WO1997045119A1 - Use of substance p antagonists for treating social phobia - Google Patents

Use of substance p antagonists for treating social phobia Download PDF

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WO1997045119A1
WO1997045119A1 PCT/EP1997/002481 EP9702481W WO9745119A1 WO 1997045119 A1 WO1997045119 A1 WO 1997045119A1 EP 9702481 W EP9702481 W EP 9702481W WO 9745119 A1 WO9745119 A1 WO 9745119A1
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benzyl
piperidineamine
dimethylbenzoyl
chlorophenyl
ethyl
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PCT/EP1997/002481
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French (fr)
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Michael Struck
Annick Vassout
Richard Katz
Deborah Bennett
Lynn Kramer
Kathleen Hauser
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Novartis Ag
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine

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Abstract

The invention relates to the use of a compound of formula (I) or of a pharmaceutically utilizable salt thereof, in which R1 is an unsubstituted or substituted aralkyl, aryloxyalkyl, heteroaralkyl, aroyl, heteroaroyl, cycloalkylcarbonyl, aralkanoyl, heteroarylalkanoyl, aralkoxycarbonyl or arylcarbamoyl radical or the acyl radical of an α-amino acid which is unsubstituted or N-substituted by lower alkanoyl or carbamoyl-lower-alkanoyl; R2 is cycloalkyl or an unsubstituted or substituted aryl or heteroaryl radical; R3 is hydrogen, alkyl, carbamoyl or an alkanoyl or alkenoyl radical which is unsubstituted or substituted by carboxyl or esterified or amidated carboxyl; R4 is an unsubstituted or substituted aryl or unhydrogenated or partially hydrogenated heteroaryl radical; X1 is methylene, ethylene, a direct linkage, a carbonyl group which may be ketalized, or an unetherified or etherified hydroxymethylene group; X2 is alkylene, carbonyl or a direct linkage; and X3 is carbonyl, oxo-lower-alkylene, oxo(aza)-lower-alkylene or an alkylene radical which is unsubstituted or substituted by phenyl, hydroxymethyl, carboxyl which may be esterified or amidated, or by hydroxyl in a position higher than α; for producing pharmaceutical products for the treatment of social phobia.

Description

USE OF SUBSTANCE P ANTAGONISTS FOR TREATING SOCIAL PHOBIA
Background of the invention
Tachykinins can be assigned to a family of peptides which have a common Phe-X-Gly-Leu- Meth-NH2 C terminal sequence. One representative of this class of substances is called substance P which, as neurotransmitter or neuromodulator, has a high affinity for the neurokinin-1 (NKi) receptor. Tachykinins are widespread in the central and peripheral nervous systems. Substance P antagonists are attributed with a valuable range of therapeutic properties. For example, it has emerged that substance P antagonists have a pronounced antiasthmatic and anxiolytic effect. The aim of further intensive efforts is to find potential further therapeutic uses of substance P antagonists able to round off the favourable profile of action of such antagonists.
Description of the invention
There is a pressing need in medicine to find an effective approach to the therapy of the two widespread pathological manifestations of panic disorder and social phobia. According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DMS) there is a clear-cut distinction between panic and anxiety disorders. Panic disorder is manifested by discrete unexpected panic attacks, most of which are not caused by external stimuli. Only when such attacks occur with a certain frequency and regularity can they be reliably assigned to the phenomenon of panic disorder. The DSM-lli-R criteria, for example, mandate e.g. for the panic disorder condition at least four attacks in 4-week period or one severe attack followed by at least a month of persistent fear of having another attack. Corresponding DSM-III criteria for social phobia include e.g. a persistent, irrational fear of, and compelling desire to avoid, a situation in which the individual is exposed to possible scrutiny by others and fears that the individual may act in way that will be humiliating or embarrassing.Social phobia is diagnosed when an individual has a central anxiety about, for example, appearing ridiculous in public or getting into embarrassing situations, and if the person, through avoiding such situations, aims at becoming socially isolated. Typical social phobias are of speaking, eating, or writing in public, using public laboratories, and attending parties or interviews. One individual may have one social phobia or many Corresponding individuals usually fear that other people will detect and πdicul there phobia
It has now been found, surprisingly, that substance P antagonists can be employed for the treatment of panic disorder and social phobia. Since the effects which have been found for substance P antagonists in preclinical animal models are analogous to those of phenelzine, fluoxetine, paroxetine and chlordiazepoxide, substance P antagonists can equally be employed clinically for the treatment of panic disorder and social phobia.
This is true in particular of compounds of the formula (I)
Figure imgf000004_0001
and their pharmaceutically utilizable salts, in which
Rι is an unsubstituted or substituted aralkyl, aryloxyalkyl, heteroaralkyl, aroyl, heteroaroyl, cycloalkylcarbonyl, aralkanoyi, heteroarylalkanoyi, aralkoxycarbonyl or arylcarbamoyi radical or the acyl radical of an α-amino acid which is unsubstituted or N-substituted by lower alkanoyl or carbamoyl-lower-alkanoyl;
R2 is cycloalkyl or an unsubstituted or substituted aryl or heteroaryl radical;
R3 is hydrogen, alkyl, carbamoyi or an alkanoyl or alkenoyl radical which is unsubstituted or substituted by carboxyl or esterified or amidated carboxyl;
R4 is an unsubstituted or substituted aryl or unhydrogenated or partially hydrogenated heteroaryl radical;
XT IS methylene, ethylene, a direct linkage, a carbonyl group which may be ketalized, or an unetheπfied or etherified hydroxymethylene group;
X2 is alkylene, carbonyl or a direct linkage; and
X3 is carbonyl, oxo-lower-alkylene, oxo(aza)-lower-alkylene or an alkylene radical which is unsubstituted or substituted by phenyl, hydroxymethyl, carboxyl which may be esterified or amidated, or by hydroxyl in a position higher than α. Said aryl, aroyl, aralkanoyi, heteroaryl and heteroaroyi radicals can be unsubstituted or substituted, such as mono-, di- or trisubstituted, in particular mono- or disubstituted, for example by aromatically bonded lower alkyl, lower alkoxy, halogen and/or trifluoromethyl. Aryl, aralkyi, aryloxyalkyi, cycloalkylcarbonyl and aroyl radicals are preferably mono- or disubstituted, such as 3-mono- or 3,5-disubstituted, in the stated manner; heteroaryl, heteroaralkyl, heteroaralkanoyl and heteroaroyi radicals are preferably unsubsituted. Aralkyi is, for example, phenyl- or diphenyl-lower-alkyl which is unsubstituted or substituted in the phenyl or naphthyl moiety.
Aryloxy-lower-alkyl is, for example, phenoxy-lower-alkyl which is unsubstituted or substituted in the phenyl moiety.
Heteroaralkyl is, for example, heteroaryl-lower-alkyl having as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6-membered and a 5- or 6-membered ring.
Aroyl is, for example, unsubstituted or substituted benzoyl, such as benzoyl, 3-lower-alkyl-, 3-lower-alkoxy-, 3-halo-, 3-dimethylamino-, 3,5-di-lower-alkyl-, 3,5-di-lower-alkoxy-, 3,5-dihalo- or 3,5-ditrifluoromethylbenzoyl, or secondarily unsubstituted or substituted naphthoyl such as 1- or 2-naphthoyl.
Heteroaroyi is, for example, an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6-membered and a 5- or 6-membered ring, such as pyridylcarbonyl or quinolinylcarbonyl.
Cycloalkanoyl is, for example, unsubstituted or substituted 3- to 8-, in particular 5- to 7-, membered cycloalkylcarbonyl such as cyclohexylcarbonyl, 3-lower-alkyl-, 3-lower-alkoxy-, 3-halo-, 3-dimethylamino-, 3,5-di-lower-alkyI, 3,5-di-lower-alkoxy-, 3,5-dihalo- or 3,5-ditrifluoromethylcyclohexylcarbonyl.
Aralkanoyi is, for example, phenyl- or diphenyl-lower-alkanoyl which is unsubstituted or substituted in the phenyl moiety. Heteroarylalkanoyi is, for example, a heteroaryl-lower-alkanoyl having as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6- membered and a 5- or 6-membered ring.
Arylcarbamoyi is, for example, N-phenylcarbamoyl which is unsubstituted or substituted in the phenyl moiety.
Acyl radicals of unsubstituted or N-alkanoylated α-amino acids are derived, in particular, from α-amino acids which occur in nature as building blocks of peptides and are unsubstituted or lower alkanoylated, for example N-C2-C7-alkanoylated, such as substituted by acetyl, propionyl, butyryl or pivaloyl. Examples are groups of the formula
-C — CH — NH-RC o (la) in which R5 is hydrogen or a lower alkyl, such as C1-C4alkyl, a radical which is unsubstituted or substituted by hydroxyl, amino, mercapto, unsubstituted or hydroxyl-substituted phenyl, carboxyl, carbamoyi or ureido, for example methyl, isopropyl, isobutyl, secondary butyl, hydroxymethyl, mercaptomethyl, 2-methylmercaptoethyl, 3-ureidopropyl, 4-aminobutyl, carboxymethyl, carbamoylmethyl, 2-carboxyethyl, 2-carbamoylethyl, benzyl or 4-hydroxybenyl, and R6 is lower alkanoyl, for example C2-C7alkanoyl, such as acetyl, propionyl, butyryl or pivaloyl. However, it can also be the acyl group of a heterocyclic α-amino acid which occurs naturally as a building block of peptides, such as prolyl, tryptophanyl or histidinyl.
Cycloalkyl is, for example, 5- to 7-membered cycloalkyl such as, in particular, cyclohexyl or secondarily cyclopentyl or cyctoheptyl.
Aryl is, for example, phenyl or, in particular as R4, naphthyl.
Heteroaryl is, for example, 6-membered monocyclic azaheteroaryl such as pyridyl, or as R4 in particular heteroaryl composed of an unhydrogenated or partially hydrogenated 5- or 6- membered mono- or diaza- or oxaheteroaryl radical and a 6-membered aryl radical, such as benzofuranyl, for example benzofuran-2-yl or -3-yl, indolyl, for example indol-2-yl or -3-yl, 2,3-dihydroindolyl, for example 2,3-dihydroindol-2-yl or -3-yl, benzimidazolyl, for example benzimidazol-2-yl, quinolyl, for example 4-quinolinyl, isoquinolinyl, for example 1 -isoquinolinyl, quinazolinyl, for example 4-quinazolinyl, or 1 ,2,3,4-tetrahydroquinolinyl, for example 1 ,2,3,4-tetrahydro-4-quinolinyl.
Heteroaryl-lower-alkanoyl having as heteroaryl radical an azaheteroaryl which is a 6- membered monocycle or a bicycle composed of a 6-membered and a 5- or 6-membered ring is, for example, corresponding heteroaryl-CrC4alkanoyl, such as 2-pyridyl- or 4-pyridylacetyl, 2,3,4,9-tetrahydro-1 H-pyrido[3,4-b]indol-3-ylcarbonyl.
Alkyl is, in particular, lower alkyl; alkylene in particular lower alkylene.
Ketalized carbonyl groups are, for example, ketalized with an aliphatic alcohol or dialcohol such as with a lower alkanol or a lower alkanediol, and are, for example, di-lower- alkoxymethylene or lower alkylenedioxymethylene.
Etherified hydroxymethylene is etherified in particular with an aliphatic alcohol such as a lower alkanol and is, for example, lower alkoxymethylene.
Carboxyl which may be esterified or amidated is, for example, carboxyl, lower alkoxycarbonyl, carbamoyi or N-mono- or N,N-di-lower-alkylcarbamoyl.
Alkanoyl or alkenoyl radicals which are unsubstituted or substituted by carboxyl or esterified or amidated carboxyl are, for example, lower alkanoyl such as C2-C7alkanoyl, such as acetyl, propionyl, butyryl or pivaloyl, carboxy-lower-alkanoyl, such as carboxy-C3-C7alkanoyl, such as succinoyl, glutaroyl or adipoyl, or carboxy-lower-alkenoyl, such as carboxy-C3-C5- alkenoyl, such as maleyl, fumaroyl or tartroyl, in which carboxyl can also be esterified or amidated, and is, for example, lower alkoxycarbonyl such as
Figure imgf000007_0001
for example methoxy- or ethoxycarbonyl, carbamoyi or N-mono- or N,N-di-lower- alkylcarbamoyl, such as N-mono- or N,N-di-CrC4alkylcarbamoyl, for example N-methyl- or N,N-dimethylcarbamoyl. Lower alkylene substituted by hydroxyl in a position higher than α is, for example, hydroxylated in position 2 to the N atom.
Lower alkylene substituted by hydroxymethyl or carboxyl which may be esterified or amidated is, for example, substituted in position 1 , 2 or, if present, 3 to the N atom by carboxyl, lower alkoxycarbonyl, carbamoyi, N-mono- or N,N-di-lower-alkylcarbamoyl or hydroxymethyl.
Lower radicals and compounds are to be anderstood to mean hereinbefore and hereinafter for example those which have up to and including 7, preferably up to and including 4, carbon atoms (C atoms).
Lower alkyl is, for example, Cι-C7alkyi, preferably CrC4alkyl, such as, in particular, methyl or secondarily ethyl, propyl, isopropyl or butyl, but can also be isobutyl, secondary butyl, tertiary butyl or a C5-C7alkyl such as pentyl, hexyl or heptyl group.
Lower alkylene is, for example, CrCyalkylene, preferably Cι-C4alkylene, such as methylene, ethylene, 1 ,3-propylene, 1 ,4-butylene or 1 ,5-pentylene.
Phenyl- or diphenyl-lower-alkyl which is unsubstituted or substituted in the phenyl is, for example, corresponding phenyl or diphenyl-CrC4alkyl, such as benzyl, 2,4-dichlorobenzyl, 3,5-ditrifluoromethylbenzyl, 2-phenylethyl or 2,2-diphenylethyt.
The phenyl- or diphenyl-lower-alkanoyl which is unsubstituted or substituted in the phenyl moiety is, for example, corresponding phenyl- or diphenyl-d-C4alkanoyl, such as 2,2-diphenylacetyl or 2,3-diphenylpropionyi.
Phenoxy-lower-alkyl which is unsubstituted or substituted in the phenyl is, for example, phenoxy-CrC4alkyl substituted by halogen and/or triazolyl, such as 2-[2-(1H-1 ,2,4-triazol-1 - yl)-4-chlorophenoxy]ethyl.
Heteroaryl-lower-alkyI having as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6-membered and 5- or 6-membered ring is, for example, pyridyl- or quinolinyl-CrC4alkyl, such as 4-quinolinylmethyl. Lower alkoxy is, for example, d-C7alkoxy, preferably d-C4alkoxy, such as methoxy, ethoxy, propyloxy, isopropyloxy or butyloxy, but can also be iobutyloxy, secondary butyloxy, tertiary butyloxy or a pentyloxy, hexyloxy or heptyloxy group.
Halogen is, for example, halogen of atomic number up to and including 35 such as chlorine or fluorine, also bromine.
Lower alkoxycarbonyl is, for example, CrC7alkoxycarbonyl, preferably CrC4alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl or butyloxycarbonyl, but can also be isobutyloxycarbonyl, secondary butyloxycarbonyl, tertiary butyloxycarbonyl or a pentyloxycarbonyl, hexyloxycarbonyl or heptyloxycarbonyl group.
N-Lower-alkylcarbamoyl is, for example, N-Cι-C7alkylcarbamoyl, preferably N-CrC4alkyl- carbamoyl, such as methylcarbamoyi, ethylcarbamoyi, propylcarbamoyl, isopropylcarbamoyl or butylcarbamoyl, but can also be isobutylcarbamoyl, secondary butylcarbamoyl, tertiary butylcarbamoyl or a pentylcarbamoyl, hexylcarbamoyl or heptylcarbamoyl group.
N,N-Di-lower-alkylcarbamoyl is, for example, N,N-di-CrC7alkylcarbamoyl, preferably N,N-di- d-dalkylcarbamoyl, such as N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-ethyl-N- methylcarbamoyl, N.N-dipropylcarbamoyl, N-methyl-N-propylcarbamoyl, N-isopropyl- N-methylcarbamoyl or N-butyl-N-methylcarbamoyl, but can also be N-isobutyl-N-methyl- carbamoyl, N-methyl-N-secondary-butylcarbamoyl, N-methyl-N-tertiary-butylcarbamoyl or an N-methyl-N-pentylcarbamoyl, N-hexyl-N-methylcarbamoyi or N-heptyl-N-methylcarbamoyl group.
Lower alkylene substituted by hydroxyl in a position higher than α and lower than ω is, for example, 1 ,3-(2-hydroxy)propylene, 1 ,4-(2-hydroxy)butylene, 1 ,4-(3-hydroxy)butylene, 1 ,5-(2-hydroxy)pentylene, 1 ,5-(3-hydroxy)pentylene or 1 ,5-(4-hydroxy)pentyiene.
Carboxyl-substituted lower alkylene is, for example, carboxy methylene, 1 - or 2-carboxy- ethylene, 1 ,3-(2-carboxy)propylene, 1 ,4-(2-carboxy)butylene, 1 ,4-(3-carboxy)butylene, 1 ,5-(2-carboxy)pentylene, 1 ,5-(3-carboxy)pentylene or 1 ,5-(4-carboxy)pentylene. Lower alkylene substituted by lower alkoxycarbonyl is, for example, lower alkoxycarbonyl- methylene, 1 - or 2-lower-alkoxycarbonylethylene, 1 ,3-(2-lower-alkoxycarbonyl)propylene, 1 ,4-(2-lower-alkoxycarbonyl)butylene, 1 ,4-(3-lower-alkoxycarbonyl)butylene, 1 ,5-(2-lower- alkoxycarbonyl)pentylene, 1 ,5-(3-lower-alkoxycarbonyl)pentylene or 1 ,5-(4-lower-alkoxy- carbonyl)pentylene, where lower alkoxycarbonyl is, in each case, for example CrC4alkoxy- carbonyl, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl.
Lower alkylene substituted by carbamoyi, N-mono- or N,N-di-lower-alkylcarbamoyl is, in particular, substituted by carbamoyi and is, for example, carbamoylmethylene, 1 - or 2-carbamoylethylene, 1 ,3-(2-carbamoyl)propylene, 1 ,4-(2-carbamoyl)butylene, 1 ,4-(3-carbamoyl)butylene, 1,5-(2-carbamoyl)pentylene, 1 ,5-(3-carbamoyl)pentylene or 1 ,5-(4-carbamoyl)pentylene.
Lower alkylene substituted by hydroxymethyl is, for example, 2-hydroxyethylidene, 2,3-(1 -hydroxy)propylene, 1 ,3-(2-hydroxymethyl)propylene, 2,4-(1-hydroxy)butyiene, 1 ,4-(2-hydroxymethyl)butylene, 1 ,4-(3-hydroxymethyl)butylene, 1 ,5-(2-hydroxymethyl)- pentylene, 1 ,5-(3-hydroxymethyl)pentylene or 1 ,5-(4-hydroxymethyl)pentylene.
Lower alkoxymethylene is, for example, Cι-C4alkoxymethylene such as methoxymethylene, ethoxymethylene, propyloxymethylene or butyloxymethylene.
Di-lower-alkoxymethylene is, for example, di-d-C4alkoxymethylene, such as dimethoxymethylene, diethoxymethylene, dipropyloxymethylene or dibutyloxymethylene.
Lower alkylenedioxymethylene is, for example, 5- to 8-membered, in particular 5- or 6- membered, 1 ,3-dioxa-2-cycloalkyl, such as 1 ,3-dioxa-2-cyclobutyl, 1 ,3-dioxa-2-cyclopentyl {1 ,3-dioxolan-2-yl), 1 ,3-dioxa-2-cyclohexyl (1 ,3-dioxan-2-yl) or 1 ,3-dioxa-2-cycloheptyl.
Compounds of the formula (I) have basic or, if R3 and/or X3 is substituted by carboxyl, amphoteric characteristics and are accordingly able to form acid addition salts and, where appropriate, internal salts. Acid addition salts of compounds of the formula (I) are, for example, their pharmaceutically utilizable salts with suitable mineral acids such as hydrohalic acids, sulfuric acid or phosphoric acid, for example hydrochlorides, hydrobromides, sulfates, bisulfates or phosphates, or salts with suitable aliphatic or aromatic sulfonic acids or N-substituted sutfamic acids, for example methanesulfonates, benzenesulfonates, p-toluenesulfonates or N-cyclohexylsulfamates (cyclamates).
Only the pharmaceutically utilizable non-toxic salts are used in therapy.
The above compounds and their preparation are described, for example, in European Patent Application having the publication no. 532,456 (EP 532,456).
The novel action of the compounds of the formula (I) and their salts can be established, for example, in the following design of tests: adult male rats, referred to as residents, and young preadult rats, referred to as intruders, are put together in the cage which is home to the adult rats. The activity of the intruder with regard to the resident, which is manifested by sniffing, anogenital inspection, nose contact, licking and playing together, is recorded manually and recorded cumulatively over a period of 5 minutes. In this design of tests, phenelzine, fluoxetine, paroxetine and chlordiazepoxide are active in the submilligram and low milligram range since they lead to a significant intensification and increase in social behaviour; all these substances are employed as effective therapeutic treatment of panic disorder in humans. The dose range in which a distinct activity is to be observed in this test on rats is estimated to be a range from about 0.1 to about 10 mg/kg orally.
The results of analogous experiments with a compound of the formula (I) or a salt thereof reveals a qualitatively and quantitatively comparable increase in the time spent by the intruder investigating the resident (MED in the submilligram range). The conclusion which emerges from these tests is that administration of compounds of the formula (I) or a salt thereof leads, through inhibition of the panic behaviour which is actually to be expected, to a significant intensification of the social behaviour in the test animals. Accordingly, exactly like phenelzine, fluoxetine and paroxetine, the compounds of the formula (I) and their salts can be employed for the treatment of panic disorder and social phobia. The use of compounds of formula (I) and pharmaceutically acceptable salts thereof can be established in clinical trials, e.g. as described as follows: The compounds to be used for the treatment of social phobia are administered to patients who have primary DSM-III-R diagnosis of social phobia, e.g. diagnosed by using the Structured Clinical Interview for DSM-III-R, e.g. in a 12 week open clinical trial. The treatment begins e.g. using 10 mg of a Substance P receptor antagonist daily and may be increased according to clinical response and side effects. Patients complete theirself-report measures at baseline and at e.g. weeks 4, 8, and 12. These measures include the fear of negative evaluation scale, social avoidance and distress scale, the social anxiety thoughts questionnaire, the fear questionnaire, the state-trait anxiety inventory, the Beck depression inventory, the social adjustment scale self-report, and the Sheehan disability scale. The responders e.g. at endpoint rate on the clinical global impression change by defining moderately or marketly improved.
The invention therefore primarily relates to the use of a substance P antagonist, in particular one of the compounds of the formula (I) defined hereinbefore and hereinafter, or a pharmaceutically utilizable salt thereof, for the production of pharmaceutical products for the treatment of panic disorder and social phobia.
The invention furthermore relates to a method for the treatment of panic disorder and social phobia, wherein a therapeutically effective amount of a substance P antagonist, in particular one of the compounds of the formula (I) defined hereinbefore or hereinafter, or a pharmaceutically utilizable salt thereof, is administered to a warm-blooded animal including man in need.
The invention likewise relates to pharmaceutical products for the treatment of panic disorder and social phobia, which comprise a substance P antagonist, in particular one of the compounds of the formula (I) defined hereinbefore and hereinafter, or a pharmaceutically utilizable salt thereof, with or without auxiliaries and additives.
The invention furthermore relates to the use of a substance P antagonist, in particular one of the compounds of the formula (I) defined hereinbefore and hereinafter, or a salt thereof, for the treatment of panic disorder and social phobia. The invention primarily relates to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which Ri is a phenyl-, diphenyl-, naphthyl- or fluorenyl-lower-alkyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, or a phenoxy- lower-alkyl radical which is unsubstituted or substituted in the phenyl moiety by halogen and/or triazolyl, or a heteroaryl-lower-alkyl radical which has as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6-membered and a 5- or 6-membered ring, or a benzoyl, naphthoyl, fluorenoyl or 3- to 8-membered cycloalkylcarbonyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxyl, di-lower-alkylamino, halogen, cyano and/or trifluoromethyl, or a phenyl- or diphenyl-lower-alkanoyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, or a heteoaryl- lower-alkanoyl radical which has as heteroaryl radical an azaheteroaryl which is a 6- membered monocycle or a bi- or tricycle composed of a 6-membered and one or two 5- or 6-membered ring(s), or a phenyl-lower-alkoxycarbonyl or N-phenylcarbamoyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower- alkylamino or halogen and/or trifluoromethyl, or the acyl radical of an α-amino acid which is unsubstituted or N-substituted by lower alkanoyl or carbamoyl-lower-alkanoyi and occurs in nature as building block of peptides, R2 is 5- to 7-membered cycloalkyl or a phenyl, naphthyl or 6-membered monocyclic azaheteroaryl radical which is unsubstituted or substituted by aromatically bonded lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, R3 is hydrogen, lower alkyl, carbamoyi, lower alkanoyl, carboxy-lower-alkanoyl or carboxy-lower- alkenoyl, lower alkoxycarbonyl-lower-alkyl, carbamoyl-lower-alkanoyl, N-mono- or N,N-di- lower-alkylcarbamoyl-lower-alkanoyl, N-cycloalkylcarbamoyl-lower-alkanoyl or N-phenyl- carbamoyl-lower-alkanoyl R4 is a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, or a heteroaryl radical which is unsubstituted or C-substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl and possibly N-substituted by lower alkanoyl and is composed of an unhydrogenated or partially hydrogenated 5- or 6-membered mono- or diaza- or oxaheteroaryl radical and a 6-membered aryl radical, Xi is methylene, ethylene, a carbonyl group which may be ketalized by a lower alkanol or a lower alkanediol, or a hydroxymethylene group which is unetherified or etherified with a lower alkanol, or a direct linkage, X2 is carbonyl, lower alkylene or a direct linkage, and X3 is carbonyl, oxo-lower- alkylene, oxo(aza)-lower-alkylene or a lower alkylene radical which is unsubstituted or substituted by phenyl or in position 1 , 2 or, if present, 3 to the N atom by carboxyl, lower alkoxycarbonyl, carbamoyi, N-mono or N,N-di-lower-a!kylcarbamoyl or hydroxymethyl, and to pharmaceutical products containing corresponding compounds.
The invention primarily relates to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which Ri is phenyl- or dιphenyl-d-C4alkyl, which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di- lower-alkylammo, halogen and/or trifluoromethyl, such as benzyl, 2,4-dιchlorobenzyl, 3,5-ditrifluoromethylbenzyl, 2-phenylethyl or 2,2-dιphenylethyl, or phenoxy-d-C4alkyl, pyridyl- or quιnolinyl-d-C4alkyl, which is unsubstituted or substituted in the phenyl by halogen and/or triazolyl, such as 4-quιnolinylmethyl, or benzoyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as benzoyl, 3-lower-alkyl-, 3-lower-alkoxy-, 3-halo-, 3-dimethylamιno-, 3,5-di-lower- alkyl-, 3,5-di-lower-alkoxy-, 3,5-dihalo- or 3,5-dιtrifluoromethylbenzoyl, or secondarily naphthoyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, di-lower- alkylamino, halogen and/or trifluoromethyl, such as 1 - or 2-naphthoyl, or pyndylcarbonyl or quinolinylcarbonyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, or 5- to 7-membered cycloalkylcarbonyl which is unsubstituted or substituted by lower alkyl, lower akoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as cyclohexylcarbonyl, 3-methyl-, 3-methoxy-, 3-chloro-, 3-dimethylamιno-, 3,5- dimethyl-, 3,5-dιmethoxy-, 3,5-dichloro- or 3,5-ditrifluoromethylcyclohexylcarbonyl, or phenyl- or diphenyl-Cι-C4alkanoyl which is unsubstituted or substituted in the phenyl by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as 2,2- diphenylacetyl or 2,3-dιphenylpropionyl, or N-phenylcarbamoyl which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, or a group of the formula (la)
R.
-C — CH — NH — FL
0 (la)
in which Rs is hydrogen, Cι-C4alkyl which is unsubstituted or substituted by hydroxyl, mercapto, ammo, unsubstituted or hydroxy-substituted phenyl, carboxyl, carbamoyi or ureido, and R6 is C2-dalkanoyl, R2 is 5- to 7-memebered cycloalkyl or a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by d dalkyl, d-dalkoxy, halogen and/or trifluoromethyl, R3 is hydrogen, d.C7alkyl, carbamoyi, C2-C7alkanoyl, carboxy- d dalkanoyl or carboxy-C2-C4alkenoyl, R4 is phenyl or naphthyl which is unsubstituted or substituted by d-C4alkyl, Cι.C4alkoxy, halogen and/or trifluoromethyl, or unsubstituted pyridyl, benzofuranyl, indolyl, 2,3-dihydroindolyl, benzimidazolyl, quinolyl or 1 ,2,3,4-tetra- hydroquinolinyl, Xi is methylene, hydroxymethylene, CrC4alkoxy methylene, carbonyl or di- Ci-d-alkoxymethylene or a direct linkage, X2 is CrC7alkylene, carbonyl or a direct linkage, and X3 is carbonyl, Cι-C4alkylene, carboxy-d-C4alkylene, Cι-C4alkoxycarbonyl-d-C4- alkylene, carbamoyl-d-C4alkylene or hydroxymethyl-d-C4alky!ene, and to pharmaceutical products comprising corresponding compounds.
The invention primarily relates to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which RT is benzoyl, naphthoyl or phenyl- dd4alkanoyl which is unsubstituted or substituted by d-C4alkyl such as methyl, d.C4alkoxy such as methoxy, halogen and/or trifluoromethyl, or unsubstituted pyridylcarbonyl or quinolinylcarbonyl, or a group of the formula (la) in which R5 is hydrogen, d-C4alkyl which is unsubstituted or substituted by hydroxyl, mercapto, amino, unsubstituted or hydroxyl-substituted phenyl, carboxyl, carbamoyi or ureido, for example methyl, isopropyl, isobutyl, secondary butyl, hydroxymethyl, mercaptomethyl, 2-methylmercapto- ethyl, 3-ureidopropyl, 4-aminobutyl, carboxymethyl, carbamoylmethyl, 2-carboxyethyl, 2-carbamoylethyl, benzyl or 4-hydroxybenzyl, and R6 is C2-C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, R2 is 5- to 7-membered cycloalkyl, in particular cyclohexyl, or secondarily cyclopentyl or cycloheptyl, or a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by d-C4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen and/or trifluoromethyl, R3 is hydrogen, d-dalkyl such as methyl, ethyl, propyl, isopropyl or butyl, isobutyl, secondary butyl or tertiary butyl, carbamoyi, C2-C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, carboxy-Cι-C4alkanoyl such as succinoyl, glutaroyl or adipoyl, or carboxy-C3-C5alkenoyl such as maleyl, fumaroyl or tartroyl, R4 is phenyl or naphthyl which is unsubstituted or substituted by CrC4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen and/or trifluoromethyl, or unsubstituted pyridyl, benzofuranyl, indolyl, benzimidazolyl or quinolyl, Xi is methylene, hydroxymethylene, d-dalkoxy- methylene such as methoxymethylene, ethoxymethylene, propyloxymethylene or butyloxymethylene, carbonyl, di-d-C4alkoxymethylene such as dimethoxymethylene, diethoxymethylene, dipropyloxymethylene or dibutyloxymethylene, or a direct linkage, X2 is
Cι-C7alkylene such as methylene or secondarily ethylene or 1 ,3-propylene, carbonyl or a direct linkage, and X3 is carbonyl, d-C4alkylene such as methylene, ethylene or
1 ,3-propylene, carboxy-d-C4alkylene such as 1 ,3-(2-carboxy)propylene, 1 ,4-(2-carboxy)- butylene, 1 ,4-(3-carboxy)butylene, C1-C4alkoxycarbonyl-C1-C4-alkylene such as
1 ,3-(2-d C4alkoxycarbonyl)propylene, 1 ,4-(2-d-C4alkoxycarbonyl)butylene, 1 ,4-(3-d-C4. alkoxycarbonyl)butylene, 1 ,5-(2-d-C4alkoxycarbonyl)pentylene, 1 ,5-(3-Cι-C4alkoxy- carbonyl)pentylene or 1 ,5-(4-Cι-C4alkoxycarbonyl)pentylene, where Cι-C4alkoxycarbonyl is, in each case, for example methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl, or carbamoyl-CrC4alkylene such as 1 ,3-(2-carbamoyl)propylene,
1 ,4-(2-carbamoyl)butylene, 1 ,4-(3-carbamoyl)butylene, 1 ,5-(2-carbamoyl)pentylene,
1 ,5-(3-carbamoyl)pentylene or 1 ,5-(4-carbamoyl)pentylene or hydroxymethyl-d-C4alkylene, such as 1 ,3-(2-hydroxymethyl)propylene, 1 ,4-(2-hydroxymethyl)butylene, 1 ,4-(3-hydroxy- methyl)butylene, 1 ,5-(2-hydroxymethyl)pentylene, 1 ,5-(3-hydroxymethyl)pentylene or
1 ,5-(4-hydroxymethyl)pentylene, and to pharmaceutical products comprising corresponding compounds.
The invention relates above all to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which R, is benzoyl which is unsubstituted or mono- or disubstituted by d-C4alkyl such as methyl, Cι-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, or unsubstituted naphthoyl or phenyl-d-C4alkanoyl, R2 is phenyl which is unsubstituted or mono- or disubstituted by CrC4alkyl such as methyl, CrC4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine and/or trifluoromethyl, or unsubstituted pyridyl, R3 is hydrogen, d-C4alkyl such as methyl, ethyl, propyl or isopropyl, carbamoyi or C2-C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, R4 is phenyl which is unsubstituted or mono- or disubstituted by C,-C4alkyl such as methyl, Cι-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine and/or trifluoromethyl, or unsubstituted naphthyl, pyridyl, benzofuranyl, indolyl, benzimidazolyl or quinolyl, Xi is methylene, hydroxymethylene, carbonyl or a direct linkage, X2 is a direct linkage, and X3 is Cι-C4alkylene such as methylene or secondarily ethylene or 1 ,3- propylene, and to pharmaceutical products comprising corresponding compounds. The invention relates above all to the corresponding use of a compound of the formula (lb) or of a pharmaceutically utilizable salt thereof
Figure imgf000017_0001
in which X and Y are, independently of one another, N and/or CH, and ring A is unsubstituted or substituted one or more times by substituents selected from the group consisting of lower alkyl, lower alkoxy, halogen, nitro and trifluoromethyl; and to pharmaceutical products comprising corresponding compounds.
The invention relates above all to the corresponding use of a compound of the formula (Ic)
Figure imgf000017_0002
or of a pharmaceutically utilizable salt thereof, in which X is N or CH and Y is N; and Z is halogen such as chlorine; and to pharmaceutical products comprising corresponding compounds. The invention relates above all to the corresponding use of a compound of the formula (lc) in which X is N or CH and Y is N; and Z is halogen such as chlorine; and to pharmaceutical products comprising corresponding compounds.
The invention relates above all to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which Ri is benzoyl which is unsubstituted or mono- or disubstituted by d-C4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, or unsubstituted naphthoyl, R2 is phenyl which is unsubstituted or mono- or disubstituted by halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, R3 is hydrogen, R4 is unsubstituted quinolyl, Xi is methylene, X2 is a direct linkage, and Xs is d-C4alkylene such as methylene or secondarily ethylene or 1 ,3-propylene, and to pharmaceutical products comprising corresponding compounds.
The invention relates above all to the corresponding use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof selected from the group consisting of:
(2R*,4S*)-2-Benzyl-1-(2-naphthoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-trifluoromethylbenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-bis-(trifluoromethyl)-benzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(1-naphthoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2-quinolinoyl)-N-(4-quinolylmethy!)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(4-chloro-phenylacetyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(benzyloxycarbonyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2-phenylethyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2-naphthylacetyt)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(4-quinolylmethyl)-N-(4-quinolylmethyl)-4-piperidineamine or a salt thereof. (2R*,4S*)-2-Benzyl-1-(2l4-dichlorobenzyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(2,2-diphenylethyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(phenylcarbamoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(diphenylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(2-pyridylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(4-pyridylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(2,3-diphenylpropionyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((3S)-(2,3,4,9-tetrahydro-1 H-pyrido[3,4-b]indol-3-yl)- carbonyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-methoxybenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3-N,N-dimethylaminobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(cis,cis-3,5-dimethylcyclohexylcarbonyl)-N-(4-quinolyl- methyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-bis-(trifluoromethyl)benzyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2S*,4R*)-2-Benzyl-1-(2-(5-chloro-(1 H-1 ,2,4-triazol-1-yl)phenoxy)ethyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-((S)-phenylalanyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-((R)-phenylalanyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-((S)-N-acetylphenylalanyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((R)-N-acetylphenylalanyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((S)-N-(4-carbamoylbutyryl)phenylalanyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((R)-N-(4-carbamoylbutyryl)phenylalanyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-benzoyl-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-(3-carbamoyl- propionyl)-4-piperidineamine; (2R.4S)- or (2R,4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-quιnolyimethyl)-4- piperidineamine;
(2S.4R) and (2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-phenethyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-quinolylmethyl)-4-pιperιdιneamιne;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinolylmethyl)-4-pιperidιneamine;
(2R/4S)- or (2R/4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-benzyl-4- pipeπdineamine;
(2S/4R)- or (2S/4S) -2- Benzyl- 1 -(3,5-dimethylbenzoyl)-N-benzyl-4- piDendineamine;
(2R/4S)- or (2R/*R)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(4-pyrιdylmethyl)-4- piperidmeamine;
(2R/4S)- or (2R/4R)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(3-pyrιdylmethyl)-4- pipendineamine;
(2S,4R)- and (2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-quιnolylmethyl)-4- pipeπdineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-benzyl-N-carbamoyl-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-phenylpropyl)-4-piperidιneamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-phenylpropyl)-4-pιperιdιneamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-methoxybenzyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-methoxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-methoxyphenyl)ethyl]-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2-methoxyphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-methoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-methoxyphenyl)propyl]-4- pipendtneamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2-trifluoromethylbenzyl)-4- pipeπdineamine, (2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-trifluoromethylbenzyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-trifluoromethylphenyl)ethyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-trifluoromethylbenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-trifluoromethylbenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-trifluoromethylbenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-trifluoromethylbenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-trifluoromethylphenyl)propyl]-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-trifluoromethylphenyl)propyl]-4- pipeπdineamine; (2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,3-dιmethoxybenzyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,3-dιmethoxybenzyl)-4- pipendineamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,3-dιmethoxyphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[2-(2,3-dιmethoxyphenyl)ethyl]-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[3-(2,3-dιmethoxyphenyl)propyl]-4- pipendineamine,
(2S,4S)-2-Benzyi-1-(3,5-dιmethylbenzoyl)-N-[3-(2,3-dιmethoxyphenyl)propyl]-4- pipeπdineamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,4-dιmethoxybenzyl)-4- pipendineamine; (2S,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-(2,4-dιmethoxybenzyl)-4-
Dipendineamine;
(2R,4S)-2-Benzy!-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,4-dιmethoxyphenyl)ethyl]-4- pipeπdineamme, (2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,4-dιmethoxyphenyl)ethyl]-4- pipeπdineamine, (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,4-dιmethoxyphenyl)propyl]-4- pipendineamine, (2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(2,4-dιmethoxyphenyl)propyl]-4- piperidmeamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,5-dιmethoxybenzyl)-4- pipeπdineamine, (2S,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-(2,5-dιmethoxybenzyl)-4- pipeπdineamine; (2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,5-dιmethoxyphenyl)ethyl]-4- pipeπdineamine; (2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,5-dιmethoxyphenyl)ethyl]-4- pipeπdineamine, (2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[3-(2,5-dιmethoxyphenyl)propyl]-4- pipendineamine, (2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(2,5-dιmethoxyphenyl)propyl)-4- pipeπdineamine,
(2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-(2,6-dιmethoxybenzyl)-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,6-dιmethoxybenzyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[2-(2,6-dιmethoxyphenyl)ethyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,6-dιmethoxyphenyl)ethyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(2,6-dιmethoxyphenyl)propyl]-4- piperidmeamine,
(2S,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[3-(2,6-dιmethoxyphenyl)propyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,3-methylenedιoxybenzyl)-4- pipendineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2,3-methylenedιoxybenzyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,3-methylenedιoxyphenyl)ethyl]-
4-pιperιdιneamιne,
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,3-methylenedιoxyphenyl)ethyl]-
4-pιperιdιneamιne;
(2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[3-(2,3- methylenedιoxyphenyl)propyl]-4-piperidιneamιne;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(2,3- methylenedιoxyphenyl)propyl]-4-pιperidineamιne;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,4-methylenedιoxybenzyl)-4- pipendineamine,
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2,4-methylenedιoxybenzyl)-4- piperidmeamine,
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,4-methylenedιoxyphenyl)ethyl]-
4-pιpeπdιneamιne,
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2,4-methylenedιoxyphenyl)ethyl]-
4-pιpeπdιneamιne, (2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[3-(2,4- methylenedιoxyphenyl)propyl]-4-pιpeπdineamιne;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,4- methylenedioxyphenyl)propyl]-4-piperidιneamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-ιndolylmethyl)-4-piperidιneamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-ιndolylmethyl)-4-pιperιdιneamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-ιndolylmethyl)-4-piperidιneamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-pιperιdιneamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinoiιnylmethyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quιnolinylmethyl)-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-pιperιdιneamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-(2-chlorobenzyl)-4-pιperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidmeamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-pιperidineamιne;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-pιperidιneamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-pιperιdιneamιne, (2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyt)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-;3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dtmethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine; (2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine; (2S,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamme;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dιmethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- pipendineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedιoxybenzyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrιfluoromethylbenzoyl)-N-(2-ιndolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-indolylmethyl)-4- piperidineamme;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-ιndolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-ιndolylmethyl)-4- pipendineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-quιnolιnylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιtrifluoromethylbenzoyl)-N-(2-quinolιnylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιtrifluoromethylbenzoyl)-N-(3-quinolinylmethyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(3-quιnolιnylmethyl)-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrιfluoromethylbenzoyl)-N-(2-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιtrιfluoromethylbenzoyl)-N-(2-chlorobenzyl)-4- pipeπdineamine, (2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl -N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl -N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl •N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbeπzoyl -N-(3-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl N-(3-chlorobenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl -N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyi; -N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl -N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S , 4S)-2-Benzyl- 1 - (3 ,5-ditrif luoromethylbenzoyl N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyi; N-(4-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl N-(4-chlorobenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl ■N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl -N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl ■N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl ■N-(4-methoxy- 1 -naphthyl- methyl)-4-piperidineamine; (2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(4-methoxy-1 -naphthyl- methyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[3-(3-chlorophenyl)propylj-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιchlorobenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-chlorobenzyl)-4-pιperιdιneamιne;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(4-chlorobenzyl)-4-pιperιdιneamιne;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιchlorobenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(3,4-ethylenedιoxybenzyl)-4- pipendineamine,
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,4-ethylenedιoxybenzyl)-4- pipendineamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιmethoxybenzoyl)-N-(2-ιndolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιmethoxybenzoyl)-N-(2-ιndolylmethyl)-4-- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-ιndolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιmethoxybenzoyl)-N-(3-ιndolylmethyl)-4-- pipendineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιmethoxybenzoyl)-N-(2-quιnolιnylmethyl)-4- pipendineamine,
(2S,4S)-2-Benzyl-1 -(3,5-dιmethoxybenzoyl)-N-(2-quιnolιnylmethyl)-4- pipeπdineamine, (2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-(3-chlorobenzyl)-4-- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-chlorobenzyl)-4-- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R.4S) and (2R,4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-phenethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-bis-(trifluoromethyl)-benzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(2,4-dichlorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(phenylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2,6-dichiorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dibromobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(9-fluorenoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3-toluoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-bromobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dihydroxybenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-cyanobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(4-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(9-fluorenyl)-N-(4-quinolylmethyl)-4-piperidineamine; (2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-methyl-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-cyclohexyl- carbamoyl-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N- phenylcarbamoyl-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-phenylethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-bis-(trifluoromethyl)-benzoyl)-N-(2-phenylethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-naphthoyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,5-dimethylbenzoyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(5-methoxy-2-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(1-naphthoyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(phenylacetyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-methoxybenzyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(N-acetyl-3-indolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-benzo[b]furanylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-methyl-2-benzo[b]thiophenyl- methyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(5-methoxy-3-indolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-indolylmethyl)-4-piperidineamine; (2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-phenylcarbamoyl-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-diphenylmethyl-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,4-dihydro-2H-1-benzopyran-2- carbonyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(4-methoxybenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*,1 'R*)-N-Benzyl-1 -(3,5-dimethylbenzoyl)-2-(1 '-hydroxy-1 '-phenylmethyl)-
4-piperidineamine;
(2R*,4S*,1 'R*)-2-(1 '-hydroxy-1 '-phenylmethyl)-1 -(3,5-dimethylbenzoyl)-N-(4- quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'S*)-1 -(3,5-Dimethytbenzoyl)-2-(1'-hydroxy-1 ,-phenylmethyl)-N-(4- quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'R*)-2-{1 '-Hydroxy-1 '-(4-chlorophenyl)methyl}-1 -(3,5-dimethylbenzoyl)-
N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'S*)-1 -(3,5-Dimethylbenzoyl)-2-{1 '-hydroxy-1 '-(4-chlorophenyl)-methyl}-
N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'S*)-1 -(3,5-Dimethylbenzoyl)-2-{1 '-hydroxy-1 '-(3,4-dichlorophenyl)-- methyl}-N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*)-N-Benzyl-1 -(3,5-dimethylbenzoyl)-2-benzoyl-4-piperidineamine;
(2R*,4S*)-2-(4-Chlorobenzyl)-1 -(3,5-dimethylbenzoyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-2-(3,4-Dichlorobenzyl)-1 -(3,5-dimethylbenzoyl)-N-(4-quinolinylmethyl)-
4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-phenyl-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dichlorobenzoyi)-2-phenyl-N-(4-quinoiinmethyl)-4- piperidineamine;
(2R*,4S*)-1-(1 -Naphthoyl)-2-phenyl-N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(1 -naphthyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2-naphthyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-methoxyphenylmethyl)-N-(4-quinolinyl- methyl)-4-piperidineamine; (2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(3-methoxyphenylmethyl)-N-(4-quιnolιnyl- methyl)-4-pιperιdιneamιne,
(2R*,4S*)-1-(3,5-Dιmethylbenzoyl -2-(4-nιtrobenzyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1-(3,5-Dιmethylbenzoyϊ -2-(4-trιfluoromethylphenylmethyl)-N-(4- quιnolιnylmethyl)-4-pιperιdιneamιn e;
(2R*,4S*)-1-(3,5-Dιmethylbenzoyl -2-(2,4-dιchlorophenylmethyl)-N-(4-quιnoltnyl- methyl)-4-pιperιdιneamιne,
(2R*,4S*)-1-(3,5-Dιmethylbenzoyl -2-(2-phenylethyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dιmethylbenzoyl -2-(2-phenylethenyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-benzoyl-N-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(4-chlorobenzoyl)-N-(4-quιnolιnylmethyl)-4- pioeπdineamine,
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl -2-(2-naphthyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyt -2-(4-methoxybenzyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(3-methoxybenzyl)-(4-quιnolιnylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(4-nιtrobenzyl)-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(4-tπfluoromethylbenzyl)-(4-quιnolιnyl- methyl)-4-pιperιdιneamιne;
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(2,4-dιchlorobenzyl)-(4-quιnolιnylmethyi)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(2-phenylethyl)-(4-quιnolιnylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(2-phenylethenyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine,
(2R*,4S*)-1 -(3,5-Dιmethylbenzoyl -2-(benzoylmethyl)-N-(4-quιnolιnylmethyl)-4- piperidineamine, (2R*,4S*)-1 -(3,5-Dιmethylbenzoyl)-2-(4-chlorobenzoylmethyl)-N-(4-quιnolιnyl- methyl)-4-pιperιdιneamιne,
(2R,4S)-N-[1 -(3,5-Bιstrιfluoromethylbenzoyl)-2-benzyl-4-pιperιdιnyl]quιnolιne-4-carboxamιde,
(2R,4S)-N-[1 -(3,5-Bιstrιfluoromethylbenzoyl)-2-benzyipιperιdιnyl]quιnazolιne-4-carboxamιde;
(2R,4S)-N-[1 -(3,5-Bιstrιfluoromethylbenzoyl)-2-(4-chlorobenzyl)-4-pιperιdιnyl]quιnolιne-4- carboxamide,
(2R,4S)-N-[1 -(3,5-Bιstrιfluoromethylbenzoyl)-2-(4-chlorobenzyl)pιperιdιnyl]quιnazolιne-4- carboxamide,
(2R,4S)-N-[1-(3,5-Bιstrifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperιdιnyl]ιsoquιnolιne-1- carboxamide,
(2R,4S)-N-[1 -(3,5-Bιstrιfluoromethylbenzoyl)-2-(4-nιtrobenzyl)pιperιdιnyl]quιnazolιne-4- carboxamide, or a salt thereof in each case
The compounds of the formula (I) for the novel use can be used, for example, in the form of pharmaceutical products which comprise a therapeutically effective amount of the active substance, with or without inorganic or organic, solid or liquid, pharmaceutically utilizable vehicles suitable for enteral, for example oral, or parenteral administration Thus, tablets or gelatin capsules which have the active substance together with diluents, for example lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or lubricants, for example diatomaceous earth, talc, steaπc acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol Tablets may likewise have binders, for example magnesium aluminium silicate, starches such as maize, wheat, rice or arrowroot starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone and, if required, disintegrants, for example starches, agar, alginic acid or a salt thereof, for example sodium alginate, and/or effervescent mixtures, or absorbents, dyes, flavourings and sweeteners. It is furthermore possible for the novel compounds of the formula (I) to be used in the form of products which can be administered parenterally or of infusion solutions. Solutions of this type are preferably isotonic aqueous solutions or suspensions, it being possible to prepare the latter, for example in the case of lyophilized products which comprise the active substance alone or together with an excipient, for example mannitol, before use. The pharmaceutical products can be sterilized and/or comprise ancillary substances, for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubihzers, salts to control the osmotic pressure and/or buffers The present pharmaceutical products which, if required, may comprise further pharmacologically active substances, are produced in a manner known per se, for example by conventional mixing, granulating, coating, dissolving or lyophilizing processes, and comprise from about 0.1 % to 100%, in particular from about 1 % to about 50%, lyophilizates up to about 100%, of the active substance.
The dosage may depend on various factors such as mode of administration, species, age and/or individual condition. The doses to be administered each day are between about 0.25 and about 10 mg/kg, and for warm-blooded species with a bodyweight of about 70 kg preferably between about 20 mg and about 500 mg, on oral administration.
Example 1 : Tablets, each comprising e.g. 50 mg of (2R,4S)-2-benzyl-1 -(3,5- dimethylbenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine or a pharmaceutically acceptable salt, for example the dihydrochloride, thereof, can be prepared as follows:
Composition (10 000 tablets) active ingredient 500.0 g lactose 500.0 g potato starch 352.0 g gelatin 8.0 g talc 60.0 g magnesium stearate 10.0 g silicon dioxide (highly dispersed) 20.0 g ethano! q.s.
The active ingredient is mixed with the lactose and 292 g of potato starch and the mixture is moistened with an ethanolic solution of the gelatin and granulated through a sieve. After drying, the remainder of the potato starch, the magnesium stearate, the talc and the silicon dioxide are mixed in and the mixture is compressed to form tablets, each weighing 145.0 mg and comprising 50.0 mg of active ingredient; the tablets may, if desired, be provided with breaking notches for finer adaptation of the dose. Example 2: Film-coated tablets, each comprising 100 mg of (2R,4S)-2-benzyl-1 -(3,5- dimethylbenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine or a pharamceutiacally acceptable salt, for example the dihydrochloride, thereof, can be prepared as follows:
Composition (for 1000 film-coated tablets) active ingredient 100.0 g lactose 100.0 g corn starch 70.0 g talc 8.5 g calcium stearate 1.5 g hydroxypropylmethylcellulose 2.36 g shellac 0.64 g water q.s. methylene chloride q.s.
The active ingredient, the lactose and 40 g of the corn starch are mixed and moistened with a paste prepared from 15 g of corn starch and water (with heating) and granulated. The granules are dried, the remainder of the corn starch, the talcum and the calcium stearate are added and mixed with the granules. The mixture is compressed to form tablets (weight: 280 mg) which are then film-coated with a solution of the hydroxypropylmethylcellulose and the shellac in methylene chloride; final weight of the film-coated tablet: 283 mg.
Example 3: Hard gelatin capsules, comprising 100 mg of active ingredient, for example. (2R,4S)-2-benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine or a pharmaceutically acceptable salt, for example the dihydrochloride, thereof, can be prepared, for example, as follows:
Composition (for 1000 capsules) active ingredient 100.0 g lactose 250.0 g microcrystalline cellulose 30.0 g sodium lauryl sulfate 2.0 g magnesium stearate 8.0 g
The sodium lauryl sulfate is added to the lyophilised active ingredient through a sieve of 0.2 mm mesh size. The two components are intimately mixed. Then first the lactose is added through a sieve of 0.6 mm mesh size and then the microcrystalline cellulose is added through a sieve of 0.9 mm mesh size. The mixture is then intimately mixed again for 10 minutes. Finally the magnesium stearate is added through a sieve of 0.8 mm mesh size. After mixing for a further 3 minutes, size 0 hard gelatin capsules are each filled with 390 mg of the resulting formulation.

Claims

WHAT IS CLAIMED IS:
1 . The use of a substance P antagonist for producing pharmaceutical products for the treatment of social phobia.
2. The use of a compound of the formula (I)
Figure imgf000041_0001
or of a pharmaceutically utilizable salt thereof, in which
RT is an unsubstituted or substituted aralkyi, aryloxyalkyi, heteroaralkyl, aroyl, heteroaroyi, cycloalkylcarbonyl, aralkanoyi, heteroarylalkanoyi, aralkoxycarbonyl or arylcarbamoyi radical or the acyl radical of an α-amino acid which is unsubstituted or N-substituted by lower alkanoyl or carbamoyi-lower-alkanoyl;
R2 is cycloalkyl or an unsubstituted or substituted aryl or heteroaryl radical;
R3 is hydrogen, alkyl, carbamoyi or an alkanoyl or alkenoyl radical which is unsubstituted or substituted by carboxyl or esterified or amidated carboxyl;
R4 is an unsubstituted or substituted aryl or unhydrogenated or partially hydrogenated heteroaryl radical;
Xi is methylene, ethylene, a direct linkage, a carbonyl group which may be ketalized, or an unetherified or etherified hydroxymethylene group;
X2 is alkylene, carbonyl or a direct linkage; and
Xa is carbonyl, oxo-lower-alkylene, oxo(aza)-lower-alkylene or an alkylene radical which is unsubstituted or substituted by phenyl, hydroxymethyl, carboxyl which may be esterified or amidated, or by hydroxyl in a position higher than α; according to claim for producing pharmaceutical products for the treatment of social phobia.
3. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which RT is a phenyl-, diphenyl-, naphthyl- or fluorenyl-lower-alkyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower- alkylamino, halogen and/or trifluoromethyl, or a phenoxy-lower-alkyl radical which is unsubstituted or substituted in the phenyl moiety by halogen and/or triazolyl, or a heteroaryl- lower-alkyl radical which has as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bicycle composed of a 6-membered and a 5- or 6-membered ring, or a benzoyl, naphthoyl, fluorenoyl or 3- to 8-membered cycloalkylcarbonyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxyl, di-lower-alkylamino, halogen, cyano and/or trifluoromethyl, or a phenyl- or diphenyl-lower-alkanoyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower- alkylamino, halogen and/or trifluoromethyl, or a heteroaryl-lower-alkanoyl radical which has as heteroaryl radical an azaheteroaryl which is a 6-membered monocycle or a bi- or tricycle composed of a 6-membered and one or two 5- or 6-membered ring(s), or a phenyl-lower- alkoxycarbonyl or N-phenylcarbamoyl radical which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino or halogen and/or trifluoromethyl, or the acyl radical of an α-amino acid which is unsubstituted or N- substituted by lower alkanoyl or carbamoyl-lower-alkanoyl and occurs in nature as building block of peptides, R2 is 5- to 7-membered cycloalkyl or a phenyl, naphthyl or 6-membered monocyclic azaheteroaryl radical which is unsubstituted or substituted by aromatically bonded lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, R3 is hydrogen, lower alkyl, carbamoyi, lower alkanoyl, carboxy-lower-alkanoyl or carboxy-lower-alkenoyl, lower alkoxycarbonyl-lower-alkyl, carbamoyl-lower-alkanoyl, N-mono- or N,N-di-lower- alkylcarbamoyl-lower-alkanoyl, N-cycloalkylcarbamoyl-lower-alkanoyl or N-phenylcarbamoyl- lower-alkanoyl, R4 is a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, or a heteroaryl radical which is unsubstituted or C-substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl and possibly N-substituted by lower alkanoyl and is composed of an unhydrogenated or partially hydrogenated 5- or 6-membered mono- or diaza; or oxaheteroaryl radical and a 6-membered aryi radical, X, is methylene, ethylene, a carbonyl group which may be ketalized by a lower alkanol or a lower alkanediol, or a hydroxy¬ methylene group which is unetherified or etherified with a lower alkanol, or a direct linkage, X2 is carbonyl, lower alkylene or a direct linkage, and X3 is carbonyl, oxo-lower-alkylene, oxo(aza)-lower-alkylene or a lower alkylene radical which is unsubstituted or substituted by phenyl or in position 1 , 2 or, if present, 3 to the N atom by carboxyl, lower alkoxycarbonyl, carbamoyi, N-mono or N,N-di-lower-alkylcarbamoyl or hydroxymethyl; according to claim 2.
4. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which Ri is phenyl- or diphenyl-d-C4alkyl, which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as benzyl, 2,4-dichlorobenzyl, 3,5-ditrifluoromethylbenzyl, 2-phenylethyl or 2,2- diphenylethyl, or phenoxy-d-C4alkyl, pyridyl- or quinolinyl-CrC4alkyl, which is unsubstituted or substituted in the phenyl by halogen and/or triazolyl, such as 4-quinolinylmethyi, or benzoyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, di-lower- alkylamino, halogen and/or trifluoromethyl, such as benzoyl, 3-lower-alkyl-, 3-lower-alkoxy-, 3-halo-, 3-dimethylamino-, 3,5-di-lower-alkyl-, 3,5-di-lower-alkoxy-, 3,5-dihalo- or 3,5- ditrifluoromethylbenzoyl, or secondarily naphthoyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as 1 - or 2-naphthoyl, or pyridylcarbonyl or quinolinylcarbonyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl, or 5- to 7-membered cycloalkylcarbonyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, di- lower-alkylamino, halogen and/or trifluoromethyl, such as cyclohexylcarbonyl, 3-methyl-, 3- methoxy-, 3-chloro-, 3-dimethylamino-, 3,5-dimethyl-, 3,5-dimethoxy-, 3,5-dichloro- or 3,5- ditrifluoromethylcyclohexylcarbonyl, or phenyl- or diphenyl-Cι-C4a!kanoyl which is unsubstituted or substituted in the phenyl by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, such as 2,2-diphenylacetyl or 2,3-diphenylpropionyl, or N- phenylcarbamoyl which is unsubstituted or substituted in the phenyl moiety by lower alkyl, lower alkoxy, di-lower-alkylamino, halogen and/or trifluoromethyl, or a group of the formula (la)
ft
-C — CH — NH-R.
(la)
in which R5 is hydrogen, d-dalkyl which is unsubstituted or substituted by hydroxyl, mercapto, amino, unsubstituted or hydroxy-substituted phenyl, carboxyl, carbamoyi or ureido, and R6 is C2-C7alkanoyl, R2 is 5- to 7-membered cycloalkyl or a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by d.C4alkyl, d-C4alkoxy, halogen and/or trifluoromethyl, R3 is hydrogen, d_C7alkyl, carbamoyi, C2-C7alkanoyl, carboxy- d.C4alkanoyl or carboxy-C2-C4alkenoyl, R4 is phenyl or naphthyl which is unsubstituted or substituted by d-C4alkyl, d.dalkoxy, halogen and/or trifluoromethyl, or unsubstituted pyridyl, benzofuranyl, indolyl, 2,3-dihydroindolyl, benzimidazolyl, quinolyl or 1 ,2,3,4-tetra- hydroquinolinyl, Xi is methylene, hydroxymethylene, CrC4alkoxymethylene, carbonyl or di- CrC4-alkoxymethylene or a direct linkage, X2 is d-C7alkylene, carbonyl or a direct linkage, and X3 is carbonyl, d-C4alkylene, carboxy-d-C4alkylene, C1-C4alkoxycarbonyl-d-C4- alkylene, carbamoyl-d-C4alkylene or hydroxymethyl-Cι-C4alkylene; according to claim 2.
5. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which
RT is benzoyl, naphthoyl or phenyl-d.C4alkanoyl which is unsubstituted or substituted by d dalkyl such as methyl, C1-C4alkoxy such as methoxy, halogen and/or trifluoromethyl, or unsubstituted pyridylcarbonyl or quinolinylcarbonyl, or a group of the formula (la) in which R5 is hydrogen, d-C4alkyl which is unsubstituted or substituted by hydroxyl, mercapto, amino, unsubstituted or hydroxyl-substituted phenyl, carboxyl, carbamoyi or ureido, for example methyl, isopropyl, isobutyl, secondary butyl, hydroxymethyl, mercaptomethyl, 2- methylmercaptoethyl, 3-ureidopropyl, 4-aminobutyl, carboxymethyl, carbamoylmethyl, 2- carboxyethyl, 2-carbamoylethyl, benzyl or 4-hydroxybenzyl, and R6 is C2-C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, R2 is 5- to 7-membered cycloalkyl, in particular cyclohexyl, or secondarily cyclopentyl or cycloheptyl, or a phenyl, naphthyl or pyridyl radical which is unsubstituted or substituted by d-C4alkyl such as methyl, CrC4alkoxy such as methoxy, halogen and/or trifluoromethyl, R3 is hydrogen, d-C7alkyl such as methyl, ethyl, propyl, isopropyl or butyl, isobutyl, secondary butyl or tertiary butyl, carbamoyi, C2- C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, carboxy-d-C4alkanoyl such as succinoyl, glutaroyl or adipoyi, or carboxy-C3-C5alkenoyl such as maleyl, fumaroyl or tartroyi, R4 is phenyl or naphthyl which is unsubstituted or substituted by Cι-C4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen and/or trifluoromethyl, or unsubstituted pyridyl, benzofuranyl, indolyl, benzimidazolyl or quinolyl, Xi is methylene, hydroxymethylene, Cr dalkoxymethylene such as methoxymethylene, ethoxymethylene, propyloxymethylene or butyloxymethylene, carbonyl, di-d-C4alkoxymethylene such as dimethoxymethylene, diethoxymethylene, dipropyloxymethylene or dibutyloxymethylene, or a direct linkage, X2 is Cι-C7alkylene such as methylene or secondarily ethylene or 1 ,3-propylene, carbonyl or a direct linkage, and X3 is carbonyl, Cι-C4alkylene such as methylene, ethylene or 1 ,3-propylene, carboxy-d-dalkylene such as 1 ,3-(2-carboxy)propylene, 1 ,4-(2-carboxy)- butylene, 1 ,4-(3-carboxy)butylene, CrC4alkoxycarbonyl-Cι-C4-alkylene such as 1 ,3-(2-d.C4alkoxycarbonyl)propylene, 1 ,4-(2-Cι-C4alkoxycarbonyl)butylene, 1 ,4-(3-d-C4. alkoxycarbonyl)butylene, 1 ,5-(2-CrC4alkoxycarbonyl)pentylene, 1 ,5-(3-CrC4alkoxy- carbonyl)pentylene or 1 ,5-(4-d-C4alkoxycarbonyl)pentylene, where d-C4alkoxycarbonyl is, in each case, for example methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl, or carbamoyl-Cι-C4alkylene such as 1 ,3-(2-carbamoyl)propylene, 1 ,4-(2-carbamoyl)butylene, 1 ,4-(3-carbamoyl)butylene, 1 ,5-(2-carbamoyl)pentylene, 1 ,5-(3-carbamoyl)pentylene or 1 ,5-(4-carbamoyl)pentylene or hydroxymethyl-d-C4alkylene, such as 1 ,3-(2-hydroxymethyl)propylene, 1 ,4-(2-hydroxymethyl)butylene, 1 ,4-(3-hydroxy- methyl)butylene, 1 ,5-(2-hydroxymethyl)pentylene, 1 ,5-(3-hydroxymethyl)pentylene or 1 ,5-(4-hydroxymethyl)pentylene; according to claim 2.
6. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which
Ri is benzoyl which is unsubstituted or mono- or disubstituted by Cι-C4alkyl such as methyl, Cι-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, or unsubstituted naphthoyl or phenyl-d-C4alkanoyl, R2 is phenyl which is unsubstituted or substituted by CrC4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine and/or trifluoromethyl, or unsubstituted pyridyl, R3 is hydrogen, CrC4alkyl such as methyl, ethyl, propyl or isopropyl, carbamoyi or C2-C7alkanoyl such as acetyl, propionyl, butyryl or pivaloyl, R4 is phenyl which is unsubstituted or mono- or disubstituted by d-C4alkyl such as methyl, d-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine and/or trifluoromethyl, or unsubstituted naphthyl, pyridyl, benzofuranyl, indolyl, benzimidazolyl or quinolyl, Xi is methylene, hydroxymethylene, carbonyl or a direct linkage, X2 is a direct linkage, and X3 is CrC4alkylene such as methylene or secondarily ethylene or 1 ,3-propylene; according to claim 2.
7. The use of a compound of the formula (lb)
Figure imgf000046_0001
or of a pharmaceutically utilizable salt thereof, in which
X and Y are, independently of one another, N and/or CH, and ring A is unsubstituted or substituted one or more times by substituents selected from the group consisting of lower alkyl, lower alkoxy, halogen, nitro and trifluoromethyl; according to claim 2.
8. The use of a compound of the formula (Ic)
Figure imgf000046_0002
or of a pharmaceutically utilizable salt thereof, in which X is N or CH and Y is N; and Z is halogen such as chlorine; according to claim 2.
9. The use of a compound of the formula (Ic) or of a pharmaceutically utilizable salt thereof, in which X is N or CH and Y is N; and Z is halogen such as chlorine; according to claim 2.
10. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof, in which R, is benzoyl which is unsubstituted or mono- or disubstituted by d-dalkyl such as methyl, d-C4alkoxy such as methoxy, halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, or unsubstituted naphthoyl, R2 is phenyl which is unsubstituted or mono- or disubstituted by halogen of atomic number up to and including 35, such as chlorine, and/or trifluoromethyl, R3 is hydrogen, R4 is unsubstituted quinolyl, X, is methylene, X2 is a direct linkage, and X3 is d-C4alkylene such as methylene or secondarily ethylene or 1 ,3-propylene; according to claim 2.
11. The use of a compound of the formula (I) or of a pharmaceutically utilizable salt thereof according to claim 2, selected from the group consisting of:
(2R*,4S*)-2-Benzyl-1- 2-naphthoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1- 3-trifluoromethylbenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 3,5-bis-(trifluoromethyl)-benzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 3,5-dimethoxybenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 1 -naphthoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 2-quinolinoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1- 4-chloro-phenylacetyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 - benzyloxycarbonyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 2-phenylethyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1- 2-naphthylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1- 4-quinolylmethyl)-N-(4-quinolylmethyl)-4-piperidineamine or a salt thereof.
(2R*,4S*)-2-Benzyl-1- 2,4-dichlorobenzyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 2,2-diphenylethyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - phenylcarbamoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - diphenylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 - 2-pyridylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine; (2R*,4S*)-2-Benzyl-1-(4-pyridylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2,3-diphenylpropionyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-((3S)-(2,3,4,9-tetrahydro-1 H-pyrido[3,4-b]indol-3-yl)- carbonyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-methoxybenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3-N,N-dimethylaminobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(cis,cis-3,5-dimethylcyclohexylcarbonyl)-N-(4-quinolyl- methyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-bis-(trifluoromethyl)benzyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2S*,4R*)-2-Benzyl-1 -(2-(5-chloro-(1 H-1 ,2,4-triazol-1 -yl)phenoxy)ethyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-((S)-phenylalanyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((R)-phenylalanyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((S)-N-acetylphenylalanyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -((R)-N-acetylphenylalanyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-((S)-N-(4-carbamoylbutyryl)phenylalanyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-((R)-N-(4-carbamoylbutyryl)phenylalanyl)-N-(4- quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -benzoyl-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyi-1 -(3-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-(3-carbamoyl- propionyl)-4-piperidineamine;
(2R.4S)- or (2R,4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2S,4R) and (2S,4S)-2-Benzyt-1-(3,5-dimethylbenzoyl)-N-(2-phenethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolylmethyl)-4-piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinolylmethyl)-4-piperidineamine;
(2R/4S)- or (2R/4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-benzyl-4- piperidineamine;
(2S/4R)- or (2S/4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-benzyl-4- piperidineamine;
(2R/4S)- or (2R/4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-pyridylmethyl)-4- piperidineamine;
(2R/4S)- or (2R/4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-pyridylmethyl)-4- piperidineamine;
(2S,4R)- and (2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-benzyl-N-carbamoyl-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-phenylpropyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-phenylpropyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-methoxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-methoxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-methoxyphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-methoxyphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-methoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2-methoxyphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-trifluoromethylbenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-trifluoromethylbenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-trifluoromethylphenyl)ethyl]-4- piperidineamine; (2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-trifluoromethylbenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-trifluoromethylbenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethy!benzoyl)-N-[2-(3-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-trifluoromethylbenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-trifluoromethylbenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-trifluoromethylphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-trifluoromethylphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,3-dimethoxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,3-dimethoxybenzyl)-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,3-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2,3-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2,3-dimethoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,3-dimethoxyphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,4-dimethoxybenzyl)-4- piperidineamine;
(2S,4S)-2-Beπzyl-1 -(3,5-dimethylbenzoyl)-N-(2,4-dimethoxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,4-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,4-dimethoxyρhenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,4-dimethoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2,4-dimethoxyphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2,5-dimethoxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,5-dimethoxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,5-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,5-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2,5-dimethoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,5-dimethoxyphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Beπzyl-1 -(3,5-dimethylbenzoyl)-N-(2,6-dimethoxybenzyl)-4- piperidineamine; (2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,6-dimethoxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2,6-dimethoxyphenyl)ethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2,6-dimethoxyphenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2,6-dimethoxyphenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,6-dimethoxyphenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2,3-methylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2,3-methylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2,3-methylenedioxyphenyl)ethyl]-
4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,3-methylenedioxyphenyl)ethyl]-
4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2,3- methylenedioxyphenyl)propyl]-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,3- methytenedioxyphenyl)propyl]-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2,4-methylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2,4-methylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2,4-methylenedioxyphenyl)ethyl]-
4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2,4-methylenedioxyphenyl)ethyl]-
4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,4- methylenedioxyphenyl)propyl]-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2,4- methylenedioxyphenyl)propyl]-4-piperidineamine; (2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dιmethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamme;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- ptperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbeπzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Beπzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2S ,4S) -2-Benzyl-1 - (3, 5-dimethyl benzoyl)-N- (4-methoxy- 1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(2-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethylbenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-indolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-indolylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-indolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-indolytmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifiuoromethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(2-chlorobenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine; (2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidmeamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(3-chlorobenzyl)-4- piperidmeamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3-chlorobenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιtrifluoromethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzy!-1 -(3,5-ditrifluoromethylbenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(4-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(4-chlorobenzyl)-4- pipeπdineamme;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-t2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-[3-(4-chlorophenyt)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(4-methoxy-1-naphthyl- methyl)-4-piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(4-methoxy-1-naphthyl- methyl)-4-pιperidιneamine;
(2R,4S)-2-Benzyl-1-(3,5-ditrifluoromethylbenzoyl)-N-(3,4-ethylenedιoxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-ditrifluoromethylbenzoyl)-N-(3,4-ethylenedιoxybenzyl)-4- pipeπdineamine; (2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(2-ιndolylmethyl)-4-pιperιdιneamιne;
(2S,4S)-2-Benzyl-1-(3,5-dιchlorobenzoyl)-N-(2-ιndolylmethyl)-4-pιperιdιneamιne,
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(3-ιndolylmethyl)-4-pιperιdιneamιne;
(2S,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(3-ιndolylmethyl)-4-pιperidιneamine;
(2R.4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(2-quιnolinylmethyl)-4- pipendineamine,
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(2-quinolιnylmethyl)-4- piperidineamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(3-quinolιnylmethyl)-4- pipeπdineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(3-quιnolinylmethyl)-4- pipendineamine,
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(2-chlorobenzyl)-4-pιperιdιneamιne;
(2S,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-chlorobenzyl)-4-pιperidιneamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- pioeridineamme;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- pipendineamme;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- pipendineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamme;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(3-chlorobenzyl)-4-pιperidιneamιne;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-chlorobenzyl)-4-piperιdιneamιne;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidmeamine;
(2S,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- pipeπdineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dιchlorobenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidmeamine;
(2R,4S)-2-Benzyl-1 -(3,5-dιchlorobenzoyl)-N-(4-chlorobenzyl)-4-pιperιdιneamιne, (2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichiorobenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-indolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-indolytmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-indolylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-indolylmethyl)-4~ piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-quinolinylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-(3-quinolinylmethyl)-4- piperidineamine; (2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-chlorobenzyl)-4-- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(2-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(2-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[3-(2-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[2-(3-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(3-chlorophenyl)propyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-chlorobenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-chlorobenzyl)-4-piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-[2-(4-chlorophenyl)ethyl]-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-[3-(4-chlorophenyl)propyl]-4- piperidineamine; (2R,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-(4-methoxy-1-naphthylmethyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(4-methoxy-1 -naphthylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-dimethoxybenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2S,4S)-2-Benzyl-1-(3,5-dimethoxybenzoyl)-N-(3,4-ethylenedioxybenzyl)-4- piperidineamine;
(2R,4S) and (2R,4R)-2-Benzyl-1 -(3,5-dimethylbenzoyl)-N-(2-phenethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1 -(3,5-bis-(trifluoromethyl)benzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R,4S)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2,4-dichlorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(phenylacetyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2,6-dichlorobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dibromobenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(9-fluorenoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3-toluoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3-bromobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dihydroxybenzoyl)-N-(4-quinolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3-cyanobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(2-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(4-chlorobenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(9-fluorenyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-methyl-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N-cyclohexyl- carbamoyl-4-piperidineamine; (2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(4-quinolylmethyl)-N- phenylcarbamoyl-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-phenylethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-bis-(trifluoromethyl)benzoyl)-N-(2-phenylethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(2-naphthoyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,5-dimethylbenzoyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyI)-N-(4-quinolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(5-methoxy-2-indolylcarbonyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-(1 -naphthoyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(phenylacetyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-methoxybenzyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-((N-acetyl)-3-indolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(2-benzo[b]furanylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-((3-methyl)-2-benzo[b]thiophenyl- methyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-((5-methoxy)-3-indolylmethyl)-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3-indolylmethyl)-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1-(3,5-dichlorobenzoyl)-N-phenylcarbamoyl-4- piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-diphenylmethyl-4-piperidineamine;
(2R*,4S*)-2-Benzyl-1 -(3,5-dichlorobenzoyl)-N-(3,4-dihydro-2H-1-benzopyran-2- carbonyl)-4-piperidineamine; (2R*,4S*)-2-Benzyl-1 -(4-methoxybenzoyl)-N-(4-quinolylmethyl)-4-piperidineamine;
(2R*,4S*,1 'R*)-N-Benzyl-1 -(3,5-dimethylbenzoyl)-2-(1 '-hydroxy-1 '-phenylmethyl)-
4-piperidineamine;
(2R*,4S*,1 'R*)-2-(1 '-hydroxy-1 '-phenylmethyl)-1 -(3,5-dimethylbenzoyl)-N-(4- quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'S*)-1 -(3,5-Dimethylbenzoyl)-2-(1 '-hydroxy-1 '-phenylmethyl)-N-(4- quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'R*)-2-{1 '-Hydroxy-1 '-(4-chlorophenyl)methyl}-1 -(3,5-dimethylbenzoyl)-
N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 *S*)-1 -(3,5-Dimethylbenzoyl)-2-{1 '-hydroxy-1 '-(4-chlorophenyl)-methyl}-
N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,1 'S*)-1 -(3,5-Dimethylbenzoyl)-2-{1 '-hydroxy-1 '-(3,4-dichlorophenyl)- methyl}-N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*,)-N-Benzyl-1-(3,5-dimethylbenzoyl)-2-benzoyl-4-piperidineamine;
(2R*,4S*)-2-(4-Chlorobenzyl)-1-(3,5-dimethylbenzoyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-2-(3,4-Dichlorobenzyl)-1-(3,5-dimethylbenzoyl)-N-(4-quinolinylmethyl)-
4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-phenyl-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dichlorobenzoyl)-2-phenyl-N-(4-quinolinmethyl)-4- piperidineamine;
(2R*,4S*)-1-(1 -Naphthoyl)-2-phenyl-N-(4-quinolinylmethyl)-4-piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(1 -naphthyl)-N-(4-quinolinylmethyl)-4- , piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2-naphthyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-methoxyphenylmethyl)-N-(4-quinolinyl- methyl)-4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(3-methoxyphenylmethyl)-N-(4-quinolinyl- methyl)-4-piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(4-nitrobenzyl)-N-(4-quinolinylmethyl)-4- piperidineamine; (2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(4-trifluoromethylphenylmethyl)-N-(4- quinolinylmethyl)-4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2,4-dichlorophenylmethyl)-N-(4-quinolinyl- methyl)-4-piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2-phenylethyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(2-phenylethenyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-benzoyl-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(4-chlorobenzoyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2-naphthyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-methoxybenzyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(3-methoxybenzyl)-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-nitrobenzyl)-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-trifluoromethylbenzyl)-(4-quinolinyl- methyl)-4-piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(2,4-dichlorobenzyl)-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(2-phenylethyl)-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1 -(3,5-Dimethylbenzoyl)-2-(2-phenylethenyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(benzoylmethyl)-N-(4-quinolinylmethyl)-4- piperidineamine;
(2R*,4S*)-1-(3,5-Dimethylbenzoyl)-2-(4-chlorobenzoylmethyl)-N-(4-quinolinyl- methyl)-4-piperidineamine;
(2R,4S)-N-[1-(3,5-Bistrifluoromethylbenzoyl)-2-benzyl-4-piperidinyl]quinoline-4-carboxamide; (2R,4S)-N-[1 -(3,5-Bistrifiuoromethylbenzoyl)-2-benzyl-4-piperidinyl]quinazoline-4-carbox- amide;
(2R,4S)-N-[1 -(3,5-Bistrifluoromethylbenzoyl)-2-(4-chlorobenzyl)-4-piperidinyl]quinoline-4- carboxamide;
(2R,4S)-N-[1 -(3,5-Bistrifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperidinyl]quinazoline-4- carboxamide;
(2R,4S)-N-[1-(3,5-Bistrifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperidinyl]isoquinoline-1 - carboxamide; and
(2R,4S)-N-[1 -(3,5-Bistrifluoromethylbenzoyl)-2-(4-nitrobenzyl)piperidinyl]quina- zoline-4-carboxamide.
12. A pharmaceutical composition for the treatment of social phobia comprising a compound according to any one of claims 1 -1 1 or a pharmaceutically acceptable salt thereof.
13. A method of treatmenf of social phobia in warm-blooded animals including man comprising administering to an individual in need of such treatment a therapeutically effective amount of a compound according to any one of claims 1- 11 or a pharmaceutically acceptable salt thereof.
PCT/EP1997/002481 1996-05-24 1997-05-15 Use of substance p antagonists for treating social phobia WO1997045119A1 (en)

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US6090819A (en) * 1997-08-04 2000-07-18 Merck Sharp & Dohme, Ltd. Use of NK-1 receptor antagonists for treating mania
US5952330A (en) * 1997-08-04 1999-09-14 Merck Sharp & Dohme Ltd. Use of NK-1 receptor antagonists for treating mania
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US6989447B2 (en) 1999-07-23 2006-01-24 Smithkline Beecham P.L.C. Compounds
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US7534793B2 (en) 2000-07-26 2009-05-19 Smithkline Beecham P.L.C. Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity
US7205408B2 (en) 2001-01-22 2007-04-17 Smithkline Beecham, P.L.C. Quinolines and nitrogenated derivative thereof substituted in 4-position by a piperidine-containing moiety and their use as antibacterial agents
US7053089B2 (en) 2001-02-23 2006-05-30 Merck & Co., Inc. N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists
US7259157B2 (en) 2001-04-03 2007-08-21 Merck & Co., Inc. N-substituted nonaryl-heterocyclo amidyl NMDA/NR2B Antagonists
US7186730B2 (en) 2001-05-25 2007-03-06 Smithkline Beecham P.L.C. Bicyclic nitrogen-containing heterocyclic derivatives for use as antibacterials
US6906084B2 (en) * 2001-11-22 2005-06-14 Aventis Pharma Deutschland Gmbh Indole derivatives as factor Xa inhibitors
US7312212B2 (en) 2002-01-29 2007-12-25 Glaxo Group Limited Aminopiperidine derivatives
WO2004024714A1 (en) * 2002-09-10 2004-03-25 Novartis Ag Aroyl-piperidine derivatives
US7678814B2 (en) 2002-09-10 2010-03-16 Novartis Ag Aroyl-piperidine derivatives
US7592360B2 (en) 2003-06-04 2009-09-22 Merck & Co., Inc. 3-fluoro-piperidines as NMDA/NR2B antagonists
EP1809104A2 (en) * 2004-09-23 2007-07-25 Alexander Michalow Methods for regulating neurotransmitter systems by inducing counteradaptations
EP1809104A4 (en) * 2004-09-23 2009-04-29 Alexander Michalow Methods for regulating neurotransmitter systems by inducing counteradaptations
US9000174B2 (en) 2004-10-14 2015-04-07 Purdue Pharma L.P. 4-phenylsulfonamidopiperidines as calcium channel blockers
US8247442B2 (en) 2006-03-29 2012-08-21 Purdue Pharma L.P. Benzenesulfonamide compounds and their use
US8937181B2 (en) 2006-04-13 2015-01-20 Purdue Pharma L.P. Benzenesulfonamide compounds and the use thereof
US8791264B2 (en) 2006-04-13 2014-07-29 Purdue Pharma L.P. Benzenesulfonamide compounds and their use as blockers of calcium channels
US8399486B2 (en) 2007-04-09 2013-03-19 Purdue Pharma L.P. Benzenesulfonyl compounds and the use thereof
US8765736B2 (en) 2007-09-28 2014-07-01 Purdue Pharma L.P. Benzenesulfonamide compounds and the use thereof
WO2015156464A1 (en) * 2014-04-09 2015-10-15 한국화학연구원 N-(piperidin-4-yl)benzo[b]thiophenecarboxyamide derivative, preparation method therefor, and pharmaceutical composition for preventing or treating urotensin-ii receptor activity-related diseases, comprising same as active ingredient
US10189785B2 (en) * 2015-04-20 2019-01-29 Takeda Pharmaceuticals Company Limited Heterocyclic compound
US10519110B2 (en) 2015-04-20 2019-12-31 Takeda Pharmaceutical Company Limited Heterocyclic compound
US10676461B2 (en) 2016-10-18 2020-06-09 Takeda Pharmaceutical Company Limited Heterocyclic compound

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