Piperidine derivatives and hypotensives containing the same

Abstract: A piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof; wherein any of R¹, R², R³ and R⁴ may be the same or different from each other and each independently represents a hydrogen atom or other substituent; X represents an aralkyl- or aryl-containing group having from 6 to 30 carbon atoms or an alkyl group having from 4 to 30 carbon atoms or a cycloalkyl-containing group, which may optionally have substituent(s) and which may be substituted by hetero atom(s) or hetero atom-­ containing organic group(s), said alkyl group optionally containing unsaturated bond(s); Y represents a hetero atom or an optionally substituted alkylene chain, the alkylene chain optionally containing hetero atom(s) or unsaturated bond(s); and A represents an optionally substituted condensed aromatic or heterocyclic ring. The compounds are useful as hypotensives.

Description: The present invention relates to the use of piperidine derivatives as hypotensives and more particularly to the use of certain piperidine derivatives in the preparation of hypotensive medicaments. It is said that there are about 13,000,000 patients with hypertension in Japan and its frequency of occurrence becomes higher as age is advanced. Further, in the elderly, attention has been paid to hypertension more and more as a risk factor in severe heart and cerebral diseases represented by cardiac infarction or cerebral apoplexy. In recent years, calcium antagonists or angiotensin converting enzyme inhibitors have been widely used as excellent primary selection drugs for treatment of hypertension. But pharmaceutical effects or safety of these hypotensives have recently come into question. It is therefore required to develop new hypotensives having excellent pharmaceutical effects and safety which can be industrially prepared at low cost in a simple manner. US-A-4 356 184 describes 1-Piperidinylmethyl benzenamines having anti-allergic and anti-hypertensive activity. As a result of extensive investigations the present inventors have found that certain piperidine derivatives show an excellent hypotensive activity. The synthesis steps of these derivatives are simple and they can be easily prepared industrially. Accordingly, the present invention resides in the use in the preparation of a hypotensive medicament of a piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof: wherein any of R¹, R², R³ and R⁴ may be the same or different from each other and each independently represents a hydrogen atom or a halogen atom, alkyl group having 1 to 4 carbon atoms, hydroxyl group, amino group, cyano group, methoxy group, methylthio group, hydroxymethyl group, carboxyl group, trifluoromethyl group, trifluoromethoxy group, trifluoromethylthio group, trifluoromethylsulfonyl group, hydroxyamino group or nitro group; Y represents a hetero atom or an optionally substituted alkylene chain, the alkylene chain optionally containing one or more hetero atoms or one or more unsaturated bonds; and X represents an aralkyl- or aryl-containing group having from 6 to 30 carbon atoms or an alkyl group having from 4 to 30 carbon atoms or a cycloalkyl-containing group, which may optionally have substituent(s) and which may be substituted by hetero atom(s) or hetero atom-containing organic group(s), said alkyl group optionally containing unsaturated bond(s), but wherein X is not a methylbenzene-4-amine group when Y = -CH₂CH₂- or S; A represents an optionally substituted condensed aromatic or heterocyclic ring; provided that, if present, the aromatic ring of X or A is benzene, naphthalene, anthracene, pyrrole, furan, thiophene, indole, benzofuran, benzothiophane, pyridine, quinoline isoquinoline, quinolidine, acridine, phenanthridine, pyrazole, imidazole, isoxazole, oxazole, thiazole, isothiazole, pyridazine, pyrazine, purine, puteridine, triazine or benzotriazole. When used as hypotensives the above-defined piperidine derivatives may be administered by an oral or parenteral route. Those may be determined depending upon age, body weight, condition of the patient and route for administration. A daily dose is generally 0.01 to 2000 mg/kg for oral administration; in the case of parenteral administration, a daily dose is generally 0.01 to 1000 mg/kg. The piperidine derivatives may be formulated into conventional preparation forms, for example, tablets, powders, capsules, solutions, sugar-coated tables or depots, which may be prepared in a conventional manner using conventional techniques. For example, tablets can be obtained by mixing a piperidine derivative 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), swelling agents (e.g. alginic acid, corn starch or pregelatinated starch), 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 will now be described in further detail with reference to the examples below. Unless otherwise indicated, developing conditions for silica gel TLC were chloroform/methanol = 9/1; mass spectrum (MS) was performed in FD mode (m/z) and nuclear magnetic resonance spectrum (NMR) was measured using tetramethylsilane as the internal standard and deuterium chloroform as the solvent. Example 1 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-hexylpiperidine hydrochloride: A solution of 273 mg (1 mmol) of 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-hexylpiperidine, 165 mg (1 mmol) of 1-bromohexane, 745 mg (5 mmols) of sodium iodide and 414 mg (3 mmols) of potassium carbonate in 20 ml of methyl isobutyl ketone was stirred and refluxed at 120°C overnight on an oil bath. After the reaction, the mixture was washed by adding 20 ml of water thereto. Then the organic phase was separated and the solvlent was distilled off under reduced pressure. After purifying by silica gel column chromatography (eluent: methanol/chloroform, 1/100 - 1/50), the product was converted into the hydrochloride with an equimolar hydrogen chloride/dioxane solution. Amount yielded 180 mg Yield 46% TLC Rf = 0.68 MS 357 (M+) NMR 0.83 (3H, t), 1.2-1.4 (6H, m), 1.7-1.9 (2H, m), 2.31 (2H, dd), 2.53 (2H, d), 2.7-2.8 (2H, m), 3.14 (2H, dd), 3.38 (2H, dd), 3.38 (2H, d), 6.92 (2H, s), 7.2-7.4 (8H, m) Hereafter procedures were carried out in a manner similar to Example 1. Example 2 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-octylpiperidine hydrochloride: Amount yielded 300 mg Yield 72% TLC Rf = 0.71 MS 385 (M+) NMR 0.85 (3H, t), 1.2-1.4 (10H, m), 1.7-2.0 (2H, m), 2.30 (2H, dd), 2.53 (2H, d), 2.7-2.9 (2H, m), 3.13 (2H, dd), 3.38 (2H, d), 6.90 (2H, s), 7.1-7.4 (8H, m) Example 3 1-Decyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: Amount yielded 300 mg Yield 67% TLC Rf = 0.75 MS 413 (M+) NMR 0.85 (3H, t), 1.2-1.4 (14H, m), 1.7-1.9 (2H, m), 2.33 (2H, dd), 2.54 (2H, d), 2.7-2.8 (2H, m), 3.15 (2H, dd), 3.39 (2H, d), 6.92 (2H, s), 7.1-7.4 (8H, m) Example 4 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-dodecylpiperidine hydrochloride: Amount yielded 1.10 g Yield 92% TLC Rf = 0.78 MS 441 (M+) NMR 0.85 (3H, t), 1.1-1.5 (18H, m), 1.7-1.9 (2H, m), 2.32 (2H, dd), 2.54 (2H, d), 2.7-2.8 (2H, m), 3.12 (2H, dd), 3.36 (2H, d), 6.93 (2H, s), 7.1-7.4 (8H, m) Example 5 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-tetradecylpiperidine hydrochloride: Amount yielded 1.20 g Yield 95% TLC Rf = 0.78 MS 469 (M+) NMR 0.82 (3H, t), 1.1-1.5 (22H, m), 1.7-1.9 (2H, m), 2.33 (2H, dd), 2.55 (2H, d), 2.7-2.8 (2H, m), 3.15 (2H, dd), 3.40 (2H, d), 6.92 (2H, s), 7.1-7.4 (8H, m) Example 6 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-hexadecylpiperidine hydrochloride: Amount yielded 1.18g Yield 88% TLC Rf = 0.80 MS 497 (M+) NMR 0.80 (3H, t), 1.1-1.6 (26H, m), 1.7-1.9 (2H, m), 2.33 (2H, dd), 2.58 (2H, d), 2.7-2.8 (2H, m), 3.20 (2H, dd), 3.40 (2H, d), 6.88 (2H, s), 7.1-7.4 (8H, m) Example 7 1-Cyclohexylmethyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: Amount yielded 520 mg Yield 51% TLC Rf = 0.75 MS 369 (M+) NMR 0.8-2.1 (11H, m), 2.42 (2H, dd), 2.65 (2H, d), 2.78 (2H, d), 3.20 (2H, dd), 3.42 (2H, d), 6.91 (2H, s), 7.1-7.4 (8H, m) Example 8 1-Cyclohexyl-2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethane hydrochloride: Amount yielded 780 mg Yield 74% TLC Rf = 0.75 MS 383 (M+) NMR 0.8-2.1 (13H, m), 2.45 (2H, dd), 2.67 (2H, d), 2.7-2.9 (2H, m), 3.0 (2H, dd), 3.48 (2H, d), 6.94 (2H, s), 7.1-7.4 (8H, m) Example 9 1-Cyclohexyl-3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propane hydrochloride: Amount yielded 1.02 g Yield 94% TLC Rf = 0.77 MS 397 (M+) 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) Example 10 1-Cyclohexyl-4-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butane hydrochloride: Amount yielded 815 mg Yield 72% TLC Rf = 0.78 MS 411 (M+) NMR 0.8-2.1 (17H, m), 2.28 (2H, dd), 2.52 (2H, d), 2.7-2.9 (2H, m), 3.08 (2H, dd), 3.35 (2H, d), 6.92 (2H, s), 7.1-7.4 (8H, m) Example 11 1-Cyclohexyl-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)pentane hydrochloride: Amount yielded 750 mg Yield 65% TLC Rf = 0.80 MS 411 (M+) NMR 0.8-2.1 (19H, m), 2.25 (2H, dd), 2.68 (2H, d), 2.7-2.9 (2H, m), 3.12 (2H, dd), 3.38 (2H, d), 6.92 (2H, s), 7.1-7.4 (8H, m) Example 12 1-Benzyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: Amount yielded 320 mg Yield 80% TLC Rf = 0.42 MS 363 (M+) NMR 2.28 (2H, dd), 2.52 (2H, d), 3.14 (2H, dd), 3.31 (2H, d), 4.01 (2H, d), 6.90 (2H, s), 7.1-7.6 (13H, m) Example 13 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylethane hydrochloride: Amount yielded 310 mg Yield 75% TLC Rf = 0.45 MS 377 (M+) NMR 2.28 (2H, dd), 2.51 (2H, d), 3.0-3.3 (6H, m), 3.47 (2H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 14 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylpropane hydrochloride: Amount yielded 330 mg Yield 77% TLC Rf = 0.50 MS 391 (M+) NMR 2.1-2.4 (4H, m), 2.51 (2H, d), 2.65 (2H, t), 2.7-2.9 (2H, m), 3.12 (2H, dd), 3.38 (2H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 15 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxyethane hydrochloride: Amount yielded 1.95 g Yield 55% TLC Rf = 0.56 MS 393 (M+) NMR (fee base) 2.1-2.5 (2H, m), 2.58 (2H, t), 2.6-2.7 (2H, m), 4.05 (2H, t), 6.89 (2H, d), 6.92 (2H, s), 7.1-7.4 (11H, m) Example 16 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxypropane hydrochloride: Amount yielded 2.15 g Yield 48% TLC Rf = 0.58 MS 407 (M+) NMR (free base) 1.97 (2H, tt), 2.1-2.5 (6H, m), 2.54 (2H, t), 2.6-2.7 (2H, m), 3.97 (2H, dd), 6.86 (2H, d), 6.90 (2H, s), 7.1-7.4 (11H, m) Example 17 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthiopropane hydrochloride: Amount yielded 0.85 g Yield 74% TLC Rf = 0.62 MS 423 (M+) NMR (free base) 1.73 (2H, tt), 2.0-2.6 (10H, m), 2.80 (2H, t), 6.88 (2H, d), 7.1-7.4 (11H, m) Example 18 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-(3,4-dimethoxyphenyl)ethane hydrochloride: TLC Rf = 0.78 MS 450 (M+) Example 19 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl-4-fluorophenylsulfoxide hydrochloride: TLC Rf = 0.78 MS 457 (M+) Example 20 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl-4-fluorophenylsulfone hydrochloride: TLC Rf = 0.62 MS 473 (M+) Example 21 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-(2-aminophenylthio)propyl)piperidine hydrochloride: TLC Rf = 0.84 MS 439 (M+) Example 22 1-(3-(2-Cinnamoylaminophenylthio)- propyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: TLC Rf = 0.66 MS 568 (M+) NMR (free base) 1.74 (2H, tt), 2.0-2.6 (8H, m), 2.80 (2H, t), 6.59 (1H, d), 6.88 (2H, s), 7.0-7.6 (16H, m), 7.75 (1H, d), 8.5 (1H, d), 8.68 (1H, bs) Example 23 1-Cinnamyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: TLC Rf = 0.84 MS 389 (M+) NMR (free base) 2.1-2.7 (8H, m), 3.15 (2H, d), 6.25 (1H, td), 6.47 (1H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 24 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)acetophenone hydrochloride: TLC Rf = 0.71 MS 391 (M+) Example 25 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylethane hydrochloride: TLC Rf = 0.36 MS 393 (M+) Example 26 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propiophenone hydrochloride: TLC Rf = 0.74 MS 405 (M+) Example 27 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylpropane hydrochloride: TLC Rf = 0.35 MS 407 (M+) Example 28 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluoroacetophenone hydrochloride: TLC Rf = 0.80 MS 409 (M+) Example 29 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)ethane hydrochloride: TLC Rf = 0.44 MS 411 (M+) Example 30 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluoropropiophenone hydrochloride: TLC Rf = 0.80 MS 423 (M+) Example 31 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)propane hydrochloride: TLC Rf = 0.44 MS 425 (M+) Example 32 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-fluorobenzyl)piperidine hydrochloride: TLC Rf = 0.75 MS 381 (M+) Example 33 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-fluorobenzyl)piperidine hydrochloride: TLC Rf = 0.79 MS 381 (M+) Example 34 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorobenzyl)piperidine hydrochloride: TLC Rf = 0.61 MS 381 (M+) Example 35 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-trifluoromethylbenzyl)piperidine hydrochloride: TLC Rf = 0.83 MS 431 (M+) Example 36 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-trifluoromethylbenzyl)piperidine hydrochloride: TLC Rf = 0.82 MS 431 (M+) Example 37 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoromethylbenzyl)piperidine hydrochloride: TLC Rf = 0.79 MS 431 (M+) Example 38 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxybenzyl)piperidine hydrochloride: TLC Rf = 0.61 MS 393 (M+) Example 39 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxybenzyl)piperidine hydrochloride: TLC Rf = 0.61 MS 393 (M+) Example 40 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxybenzyl)piperidine hydrochloride: TLC Rf = 0.52 MS 393 (M+) Example 41 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-pentafluorobenzylpiperidine hydrochloride: TLC Rf = 0.80 MS 453 (M+) Example 42 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-(4-fluorophenyl)ethane hydrochloride TLC Rf = 0.55 MS 395 (M+) Example 43 1-(2-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine hydrochloride TLC Rf = 0.68 MS 397 (M+) Example 44 1-(3-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine hydrochloride TLC Rf = 0.58 MS 397 (M+) Example 45 1-(4-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine hydrochloride TLC Rf = 0.58 MS 397 (M+) Example 46 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methylbenzyl) piperidine hydrochloride TLC Rf = 0.74 MS 377 (M+) Example 47 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methylbenzyl) piperidine hydrochloride TLC Rf = 0.71 MS 377 (M+) Example 48 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methylbenzyl) piperidine hydrochloride TLC Rf = 0.65 MS 377 (M+) Example 49 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-heptylpiperidine hydrochloride TLC Rf = 0.70 MS 371 (M+) Example 50 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-nonylpiperidine hydrochloride TLC Rf = 0.75 MS 399 (M+) Example 51 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-undecylpiperidine hydrochloride TLC Rf = 0.75 MS 427 (M+) Example 52 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-tridecylpiperidine hydrochloride TLC Rf = 0.78 MS 455 (M+) Example 53 1-(2-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine dihydrochloride TLC Rf = 0.38 MS 392 (M+) Example 54 1-(3-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine dihydrochloride TLC Rf = 0.23 MS 392 (M+) Example 55 1-(4-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine dihydrochloride TLC Rf = 0.26 MS 392 (M+) Example 56 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-nitrobenzyl) piperidine hydrochloride TLC Rf = 0.85 MS 422 (M+) Example 57 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-nitrobenzyl) piperidine hydrochloride TLC Rf = 0.82 MS 422 (M+) Example 58 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrobenzyl) piperidine hydrochloride TLC Rf = 0.83 MS 422 (M+) Example 59 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenyl-1-butene hydrochloride TLC Rf = 0.51 MS 403 (M+) Example 60 1-Benzyloxy-2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethane hydrochloride TLC Rf = 0.58 MS 407 (M+) Test Example 1 As test animals, four male spontaneously hypertensive rats (weighing 400 to 440 g) that were sufficiently adapted for feeding and in which hypertension was confirmed were used. Physiological saline aqueous solution containing 2.5% Nicolle of sample and 2.5% ethanol was intravenously administered at once in a dose of 1 ml/kg. Blood pressure after the administration was measured by non-blood observation blood pressure measurement method. The results are shown below. Further Examples 61 to 95 are shown in Table 1 below. Test Example 2 Piperidine derivatives of Examples 61 to 95 were tested in the same manner as in Test Example 1. The results are shown below. Example Dose (mg/kg) Decrease in Blood Pressure (mmHg) 30 Minutes 4 Hours 61 10 - 131 - 105 64 10 - 32 - 13 65 10 - 8 7 66 10 - 27 - 12 67 10 - 3 - 10 68 10 - 64 - 12 69 10 - 62 - 3 70 10 - 1 4 71 10 - 91 - 22 72 10 - 22 12 73 10 - 45 6 74 10 - 9 7 75 10 - 108 0 76 10 - 130 - 4 78 10 - 122 - 8 79 10 - 115 - 25 80 10 - 98 - 25 81 10 - 8 - 16 82 10 - 87 - 1 92 10 - 66 - 10 93 10 - 95 - 12 94 10 - 47 - 9 95 10 - 94 - 12 Further Examples illustrative of the present invention are Examples 96 to 188 which follow. Example 96 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylbutane hydrochlcride: Amount yielded 180 mg Yield 41% TLC Rf = 0.50 MS 405 (M+) NMR 1.4-1.9 (4H, m), 2.28 (2H, dd), 2.52 (2H, d), 2.61 (2H, t), 2.7-2.8 (2H, m), 3.12 (2H, dd), 3.35 (2H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 97 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylpentane hydrochloride: Amount yielded 110 mg Yield 24% TLC Rf = 0.55 MS 419 (M+) NMR 1.2-1.9 (6H, m), 2.25 (2H, dd), 2.52 (2H, d), 2.60 (2H, t), 2.7-2.8 (2H, m), 3.08 (2H, dd), 3.35 (2H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 98 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylhexane hydrochloride: Amount yielded 315 mg Yield 67% TLC Rf = 0.56 MS 433 (M+) NMR 1.1-1.9 (8H, m), 2.26 (2H, dd), 2.56 (2H, d), 2.61 (2H, t), 2.7-2.8 (2H, m), 3.10 (2H, dd), 3.35 (2H, d), 6.91 (2H, s), 7.1-7.4 (13H, m) Example 99 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylheptane hydrochloride: Amount yielded 267 mg Yield 55% TLC Rf = 0.56 MS 447 (M+) NMR 1.1-1.9 (10H, m), 2.25 (2H, dd), 2.55 (2H, d), 2.65 (2H, t), 2.7-2.8 (2H, m), 3.07 (2H, dd), 3.32 (2H, d), 6.90 (2H, s), 7.1-7.4 (13H, m) Example 100 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxybutane hydrochloride: Amount yielded 1.18 g Yield 86% TLC Rf = 0.61 MS 421 (M+) NMR (free base) 1.8-2.7 (14H, m), 3.96 (2H, t), 6.87 (2H, d), 6.90 (2H, s), 7.1-7.4 (11H, m) Example 101 2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthioethane hydrochloride: Amount yielded 0.97 g Yield 87% TLC Rf = 0.55 MS 409 (M+) Example 102 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthiobutane hydrochloride: Amount yielded 0.85 g Yield 72% TLC Rf = 0.62 MS 437 (M+) NMR (free base) 1.6-2.6 (14H, m), 2.80 (2H, t), 6.88 (2H, d), 7.1-7.4 (11H, m) Example 103 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(2-nitrobenzenesulfonyl amino)ethyl)piperidine hydrochloride: TLC Rf = 0.72 MS 502 (M+) Example 104 1-(2-(2-Aminobenzenesulfonyl amino)ethyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride: TLC Rf = 0.51 MS 472 (M+) Example 105 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(2-ethoxycarbonylbenzenesulfonyl amino)ethyl)piperidine hydrochloride: TLC Rf = 0.68 MS 544 (M+) Example 106 3-(2-( 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethyl)-2,4(1H,3H)quinazolinedione hydrochloride: TLC Rf = 0.85 MS 462 (M+) Example 107 5,6-Benzo-2,4-diaza(2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethyl)tetrahydrothiopyrane-1,1-dioxide hydrochloride: TLC Rf = 0.91 MS 498 (M+) Example 108 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride: TLC Rf = 0.92 MS 532 (M+) NMR 0.77 (3H, d), 1.18 (3H, d), 1.6-3.3 (15H, m), 3.86 (3H, s), 3.92 (3H, s), 6.8-7.4 (11H, m) Example 109 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(benzoylamino)ethyl)piperidine hydrochloride: TLC Rf = 0.84 MS 420 (M+) Example 110 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(phenylcarbamoylamino)ethyl)piperidine hydrochloride: TLC Rf = 0.55 MS 435 (M+) Example 111 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4,5-trimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride: TLC Rf = 0.80 MS 563 (M+) Example 112 2-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-2-phenyl-1,3-dithiane-1,1,3,3-tetroxide hydrochloride: TLC Rf = 0.48 MS 573 (M+) Example 113 2-(3,4-Dimethoxyphenyl)-2-(3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)- propyl)-1,3-dithiane-1,1,3,3-tetroxide hydrochloride: TLC Rf = 0.48 MS 573 (M+) Example 114 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dichlorophenyl)-2-isopropylvaleronitrile hydrochloride: TLC Rf = 0.94 MS 540 (M+) Example 115 2-(3-Benzoylphenyl)-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylvaleronitrile hydrochloride: TLC Rf = 0.88 MS 548 (M+) Example 116 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2,2-diphenylvaleronitrile hydrochloride: TLC Rf = 0.74 MS 506 (M+) Example 117 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4'-dimethoxybutyrophenone hydrochloride: TLC Rf = 0.61 MS 479 (M+) Example 118 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylhexanenitrile hydrochloride: TLC Rf = 0.86 MS 430 (M+) Example 119 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylhexanenitrile hydrochloride: TLC Rf = 0.88 MS 472 (M+) Example 120 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylhexanenitrile hydrochloride: TLC Rf = 0.81 MS 546 (M+) Example 121 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylheptanenitrile hydrochloride: TLC Rf = 0.84 MS 444 (M+) Example 122 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylheptanenitrile hydrochloride: TLC Rf = 0.84 MS 486 (M+) Example 123 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylheptanenitrile hydrochloride: TLC Rf = 0.86 MS 560 (M+) Example 124 2-(3-Chloropropyl)-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.92 MS 506 (M+) Example 125 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenyl-2-phenylthiovaleronitrile hydrochloride: TLC Rf = 0.81 MS 538 (M+) Example 126 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-phenylthiovaleronitrile hydrochloride: TLC Rf = 0.91 MS 598 (M+) Example 127 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-naphthyl)valeronitrile hydrochloride: TLC Rf = 0.85 MS 580 (M+) Example 128 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-naphthyl)-2-isopropylvaleronitrile hydrochloride: TLC Rf = 0.90 MS 522 (M+) Example 129 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(2-naphthyl)valeronitrile hydrochloride: TLC Rf = 0.85 MS 480 (M+) Example 130 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(2-naphthyl)-2-isopropylvaleronitrile hydrochloride: TLC Rf = 0.87 MS 522 (M+) Example 131 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride: TLC Rf = 0.72 MS 498 (M+) Example 132 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride: TLC Rf = 0.75 MS 540 (M+) Example 133 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenyloctanenitrile hydrochloride: TLC Rf = 0.84 MS 472 (M+) Example 134 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenyloctanenitrile hydrochloride: TLC Rf = 0.88 MS 514 (M+) Example 135 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropyloctanenitrile hydrochloride: TLC Rf = 0.82 MS 574 (M+) Example 136 1-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-1-indanecarbonitrile hydrochloride: TLC Rf = 0.90 MS 456 (M+) Example 137 1-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-5,6-dimethoxy-1-indanecarbonitrile hydrochloride: TLC Rf = 0.85 MS 516 (M+) Example 138 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-methylpyrrol-2-yl)valeronitrile hydrochloride: TLC Rf = 0.61 MS 433 (M+) Example 139 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(1-methylpyrrol-2-yl)valeronitrile hydrochlcride: TLC Rf = 0.71 MS 475 (M+) Example 140 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(pyrrol-2-yl)valeronitrile hydrochloride: TLC Rf = 0.55 MS 461 (M+) Example 141 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylvaleronitrile hydrochloride: TLC Rf = 0.51 MS 550 (M+) Example 142 2-(3-Benzoylphenyl)-6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylhexanenitrile hydrochloride: TLC Rf = 0.88 MS 562 (M+) Example 143 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylhexanenitrile hydrochloride: TLC Rf = 0.52 MS 564 (M+) Example 144 2-(3-Benzoylphenyl)-7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylheptanenitrile hydrochloride: TLC Rf = 0.91 MS 576 (M+) Example 145 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylheptanenitrile hydrochloride: TLC Rf = 0.52 MS 578 (M+) Example 146 2-(3-Benzoylphenyl)-8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methyloctanenitrile hydrochloride: TLC Rf = 0.90 MS 590 (M+) Example 147 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methyloctanenitrile hydrochloride: TLC Rf = 0.61 MS 592 (M+) Example 148 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.91 MS 544 (M+) Example 149 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-methylvaleronitrile hydrochloride: TLC Rf = 0.85 MS 504 (M+) Example 150 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-ethyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.92 MS 458 (M+) Example 151 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-ethylvaleronitrile hydrochloride: TLC Rf = 0.90 MS 518 (M+) Example 152 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-propyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.93 MS 472 (M+) Example 153 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-propylvaleronitrile hydrochloride: TLC Rf = 0.91 MS 532 (M+) Example 154 2-Butyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 486 (M+) Example 155 2-Butyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride: TLC Rf = 0.90 MS 546 (M+) Example 156 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-pentyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 500 (M+) Example 157 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-pentylvaleronitrile hydrochloride: TLC Rf = 0.92 MS 560 (M+) Example 158 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-hexyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 514 (M+) Example 159 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-hexylvaleronitrile hydrochloride: TLC Rf = 0.92 MS 574 (M+) Example 160 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-heptyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 528 (M+) Example 161 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-heptylvaleronitrile hydrochloride: TLC Rf = 0.91 MS 588 (M+) Example 162 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-octyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.94 MS 542 (M+) Example 163 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-octylvaleronitrile hydrochloride: TLC Rf = 0.94 MS 602 (M+) Example 164 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-nonyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 556 (M+) Example 165 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-nonylvaleronitrile hydrochloride: TLC Rf = 0.93 MS 616 (M+) Example 166 2-Decyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.95 MS 570 (M+) Example 167 2-Decyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride: TLC Rf = 0.94 MS 630 (M+) Example 168 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butyrophenone hydrochloride: TLC Rf = 0.75 MS 419 (M+) Example 169 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylbutane hydrochloride: TLC Rf = 0.39 MS 421 (M+) Example 170 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)valerophenone hydrochloride: TLC Rf = 0.76 MS 433 (M+) Example 171 5-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylpentane hydrochloride: TLC Rf = 0.78 MS 447 (M+) Example 172 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)butane hydrochloride: TLC Rf = 0.45 MS 439 (M+) Example 173 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluorovalerophenone hydrochloride: TLC Rf = 0.84 MS 451 (M+) Example 174 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)pentane hydrochloride: TLC Rf = 0.51 MS 453 (M+) Example 175 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.86 MS 440 (M+) Example 176 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylvaleronitrile hydrochloride: TLC Rf = 0.82 MS 488 (M+) Example 177 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride: TLC Rf = 0.75 MS 500 (M+) Example 178 2-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-2-(4-fluorophenyl)-1,3-dioxolane hydrochloride: TLC Rf = 0.68 MS 481 (M+) Example 179 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluorobutyrophenone hydrochloride: TLC Rf = 0.82 MS 437 (M+) Example 180 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3,4,5-trimethoxyphenyl)valeronitrile hydrochloride: TLC Rf = 0.66 MS 562 (M+) Example 181 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-fluorophenyl)-2-isopropylvaleronitrile hydrochloride TLC Rf = 0.71 MS 500 (M+) Example 182 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3-methoxyphenyl)valeronitrile hydrochloride TLC Rf = 0.64 MS 512 (M+) Example 183 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3-methyl phenyl)valeronitrile hydrochloride TLC Rf = 0.68 MS 496 (M+) Example 184 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(2-trifluoromethylphenyl)valeronitrile hydrochloride TLC Rf = 0.78 MS 549 (M+) Example 185 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(4-trifluoromethylphenyl)valeronitrile hydrochloride TLC Rf = 0.77 MS 540 (M+) Example 186 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-ethyl-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride TLC Rf = 0.77 MS 526 (M+) Example 187 2-Butyl-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride TLC Rf = 0.80 MS 554 (M+) Example 188 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-hexyl-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride TLC Rf = 0.80 MS 582 (M+) Test Example 3 Piperidine derivatives of Examples 96 to 188 were tested in the same manner as in Test Example 1. The results are shown below. Example Dose (mg/kg) Decrease in Blood Pressure (mmHg) 30 Minutes 4 Hours 96 10 - 130 - 136 97 10 - 114 - 30 98 10 - 84 - 16 103 10 - 8 - 7 106 10 - 52 4 108 10 - 61 - 11 114 10 - 66 - 14 116 10 - 14 1 117 10 - 147 - 38 124 10 - 23 - 9 131 10 - 87 - 21 132 10 - 121 - 48 168 10 - 35 - 5 169 10 - 89 - 14 172 10 - 126 - 50 175 10 - 42 - 19 176 10 - 120 - 62 177 10 - 55 - 7 178 10 - 90 - 20 179 10 - 93 - 14 180 10 - 87 - 19 186 10 - 116 - 32 187 10 - 110 - 47 188 10 - 81 - 43 From the foregoing results, it is understood that the piperidine derivatives used according to the present invention provide excellent hypotensives. Accordingly, the present invention is extremely useful, particularly in the pharmaceutical industry.

Claims: Use in the preparation of a hypotensive medicament of a piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof: wherein any of R¹, R², R³ and R⁴ may be the same or different from each other and each independently represents a hydrogen atom or a halogen atom, alkyl group having 1 to 4 carbon atoms, hydroxyl group, amino group, cyano group, methoxy group, methylthio group, hydroxymethyl group, carboxyl group, trifluoromethyl group, trifluoromethoxy group, trifluoromethylthio group, trifluoromethylsulfonyl group, hydroxyamino group or nitro group; Y represents a hetero atom or an optionally substituted alkylene chain, the alkylene chain optionally containing one or more hetero atoms or one or more unsaturated bonds; and X represents an aralkyl- or aryl-containing group having from 6 to 30 carbon atoms or an alkyl group having from 4 to 30 carbon atoms or a cycloalkyl-containing group, which may optionally have substituent(s) and which may be substituted by hetero atom(s) or hetero atom-containing organic group(s), said alkyl group optionally containing unsaturated bond(s), but wherein X is not a methylbenzene-4-amine group when Y = -CH₂CH₂- or S; A represents an optionally substituted condensed aromatic or heterocyclic ring; provided that, if present, the aromatic ring of X or A is benzene, naphthalene, anthracene, pyrrole, furan, thiophene, indole, benzofuran, benzothiophene, pyridine, quinoline, isoquinoline, quinolidine, acridine, phenanthridine, pyrazole, imidazole, isoxazole, oxazole, thiazole, isothiazole, pyridazine, pyrazine, purine, puteridine, triazine or benzotriazole. Use according to Claim 1, wherein Y in the formula (I) represents an oxygen, sulphur or nitrogen atom or an optionally substituted alkylene chain having 2 or less carbon atoms, said alkylene chain optionally containing oxygen, sulphur and/or nitrogen atom(s) or unsaturated bond(s). Use according to Claim 1, wherein Y represents the group -CH=CH-, -CH₂CH₂-, -O-, -S- or Use according to Claim 3, wherein A represents a benzene, thiophene or pyridine ring. Use according to Claim 3 or Claim 4, wherein R¹, R², R³ and R⁴ each represents a hydrogen atom. Use according to Claim 1, wherein the piperidine derivative is any one of the following: 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-hexylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-octylpiperidine 1-Decyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-dodecylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-tetradecylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-hexadecylpiperidine 1-Cyclohexylmethyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-Cyclohexyl-2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethane 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 1-Cyclohexyl-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)pentane 1-Benzyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylethane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylpropane 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxyethane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxypropane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthiopropane 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-(3,4-dimethoxyphenyl)ethane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl-4-fluorophenylsulfoxide 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl-4-fluorophenylsulfone 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-(2-aminophenylthio)propyl)piperidine 1-(3-(2-Cinnamoylaminophenylthio)- propyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-Cinnamyl-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 2 -(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-acetophenone 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylethane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propiophenone 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylpropane 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluoroacetophenone 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)ethane 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluoropropiophenone 3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)propane 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-fluorobenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-fluorobenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-fluorobenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-trifluoromethylbenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-trifluoromethylbenzyl)piperidine 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-trifluoromethylbenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methoxybenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methoxybenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methoxybenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-pentafluorobenzylpiperidine 2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-(4-fluorophenyl)ethane 1-(2-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 1-(3-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 1-(4-Chlorobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-methylbenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-methylbenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-methylbenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-heptylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-nonylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-undecylpiperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-tridecylpiperidine 1-(2-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 1-(3-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 1-(4-Aminobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-nitrobenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-nitrobenzyl) piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-nitrobenzyl) piperidine 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -1-phenyl-1-butene 1-Benzyloxy-2-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethane 1-Cyclohexyl-6-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)hexane 1-Cyclohexyl-7-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)heptane 1-Cyclohexyl-8-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)octane 1-(4-Cyclohexylbutanoyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-(2-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-(3-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-(4-Cyanobenzyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-Picolyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-Picolyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(4-Picolyl)piperidine 1-(Decanoyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-Cyano-3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propane 1-Cyano-4-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butane 2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4'-dimetoxyacetophenone 3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4'-dimetoxyacetophenone 5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4'-dimetoxyvalerophenone 4-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4',5'-trimetoxybutyrophenone 4-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2',3',4'-trimetoxybutyrophenone 4-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-metoxybutyrophenone 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2,3-dimetoxybenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimetoxybenzyl)piperidine 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4-dimetoxybenzoyl)piperidine 1-Cyclohexyl-3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propylketone 2-Cyclohexyl-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)valeronitrile 1-(4-(3-Chloro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4-Cyclohexylbutane 1-Cyclohexyl-(4-(3-metoxy-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butane 4,9-Dihydro-4-(1-(4-cyclohexylbutyl)-4-piperidylidene)-10H-benzo[4,5]cyclohepta[1,2-b] tiophen-10-one 1-(4-Cyclohexylbutyl)-4-(9-xantylidene)piperidine 1-(4-Cyclohexylbutyl)-4-(9-tioxantylidene)piperidine 6,11-Dihydro-11-(1-(4-cyclohexylbutyl)-4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b] pyridine 4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-(3-metoxybenzyl)piperidine 1-Decyl-4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine 1-Cyclohexyl-4-(4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl ) butane 4-(4-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-pipendinyl)-3',4'-dimetoxybutyrophenone 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(3,4,5-trimetoxybenzyl)piperidine or a hydrochloride salt thereof; or any one of the following compounds or a free base form thereof: 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylbutane hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylpentane hydrochloride; 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylhexane hydrochloride; 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylheptane hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenoxybutane hydrochloride; 2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthioethane hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-phenylthiobutane hydrochloride; 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(2-nitrobenzenesulfonyl amino)ethyl)piperidine hydrochloride; 1-(2-(2-Aminobenzenesulfonyl amino)ethyl)-4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine hydrochloride; 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(2-ethoxycarbonylbenzenesulfonyl amino)ethyl)piperidine hydrochloride; 3-(2-( 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethyl)-2,4(1H,3H)quinazolinedione hydrochloride; 5,6-Benzo-2,4-diaza(2-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)ethyl)tetrahydrothiopyrane-1,1-dioxide hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride; 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(benzoylamino)ethyl)piperidine hydrochloride; 4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-(2-(phenylcarbamoylamino)ethyl)piperidine hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4,5-trimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride; 2-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-2-phenyl-1,3-dithiane-1,1,3,3-tetroxide hydrochloride; 2-(3,4-Dimethoxyphenyl)-2-(3-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)- propyl)-1,3-dithiane-1,1,3,3-tetroxide hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dichlorophenyl)-2-isopropylvaleronitrile hydrochloride; 2-(3-Benzoylphenyl)-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2,2-diphenylvaleronitrile hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-3',4'-dim ethoxybutyrophenone hydrochloride; 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylhexanenitrile hydrochloride; 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylhexanenitrile hydrochloride; 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylhexanenitrile hydrochloride; 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylheptanenitrile hydrochloride; 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylheptanenitrile hydrochloride; 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropylheptanenitrile hydrochloride; 2-(3-Chloropropyl)-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenyl-2-phenylthiovaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-phenylthiovaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-naphthyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-naphthyl)-2-isopropylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(2-naphthyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(2-naphthyl)-2-isopropylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride; 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenyloctanenitrile hydrochloride; 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenyloctanenitrile hydrochloride; 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-isopropyloctanenitrile hydrochloride; 1-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-1-indanecarbonitrile hydrochloride; 1-(3-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-5,6-dimethoxy-1- indanecarbonitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(1-methylpyrrol-2-yl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(1-methylpyrrol-2-yl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(pyrrol-2-yl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylvaleronitrile hydrochloride; 2-(3-Benzoylphenyl)-6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylhexanenitrile hydrochloride; 6-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylhexanenitrile hydrochloride; 2-(3-Benzoylphenyl)-7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methylheptanenitrile hydrochloride; 7-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methylheptanenitrile hydrochloride; 2-(3-Benzoylphenyl)-8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methyloctanenitrile hydrochloride; 8-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3-(α-hydroxybenzyl)phenyl)-2-methyloctanenitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-methyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-methylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-ethyl -2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-ethylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-propyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-propylvaleronitrile hydrochloride; 2-Butyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride; 2-Butyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-pentyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-pentylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-hexyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-hexylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-heptyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-heptylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-octyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-octylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-nonyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)-2-nonylvaleronitrile hydrochloride; 2-Decyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride; 2-Decyl-5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)butyrophenone hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylbutane hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)valerophenone hydrochloride; 5-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-phenylpentane hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)butane hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluorovalerophenone hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-1-hydroxy-1-(4-fluorophenyl)pentane hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-phenylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-(3,4-dimethoxyphenyl)valeronitrile hydrochloride; 2-(3-(4-(5H-Dibenzo(a,d]cyclohepten-5-ylidene)-1-piperidinyl)propyl)-2-(4-fluorophenyl)-1,3-dioxolane hydrochloride; 4-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-4'-fluorobutyrophenone hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-isopropyl-2-(3,4,5-trimethoxyphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-(3-fluorophenyl)-2-isopropylvaleronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-isopropyl-2-(3-methoxyphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-isopropyl-2-(3-methyl phenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-isopropyl-2-(2-trifluoromethylphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-isopropyl-2-(4-trifluoromethylphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-ethyl-2-(3-trifluoromethylphenyl)valeronitrile hydrochloride; 2-Butyl-5-(4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl) -2-(3-trifluoromethylphenyl)valeronitrile hydrochloride; 5-(4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-1-piperidinyl)-2-hexyl 2-(3-trifluoromethylphenyl)valeronitrile hydrochloride. Use according to any one of claims 1 to 6, wherein the piperidine derivative is used together with an auxiliary substance, said auxiliary substance being any of an inactive diluent, binder, swelling agent, sweetener, flavour, lubricating agent or wetting agent.

Inventors: DOMOTO HIDEKI, EGUCHI CHIKAHIKO, KAMIMURA AKIRA, SYOJI MASATAKA, TOYOTA KOZO, YOSHIMOTO RYOTA, DOMOTO, HIDEKI, EGUCHI, CHIKAHIKO, KAMIMURA, AKIRA, SYOJI, MASATAKA, TOYOTA, KOZO, YOSHIMOTO, RYOTA, DOMOTO, HIDEKI C/O CENTRAL RESEARCH LABORATORIES, EGUCHI, CHIKAHIKO C/O CENTRAL RESEARCH LAB., KAMIMURA, AKIRA C/O CENTRAL RESEARCH LABORATORIES, SYOJI, MASATAKA C/O CENTRAL RESEARCH LABORATORIES, TOYOTA, KOZO C/O CENTRAL RESEARCH LABORATORIES, YOSHIMOTO, RYOTA C/O CENTRAL RESEARCH LABORATORIES
Applicants: AJINOMOTO KK, AJINOMOTO CO., INC.
Application year: 1989
Main classification: C07D211
IPC codes: A61K31, C07D401, C07D211, C07D405, A61P9, C07D295, C07D473, C07D409, C07D413, C07D417, C07D471, C07C255