Piperidine derivatives and their use as antiarrhythmic agents

Abstract: A piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof: wherein is any of several specified aromatic-containing groups; X is selected from one of several hetero atom-containing groups or C₂ alkylene or a cyano-containing group; and Q is phenyl, cyclohexyl, piperidinyl, tetrahydropyranyl, pyridyl, pyrrolyl, N-methylpyrrolyl, thienyl, furyl, 1-hexyl, or cyano; from 1 to 3 hydrogen atoms in Q may be independently substituted by alkyl of from 1 to 3 carbon atoms, perfluoroalkyl of from 1 to 3 carbon atoms, acylamino of from 1 to 6 carbon atoms, perfluoroacylamino of from 1 to 3 carbon atoms, alkoxy of from 1 to 3 carbon atoms, alkanesulfonylamino of from 1 to 3 carbon atoms, perfluoroalkanesulfonylamino of from 1 to 3 carbon atoms, acetoxy of from 1 to 3 carbon atoms, aminocarbonyl, aminosulfonyl, fluoro, chloro, cyano, hydroxy, nitro, amino, imidazolylmethyl, cinnamoylamino, p-fluorobenzoyl, cyanomethyl, cyanoethyl, methoxyacetoxy, alkoxycarbonyl of from 1 to 3 carbon atoms; 1 is an integer of from 0 to 1; m is an integer of from 0 to 1; n is an integer of from 0 to 6. The derivatives are useful as antiarrhythmic agents.

Description: Field of the Invention The present invention relates to novel antiarrhythmic agents, more particularly to novel piperidine derivatives and their use in the treatment of arrhythmia. Background of the Invention Arrhythmia is the disfunction of cardiac normal conduction, which is a life-threatening disease, because it disturbs the rhythmic beating of the heart, worsening hemodynamics. Therefore, therapy for cardiac arrhythmia is clinically essential. Antiarrhythmic drugs have been grouped together according to the pattern of mechanism: Na channel blocker, Beta blocker, Ca channel blocker and drugs which prolong Repolarization. Drug therapy of cardiac arrhythmias is not established, because many drugs have severe adverse effects, such as undesirable hemodynamic effects, hypotension, gastrointestinal symptoms, effects on the central nervous system and arrhythmogenic effects. Also, at higher plasma concentrations of drug, cardiac toxicity may become severe, so the monitoring of plasma concentration is essential for drug therapy. It is therefore required to develop new antiarrhythmic drugs having excellent pharmaceutical effects and safety which can be industrially prepared at low cost in a simple manner. EP-A-0 370 712, EP-A-0 371 805, EP-A-0 294 183 describe piperidine derivatives having hypotensive activity. JP-A-61 227 565 discloses piperidine derivatives which are effective as serotonin antagonists. DE-A-2 027 446 discloses diphenylmethylene-N-benzyl piperidines having antiarrhythmic activity. Disclosure of the Invention It has now been found that certain piperidine derivatives have antiarrhythmic activity, which derivatives are represented by the following general fomula (I): wherein is either of the following groups: or wherein B is a fused aromatic or heterocyclic ring selected from the group consisting of benzene, pyridine and thiophene; -Z- is selected from: or X is selected from: wherein R 1 and R 2 are the same or different and are independently selected from hydrogen, methyl, ethyl, or propyl; R 3 is hydrogen, alkyl of from 1 to 12 carbon atoms, or aryl of from 6 to 12 carbon atoms; Q is phenyl, cyclohexyl, piperidinyl, tetrahydropyranyl, pyridyl, pyrrolyl, N-methylpyrrolyl, thienyl, furyl, 1-hexyl, or cyano; from 1 to 3 hydrogen atoms in Q may be independently substituted by alkyl of from 1 to 3 carbon atoms, perfluoroalkyl of from 1 to 3 carbon atoms, acylamino of from 1 to 6 carbon atoms, perfluoroacylamino of from 1 to 3 carbon atoms, alkoxy of from 1 to 3 carbon atoms, alkanesulfonylamino of from 1 to 3 carbon atoms, perfluoroalkanesulfonylamino of from 1 to 3 carbon atoms, acetoxy of from 1 to 3 carbon atoms, aminocarbonyl, aminosulfonyl, fluoro, chloro, cyano, hydroxy, nitro, amino, imidazolylmethyl, cinnamoylamino, p-fluorobenzoyl, cyanomethyl, cyanoethyl, methoxyacetoxy, alkoxycarbonyl of from 1 to 3 carbon atoms; l is an integer of from 0 to 1; m is an integer of from 0 to 1; n is an integer of from 0 to 6. These compounds may be in their free base form or in the form of a pharmaceutically acceptable salt thereof. A compound of the above formula can be prepared by the following procedure: The pharmaceutically acceptable salts of the piperidine derivatives of this invention are acid addition salts formed from the compound and an organic or inorganic acid well known in the art as providing a pharmaceutical addition salt, such as a hydrochloride, sulfate, citrate, tartarate, mesylate, maleate, fumarate, or the like. These salts are readily prepared by mixing a solution of equimolar amounts of the free base form of the compound and desired acid in a suitable solvent such as water, alcohol, or ether, followed by recovery of the product by collecting the precipitated salt or by evaporation of the solvent. When used as antiarrhythmic drugs, the piperidine derivatives of the present invention may be administered by an oral or parenteral route, which may be determined depending upon age, body weight, condition of the patient. A daily dose may generally be from about 0.001 about 2000 mg/patient or animal for oral administration; in the case of parenteral administration, a daily dose may generally be from about 0.001 to about 1000 mg/patient or animal. The piperidine derivatives of the present invention may be formulated into conventional preparation forms, for example, tablets, powders, capsules, solutions, sugar-coated tablets or depots, which may be prepared in a conventional manner using conventional techniques. For example, tablets can be obtained by mixing a piperidine derivative of the present invention with known auxiliary substances, for example, inactive diluents (e.g. lactose, calcium carbonate or calcium phosphate), binders (e.g. gum arabic, corn starch or gelatin), sweeteners (e.g. sucrose or saccharine), flavours (e.g. peppermint, Gaultheria adenothrix oil or cherry), lubricating and wetting agents (e.g. magnesium stearate, talc or carboxymethyl cellulose). The present invention further provides a novel antiarrhythmic agent which is a composition comprising a pharmaceutically effective amount of a piperidine derivative as defined above. The pharmaceutical composition of the present invention is advantageous as an antiarrhythmic drug for treating mammals including humans. This can be administered perorally in the form of tablet, capsule or elixir, or parenterally in the form of a sterile solution or suspension, for the purpose of reducing or eliminating arrhythmia. The pharmaceutical composition of the present invention can be administered to patients or animals which are to be treated generally several times each in a unit dosage of from about 0.001 to about 500 mg/patient or animal, and accordingly the total dosage of the derivative may be from about 0.001 to about 2000 mg/patient or animal/day. Of course, the amount of the dosage may be varied in accordance with the condition of the disease, the weight of the patient or animal and other factors which are considered appropriate by one skilled in the art. The above-mentioned typical combinations may be formulated as a pharmaceutical composition in a conventional manner. For example, from about 0.2 to about 500 mg of the derivative of the present invention or a pharmaceutically acceptable salt thereof or a mixture thereof is blended together with a pharmaceutically acceptable vehicle, carrier, extender, binder, antiseptic, stabilizer, flavour and the like, in an amount as required for conventional pharmaceutical preparations. Examples of pharmaceutical additives to be used for the preparation of tablets, capsules and the like are: binders such as tragacanth, gum arabic, corn starch or gelatin; vehicles such as fine crystalline cellulose; extenders such as corn starch, pre-gelatinised starch or alginic acid; sweeteners such as sucrose, lactose or saccharin; flavours such as peppermint, an oil from Gaultheria adenothrix Maxim or cherry. When the preparation is in the form of a capsule, this may further contain a liquid carrier such as a fat and oil, in addition to the above mentioned materials. Other various materials can further be employed so as to form coated pills or to vary the physical form of the preparation by a different method. For example, tablets can be coated with shellac, sugar or both. A syrup or elixir can contain the active compound together with sucrose as a sweetener, methyl- or propyl-paraben as an antiseptic, a dye, and cherry or orange essence as a flavour. A sterile composition for injection can be prepared in a conventional manner, for example, by dissolving or suspending the active substance in a vehicle such as distilled water for injection, together with a natural vegetable oil such as sesame oil, coconut oil, peanut oil, cotton seed oil, or a synthetic fat vehicle such as ethyl oleate. If desired, a buffer, an antiseptic, an antioxidant or the like can be incorporated into the composition. The present invention will be further illustrated by reference to the following examples. PREPARATION OF COMPOUNDS Retention factor (Rf) was determined by silica gel thin layer chromatography (TLC : Merck Art 5715). Unless otherwise noted, mass spectroscopy was determined on JEOL-DX 300 by FD mode; 1 H NMR spectra were obtain in CDCl 3 with tetramethylsilane as internal standard on a Varian VXR-300 spectrometer. "Intermediate (1)" represents 4-(5H-dibenzo[a, d]cyclohepten-5-ylidene)piperidine. compound 1 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-(N-imidazolylmethyl)cinnamyl]piperidine To a solution of 4-(N-imidazolylmethyl)cinnamic alcohol (4.5mmol) in CHCl3,thionyl chloride (5.4mmol) was added, and stirred for 2h at room temperature. After a usual procedure, the product was used without further purification. The product obtained according to above-mentioned procedure was dissolved in methyl isobutyl ketone, and then intermediate (1) (4.0mmol),potassium carbonate(8.75mmol)and NaI(8.75mmol) were added to the solution, stirred at 90 °C for overnight. The mixture was washed with water,extracted with CH2Cl2, washed with 1M HCl, saturated aqueous solution of NaHCO3, and then brine, dried over MgSO4. The solvent was evaporated at reduced pressure, the resulting mixture was purified by column chromatography (SiO2). MS 469(M+) NMR 2.2-2.4(4H,m) 2.5-2.6(2H,m) 2.8-2.9(2H,m) 3.28(2H,d) 5.07(2H,s) 6.38(1H,dt) 6.52(1H,d) 6.95(2H,s) 7.0.7.6(15H,m) compound 2 1-[4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butanoyl]-4-hydroxypiperidine TLC(CHCl3: MeOH=9:1) Rf=-0,58 MS 442(M+) NMR 1.4-1.6(2H,m) 1.8-2,0(4H,m) 2.1-2.2(4H,m) 2.3-2.4(4H,m) 2.5-2.6(2H,m) 2.89(1H,m) 3.19(1H,m) 3.7-3.8(2H,m) 3.9-4.0(2H,m) 4.0-4.2(2H,m) 6.91(2H,s) 7.1-7.4(8H,m) compound 3 4-[4-Dibenzo[b,e]thiepin-11(6H)-ylidene]-1-piperidinyl]-1-cyclohexylbutane According to the practically same procedure described in preparation of compound 1,4-bromo-1-cyclohexylbutane and 4-dibenzo[b,e]thiepine-11(6H)-ylidenepiperidine were used. TLC(CHCl3: MeOH=9:1) Rf=0.74 MS 431(M+) NMR 0.8-1.0(2H,m) 1.1-1.4(10H,m) 1.4-1.6(1H,m) 1.6-1.8(6H,m) 2.1-2.4(4H,m) 2.51(2H,t) 2.6-2.8(4H,m) 3.39(1H,d) 4.99(1H,s) 6.9-7.1(4H,m) 7.2-7.4(4H,m) compound 4 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine After the stepwise addition of 4-Nitrocinnamyl alcohol(5.58mmol) to a ice-cooled solution of SOCl2(10g), the mixture was stirred for a few minutes The residue obtained by general procedure was condensed with intermediate(1) (6.59mmol) in the presence of potassium carbonate. Yield 2.02mmol(36.2%) MS 434(M+) NMR 2.16-2.24(4H,m) 2.31-2.42(2H,m) 2.60-2.68(2H,m) 3.18(2H,d) 6.46(1H,dt) 6.55(1H,d) 6.92(2H,s) 7.18-7.36(8H,m), 7.42-7.48(2H,m) 8.17-8.20(2H,m) compound 5 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine(compound 4) was reduced by zinc in acetic acid at room temperature for 4h. Yield 84.5% MS 404(M+) NMR 2.20-2.42(6H,m) 2.60-3.32(4H,m) 3.40(2H,d) 6.11(1H,dt) 6.43(1H,d) 6.59-6.64(2H,s) 6.91(2H,s) 7.14-7.36(10H,m) compound 6 1-(4-Acetylaminocinnamyl)-4-(5H-dibenzo-[a,d]cyclohepten-5-ylidene)piperidine 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) was N-acetylated by acetic anhydride using triethyl amine as base. Yield 92.3% MS 446(M+) NMR 2.18(3H,s) 2.20-2.55(6H,m) 4.70(1H,bs) 6.20(1H,dt) 6.42(1H,d) 6.91(2H,s) 7.15-7.36(10H,m) 7.42-7.56(2H,m) compound 7 3-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(4-nitrophenyl)propane a) 1-Bromo-3-(4-nitrophenyl)propane 1-Bromo-3-phenylpropane(19.7mmol) was added slowly to a solution of sulfuric acid(7.4g) and nitric acid(5.4g) at ambient temperature and stirred at 60 °C. The residue ( mixture of ortho and para ) was purified by column chromatography on silica gel. Yield 63.7% NMR 2.20(2H,quint.) 2.92(2H.t) 3.40(2H.t) 7.35(2H,d) 8.16(2H,d) b) compound 7 This was prepared from 1-Bromo-3-(4-nitrophenyl)propane and intermediate(1). Yield 94.6% MS 436(M+) NMR 1.84(2H,m) 2.15(4H,m) 2.30(4H,m) 2.59(2H,m) 2.70(2H.t) 6.90(2H.s) 7.2-7.4(10H,m) 8.10(2H,d) Compound 8 1-(4-Aminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane 3-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(4-nitrophenyl)propane(compound 7) was reduced by zinc. Yield 97.3% MS 406(M+) NMR 1.70(2H,m) 2.0-2.6(12H,m) 3.48(2H,br) 6.55(2H,d) 6.85(2H,s) 6.92(2H,d) 7.20(4H,m) 7.25(4H,m) Compound 9 1-(4-Acetylaminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane This was prepared from 1-(4-Aminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane(compound 8) and acetic anhydride. Yield 92.9% MS 48(M+) NMR 1.6-1.8(4H,m) 2.15(3H,s) 2.0-2.2(2H,m) 2.2-2.4(4H,m) 2.55(4H,m) 7.1-7.4(12H,m) compound 10 N-[3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propanoyl-3,4-dimethoxyanilide MS(FAB,m/z) 481(M+) NMR 2.25-2.36 (4H,m) 2.40-2.46 (2H,m) 2.52 (2H,t) 2.70 (2H,t) 2.68-2.80 (2H,m) 3.85 (3H,s) 3.88 (3H,s) 6.79 (2H,s) 6.93 (2H,s) 7.18-7.35 (8H,m) 7.52 (1H,s) compound 11 4-[4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-butyl]tetrahydropyran MS 413(M+) NMR 1.1-1.6(10H,m) 1.7-1.8(1H,m) 2.1-2.4(8H,m) 2.5-2.6(2H,m) 3.35(2H,t) 3.93(2H,d) 6.90(2H,s) 7.2-7.4(8H,m) compound 12 1-(N-Acetyl-4-piperidinyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane a) 3-(4-Piperidinyl)-1-propanol 1-(4-Pyridyl)-1-propine-3-ol was hydrogenated with rhodium on alumina as catalyst. b) 1-Acetoxy-3-(N-acetyl-4-piperidinyl)propane This was prepared from 3-(4-Piperidinyl)-1-propanol and acetic anhydride. NMR 1.0-1.8(9H,m) 2.04(3H,s) 2.07(3H,s) 2.51(1H,t) 3.00(1H,t) 3.78(1H,br d) 4.04(2H,t) 4.58(1H,br d) c) 3-(N-Acetyl-4-piperidinyl)propanol 1-Acetoxy-3-(N-acetyl-4-piperidinyl)propane was saponificated by potassium carbonate. NMR 1.0-1.2(2H,m) 1.2-1.4(2H,m) 1.4-1.8(6H,m) 2.08(3H,s) 2.53(1H,dt) 3.02(1H,dt) 3.64(2H,t) 3.79(1H,br d) 4.58(1H,br d) d) 1-(N-Acetyl-4-piperidinyl)-3-bromopropane 3-(N-Acetyl-4-piperidinyl)propanol was brominated with phosphorus tribromide. NMR 1.0-1.2(2H,m) 1.40(2H,t) 1.50(1H,m) 1.74(2H,br t) 1.78(2H,quint) 2.08(3H,s) 2.53(1H,dt) 3.02(1H,dt) 3.40(2H,t) 3.80(1H,br d) 4.59(1H,br d) e) compound 12 Yield 77.8% MS 440(M+) NMR 1.0-1,2(2H,m) 1.22(2H,m) 1.4-1.6(3H,m) 1.68(2H,m) 2.05(3H,s) 2.1-2.6(11H,m) 2.96(1H,dt) 3.74(1H,br d) 4.55(1H,br d) 6.90(2H,s) 7.2-7.4(8H,m) compound 13 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine a) 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamoyl)piperidine 2,4-Dimethoxycinnamic acid(10.0mmol) and intermediate(1) was condencedby N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride. b) compound 13 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamoyl)piperidine was reduced with lithium alminium hydride. Yield 12.3% MS 449(M+) NMR 2.13-2.23(4H,m) 2.30-2.50(2H,m) 2.62(2H,m) 3.13(2H,d) 3.78(6H,s) 6.15(1H,tt) 6.42(2H,m) 6.68(1H,d,J=15.9Hz) 6.91(2H,s) 7.18-7.35(9H,m) compound 14 1-(4-Cyanocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine a) 4-Cyanocinnamylalcohol A Heck reaction of 4-bromobenzonitrile and acrylic acid gave 4-cyanocinnamic acid. The acid was reduced to the corresponding alcohol with ethyl chloroformate and then sodium borohydride. Yield 78.6% NMR 4.38(2H,dd) 6.49(1H,m) 6.65(1H,d) 7.44(2H,d) 7.40(2H,d) b) compound 14 MS 414(M+) NMR 2.12-2.22(4H,m) 2.30-2.42(2H,m) 2.52(2H,m) 3.15(2H,d) 6.42(2H,m) 6.92(2H,s) 7.18-7.35(8H,m) 7.40(2H,d) 7.58(2H,d) compound 15 1-Cyclohexyl-4-[4-(10,11-dihydroxy-5H-dibenzo[a,d] cyclohepten-5-ylidene)-1-piperidinyl]butane A osmium tetraoxide(0.4mmol) in acetone was added to the 50% aqueous solution of acetone dissolved in 1-Cyclohexyl-4-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butane (4.8mmol) and N-methylmorpholine-N-oxide (7.2mmol). The mixture was stirred for over night at ambient temperature. MS 445(M+) 0.7-1.4(11H,m) 1.4-1.8(8H,m) 2.6-3.0(8H,m) 3.05(1H,bs) 3.26(1H,bs) 5.21 (2H,s) 7.0-7.6(4H,m) compound 16 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-11-(4-propanoylaminocinnamyl)piperidine 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) was N-acylated. Yield 43.9% MS 460(M+) NMR 1.22(3H,t) 2.2-2.6(8H,m) 2.7-2.9(2H,m) 3.23(2H,d) 4.79(1H,bs) 6.1-6.3(1H,m) 6.43(1H,dd) 6.93(2H,s) 7.1-7.55(12H,m) compound 17 4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarbonylaminocinnamyl)piperidine This compound was prepared from 1-(4-Aminocinamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and ethyl chloroformate. Yield 56.7% MS 476(M+) NMR 1.30(3H,t) 2.2-2.9(8H,m) 3.26(2H,dd) 4.22(2H,q) 6.1-6.3(1H,m) 6.46(1H,d) 6.67(1H,bs) 6.93(2H,s) 7.1-7.4(12H,m) compound 18 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methanesulfonylaminocinnamyl)piperidine This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and methanesulfonyl chloride. Yield 67.0% MS 482(M+) NMR 2.1-2.5(6H,m) 2.5-2.7(2H,m) 3.17(2H,d) 3.39(3H,s) 6.2-6.4(1H,m) 6.49(1H,d) 6.93(2H,s) 7.1-7.5(12H,m) compound 19 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycarbonylcinnamyl)piperidine According to the practical same procedure of compound 15, this compound was obtained. MS 447(M+) NMR 2.16-2.26(4H,m) 2.30-2.44(2H,m) 2.52(2H,m) 3.14(2H,d) 3.91(3H,s) 6.38(1H,m) 6.52(1H,d) 6.92(2H,s) 7.18-7.35(9H,m) 7.52(1H,d) 7.88(1H,d) 8.01(1H,s) compound 20 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycarbonylaminocinnamyl)piperidine This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and methyl chloroformate. Yield 97.5% MS 462(M+) NMR 2.2-2.9(8H,m) 3.10(2H,m) 3.78(3H,s) 6.2-6.4(1H,m) 6.56(1H,d) 6.72(1H,bs) 6.92(2H,s) 7.1-7.4(12H,m) compound 21 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-pivaloylaminocinnamyl)piperidine This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and pivaloyl chloride. Yield 92.0% MS 488(M+) NMR 1.34(9H,s) 2.2-3.2(10H,m) 6.2-6.42(1H,m) 6.55(1H,d) 6.93(2H,s) 7.1-7.44(10H,m) 7.45-7.6(2H,m) compound 22 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoroacetylaminocinnamyl)piperidine This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and trifluoroacetic anhydride. Yield 46.0% MS 500(M+) NMR 2.4-3.7(10H,m) 6.2-6.4(1H,m) 6.58(1H,dd) 6.93(2H,s) 7.17(2H,d) 7.2-7.45(8H,m) 7.69(2H,dd) 8.36(1H,bs) compound 23 1-(4-Butanoylaminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine This compound was prepared from 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine(compound 5) and butanoic acid . Yield 68.5% MS 474(M+) NMR 0.99(3H,q) 1.6-1.8(2H,m) 2.2-2.43(6H,m) 2.44-2.7(2H,m) 2.8-3.1(2H,m) 3.35(2H,d) 5.50(1H,bs) 6.1-6.3(1H,m) 6.45(1H,dd) 6.92(2H,s) 7.1-7.4(10H,m) 7.49(2H,dd) The following compounds were prepared according to the above-mentioned procedures. compound 24 1-(4-Aminocarbonylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.23 MS 432(M+) compound 25 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoromethylcinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.85 MS 457(M+) compound 26 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-cyanomethylcinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.89 MS 428(M+) compound 27 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dichlorocinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.72 MS 457(M+) compound 28 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxy-2-nitrocinnamyl)piperidine TLC(HEXANE:Ethyl acetate=1:1) Rf=0.13 MS 457(M+) compound 29 4-Dibenzo[b,e]thiepin-11(6H)-ylidene-1 -(4-nitrocinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.89 MS 454(M+) NMR 2.1-2.3(4H,m) 2.4-2.6(2H,m) 2.6-2.8(2H,m) 3.21(2H,d) 3.41(1H,d) 4.98(1H,d) 6.48(1H,dt) 6.61(1H,d) 7.0-7.1(4H,m) 7.2-7.4(4H,m) 7.4-7.5(2H,m) 8.1-8.2(2H,m) compound 30 1-(4-Aminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-ylidenepiperidine TLC(CHCl3:MeOH=9:1) Rf=0.65 MS 424(M+) NMR 2.1-2.8(8H,m) 3.13(2H,d) 3.39(1H,d) 3.68(2H,bs) 4.95(1H,d) 6.08(1H,dt) 6.39(1H,d) 6.5-6.6(2H,m) 7.0-7.1 (5H,m) 7.1-7.3(5H,m) compound 31 1-(4-Acetylaminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-yldenepiperidine TLC(CHCl3:MeOH=9:1) Rf=0.58 MS 466(M+) NMR 2.15(3H,s) 2.2-2.9(8H,m) 3.22(2H,d) 3.40(1H,d) 4.91(1H,d) 6.21(1H,dt) 6.48(1H,d) 7.0-7.5(13H,m) compound 32 4-(5H-Dibenzo[a,d]-cyclohepten-5-ylidene)-1-(2,5-dimethoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.73 MS 449(M+) NMR 2.05-2.23(4H,m) 2.30-2.45(2H,m) 2.50-2.66(2H,m) 3.15(2H,d) 3.75(6H,s) 6.15(1H,m) 6.45-7.00(4H,m) 6.91(2H,s) 7.18-7.35(8H,m) compound 33 4-(5H-Dibenzo[a,d]cyclohepten-5-yiidene)-1-(2,3-dimethoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.90 MS 449(M+) NMR 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.5-2.7(2H,m) 3.13(2H,d) 3.77(3H,s) 3.80(3H,s) 6.28(1H,dt) 6.79(1H,d) 6.90(2H,s) 7.0-7.1(2H,m) 7.2-7.4(9H,m) compound 34 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,5-dimethoxycinnamyl)piper idine TLC(CHCl3:MeOH=9:1) Rf=0.73 MS 449(M+) NMR 2.05-2.23(4H,m) 2.28-2.42(2H,m) 2.50-2.66(2H,m) 3.10(2H,d) 3.78(6H,s) 6.10-6.42(3H,m) 6.52(2H,m) 6.91(2H,s) 7.18-7.35(8H,m) compound 35 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycinnamyl)piper idine TLC(CHCl3:MeOH=9:1) Rf=0.87 MS 419(M+) NMR 2.2-2.3(4H,m) 2.3-2.4(2H,m) 2.6-2.7(2H,m) 3.15(2H,d) 3.79(3H,s) 6.28(1H,dt) 6.80(1H,d) 6.8-6.9(1H,m) 6.92(2H,s) 7.1-7.4(11H,m) compound 36 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycinnamyl)piper idine TLC(CHCl3:MeOH=9:1) Rf=0.89 MS 419(M+) NMR 2.1-2.2(4H,m) 2.2-2.4(2H,m) 2.5-2.7(2H,m) 3.12(2H,d) 3.78(3H,s) 6.23(1H,dt) 6.42(1H,d) 6.7-6.9(4H,m) 6.92(2H,s) 7.2-7.4(8H,m) compound 37 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycinnamyl)piper idine TLC(CHCl3:MeOH=9:1) Rf=0.85 MS 419(M+) NMR 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.6-2.7(2H,m) 3.12(2H,d) 3.79(3H,s) 6.12(1H,dt) 6.41(1H,d) 6.83(2H,d) 6.91(2H,s) 7.1-7.3(10H,m) compound 38 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.93 MS 436(M+) NMR 2.7-3.0(8H,m) 3.3-3.4(4H,m) 3.75(2H,d) 6.7-6.8(2H,m) 7.0-7.2(8H,m) 7.5-7.6(2H,m) 8.1-8.2(2H,m) compound 39 1 -(4-Aminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.64 MS 405(M+) NMR 2.4-2.5(4H,m) 2.6-2.7(2H,m) 2.81(2H,dt) 3.12(2H,d) 3.3-3.4(2H,dt) 3.67(2H,bs) 6.08(1H,dt) 6.39(1H,d) 6.60(2H,d) 7.0-7.2(10H;m) compound 40 1-(4-Acetylaminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.54 MS 448(M+) NMR 2.4-2.6(4H,m) 2.7-2.8 (8H,m) 3.21(2H,d) 6.21(1H,dt) 6.44(1H,d) 7.0-7.2(8H,m) 7.34(2H,d) 7.44(2H,d) compound 41 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorocinnamyl)piper idine TLC(CHCI3:MeOH=9:1) Rf=0.88 MS 445(M+) NMR 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.6-2.8(2H,m) 3.09(2H,d) 6.17(1H,dt) 6.42(1H,d) 6.87(2H,s) 6.9-7.0(2H,m) 7.2-7.3(10H,m) compound 42 3-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(3-pyridyl)-1-propene TLC(CHCl3:MeOH 9:1) Rf=0.44 MS 390(M+) NMR 2.1-2.2(4H,m) 2.3-2.5(2H,m) 2.55-2.65(2H,m) 3.09(2H,d) 6.31(1H,dt) 6.43(1H,d) 6.90(2H,s) 7.1-7.3(9H,m) 7.62(1H,d) 8.41(1H,dd) 8.54(1H,d) compuond 43 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.55 MS(FAB.m/z) 406(MH+) NMR 2.1-2.3(4H,m) 2.3-2.5(2H,m) 2.6-2.8(2H,m) 3.07(2H,d) 5.97(1H,dt) 6.37(1H,d) 6.63(2H,d) 6.87(2H,s) 7.0-7.3(11H,m) compound 44 1-(4-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3: MeOH:9:1) Rf=0.87 MS 447(M+) NMR 2.1-2.2(4H,m)2.29(3H,s) 2.3-2.4(2H,m) 2.6-2.7(2H,m) 3.12(2H,d) 6.21(1H,dt) 6.43(1H,d) 6.92(2H,s) 6.9-7.0(2H,m) 7.2-7.4(10H,m) compound 45 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxy-3-methoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.87 MS 435(M+) NMR 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.6-2.7(2H,m) 3.08(2H,d) 3.81(3H,s) 6.09(1H,dt) 6.39(1H,d) 6.78(lH,s) 6.8-6.9(2H,m) 6.87(2H,s) 7.1-7.3(9H,m) compound 46 1-(4-Acetoxy-3-methoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.83 MS 477(M+) NMR 2.1-2.2(4H,m) 2.29(3H,s) 2.3-2.4(2H,m) 2.6-2.7(2H,m) 3.09(2H,d) 3.81(3H,s) 6.08(lH,dt) 6.38(1H,d) 6.80(2H,s) 6.9-7.4(11H,m) 7.2-7.4(9H,m) compound 47 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-hydroxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.45 MS 405(M+) NMR(CD3OD) 2.10-2.30(4H,m) 2.31-2.50(2H,m) 2.70(2H,m) 3.16(2H,d) 6.42(1H,m) 6.70(1H,m) 6.84-6.95(2H,m) 6.95(2H,s) 7.10-7.38(10H,m) compound 48 1-(3-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH= 9:1) Rf=0.80 MS 447(M+) NMR 2.13-2.24(4H,m) 2.30-2.45(2H,m) 2.62(2H,m) 3.14(2H,d) 6.28(1H,m) 6.43(1H,d) 6.92(2H,s) 6.92-6.97(1H,m) 7.04(1H,s) 7.18-7.35(10H,m) compound 49 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[3-(2-methoxyacetoxy)cinnamyl]piperidine TLC(CHCl3:MeOH=9:1) Rf=0.65 MS 477(M+) NMR(hydrochloride) 2.21-2.40(2H,m) 2.48-2.60(4H,m) 2.92-3.15(2H,m) 3.20-3.65(2H,m) 3.54(3H,s) 4.26(2H,s) 6.40-6.60(2H,m) 6.92(2H,s) 7.00-7.39(12H,m) compound 50 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycarbonylcinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.55 MS 447(M+) NMR 2.52-2.68(4H,m) 2.92-3.10(2H,m) 3.30-3.50(2H,m) 3.62(2H,d) 6.42(1H,dt) 6.91(2H,s) 7.18(1H,d) 7.24-7.40(8H,m) 7.42-7.60(3H,m) 7.90-7.95(1H,m) compound 51 4-(5H-Dibenzo[a,d]cyclohep ten-5-ylidene)-1-(4-methoxycarbonylcinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.50 MS 447(M+) NMR 2.15-2.24(4H,m) 2.32-2.45(2H,m) 2.60-2.68(2H,m) 3.16(2H,d) 3.90(3H,s) 6.39(1H,dt) 6.50(1H,d) 6.92(2H,s) 7.20-7.36(8H,m) 7.37-7.41(2H,m) 7.96-8.00(lH,m) compound 52 4-(5H-Dibenzo[a,d]-cyclohepten-5-ylidene)-1-(3-methoxy-2-nitrocinnamyl)piperidine TLC(HEXANE:EtOAc=1:1) Rf=0.30 MS 464(M+) NMR 2.1-2.23(3H,m) 2.24-2.42(2H,m) 2.43-2.7(3H,m) 3.07(2H,d) 3.81(3H,s) 6.37(2H,s) 6.8-7.0(3H,m) 7.05-7.4(10H,m) compound 53 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarboxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.83 MS 477(M+) NMR 1.23(3H,t) 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.5-2.7(2H,m) 3.13(2H,d) 4.18(2H,q) 6.24(1H,d) 6.43(1H,d) 6.90(2H,s) 7.0-7.1(2H,m) 7.1-7.4(10H,m) compound 54 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxyacetoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.75 MS 477(M+) NMR 2.0-2.2(4H,m) 2.4-2.6(2H,m) 2.5-2.7(2H,m) 3.17(2H,d) 3.52(3H,s) 4.24(2H,s) 6.22(1H,dt) 6.44(1H,d) 6.95(2H,s) 7.0-7.4(12H,m) compound 55 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dihydroxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.35 MS(FAB.m/z) 422(M+) NMR 2.0-2.3(4H,m) 2.4-2.6(2H,m) 2.6-2.8(2H,m) 3.17(2H,dt) 6.27(1H,dt) 6.41(1H,d) 6.87(2H ,s) 6.9-7.5(13H,m) compound 56 4-Dibenzo[b,e]thiepin-11(6H)-ylidene-1-(2,4-dimethoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.75 MS 469(M+) compound 57 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.71 MS 451(M+) compound 58 1-(4-Aminosulfonylcinnamyl)-4-dibenzo[b,e]oxepin-11(6H)-ylidenepiperidine TLC(CHCl3:MeOH=9:1) Rf=0.32 MS 475(M+) compound 59 1-(4-Aminosulfonylcinnamyl)-4-(9-thioxanthylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.35 MS 475(M+) compound 60 1-(4-Aminosulfonylcinnamyl)-4-(9-xanthylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.31 MS 458 (M+) compound 61 1-(4-Aminosulfonylcinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.34 MS 471(M+) compound 62 1-(4-Aminosulfonyl-α-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.29 MS 483(MH+) compound 63 1-(4-Aminosulfonyl-β-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.45 MS 483(MH+) compound 64 1 -(2-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine MS 397(M+) H-NMR 2.1-2.8(8H,m) 3.63(2H,bs) 6.90(2H,s) 7.1-7.3(12H,m) compound 65 1-Cyclohexyl-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane Yield 94% MS 397(M+) H-NMR 0.8-2.1(15H,m) 2.47(2H,dd) 2.68(2H,d) 2.7-2.9(2H,m) 3.0(2H,dd) 3.49(2H,d) 6.94(2H,s) 7.1-7.4(8H,m) compound 66 1-Cyclohexyl-4-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane Yield 72% MS 411(M+) H-NMR 0.8-2.1(15H,m) 2.47(2H,dd) 2.68(2H,d) 2.7-2.9(2H,m) 3.0(2H,dd) 3.49(2H,d) 6.92(2H,s) 7.1-7.4(8H,m) compound 67 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1 -cyclohexylpiperidine Yield 95.6% TLC( CHCl3: MeOH=9:1) Rf=0.68 MS 357(M+) H-NMR(CDCL3) 0.85(3H,d,J=8Hz) 1.2-1.4(6H,m) 1.7-1.9(2H,m) 2.31(2H,dd,J=12,8Hz) 2.53(2H,d,J=12Hz) 2.7-2.8(2H,m) 3,14(2H,td,J=8,3Hz) 3.40(2H,d,J=12Hz) 6.92(2H,s) 7.2-7.4(8H,m) compound 68 1-Decyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine Yield 66.7% TLC( CHCl3:MeOH=9:1) Rf=0.75 MS 413(M+) NMR(hydrochloride) 0.85(3H,t,J=8Hz) 1.2-1.4(14H,m) 1.7-1.9(2H,m) 2.33(2H,dd,J=12,8Hz) 2.54(2H,d,J=12Hz) 2.7-2.8(2H,m) 3,15(2H,td,J=8,3Hz) 3.39(2H,d,J=12Hz) 6.92(2H,s) 7.1-7.4(8H,m) compound 69 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3,4-dichlorophenyl-2-isopropylvaleronitrile Yield 69.1% TLC( CHCl3: MeOH=9:1) Rf=0.60 MS 542(M+) H-NMR(CDCL3) 0.77(3H,d,J=8Hz) 1.18(3H,d,J=8Hz) 2.0-3.4(15H,m) 6.90(2H,s) 7.18(H,dd,J=9,2Hz) 7.2-7.4(8H,m) 7.48(1H,d,J=9Hz) 7.53(1H,s) compound 70 4-(5H-Dibenzo[a,d] cyclohepten-5-ylidene)-1-[3-[2-(cinnamoylamino)phenylthiol]-1-propyl)piperidine TLC( CHCl3:MeOH=9:1) Rf=0.66 MS 568(M+) H-NMR(CDCL3) 1.73(2H,tt,J=7,7Hz) 2.0-2.2(4H,m) 2.3-2.4(2H,m) 2.38(2H,t,J=7Hz) 2.5-2.6(2H,m) 2.78(2H,t,J=7Hz) 6.59(1H,d,J=16Hz) 6.88(2H,s) 7.08(1H,tt,J=8,lHz) 7.1-7.4(12H,m) 7.5-7.6(3H,m) 7.76(1H,d,J=16Hz) 8.55(1H,d,J=8Hz) 8.78(1H,bs,NH) compound 71 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-cinnamylpiperidine TLC( CHCl3: MeOH=9:1) Rf=0.69 MS 389(M+) H-NMR(CDCL3) 2.1-2.3(4H,m) 2.4-2.5(2H,m) 2.6-2.7(2H,m) 3.14(2H,d,J=7Hz) 6.26(2H,dt,J=16,7Hz) 6.48(2H,d,J=16Hz) 6.92(2H,s) 7.1-7.4(8H,m) compound 72 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2,2-diphenylvaleronitrile Yield 57.7% TLC( CHCl3: MeOH=9:1) Rf=0.74 MS 506(M+) H-NMR(CDCL3) 1.5-1.7(2H,m) 2.0-2.2(4H,m) 2.3-2.6(8H,m) 6.87(2H,s) 7.1-7.4(18H,m) compound 73 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)-2-isopropylvaleronitrile Yield 47.5% TLC( CHCl3: MeOH=9:1) Rf=0.75 MS 540(M+) H-NMR(CDCL3) 0.76(3H,d,J=7Hz) 1.0-1.2(1H,m) 1.5-1.6(1H,m) 1.9-2.5(13H,m) 6.88(2H,s) 7.1-7.3(8H,m) 7.48(1H,d,J=8Hz) 7.56(1H,d,J=8Hz) 7.59(1H,s) compound 74 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-fluorobenzyl)piperidine TLC(CHCl3: MeOH=9:1) Rf=0.75 MS 381(M+) H-NMR(CDCL3) 2.1-2.2(4H,m) 2.3-2.4(2H,m) 2.5-2.6(2H,m) 3.53(2H,s) 6.88(2H,s) 6.96(1H,dd,=8,8Hz) 7.04(1H,dd,J=7,7Hz) 7.1-7.4(10H,m) compound 75 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorophenylethyl)piperidine TLC( CHCl3: MeOH=9:1) Rf=0.55 MS 395(M+) H-NMR(CDCL3) 2.1-2.8(12H,m) 6.9-7.4(2H,m) compound 76 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)valeronitrile TLC( CHCl3: MeOH=9:1) Rf=0.56 MS 498(M+) H-NMR(CDCL3) 1.5-2.7(14H,m) 3.97(1H,t,J=7Hz) 6.90(2H,s) 7.1-7.6(12H,m) compound 77 1-(3-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine TLC( CHCl3: MeOH=9:1) Rf=0.62 MS 378(M+) H-NMR(CDCL3) 2.1-2.8(8H,m) 3.50(2H,s) 3.4-3.8(2H,bs) 6.5-6.8(2H,m) 6.93(2H,s) 7.0-7.4(10H,m) compound 78 4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-3',4'-dimethoxybutyrophenone TLC( CHCl3: MeOH=9:1) Rf=0.52 MS 479(M+) H-NMR(CDCL3) 1.8-2.6(12H,m) 2.95(2H,t,J=8Hz) 3.93(3H,s) 3.96(3H,s) 6.85(1H,d,J=10Hz) 6.88(2H,s) 7.2-7.4(8H,m) 7.5-7.7(2H,m) compound 79 1-(4-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidine TLC(CHCl3:MeOH=9:1) Rf=0.70 MS(FD.m/z) 388(M+) H-NMR 2.2-2.5(2H,m) 2.5-2.8(2H,m) 3.0-3.4(4H,m) 4.03(2H,d) 6.92(2H,s) 7.1-8.0(12H,m) compound 80 1-Cyclohexyl-4-[4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane TLC(HEXANE.:EtOAC=1:1) Rf=0.67 MS 413(M+) H-NMR 0.80-0.88(2H,m) 1.10-1.73(15H,m) 2.12-2.19(2H,m) 2.28-2.30(2H,m) 2.32-2.47(4H,m) 2.64-2.69(2H,m) 2.77-2.86(2H,m) 3.36-3.45(2H,m) 7.05-7.15(8H,m) compound 81 Cyclohexyl-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]methane TLC(CHCl3:MeOH=9:1) Rf=0.58 MS(FD.m/z) 369(M+) H-NMR 0.7-2.9(20H,m) 6.91(2H,s) 7.05-7.4(8H,m) compound 82 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimethoxybenzyl)piperidine TLC(CHCl3:MeOH=9:1) Rf=0.63 MS(FD.m/z) 423(M+) H-NMR 2.0-2.8(10H,m) 3.80(3H,s) 3.84(3H,s) 6.7-7.4(11H,m) 6.89(2H,s) compound 83 3-Cyanopropyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine NMR 1.62-2.72(14H,m) 6.92(2H,s) 7.10-7.30(8H,m) compound 84 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxyphenacyl)piperidine MS 451(M+) NMR 2.15-2.30(4H,m) 2.37-2.45(2H,m) 2.65-2.75(2H,m) 3.70(2H,s) 3.90(3H,s) 3.92(3H,s) 6.85(1H,d) 6.90(2H,s) 7.18-7.34(8H,m) 7.59(1H,d) 7.66(1H,dd) compound 85 1-Cyclohexyl-6-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]hexane TLC(CHCl3:MeOH=9:1) Rf=0.65 MS(FD.m/z) 439(M+) H-NMR 0.8-1.0(2H,m) 1.1-1.4(10H,m) 1.5-1.7(8H,m) 2.2-2.4(1H,m) 2.5-2.9(5H,m) 3.0-3.2(2H,m) 3.4-3.6(3H,m) 6.92(2H,s) 7.1-7.4(8H,m) compound 86 1 -(4-Cyclohexylbutyl)-4-(9-thioxanthylidene)piperidine TLC( CHCl3: MeOH=9:1) Rf=0.69 MS(FD.m/z) 417(M+) H-NMR 0.8-1.0(2H,m) 1.1-1.4(9H,m) 1.5-1.7(6H,m) 2.2-2.4(2H,m) 2.5-2.6(2H,m) 2.8-2.9(2H,m) 2.9-3.1(6H,m) 7.1-7.5(8H,m) compound 87 1 -(4-Cyclohexylbutyl)-4-(9 -xanthylidene)piperidine TLC( CHCl3: MeOH=9:1) Rf=0.74 H-NMR 0.8-1.0(2H,m) 1.1-1.4(9H,m) 1.5-1.7(6H,m) 2.3-2.4(2H,m) 2.52(4H,t) 2.91(4H,t) 7.0-7.4(8H,m) compound 88 2-(3,4-Dimethoxyphenyl)-5-[4-(4-fluorophenyl)methylene-1-piperidinyl]-2-isopropylvaleronitrile TLC(CHCl3: MeOH=9:1) Rf=0.73 MS 450(M+) H-NMR(CDCL3) 0.80(3H,d,1=8Hz) 1.20(3H,dJ=8Hz) 1.5-3.6(15H,m) 3.9-4.0(6H,m) 6.4-6.5(1H,m) 6.8-7.2(7H,m) EXAMPLES Evaluation of antiarrhythmic activity of the compounds Example 1 Female Guinea Pigs, weighing 250-350g, were anesthetized with urethane. The lead II ECG was continuously recorded. Drugs, compound 1 and compound 2, were dissolved in the 2.5% nicol 2.5% ethanol solution, and injected into the femoral vein. After 30min of drug injection ouabain was infused intravenously through the left femoral vein at a rate of 10ug/kg/min. The time, ventricular premature contractions (VPC) ventricular fibrillation (VF) and cardiac arrest (CA) appeared on ECG, were measured, and the cumulative ouabain dosage to induce ventricular premature contractions, ventricular fibrillation and cardiac arrest, respectively, was calculated. The results are summarized in Table 1. Example 2 Mongrel dogs of either sex, weighing 8-20 kg, were anesthetized with pentobarbitone sodium, 30mg/kg. The lead II ECG, atrial electrogram from catheter tip electrodes in the right atrium, and blood pressure were continuously recorded. Ouabain 40 ug/kg was injected intravenously and with an additional 10 ug/kg every 20 min until stable ventricular arrhythmias were produced. The severity of arrhythmia was expressed by the arrhythmic ratio i.e. number of ventricular ectopic beats divided by the total heart rate. The arrhythmic ratio was calculated for 60 min after bolus intravenous administration. The results are summarized in Table 2. Example 3 Mongrel dogs of either sex, weighing 8-20 kg, were anaesthetized initially with thiopentone sodium. After incubation, 1.0% halothane, vaporized with 100% 02, was administered with volume limited ventilator. Adrenaline was infused through the left femoral vein at the rate of 2.5-5 ug/kg/min. After 3 min of adrenaline infusion, drugs were injected into the right femoral vein. The lead II ECG, atrial electrogram from catheter tip electrodes in the right atrium and blood pressure were continuously recorded. The severity of ectopic beats divided by the total heart rate. The arrhythmic ratio was calculated for 15 min after drug administration. The results are summarized in Table 3. Compound # Dose (mg/kg) VPC (µg/kg) VF (µg/kg) CA (µg/kg) control 153 221 324 9 1 169 236 294 10 1 166 245 304 11 1 163 256 304 13 1 144 333 416 15 1 172 217 273 16 1 184 275 380 17 1 203 330 395 19 1 181 366 420 20 1 163 334 393 21 1 178 346 409 22 0.3 142 442 499 23 1 168 250 306 24 1 212 308 374 25 1 152 606 646 26 1 125 556 579 27 1 159 342 413 28 1 149 344 399 29 1 160 298 368 30 1 175 357 427 31 1 254 334 422 32 1 170 321 372 33 1 152 295 357 34 1 225 386 454 35 1 203 372 469 36 3 205 617 656 37 1 147 335 389 38 1 180 347 431 39 1 240 265 351 40 1 212 247 334 41 1 140 311 380 43 1 146 259 344 44 3 205 441 476 45 3 202 398 458 46 1 193 264 350 47 1 175 320 374 48 3 187 254 309 49 1 136 280 346 50 3 174 384 448 51 1 203 367 419 52 1 186 534 586 53 1 232 294 356 54 1 186 389 454 55 1 211 322 398 56 1 121 309 365 57 1 146 325 381 58 3 164 264 312 59 3 155 193 245 61 1 153 373 432 63 1 171 282 363 65 1 182 239 289 66 1 178 257 305 67 1 196 205 274 68 1 179 310 369 69 1 154 279 337 70 1 172 302 358 71 1 200 329 383 72 1 183 267 329 73 1 160 285 339 74 1 176 261 305 75 1 168 277 335 76 1 184 270 318 77 1 162 240 292 78 1 199 260 305 79 1 185 254 318 80 1 204 257 312 81 1 178 228 273 82 1 169 286 338 85 1 178 301 357 86 1 174 264 305 87 1 178 264 312 88 1 168 244 311 time after administration (min) Arrhythmic Ratio Compound #22 30ug/kg Compound #66 300ug/kg 0 1.00 1.00 2 1.00 0.80 4 1.00 0.71 6 0.60 0.41 8 0.77 0.19 10 0.50 0.19 12 0.50 0.43 15 0.50 0.43 20 0.00 0.38 30 0.00 0.45 60 0.00 0.45 time after administration (min) Arrhythmic Ratio Compound #22 10ug/kg Compound #66 300ug/kg 0 1.00 1.00 2 0.80 0.66 4 0.50 0.41 6 0.00 0.18 8 0.00 0.08 10 0.00 0.07 12 0.00 0.07 15 0.00 0.00

Claims: Use in the preparation of an antiarrhythmic medicament of a piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof: wherein is either of the following groups: or wherein B is a fused aromatic or heterocyclic ring selected from the group consisting of benzene, pyridine and thiophene; -Z- is selected from: or X is selected from: wherein R 1 and R 2 are the same or different and are independently selected from hydrogen, methyl, ethyl, or propyl; R 3 is hydrogen, alkyl of from 1 to 12 carbon atoms, or aryl of from 6 to 12 carbon atoms; Q is phenyl, cyclohexyl, piperidinyl, tetrahydropyranyl, pyridyl, pyrrolyl, N-methylpyrrolyl, thienyl, furyl, 1-hexyl, or cyano; wherein from 1 to 3 hydrogen atoms in Q may be independently substituted by alkyl of from 1 to 3 carbon atoms, perfluoroalkyl of from 1 to 3 carbon atoms, acylamino of from 1 to 6 carbon atoms, perfluoroacylamino of from 1 to 3 carbon atoms, alkoxy of from 1 to 3 carbon atoms, alkanesulfonylamino of from 1 to 3 carbon atoms, perfluoroalkanesulfonylamino of from 1 to 3 carbon atoms, acetoxy of from 1 to 3 carbon atoms, aminocarbonyl, aminosulfonyl, fluoro, chloro, cyano, hydroxy, nitro, amino, imidazolylmethyl, cinnamoylamino, p-fluorobenzoyl, cyanomethyl, cyanoethyl, methoxyacetoxy, alkoxycarbonyl of from 1 to 3 carbon atoms: 1 is an integer of from 0 to 1; m is an integer of from 0 to 1; n is an integer of from 0 to 6. Use according to Claim 1,wherein in the general formula (I): wherein B is benzene, and Z is Use according to claim 1 or claim 2, wherein in the general formula (I) X is Use according to any one of claims 1 to 3, wherein in the general formula (I) Q is phenyl, wherein from 1 to 3 hydrogen atoms in Q may be independently substituted by alkyl of from 1 to 3 carbon atoms, perfluoroalkyl of from 1 to 3 carbon atoms, acylamino of from 1 to 6 carbon atoms, perfluoroamino of from 1 to 3 carbon atoms, alkoxy of from 1 to 3 carbon atoms, alkanesulfonylamino of from 1 to 3 carbon atoms, perfluoroalkanesulfonylamino of from 1 to 3 carbon atoms, acetoxy of from 1 to 3 carbon atoms, aminocarbonyl, aminosulfonyl, fluoro, chloro, cyano, hydroxy, nitro, amino, imidazolylmethyl, cinnamoylamino, p-fluorobenzoyl, cyanomethyl, cyanoethyl, methoxyacetoxy, alkoxycarbonyl of from 1 to 3 atoms. Use according to claim 1, wherein the piperidine derivative is a compound selected from any of the following: 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-(N-imidazolylmethyl)cinnamyl]piperidine, 1-[4- [4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butanoyl]-4-hydroxypiperidine, 4- [4-Dibenzo[b,e]thiepin-11(6H)-ylidene]-1-piperidinyl]-1-cyclohexylbutane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Acetylaminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 3- [4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(4-nitrophenyl)propane, 1-(4-Aminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 1-(4-Acetylaminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, N- [3-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-piperidinyl]propanoyl-3, 4-dimethoxyanilide, 4- [4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-butyl]tetrahydropyran, 1-(N-Acetyl-4-piperidinyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine, 1-(4-Cyanocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-Cyclohexyl-4- [4-(10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-propanoylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarbonylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methanesulfonylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycarbonylaminocinnamyl)piperidine, 4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-(4-pivaloylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoroacetylaminocinnamyl)piperidine, 1-(4-Butanoylaminocinnamyl)-4- (5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminocarbonylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoromethylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-cyanomethylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dichlorocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxy-2-nitrocinnamyl)piperidine, 4-Dibenzo [b,e]thiepin-11(6H)-ylidene-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-ylidenepiperidine, 1-(4-Acetylaminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-ylidenepiperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,5-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,5-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycinnamyl)piperidine, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycinnamyl)piperidine, 4-(10,11-Dihydro-5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Acetylaminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorocinnamyl)piperidine, 3- [4-5(H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(3-pyridyl)-1-propene, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxycinnamyl)piperidine, 1-(4-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxy-3-methoxycinnamyl)piperidine, 1-(4-Acetoxy-3-methoxycinnamyl)-4- (5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-hydroxycinnamyl)piperidine, 1-(3-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[3-(2-methoxyacetoxy)cinnamyl]piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxy-2-nitrocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarboxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxyacetoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dihydroxycinnamyl)piperidine, 4-Dibenzo [b,e]thiepin-11(6H)-ylidene-1-(2,4-dimethoxycinnamyl)piperidine, 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-dibenzo[b,e]oxepin-11(6H)-ylidenepiperidine, 1-(4-Aminosulfonylcinnamyl)-4-(9-thioxanthylidene)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-(9-xanthylidene)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminosulfonyl-a-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminosulfonyl-β-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(2-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-Cyclohexyl-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 1-Cyclohexyl-4-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-cyclohexylpiperidine, 1-Decyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 5-[4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3,4-dichlorophenyl-2-isopropylvaleronitrile, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[3-[2-(cinnamoylamino)phenylthio]-1-propyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-cinnamylpiperidine, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2,2-diphenylvaleronitrile, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)-2-isopropylvaleronitrile, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-fluorobenzyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorophenylethyl)piperidine, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)valeronitrile, 1-(3-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-3',4'-dimethoxybutyrophenone, 1-(4-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidine, 1-Cyclohexyl-4- [4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, Cyclohexyl-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]methane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimethoxybenzyl)piperidine, 3-Cyanopropyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxyphenacyl)piperidine, 1-Cyclohexyl-6-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]hexane, 1-(4-Cyclohexylbutyl)-4-(9-thioxanthylidene)piperidine, 1-(4-Cyclohexylbutyl)-4-(9-xanthylidene)piperidine, 2-(3,4-Dimethoxyphenyl)-5-[4-(4-fluorophenyl)methylene-1-piperidinyl]-2-isopropylvaleronitrile, or a pharmaceutically acceptable salt thereof. Use according to claim 1,wherein the piperidine derivative is the compound 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-1-(3-methoxy-2-nitrocinnamyl)piperidine or a pharmaceutically acceptable salt thereof. Use according to any preceding claim, wherein the antiarrhythmic medicament is a composition comprising a mixture of the piperidine derivative or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable vehicle, diluent, carrier, extender, binder, swelling agent, lubricating or wetting agent, antiseptic, stabiliser, buffer, antioxidant, sweetener or flavour. Use according to claim 7, wherein the composition is in unit dosage form. Use according to claim 8, wherein the composition contains from 0.2 to 500 mg of the piperidine derivative or pharmaceutically acceptable salt thereof. Use according to any one of claims 7 to 9, wherein the composition is in the form of a tablet, capsule, elixir, or a sterile solution or suspension. A piperidine derivative which is a compound selected from any of the following: 4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-[4-(N-imidazolylmethyl)cinnamyl]piperidine, 1-[4-[4-(5H-Dibenzo [a,d] cyclohepten-5-ylidene)-1-piperidinyl]butanoyl]-4-hydroxypiperidine, 4-[4-Dibenzo[b,e]thiepin-11(6H)-ylidene]-1-piperidinyl]-1-cyclohexylbutane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Acetylaminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 3- [4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(4-nitrophenyl)propane, 1-(4-Aminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 1-(4-Acetylaminophenyl)-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, N-[3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propanoyl-3,4-dimethoxyanilide, 4-[4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-butyl]tetrahydropyran, 1-(N-Acetyl-4-piperidinyl)-3-[4- (5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine, 1-(4-Cyanocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-Cyclohexyl-4-[4-(10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-propanoylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarbonylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methanesulfonylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycarbonylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-pivaloylaminocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoroacetylaminocinnamyl)piperidine, 1-(4-Butanoylaminocinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminocarbonylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoromethylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-cyanomethylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dichlorocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxy-2-nitrocinnamyl)piperidine, 4-Dibenzo [b,e]thiepin-11(6H)-ylidene-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-ylidenepiperidine, 1-(4-Acetylaminocinnamyl)-4-dibenzo[b,e]thiepin-11(6H)-ylidenepiperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,5-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-(3,5-dimethoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycinnamyl)piperidine, 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrocinnamyl)piperidine, 1-(4-Aminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Acetylaminocinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorocinnamyl)piperidine, 3-[4-5(H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-1-(3-pyridyl)-1-propene, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxycinnamyl)piperidine, 1-(4-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-hydroxy-3-methoxycinnamyl)piperidine, 1-(4-Acetoxy-3-methoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-hydroxycinnamyl)piperidine, 1-(3-Acetoxycinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-[3-(2-methoxyacetoxy)cinnamyl]piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxycarbonylcinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxy-2-nitrocinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-ethoxycarboxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxyacetoxycinnamyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dihydroxycinnamyl)piperidine, 4-Dibenzo [b,e]thiepin-11(6H)-ylidene-1-(2,4-dimethoxycinnamyl)piperidine, 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,4-dimethoxycinnamyl)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-dibenzo[b,e]oxepin-11(6H)-ylidenepiperidine, 1-(4-Aminosulfonylcinnamyl)-4-(9-thioxanthylidene)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-(9-xanthylidene)piperidine, 1-(4-Aminosulfonylcinnamyl)-4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminosulfonyl-α-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(4-Aminosulfonyl-β-methylcinnamyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-(2-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 1-Cyclohexyl-3-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]propane, 1-Cyclohexyl-4-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-cyclohexylpiperidine, 1-Decyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3,4-dichlorophenyl-2-isopropylvaleronitrile, 4- (5H-Dibenzo[a,d]cyclohepten-5-ylidene) -1- [3- [2-(cinnamoylamino)phenylthio]-l-propyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-cinnamylpiperidine, 5-[4-(5H-Dibenzo [a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2,2-diphenylvaleronitrile, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)-2-isopropylvaleronitrile, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-fluorobenzyl)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorophenylethyl)piperidine, 5-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-2-(3-trifluoromethylphenyl)valeronitrile, 1-(3-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]-3',4'-dimethoxybutyrophenone, 1-(4-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidine, 1-Cyclohexyl-4-[4-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]butane, Cyclohexyl-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]methane, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimethoxybenzyl)piperidine, 3-Cyanopropyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine, 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimethoxyphenacyl)piperidine, 1-Cyclohexyl-6-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl]hexane, 1-(4-Cyclohexylbutyl)-4-(9-thioxanthylidene)piperidine, 1-(4-Cyclohexylbutyl)-4-(9-xanthylidene)piperidine, 2-(3,4-Dimethoxyphenyl)-5-[4-(4-fluorophenyl)methylene-1-piperidinyl]-2-isopropylvaleronitrile, or a pharmaceutically acceptable salt therof. A piperidine derivative which is the compound: 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxy-2-nitro cinnamyl)piperidine, or a pharmaceutically acceptable salt thereof. A composition for treating cardiac arrhythmia comprising a mixture of the piperidine derivative or pharmaceutically acceptable salt thereof according to claim 11 or claim 12 and a pharmaceutically acceptable vehicle, diluent, carrier, extender, binder, swelling agent, lubricating or wetting agent, antiseptic, stabilizer, buffer, antioxidant, sweetener or flavour. A composition according to claim 13 in unit dosage form. A composition according to claim 14, containing from 0.2 to 500 mg of the piperidine derivative or pharmaceutically acceptable salt thereof. A composition according to any one of claims 13 to 15 in the form of a tablet, capsule, elixir, or a sterile solution or suspension.

Inventors: EGUCHI CHIKAHIKO, GYOTOKU YUICHI, HIRASAWA AKIRA, SHOJI MASATAKA, YOSHIMOTO RYOTA, EGUCHI, CHIKAHIKO, GYOTOKU, YUICHI, HIRASAWA, AKIRA, SHOJI, MASATAKA, YOSHIMOTO, RYOTA, Eguchi, Chikahiko, c/o Central Res. Lab., Gyotoku, Yuichi, c/o Central Res. Lab., Hirasawa, Akira, c/o Central Res. Lab., Shoji, Masataka, c/o Central Res. Lab., Yoshimoto, Ryota, c/o Central Res. Lab.
Applicants: AJINOMOTO KK, AJINOMOTO CO., INC.
Application year: 1991
Main classification: C07D211
IPC codes: C07D211, C07D401, C07D295, C07D409, C07D521, C07D405