WO2004111004A1 - Substituted piperazine carbamates for use as inhibitors of hormone sensitive lipase - Google Patents

Substituted piperazine carbamates for use as inhibitors of hormone sensitive lipase Download PDF

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Publication number
WO2004111004A1
WO2004111004A1 PCT/DK2004/000397 DK2004000397W WO2004111004A1 WO 2004111004 A1 WO2004111004 A1 WO 2004111004A1 DK 2004000397 W DK2004000397 W DK 2004000397W WO 2004111004 A1 WO2004111004 A1 WO 2004111004A1
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Prior art keywords
pyridin
piperazine
carboxylic acid
ethyl
methyl
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PCT/DK2004/000397
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French (fr)
Inventor
Holger Claus Hansen
Johannes Cornelis De Jong
Per VEDSØ
Poul Jacobsen
Søren EBDRUP
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Novo Nordisk A/S
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Priority to EP04736504A priority Critical patent/EP1636187A1/en
Priority to JP2006515705A priority patent/JP2006527212A/en
Publication of WO2004111004A1 publication Critical patent/WO2004111004A1/en
Priority to US11/299,649 priority patent/US20060160820A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C07D213/643—2-Phenoxypyridines; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to novel substituted piperazine carbamates, to phar- maceutical compositions comprising these compounds, to the use of these compounds as pharmaceutical compositions, and to methods of treatment employing these compounds and compositions.
  • the present compounds are inhibitiors of hormone sensitive lipase. As a result, the compounds are useful for the treatment and/or prevention of diseases and disorders related to hormone sensitive lipase.
  • the overall energy homeostasis of a mammalian system requires a high degree of regulation to ensure the availability of the appropriate substrate at the appropriate time.
  • Plasma glucose levels rise during the post-prandial state, to return to pre-prandial levels within 2-3 hours. During these 2-3 hours, insulin promotes glucose uptake by skeletal muscle and adipose tissue and decreases the release of free fatty acids (FFA) from adipocytes, to ensure that the two substrates do not compete with each other.
  • FFA free fatty acids
  • HSL Hormone-sensitive lipase
  • adipocytes HSL catalyses the conversion of triglycerides to glycerol and fatty acids. It is through the regulation of this enzyme that the levels of circulating FFA are modulated. Insulin leads to the inactivation of HSL with a subsequent fall in plasma FFA levels during the post-prandial state, followed by the activation of the enzyme when the insulin concen- tration falls and catecholamines rise during the post-absorptive period.
  • HSL The activation of HSL leads to an increase in plasma FFA, as they become the main source of energy during fasting.
  • the activation-inactivation of HSL is primarily mediated through the cAMP-protein kinase A and AMP-dependent kinase pathways.
  • cAMP-protein kinase A a cAMP-protein kinase A and AMP-dependent kinase pathways.
  • nicotinic acid and its derivatives that decrease the activation of HSL via these pathways and cause a decrease in lipolysis that leads to a reduction in the FFA levels.
  • These drugs have a beneficial effect in the utilization of glucose and in the normalization of the excess triglyceride synthesis seen in patients with elevated FFA. However, since these pathways are used by other processes in the body, these drugs have severe side effects.
  • Piperazines similar to the compounds of the present invention have previously been prepared, and their properties have been investigated for a number of pharmaceutical appli- cations, e.g. CNS disorders.
  • HSL inhibitors WO 01/87843, WO 01/17981 , WO 01/66531 , WO 01/83497, and WO 01/26664.
  • the structures of these compounds are very different from that of the present compounds.
  • none of the HSL inhibitors disclosed in these publications contain piperazine and carbamate substructures as in the compounds of the present invention.
  • piperazine compounds that specifically inhibit the lipolytic activity of HSL and which are expected to decrease in plasma FFA levels. These compounds can be used to treat disorders where a decreased level of plasma FFA is desired, such as insulin resistance, syndrome X, dyslipidemia, abnormalities of lipoprotein metabolism.
  • One object of the present invention is to provide compounds and pharmaceutical compositions that inhibit the lipolytic activity of HSL.
  • a further object is to provide compounds which have good pharmaceutical properties such as solubility, bioavailability, specificity etc.
  • halogen in the present context designates an atom selected from the group consisting of F, Cl, Br and I.
  • C 1-6 -alkyl in the present context designates a saturated, branched or straight hydrocarbon group having from 1 to 6 carbon atoms.
  • Representative examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, isopentyl, neopentyl, terf-pentyl, n-hexyl, isohexyl and the like.
  • C 2-6 -alkyl in the present context designates a saturated, branched or straight hydrocarbon group having from 2 to 6 carbon atoms.
  • C 1-6 -alkoxy in the present context designates a group -O-C 1-6 -alkyl wherein C 1-6 -alkyl is as defined above.
  • Representative examples include, but are not limited to, meth- oxy, ethoxy, n-propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, ferf-butoxy, n-pentoxy, isopentoxy, neopentoxy, terf-pentoxy, n-hexoxy, isohexoxy and the like.
  • C 2-6 -alkenyl as used herein, represent an olefinically unsaturated ; branched or straight hydrocarbon group having from 2 to 6 carbon atoms and at least one double bond.
  • groups include, but are not limited to, vinyl, 1-propenyl, 2- propenyl, allyl, iso-propenyl, 1 ,3-butadienyl, 1-butenyl, hexenyl, pentenyl and the like.
  • C 3 . 10 -cycloalkyr represents a saturated mono-, bi-, tri- or spirocarbocyclic group having from 3 to 10 carbon atoms.
  • Representative examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclode- cyl, bicyclo[3.2.1]octyl, spiro[4.5]decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like.
  • Ca-s-heterocyclyl represents a saturated 3 to 8 membered ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur.
  • Representative examples are pyrrolidyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, azirid- inyl, tetrahydrofuranyl and the like.
  • aryl represents a carbocyclic aromatic ring system being either monocyclic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl and the like.
  • Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 1,2,3,4-tetrahydronaphthyl, 1 ,4-dihydronaphthyl and the like.
  • heteroaryl represents a heterocyclic aromatic ring system containing one or more heteroatoms selected from nitrogen, oxygen and sulfur such as furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1 ,2,3-triazoiyl, 1 ,2,4- triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1 ,3,5- triazinyl, 1 ,2,3-oxadiazolyl, 1 ,2,4-oxadiazolyl, 1 ,2,5-oxadiazolyl, 1 ,3,4-oxadiazolyl, 1 ,2,3- thiadiazolyl, 1 ,2,4-thiadia
  • Heteroaryl is also intended to include the partially hydrogen- ated derivatives of the heterocyclic systems enumerated above.
  • Non-limiting examples of such partially hydrogenated derivatives are 2,3-dihydrobenzofuranyl, 3,4-dihydroisoquinolinyl, pyrrolinyl, pyrazolinyl, indolinyl, oxazolidinyl, oxazolinyl, oxazepinyl and the like.
  • perhalomethyl designates a methyl moiety substituted with three halogen atoms.
  • Non-limiting examples of perhalomethyl are CF 3 , CCI 3 , and CF 2 CI.
  • perhalomethoxy designates a perhalomethyl linked via an oxygen atom, e.g. -0-CF 3 , -0-CCl 3 , and -0-CF 2 Cl
  • ring system as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and they encompass moieties with zero, one or more hetereatoms selected from nitrogen, oxygen and sulphur.
  • Non-limiting exam- pies of such ring systems are aryl, C 3-8 -heterocyclyl and heteroaryl.
  • heterocyclic system includes aromatic as well as non- aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and containing in their ring structure one or more heteroatoms selected from nitrogen, oxygen and sulfur.
  • Non- limiting examples of such heterocyclic systems are C 3-8 -heterocyclyl and heteroaryl. Certain of the above defined terms may occur more than once in the structural formulae, and upon such occurrence each term shall be defined independently of the other.
  • treatment means the management and care of a patient having developed a disease, condition or disorder, as well as the management and care of an individual at risk of developing the disease, condition or disorder prior to the clinical onset of said disease, condition or disorder.
  • the purpose of treatment is to combat the disease, condition or disorder, as well as to to combat the development of the disease, condition or disorder.
  • Treatment includes the administration of the active compounds to prevent or delay the onset of the symptoms or complications and to eliminate or control the disease, condition or disorder as well as to alleviate the symptoms or complications associated with the disease, condition or disorder.
  • the term "effective amount” as used herein means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment.
  • modulate as used herein means to influence, i.e. to modulate a parameter means to influence that parameter in a desired way. Examples are to modulate insulin secretion from beta cells and to modulate the plasma level of free fatty acids.
  • medicament means a pharmaceutical composition suitable for administration of the pharmaceutically active compound to a patient.
  • pharmaceutically acceptable means suited for normal pharmaceutical applications, i.e. giving rise to no adverse events in patients etc.
  • the present invention relates to a compound of the general formula (I) :
  • R 1 and R 2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C 1-6 -alkyl, Ci_s-alkoxy, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 - cydoalkyl, wherein each of hydroxy, sulfanyl, sulfo, C 1-6 -alkyl, Ci -6 -alkoxy, C 2-6 -alkenyl, aryl, heteroaryl, C 3 -g-heterocyclyl and C 3-10 -cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C 1-6 -alkyl, C 1-6 -alkoxy, C 2-6 -alkenyl
  • X is N or CR 3
  • Y is N or CR 4
  • Z is N or CR 5 ; provided that X, Y and Z are not all CH;
  • R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3 ⁇ -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 - heterocyclyl and C 3-1o -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and Cs-io-cycloalkyl, wherein each of
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from C 2-6 -alkyl, C 2 ⁇ -alkenyl, aryl, heteroaryl, C 3- 8-heterocyclyl and C 3- i 0 - cycloalkyl, wherein each of C 2-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3- 1o -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-e -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3 .
  • each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, Cs- ⁇ -heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C 1-6 -alkyl, perhalomethyl and perhalomethoxy;
  • 4-(4-FIuorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Chlorobenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester, 4-(4-Methylbenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester,4- (4-Methoxybenzyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester,
  • 4-Octylpiperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester, 4-(3-Dimethylamino-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-[2-(2-Hydroxyethoxy)ethyI]piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester, or 4-(1 -Methyl-piperidin-4-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
  • the invention concerns a compound wherein R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C 1-6 -alkyl, C 2-6 - alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-1 o-cycloalkyl, wherein each of hydroxy, sul- fanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 - cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3- 8 -heterocyclyl and C 3-10
  • the invention concerns a compound wherein R 6 is selected from aryl, heteroaryl, C ⁇ -heterocyclyl and Cs-io-cycloalkyl, wherein each of aryl, heteroaryl, C 3-8 - heterocyclyl and C 3- i 0 -cycloalkyI is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-1o -cycloalkyl is optionally substituted with one or more substituents
  • the invention concerns a compound wherein R 6 is an aryl which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2 - 6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C 1-6 - alkyl, perhalomethyl and perhalomethoxy;
  • the invention concerns a compound wherein R 6 is an aryl
  • the invention concerns a compound wherein R 6 is a pyridyl which is optionally substituted.
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C 1-6 -alkyl, C 1-6 -alkoxy, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 - cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C 1-6 -alkyl, C 1-6 -alkoxy, C 2-6 -alkenyl, aryl, heteroaryl, C 3 ⁇ -heterocyclyl and C 3-10 -cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C 1-6 -alkyl, Ci -6 -alkoxy, C 2-6 -alkenyl,
  • X is N or CR 3
  • Y is N or CR 4
  • Z is N or CR 5 ; provided that X, Y and Z are not all CH;
  • R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci -6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 - heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, d- 6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloaIkyl, wherein each of
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of:
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are hydrogen ,
  • X is N or CR 3
  • Y is N or CR 4
  • Z is N or CR 5 ; provided that X, Y and Z are not all CH;
  • R 3 , R 4 and R 5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-1 o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 - heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, d-e-alkyl, C 2-6 -aIkenyl, aryl, heteroaryl, C ⁇ s-heterocyclyl and Cs-io-cycloalkyl, wherein each of
  • 6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen', amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and Cs- 10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C 1-6 - alkyl, perhalomethyl and per
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of:
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are hydrogen
  • X is CR 3 , Y is C-H, Z is N or CH;
  • R 3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C 1-6 - alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-1 o-cycloalkyl, wherein each of hy- droxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C ⁇ -heterocyclyl and C 3- 10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3- 8-heterocyclyl and C 3-10 -cycIoalkyl, wherein each of
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of:
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are hydrogen
  • X is CR 3 , Y and Z is C-H;
  • R 3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, Ci -6 - alkyl, C 2- 6-alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3 ⁇ -heterocyclyl and C 3- 10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3- 8 -heterocyclyl and C 3-10 -cycl
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of:
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are hydrogen
  • X is CR 3 , Y is C-H, Z is CH;
  • R 3 are independently selected from hydroxy, amino, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and Q M o-cycloalkyl, wherein each of hydroxy, amino, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, Cs-g-heterocyclyl and C 3-10 -cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2 - 6 -alkenyl, aryl, heteroaryl, Ca-g-heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, d- ⁇ -alkyl, C 2-6 -alkenyl,
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of:
  • the invention concerns a compound of the general formula (I) :
  • R 1 and R 2 are hydrogen
  • X is CR 3 , Y is C-H, Z is CH;
  • R 3 are independently selected from hydroxy, amino, C 1-6 -alkyl, C 2-6 -aIkenyl, aryl, heteroaryl, Ca- ⁇ -heterocyclyl and C 3-10 -CyClOaIkYl, wherein each of hydroxy, amino, Ci -6 -alkyl, C 2 .
  • 6 -alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C 3-10 -CyClOaIkYl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C 3-10 -cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 3-8 -heterocyclyl and C3-iQ-cycloalkyl is optionally substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C
  • A is selected from CH 2 and CH 2 CH 2 ;
  • R 6 is selected from the list consisting of: ⁇ , Cf - p and with the proviso that said compound is not
  • the invention concerns a compound wherein A is CH 2 CH 2 . In another embodiment the invention concerns a compound wherein A is CH 2 .
  • the invention is concerned with compounds wherein R 1 is hydrogen.
  • the invention is concerned with compounds wherein R 2 is hydrogen.
  • the invention is concerned with compounds wherein R 1 is hydrogen and R 2 is hydrogen.
  • the invention is concerned with compounds wherein X is N. In another embodiment the invention is concerned with compounds wherein X is CH. In another embodiment the invention is concerned with compounds wherein X is C-R 3 .
  • the invention is concerned with compounds wherein Z is N.
  • the invention is concerned with compounds wherein Z is C-R 5 . In another embodiment the invention is concerned with compounds wherein Z is CH.
  • the invention is concerned with compounds wherein Y is N.
  • the invention is concerned with compounds wherein Y is CH.
  • the invention is concerned with compounds wherein Y is C-R 4 .
  • the invention is concerned with compounds wherein only one of X, Y and Z is N.
  • the invention is concerned with compounds wherein X is C-R 3 , Y is
  • C-R 4 and Z is C-R 5 .
  • the invention is concerned with compounds wherein X is C-R 3 .
  • the invention is concerned with compounds, having one free - COOH group.
  • the invention is concerned with compounds having one free amino group, or one monosubstituted amino group or one disubstituted amino group. In another embodiment the invention is concerned with compounds having one substituted or unsubstituted pyridine ring.
  • the invention is concerned with compounds having one substituted or unsubstituted imidazole ring.
  • the invention is concerned with compounds wherein the molar weight of said compound is less than 650 g/mole.
  • cLog P of a compound which has no ionisable group is calculated using Sybyl 6.6 from Tripos Corporation, version 4.0 (provided by Biobyte Corp., Claremont CA, USA).
  • the invention is concerned with compounds wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 5.0.
  • the invention is concerned with compounds wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 4.0.
  • a number of other properties of the compounds are calculated using Sybyl 6.6. from Tripos Corporation, i.e. the number of H-bond donors, the number of H-bond acceptors, the number of rotatable bonds.
  • the polar surface area (PSA) is calculated using the SAVoI program Based on SAVoI 3.7 using AIIinger vdw radii.
  • Polar atoms are oxygens, nitrogens, plus hydrogens attached to O and N developed by R. S. Pearlman, J. M. Skell and F. Deanda, Laboratory for Molecular Graphics and Theoretical Modeling, College of Pharmacy, Universi- ty of Texas, Austin, TX 78712, U.S.A.
  • the invention is concerned with compounds wherein the ACD LogD is in the range from 0.8 to 3.0.
  • the invention is concerned with compounds wherein the number of H-bond donors is 0, 1 , 2 or 3. In another embodiment the invention is concerned with compounds wherein the number of H-bond donors is 0 or 1 or 2
  • the invention is concerned with compounds wherein the number of H-bond acceptors is in the range from 4 to 9. In another embodiment the invention is concerned with compounds wherein the number of H-bond acceptors is in the range from 5 to 8. In another embodiment the invention is concerned with compounds wherein the number of rotatable bonds of said compound is in the range from 6 to 15.
  • the invention is concerned with compounds wherein the number of rotatable bonds of said compound is in the range from 7 to 12. In another embodiment the invention is concerned with compounds wherein the polar surface area (PSA) is in the range from 40 A 2 to120 A 2 .
  • PSA polar surface area
  • the invention is concerned with compounds wherein the polar surface area (PSA) is in the range from 40 A 2 to80 A 2 .
  • PSA polar surface area
  • the invention is concerned with a compound selected from the group consisting of 4-(2-Pyridin-2-yl-ethyI)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl- benzyl)-phenyl ester,

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Abstract

Novel substituted piperazine carbamates of formula (I), pharmaceutical compositions comprising them and use thereof in the treatment and/or prevention of diseases and disorders related to hormone sensitive lipase. More particularly, the compounds are useful for the treatment and/or prevention of diseases and disorders in which modulation of the activity of hormone sensitive lipase is beneficial.

Description

SUBSTITUTED PIPERAZINE CARBAMATES FOR USE AS INHIBITORS OF HORMONE SENSITIVE LIPASE
FIELD OF THE INVENTION
The present invention relates to novel substituted piperazine carbamates, to phar- maceutical compositions comprising these compounds, to the use of these compounds as pharmaceutical compositions, and to methods of treatment employing these compounds and compositions. The present compounds are inhibitiors of hormone sensitive lipase. As a result, the compounds are useful for the treatment and/or prevention of diseases and disorders related to hormone sensitive lipase.
BACKGROUND OF THE INVENTION
The overall energy homeostasis of a mammalian system requires a high degree of regulation to ensure the availability of the appropriate substrate at the appropriate time. Plasma glucose levels rise during the post-prandial state, to return to pre-prandial levels within 2-3 hours. During these 2-3 hours, insulin promotes glucose uptake by skeletal muscle and adipose tissue and decreases the release of free fatty acids (FFA) from adipocytes, to ensure that the two substrates do not compete with each other. When plasma glucose levels fall, an elevation in plasma FFA is necessary to switch from glucose to fat utilization by the various tissues. In individuals with insulin resistance, FFA levels do not fall in response to insulin, as they do in normal individuals, preventing the normal utilization of glucose by skeletal muscle, adipose and liver. Furthermore, there is a negative correlation between insulin sensitivity and plasma FFA levels.
Hormone-sensitive lipase (HSL) is an enzyme, expressed in adipose tissue, macro- phages, muscle, adrenal, testis and islets (Kraemer and Shen, J. Lipid Res. 2002, 43, 1585- 1594). In the adipocytes HSL catalyses the conversion of triglycerides to glycerol and fatty acids. It is through the regulation of this enzyme that the levels of circulating FFA are modulated. Insulin leads to the inactivation of HSL with a subsequent fall in plasma FFA levels during the post-prandial state, followed by the activation of the enzyme when the insulin concen- tration falls and catecholamines rise during the post-absorptive period. The activation of HSL leads to an increase in plasma FFA, as they become the main source of energy during fasting. The activation-inactivation of HSL is primarily mediated through the cAMP-protein kinase A and AMP-dependent kinase pathways. There are compounds like nicotinic acid and its derivatives, that decrease the activation of HSL via these pathways and cause a decrease in lipolysis that leads to a reduction in the FFA levels. These drugs have a beneficial effect in the utilization of glucose and in the normalization of the excess triglyceride synthesis seen in patients with elevated FFA. However, since these pathways are used by other processes in the body, these drugs have severe side effects.
Piperazines similar to the compounds of the present invention have previously been prepared, and their properties have been investigated for a number of pharmaceutical appli- cations, e.g. CNS disorders.
Several publications disclose the preparation and use of HSL inhibitors (WO 01/87843, WO 01/17981 , WO 01/66531 , WO 01/83497, and WO 01/26664). However, the structures of these compounds are very different from that of the present compounds. Thus, none of the HSL inhibitors disclosed in these publications contain piperazine and carbamate substructures as in the compounds of the present invention.
We have found piperazine compounds that specifically inhibit the lipolytic activity of HSL and which are expected to decrease in plasma FFA levels. These compounds can be used to treat disorders where a decreased level of plasma FFA is desired, such as insulin resistance, syndrome X, dyslipidemia, abnormalities of lipoprotein metabolism. One object of the present invention is to provide compounds and pharmaceutical compositions that inhibit the lipolytic activity of HSL. A further object is to provide compounds which have good pharmaceutical properties such as solubility, bioavailability, specificity etc.
DEFINITIONS The following is a detailed definition of the terms used to describe the compounds of the invention.
The term "halogen" in the present context designates an atom selected from the group consisting of F, Cl, Br and I.
The term "C1-6-alkyl" in the present context designates a saturated, branched or straight hydrocarbon group having from 1 to 6 carbon atoms. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, n-pentyl, isopentyl, neopentyl, terf-pentyl, n-hexyl, isohexyl and the like.
The term "C2-6-alkyl" in the present context designates a saturated, branched or straight hydrocarbon group having from 2 to 6 carbon atoms. Representative examples in- elude, but are not limited to, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, ferf-butyl, n- pentyl, isopentyl, neopentyl, ferf-pentyl, n-hexyl, isohexyl and the like.
The term "C1-6-alkoxy" in the present context designates a group -O-C1-6-alkyl wherein C1-6-alkyl is as defined above. Representative examples include, but are not limited to, meth- oxy, ethoxy, n-propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, ferf-butoxy, n-pentoxy, isopentoxy, neopentoxy, terf-pentoxy, n-hexoxy, isohexoxy and the like.
The term "C2-6-alkenyl" as used herein, represent an olefinically unsaturated ; branched or straight hydrocarbon group having from 2 to 6 carbon atoms and at least one double bond. Examples of such groups include, but are not limited to, vinyl, 1-propenyl, 2- propenyl, allyl, iso-propenyl, 1 ,3-butadienyl, 1-butenyl, hexenyl, pentenyl and the like.
The term "C3.10-cycloalkyr as used herein represents a saturated mono-, bi-, tri- or spirocarbocyclic group having from 3 to 10 carbon atoms. Representative examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclode- cyl, bicyclo[3.2.1]octyl, spiro[4.5]decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like. The term "Ca-s-heterocyclyl" as used herein represents a saturated 3 to 8 membered ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Representative examples are pyrrolidyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, azirid- inyl, tetrahydrofuranyl and the like.
The term "aryl" as used herein represents a carbocyclic aromatic ring system being either monocyclic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl and the like. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 1,2,3,4-tetrahydronaphthyl, 1 ,4-dihydronaphthyl and the like. The term "heteroaryl" as used herein represents a heterocyclic aromatic ring system containing one or more heteroatoms selected from nitrogen, oxygen and sulfur such as furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1 ,2,3-triazoiyl, 1 ,2,4- triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1 ,3,5- triazinyl, 1 ,2,3-oxadiazolyl, 1 ,2,4-oxadiazolyl, 1 ,2,5-oxadiazolyl, 1 ,3,4-oxadiazolyl, 1 ,2,3- thiadiazolyl, 1 ,2,4-thiadiazolyl, 1 ,2,5-thiadiazolyl, 1 ,3,4-thiadiazolyl, tetrazolyl, thiadiazinyl, indo- IyI, isoindolyl, benzofuranyl, benzothiophenyl (thianaphthenyl), indazolyl, benzimidazolyl, benzthiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, purinyl, quinazolinyl, quinolizinyl, quinolinyl, isoquinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, azepinyl, di- azepinyl, acridinyl and the like. Heteroaryl is also intended to include the partially hydrogen- ated derivatives of the heterocyclic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 2,3-dihydrobenzofuranyl, 3,4-dihydroisoquinolinyl, pyrrolinyl, pyrazolinyl, indolinyl, oxazolidinyl, oxazolinyl, oxazepinyl and the like.
The term "perhalomethyl" as used herein designates a methyl moiety substituted with three halogen atoms. Non-limiting examples of perhalomethyl are CF3, CCI3, and CF2CI. The term "perhalomethoxy" as used herein designates a perhalomethyl linked via an oxygen atom, e.g. -0-CF3, -0-CCl3, and -0-CF2Cl
The term "ring system" as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and they encompass moieties with zero, one or more hetereatoms selected from nitrogen, oxygen and sulphur. Non-limiting exam- pies of such ring systems are aryl, C3-8-heterocyclyl and heteroaryl.
The term "heterocyclic system" as used herein includes aromatic as well as non- aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and containing in their ring structure one or more heteroatoms selected from nitrogen, oxygen and sulfur. Non- limiting examples of such heterocyclic systems are C3-8-heterocyclyl and heteroaryl. Certain of the above defined terms may occur more than once in the structural formulae, and upon such occurrence each term shall be defined independently of the other.
The term "optionally substituted" as used herein means that the groups in question are either unsubstituted or substituted with one or more of the substituents specified. When the groups in question are substituted with more than one substituent the substituents may be the same or different.
The terms "disease", "condition" and "disorder" as used herein are used interchangeably to specify a state of a patient which is not the normal physiological state of man. The term "treatment" as used herein means the management and care of a patient having developed a disease, condition or disorder, as well as the management and care of an individual at risk of developing the disease, condition or disorder prior to the clinical onset of said disease, condition or disorder. The purpose of treatment is to combat the disease, condition or disorder, as well as to to combat the development of the disease, condition or disorder. Treatment includes the administration of the active compounds to prevent or delay the onset of the symptoms or complications and to eliminate or control the disease, condition or disorder as well as to alleviate the symptoms or complications associated with the disease, condition or disorder.
The term "effective amount" as used herein means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment. The term "modulate" as used herein means to influence, i.e. to modulate a parameter means to influence that parameter in a desired way. Examples are to modulate insulin secretion from beta cells and to modulate the plasma level of free fatty acids.
The term "medicament" as used herein means a pharmaceutical composition suitable for administration of the pharmaceutically active compound to a patient..
The term "pharmaceutically acceptable" as used herein means suited for normal pharmaceutical applications, i.e. giving rise to no adverse events in patients etc.
DESCRIPTION OF THE INVENTION
In one aspect the present invention relates to a compound of the general formula (I) :
Figure imgf000006_0001
wherein
R1 and R2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C1-6-alkyl, Ci_s-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cydoalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl, Ci-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-g-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl;
X is N or CR3, Y is N or CR4, Z is N or CR5; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-1O-CyClOaIkYl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-10-CyClOaIkYl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from C2-6-alkyl, C2^-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0- cycloalkyl, wherein each of C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-e-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-β-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
and with the proviso that said compound is not 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2~ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- phenyl ester,
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester, 4-(2-Pyridin-4-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Thienylethyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester,
4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)- phenyl ester, 4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester,
4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4-chloro-phenyl)- ethylcarbamoyl]-phenyl ester 4-(5-Chloro-thiophen-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Chlorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(3,4-Methylenedioxy-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid pyrazol-1-yl ester,
4-Benzyl-piperazine-1 -carboxylic acid 3-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-pyrazol-1 -yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3,4,5-tribromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-chloro-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(4-methoxy-phenyl)-pyrazoI-1 -yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(4-nitro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(2-fluoro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-pyridin-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-phenylsulfanyl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-thiophen-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-chloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-bromo-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-iodo-imidazol-1-yl ester, 4-Benzyl-piperaziπe-1 -carboxylic acid 2-methyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-(4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-(4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-thiophen-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-pyridin-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2,5-dichIoro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-2,5-dichloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-2-chloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-(4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-(4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-thiophen-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-pyridin-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester, 4-(4-tert-Butylbenzyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)phenyl ester,
4-(4-FIuorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Chlorobenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester, 4-(4-Methylbenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester,4- (4-Methoxybenzyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyI ester,
4-(2-Chloro-6-fluoro-benzyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid 4-iodo-pyrazol-1-yl ester,
4-(4-Fluoro-benzyl)-piperazine-1 -carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Naphthalen-1 -ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-(3,4-Dichloro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-(3-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifIuoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(3-Fluoro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Fluorobenzyl)-piperazine-1 -carboxylic acid 4-(4,6-dimethyl-pyrimidin-2-ylsulfanyl)- phenyl ester, 4-(4-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)-
phenyl ester, H-d NNC 0076-0000-1448
4-(4-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester,
4-(4-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Phenethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Phenylpropyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Phenylbutyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Phenylbutyl)piperazine-1 -carboxylic acid 4-chlorophenyl ester, 4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester^-Cyclohexylmethyl-piperazine-i -carboxylic acid 4-(4-trifluoromethyl- phenoxy)-phenyl ester,
4-Cyclohexylmethyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester, 4-(2-Cyclohexyl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-chloro-phenyI)-ethylcarbamoyl]- phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester, 4-(2-Hydroxyethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl ester,
4-(Pyrrolidinocarbonylmethyl)- piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-(lsopropylaminocarbonylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Ethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Propyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Butyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(3-Hydroxypropyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-(2-Hydroxyethoxy)ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-[2-(2-Hydroxyethoxy)ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Octylpiperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester, 4-(3-Dimethylamino-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-[2-(2-Hydroxyethoxy)ethyI]piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester, or 4-(1 -Methyl-piperidin-4-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
In one embodiment the invention concerns a compound wherein R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sul- fanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, d-6-aIkyl, perhalomethyl and perhalomethoxy;
In another embodiment the invention concerns a compound wherein R6 is selected from aryl, heteroaryl, C^-heterocyclyl and Cs-io-cycloalkyl, wherein each of aryl, heteroaryl, C3-8- heterocyclyl and C3-i0-cycloalkyI is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
In another embodiment the invention concerns a compound wherein R6 is an aryl which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy; In another embodiment the invention concerns a compound wherein R6 is a phenyl which is optionally substituted.
In another embodiment the invention concerns a compound wherein R6 is a pyridyl which is optionally substituted.
In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000012_0001
wherein
R1 and R2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C1-6-alkyl, Ci-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl;
X is N or CR3, Y is N or CR4, Z is N or CR5; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^-heterocyclyl and C^o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^a-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2; R6 is selected from the list consisting of:
O' . Cf - p and with the proviso that said compound is not 4-Benzyl-piperazine-i-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000013_0001
wherein
R1 and R2 are hydrogen ,
X is N or CR3, Y is N or CR4, Z is N or CR5; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, d-e-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C^s-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2.6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen', amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
Figure imgf000014_0001
and with the proviso that said compound is not 4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000014_0002
wherein
R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is N or CH;
R3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl, wherein each of hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl and C3-10-cycIoalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-i0-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, Ci-6-alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
O. Cr -p and with the proviso that said compound is not 4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trif luoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yI-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000015_0001
wherein
R1 and R2 are hydrogen
X is CR3, Y and Z is C-H; R3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, Ci-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-i0-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, amino, sulfo, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-i0-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
Figure imgf000016_0001
and with the proviso that said compound is not 4-Benzyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000016_0002
wherein
R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is CH;
R3 are independently selected from hydroxy, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and QMo-cycloalkyl, wherein each of hydroxy, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-g-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Ca-g-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, d-β-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-β-heterocyclyl and C3-i0-cycloaIkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
(XG -p and with the proviso that said compound is not
4-Benzyl-piperazine-i-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyI)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof. In another embodiment the invention concerns a compound of the general formula (I) :
Figure imgf000018_0001
wherein
R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is CH;
R3 are independently selected from hydroxy, amino, C1-6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, Ca-β-heterocyclyl and C3-10-CyClOaIkYl, wherein each of hydroxy, amino, Ci-6-alkyl, C2.6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3-10-CyClOaIkYl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-iQ-cycloalkyl is optionally substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-aIkyI, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of: α , Cf - p and with the proviso that said compound is not
4-Benzyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof. In another embodiment the invention concerns a compound wherein A is CH2CH2. In another embodiment the invention concerns a compound wherein A is CH2.
In another embodiment the invention is concerned with compounds wherein R1 is hydrogen.
In another embodiment the invention is concerned with compounds wherein R2 is hydrogen.
In another embodiment the invention is concerned with compounds wherein R1 is hydrogen and R2 is hydrogen.
In another embodiment the invention is concerned with compounds wherein R2 is selected from the group consisting of
Figure imgf000019_0001
In another embodiment the invention is concerned with compounds wherein R2 is selected from the group consisting of
Figure imgf000019_0002
In another embodiment the invention is concerned with compounds wherein R2 is selected from the group consisting of
Figure imgf000020_0001
In another embodiment the invention is concerned with compounds wherein R2 is selected from the group consisting of
Figure imgf000020_0002
In another embodiment the invention is concerned with compounds wherein X is N. In another embodiment the invention is concerned with compounds wherein X is CH. In another embodiment the invention is concerned with compounds wherein X is C-R3.
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000020_0003
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000021_0001
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000021_0002
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000021_0003
In another embodiment the invention is concerned with compounds wherein Z is N.
In another embodiment the invention is concerned with compounds wherein Z is C-R5. In another embodiment the invention is concerned with compounds wherein Z is CH.
In another embodiment the invention is concerned with compounds wherein Y is N.
In another embodiment the invention is concerned with compounds wherein Y is CH.
In another embodiment the invention is concerned with compounds wherein Y is C-R4.
In another embodiment the invention is concerned with compounds wherein only one of X, Y and Z is N.
In another embodiment the invention is concerned with compounds wherein X is C-R3, Y is
C-R4 and Z is C-R5.
In another embodiment the invention is concerned with compounds wherein Y and Z are both
CH. In another embodiment the invention is concerned with compounds wherein X is C-R3.
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000022_0001
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000022_0002
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000022_0003
In another embodiment the invention is concerned with compounds wherein R3 is selected from the group consisting of
Figure imgf000022_0004
In another embodiment the invention is concerned with compounds, having one free - COOH group.
In another embodiment the invention is concerned with compounds having one free amino group, or one monosubstituted amino group or one disubstituted amino group. In another embodiment the invention is concerned with compounds having one substituted or unsubstituted pyridine ring.
In another embodiment the invention is concerned with compounds having one substituted or unsubstituted imidazole ring.
In another embodiment the invention is concerned with compounds wherein the molar weight of said compound is less than 650 g/mole.
The property cLog P of a compound which has no ionisable group is calculated using Sybyl 6.6 from Tripos Corporation, version 4.0 (provided by Biobyte Corp., Claremont CA, USA). In another embodiment the invention is concerned with compounds wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 5.0.
In another embodiment the invention is concerned with compounds wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 4.0.
A number of other properties of the compounds are calculated using Sybyl 6.6. from Tripos Corporation, i.e. the number of H-bond donors, the number of H-bond acceptors, the number of rotatable bonds. The polar surface area (PSA) is calculated using the SAVoI program Based on SAVoI 3.7 using AIIinger vdw radii. Polar atoms are oxygens, nitrogens, plus hydrogens attached to O and N developed by R. S. Pearlman, J. M. Skell and F. Deanda, Laboratory for Molecular Graphics and Theoretical Modeling, College of Pharmacy, Universi- ty of Texas, Austin, TX 78712, U.S.A.
In another embodiment the invention is concerned with compounds wherein the ACD LogD is in the range from 0.8 to 3.0.
In another embodiment the invention is concerned with compounds wherein the number of H-bond donors is 0, 1 , 2 or 3. In another embodiment the invention is concerned with compounds wherein the number of H-bond donors is 0 or 1 or 2
In another embodiment the invention is concerned with compounds wherein the number of H-bond acceptors is in the range from 4 to 9. In another embodiment the invention is concerned with compounds wherein the number of H-bond acceptors is in the range from 5 to 8. In another embodiment the invention is concerned with compounds wherein the number of rotatable bonds of said compound is in the range from 6 to 15.
In another embodiment the invention is concerned with compounds wherein the number of rotatable bonds of said compound is in the range from 7 to 12. In another embodiment the invention is concerned with compounds wherein the polar surface area (PSA) is in the range from 40 A2 to120 A2.
In another embodiment the invention is concerned with compounds wherein the polar surface area (PSA) is in the range from 40 A2 to80 A2.
In another embodiment the invention is concerned with a compound selected from the group consisting of 4-(2-Pyridin-2-yl-ethyI)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl- benzyl)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1-carboxyiic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro- 2H-[1 ,3']bipyridinyl-6'-yl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester,
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, and
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester. In another embodiment the invention is concerned with a compound selected from the group consisting of
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4I4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyridinyl-6'-yl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1,3']bipyridinyl-6'-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester
4-[2-(1 -Methyl- 1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl- butylcarbamoyl)-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dinnethyl-butylcarbannoyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2~ ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H- [1 ,3']bipyridinyl-6'-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H- [1 ,3']bipyridinyl-6'-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1.S'Jbipyridinyl-δ'-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyridinyl-6'-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1 ,3']bipyridinyl-6'-yl ester '
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1.S'Jbipyridinyl-δ'-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2l-l-
[1 ,3']bipyridinyl-6'-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1.S'jbipyridinyl-θ'-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-314,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-
3,4,5,6-tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-t3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1-yl)-ethyl]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-
1 -yl )-ethyl] -pyrid in-2-y I ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl )-ethyl]-pyrid in-2-y] ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -y] )-eth yl]-pyrid in-2-y I ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl )-ethyl]-pyr id in -2-y I ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-pyridin-2-yl ester
4-[2-(1H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1- yl)-ethyl]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperϊdin-1 -y I )-ethyl]-pyrid i n-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(6-Methyl~pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin- 2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)- pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-
2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(1H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)- pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-
2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]~ phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(1-methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1-methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1 -Methyl- 1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(3-Methyl-isoxazoI-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-
2-yl)-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl )-pyrid in-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro- isoindol-2-yl)-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyrid in-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(1,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxyiic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-[2-(1H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4~yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 , 1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl- amino)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-
1-yl)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester
4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethy!)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylnnethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester 4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(2-Thiazol~2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethylj-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 -yl)- pyridin-3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 -yl)- pyridin-3-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1- yl )-pyr id in-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyrid in-3-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 -yl)- pyridin-3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1-yl)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yI)-propyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1-yl)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-
1-yl)-pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1-yl)-pyridin-3-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- ' imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- ■ phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl- benzoylamino)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-t2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1-carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 - ylmethyl)-benzoylannino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-t2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-t4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperaziπe-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl )-propyi]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1-Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyi]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyi-pyridin-2- ylmethyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 -Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(1H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmetriyl)-phenyl ester
4-Pyridin-3-ylmethyi-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- • ylsulfanyl)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester >
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-t2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1-Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyI-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperaziπe-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxyiic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl~pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yI)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)- ethyl]-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- ' phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)- ethyl]-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyrazin~2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2~yl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)- ethyl]-phenyl ester and
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester In another aspect the present invention relates to a pharmaceutical composition comprising a compound of general formula I or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
In one embodiment the invention is concerned with a pharmaceutical composition in unit dosage form, comprising from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of said compound according to the invention or pharmaceutically acceptable salt thereof.
In another embodiment the invention is concerned with a pharmaceutical composition for use as a medicament for inhibiting the lipolytic activity of hormone-sensitive lipase against triacyl- glycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters, said composition comprising a compound according to the invention or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
In another embodiment the invention is concerned with a pharmaceutical composition which is for oral administration.
In another embodiment the invention is concerned with a pharmaceutical composition which is for nasal, transdermal, pulmonal, or parenteral administration.
In another aspect the present invention relates to use of a compound according to the invent- tion for the preparation of a pharmaceutical composition.
In one embodiment the invention is concerned with use of a compound according to the in- vention for inhibition of hormone sensitive lipase.
In another embodiment the invention is concerned with use of a compound according to the invention for preparation of a pharmaceutical composition for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters.
In another embodiment the invention is concerned with use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment or prevention of any disorder where it is desirable to modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, in- sulin and/or glucose; and/or modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA's as well as citrate or malonyl-CoA; and/or increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic β cells; and/or modulate insulin secretion from pancreatic β cells.
In another embodiment the invention is concerned with the above use wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1, diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, atheroschlerosis, hypertension, abnormalities of lipoprotein metabolism and any combination thereof.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of dyslipidemia.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of hyperlipidemia.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of hyperglycemia.
In another embodiment the invention is concerned with the use of a compound according to the invention for lowering HbA10.
In another embodiment the invention is concerned with the preparation of a pharmaceutical composition for the treatment and/or prevention of diabetes type 2.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention impaired glucose tolerance. In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of metabolic syndrome X.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for the treatment and/or prevention of atheroschlerosis.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for delaying or prevention of the progression from impaired glucose tolerance to diabetes type 2.
In another embodiment the invention is concerned with the use of a compound according to the invention for the preparation of a pharmaceutical composition for delaying or prevention of the progression from non-insulin requiring diabetes type 2 to insulin requiring diabetes type 2.
In another embodiment the invention is concerned with the use according to above indica- tionns wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is used.
In another embodiment the invention is concerned with the use according to above indications, wherein metformin is also used.
In another aspect the present invention is related to a method of treating a disorder of a patient where modulation of the activity of hormone-sensitive lipase is desired, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to the present invention or a pharmaceutically acceptable salt thereof.
In one embodiment the invention is concerned with a method of treating a disorder of a patient where lowering of the activity of hormone-sensitive lipase is desired, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to the invention or a pharmaceutically acceptable salt thereof. In another embodiment the invention is concerned with the above methods wherein said administration is carried out by the oral, nasal, transdermal, pulmonal, or parenteral route.
In another embodiment the invention is concerned with the above methods wherein said dis- order is selected from the group consisting of insulin resistance, diabetes type 1 , diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, atheroschlerosis, hypertension, abnormalities of lipoprotein metabolism and any combination thereof.
In another embodiment the invention is concerned with the above methods wherein the therapeutically effective amount of the compound is from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of said compound per day.
In another embodiment the invention is concerned with the above methods wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is administered to the patient.
In another embodiment the invention is concerned with above methods wherein metformin is also administered to the patient.
In another aspect the present invention relates to a process P1 for the preparation of a compound according to the invention or its pharmaceutically acceptable salt, which comprises reacting the appropriate phenol with the appropriate carbamoylating reagent in a solvent ac- cording to the reaction scheme Pi
IPil
Figure imgf000071_0001
and isolating the disubstituted carbamate product.
In one embodiment of the invention said carbamoylating reagent
Figure imgf000072_0001
is selected from the group consisting of
Figure imgf000072_0002
In another embodiment of the invention said solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide and N-methylpyrolidone.
In another embodiment of the invention said base is selected from the group consisting of triethylamine, N,N-diisopropyl-N-ethylamine and DABCO.
In another aspect the present invention realtes to a process P2 for the preparation of a compound according to any one of claims 1-56, said process comprising the treatment of the appropriate amine with the appropriate acylating reagent in a solvent according to the reaction scheme P2
Figure imgf000072_0003
wherein Lv is a leaving group, and isolating the disubstituted carbamate as a salt with the acid H-Lv.
In one embodiment of the invention Lv is Cl. In another embodiment of the invention said solvent is selected from the group consisting of diethyl ether, tetrahydrofuran and dichloromethane.
In another embodiment of the invention said base is selected from the group consisting of trimethylamine, triethyiamine, ethyl-diisopropyl-amine and 1 ,4-diazabicyclo[2.2.2]octane.
In another embodiment of the invention said base is present as a functionality in the sub- stituent R6, thus forming a salt with the acid H-Lv. The present invention also encompasses pharmaceutically acceptable salts of the present compounds. Such salts include pharmaceutically acceptable acid addition salts, pharmaceutically acceptable base addition salts, pharmaceutically acceptable metal salts, ammonium and alkylated ammonium salts. Acid addition salts include salts of inorganic acids as well as organic acids. Representative examples of suitable inorganic acids include hydrochloric, hydrobromic, hydroiodic, phosphoric, sulfuric, nitric acids and the like. Representative examples of suitable organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, glycolic, lactic, maleic, malic, malonic, mandelic, oxalic, picric, pyruvic, salicylic, succinic, methanesulfonic, ethanesulfonic, tartaric, ascorbic, pamoic, bismethylene salicylic, ethanedisulfonic, gluconic, citraconic, aspartic, stearic, palmitic, EDTA, glycolic, p-aminobenzoic, glutamic, benzenesulfonic, p-toluenesulfonic acids, sulphates, nitrates, phosphates, perchlorates, borates, acetates, benzoates, hydroxynaph- thoates, glycerophosphates, ketoglutarates and the like. Further examples of pharmaceutically acceptable inorganic or organic acid addition salts include the pharmaceutically accept- able salts listed in J. Pharm. Sci. 1977, 66, 2, which is incorporated herein by reference. Examples of metal salts include lithium, sodium, potassium, magnesium, zinc, calcium salts and the like. Examples of amines and organic amines include ammonium, methylamine, di- methylamine, trimethylamine, ethylamine, diethylamine, propylamine, butylamine, tetrame- thylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, choline, N,N'-dibenzylethylenediamine, N-benzylphenylethylamine, N-methyl-D-glucamine, guanidine and the like. Examples of cationic amino acids include lysine, arginine, histidine and the like.
The pharmaceutically acceptable salts are prepared by reacting the compound of formula I with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, so- dium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, THF, methanol, t-butanol, dioxane, isopropanol, ethanol etc. Mixture of solvents may be used. Organic bases like lysine, arginine, diethanolamine, choline, guandine and their derivatives etc. may also be used. Alternatively, acid addition salts wherever applicable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, ni- trie acid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc. Mixture of solvents may also be used. The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, enzymatic resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as brucine, (R)- or (S)-phenylethylamine, cinchona alkaloids and their derivatives and the like. Commonly used methods are compiled by Jaques et al in "Enantiomers, Racemates and Resolu- tion" (Wiley Interscience, 1981 ). More specifically the compound of formula I may be converted to a 1:1 mixture of diastereomeric amides by treating with chiral amines, aminoacids, aminoalcohols derived from aminoacids; conventional reaction conditions may be employed to convert acid into an amide; the dia-stereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formula I may be pre- pared by hydrolysing the pure diastereomeric amide.
Various polymorphs of compound of general formula I forming part of this invention may be prepared by crystallization of compound of formula I under different conditions. For example, using different solvents commonly used or their mixtures for recrystallization; crystallizations at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calo- rimetry, powder X-ray diffraction or such other techniques.
The invention also encompasses prodrugs of the present compounds, which on ad- ministration undergo chemical conversion by metabolic processes before becoming active pharmacological substances. In general, such prodrugs will be functional derivatives of the present compounds, which are readily convertible in vivo into the required compound of the formula I. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.
The invention also encompasses active metabolites of the present compounds. The invention also relates to pharmaceutical compositions comprising, as an active ingredient, at least one compound of the formula I or any optical or geometric isomer or tautomeric form thereof including mixtures of these or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers or diluents. Furthermore, the invention relates to the use of compounds of the general formula I or their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts or pharmaceutically acceptable solvates thereof for the preparation of a pharmaceutical composition for the treatment and/or prevention of disorders where a decreased ■ level of plasma FFA is desirable, such as the conditions mentioned above.
In another aspect, the present invention relates to a method of treating and/or preventing type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.
In a still further aspect, the present invention relates to the use of one or more compounds of the general formula I, or pharmaceutically acceptable salts thereof, for the preparation of a pharmaceutical composition for the treatment and/or prevention of type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.
In a still further aspect, the present compounds are useful for the delaying or pre- vention of the progression from impaired glucose tolerance to type 2 diabetes.
In a still further aspect, the present compounds are useful for the delaying or prevention of the progression from non-insulin requiring type 2 diabetes to insulin requiring type 2 diabetes.
In another aspect, the present compounds reduce triglyceride levels and are accord- ingly useful for the treatment and/or prevention of ailments and disorders such as diabetes and/or obesity.
In still another aspect, the compounds of general formula I are useful for the treatment of hyperglycemia, elevated HbA10 level, hyperinsulinemia, type 1.5 diabetes, latent autoimmune diabetes in adults, maturity onset diabetes, beta-cell apoptosis, hemochromatosis induced diabetes, impaired glucose tolerance, impaired fasting glucose, metabolic syndrome X, insulin resistance, impaired lipid tolerance, cystic fibrosis related diabetes, polycystic ovarian syndrome, and gestational diabetes.
In still another aspect, the compounds of general formula I are useful for the treat- ment of obesity, dyslipidemia, diabetic dyslipidemia, hyperlipidemia, hypertriglyceridemia, hyperlipoproteinemia, hypercholesterolemia, hypertension, essential hypertension, acute hypertensive emergency, arteriosclerosis, atherosclerosis, restenosis, intermittent claudication (atherosclerosis oblitterens), cardiovascular disease, cardiomyopathy, cardiac hypertrophy, left ventricular hypertrophy, coronary artery disease, early coronary artery disease, heart in- sufficiency, exercise tolerance, chronic heart failure, mild chronic heart failure, arrhythmia, cardiac dysrythmia, syncopy, heart attack, myocardial infarction, Q-wave myocardial infarction, stroke, acute coronary syndrome, angina pectoris, unstable angina, cardiac bypass re- occlusion, diastolic dysfunction, systolic dysfunction, non-Q-wave cardiac necrosis, catabolic changes after surgery, acute pancreatitis, and irritable bowel syndrome
In still another aspect, the compounds of general formula I may be useful for the treatment of diabetic retinopathy, background retinopathy, preproliferative retinopathy, proliferative retinopathy, macular edema, cataracts, nephropathy, nephrotic syndrome, diabetic nephropathy, microalbuminuria, macroalbuminuria, neuropathy, diabetic neuropathy, distal symmetrical sensorimotor polyneuropathy, and diabetic autonomic neuropathy.
In still another aspect, the compounds of general formula I are useful for increasing the number of beta-cells in a patient, increasing the size of beta-cells in a patient or stimulating beta-cell proliferation, modulating beta-cell function and insulin secretion in a patient in need thereof, which method comprises administration of an effective amount of a compound of formula I to a patient in need thereof.
The compounds of the invention are also believed to be useful for reducing body weight in a patient in need thereof. The compounds of the invention are also believed to be useful for weight neutral treatment of above mentioned diseases.
The compounds of the invention are also believed to be useful for redistributing fat in a patient in need thereof. The compounds of the invention are also believed to be useful for redistributing central fat in a patient in need thereof.
The compounds of the invention are also believed to be useful for reducing or preventing central obesity.
The compounds of the invention are also believed to be useful for reducing postprandial serum lipid excursions. The compounds of the invention are also believed to be useful for the treatment of fatty acid oxidation disorders such as MCAD.
In still another aspect, the compounds of general formula I are believed to be useful for the treatment of a disease, condition or disorder wherein cholesterol is a precursor. Such dis- eases, conditions or disorders may relate to testosterone, e.g. male contraception, excessive testosterone levels, PCOS and prostate cancer. They may also relate to Cortisol or corticotropin, e.g. Cushing disease.
The compounds of the invention are also believed to be useful for the treatment of cancer. Thus, the compounds of the general formula I. may be useful for the treatment of insulinoma (pancreatic islet cell tumors), e.g. malignant insulinomas and multiple insulinomas, adipose cell carcinomas, e.g. lipocarconoma.
The compounds of the invention are also believed to be useful for the treatment of phaechromocytoma and other diseases with increased catecholamine incretion. The compounds of the invention are also believed to be useful for the treatment of prostate cancer, e.g. adenocarcinoma.
In still another aspect, the compounds of general formula I may be useful for the treatment of hepatic steatosis.
In still another aspect, the compounds of general formula I may be useful for the treatment of cirrhosis.
In still another aspect, the compounds of general formula I may be useful for the treatment of
AIDS or an AIDS related diseases, condition or disorders
In still another aspect, the compounds of general formula I may be useful for the treatment of lipodystrophy In still another aspect, the compounds of general formula I may be useful for the treatment of lactic acidosis.
In yet another aspect, the compounds of the present invention are expected to be useful for the treatment of CNS diseases, conditions or disorders.
Thus, the compound of the present invention may be used for the treatment of Parkinsons disease, Alzheimers disease, ADHD (Attention Deficit Hyperactivity Disorder), feeding disorders such as bulimia and anorexia, depression, anxiety, cognitive memory disorders, age related cognitive decline, mild cognitive impairment and schizophrenia.
In yet another aspect, the compounds of the present invention may be useful for the treat- ment of inflammatory disorders, e.g. rheumatoid arthritis, psoriasis, systemic inflammatory response syndrome, sepsis and the like.
The present compounds may also be administered in combination with one or more further pharmacologically active substances eg., selected from antiobesity agents, antidiabet- ics, antihypertensive agents, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complications and disorders resulting from or associated with obesity.
Thus, in a further aspect of the invention the present compounds may be adminis- tered in combination with one or more antiobesity agents or appetite regulating agents.
Such agents may be selected from the group consisting of CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melano- cortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releasing factor) agonists, CRF BP (corticotropin releasing factor binding protein) an- tagonists, urocortin agonists, β3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, mixed serotonin and noradrenergic compounds, 5HT (serotonin) agonists, bombesin agonists, galanin antagonists, growth hormone, growth hormone releasing compounds, TRH (thyreotropin re- leasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA agonists (bromocriptin, doprexin), lipase/amylase inhibitors, RXR (retinoid X receptor) modulators or TR β agonists.
In one embodiment of the invention the antiobesity agent is leptin.
In another embodiment the antiobesity agent is dexamphetamine or amphetamine. In another embodiment the antiobesity agent is fenfluramine or dexfenfluramine.
In still another embodiment the antiobesity agent is sibutramine.
In a further embodiment the antiobesity agent is orlistat.
In another embodiment the antiobesity agent is mazindol or phentermine.
Suitable antidiabetics comprise insulin, exendin-4, GLP-1 (glucagon like peptide-1) and derivatives thereof such as those disclosed in WO 98/08871 to Novo Nordisk A/S, which is incorporated herein by reference as well as orally active hypoglycaemic agents.
The orally active hypoglycaemic agents preferably comprise sulphonylureas, bigua- nides, meglitinides, glucosidase inhibitors, glucagon antagonists such as those disclosed in WO 99/01423 to Novo Nordisk A/S and Agouron Pharmaceuticals, Inc., GLP-1 agonists, po- tassium channel openers such as those disclosed in WO 97/26265 and WO 99/03861 to
Novo Nordisk A/S which are incorporated herein by reference, DPP-IV (dipeptidyl peptidase- IV) inhibitors, inhibitors of hepatic enzymes involved in stimulation of gluconeogenesis and/or glycogenosis, glucose uptake modulators, compounds modifying the lipid metabolism such as antihyperlipidemic agents and antilipidemic agents as HMG CoA inhibitors (statins), com- pounds lowering food intake, RXR agonists and agents acting on the ATP-dependent potassium channel of the β-cells.
In one embodiment of the invention the present compounds are administered in combination with insulin. In a further embodiment the present compounds are administered in combination with a sulphonylurea eg. tolbutamide, glibenclamide, glipizide or glicazide.
In another embodiment the present compounds are administered in combination with a biguanide eg. metformin.
In yet another embodiment the present compounds are administered in combination with a meglitinide eg. repaglinide or senaglinide.
In a further embodiment the present compounds are administered in combination with an α-glucosidase inhibitor eg. miglitol or acarbose.
In another embodiment the present compounds are administered in combination with an agent acting on the ATP-dependent potassium channel of the β-cells eg. tolbutamide, , glibenclamide, glipizide, glicazide or repaglinide.
Furthermore, the present compounds may be administered in combination with nateglinide.
In still another embodiment the present compounds are administered in combination with an antihyperlipidemic agent or antilipidemic agent eg. cholestyramine, colestipol, clofi- brate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucol or dextrothyroxine.
In a further embodiment the present compounds are administered in combination with more than one of the above-mentioned compounds eg. in combination with a sulphonylurea and metformin, a sulphonylurea and acarbose, repaglinide and metformin, insulin and a sulphonylurea, insulin and metformin, insulin, insulin and lovastatin, etc. Furthermore, the present compounds may be administered in combination with one or more antihypertensive agents. Examples of antihypertensive agents are β-blockers such as alprenolol, atenolol, timolol, pindolol, propranolol and metoprolol, ACE (angiotensin converting enzyme) inhibitors such as benazepril, captopril, alatriopril, enalapril, fosinopril, lisi- nopril, quinapril and ramipril, calcium channel blockers such as nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem and verapamil, and α-blockers such as doxazosin, urapidil, prazosin and terazosin. Further reference can be made to Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995.
It should be understood that any suitable combination of the compounds according to the invention with one or more of the above-mentioned compounds and optionally one or more further pharmacologically active substances are considered to be within the scope of the present invention.
The present invention also relates to processes according to reaction schemes Pi and P2 for the preparation of the above said novel compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts or pharmaceutically acceptable solvates.
The compounds of the invention may be administered alone or in combination with pharmaceutically acceptable carriers or excipients, in either single or multiple doses. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995. The compositions may appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications.
The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) route, the oral route being preferred. It will be appreciated that the preferred route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen. Pharmaceutical compositions for oral administration include solid dosage forms such as capsules, tablets, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings or they can be formulated so as to provide controlled release of the active ingredient such as sustained or prolonged release according to methods well-known in the art. Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syrups and elixirs.
Pharmaceutical compositions for parenteral administration include sterile aqueous and non-aqueous injectable solutions, dispersions, suspensions or emulsions as well as sterile powders to be reconstituted in sterile injectable solutions or dispersions prior to use. De- pot injectable formulations are also contemplated as being within the scope of the present invention.
Other suitable administration forms include suppositories, sprays, ointments, cremes, gels, inhalants, dermal patches, implants etc. The therapeutic dose of the compound will depend upon the frequency and mode of administration, the sex, age, weight and general condition of the subject treated, the nature and severity of the condition treated and any concomitant diseases to be treated and other factors evident to those skilled in the art. The formulations may conveniently be presented in unit dosage form by methods known to those skilled in the art. In one embodiment the com- position in unit dosage form, comprises from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg of the compound of formula I pharmaceutically acceptable salt thereof.
In a still further embodiment the pharmaceutical composition is for oral, nasal, transdermal, pulmonal, or parenteral administration. For parenteral routes, such as intravenous, intrathecal, intramuscular and similar administration, typically doses are in the order of about half the dose employed for oral administration.
The compounds of this invention are generally utilized as the free substance or as a pharmaceutically acceptable salt thereof. One example is an acid addition salt of a com- pound having the utility of a free base. When a compound of the invention contains a free base such salts are prepared in a conventional manner by treating a solution or suspension of a free base of the compound with a chemical equivalent of a pharmaceutically acceptable acid, for example, inorganic and organic acids. Representative examples are mentioned above. Physiologically acceptable salts of a compound with a hydroxy group include the an- ion of said compound in combination with a suitable cation such as sodium or ammonium ion.
For parenteral administration, solutions of the present compounds in sterile aqueous solution, aqueous propylene glycol or sesame or peanut oil may be employed. Such aqueous solutions should be suitable buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. The aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous media employed are all readily available by standard techniques known to those skilled in the art.
Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solution and various organic solvents. Examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid es- ters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents. The pharmaceutical compositions formed by combining the compounds of the invention and the pharmaceutically acceptable carriers are then readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy.
Formulations of the present invention suitable for oral administration may be pre- sented as discrete units such as capsules or tablets, each containing a predetermined amount of the active ingredient, and which may include a suitable excipient. These formulations may be in the form of powder or granules, as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion.
If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution. A typical tablet which may be prepared by conventional tabletting techniques may contain:
Core:
Active compound (as free compound or salt thereof) 5 mg
Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, microcryst. (Avicel) 70 mg
Modified cellulose gum (Ac-Di-SoI) 7.5 mg
Magnesium stearate q.s.
Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx. 0.9 mg
*Acylated monoglyceride used as plasticizer for film coating.
The compounds of the invention may be administered to a patient which is a mammal, especially a human in need thereof. Such mammals include also animals, both domestic animals, e.g. household pets, and non-domestic animals such as wildlife.
In a further aspect of the invention the present compounds may be administered in combination with further pharmacologically active substances e.g. an antidiabetic or other pharmacologically active material, including other compounds for the treatment and/or prevention of insulin resistance and diseases, wherein insulin resistance is the pathophysiological mechanism.
Furthermore, the compounds according to the invention may be administered in combination with antiobesity agents or appetite regulating agents.
EXAMPLES
The intermediate 4-(4-trifluoromethyl-benzyl)-phenol was prepared as described in PCT/DK02/00852.
Example 1
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trif luoromethyl-benzyl)-phenyl ester
a) 4-[4-(Trifluoromethyl)benzyl]phenyl chloroformate
Ethyidiisopropylamine (0.7 ml_, 4.02 mmol) was added to a solution of 4-(4- trifluoromethyl-benzyl)-phenol (1.0 g, 4.0 mmol) in 20% phosgene in toluene (3 ml, 5.5 mmol) with stirring at 0 0C. The mixture was stirred in the melting ice bath for 3h and evaporated to dryness. The residue was triturated with three portions of diethyl ether and the combined or- ganic phase was evaporated to dryness to give 1.12 g (89%) of crude chloroformate, which was used in the following step without further purification. 1H NMR (400 MHz, CDCI3): δ 4.04 (s, 2 H), 7.15 (d, 2 H), 7.21 (d, 2 H), 7.28 (d, 2 H), 7.56 (d, 2 H).
b) 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)- phenyl ester
Ethyidiisopropylamine (0.21 ml_, 1.21 mmol) was added to a solution of 4-[4- (trifluoromethyl)benzyl]phenyl chloroformate (314 mg, 1.0 mmol) in dichloromethane (3 mL) followed by 1-(2-pyridin-2-yl-ethyl)-piperazine (192 mg, 1.0 mmol) and the mixture was stirred under nitrogen at 100 0C in a sealed flask over night. The mixture was evaporated to dryness and the residue was purified by flash column chromatography (SiO2, ethyl ace- tate/methanol (4:1)) to give 165 mg (35%) of the pure product as white crystals. 1H NMR (400 MHz, CDCI3): δ 2.58 (m, 4 H), 2.83 (m, 2 H), 3.01 (m, 2 H), 3.59 (br s, 2 H), 3.68 (br s, 2 H), 4.02 (s, 2 H), 7.04 (d, 2 H), 7.13 (t, 1 H), 7.15 (d, 2 H), 7.20 (d, 1 H), 7.28 (d, 2 H), 7.53 (d, 2 H), 7.61 (m, 1 H), 8.54 (d, 1 H); HPLC-MS: m/z = 470 (M+1)+, Rt = 3.32 min. Example 2
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
Ethyldiisopropylamine (0.21 mL, 1.21 mmol) was added to a solution of 4-[4-
(trifluoromethyl)benzyl]phenyl chloroformate (314 mg, 1.0 mmol) in dichloromethane (3 mL) followed by 1-pyridin-2-ylmethyl-piperazine (177 mg, 1.0 mmol) and the mixture was stirred under nitrogen at 100 0C in a sealed flask over night. The mixture was evaporated to dryness and the residue was purified by flash column chromatography (Siθ2, ethyl acetate/methanol (4:1)) to give 125 mg (27%) of the pure product. 1H NMR (400 MHz, CDCI3): δ 2.56 (m, 4 H), 3.61 (s, 2 H), 3.70 (s, 2 H), 3.71 (s, 2 H), 4.01 (s, 2 H), 7.04 (d, 2 H), 7.14 (d, 2 H), 7.20 (m, 1 H), 7.28 (d, 2 H), 7.42 (d, 1 H), 7.53 (d, 2 H), 7.68 (m, 1 H), 8.59 (d, 1 H); HPLC-MS: m/z = 456 (M+1)+, Rt = 3.58 min.
Example 3
4-(2-Pyridin-2-yI-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
Phosgene (5 mL, 20% in toluene) was added to a stirred suspension of 6'-hydroxy- 4,4-dimethyl-4,5-dihydro-3H-[1 ,3']bipyridinyl-2,6-dione (0.47 g, 2.00 mmol, ref;
PCT/DK02/00852) and triethylamine (0.29 mL, 2.00 mmol) in dichloromethane (10 mL). After stirring for 0.5 hours at room temperature, the solvent and excess phosgene were evaporated under reduced pressure. Dichloromethane (10 mL) was added to the residue, followed by 1 ,4-diazabicyclo[2.2.2]octane (224 mg, 2.00 mmol) and 1-(2-(2-pyridylethyl))piperazine (0.38 g, 2.00 mmol). Stirring was continued for 0.5 hours at room temperature. The product was purified by flash column chromatography (SiO2, acetone), followed by a second chromatography (SiO2, gradient of 0-60% methanol in ethyl acetate) yielding the title compound (0.28 g, 31% yield) as a white solid.
1H NMR (300MHz, CDCI3): δ 1.21 (s, 6H), 2.59 (m, 4H), 2.69 (s, 4H), 2.83 (m, 2H), 3.00 (m, 2H), 3.60 (m, 2H), 3.71 (m, 2H), 7.12 (dd, 1 H), 7.20 (d, 1 H), 7.24 (d, 1H), 7.50 (dd, 1H), 7.60 (dt, 1 H), 8.10 (d, 1H), 8.53 (d, 1H); HPLC-MS (Method A): m/z = 452 (M+H)+; Rt = 1.72 min. Example 4
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro- 2H-[1 ,3']bipyridinyl-6'-yl ester
Phosgene (5 mL, 20% in toluene) was added to a stirred suspension of β'-hydroxy-
4,4-dimethyl-4,5-dihydro-3H-[1 ,3']bipyridinyi-2,6-dione (0.47 g, 2.00 mmol, ref; PCT/DK02/00852) and triethylamine (0.29 mL, 2.00 mmol) in dichloromethane (10 mL). After stirring for 0.5 hours at room temperature, the solvent and excess phosgene were evaporated under reduced pressure. Dichloromethane (10 mL) was added to the residue, followed by 1 ,4-diazabicyclo[2.2.2]octane (224 mg, 2.00 mmol) and 1-[(2-pyridyl)methyl]piperazine (0.35 g, 2.00 mmol). Stirring was continued for 0.5 hours at room temperature. The product was purified by flash column chromatography (SiO2, gradient of 0-50% methanol in ethyl acetate) yielding the title compound (318 mg, 36% yield) as an off-white solid. 1H NMR (300MHz, CDCI3): £1.21 (s, 6H), 2.48 (t, 4H), 2.69 (s, 4H), 3.64 (m, 2H), 3.71 (s + m, 4H), 7.18 (m, 1 H), 7.23 (d, 1 H), 7.41 (d, 1 H), 7.50 (dd, 1H), 7.69 (dt, 1 H), 8.10 (d, 1H), 8.59 (m, 1 H); HPLC-MS (Method A): m/z = 438 (M+H)+; Rt = 2.06 min.
Example 5
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
Phosgene (5 mL, 20% in toluene) was added to a stirred suspension of Λ/-(6- hydroxy-pyridin-3-yl)-benzamide (0.43 g, 2.00 mmol, ref; PCT/DK02/00852) and triethylamine (0.29 mL, 2.00 mmol) in dichloromethane (10 mL). After stirring for 0.5 hours at room temperature, the solvent and excess phosgene were evaporated under reduced pressure. Dichloromethane (10 mL) was added to the residue, followed by 1 ,4-diazabicyclo[2.2.2]octane (224 mg, 2.00 mmol) and 1-(2-(2-pyridylethyl))piperazine (0.38 g, 2.00 mmol). Stirring was continued for 0.5 hours at room temperature. The product was purified by flash column chromatography (SiO2, gradient of 0-65% methanol in ethyl acetate) yielding the title compound (143 mg, 17% yield). 1H NMR (300MHz, CDCI3): £2.45 (br.s, 1H), 2.58 (m, 4H), 2.85 (m, 2H), 3.00 (m, 2H), 3.56 (m, 2H), 3.70 (m, 2H), 6.96 (d, 1 H), 7.14 (m, 1H), 7.21 (d, 1H)1 7.43 (m, 1H), 7.53 (m, 1H), 7.62 (m, 1 H), 7.90 (d, 2H), 8.09 (dd,1 H), 8.38 (d, 1 H), 8.52 (m, 1H), 8.83 (s, 1 H); HPLC-MS (Method A): m/z = 432 (M+H)+; Rt = 1.83 min. Example 6
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 5-benzoylamino-pyridin-2-yI ester
Phosgene (5 ml_, 20% in toluene) was added to a stirred suspension of Λ/-(6- hydroxy-pyridin-3-yl)-benzamide (0.43 g, 2.00 mmol, ref; PCT/DK02/00852) and triethylamine (0.29 ml_, 2.00 mmol) in dichloromethane (10 ml_). After stirring for 0.5 hours at room temperature, the solvent and excess phosgene were evaporated under reduced pressure. Dichloromethane (10 mL) was added to the residue, followed by 1 ,4-diazabicyclo[2.2.2]octane (224 mg, 2.00 mmol) and 1-[(2-pyridyl)methyl]piperazine (0.35 g, 2.00 mmol). Stirring was continued for 0.5 hours at room temperature. The product was purified by flash column chromatography (SiO2, gradient of 0-45% ethyl acetate in tetrahydrofuran) yielding the title compound (278 mg, 33% yield) as a white solid.
1H NMR (300MHz, CDCI3): J2.56 (m, 4H), 3.58 (m, 2H), 3.71 (s, 2H + m, 2H), 6.94 (d, 1H), 7.20 (m, 1H), 7.42 (m, 3H), 7.52 (m, 1H), 7.70 (dt, 1 H), 7.91 (d, 2H), 8.09 (dd, 1 H), 8.39 (d, 1 H), 8.60 (m, 1 H), 8.96 (s, 1 H); HPLC-MS (Method A): m/z = 418 (M+H)+; Rt = 2.04 min.
Example 7
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester Tyramin (10 mmol), 3,3-dimethylglutaric anhydride (21 mmol) and DCM (10 mL) were stirred at room temperature over night. The mixture was concentrated and added thio- nyl chloride (50 mmol) and pyridine (1mL) and stirred for 16 h. Addition of water and separation of the organic phase followed by evaporation of the organic phase. The residue was dissolved in EtOH (ca 1mL) and added 1N NaOH and stirred at 50 0C for 1 h. pH was adjusted to 8 using 1 N HCI and extracted with DCM. The organic phase was dried and evaporated to dryness to give a crude which was purified by flash chromatography (Quad flash 40, EtOAc- heptane 1:1) to give 11% of 1-[2-(4-hydroxy-phenyl)-ethyl]-4,4-dimethyl-piperidine-2,6-dione as beige crystals.
To a solution of 1-[2-(4-hydroxy-phenyl)-ethyl]-4,4-dimethyl-piperidine-2,6-dione (0.22 mmol) prepared as described above and ethyldiisopropylamine (0.22 mmol) in CH2CI2 (5 mL) at -30 0C was added trichloromethyl chloroformiate (0.29 mmol). The solution was stirred at -30 0C for 10 min and at reflux temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2CI2 (5 mL) and cooled to 0 0C before addition of1-(2-(2- pyridylethyl))-piperazine (0.26 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by preparative HPLC (Gilson) to give the title compound as its TFA salt in 28% yield as colorless crystals.
1H NMR (400MHz; CDCI3): δ 1.05 (s, 6H), 2.48 (s, 4H), 2.79-2.84 (m, 2H), 3.27 (br s, 4H), 3.45 (t, 2H), 3.58 (t, 2H), 3.87-4.04 (m, 6H), 7.02 (d, 2H), 7.18 (d, 2H), 7.41 (dd, 1 H), 7.51 (d, 1 H), 7.89 (dt, 1 H), 8.59 (d, 1 H), 9.24 (br s, 2H); HPLC-MS : m/z = 479.2 (M+1 ); Rt = 1.87 min.
Example 8
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
a) 4-(3-Pyridin-3-yl-propionyl)-piperazine-1 -carboxylic acid tert-butyl ester
3-(3-Pyridyl)-propionic acid (4.07 g, 27 mmol) was added in small portions to a stirred solution of carbonyldiimidazole (4.37 g, 27 mmol) in dry dichloromethane (40 ml) at room temperature. After 10 min. a solution of 1-(tert-butoxycarbonyl)-piperazine (2.51 g, 13.5 mmol) in dry dichloro-methane (20 ml) was added dropwise and the mixture was stirred for 21 h. Water (50 ml) was added and after 2Vk h the non-aqueous phase was separated, washed with saturated aqueous sodium bicarbonate (50 ml) and then with water (50 ml), dried over sodium sulfate and filtered. Evaporation of the solvent gave the title compound as white crystals. Yield 3.90 g (91%); m.p. 125 - 126 0C; IR (KBr) v 1679, 1638 (C=O) cm"1.
b) 1-Piperazin-1-yI-3-pyridin-3-yl-propan-1-one
A stirred mixture of 4-(3-pyridin-3-yl-propionyl)-piperazine-1 -carboxylic acid tert-butyl ester (1.50 g, 4.70 mmol) in ethanol (10 ml) was heated on an oil bath at 100 0C. Concentrated hydrochloric acid (3 ml) was added. After 15 min the solvent was removed in vacuo. Residual water was removed by addition of toluene followed by evaporation. The residue was crystallized from ethanol, filtered and dried to give the dihydrochloride of the title com- pound. Yield 0.95 g (69%); m.p. 219 - 220 0C; LC-MS m/z: 220 (M+H) Rt = 0.26 min.. IR
(KBr) v 1655 (C=O) cm"1. The free base was isolated as a yellow oil, LC-MS m/z: 220 (M+H) Rt = 0.25 min; IR (film on KBr) v 1634 (C=O) crτϊ1.
c) 1 ~(3-Pyridin-3-yl-propyl)-piperazine Reduction of 1-piperazin-1-yl-3-pyridin-3-yl-propan-1-one (0.36 g, 1.64 mmol) in dry THF (5 ml) with excess 1 M lithium aluminium hydride in THF (5 ml) under standard conditions (Husbands et al., J.Med.Chθm. 42 (21 ) 1999, 4446 - 4455; and Matecka et al., J.Med.Chem. 39 (24) 1996, 4704 - 4716) gave the title compound as a yellow oil; yield 0.298 g (88%); LC-MS m/z: 206 (M+H) Rt = 0.3 min. The crude product was used in the next step without purification.
d) 4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester
A solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate (0.24 g, 0.76 mmol) in dry dichlormethane (5 ml) was added at room temperature to a stirred solution of 1- (3-pyridin-3-yl-propyI)-piperazine (0.16 g, 0.78 mmol) in the same solvent (5 ml). The solvent was removed in vacuo after 2 h and the residue was suspended in a mixture of ether (10 ml), a 1.5 M solution of HCI in ether (1 ml) and ethanol (10 ml). Then the solvent was removed in vacuo and the residue triturated with ether (3 x 10 ml) and dried to give the hydrochloride of the title compound as an amorphous yellow solid; yield 0.28 g (68%). The crude product was purified by dissolution in ethanol, treatment with charcoal, filtration, evaporation, trituration of the residue with acetone and drying . Yield 0.16 g (38%), amorphous yellow solid, m.p. 203 - 208 °C; IR (KBr) v 2682, 2598, 2461 (N+-H), 1714 (C=O) cm"1; LC-MS m/z: 487 (M+H) R1 = 2.3 min. 1H NMR (DMSO) 11.77 (br, 1H), 8.94-8.89 (~s, 1 H), 8.83-8.78 (~d, 1H), 8.60-8.56 (~s, 1H), 8.53-8.48 (~d, 1H), 8.28-8.23 (~dd, 1H), 8.03-7.97 (~dd, 1H), 7.30-7.22 (m, 5H)1 4.38-4.0 (br m, 2H), 4.0-3.3 (br, 4H + water, 3.3-3.0 (br, 4H), 3.0-2.84 (~t, 2H), 2.25-2.10 (m, 2H); 13C NMR (DMSO) δ (ref. DMSO at 39.50 ppm): 165.51, 152.68, 150.02, 147.98, 145.21 (J = 4.4 Hz), 145.08, 141.90, 140.30, 140.15, 137.66 ( J = 2.9 Hz), 126.64, 123.88 ( J = 271.5 Hz), 123.10, 122.47, 120.41 (J = 32.9), 111.83, 54.56, 50.19, 41.0 og 41.9 (br, overlapping DMSO), 28.69, 23.65 ppm.
Example 9 4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
a) 4-(2-Pyridin-3-yl-acetyl)-piperazine-1-carboxylic acid tert-butyl ester The title compound was prepared from 1-(tert-butoxycarbonyl)-piperazine (2.04 g, 11 mmol) carbonyldiimidazole (3.55 g, 22 mmol) and 3-pyridyl-acetic acid (3.00 g, 22 mmol) under standard conditions as described in Example 8 a) above; yield 2.86 g (86%) pale crys- tals; m.p. 113 - 114 0C; LC-MS m/z: 306 (M+H), 250 (M+H-56), R1 = 1.7 min; IR v 1686, 1632 cm "1.
b) 1 -Piperazin-1 -yI-2-pyridin-3-yl-ethanone
A solution of 4-(2-pyridin-3-yl-acetyl)-piperazine-1 -carboxylic acid tert-butyl ester
(1.76 g, 5.76 mmol) in ethanol (10 ml) was cooled on an ice bath at room temperature 5 0C. Concentrated hydrochloric acid (3 ml) was added dropwise, keeping the temperature below 15 °C and then the mixture was allowed to stand at room temperature for 40 h. The solvent was evaporated, the residue treated with toluene and the mixture evaporated again. The sticky residue crystallized by stirring with ethanol (12 ml). The precipitate was filtered off and dried to give the dihydrochloride of the title compound; yield 1.45 g (91%) cream coloured crystals; m.p. 179 - 181 0C; LC-MS m/z: 206 (M+H), Rt = 0.5 min; IR (KBr) n 1654 cm"1. The free base was isolated as a pale solid, m.p. 85 - 87 0C; IR (KBr) n 1634 cm"1.
c) 1-(2-Pyridin-3-yl-ethyl)-piperazine
Reduction of 1 -piperazin-1 -yl-2-pyridin-3-yI-ethanone (0.27 g, 1.32 mmol) in dry THF (6 ml) with excess 1 M lithium aluminium hydride in THF (4 ml) under standard conditions (Husbands et al., J.Med.Chem. 42 (21) 1999, 4446 - 4455; and Matecka et al., J.Med.Chem. 39 (24) 1996, 4704 - 4716) gave after work-up a mixture of starting material and the title compound. By repeating the reduction procedure, the title compound was obtained as a yellow oil, 0.18 g (72%); LC-MS m/z: 192 (M+H) R1 = 0.23 min. The crude product was used in the next step without purification.
d) 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
A solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate (0.28 g, 0.89 mmol) in dry dichlormethane (5 ml) was added to a stirred solution of 1-(2-pyridin-3-yl-ethyl)- piperazine (0.17 g, 0.89 mmol) in the same solvent (5 ml) on an ice bath at 0 0C. After com- pletion of the addition, the ice bath was removed. After 3 h the solvent was removed in vacuo and the residue was triturated with ether (3 x 10 ml) and dried, giving an almost pure crude product as a light yellow powder. Yield 0.27 g (60%), m.p. 173 - 179 0C; IR (KBr) v 1714 (C=O) cm"1; LC-MS m/z: 473 (M+H) Rt = 2.3 min. Recrystallization from ethanol gave a sample with m.p. 206 - 208 0C.
Example 10
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester a) 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid tert-butyl ester
Acetic acid (1.5 ml) was added to a stirred solution of crude 3-pyridin-2-yl- propionaldehyde (1.16 g; < 8.58 mmol) (prepared from 2-methyl-pyridine and 2-bromo-1 ,1- diethoxy-ethane according to S.A. Fleming, V.D. Bachelder, D. Vance, J.Heterocycl.Chem. 28 (8); 1991; 2061 - 2063) and 1-(tert-butoxycarbonyl)-piperazine (1.92 g, 10.3 mmol) in methanol (20 ml). After stirring at room temperature for 40 min. sodium cyanoborohydride (1.08 g, 17.2 mmol) was added in small portions, allowing the temperature to rise to 30 - 40 °C. The resulting yellow solution was left at ambient temperature for 2Y≥ days. Approx. 2/3 of the solvent was evaporated. Saturated aqueous sodium bicarbonate (25 ml) was added to the residue and the mixture was extracted with ethyl acetate (2 x 25 + 2 x 10 ml). The com- bined extracts were dried and the solvent was evaporated off to give 3.2 g of an amber oil. Purification by flash chromatography (silica gel, dichloromethane/methanol 92.5 : 7.5) of 1.8 g of the crude product yielded the title compound, 0.93 g; LC-MS m/z: 306 (M+H), Rt = 1.1 min.
b) 1-(3-Pyridin-2-yl-propyl)-piperazine
Concentrated hydrochloric acid (1 ml) was added to a stirred solution of 4-(3-pyridin- 2-yl-propyl)-piperazine-1 -carboxylic acid tert-butyl ester (0.9 g) in ethanol (3 ml) at ambient temperature. After standing overnight the solvent was evaporated off providing the dihydro- chloride of the title compound as a white amorphous solid. Yield 0.79 g (96%); LC-MS m/z: 206 (M+H) Rt= 0.4 min.
The product was dissolved in ethanol (20 ml) and a solution of sodium hydroxide (0.27 g) in ethanol (10 ml) was added. The solvent was evaporated off and the residue was extracted with ether (30 + 3 x 10 ml). The combined extracts were filtered through decalite and the solvent was removed giving the title compound as a pale oil. Yield 0.37 g (62%). LC- MS m/z: 206 (M+H), R, = 0.5 min.; 1H NMR (DMSO) δ 8.54-8.50 (m, 1 H), 7.61-7.55 (m, 1H), 7.18-7.13 (m, 1 H), 7.13-7.06 (m, 1 H), 2.92-2.84 (br m, 4H), 2.84-2.77 (m, 2H), 2.5-2.3 (br m, 6H), 1.99-1.89 (quint, 2H), 1.8 (br, 1 H) + minor impurities; 13C NMR (DMSO) δ (ref. CDCI3 at 77.00 ppm) 161.85, 149.14, 136.15, 122.67, 120.88, 58.56, 54.51, 46.06, 36.16, 26.69 ppm.
c) 4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxyIic acid 4-(5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester
A solution of 1-(3-pyridin-2-yl-propyl)-piperazine (0.213 g, 1.04 mmol) in tert- butylmethylether (4 ml) was dried over 4 A molecular sieves for several hours and then added during 2 min to a stirred solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloro- formate (0.33 g, 1.04 mmol) in the same solvent (4 ml) cooled on an ice bath at 0 0C. A white precipitate formed immediately. The ice bath was removed after completion of the addition. After stirring for 134 h the precipitate was filtered off, rinsed on the filter with small portions of -butylmethylether, then with acetone, and dried to give the title compound as a white solid. Yield 0.37 g (68%), m.p. 204 - 205 0C; IR (KBr) v 1714 (C=O) cm"1; LC-MS m/z: 487 (M+H) Rt = 2.3 min.; 1H NMR (DMSO) δ 8.60-8.56 (~s, 1 H), 8.56-8.52 (~d, 1 H), 8.28-8.22 (~dd, 1H), 7.83-7.76 (~ddd, 1H), 7.40-7.35 (m, 6H), 4.06-3.6 (br d, 4H), 3.66-3.20 (br, 4H + water), 3.20-3.09 (m, 2H), 2.90-2.81 (~t, 2H), 2.25-2.13 (quint, 2H).
PHARMACOLOGICAL METHODS
Compounds of formula I may be evaluated in vitro for their efficacy and potency to inhibit HSL, and such evaluation may be performed as described below.
ASSAYS
Hormone-sensitive lipase (HSL)
Materials. The Hormone-sensitive lipase was provided by Dr. Cecilia Holm, from Lund University Sweden or produced and purified by Novo Nordisk (NN) using the reagents and protocols used by Dr. Holm. The substrates used are: 3H-labeled triolein (TO) from Am- ersham, Buckinghamshire, U.K. cat No. TRA191; 5-20 Ci/mmol dissolved in toluene, triolein (Sigma, Cat. No. T-1740), fluorochrome-labeled triacylglyceride (c/s-octadec-9-enoic acid 2- [12-(7-nitrobenzo[1 ,2,5]oxadiazol-4-ylamino)dodecanoyloxy]-1 -c/s-octadec-9- enoyloxymethyl-ethyl ester) prepared by Novo Nordisk (NN) by conventional methods, and 1 ,3-(di[3H]-stearin), 2-(PEG-Biotin)glycerol prepared in collaboration with Amersham Pharmacia Biotech, UK and described in WO 01/073442. Phosphatidyl choline (PC) and phosphatidyl inositol (Pl) are from Sigma (St Luis MO cat. Nos. P-3556 and P-5954 respectively). All other reagents are of commercial grade and obtained from various commercial sources.
Methods.
3190.1: Assay for determination of percent inhibition of hormone sensitive lipase by compound at 10μM sample concentration. A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as substrate with a standard concentration of highly purified HSL (12μg/mL initial concentration corresponding to 600ng/mL final concentration). BSA is added as product acceptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluorescent properties of the fluorochrome. The changes can be monitored on a fluorimeter with an excitation wavelength of 450nm and an emission wavelength of 545nm.
Compound and HSL (20μL compound, 10μL enzyme and 70μL PED-BSA buffer) is pre-incubated for 30min at 250C before addition of substrate (100μL). Amount of formed product is measured after 120min incubation at 370C.
Results are given as percent activity relative to a non-inhibited sample (no com- pound).
3190.2: Assay for determination of IC50 value for the inhibition of hormone sensitive lipase by compound. Standard concentrations of compound are 100//M and 5-fold dilutions (initial con- centration corresponding to 10//M final concentration and 5-fold).
A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as substrate with a standard concentration of highly purified HSL (12μg/mL initial concentration corresponding to 600ng/mL final concentration). BSA is added as product acceptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluo- rescent properties of the fluorochrome. The changes can be monitored on a fluorimeter with an excitation wavelength of 450nm and an emission wavelength of 545nm.
Compound and HSL (20μL compound, 10μL enzyme and 70μL PED-BSA buffer) is pre-incubated for 30min at 250C before addition of substrate (100μL). Amount of formed product is measured after 120min incubation at 370C.
Results are given as IC50 values after 4PL fit of obtained activity data.
RESULTS
With these methods the compounds of the examples are found to be inhibitors of
HSL : Table 1. Inhibition of HSL by compounds of the examples according to above assay 3190.1 (% activity relative to non-inhibited sample).
Figure imgf000094_0001

Claims

1. A compound of the general formula (I) :
Figure imgf000095_0001
wherein
R1 and R2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C1-6-alkyl, Ci-6-alkoxy, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocycIyl and C3--I0- cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryi, Cs-s-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryi, C3-8- heterocyclyl, and C3-10-cycloalkyl;
X is N or CR3, Y is N or CR4, Z is N or CR5; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, d-6-alkyI, C2-6-alkenyl, aryl, heteroaryi, C^s-heterocyclyl and C3.10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-aIkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C^o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocyclyl and C3-i0-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, Chalky!, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, C3-8-heterocycIyl and C3-10- cycloalkyl, wherein each of C2-6-alkyl, C2-6-aIkenyI, aryl, heteroaryi, C3-8-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocycIyl and C3-10-cycloaikyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
and with the proviso that said compound is not 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester, 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-Pyridin-3-ylmethyl~piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- phenyl ester,
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl es- ter,
4-(2-Pyridin-4-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Thienylethyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester, 4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)- phenyl ester,
4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester,
4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4-chloro-phenyl)- ethylcarbamoyl]-phenyl ester
4-(5-Chloro-thiophen-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(4-Chlorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3,4-Methylenedioxy-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-pyrazoM-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3,4,5-tribromo-pyrazoI-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-chloro-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-iodo-pyrazol-1 -yl ester,
4-Benzyl-piperazine-1 -carboxylic acid 3-(4-methoxy-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(4-nitro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-(2-fluoro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-pyridin-2-yl-pyrazol-1 -yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-phenylsulfanyl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-thiophen-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-chloro-imidazol-1 -yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-bromo-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-iodo-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-methyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-(4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-(4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-thiophen-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2-pyridin-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 2,5-dichloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-2,5-dichloro-imidazol-1 -yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-bromo-2-chloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-(4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-(4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-thiophen-2-yl-imidazol-1-yI ester, 4-Benzyl-piperazine-1 -carboxylic acid 5-pyridin-2-yl-imidazoi-1 -yl ester,
4-Benzyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester,
4-(4-tert-Butylbenzyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester,
4-(4-Fluorobenzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(4-Chlorobenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester,
4-(4-Methylbenzyl)piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester,4-
(4-Methoxybenzyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Chloro-6-fluoro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Benzyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)phenyl ester,
4-Benzyl-piperazine-1 -carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-(4-Fluoro-benzyl)-piperazine-1-carboxyIic acid 4-iodo-pyrazoI-1-yl ester, 4-Naphthalen-1 -ylmethyl-piperazine-1 -carboxylic acid 4-(5-trif luoromethyl-pyridin-2-yloxy)- phenyl ester
4-(3,4-Dichloro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-(3-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(3-Fluoro-benzyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Fluorobenzyl)-piperazine-1 -carboxylic acid 4-(4,6-dimethyl-pyrimidin-2-ylsulfanyl)- phenyl ester, 4-(4-Methoxy-benzyI)-piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- phenyl ester,
4-(4-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester,
4-(4-Methoxy-benzyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyI-butylcarbamoyl)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Phenethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(3-Phenylpropyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl ester, 4-(4-Phenylbutyl)piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(4-Phenylbutyl)piperazine-1 -carboxylic acid 4-chlorophenyl ester, 4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,4-Cyclohexylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl- phenoxy)-phenyl ester,
4-Cyclohexylmethyl-piperazine-1 -carboxylic acid 4-(3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester, 4-(2-Cyclohexyl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)- phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-chIoro-phenyl)-ethylcarbamoyl]- phenyl ester,
4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- phenyl ester, 4-Cyclopropylmethyl-piperazine-1 -carboxylic acid 4-(2-cyclohexyl-acetylamino)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyI)-phenyl ester,
4-(2-Hydroxyethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(Pyrrolidinocarbonylmethyl)- piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-(lsopropylaminocarbonylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Ethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Propyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Butyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Hydroxypropyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-(2-Hydroxyethoxy)ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-[2-(2-Hydroxyethoxy)ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
4-Octylpiperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)phenyl ester, 4-(3-Dimethylamino-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-[2-(2-Hydroxyethoxy)ethyl]piperazine-1 -carboxylic acid 4-(4-trifluoromethylphenoxy)phenyl ester, or
4-(1 -Methyl-piperidin-4-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
2. A compound according to claim 1 , wherein R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and Ca.io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycioalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and Cs^o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
3. A compound according to any one of claims 1-2, wherein R6 is selected from aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, Ci-6-alkyl, perhalomethyl and perhalomethoxy;
4. A compound according to any one of claims 1-3, wherein R6 is an aryl which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, per- halomethyl and perhalomethoxy;
5. A compound according to claim 4, wherein R6 is a phenyl which is optionally substituted.
6. A compound according to claim 4, wherein R6 is a pyridyl which is optionally substituted.
7. A compound of the general formula (I) :
Figure imgf000100_0001
wherein
R1 and R2 are independently selected from hydrogen, hydroxy, sulfanyl, amino, halogen, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyI and C3-10- cycloalkyl, wherein each of hydroxy, suifanyl, sulfo, Ci-6-alkyI, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C^-heterocyclyl and C3-i0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, perhalomethyl, perhalomethoxy, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl;
X is N or CR3, Y is N or CR4, Z is N or CR5; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo,
Figure imgf000101_0001
and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_3-heterocyclyI and CMo-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycIoalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^s-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
O. Cf -?X> and with the proviso that said compound is not 4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl~piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
8. A compound of the general formula (I) :
Figure imgf000102_0001
wherein R1 and R2 are hydrogen
X is N or CR , Y is N or CR4, Z is N or CR&; provided that X, Y and Z are not all CH;
R3, R4 and R5 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyI, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyI, wherein each of hydroxy, sulfanyl, amino, sulfo, C^-alky!, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C^o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6- alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
Figure imgf000102_0002
and with the proviso that said compound is not
4-Benzyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4~(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyI-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or ehantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
9. A compound of the general formula (I) :
Figure imgf000103_0001
wherein
R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is N or CH;
R3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs^-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3^-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Ci-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-β- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C^-alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
O . Cf - p and with the proviso that said compound is not
4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyI-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
10. A compound of the general formula (I) :
Figure imgf000104_0001
wherein
R1 and R2 are hydrogen
X is CR3, Y and Z is C-H;
R3 are independently selected from hydrogen, hydroxy, sulfanyl, fluor, amino, sulfo, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocycIyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-aikyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl and C^o-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloaIkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyI, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy; A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
O . O - p and with the proviso that said compound is not
4-Benzyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trif luoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
11. A compound of the general formula (I) :
Figure imgf000105_0001
wherein R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is CH;
R3 are independently selected from hydroxy, amino, C^-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3--ιo-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C^a-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Ca^-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, C1-6-alkyl, perhalomethyl and perhalomethoxy;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
Figure imgf000106_0001
and with the proviso that said compound is not 4-Benzyl-piperazine-i-carboxylic acid 4-(5-trifluoromethyi-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
12. A compound of the general formula (I) :
R2 R1
xf Y-VZ oAv N —> f _A_R6 (l) wherein R1 and R2 are hydrogen
X is CR3, Y is C-H, Z is CH;
R3 are independently selected from hydroxy, amino, C1-6-aikyl, C2-6-aIkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-i0-cycloalkyl, wherein each of hydroxy, amino, d-6-alkyl, C2-6-alkenyl, aryl, heteroaryi, Cs-s-heterocyclyl and Cs^o-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocyclyl and Ca-io-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Ca-β-heterocyclyl and C3-io-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, Ca-s-heterocyclyl and C^o-cycloalkyl;
A is selected from CH2 and CH2CH2;
R6 is selected from the list consisting of:
CJ . Or - X T r and with the proviso that said compound is not
4-Benzyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yIoxy)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, or carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,
as well as any diastereomer or enantiomer or tautomeric form thereof including mixtures of these or pharmaceutically acceptable salts thereof.
13. A compound according to any one of claims 1-12, wherein A is CH2CH2.
14. A compound according to any one of claims 1-12, wherein A is CH2.
15. A compound according to any one of claims 1-14, wherein R1 is hydrogen.
16. A compound according to any one of claims 1-14, wherein R2 is hydrogen.
17. A compound according to any one of claims 1-16, wherein R1 is hydrogen and R2 is hydrogen.
18. A compound according to any one of claims 1-15, wherein F ic2 is selected from the group consisting of
Figure imgf000108_0001
19. A compound according to any one of claims 1-15, wherein R2 is selected from the group consisting of
Figure imgf000108_0002
20. A compound according to any one of claims 1-15, wherein R2 is selected from the group consisting of
Figure imgf000108_0003
21. A compound according to any one of claims 1-15, wherein R2 is selected from the group consisting of
Figure imgf000108_0004
22. A compound according to any one of claims 1-21, wherein X is N.
23. A compound according to any one of claims 1-21, wherein X is CH.
24. A compound according to any one of claims 1-21, wherein X is C-R3.
25. A compound according to any one of claims 1-24, wherein R3 is selected from the group consisting of
Figure imgf000109_0001
26. A compound according to any one of claims 1-24, wherein R3 is selected from the group consisting of
Figure imgf000109_0002
27. A compound according to any one of claims 1-24, wherein R3 is selected from the group consisting of
Figure imgf000109_0003
28. A compound according to any one of claims 1-24, wherein R3 is selected from the group consisting of
Figure imgf000110_0001
29. A compound according to any one of claims 1-28, wherein Z is N.
30. A compound according to any one of claims 1-28, wherein Z is C-R5.
31. A compound according to any one of claims 1-28, wherein Z is CH.
32. A compound according to any one of claims 1-31 , wherein Y is N.
33. A compound according to any one of claims 1-31 , wherein Y is CH.
34. A compound according to any one of claims 1-31 , wherein Y is C-R4.
35. A compound according to any one of claims 1-34, wherein only one of X, Y and Z is N.
36. A compound according to any one of claims 1-21 , 23-28, 30-31 , or 33-35, wherein X is C- R3, Y is C-R4 and Z is C-R5.
37. A compound according to any one of claims 1-26, wherein Y and Z are both CH.
38. A compound according to claim 37, wherein X is C-R3.
39. A compound according to claim 38, wherein R3 is selected from the group consisting of
Figure imgf000111_0001
40. A compound according to claim 38, wherein R3 is selected from the group consisting of
Figure imgf000111_0002
41. A compound according to claim 38, wherein R3 is selected from the group consisting of
Figure imgf000111_0003
42. A compound according to claim 38, wherein R3 is selected from the group consisting of
Figure imgf000111_0004
43. A compound according to any one of claims 1-42, having one free -COOH group.
44. A compound according to any one of claims 1-43, having one free amino group, or one monosubstituted amino group or one disubstituted amino group.
45. A compound according to any one of claims 1-44, having one substituted or unsubsti- tuted pyridine ring.
46. A compound according to any one of claims 1-45, having one substituted or unsubsti- tuted imidazole ring.
47. A compound according to any one of claims 1-46, wherein the molar weight of said compound is less than 650 g/mole.
48. A compound according to any one of claims 1-47, wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 5.0.
49. A compound according to any one of claims 1-48, wherein the compound contains no ionisable group and wherein cLog P is in the range from 1.0 to 4.0.
50. A compound according to any one of claims 1-49, wherein the ACD LogD is in the range from 0.8 to 3.0.
51. A compound according to any one of claims 1-50, wherein the number of H-bond donors is O, 1, 2 or 3.
52. A compound according to any one of claims 1-51 , wherein the number of H-bond donors is O, 1, or 2 .
53. A compound according to any one of claims 1-52, wherein the number of H-bond donors is 0 or 1.
54. A compound according to any one of claims 1-53, wherein the number of H-bond accep- tors is in the range from 4 to 9.
55. A compound according to any one of claims 1-54, wherein the number of H-bond acceptors is in the range from 5 to 8.
56. A compound according to any one of claims 1-55, wherein the number of rotatable bonds of said compound is in the range from 6 to 15.
57. A compound according to any one of claims 1-56, wherein the number of rotatable bonds of said compound is in the range from 7 to 12.
58. A compound according to any one of claims 1-57, wherein the polar surface area (PSA) is in the range from 40 A2 to120 A2.
59. A compound according to any one of claims 1-58, wherein the polar surface area (PSA) is in the range from 40 A2 to80 A2.
60. A compound according to claim 1 , where the compound is selected from the group consisting of 4-(2-Pyridin-2-yI-ethyl)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester,
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester,
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3'] bipy rid i nyl-6'-yI ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro- 2H-[1 ,3']bipyridinyl-6'-yl ester,
4-(2-Pyridin-2-yl-ethyI)-piperazine-1 -carboxylic acid 5-benzoyIamino-pyridin-2-yl ester,
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester, 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester,
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester,
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, and 4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester.
61. A compound according to claim 1 , where the compound is selected from the group con- sisting of
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyridinyl-6'-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrariydro-2l-l-
[1 ,3*]bipyridinyl-6'-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester 4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyI-pyridin-2- yloxy)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester 4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyi]-piperazine-1 -carboxylic acid 4-(5-chloro-pyridin-2-yloxy)- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-chloro-pyridin-2-yloxy)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester 4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl- butylcarbamoyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 -Methyl- 1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2- ylmethyl)-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-methyl-pyridin-2-ylmethyl)- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-trifluoromethyl-benzyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H- [1 ,3']bipyridinyl-6'-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H- [1 ,3']bipyridinyl-6'-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2)6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyridinyl-6'-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1 ,3']bipyridinyl-6'-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1 ,3l]bipyridinyl-6'-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyridinyl-6'-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-2H-
[1 ,3']bipyπdinyl-6'-yl ester ;
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6-tetrahydro-
2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(1 -Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-
3,4,5,6-tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4,4-dimethyl-2,6-dioxo-3,4,5,6- tetrahydro-2H-[1 ,3']bipyridinyl-6'-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethy l]-pyrid in -2-yl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-py rid in-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyrid in-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-
1-yl)-ethyl]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-pyrid in-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl )-ethyl]-pyrid in-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1-yl)-ethyl]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1- yl)-ethyl]-pyridin-2-yl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-benzoylamino-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin- 2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-Pyrϊdin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)- pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-
2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2- yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)- pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(3-tert-butyl-thioureido)-pyridin-
2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-t2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-t2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-Pyrazin-2~ylmethyl-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(1-methyl-1H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1-methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 -methyl-1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-benzoylamino-phenyl ester 4-(5-Carboxy-pyridin-2-ylnnethyl)-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-benzoylamino-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-
2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-
2-yl )-py rid i n-2-y I ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)-pyridin- 2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2-yl)- pyridin-2-yl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro- isoindol-2-yl)-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(1 ,3-dioxo-octahydro-isoindol-2- yl)-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid quinolin-7-yl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid quinolin-7-yl ester 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1,1 ,3,3-tetramethyl-butylcarbamoyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl-butylcarbamoyl)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetrametriyl-butylcarbamoyl)- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- butylcarbamoyl)-phenyl ester
, 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 ,1 ,3,3-tetramethyl- buty!carbamoyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl-amino)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(cyclohexanecarbonyl- amino)-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(cyclohexanecarbonyl-amino)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethylj-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)- ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-
1-yl)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 -yl)- ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-t2-(4,4-dimethyl-2,6-dioxo-piperidin-1 - yl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4,4-dimethyl-2,6-dioxo- piperidin-1 -yl)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(6-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(6-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmetrιyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethy!)- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester 4-[2-(1 H-Imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 H-imidazol-2-ylsulfanylmethyl)- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(1 H-imidazol-2- ylsulfanylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-prιenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-yImethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl )-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethylj-phenyl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1- yl)-pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1-yl)- pyridin-3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1- yl)-pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 -yl)- pyridin-3-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1-yl)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1- yl)-pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 - yl)-pyridin-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1 -yl)- pyridin-3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester 4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-trtioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-1- yl)-pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo-imidazolidin-
1-yl)-pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1-yl)-pyridin-3-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-isopropyl-5-oxo-2-thioxo- imidazolidin-1 -yl)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-morpholin-4-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-Pyrazin-2-ylmethy!-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl-benzoylamino)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-morpholin-4-ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
3-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-3-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-3-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoy!amino)-pyridin-3-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 6-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-3-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4~(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl- benzoylamino)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl-benzoylamino)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl- benzoylamino)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl-benzoylamino)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1-ylmethyl- benzoylamino)-phenyl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxyϋc acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-piperidin-1 -ylmethyl- benzoylamino)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Pyridin-3-yI-ethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)-pyridin-
2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl-benzoylamino)- pyridin-2-yl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl-benzoylamino)- pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(1-Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 5-(4-piperidin-1-ylmethyl- benzoylamino)-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-(4-piperidin-1 -ylmethyl- benzoylamino)-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethy l-p iperid in-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester 4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 - ylmethyl)-benzoylannino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-ethyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperaziπe-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(4-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4~(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(3-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylannino]-pyridin-2-yl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1-ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]~piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 -ylmethyl)- benzoylamino]-pyridin-2-yl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 5-[4-(2-methyl-piperidin-1 - ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 5-[4-(2-methyl-piperidin-1- ylmethyl)-benzoylamino]-pyridin-2-yl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester 4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- ylmethyl)-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(4-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-(4-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(1H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester 4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester 4-t3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-t2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2- ylmethyl)-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-(3-methyl-pyridin-2-ylmethyl)- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1-carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1-carboxylic acid 4-[2-(1-methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperaziπe-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2-ylsulfanyl)- ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(1 -methyl-1 H-imidazol-2- ylsulfanyl)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester 4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)- ethylj-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-ylsulfanyl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester 4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyi]-phenyi ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-3-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]- phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yioxy)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester 4-[2-(1-Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]- phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(pyridin-4-yloxy)-ethyl]-phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyhdin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-t2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)- ethylj-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(6-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester . 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester , 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyιϊdin-2-yl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(4-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-(3-Pyridin-3-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)- ethylj-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1-carboxylic acid 4-t2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester 4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester 4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(3-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyridin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyrimidin-4-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-Pyrazin-2-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(6-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(6-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Pyridin-3-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-3-yl-propyl)-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(3-Pyridin-2-yl-propyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-(6-Methyl-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-Pyridin-3-ylmethyl-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(4-Methyl-thiazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-t2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Carboxy-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)- ethyl]-phenyl ester
4-(5-Carboxy-pyridin-2-ylmethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(5-Methyl-pyridin-2-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[3-(5-Methyl-pyridin-2-yl)-propyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-(2-Thiazol-2-yl-ethyl)-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(2-Methyl-thiazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 H-Pyrrol-2-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]-phenyl ester
4-[2-(1 H-lmidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
4-[2-(1 -Methyl-1 H-imidazol-4-yl)-ethyl]-piperazine-1 -carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)- ethyl]-phenyl ester and
4-[2-(3-Methyl-isoxazol-5-yl)-ethyl]-piperazine-1-carboxylic acid 4-[2-(5-methyl-pyridin-2-yl)-ethyl]- phenyl ester
62. A pharmaceutical composition comprising a compound as defined in any one of claims 1-61 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
63. The composition according to claim 62, wherein said composition is in unit dosage form, comprising from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of said compound according to any one of claims 1-61 or pharmaceutically acceptable salt thereof.
64. A pharmaceutical composition for use as a medicament for inhibiting the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters, said composition comprising a compound according to any one of claims 1-61 or a pharmaceutically acceptable salt thereof together with a pharmaceutically accept- able carrier or diluent.
65. A pharmaceutical composition according to any one of claims 62-64, which is for oral administration.
66. A pharmaceutical composition according to any one of claims 62-64 for nasal, transdermal, pulmonal, or parenteral administration.
67. Use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition.
68. Use of a compound according to any one of claims 1-61 for inhibition of hormone sensitive lipase.
69. Use of a compound according to any one of claims 1-61 for preparation of a pharmaceu- tical composition for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters.
70. Use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment or prevention of any disorder where it is desirable to
modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, in- sulin and/or glucose; and/or
modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA's as well as citrate or malonyi-CoA; and/or
increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic β cells; and/or
modulate insulin secretion from pancreatic β cells.
71. The use according to claim 70, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1 , diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, atheroschlerosis, hypertension, abnormalities of lipoprotein metabolism and any combination thereof.
72. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of dyslipidemia.
73. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of hyperlipidemia.
74. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of hyperglycemia.
75. The use of a compound according to any one of claims 1-61 for lowering HbAi0.
76. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of diabetes type 2.
77. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention impaired glucose tolerance.
78. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of metabolic syndrome X.
79. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for the treatment and/or prevention of atheroschlerosis.
80. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for delaying or prevention of the progression from impaired glucose tolerance to diabetes type 2.
81. The use of a compound according to any one of claims 1-61 for the preparation of a pharmaceutical composition for delaying or prevention of the progression from non-insulin requiring diabetes type 2 to insulin requiring diabetes type 2.
82. The use according to any one of claims 67-81 , wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is used.
83. The use according to any one of claims 67-81 , wherein metformin is also used.
84. A method of treating a disorder of a patient where modulation of the activity of hormone- sensitive lipase is desired, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to any one of claims 1-61 or a pharmaceutically acceptable salt thereof.
85. A method of treating a disorder of a patient where lowering of the activity of hormone- sensitive lipase is desired, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to any one of claims 1-61 or a pharmaceutically acceptable salt thereof.
86. The method according to any one of claims 84-85, wherein said administration is carried out by the oral, nasal, transdermal, pulmonal, or parenteral route.
87. The method according to any one of claims 84-86, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1 , diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, atheroschlerosis, hypertension, abnormalities of lipoprotein metabolism and any combination thereof.
88. The method according to any one of claims 84-87, wherein the therapeutically effective amount of the compound is from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of said compound per day.
89. The method according to any one of claims 84-88, wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is administered to the patient.
90. The method according to any one of claims 84-89, wherein metformin is also administered to the patient.
91. A process for the preparation of a compound according to any one of claims 1-61 or its pharmaceutically acceptable salt, which comprises reacting the appropriate phenol with the appropriate carbamoylating reagent in a solvent according to the reaction scheme P1
Figure imgf000160_0001
and isolating the disubstituted carbamate product.
92. The process according to claim 91 , wherein said carbamoylating reagent
Figure imgf000160_0002
is selected from the group consisting of
Figure imgf000160_0003
93. The process according to any one of claims 91-92, wherein said solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide and N-methylpyrolidone.
94. The process according to any one of claims 91-93, wherein said base is selected from the group consisting of triethylamine, N,N-diisopropyl-N-ethylamine and DABCO.
95. A process for the preparation of a compound according to any one of claims 1-61, said process comprising the treatment of the appropriate amine with the appropriate acylating reagent in a solvent according to the reaction scheme P2
Figure imgf000161_0001
wherein Lv is a leaving group, and isolating the disubstituted carbamate as a salt with the acid H-Lv.
96. The process according to claim 90, wherein Lv is Cl.
97. The process according to any one of claims 90-91 , wherein said solvent is selected from the group consisting of diethyl ether, tetrahydrofuran and dichloromethane.
98. The process according to any one of claims 90-92, wherein said base is selected from the group consisting of trimethyiamine, triethylamine, ethyl-diisopropyl-amine and 1 ,A- diazabicyclo[2.2.2]octane.
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