 ml, 3.65 mmol) were dissolved in medianol (1 ml) and heated to 60°C. 37% Formalin (0.27 ml, 3.60 mmol) was added to this solution widi stirring and the stirring was further continued for 2 hours. The reaction solution was diluted wid dichloromediane, washed widi water, dien dried over sodium sulfate. Solvent was distilled off under reduced pressure to give a crude product, which was crystallized from methanol to give 1.1 g of 7-[4- (4-chloroberi__hyd_yI)piperazino-l-methyl]-2-hydroxy-4-isopropyi-2,4,6-cycIoheptatrien-l-oneas a pale yellow crystal (yield, 78%). Melting point, 69-71°C. MS m/z 462.2067 (462.2074 calculated as C 2 gH 31 ClN 2 O2) *H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=7.0 Hz), 2.43 (m, 4H), 2.57 (m, 4H), 2.88 (qui, IH, J=7.0 Hz), 3.70 (s, 2H), 4.23 (s, IH), 6.95 (dd, IH, J-= 1.4 and 10.3 Hz), 7.1-7.4 (10H), 7.72 (d, IH, J=10.3 Hz). Example 2 Production of 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy- 2,4,6-cycloheptatrien-l-one: Hinokitiol (20 g, 0.12 mol) and potassium hydroxide (8 g, 0.12 mol) were dissolved in water (80 ml), and 37% Formalin (12 ml, 0.16 mmol) was added diereto. The reaction solution was heated at 100°C for 5 hours while stirring. The reaction solution was neutralized widi 6 N HCl, then the reaction product was extracted widi dichloromediane. The extract was dried over sodium sulfate, tiien concentrated under reduced pressure. The residue was dissolved in acetone (200 ml), potassium carbonate (34 g, 0.25 mol) and dimediyl sulfate (16 ml, 0.16 mol) were added diereto, and die solution was heated and refluxed for an hour with stirring. The precipitate was removed by filtration, and filtrate was concentrated under reduced pressure. The filtration residue was washed widi dichloromethane. The resultant was washed widi water and dried over sodium sulfate. The solvent was distilled off under reduced pressure and d e residue was purified by silica gel column chromatography [(eluent: hexane/ethyl acetate (1:4)] to give 18.5 g of 7- hydroxymedιyl-4-isopropyl-2-medιyoxy-2,4,6-cycloheptatrien-l-one as a pale yellow oil (yield, 74%). This oil was solidified when allowed to stand at room temperature. 1H NMR (CDC1 3 ) δ(ppm) 1.29 (d, 6H, 6.9 Hz), 2.89 (qui, IH, J=6.9 Hz), 3.97 (s, 3H), 4.67 (s, 2H), 6.77 (s, IH), 6.84 (d, IH, J=9.2 Hz), 7.44 (d, IH, J=9.2 Hz). 7-hydroxymedιyl-4-isopropyl-2-medιoxy-2,4,6-cycloheptatrien-l-one(2.81 g, 13.5 mmol) and pyridine (1.31 ml, 16.2 mmol) were dissolved in dichloromediane (5 ml) and cooled to 0°C. The solution was stirred while medianesulfonyl chloride (1.25 ml, 16.2 mmol) was added diereto. After stirred at 0°C for 2 hours, the reaction solution was slowly brought back to room temperature. After 2 hours, the reaction solution was diluted widi dichloromediane, washed widi aqueous saturated sodium bicarbonate, water and 2 N HCl, dien dried over sodium sulfate. The solvent was distilled off under reduced pressure and die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1:1)] to give 1.38 g of 7-chlorometiιyl-4-isopropyl- 2-methoxy-2,4,6-cycloheptatrien-l-one (yield: 45%) as a pale yellow oil. This oil was solidified when allowed to stand at room temperature. MS m/z 226 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.29 (d, 6H, 6.8 Hz), 2.89 (qui, IH, J=6.8 Hz), 4.00 (s, 3H), 4.73 (s, 2H), 6.72 (s, IH), 6.82 (d, IH, 9.2 Hz), 7.62 (d, IH, J = 9.2 Hz). 7-chloromedιyl-4-isopropyi-2-medιoxy-2,4,6-cycioheptatrien-l-one (408 mg, 1.80 mmol), l-(4-chlorobenzhydryl)piperazine (619 mg, 2.16 mmol), triediylamine (0.3 ml, 2.15 mmol) were dissolved in chloroform (5 ml) and heated and refluxed for 20 hours. The reaction solution was diluted wid dichloromediane, washed with water, and dried over sodium sulfate. After solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1: 1)] to give 703 mg of 7-[4- (4-chlorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one as a pale yellow amorphous powder (yield: 82%). MS m/z 476 (M + ) ! H NMR (CDCI3) δ(ppm) 1.26 (d, 6H, J=7.3 Hz), 2.43 (m, 4H), 2.57 (m, 4H), 2.85 (qui, IH, J = 7.3 Hz), 3.65 (s, 2H), 3.93 (s, 3H), 4.23 (s, IH), 6.68 (s, IH), 6.80 (d, IH, J=9.2 Hz), 7.1- 7.4 (9H), 7.67 (d, IH, J=9.2 Hz). Example 3 Production of 7-{ 1 -[4-(4-chloroben__hydryl)piperazinomemyl]-a-phenyl}-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one 7-hydroxymed yl-4-isopropyl-2-medιoxy-2,4,6-cycloheptatrien-l-one(20g, 96 mmol) was dissolved in chloroform (300 ml), to which was added active manganese dioxide (80 g, 920 mmol) in several portions, and the resultant was stirred at room temperature for 4 hours. The insoluble matter was removed by filtration under reduced pressure, die filtrate was concentrated under reduced pressure and the resulting crude product was recrystallized from toluene to give 12.31 g of7-formyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one as yellow needle-like crystal (yield: 62%). Melting point of the product was 73-75°C. 10% aqueous sodium hydroxide (50 ml) was added to die aldehyde (5 g, 24 mmol) and stirred overnight at room temperature. The reaction solution was acidified with 10% dilute hydrochloric acid, then extracted with mediylene chloride, washed with water, dried, and solvent was distilled off to give a crude crystal (4.78 g). The crude crystal was recrystallized from ethyl acetate/hexane to give 7-formyl-4-isopropyl-2-hydroxy-2,4,6- cycloheptatrien-1-one as a colorless needle-like crystal (yield: quantitative). This compound showed melting point of 76°C, which is identical to that described in die literature (Sci. Repts. Tohoku Univ., I, 37, 367 (1953)]. The compound (1.94 g, 10 mmol) was dissolved in tetrahydrofuran (20 ml), to which was added dropwise 2 M phenyl lithium solution (5.2 ml, ca 10 mmol) in a nitrogen atmosphere while cooling to -78°C. The resultant was stirred for 10 minutes. An aqueous saturated sodium chloride was added to die reaction solution, and die resultant was extracted widi mediylene chloride, dried and the solvent was distilled off. The residue was purified by silica gel column chromatography to give 1.95 g of 7-(c.-hydroxybenzyl)-4-isopropyl-2-methoxy- 2,4,6-cycloheptatrien-l-one as brown oil (yield: 71%). The compound (1 g, 3.7 mmol) and l-(4- chlorobenzhydryl)piperazine (1.27 g, 4.4 mmol) were heated and refluxed in xylene (20 ml) for 2 hours, solvent was distilled off under reduced pressure and die residue was purified by silica gel column chromatography [(ethyl acetate/hexane (1:2)] to give 1.71 g of 7-{l-[4-(4- chlorobenzhydryl)piperazinomethyl]-Q:-phenyl}-4-isopropyl-2-hydroxyl-2,4,6-cycloheptatrien-l-one (yield: 86%). MS m/z 538.540 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.21 (d, 6H, J=6.7 Hz), 2.42 (bs, 8H), 2.82 (m, IH), 4.22 (s, IH), 5.03 (s, IH), 6.8-8.1 (m, 17H). The compound (1.5 g, 2.8 mmol) was heated and refluxed wid dimed yl sulfate (0.46 g, 3.6 mmol) and potassium carbonate (1.15 g, 8.3 mmol) in acetone (20 ml) for an hour. After water was added to d e reaction solution, the resultant was extracted with mediylene chloride, washed widi water, dried and solvent was distilled off. The resulting residue was purified by silica gel column chromatography (ediyl acetate/hexane (1:3-1:1) to give 0.99 g of 7-{l-[4-(4- chlorobenzhydryl)]piperazinomethyl-α-phenyl }-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien- 1 -one as a pale brown amorphous powder (yield: 64%). MS m/z 552.554 (M + ) X H NMR (CDC1 3 ) δ(ppm) 1.22 (d, 6H, J=6.5 Hz), 2.38 (bs, 8H), 2.8 (m, IH), 3.87 (s, 3H), 4.21 (s, IH), 5.06 (s, IH), 6.59 (s, IH), 6.82 (d, IH, J= 10 Hz), 7.0-7.6 (m, 14H), 7.97 (d, IH, J=10 Hz). Example 4 Production of 7-{ l-[4-(4-chlorobenzhydryl)]piperazinomethyl-α-medιyl}-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one 7-formyl-4-isopropyl-2-hydroxy-2,4,6-cycIoheptatrien-l-one (2.00 g, 10 mmol) was dissolved in tetrahydrofuran (20 ml) and cooled to -78°C in a dry ice/acetone badi. A solution of mediyllidiium the edier (1.4 M, 15 ml) was added dropwise to die solution, dien dry ice/acetone batii was removed and stirring was continued until die insolubles were dissolved. An aqueous saturated ammonium chloride was added to d e reaction mixture and extracted widi mediylene chloride. The mediylene chloride layer was washed widi water, dried over anhydrous sodium sulfate and solvent was distilled off to give 2.18 g of 7-(α-hydroxyed yl)-4-isopropyl-2-hydroxy- 2,4,6-cycloheptatrien-l-one as a reddish brown oil (yield: quantitative). MS m/z 208 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.28 (d, 6H, J=6.7 Hz), 1.53 (d, 3H, J=6.2 Hz), 2.92 (m, IH), 5.17 (q, IH, J=6.2 Hz), 7.03 (d, IH, J=10.3 Hz), 7.36 (s, IH), 7.66 (d, IH, J= 10.3 Hz). The compound (2.09 g, 10 mmol) was heated and refluxed with l-(4- chlorobenzhydry piperazine) (3.17 g, 11 mmol) in toluene (30 ml) for 1.5 hours. Then, solvent was distilled off under reduced pressure, die residue was dissolved in acetone (50 ml). Potassium carbonate (4.19 g, 30 mmol) and dimediyl sulfate (1.66 g, 13 mmol) were added and die resultant was heated and refluxed. After 2 hours, dimediyl sulfate (0.64 g, 5.i mmol) and potassium carbonate (2.1 g, 15 mmol) were further added and the resultant was heated and refluxed for 30 minutes. The reaction solution was filtered and the residue obtained after concentration of the filtrate was purified by silica gel column chromatography [ethyl acetate/hexane (1:1)] to give 1.82 g of 7-{ l-[4-(4-chlorobenzhydryl)]piperazinomethyl-c--methyI}-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one as a pale brown oil (yield: 37%). MS m/z 490.492 (M + ) H NMR (CDC1 3 ) δ(ppm) 1.21 (d, 3H, J=6.5 Hz), 1.25 (d, 6H, J=6.5 Hz), 1.27 (s, 3H), 2.3- 2.6 (8H), 2.83 (IH, m), 3.92 (s, 3H), 4.07 (m, IH), 4.18 (s, IH), 6.66 (s, IH), 6.79 (d, IH, J=9.7 Hz), 7.1-7.4 (m, 9H), 7.7 (d, IH, J=9.7 Hz). Example 5 Production of 7-{l-[4-(4-chlorobenzhydryl)]piperazinomethyl]-Q:-butyl}-4-isopropyl-2- medιoxy-2,4,6-cycloheptatrien- 1 -one 7-formyl-4-isopropyl-2-hydroxy-2,4,6-cycloheptatrien-l-one (1.95 g, 10 mmol) was dissolved in tetrahydrofuran (30 ml) and the resultant was cooled to -78°C in a dry ice/acetone bath. A solution of n-butyllithium in hexane (1.6 M, 14 ml) was added dropwise to the solution, d en, die dry ice/acetone badi was removed and die resultant was stirred until insoluble matter was dissolved. An aqueous saturated ammonium chloride was added to die reaction mixture and die resultant was extracted with mediylene chloride. The mediylene chloride layer was washed widi water, dien dried over anhydrous sodium sulfate. Solvent was distilled off to give 2.72 g of 7-(α-hydroxybutyl)-4-isopropyl-2-hydroxy-2,4,6-cycloheptatrien-l-one as a reddish brown oil (yield: quantitative). The compound (2.4 g, 9 mmol) and l-(4-chlorobenzhydryl)piperazine (2.6 g, 10 mmol) were heated and refluxed in toluene (30 ml) for 2 hours, then solvent was distilled off under reduced pressure and die residue was dissolved in acetone (50 ml), to which were added potassium carbonate (4.23 g, 31 mmol) and dimethyl sulfate (1.93 g, 15 mmol), and the resultant was heated and refluxed for 1.5 hours. The reaction solution was filtered and the residue obtained by concentration of the filtrate was purified by silica gel column chromatography (ethyl acetate/hexane, 1 :2-l : 1) to give 1.55 g of 7-{l-[4-(4-chlorobenzhydryl)piperazinomedιyl]-o.-butyl}- 4-isopropyl-2-medιoxy-2,4,6-cycloheptatrien-l-one as a pale brown oil (yield: 32%). MS m/z 532.534 (M + ) J H NMR (CDC1 3 ) δ(ppm) 0.788 (t, 3H, J=6.8 Hz), 1.0-1.8 (m, 6H), 1.27 (d, 6H, J=6.7 Hz), 2.1-2.7 (8H), 2.84 (m, IH), 3.92 (s, 3H), 4.16 (s, IH), 4.22 (m, IH), 6.66 (s, IH), 6.78 (d, IH, J= 10 Hz), 7.1-7.4 (m, 9H), 7.51 (d, IH, J = 10 Hz). Example 6 Production of 7-(4-benzhydrylpiperazino-l-methyl)-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien- 1 -one 7-hydroxymethyl-4-isopropyl-2-medιoxy-2,4,6-cycloheptatrien-l-one(400 mg, 1.92 mmol) was dissolved in chloroform (25 ml), to which were added triethylamine (291 mg, 2.88 mmol) and medianesulfonyl chloride (263 mg, 2.30 mmol) and die resultant was stirred at room temperature for 14 hours. The reaction solution was washed widi water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in chloroform (30 ml), to which were added triethylamine (291 mg, 2.88 mmol) and 4- benzhydrylpiperazine (485 mg, 1.92 mmol) and die resultant was stirred at 60°C for 14 hours. The reaction solution was washed widi water, and die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography and 417 mg of 7-(4-benzhydrylpiperazino-l-methyl)-4-isopropyl- 2-methoxy-2,4,6-cycloheptatrien-l-one was obtained as a yellowish brown amorphous powder from the hexane/ethyl acetate (l:l)-eluted fraction (yield: 49%). MS m/z 442 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=6.8 Hz), 2.4-2.6 (8H), 2.83 (qui, IH, J=6.8 Hz), 3.64 (s, 2H), 3.93 (s, 3H), 4.24 (s, IH), 6.68 (s, IH), 6.80 (d, IH, J=9.8 Hz), 7.1-7.5 (10H), 7.66 (d, IH, J=9.8 Hz). Example 7 Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l -methyl]-4-isopropyl-2-medιoxy- 2,4,6-cycloheptatrien- 1 -one 7-chloromedιyl-4-isopropyl-2-medιoxy-4-isopropyl-2,4,6-cycloheptatrien-l-one (500 mg, 2.21 mmol), l-(4,4'-difluorobenzhydryl)piperazine (820 mg, 2.84 mmol) and triethylamine (0.4 ml, 2.87 mmol) were dissolved in chloroform (5 ml), and heated and refluxed for 20 hours. The reaction solution was diluted widi dichloromediane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (3:7)] to give 808 mg of 7-[4- (4,4'-(difluorobenzhydryl)piperazino-l-mediyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one (yield: 76%) as a pale yellow amorphous powder. MS m/z 478 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=6.8 Hz), 2.41 (m, 4H), 2.57 (m, 4H), 2.85 (qui, IH, J=6.8 Hz), 3.66 (s, 2H), 3.93 (s, 3H), 4.23 (s, IH), 6.69 (s, IH), 6.80 (d, IH, J=9.2 Hz), 6.96 (t, 4H, J=8.9 Hz), 7.34 (dd, 4H, J=8.9, 5.4 Hz), 7.66 (d, IH, J=9.2 Hz). Example 8 Production of 7-{4-[4,4 , -di(trifluoromethyl)benzhydryl]piperazino-l-methyl}-4-isopropyl- 2-methoxy-2,4,6-cycloheptatrien-l-one 7-hydroxymedιyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one(423 mg, 2.03 mmol) was dissolved in chloroform (25 ml), to which were added triethylamine (284 mg, 2.81 mmol) and medianesulfonyl chloride (268 mg, 2.34 mmol), and die resultant was stirred at room temperature for 13 hours. The reaction solution was washed widi water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in chloroform (30 ml) to which were added triethylamine (237 mg, 2.34 mmol) and 4- [4,4'-di(trifluoromethyl)benzhydryl]piperazine (500 mg, 1.56 mmol), and die resultant was heated and refluxed for 4 hours. The reaction solution was washed with water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography [eluent: hexane/ed yl acetate (1:1)] to give 520 mg of 7-{4-[4,4'-di(trifluoromethyl)benzhydryl]piperazino-l-methyl}-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one as a yellow amorphous powder (yield: 65%). MS m/z 578 (M + ) l H NMR (CDC1 3 ) δ(ppm) 1.27 (d, 6H, J=6.8 Hz), 2.4-2.6 (8H), 2.85 (qui, IH, J=6.8 Hz), 3.65 (s, 2H), 3.94 (s, 3H), 4.39 (s, IH), 6.69 (s, IH), 6.80 (d, 3H, J=9.6 Hz), 7.6 (6H), 7.65 (d, IH, J=9.6 Hz). Example 9 Production of 4-isopropyI-2-methoxy-7-[4-(4-trifluoromethylbenzhydryl)piperazino-l- medιyl]-2,4,6-cycloheptatrien-l-one 7-hydroxymedιyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one(234 mg, 1.12 mmol) was dissolved in chloroform (15 ml), to which were added triediylamine (171 mg, 1.69 mmol) and methanesulfonyl chloride (161 mg, 1.41 mmol), and die resultant was stirred at room temperature for 11 hours. The reaction solution was washed widi water, the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in chloroform (20 ml), to which were added triethylamine (142 mg, 1.41 mmol) and 4- (4-trifluoromethylbenzhydryl)piperazine (364 mg, 0.94 mmol) and die resultant was stirred at 60°C for 14 hours. The reaction solution was washed widi water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 272 mg of 4-isopropyl-2-methoxy-7-[4-(4- tr ifluoromethylbenzhydry piperazino- 1 -medιyl]-2,4,6-cycloheptatrien- 1 -oneas ayellow amorphous powder from hexane/ethyl acetate (l:l)-eluted fraction (yield: 50%). MS m/z 510 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=6.8 Hz), 2.4-2.6 (8H), 2.85 (qui, IH, J=6.8 Hz), 3.64 (s, 2H), 3.93 (s, 3H), 4.31 (s, IH), 6.68 (s, IH), 6.80 (d, IH, J=9.2 Hz), 7.2-7.4 (5H), 7.45- 7.60 (4H), 7.66 (d, IH, J=9.2 Hz). Example 10 Production of 7-[4-(4-chloro-4'-med oxybenzhydryl)piperazino-l-methyl]-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one 7-hydroxymethyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one(480 mg, 2.30 mmol) was dissolved in chloroform (20 ml), to which were added triethylamine (350 mg, 3.45 mmol) and medianesulfonyl chloride (330 mg, 2.88 mmol), and die resultant was stirred at room temperature for 11 hours. The reaction solution was washed widi water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in chloroform (30 ml), to which were added triediylamine (291 mg, 2.88 mmol) and 4- (4-chloro-4'-methoxybenzhydryl)piperazine (608 mg, 1.92 mmol), and the resultant was heated and refluxed for 7 hours. The reaction solution was washed widi water, die organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 482 mg of 7-[4-(4-chloro-4'- methoxybenzhydryl)piperazino-l-medιyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one as a pale yellow amorphous powder from the hexane/ediyl acetate (l:l)-eluted fraction (yield: 49%). MS m/z 510 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=6.8 Hz), 2.4-2.6 (8H), 2.85 (qui, IH, J=6.8 Hz), 3.64 (s, 2H), 3.93 (s, 3H), 4.31 (s, IH), 6.68 (s, IH), 6.80 (d, IH, J=9.2 Hz), 7.2-7.4 (5H), 7.45- 7.60 (4H), 7.66 (d, IH, J=9.2 Hz). Example 11 Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-ethoxy-4- isopropyl-2,4,6-cycloheptatrien-l-one 60% oily sodium hydride (256 mg, 6.4 mmol) was added to a solution of 2-hydroxy-7- hydroxymedιyl-4-isopropyl-2,4,6-cycloheptatrien-l-one(l .13 g, 5.82 mmol) in dimediylformamide (5 ml) with stirring. Then, ethyl iodide (0.7 ml, 8.75 mmol) was added and the reaction mixture was heated at 70°C for 3 hours. The reaction solution was diluted widi dichloromediane, washed widi water, and dried over sodium sulfate. After die solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (2:3)] to give 485 mg of 2-ethoxy-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-l-one as a pale yellow amorphous powder (yield: 76%). *H NMR (CDC1 3 ) δ(ppm) 1.26 (d, 6H, J=6.8 Hz), 1.55 (t, 3H, J=6.8 Hz), 2.87 (qui, 2H, J=6.8 Hz), 4.16 (q, 2H, J=6.8 Hz), 4.66 (s, 2H), 6.80 (s, IH), 6.85 (d, IH, J=9.2 Hz), 7.46 (d, IH, J =9.2 Hz). 2-edιoxy-7-hydroxymedιyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (485 mg, 2.18 mmol) and triethylamine (0.36 ml, 2.58 mmol) were dissolved in dichloromediane (2 ml) and cooled to 0°C. Methanesulfonyl chloride (0.2 ml, 2.58 mmol) was added to the solution widi stirring, and stirring was continued for another one hour at 0°C. Then, the reaction solution was slowly warmed to room temperature. After 4 hours, die reaction solution was diluted widi dichloromethane, washed widi an aqueous saturated sodium bicarbonate and dried over sodium sulfate. After solvent was distilled off under reduced pressure, l-(4-4'- difluorobenzhydry piperazine (756 mg, 2.62 mmol) and triethylamine (0.36 ml, 2.58 mmol) were added to die residue, and d e resultant was dissolved in chloroform (15 ml). The reaction solution was heated and refluxed for 7 hours, diluted widi dichloromediane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (3:7)] to give 638 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-ethoxy-4-isopropyl-2,4,6- cycloheptatrien-1-one as a pale yellow amorphous powder (yield: 59%). MS m/z 492 (M + ) ! H NMR (CDCI3) δ(ppm) 1.25 (d, 6H, J=7.0 Hz), 1.52 (t, 3H, J=7.0 Hz), 2.40 (m, 4H), 2.55 (m, 4H), 2.82 (qui, IH, J=7.0 Hz), 3.62 (s, 2H), 4.12 (1, 2H, J=7.0 Hz), 4.23 (s, IH), 6.70 (s, IH), 6.78 (d, IH, J=9.2 Hz), 6.70 (t, 4H, J = 8.9 Hz), 7.34 (dd, 4H, J=8.9, 5.4 Hz), 7.63 (d, IH, J=9.2 Hz). Example 12 Production of 2-butoxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-4-isopropyl- 2,4,6-cycloheptatrien-l-one A solution of 2-hydroxy-7-hydroxymedιyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (1.26 g, 6.49 mmol) in dimediylformamide (5 ml) was stirred, and 60% oily sodium hydride (285 mg, 7.13 mmol) was added in small portions to die solution. Subsequently, butyl iodide (1.1 ml, 9.6 mmol) was added and die reaction solution was heated at 80°C for 4 hours. The solution was diluted with dichloromediane, washed widi water and dried over sodium sulfate. Solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1:1)] to give 612 mg of 2-butoxy-7-hydroxymedιyl- 4-isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown oil (yield, 38%). ! H NMR (CDC1 3 ) δ(ppm) 1.00 (t, 3H, J = 7.3 Hz), 1.27 (d, 6H, J=6.8 Hz), 1.55 (m, 2H), 1.92 (m, 2H), 2.89 (qui, IH, J = 6.8 Hz), 4.07 (t, 2H, J=7.0 Hz), 4.65 (d, 2H, J=5.4 Hz), 6.79 (s, IH), 6.81 (d, IH, J=9.2 Hz), 7.4 (d, IH, J = 9.2 Hz). 2-butoxy-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (612 mg, 2.44 mmol) and triediylamine (0.41 ml, 2.94 mmol) were dissolved in dichloromediane (2 ml), and cooled to 0°C. The solution was stirred, while methanesulfonyl chloride (0.23 ml, 2.97 mmol) was added thereto. Stirring was further continued at o°C for an hour, then the reaction solution was gradually warmed to room temperature. After 4 hours, the solution was diluted wid dichloromethane and washed widi aqueous saturated sodium bicarbonate and dried over sodium sulfate. After solvent was distilled off under reduced pressure, l-(4,4'-difluorobenzhydryl)piperazine (846 mg, 2.93 mmol) and triediylamine (0.41 ml, 2.94 mmol) were added to die residue, which was dissolved in chloroform (15 ml). After heated and refluxed for 12 hours, the solution was diluted widi dichloromediane, washed with water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (7:3)] and 823 mg of 2-butoxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l- methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one was obtained as a pale yellow amorphous powder was obtained (yield: 64%). MS m/z 520 (M + ) 1H NMR (CDC1 3 ) δ(ppm) 0.98 (t, 3H, J=7.3 Hz), 1.25 (d, 6H, J=7.0 Hz), 1.53 (m, 2H), 1.89 (m, 2H), 2.40 (m, 4H), 2.55 (m, 4H), 2.82 (qui, IH, J=7.0 Hz), 3.62 (s, 2H), 4.03 (t, 2H, J=6.8 Hz), 4.23 (s, IH), 6.70 (s, IH), 6.77 (d, IH, J=9.2 Hz), 6.96 (t, 4H, J = 8.9 Hz), 7.34 (dd, 4H, J = 8.9, 5.4 Hz), 7.62 (d, IH, J=9.2 Hz). Example 13 Production of 2-benzyloxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4- isopropyl-2,4,6-cycloheptatrien-l-one A solution of 2-hydroxy-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (1.15 g, 5.92 mmol) in dimediylformamide (5 ml) was stirred while 60% oily sodium hydride (260 mg, 6.50 mmol) was gradually added diereto. Subsequently, benzyl chloride (1 ml, 8.41 mmol) was added, dien the reaction solution was heated at 80°C for 4 hours. The reaction solution was diluted with dichloromethane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1:1)] to give 729 mg of 2-benzyloxy-7-hydroxymethyl-4-isopropyl- 2,4,6-cycloheptatrien-l-one (yield: 43%) as a pale yellowish brown oil. 1H NMR (CDC1 3 ) δ(ppm) 1.12 (d, 6H, J=6.8 Hz), 2.77 (qui, IH, J=6.8 Hz), 4.67 (d, IH, J=5.9 Hz), 5.29 (s, 2H), 6.80 (d, IH, J=9.4 Hz), 6.83 (s, IH), 7.3-7.5 (6H). 2-benzyloxy-7-hydroxymediyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (729 mg, 2.56 mmol) and triethylamine (0.43 ml, 3.09 mmol) were dissolved in dichloromethane (2 ml), and cooled to 0°C. Medianesulfonyl chloride (0.24 ml, 3.1 mmol) was added to the solution widi stirring. Further, stirring was continued at 0°C for an hour, dien the reaction solution was gradually warmed to room temperature. After 4 hours, die solution was diluted with dichloromediane, washed widi aqueous saturated sodium bicarbonate and dried over sodium sulfate. After solvent was distilled off under reduced pressure, l-(4,4'-difluorobenzhydryl)piperazine (887 mg, 3.08 mmol) and triediylamine (0.43 ml, 3.09 mmol) were added to d e residue, which was dissolved in chloroform (15 ml). The solution was heated and refluxed for 6 hours, then diluted with dichloromethane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (7:3)] to give 776 mg of 2-benzyloxy-7-[4-(4,4'- difluorobenzhydryl)piperazino-i-methyl]-4-isopropyi-2,4,6-cycioheptatrien-l-one as a pale yeilow amorphous powder (yield: 55%). MS m/z 554 (M + ) ! H NMR (CDCI3) δ(ppm) 1.11 (d, 6H, J=6.8 Hz), 2.41 (m, 4H), 2.56 (m, 4H), 2.73 (qui, IH, J=6.8 Hz), 3.64 (s, 2H), 4.23 (s, IH), 5.24 (s, 2H), 6.76 (s, IH), 6.77 (d, IH, J=9.4 Hz), 6.96 (t, 4H, J = 8.9 Hz), 7.34 (dd, 4H, J=8.9, 5.4 Hz), 7.2-7.5 (5H), 7.62 (d, IH, J=9.4 Hz). Example 14 Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-[2-(3,4- dimethoxyphenyl)ethoxy]-4-isopropyl-2,4,6-cycloheptatrien-l-one A solution of 2-hydroxy-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (844 mg, 4.35 mmol) in dimediylformamide (5 ml) was stirred while 60% oily sodium hydride (191 mg, 4.78 mg) in small portions were added diereto. Subsequently, 3,4-dimethoxyphenethyl iodide (2.54 mg, 8.70 mmol) was added, dien the solution was heated at 80°C for 7 hours. The solution was diluted with dichloromethane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (3:2)] to give 169 mg of 2-[2-(3,4- dimedιoxyphenyl)edιoxy]-7-hydroxymedιyl-4-isopropyl-2,4,6-cycloheptatrien-l-oneas a yellowish brown oil (yield: 11%). J H NMR (CDC1 3 ) δ(ppm) 1.24 (d, 6H, J=6.8 Hz), 2.80 (qui, IH, J=6.8 Hz), 3.19 (t, 2H, J=6.8 Hz), 3.86 (s, 3H), 3.91 (s, 3H), 4.22 (t, 2H, J=6.8 Hz), 4.66 (s, 2H), 6.75 (s, IH), 6.8- 7.0 (4H), 7.43 (d, IH, J=9.2 Hz). 2-[2-(3,4-dimedιoxyphenyl)ethoxy]-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-l- one (169 mg, 0.472 mmol) and triethylamine (0.08 ml, 0.574 mmol) were dissolved in dichloromethane (1 ml), to which was added methanesulfonyl chloride (44 μl, 0.568 mmol) at room temperature. After the solution was stirred at room temperature for 5 hours, solvent was distilled off under reduced pressure. l-(4,4'-difluorobenzhydryl)piperazine (164 mg, 0.569 mmol) and triethylamine (0.08 ml, 0.574 mmol) were added to die residue, which were dissolved in chloroform (5 ml). The solution was heated and refluxed for 12 hours, then diluted with dichloromediane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1 : 1)] to give 157 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-mediyl]-2- [2-(3,4-dimedιoxyphenyl]ethoxy}-4-isopropyl-2,4,6-cycloheptatrien-l-oneas a yellowish brown oil (yield: 53%). MS m/z 628 (M + ) l R NMR (CDC1 3 ) δ(ppm) 1.21 (d, 6H, J=7.0 Hz), 2.41 (m, 4H), 2.55 (m, 4H), 2.78 (qui, IH, J=7.0 Hz), 3.17 (t, 2H, J=7.0 Hz), 3.62 (s, 2H), 3.86 (s, 3H), 3.90 (s, 3H), 4.18 (t, 2H, J=7.0 Hz), 4.23 (s, IH), 6.66 (s, IH), 6.7-6.9 (4H), 6.96 (t, 4H, J=8.9 Hz), 7.34 (dd, 4H, J=8.9, 5.4 Hz), 7.63 (d, IH, J=9.2 Hz). Example 15 Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[3-(N- medιyl-N-phenedιylamino)propoxy]-2,4,6-cycloheptatrien- 1 -one 60% oily sodium hydride (292, mg, 7.3 mmol) in small portions were added to a solution of 2-hydroxy-7-hydroxymedιyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (1.29 g, 6.64 mmol) in dimediylformamide (5 ml) with stirring. After addition of 1,3-dibromopropane (1.35 ml, 13.3 mmol), the solution was heated at 80°C for 4 hours. The solution was diluted widi dichloromethane, washed widi water, and dried over sodium sulfate. After solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: hexane/ethyl acetate (1:1)] to give 293 mg of 2-(3-bromopropoxy)-7-hydroxymediyl-4-isopropyl- 2,4,6-cycloheptatrien-l-one as a pale yellow crystal (yield: 14%). l R NMR (CDC1 3 ) δ(ppm) 1.29 (d, 6H, J=7.0 Hz), 2.46 (qui, 2H, J=5.9 Hz), 2.88 (qui, IH, J=7.0 Hz), 3.69 (t, 2H, J=5.9 Hz), 4.22 (t, 2H, J=5.9 Hz), 4.66 (s, 2H), 6.84 (s, IH), 6.85 (d, IH, J=9.4 Hz), 7.44 (d, IH, J=9.4 Hz). 2-(3-bromopropoxy-7-hydroxymediyl-4-isopropyl-2,4,6-cycloheptatrien-l-one (280 mg, 0.89 mmol), N-phenethylamine (0.15 ml, 1.03 mmol), triethylamine (0.15 ml, 1.08 mmol) were dissolved in chloroform (5 ml), and the solution was heated and refluxed for 5 hours. The solution was diluted widi dichloromediane, washed widi water and dried over sodium sulfate. After solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent: chloroform/medianol (10:1)] to give 242 mg of 7-hydroxymedιyl-4- isopropyl-2-[3-(N-methyl-N-phenethylamino)propoxy]-2,4,6-cycloheptatrien-l-one as a yellowish brown oil (yield: 74%). *H NMR (CDC1 3 ) δ(ppm) 1.27 (d, 6H, J=6.8 Hz), 2.10 (qui, 2H, J=6.5 Hz), 2.34 (m, 3H), 2.6-2.9 (7H), 4.07 (t, 2H, J=6.5 Hz), 4.66 (s, 2H), 6.78 (s, IH), 6.83 (d, IH, J=9.5 Hz), 7.1- 7.3 (5H), 7.46 (d, IH, J=9.5 Hz). 7-hydroxymethyl-4-isoρropyl-2-[3-(N-methyl-N-phenethylamino)propoxy]-2,4,6- cycloheptatrien-1-one (242 mg, 0.655 mmol) and triediylamine (0.11 ml, 0.789 mmol) were dissolved in dichloromethane (1 ml), to which was added methanesulfonyl chloride (61 μl, 0.788 mmol) at room temperature for 5 hours, the solvent was distilled off under reduced pressure. 1- (4,4'-difluorobenzhydryl)piperazine (230 mg, 0.798 mmol) and triediylamine (0.11 ml, 0.789 mmol) were added to the residue, and die resultant was dissolved in chloroform (5 ml). The solution was heated and refluxed for 16 hours, diluted widi dichloromethane, washed widi water and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, die residue was purified by silica gel column chromatography [eluent: chloroform/medianol (30: 1)] to give 156 mg of 7-difluorobenzhydryi)piperazino-l-methyi]-4-isopropyi-2-[3-N-methyl-N- phenethylamino)propoxy]-2,4,6-cycloheptatrien-l-one as a yellowish brown oil (yield: 37%). MS m/z 639 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.24 (d, 6H, J=6.8 Hz), 2.07 (qui, 2H, J=6.5 Hz), 2.32 (s, 3H), 2.40 (m, 4H), 2.54 (m, 4H), 2.3-2.9 (6H), 3.62 (s, 2H), 4.03 (t, 2H, J=6.5 Hz), 4.23 (IH), 6.69 (s, IH), 6.78 (d, IH, J = 9.2 Hz), 6.96 (t, 4H, J = 8.9 Hz), 7.1-7.3 (5H), 7.34 (dd, 4H, J = 8.9, 5.4 Hz), 7.63 (d, IH, J =9.2 Hz). Example 16 Production of 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-2-methoxy-2,4,6- cy cloheptatrien- 1 -one Tropolone (1 g, 8.0 mmol) and 4-(4-chlorobenzhydryl)piperazine (2.82 g, 9.6 mmol) were dissolved in medianol (40 ml), to which were added 37% formalin (800 mg, 9.6 mmol) and acetic acid (590 mg, 9.6 mmol), and the resultant was stirred at 60°C for an hour. Water was added to die solution which was extracted wid chloroform, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography [eluent: chloroform/medianol (100:1)] to give 600 mg of 7-[4-(4-chlorobenzhydryl)piperazino-l- methyI]-2-hydroxy-2,4,6-cycloheptatrien-l-one as a pale yellowish brown amorphous powder (yield: 18%), MS m/z 420 (M + ) *H NMR (CDC1 3 ) δ(ppm) 2.4-2.6 (8H) 3.73 (s, 2H), 4.24 (s, IH), 7.04 (m, IH), 7.2-7.4 (1 IH), 7.85 (d, IH, J=9.7 Hz). 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-2-hydroxy-2,4,6-cycloheptatrien-l- one (200 mg, 0.47 mmol) was dissolved in acetone (50 ml), to which were added potassium carbonate (263 mg, 1.9 mmol) and dimediyl sulfate (78 mg, 0.62 mmol) and die resultant was heated and refluxed for an hour. Water was added to die solution, which was extracted with chloroform, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography [eluent: chloroform/medianol (100:1)] togive20mgof7-[4-(4-chlorobenzhydryl)piperazino-l-medιyl]-2-methoxy-2,4,6-cycloheptatrien-l- one as a pale brown amorphous powder (yield: 10%). MS m/z 434 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 2.4-2.6 (8H), 3.67 (s, IH), 3.92 (s, 3H), 4.23 (s, IH), 6.72 (d, IH, J=9.5 Hz), 6.90 (bt, IH, J=9.7 Hz), 7.03 (bt, IH, J=9.7 Hz), 7.2-7.4 (9H), 7.76 (d, IH, J=9.7 Hz). Example IB Production of 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3- phenethylbenzodiiazoline (laB) Benzothiazolin-2-one (5.15 g, 34.1 mmol) was dissolved in dimediylformamide (100 ml) and to the solution was added 60% sodium hydride (1.36 g, 34.1 mmol) which was stirred at room temperature until generation of hydrogen gas stopped. Then S-phenylethylbromide (4.89 ml, 35.8 mmol) was added to die solution which was stirred at room temperature for 17 hours. To the reaction solution was added a saturated aqueous solution of ammonium chloride, followed by extraction widi ediyl acetate. The organic layer was washed in turn with a saturated sodium bicarbonate solution and saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The crude product dius obtained was purified by subjecting it to silica gel column chromatography to give 6.49 g of 3-phenethylbenzothiazoline-2-one as a white amoφhous powder form n-hexane/ethyl (4:l)-eluted fraction (yield: 80%). *H NMR (CDC1 3 ) δ(ppm) 5.16 (2H, s), 6.96 (IH, dd, J = 8.1 Hz), 7.13 (IH, ddd, J = 8, 8, 1 Hz), 7.27-7.36 (5H, m), 7.43 (IH, ddd, J=8, 1 Hz). (lbB) 3-phenedιylbenzodιiazolin-2-one (2.0 g, 7.83 mmol) was heated at reflux in ethanol (90 ml)/potassium hydroxide (10.0 g) under nitrogen atmosphere for 17 hours. After cooling, the reaction solution was neutralized widi hydrochloric acid and dried over anhydrous magnesium sulfate, and d en die solvent was distilled off under reduced pressure to give 2-(2-phenyl)- ethylaminodiiophenol. This was dissolved in toluene (18 ml) and to die solution was added 7- formyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one (1.63 g, 7.90 mmol), followed by heating at reflux for 17 hours under nitrogen atmosphere. The reaction solution was concentrated under reduced pressure and die crude product was purified by subjecting it to silica gel column chromatography to obtain 2.04 g of 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)- 3-phenethylbenzothiazoline as a blown amoφhous powder from toluene/acetone (6:l)-eluted fraction (yield: 62%). ! H NMR (CDC1 3 ) δ(ppm) 1.25 (6H, d, J=7 Hz), 2.77-2.97 (3H, m), 3.22 (IH, ddd, J= 15, 10, 6 Hz), 3.69 (IH, ddd, J= 15, 10, 6 Hz), 3.97 (3H, s), 6.43 (IH, s), 6.61 (IH, d, J = 8 Hz), 6.69 (lH ddd, J=8, 8, 1 Hz), 6.74 (IH, s), 6.80 (IH, d, J= 10 Hz), 6.69-7.03 (2H, m), 7.13-7.30 (5H, m), 7.48 (IH, d, J= 10 Hz). MS (m/e): 417 (M + , 35%), 412 (100%), 312 (17%) Examples 2aB to 14aB According to die same reaction operation as that of Example la, various N-substituted benzothiaozolines were synthesized. The results are shown in Table 4 below. Table 4 N-substituted Ex. No. Aikylating agent benzot iazolinone Yield(%) Η NMRCCDCfl,) $(pρra) < 2a B Mel ° 98 3.46(3H,S),7.04ClH.d,J-8Hz). N 7.17(lH.ddd.J-8.8-lHz), " I Me 7.33(lH.ddd.J-8.8.1Hz). 7.43(lH.dd.J-8.1»z) • 3a B 7.26-7.36C5H.πι). 7.43(lH,dd.J=8,lHz) 4a B 75 5.28(2H.S).7.10-7.23C5H. ). Cfl-HCfl •■ OT 7. 3(111. "0 7.63(lH. .J=8.8,2Hz). 8-57(lH.d.J=5Hz) Table 4 (continued) N-substituted Ex. No. Aikylating agent benzothiazolinone Yield (%) Η NMR(CDCfl 3 S (ppm) 5a B . N--> Cfl-HCfi ° ,1Hz). 7.62(111, ddd. J=8.8-2Hz). 8.54(lH.dd,J=5 . 2Hz),8.64(lH.d,J=2Hz) 6a B N^ H.d.J=8Hz). ^._ ■ Cfl-HCfl ° 8.56(lH.m).8.58(lH.m) Table 4 (continued) N-substituted Ex. No. Aikylating agent benzothiazolinone Yield (%) '11 NMR(CDCfl.) S (pp 8a B MeO .81(311. S). MeO OTs ° .t.J=8Hz). 84(2H.m). OMe 7.14(111. ddd. J=8, 8.1Hz). 7.28(lH.ddd. J=8.8,1Hz). 7.43(lH.dd,J=8.2Hz) 7.55(lH.dd.J=7.7Hz), 7.74(111. dd.J=8-lHz). 7.79(111. dd.J=8Hz). 8.10(211. d.J=8Hz) Table 4 (continued) N-substituted 'II NMR(CDCβj) δ(ppm) = Ex. N o. Aikylating agent benzothiazolinone Yield ( % ) lOaβ 64 1.89(2H,qui, J=7HZ), Cβ 2.30(3H.S),2.46(2H.t.J=7Hz). 2.60(2H,dd,J=10,6Hz). 2-77(2H,dd.J=10.6Hz). 3.94(211. t.J=7Hz).7.05(lH,d, J=81lz), 7.14(lH.ddd.J=8.8,lHz). 7.17-7.20(3H. n.).7.26-7.31(3ll, ), 7.42(l.!.dd,J=8,lHz) 7.43(lll.dd.J=8.1Hz) Table 4 (continued) N-substituted Ex. No. Aikylating agent benzothiazol inone Yield ( % ) l H NMR(CDC 3 <5(ppm) 12a B 55 1.90(2H.qui, J=7Hz),2.23(6H,S), i (Note 1) ■ Cβ*HCβ « 3D 2-34(2H.L.J=7Hz).4.01(2H.t,J=7Hz). I 7.15(lH,d.J=8Hz). 7.15(111. dd.J=8.8Hz). 7.3KlH,ddd,J=8.8.111z-). 7. 3(111. dd.J=8,lHz) 13aB (Note 2) ke) . 7.25-7.36(5H.m).7.40UH,d,J=9Hz) Note 1: Sodium ethoxide solution was used in place of sodium hydride. Note 2: By using 1 ,3-dibromopropane, according to the same manner as that of Example 1(a), 3-(3-bromopropyl)benzothiazoline- 2-one was obtained in a yield of 64%. The resulting bro o compound was heated at reflux with 4- (4,4 '- difluorobenzhydryl)piperadine in toluene under the existence of potassium carbonate to obtain the N-substituted benzothiazolinone compound 13(a) in a yield of 85%. Exa ples 2bB to 14bB According to die same reaction operation as diat of Example 1(b), various compounds [la] were syndiesized. The results are shown in Table 5. Table 5 6.75C1H.S).6- 86(1H, d.J-lOHz). 6.99(lH.dd.J=8-8Hz). 7.-56(lH.d.J = 10Hz) 3b B ) MeO 6.72(lh.br.S).6.81(lH.d.J=10Hz). 6.95(lH,ddd.J=8.8.111z). 7.00(lH,dd,J=8,lHz).7.21-7.28(5l..m), 7.56(lH.d.J=101tz) 7.55(lH.d.J=8Hz). 7.65(lH.ddd.J=8.8.2Hz). 7.26-7.30(lH.m).7.80(lH.d.J-=8Hz). .36(211, d. J-6H»).8- 57(211, d.J-6llz) 7.15(lH.dd.J=8.5Hz). 7.29(lH.d.J-8Hz). 7.62(lH.ddd.J=8.8,2Hz), 6..56(lH.d,J=8Hz), 6.65(lH.dd,J=7,7Hz).6.73(lH.S). 6.82(lH.d.J=9Hz).6.95(lH.d.J=71Iz), 6-96(lH,dd.J*8Hz).7.14-7.26(511, m). 7.45ClH.d-J-10Hz) llbB 6.84(lH.d.J=9Hz).6-96(lH.d.J=7Hz). 6.98(111. dd.J-7,7Hz). 7.51(lH.d,J=10Hz) 6- 83(lH.d.J = 10Hz), 6- 95-6.99(211.1.0. 6.81(lH < d.J-10Hz).6.93-6.99(6ll.m). 7.79 ( lH.d.J-10Hz) Note 1: 7-formyl-4-isopropyl-2-hydroxy-2, 4, 6- cycloheptatriene-1-one was used as aldehide. Example 15B Production of 2-[2'-oxo-3'-(l-piperazinyl)-5'-isopropyl-3',5',7'-cycloheptatrienyl]-3- phenethylbenzothiazoline 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7 ! -cycioheptatrienyi)-3-phenethylbenzothiazoline (compound lb) (100 mg, 0.24 mmol) was heated at reflux widi piperazine (31 mg, 0.36 mmol) in toluene (6 ml) for 3.5 hours. The reaction solution was concentrated under reduced pressure and die resulting crude product was purified by subjecting it to silica gel tiiin-layer chromatography (developing solvent: chloroform/medianol = 10/1) to obtain 105 mg of 2-(2'-oxo-3'-(l- piperazinyl-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenethylbenzothiazolineasanorangeviscose liquid (yield: 93%). *H NMR (CDC1 3 ) δ(ppm) 1.22 (6H, d, J=7 Hz), 2.71 (IH, br s), 2.80 (IH, m), 2.88 (2H, m), 3.17 (4H, br s), 3.22 (IH, m), 3.34 (4H, br s), 3.70 (IH, m), 6.38 (IH, s), 6.59 (IH, d, J=8 Hz), 6.65-6.74 (3H, m), 6.97 (2H, d, J=8 Hz), 7.14-7.30 (5H, m), 7.40 (IH, d, J= 10 Hz). Example 16B Production of 2-{2'-oxo-3'-[2-(N,N-dimethylamino)-ethyl]-5'-isopropyl-3',5',7'- cycloheptatrienyl]}-3-phenethylbenzothiazoline A solution of compound lb (100 mg, 0.24 mmol) and N,N-dimedιyl-edιylenediamine (36 mg, 0.41 mmol) in toluene (6 ml) was refluxed for 2.5 hours. The reaction solution was concentrated under reduced pressure and die resulting crude product was purified by subjecting it to silica gel thin- layer chromatography [developing solvent: chloroform/iiiethanol (10:1)] to obtain 82.5 mg of 2- (2'-oxo-3'-[2-(N,N-diethylamino)ethyl]amino-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3- phenethylbenzothiazoline as a yellow amoφhous powder (yield: 73%). *H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=7 Hz), 2.32 (6H, s), 2.68 (2H, m), 2.38-2.94 (3H, m), 3.22 (IH, m), 3.37 (2H, m), 3.68 (IH, m), 6.53 (IH, s), 6.59 (IH, t, J=8 Hz), 6.64-6.70 (2H, m), 6.98 (2H, d, J=7 Hz), 7.15-7.13 (6H, m), 7.55 (IH, d, J= 10 Hz), 7.77 (IH, br s). Example 17B Production of 2-(2'-oxo-3'-medιoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenedιyl- 1 , 1-dioxobenzothiazoline The compound lb (50 mg, 0.12 mmol) was dissolved in chloroform (10 ml) and die mixture was cooled to 0°C. To this was added m-chloroperbenzoic acid (83 mg, 0.48 mmol) which was stirred at 0°C for 17 hours. To die reaction solution was added saturated aqueous sodium bicarbonate solution, followed by extraction widi ediyl acetate. The organic layer was washed widi saline and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by subjecting it to silica gel chromatography to obtain 36 mg of 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenediyl-l,l- dioxobenzothiazoline as a blown amoφhous powder from toluene/acetone (4:l)-eluted fraction (yield: 66%). ] H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=7 Hz), 2.83-2.92 (3H, m), 3.27 (IH, m), 3.82 (IH, m), 3.99 (3H, s), 6.17 (IH, s), 6.73-6.94 (2H, m), 7.13-7.29 (6H, m), 7.47 (IH, ddd, J = 8, 8, 1 Hz), 7.57 (IH, dd, J = 8, i Hz). MS (m/e): 449 (M + , 13%), 342 (100%), 105 (64%), 91 (89%) Example 18B Productionof2-(2'-oxo-3'-medioxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenethyl-l- oxobenzothiazoline The compound lb (52 mg, 0.13 mmol) was dissolved in chloroform (5 ml) and the mixture was cooled to 0°C. To this was added m-chloroperbenzoic acid (22.9 mg, 0.13 mmol) which was stirred for 3 hours. To the reaction solution was added saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saline and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by subjecting it to silica gel chromatography to obtain 49 mg of 2- (2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenethyl-l-oxo-benzothiazoline as a blown amoφhous powder from toluene/acetone (l:l)-eluted fraction (yield: 90%). J H NMR (CDC1 3 ) δ(ppm) 1.25 (6H, d, J=7 Hz), 2.77 (6H, s), 2.83 (IH, m), 3.95 (3H, s), 4.27 (2H, s), 6.68-6.71 (2H, m), 6.94 (IH, m), 7.03-7.16 (3H, m), 7.52 (IH, d, J= 10 Hz). Example 1C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2- dimethylaminoethylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (130 mg, 0.27 mmol) and N,N-dimedιylethylenediamine (0.05 ml, 0.46 mmol) were dissolved in toluene (5 ml) and the resulting solution was heated at reflux for 6 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50:1 to 30:1)] to give 71 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimediylaminoethylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 49%). MS m/z 534 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.27 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.56 (4H, m), 2.65 (2H, t, J=6.0 Hz), 2.85 (IH, qui, J=6.8 Hz), 3.34 (2H, q, J=6.0 Hz), 3.70 (2H, s), 4.23 (IH, s), 6.46 (IH, s), 6.61 (IH, d, J=9.6 Hz), 6.95 (4H, t, J=8.6 Hz), 7.33 (4H, dd, J=8.6 and 5.5 Hz), 7.61 (IH, d, J=9.6 Hz), 7.67 (IH, broad t). Example 2C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-3- dimediylaminopropylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (153 mg, 0.32 mmol) and N,N-dimethyl-l,3-propanediamine (0.08 ml, 0.64 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 5 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (10: 1)] to give 124 mg of 7-[4-(4,4'-difluorober_zhydryl)piperazino-l-methyl]-2-(N-3-dime-hylam opropylam_ικ) -isopropyl- 2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 71 %). MS m/z 548 (M + ) l E NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 1.90 (2H, qui, J=6.8 Hz), 2.25 (6H, s), 2.42 (2H, t, J=6.8 Hz). 2.42 (4H, m), 2.57 (4H, m), 2.86 (IH, qui, J=6.8 Hz), 3.37 (2H, q, J=6.8 Hz), 3.70 (2H, s), 4.23 (IH, s), 6.51 (IH, s), 6.62 (IH, d, J = 10.0 Hz), 6.95 (4H, t, J=8.7 Hz), 7.34 (4H, dd, J = 8.7 and 5.4 Hz), 7.53 (IH, broad t), 7.62 (IH, d, J= 10.0 Hz). Example 3C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-me yl]-4-isopropyl-2-(N-2- methylaminoethylamino)-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyI-2-methoxy-2,4,6- cycloheptatrien-1-one (228 mg, 0.48 mmol) and N-mediylediylenediamine (0.063 ml, 0.72 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 5 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel preparative thin-layer chromatography [developing solvent: chloroform/methanol (10: 1), twice developing] to give 88 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino- 1 -methyl]-4-isopropyl- 2-(N-2-medιylaminoethylamino)-2,4,6-cycIoheptatrien-l-one as a yellowish brown amoφhous powder (yield: 35%). MS m/z 520 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 2.45 (4H, m), 2.51 (3H, s), 2.63 (4H, m), 2.89 (IH, qui, J=6.8 Hz), 3.00 (2H, t, J=5.9 Hz), 3.49 (2H, q, J=5.9 Hz), 3.76 (2H, s), 4.24 (IH, s), 6.54 (IH, s), 6.64 (IH, d, J = 10.3 Hz), 6.95 (4H, t, J=8.9 Hz), 7.33 (4H, dd, J = 8.9 and 5.4 Hz), 7.61 (IH, broad t), 7.66 (IH, d, J= 10.3 Hz). Example 4C Production of 2-(N-2-aminoethylamino)-7-[4-(4,4'-difluoroberιzhydryl)piperazino-l-medιyl]- 4-isopropyI-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (185 mg, 0.39 mmol) and ediylenediamine (0.077 ml, 1.15 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 5 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (10:1) - chloroform/methanol/aqueous ammonia (5: 1 :0.1)] to give 142 mg of 2-(N-2-aminoethylamino)-7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 72%). MS m/z 506 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.57 (4H, m), 2.86 (IH, qui, J=6.8 Hz), 3.07 (2H, t, J = 6.0 Hz), 3.40 (2H, q, J = 6.0 Hz), 3.70 (2H, s), 4.23 (IH, s), 6.53 (IH, s), 6.64 (IH, d, J=9.7 Hz), 6.96 (4H, t, J = 8.6 Hz), 7.34 (4H, dd, J = 8.6 and 5.4 Hz), 7.54 (IH, broad t), 7.63 (IH, d, J=9.7 Hz). Example 5C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2- dimethylaminoethyl-N-methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (151 mg, 0.32 mmol) and N,N,N'-trimedιyledιylenediamine (0.08 ml, 0.63 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 5 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel chromatography [eluent: chloroform/medianol (10: 1)] to give 148 mg of 7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimediylaminoethyl-N-mediylamino)- -isopropyl- 2,4,6-cycloheptatrien-l-one as a yellowish brown oily product (yield: 85%). MS m/z 543 (M + ) *H NMR (CDC1 3 ) δ(ppm)1.21 (6H, d, J=6.8 Hz), 2.25 (6H, s), 2.38 (4H, ), 2.53 (4H, m), 2.55 (2H, t, J=7.3 Hz), 2.76 (IH, qui, J=6.8 Hz), 3.01 (3H, s), 3.52 (2H, t, J=7.3 Hz), 3.59 (2H, s), 4.21 (IH, s), 6.43 (IH, s), 6.46 (IH, d, J=9.2 Hz), 6.95, (4H, t, J = 8.8 Hz), 7.33 (4H, dd, J = 8.8 and 5.4 Hz), 7.36 (IH, d, J=9.2 Hz). Example 6C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l -methyl]-2-(N-2- dimedιylaminoethyl-N-edιylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (150 mg, 0.31 mmol) and N,N-dimethyl-N'-ethylethylenediamine (0.1 ml, 0.64 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/medianol (10: 1)] to give 157 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethyl-N-edιylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown oily product (yield: 89%). MS m/z 562 (M + ) l E NMR (CDC1 3 ) δ(ppm) 1.18 (3H, t, J=7.0 Hz), 1.21 (6H, 3, J=7.0 Hz), 2.29 (6H, s), 2.38 (4H, ), 2.53 (4H, m), 2.55 (2H, t, J=7.2 Hz), 3.51 (2H, t, J=7.0 Hz), 3.58 (2H, s), 4.21 (IH, s), 6.42 (IH, d, J=9.7 Hz), 6.44 (IH, s), 6.95 (4H, t, J=8.7 Hz), 7.33 (4H, dd, J = 8.7 and 5.7 Hz), 7.33 (IH, d, J=9.7 Hz). Example 7C Prcκluctionof2-(N-2-diethylaminoethyiamino)-7-[4-(4,4'-difiuorobenzhydryl)piperazino-l- methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (150 mg, 0.31 mmol) and N,N-died yledιylenediamine (0.088 ml, 0.63 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 4 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/medianol (10:1)] to give 141 mg of 2-(N-2-diethylaminoethylamino)-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-4-isopropyl- 2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 80%). MS m/z 562 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.06 (6H, d, J=7.3 Hz), 1.27 (6H, d, J=6.8 Hz), 2.42 (4H, m), 2.57 (4H, m), 2.60 (4H, q, J=7.3 Hz), 2.79 (2H, t, J=6.3 Hz), 2.85 (IH, qui, J = 6.8 Hz), 3.33 (2H, q, J=6.3 Hz), 3.71 (2H, s), 4.23 (IH, s), 6.48 (IH, s), 6.61 (IH, d, J = 10.3 Hz), 6.95 (4H, t, J=8.7 Hz), 7.34 (4H, dd, J=8.7 and 5.4 Hz), 7.62 (IH, d, J = 10.3 Hz), 7.67 (IH, broad t). Example 8C Production of 2-[N-2-(N'-2-aminoethylamino)ethylamino]-7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (162 mg, 0.34 mmol) and diediylenetriamine (0.073 ml, 0.68 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 7 hours. After the solvent was distilled off under reduced pressure, d e residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (10:1) - chloroform/methanol/aqueous ammonia (4:1:0.1)] to give 141 mg of 2-[N-2-(N'-2-aminoethylamino)ethylamino]-7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown oily product (yield: 76%). MS m/z 549 (M + ) l H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.56 (4H, m), 2.72 (2H, m), 2.81 (2H, m), 2.85 (IH, qui, J=6.8 Hz), 3.01 (2H, t, J=5.9 Hz), 3.42 (2H, q, J=5.9 Hz), 3.69 (2H, s), 4.23 (IH, s), 6.51 (IH, s), 6.63 (IH, d, J= 10.3 Hz), 6.95 (4H, t, J=8.5 Hz), 7.34 (4H, dd, J=8.5 and 5.7 Hz), 7.60 (IH, broad t), 7.62 (IH, d, J= 10.3 Hz). Example 9C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2- pyridylamino)edιylamino]-2,4,6-cycloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (153 mg, 0.32 mmol) and N-(2-pyridyl)ethylenediamine (226 mg, 1.65 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50: 1)] to give 180 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2- pyridylamino)ethylamino]-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 96%). MS m/z 583 (M + ) ] H NMR (CDC1 3 ) δ(ppm) 1.25 (6H, d, J=6.9 Hz), 2.41 (4H, m), 2.56 (4H, m), 2.82 (IH, qui, J=6.9 Hz), 3.62 (2H, m), 3.69 (2H, s), 3.72 (2H, m), 4.23 (IH, s), 4.72 (IH, broad t), 6.39 (IH, d, J = 8.4 Hz), 6.57-6.66 (3H), 6.95 (4H, t, J = 8.9 Hz), 7.31-7.41 (5H), 7.62 (IH, d, J= 10.0 Hz), 7.64 (IH, broad t), 8.14 (IH, d, J=3.5 Hz). Example 10C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-mediyl]-4-isopropyl-2-[N-2-(2- pyrimidylamino)ethylamino]-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (156 mg, 0.33 mmol) and N-(2-pyrimidyl)ethylenediamine (108 mg, 0.78 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (10: 1)] to give 159 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2- pyrimidylamino)edιylamino]-2,4,6-cycloheptatrien-l-oneas a yellowish brown amoφhous powder (yield: 84%). MS m/z 584 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.27 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.56 (4H, s), 284 (IH, qui, J=6.8 Hz), 3.61 (2H, m), 3.69 (2H, s), 3.75 (2H, m), 4.23 (IH, s), 5.62 (IH, broad t), 6.57 (IH, t, J=4.8 Hz), 6.64 (IH, d, J= 10.3 Hz), 6.70 (IH, s), 6.95 (4H, t, J = 8.8 Hz), 7.34 (4H, dd, J = 8.8 and 5.4 Hz), 7.62 (IH, d, J = 10.3 Hz), 7.71 (IH, broad t), 8.31 (IH, d, J=4.8 Hz). Example 11C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino- 1 -medιyl]-4-isopropyl-2- [N-2-(2-pyridyl)edιylamino]-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (153 mg, 0.32 mmol) and 2-(2-aminoedιyl)pyridine (0.077 ml, 0.64 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50:1)] to give 134 mg of 7-[4- (4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2-pyridyl)ethylamino]-2,4,6- cycloheptatrien-1-one as a yellowish brown amoφhous powder (yield: 75%). MS m/z 568 (M + ) l H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.9 Hz), 2.41 (4H, m), 2.55 (4H, m), 2.85 (IH, qui, J=6.9 Hz), 3.20 (2H, t, J=6.6 Hz), 3.68 (2H, s), 3.75 (2H, q, J=6.6 Hz), 4.23 (IH, s), 6.55 (IH, s), 6.62 (IH, d, J= 10.0 Hz), 6.95 (4H, t, J = 8.7 Hz), 7.16 (IH, dd, J=7.6 and 4.9 Hz), 7.21 (IH, d, J=7.6 Hz), 7.33 (4H, dd, J = 8.7 and 5.3 Hz), 7.57 (IH, broad t), 7.59-7.65 (2H), 8.59 (IH, d, J=4.3 Hz). Example 12C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(N-2- py r idylmethyl amino)-2 ,4,6-cycloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (158 mg, 0.33 mmol) and 2-(2-aminomedιyl)pyridine (0.051 ml, 0.50 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 4 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel preparative diin-layer chromatography [eluent: chloroform/methanol (50: 1); three times developing] to give 82 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyI-2-(N- 2-pyridylmedιylamino)-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 45%). MS m/z 554 (M + ) l K NMR (CDC1 3 ) δ(ppm) 1.12 (6H, d, J=6.8 Hz), 2.42 (4H, m), 2.57 (4H, m), 2.76 (IH, qui, J=6.8 Hz), 3.72 (2H, s), 4.23 (IH, s), 4.69 (2H, d, J=5.9 Hz), 6.47 (IH, s), 6.63 (IH, d, J= 10.3 Hz), 6.96 (4H, t, J=8.7 Hz), 7.17-7.26 (2H), 7.33 (4H, dd, J=8.7 and 5.3 Hz), 7.62- 7.65 (2H), 8.09 (IH, broad t), 8.62 (IH, d, J=4.9 Hz). Example 13C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2- hydroxy ethyl amino)-4-isopropyl -2 ,4 ,6-cy cloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (265 mg, 0.55 mmol) and 2-aminoedιanol (0.05 ml, 0.83 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (20:1)] to give 185 mg of 7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-hydroxyethyiamino)-4-isopropyl-2,4,6- cycloheptatrien-1-one as a yellowish brown amoφhous powder (yield: 66%). MS m/z 507 (M + ) l H NMR (CDC1 3 ) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.56 (4H, m), 2.86 (IH, qui, J = 6.8 Hz), 3.51 (2H, q, J = 5.4 Hz), 3.69 (2H, s), 3.94 (2H, t, J = 5.4 Hz), 4.23 (IH, s), 6.57 (IH, s), 6.65 (IH, t, J= 10.0 Hz), 6.95 (4H, t, J = 8.7 Hz), 7.33 (4H, dd, J = 8.7 and 5.5 Hz), 7.59 (IH, broad t), 7.63 (IH, d, J = 10.0 Hz). Example 14C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(N-2- methoxyethylamino)-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (161 mg, 0.34 mmol) and 2-methoxyethylamine (0.088 ml, 1.01 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (10:1)] to give 115 mg of 7-[4- (4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(N-2-methoxyethylamino)-2,4,6- cycloheptatrien-1-one as a yellowish brown amoφhous powder (yield: 66%). MS m/z 521 (M + ) J H NMR (CDCI3) δ(ppm) 1.26 (6H, d, J=6.8 Hz), 2.41 (4H, m), 2.57 (4H, m), 2.85 (IH, qui, J=6.8 Hz), 3.41 (3H, s), 3.49 (2H q, J=5.6 Hz), 3.69 (2H, t, J=5.6 Hz), 3.70 (2H, s), 4.23 (IH, s), 6.52 (IH, s), 6.63 (IH, d, J= 10.3 Hz), 6.95 (4H, t, J = 8.6 Hz), 7.33 (4H, dd, J = 8.6 and 5.4 Hz), 7.54 (IH, broad t), 7.62 (IH, d, J= 10.3 Hz). Example 15C Productionofmediyl2-{N-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-mediyl]-4-isopropyl- 1 -oxo-2 ,4 ,6-cy cl oh eptatr ien-2-yl amino} acetate 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (159 mg, 0.33 mmol), glycine methyl ester hydrochloride (83 mg, 0.66 mmol) and diisopropylediylamine (0.11 ml, 0.63 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 5 hours. After the solvent was distilled off under reduced pressure, die residue was diluted widi dichloromethane, washed widi 2N NaOH, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50:1)] to give 52 mg of methyl 2-{N-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopiOpyl-l- oxo-2,4,6-cycloheptatrien-2-ylamino}acetate as a yellowish brown amoφhous powder (yield: 29%). MS m/z 535 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.25 (6H, d, J=7.0 Hz), 2.43 (4H, m), 2.57 (4H, m), 2.85 (IH, qui, J=7 Hz), 3.70 (2H, s), 3.81 (3H, s), 4.10 (2H, d, J=5.7 Hz), 4.23 (IH, s), 6.31 (lH,s), 6.68 (IH, d, J=8.6 Hz), 6.96 (4H, t, J-8.7 Hz), 7.34 (4H, dd, J=8.7 and 5.5 Hz), 7.67 (1H, d, J=8.6 Hz), 7.69 (IH, broad t). Example 16C Productionofethyl3-{N-7-[4-(4,4 * -difluorobenzhydryl)piperazino-l -methyl] -4-isopropyl-l- oxo-2,4,6-cycloheptatrien-2-ylamino}propionate 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (159 mg, 0.33 mmol), 3-alanine ethyl ester hydrochloride (98 mg, 0.64 mmol) and diisopropylediylamine (0.11 ml, 0.63 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, the residue was diluted widi dichloromethane, washed widi 2N NaOH, dried over anhydrous sodium sulfate and dien concentrated under reduced pressure. The residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50: 1)] to give 154 mgof ediyl 2-{N-7-[4-(4,4'-difluorobenzhydryl)piperazino- 1 -methyl]-4-isopropyl- 1 -oxo- 2,4,6-cycloheptatrien-2-ylamino}propionate as a yellowish brown amoφhous powder (yield: 86%). MS m/z 563 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.27 (6H, d, J=6.8 Hz), 1.27 (3H, t, J=7.2 Hz), 2.41 (4H, m), 2.56 (4H, m), 2.72 (2H, t, J=6.7 Hz), 2.87 (IH, qui, J=6.8 Hz), 3.65 (2H, q, J=6.7 Hz), 3.69 (2H, s), 4.18 (2H, q, J=7.2 Hz), 4.23 (IH, s), 6.51 (IH, s), 6.65 (IH, d, J= 10.3 Hz), 6.95 (4H, t, J = 8.6 Hz), 7.34 (4H, dd, J = 8.6 and 5.4 Hz), 7.45 (IH, broad t), 7.64 (IH, d, J=10.3 Hz). Example 17C Productionof7-[4-(4,4'-difluorobenzhydryl)piperazino- 1 -methyl]-4-isopropyl-2-piperidino- 2 ,4,6-cycloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (100 mg, 0.21 mmol) and piperidine (0.031 ml, 0.31 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, d e residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (50:1)] to give 68 mg of 7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-piperazino-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 61%). MS m/z 531 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.22 (6H, d, J = 6.8 Hz), 1.65 (2H, m), 1.75 (4H, m), 2.39 (4H, m), 2.53 (4H, m), 2.77 (IH, qui, J=6.8 Hz), 3.19 (4H, m), 3.60 (2H, s), 4.22 (IH, s), 6.58 (IH, d, J=9.2 Hz), 6.65 (IH, s), 6.96 (4H, t, J = 8.9 Hz), 7.34 (4H, dd, J=8.9 and 5.4 Hz), 7.45 (IH, d, J=9.2 Hz). Example 18C Production of 7-[4-(4,4'-difluorobenzhydryl)piperaz_no-l-medιyl]-4-isopropyl-2-moφholino- 2 ,4,6-cycloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (213 mg, 0.45 mmol) and moφholine (0.058 ml, 0.67 mmol) were dissolved in toluene (2 ml) and die resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform methanol (50:1)] to give 157 mg of 7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-morpholino-2,4,6-cycloheptatrien- 1-one as a yellowish brown amoφhous powder (yield: 66%). MS m/z 533 (M + ) ] H NMR (CDC1 3 ) δ(ppm) 1.23 (6H, d, J=6.9 Hz), 2.39 (4H, m), 2.53 (4H, m), 2.79 (IH, qui, J=6÷9 Hz), 3.22 (4H, m), 3.58 (2H, s), 3.90 (4H, m), 4.22 (IH, s), 6.62 (IH, s), 6.67 (IH, d, J=9.2 Hz), 6.96 (4H, t, J=8.9 Hz), 7.34 (4H, dd, J = 8.9 and 5.4 Hz), 7.61 (IH, broad t), 7.50 (IH, d, J=9.2 Hz). Example 19C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyI-2-(l- piperadino)-2,4,6-cycloheptatrien-l-one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (353 mg, 0.74 mmol) and piperazine (140 mg, 1.63 mmol) were dissolved in toluene (2 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/medianol (20:1)] to give 97 mg of 7-[4-(4,4'- difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(l-piperadino)-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 25%). MS m/z 532 (M + ) ! H NMR (CDC1 3 ) δ(ppm) 1.22 (6H, d, J=6.8 Hz), 2.39 (4H, m), 2.53 (4H, m), 2.78 (IH, qui, J=6.8 Hz), 3.07 (4H, m), 3.18 (4H, m), 3.58 (2H, s), 4.22 (lH,s), 6.63 (IH, s), 6.64 (IH, d, J=9.2 Hz), 6.96 (4H, t, J=8.9 Hz), 7.34 (4H, dd, J=8.9 and 5.4 Hz), 7.48 (IH, d, J=9.2 Hz). Example 20C Production of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-[4-(3-ethylamino-2- pyridyl)piperazino] -4-isopropyl-2 ,4,6-cycloheptatrien- 1 -one 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one (200 mg, 0.42 mmol) and l-(3-edιylamino-2-pyridyl)piperazine (129 mg, 0.63 mmol) were dissolved in toluene (6 ml) and the resulting solution was heated at reflux for 12 hours. After the solvent was distilled off under reduced pressure, die residue was purified by subjecting it to silica gel column chromatography [eluent: hexane/ethyl acetate (1:1) - hexane/ediyl acetate (3:7)] to give 57 mg of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-medιyl]-2-[4-(3- ethylamino-2-pyridyl)piperazino]-4-isopropyl-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield : 21%). MS m/z 652 (M + ) *H NMR (CDC1 3 ) δ(ppm) 1.24 (6H, d, J=6.8 Hz), 1.30 (3H, t, J-7.0 Hz), 2.40 (4H, m), 2.54 (4H, m), 2.80 (IH, qui, J=6.8 Hz), 3.15 (2H, m), 3.30 (4H, m), 3.43 (4H, m), 3.61 (2H, s), 4.22 (IH, s), 6.65 (IH, d, J=9.3 Hz), 6.72 (IH, s), 6.83 (IH, dd, J=7.8 and 1.4 Hz), 6.95 (4H, d, J = 8.6 Hz), 7.33 (4H, dd, J=8.6 and 5.5 Hz), 7.48 (IH, d, J=9.3 Hz), 7.73 (IH, dd, J=4.9 and 1.4 Hz). Example 21C Production of 7-[4-(4,4'-difluorobenzhydryl)-2,6-dimethylpiperazino-l-methyl]-4- isopropyl-2-methoxy-2,4,6-cycloheptatrien- 1 -one 7Chloromethyl-4-isopropyl-2-metiioxy-2,4,6-cycloheptatrien-l-one (174 mg, 0.77 mmol) and l-(4,4'-difluorobenzhydryl)-3,5-dimediylpiperazine (294 mg, 0.93 mmol) and triediylamine (0.13 ml, 0.93 mmol) were dissolved in toluene (5 ml) and die resulting solution was heated at reflux for 12 hours. The reaction solution was diluted widi dichloromediane, washed widi a saturated aqueous solution of NaHCO 3 , dried over anhydrous sodium sulfate and dien concentrated under reduced pressure. The residue was purified by subjecting it to silica gel column chromatography [eluent: chloroform/methanol (100:1)] to give 66 mg of 7-[4-(4,4'- difluorobeιι_dιydryl)-2,6-dimemylpiperazino-l^nethyl]-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien- 1-one as a yellowish brown amoφhous powder (yield: 17%). MS m/z 506 (M + ) l H NMR (CDC1 3 ) δ(ppm) 0.74 (6H, d, J=5.9 Hz), 1.27 (6H, d, J=6.8 Hz), 1.76 (2H, t, J= 10.8 Hz), 2.68 (2H, d, J= 10.8 Hz), 2.76 (2H, m), 2.86 (IH, qui, J=6.8 Hz), 3.74 (2H, s), 3.94 (3H, s), 4.17 (IH, s), 6.72 (IH, s), 6.87 (IH, d, J=9.7 Hz), 6.98 (4H, t, J=8.6 Hz), 7.35 (4H, dd, J=8.6 and 5.7 Hz), 8.09 (IH, d, J=9.7 Hz). Example 22C Production of 7-[4-(4,4'-difluorobenzhydryl)-2-methylpiperazino-l-methyl]-4-isopropyl-2- methoxy-2,4,6-cycIoheptatrien-l-one 7-Chloromedιyl-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one (317 mg, 1.4 mmol), l-(4,4'-difluorobenzhydryl)-3-medιylpiperazine (423 mg, 1.4 mmol) and triethylamine (0.2 ml, 1.43 mmol) were dissolved in chloroform (5 ml) and die resulting solution was heated at reflux for 12 hours. The reaction solution was diluted widi dichloromediane, washed widi a saturated aqueous solution of NaHCO 3 , dried over anhydrous sodium sulfate and dien concentrated under reduced pressure. The residue was purified by subjecting it to silica gel column chromatography [eluent: hexane/ethyl acetate (2:3)] to give 273 mg of 7-[4-(4,4'-difluorobenzhydryl)-2- methylpiperazino-l-methyl]-4-isopropyl-2-medιoxy-2,4,6-cycloheptatrien-l-one as a yellowish brown amoφhous powder (yield: 40%). MS m/z 492 (M + ) l H NMR (CDC1 3 ) δ(ppm) 0.99 (3H, d, J=6.5 Hz), 1.26 (6H, d, J=6.8 Hz), 1.94 (IH, t, J=8.4 Hz), 2.14 (IH, t, J = 8. Hz), 2.40 (IH, t, J = 10.5 Hz), 2.5-2.75 (4H), 2.85 (IH, qui, J = 6.8 Hz), 3.49 IH, d, J= 17.6 Hz), 3.91 (IH, d, J= 17.6 Hz), 3.93 (3H, s), 4.20 (IH, s), 6.70 (IH, s), 6.84 (IH, d, J=9.7 Hz), 6.96 (4H, m), 7.34 (4H, m), 7.80 (IH, d, J = 9.7 Hz). Example 23C Production of 7-[4-(4,4'-difluorobenzhydryl)hexahydro-lH-l,4-diazepin-l-ylmethyl]-4- isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one 7-Chloromethyl-4-isopropyl-2-medιoxy-2,4,6-cycIoheptatrien-l-one (250 mg, 1.1 mmol), l-(4,4'-difluorobenzhydryl)hexahydro-lH-,4-diazepine (667 mg, 2.21 mmol) and triethylamine (0.23 ml, 1.65 mmol) were dissolved in chloroform (15 ml) and die resulting solution was heated at reflux for 12 hours. The reaction solution was diluted widi dichloromediane, washed widi a saturated aqueous solution of NaHCO 3 , dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by subjecting it to silica gel column chromatography [eluent: hexane/ethyl acetate (2:3)] to give 108 mg of 7-[4-(4,4'- difluorobenzhydryl)hexahydro-lH-l,4-diazepin-l-ylmethyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one as a yellowish brown amoφhous powder (yield: 20%). MS m/z 492 (M + ) J H NMR (CDC1 3 ) δ(ppm) 1.28 (6H, d, J=7.0 Hz), 1.77 (2H, m), 2.65-2.95 (9H), 3.79 (2H, s), 3.94 (3H, s), 4.62 (IH, s), 6.70 (IH, s), 6.85 (IH, d, J= 10.0 Hz), 6.96 (4H, t, J = 8.8 Hz), 7.36 (4H, dd, J=8.8 and 5.4 Hz), 7.78 (IH, d, J= 10.0 Hz).

Claims: CLAIMS 1. A tropolone derivative of the formula: wherein R 10 is a moiety of the formula II or III wherein R 41 is (a) -OR 3 , (b) -ORe, (c) -NR 7 R 8 , (d) -N ^MCH^-R^, or (e) a group represented by the formula IV wherein R5 is (a) hydrogen, or (b) C r C 5 alkyl; wherein Rg is (a) hydrogen, (b) C r C 5 alkyl, (c) C r C 5 alkyl substituted by OH, COOR 5 or CN, or containing O, S, or N as heteroatoms, (d) C 7 -C 2 o aralkyl, or (e) substituted C 7 -C 20 aralkyl containing O, S or N as heteroatoms; wherein R 7 and Rg are the same or different and are: (a) hydrogen, (b) C r C 5 alkyl, (c) C r C 5 alkyl substituted by -OH, -COOR 5 , or -CN, (d) C 7 -C 20 aralkyl, (e) C 7 -C 2Q aralkyl containing O, S or N as heteroatoms, or ( ) R 7 and Rg together form a 5 to 7 membered ring may contain 1-3 of die following ring substituents; (i) -CH 2 -, 00 -O-, or (iii) -NR9-; wherein R9 is (a) hydrogen, (b) C--C 5 alkyl, or (c) C7-C20 aralkyl, or (d) C 7 -C 20 aralkyl containing O, S or N as heteroatoms; wherein RJJ is (a) hydrogen, (b) C r C 3 alkyl, (c) substituted or unsubstituted aryl, or (d) substituted or unsbustituted heterocycle; wherein R 21 and R 31 are die same or different and are (a) hydrogen, or (b) C,-C 3 alkyl; wherein Rg j is (a) substituted or unsubstituted aryl, (b) substituted or unsubstituted heterocycle, (c) -OR 71 , (d) -CO 2 R 81 , or wherein R 1, R71, and R 1 are the same or different and are (a) hydrogen, or (b) C r C 3 alkyl; wherein R^ and R 101 are die same or different and are (a) hydrogen, (b) C r C 3 alkyl, (c) a substituted or unsubstituted aryl group, or (d) a substituted or unsubstituted heterocycle; wherein R 201 is (a) hydrogen, (b) C r C 5 alkyl, (c) C 2 -C 20 aralkyl, (d) C 6 -C 10 arylsulfonyl, or (e) C 6 -C 10 arylsulfonyl containing O, S, or N as additional heteroatoms; wherein Ar j and Ar 2 are the same or different aryl group optionally substituted by (a) halogen, (b) trihalomethyl, (c) C 6 -C 10 aryl, or (d) Cg-C jQ aryl substituted by C j -C 3 alkoxy; wherein X is (a) -O-, (b) -CH 2 -, or (c) -N-(CH 2 ) p -R π ; wherein m is 1, 2, 3, or 4; wherein n is 0, 1, or 2; wherein p is 0, 1, or 2; and wherein q is i or 2; or a pharmaceutically acceptable ester or salt diereof. 2. A tropolone derivative of Claim 1 wherein R 4i is OR 3 (wherein R 3 is definitions (a) to (e)), R 10 is a moiety of die Formula II, R 21 and R 3 j are hydrogen and q is 1, represented by die formula: or a pharmaceutically acceptable ester or salt thereof. 3. A tropolone derivative of Claim 1, wherein R 41 is -0 or -NR 7 R 8 , R 10 is a moiety of Formula III, R j is definitions (a) to (c), R 3 and R 4 are definitions (a), (b), and (f) to (k), represented by die formula: or a pharmaceutically acceptable ester or salt thereof. 4. A tropolone derivative of Claim 1 , wherein R 41 is -N (R5i)-(CH 2 ) m -R6 1 or a group of die Formula IV; R 10 is a group of the Formula II, represented by the formula: or a pharmaceutically acceptable ester or salt thereof. 5. A pharmaceutical composition for preventing or treating ischemic diseases which is characterized by containing die tropolone derivative of Claim 1 or a pharmaceutically acceptable ester or salt thereof as an active ingredient. 6. A compound of Claim 2, selected from the group consisting of 7-[4-(4-chlorober___hydryl)piperazino-l-methyl]-2-hydroxy_4-isopropyl-2,4,6-cycloheptatrien- 1-one; 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-medioxy-2,4,6-cycloheptatrien- 1-one; 7-{l-[4-(4-chlorobenzhydryl)piperazinomethyl]-α-phenyl}-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien- 1 -one; 7-{l-[4-(4-chlorobenzhydryl)]piperazinomedιyl-c--methyl}-4-isopropyI-2-medιoxy-2,4,6- cycloheptatrien-1-one; 7-{l-[4-(4-chlorobenzhydryl)]piperazinomethyl]-α-butyl}-4-isopropyl-2-methoxy-2,4,6- cy cloheptatrien- 1 -one; 7-(4-benzhydrylpiperazino-l-methyl)-4-isopropyl-2-methoxy-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien-1-one; 7-{4-[4,4'-di(trifluoromediyl)benzhydryl]piperazino-l-methyl}-4-isopropyl-2-medioxy-2,4,6- cycloheptatrien- 1 -one; 4-isopropyl-2-methoxy-7-[4-(4-trifluoromethylbenzhydryl)piperazino-l-methyl]-2,4,6- cycloheptatr ien- 1 -one; 7-[4-(4-chloro-4'-methoxybenzhydryl)piperazino-l-medιyl]-4-isopropyl-2-mεdιoxy-2,4,6- cycloheptatrien-1-one; 7-[4-(4-fluoro-3',4'-dimethoxyber_zhydryl)piperazino-l-methyl]-4-isopropyl-2-medioxy- 2,4,6-cycloheptatrien-l -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-ethoxy-4-isopropyl-2,4,6- cycloheptatrien- 1 -one; 2-butoxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2,4,6- cy cloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-phenoxy-2,4,6- cycloheptatrien-1-one; 2-benzyloxy-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyI-2,4,6- cycloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyI]-2-[2-(3,4-dimethoxyphenyl)ethoxy]-4- isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-[3-(dimethylamino)propoxy]-4- isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino- l -methyl]-2-[3-(N-methyl-N- phenethylamino)propoxy]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4-chlorobenzhydryl)piperazino-l-mediyl]-2-medioxy-2,4,6-cycloheptatrien-l-one; and 7-[4-(4-chlorobenzhydryl)piperazino-l-medιyl]-2-methoxy-4-phenyl-2,4,6-cycloheptatrien-l- one. 7. A compound of Claim 3, selected from the group consisting of 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenedιylbenzodιiazoline; 2-(2'-oxo-3 , -methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-methylbenzodιiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-benzylbenzodiiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(2-picolyl)benzodιiazoline; 2-(2'-oxo-3'-medιoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(3-picolyl)benzothiazoline; 2-(2'-oxo-3'-medιoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(4-picolyl)benzodιiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-[2-pyridyl)ethyl]; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3' ,5 ' ,7'-cycloheptatrienyl)-3-[2-(3 ,4- dimed oxyphenyl)ethyl]benzodιiazoline; 2-(2 ' -oxo-3 ' -methoxy-5 ' -isopropyl -3 ' ,5 ' ,7 ' -cycloh eptatrienyI)-3-(2- quinolyl)methyIbenzothiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-[3-(N-methyl-N- phenethylamino)propyl]benzodιiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-[2-(N,N- dimedιylamino)ethyl]benzothiazoline; 2-(2'-oxo-3 '-methoxy-5'-isopropyl-3',5' ,7'-cycloheptatrienyl)-3-[2-(N,N- dimethylamino)propyl]benzothiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-{3-(4-(4,4'- difluorobenzhydryl)piperadin-l-yl)propyl}benzothiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-methylbenzothiazoline 2-(2'-oxo-3 '-(l -piperadinyl)-5'-isopropyl-3 ' ,5',7'-cycloheptatrienyl)-3- phenediylbenzothiazoline; 2-(2'-oxo-3'-(2-(N,N-dimethyl)aminoethyl)amino-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3- phenediylbenzodiiazoline; 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-(2-phenethyl-l , l- dioxobenzothiazoline; and 2-(2'-oxo-3'-methoxy-5'-isopropyl-3',5',7'-cycloheptatrienyl)-3-phenethyl-l- oxobenzothiazoline. 8. A compound of Claim 4, selected from the group consisting of 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimedιylaminoethylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-3-dimediylaminopropylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4, 4' -difluorobenzhydryl)piperazino-l -methyl ]-4-isopropyl -2-(N-2- medιylaminoedιylamino)-2,4,6-cycloheptatrien-l-one; 2-(N-2-aminoethylamino)-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl- 2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- ethylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 2-N-2-diethylaminoedιylamino)-7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4- isopropyl-2,4,6-cycloheptatrien-l -one; 2-[N-2-(N'-2-aminoethylamino)ethylamino]-7-[4-(4,4'-difluorobenzhydryl)piperazino-l- methyl]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l -methyl] -4-isopropyI-2-[N-2-(2- pyridylamino)ed ylamino]-2,4,6-cycloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-[N-2-(2- pyrimidylamino)ethylamino]-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyI]-4-isopropyl-2-[(N-2-(2- pyridyl)edιylamino]-2,4,6-cycloheptatrien-l-one; 7-[4-(4, 4' -difluorobenzhy dry l)piperazino-l -methyl] -4-isopropyl -2-(N-2- pyridylmed ylamino)-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-hydroxyethylam_no)-4-isopropyl- 2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobeιιzhydryl)piperazino-l-meώyl]--Hisopropyl-2-(N-2-medιoxy«hylamino)- 2,4,6-cycloheptatrien- 1 -one; methyl 2-{N-7-[4-(4,4'-difluorobei_zhydryl)piperazino-l-methyl]-4-isopropyl-l-oxo-2,4,6- cycloheptatrien-2-ylamino}acetate; ethyl S-JN^-^^^'-difluorobenzhydry piperazino-l-methyll^-isopropyl-l-oxo^^.ό- cycloheptatrien-2-ylamino}propionate; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyI-2-piperidino-2,4,6- cycloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-morpholino-2,4,6- cycloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-4-isopropyl-2-(l-piperazino)-2,4,6- cycloheptatrien- 1 -one; 7-[4-(4, 4' -difluorobenzhydryl)piperazino-l -methyl] -2-[4-(3-ethylamino-2- pyridyl)piperazino]-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)-2,6-dimedιylpiperazino-l-methyl]-4-isopropyl-2-methoxy- 2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)-2-methylpiperazino-l-methyl]-4-isopropyl-2-methoxy-2,4,6- cycloheptatrien- 1 -one; 7-[4-(4,4'-difluorobenzhydryl)hexahydro-lH-l,4-diazepin-l-ylmethyl]-4-isopropyl-2- methoxy-2,4,6-cycloheptatrien-l-one; 7-[4-(4, 4' -difluorobenzhy dry l)-2,6-dimethylpiperazino-l -methyl] -2-(N-2- dimedιylaminoedιyl-N-methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)-2-medιylpiperazino-l-medιyl]-2-(N-2-dimemylaminoedιyl-N- methylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)hexahydro-lH-l ,4-diazepin-l-ylmethyl]-2-(N-2- dimediylaminoediyl-N-mediylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4-chlorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimediylaminoethyl-N-methylamino)- 4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-(4-benzhydrylpiperazino-l-methyl)-2-(N-2-dimethylaminoethyl-N-methylamino)-4- isopropyl-2,4,6-cycloheptatrien-l-one; 2-(N-2-dimethylam ino ethyl -N-m ethyl am i no) -4-isopropyl -7 - [4-(4 - trifluoromedιylbenzhydryl)piperazino-l-methyl]-2,4,6-cycloheptatrien-l-one; 7-[4-(4-chloro-4'-methoxybenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- medιylamino)-4-isopropyl-2,4,6-cycloheptatrien-l-one; 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyl-N- medιylamino)-2,4,6-cycloheptatrien-l-one; and 7-[4-(4,4'-difluorobenzhydryl)piperazino-l-methyl]-2-(N-2-dimethylaminoethyI-N- methylamino)-4-phenyl-2,4,6-cycloheptatrien-l-one.

Inventors: ITOH NORIIE, KUNIHARA MINEO, KUSHIDA HIROSHI, MC WHORTER WILLIAM W, NOMURA SYUNJI, OZAWA KAZUNORI, TANIGUCHI MIKIO, TSUZUKI TAZUO, ITOH, NORIIE, KUNIHARA, MINEO, KUSHIDA, HIROSHI, MC WHORTER, WILLIAM, W., NOMURA, SYUNJI, OZAWA, KAZUNORI, TANIGUCHI, MIKIO, TSUZUKI, TAZUO
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1991
Main classification: C07D295
IPC codes: A61K31, A61P9, A61P25, A61P43, C07D213, C07D239, C07D241, C07D243, C07D277, C07D295, C07D401, C07D417