Spiro compounds and methods for the modulation of chemokine receptor activity

Information

  • Patent Application
  • 20050075326
  • Publication Number
    20050075326
  • Date Filed
    July 19, 2004
    20 years ago
  • Date Published
    April 07, 2005
    19 years ago
Abstract
Novel compounds represented by formula I:
Description
FIELD OF THE INVENTION

The present invention relates to novel spiro compounds and a method of modulating chemokine receptor activity using these compounds. The present invention is also directed to novel spiro compounds which are useful in the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity. The present invention is further directed to a method of blocking cellular entry of HIV in a subject and to compositions using these compounds.


BACKGROUND OF THE INVENTION

Chemokines are chemotactic cytokines that are released by a wide variety of cells to attract macrophages, T cells, eosinophils, basophils and neutrophils to sites of inflammation and they also play a role in the maturation of cells of the immune system. Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma, rhinitis and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. Chemokines are small 70 to 80 amino acid proteins with well-characterized three-dimensional structures, usually stabilized by two disulfide bridges. They are divided into four families on the basis of pattern of conserved cysteine residues. Chemokine receptors have been designated such as, CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, and CXCR4 and therefore agents which modulate these receptors may be useful in the prevention and treatment of diseases as mentioned above.


One of them, the C—C chemokines family, includes potent chemoattractants of monocytes and lymphocytes such as RANTES (Regulated on Activation, Normal T Expressed and Secreted), eotaxin, MIP-1α and MIP-1β (Macrophage Inflammatory Proteins) and human monocyte chemotactic proteins 1-3 (MCP-1, MCP-2 and MCP-3). More specifically, C—C chemokine receptor 5 (CCR5), a β-chemokine receptor with a seven-transmembrane-protein structure, was found to serve as a coreceptor for non-syncytium-inducing or macrophage-tropic HIV-1 (R5 viruses). It was also established that CCR5 is the principal chemokine receptor required for the entry of HIV into the cell during primary infection. Therefore, interfering with the interaction between the viral receptor CCR5 and HIV can block HIV entry into the cell. It would therefore be useful to provide novel compounds which are modulators of chemokine receptor activity.


SUMMARY OF THE INVENTION

In one aspect, the present invention provides novel compounds represented by formula (I):
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or pharmaceutically acceptable salts, hydrates or solvates thereof,


wherein Y, Z and X are each independently chosen from CH2, C═O or CR4R5;


W is H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl) optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), optionally substituted C6-12 aryl, optionally substituted 3 to 10 membered heterocycle, optionally substituted C6-12 aralkyl or optionally substituted C3-10 heteroaralkyl;


R1 is H, OH, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), optionally substituted C6-12 aryl, NR8R9, optionally substituted O—C1-6 alkyl, optionally substituted O—C6-12 aryl, optionally substituted O—C6-12 aralkyl,
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R2 is optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle;


R3 is H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), or optionally substituted C6-12 aryl;


R4 and R5 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl), or optionally substituted C6-12 aryl;


R6 and R″6 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-4 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-4 alkenyl), or optionally substituted C2-10 alkynyl (e.g. C2-4 alkynyl) and R7 is H, optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C6-12 aryl, optionally substituted 3 to 10 membered heterocycle, optionally substituted C6-12 aralkyl or optionally substituted 3 to 10 membered heteroaralkyl, or R″6 and R7 can be taken together to form an optionally substituted 3 to 10 membered heterocycle; and


R8 and R9 are each independently H, optionally substituted C1-10 alkyl (e.g. C1-6 alkyl), optionally substituted C2-10 alkenyl (e.g. C2-6 alkenyl), or optionally substituted C2-10 alkynyl (e.g. C2-6 alkynyl).


In another aspect, there is provided a method of modulating chemokine receptor activity in a subject comprising administering to the subject an effective amount of a compound of formula (I) or composition of the invention.


In still another aspect, there is provided a method for prevention or treatment of certain inflammatory diseases, immunoregulatory diseases, organ transplantation reactions and in the prevention and treatment of infectious diseases such as HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In still another aspect, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject comprising administering to the subject in need thereof an effective amount of a compound of formula (I) or composition of the invention to block HIV from cellular entry in said subject.


In still another aspect, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.


In another aspect, there is provided a pharmaceutical formulation comprising the compound of the invention in combination with a pharmaceutically acceptable carrier or excipient.


In another aspect of the invention is the use of a compound according to formula (I), for the manufacture of a medicament for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity.







DETAILED DESCRIPTION OF THE INVENTION

In one embodiment, compounds of the present invention comprise those wherein the following embodiments are present, either independently or in combination.


In one embodiment, the present invention provides novel compounds represented by formula I:
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, X, W, R1, R2 and R3 are defined above.


In one embodiment, the present invention provides novel compounds represented by formula (Ia):
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, X, W, R1, R2 and R3 are defined above.


In one embodiment, the present invention provides novel compounds represented by formula (Ib):
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Z, X, W, R1, R2 and R3 are defined above.


In one embodiment, the present invention provides novel compounds represented by formula (Ic):
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, W, R1, R2 and R3 are defined above.


In one embodiment, the present invention provides novel compounds represented by formula (Id):
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein W, R1, R2 and R3 are defined above.


In one embodiment, the compounds of the present invention are in the (S)-enantiomer as represented by formula (Ie):
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or pharmaceutically acceptable salts, hydrates or solvates thereof wherein Y, Z, X, W, R1, R2 and R3 are defined above.


In one embodiment, W is chosen from optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.


In a further embodiment, W is optionally substituted C6-12 aryl.


In a further embodiment, W is optionally substituted 3 to 10 membered heterocycle.


In further embodiments:


W is phenyl;


W is phenyl substituted with a halogen;


W is phenyl substituted with Br;


W is phenyl substituted with F;


W is phenyl substituted with Cl;


W is phenyl substituted with at least one halogen;


W is phenyl substituted with a C1-3 alkoxy;


W is phenyl substituted with methoxy;


W is phenyl substituted with ethoxy;


W is phenyl substituted with SO2C1-3alkyl;


W is phenyl substituted with methanesulfonyl;


W is phenyl substituted with difluoromethoxy;


W is phenyl substituted with trifluoromethoxy;


W is phenyl substituted with trifluoromethyl;


W is phenyl substituted with CN;


W is phenyl substituted with pyrrazoyl;


W is phenyl optionally substituted in the para (p) position.


W is optionally substituted pyridine.


In a further embodiment, R1 is chosen from:
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In a further embodiment, R1 is:
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wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.


In further embodiments, R1 is:
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wherein:


R7 is methyl;


R7 is ethyl;


R7 is isopropyl;


R7 is cyclopropyl;


R7 is cyclobutyl;


R7 is cyclopentyl;


R7 is cyclohexyl;


R7 is cycloheptyl;


R7 is 4,4-difluorocyclohexyl;


R7 is CH2-cyclopropyl;


R7 is CH2-cyclobutyl;


R7 is CH2-cyclopentyl;


R7 is CH2-cyclohexyl.


R7 is phenyl;


R7 is phenyl substituted with methyl;


R7 is phenyl substituted with at least one methyl;


R7 is phenyl substituted with a halogen;


R7 is phenyl substituted with at least one halogen;


R7 is phenyl substituted with Cl;


R7 is phenyl substituted with Br;


R7 is phenyl substituted with F;


R7 is phenyl substituted with at least one Cl;


R7 is phenyl substituted with methoxy.


R7 is benzyl;


R7 is benzyl substituted with methyl;


R7 is benzyl substituted with at least one methyl;


R7 is benzyl substituted with a halogen;


R7 is benzyl substituted with at least one halogen;


R7 is benzyl substituted with Cl;


R7 is benzyl substituted with Br;


R7 is benzyl substituted with F;


R7 is benzyl substituted with at least one Cl;


R7 is benzyl substituted with methoxy.


R7 is optionally substituted pyridine.


In a further embodiment, R1 is:
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wherein R6 and R6 are as defined above and R7 is optionally substituted C6-12 aryl, or R6 and R7 can be taken together to form an optionally substituted 3 to 10 membered heterocycle.


In a further embodiment, R1 is:
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wherein:


R7 is phenyl;


R7 is phenyl substituted with methyl;


R7 is phenyl substituted with at least one methyl;


R7 is phenyl substituted with a halogen;


R7 is phenyl substituted with at least one halogen;


R7 is phenyl substituted with Cl;


R7 is phenyl substituted with Br;


R7 is phenyl substituted with F;


R7 is phenyl substituted with at least one Cl;


R7 is phenyl substituted with methoxy;


R7 is naphthyl.


R″6 and R7 can be taken together to form an optionally substituted piperidine.


R6 and R7 can be taken together to form an optionally substituted morpholine.


R6 and R7 can be taken together to form a morpholine.


R6 and R7 can be taken together to form an optionally substituted pyrrolidine.


R6 and R7 can be taken together to form a 3,3-difluoropyrrolidine.


In a further embodiment, R1 is:
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wherein R6 is as defined above and R7 is optionally substituted C1-10 alkyl.


In further embodiments, R1 is:
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wherein:


R7 is methyl;


R7 is ethyl;


R7 is tert-butyl;


R7 is cyclobutyl;


R7 is cyclopentyl;


R7 is cyclohexyl.


In a further embodiment, R1 is:
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wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl, optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.


In a further embodiment, R1 is:
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wherein:


R7 is optionally substituted phenyl;


R7 is optionally substituted C1-10 alkyl;


R7 is isopropyl.


In a further embodiment, R1 is:
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wherein R6 is as defined above and R7 is chosen from optionally substituted C1-10 alkyl or optionally substituted C6-12 aryl.


In a further embodiment, R1 is:
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wherein:


R7 is optionally substituted cyclohexyl.


R7 is optionally substituted phenyl.


In a further embodiment, R2 is chosen from optionally substituted C6-12 aryl or optionally substituted 3 to 10 membered heterocycle.


In further embodiments:


R2 is optionally substituted C6-12 aryl.


R2 is phenyl;


R2 is phenyl substituted with halogen;


R2 is phenyl substituted with Cl;


R2 is phenyl substituted with at least one halogen;


R2 is phenyl substituted with methoxy;


R2 is phenyl substituted with at least one methoxy.


In a further embodiments:


R2 is optionally substituted 3 to 10 membered heterocycle.


R2 is optionally substituted thienyl.


R2 is optionally substituted pyridyl.


In a further embodiment, R3 is chosen from H or optionally substituted C1-4 alkyl.


In one embodiment, R3 is H.


In one embodiment, R3 is methyl.


The compounds of the present invention may have an asymmetric center. As two optical isomers can independently be obtained from each asymmetric center, compounds of the invention having one asymmetric center can be in the form of the enantiomers, i.e., the (+) enantiomer or (−) enantiomer, in pure or partially purified form, as well as mixtures of enantiomers.


In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 99%.


In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 95%.


In one embodiment, the compounds of the present invention are the (+) enantiomer having an enantiomeric excess of 90%.


In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 99%.


In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 95%.


In one embodiment, the compounds of the present invention are the (−) enantiomer having an enantiomeric excess of 90%.


Compounds of the present invention have also two asymmetric centers. As two optical isomers can independently be obtained from each asymmetric center, compounds of the invention having two asymmetric centers can be in the form of the diastereomers. It is intended that all the possible diastereomers in mixtures and as pure or partially purified compounds are included in this invention.


In one embodiment, the compounds of the present invention are in the form of the (R,R)-diastereomer;


In one embodiment, the compounds of the present invention are in the form of the (S,R)-diastereomer;


In one embodiment, the compounds of the present invention are in the form of the (R,S)-diastereomer;


In one embodiment, the compounds of the present invention are in the form of the (S,S)-diastereomer.


In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 99%.


In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 95%.


In one embodiment, the compounds of the present invention are a (R,R)-diastereomer having an optical purity in excess of 90%.


In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 99%.


In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 95%.


In one embodiment, the compounds of the present invention are a (S,R)-diastereomer having an optical purity in excess of 90%.


In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 99%.


In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 95%.


In one embodiment, the compounds of the present invention are a (R,S)-diastereomer having an optical purity in excess of 90%.


In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 99%.


In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 95%.


In one embodiment, the compounds of the present invention are a (S,S)-diastereomer having an optical purity in excess of 90%.


In one embodiment, there is provided a method of modulating chemokine receptor activity in a subject comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In another embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In a further embodiment, there is provided a method for prevention or treatment of certain inflammatory diseases, immunoregulatory diseases, organ transplantation reactions and in the prevention and treatment of infectious diseases such as HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In another embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of formula (I) to block HIV from cellular entry in said subject.


In still another aspect, there is provided a method for prevention or treatment of HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In still another aspect, there is provided a method for delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of formula (I) or composition of the invention.


In a further embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.


In a further embodiment, there is provided a method for the prevention or treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.


In still another aspect, there is provided a method for blocking cellular entry of HIV in a subject or for the prevention or treatment of HIV infections in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.


In still another aspect, there is provided a method for delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a pharmaceutical combination comprising at least one compound of formula (I) and at least one further therapeutic agent.


In another embodiment, there is provided a combination useful for the prevention or treatment of diseases associated with the modulation of chemokine receptor activity which is a therapeutically effective amount of a compound of formula (I) and therapeutically effective amount of at least one further therapeutic agent.


In one embodiment, combinations of the present invention comprise those wherein the following embodiments are present, either independently or in combination.


In a further embodiment, the pharmaceutical combinations of this invention may contain at least one further therapeutic agent chosen from an agent used in inflammatory diseases, immunoregulatory diseases and in organ transplantation reactions.


In another embodiment, the pharmaceutical combination of this invention may contain at least one further therapeutic agent which is an antiviral agent.


In one embodiment, the pharmaceutical combination of this invention may contain at least one further antiviral agent which is chosen from nucleoside and nucleotide analog reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, attachment and fusion inhibitors, integrase inhibitors or maturation inhibitors.


In one embodiment, the pharmaceutical combinations of this invention may contain at least one other antiviral agent which is a nucleoside and nucleotide analog reverse transcriptase inhibitors chosen from 3TC (lamivudine, Epivir®), AZT (zidovudine, Retrovir®), Emtricitabine (Coviracil®, formerly FTC), d4T (2′,3′-dideoxy-2′,3′-didehydro-thymidine, stavudine and Zerit®), tenofovir (Viread®), 2′,3′-dideoxyinosine (ddl, didanosine, Videx®), 2′,3′-dideoxycytidine (ddC, zalcitabine, Hivid®), Combivir® (AZT/3TC or zidovudine/lamivudine combination), Trivizir® (AZT/3TC/abacavir or zidovudine/lamivudine/abacavir combination), abacavir (1592U89, Ziagen®), SPD-754, ACH-126,443 (Beta-L-Fd4C), Alovudine (MIV-310), DAPD (amdoxovir), Racivir, 9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]guanine or 2-amino-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a non-nucleoside reverse transcriptase inhibitor chosen from Nevirapine (Viramune®, NVP, BI-RG-587), delavirdine (Rescriptor®, DLV), efavirenz (DMP 266, Sustiva®), (+)-Calanolide A, Capravirine (AG1549, formerly S-1153), DPCO83, MIV-150, TMC120, TMC125 or BHAP (delavirdine), calanolides or L-697,661 (2-Pyridinone 3benzoxazolMeNH derivative).


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which ia a protease inhibitor chosen from nelfinavir (Viracept®, NFV), amprenavir (141W94, Agenerase®), indinavir (MK-639, IDV, Crixivan®), saquinavir (Invirase®, Fortovase®, SQV), ritonavir (Norvir®, RTV), lopinavir (ABT-378, Kaletra®), Atazanavir (BMS232632), mozenavir (DMβ-450), fosamprenavir (GW433908), R0033-4649, Tipranavir (PNU-140690), TMC114 or VX-385.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an attachment and fusion inhibitor chosen from T-20 (enfuvirtide, Fuzeon®), T-1249, Schering C (SCH-C), Schering D (SCH-D), FP21399, PRO-140, PRO 542, PRO 452, TNX-355, GW873140 (AK602), TAK-220, UK-427,857 or soluble CD4, CD4 fragments, CD4-hybrid molecules, BMS-806, BMS-488043,AMD3100, AMD070 or KRH-2731.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an integrase inhibitor chosen from S-1360, L-870,810, L-870,812 or C-2507.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a maturation inhibitor and is PA-457.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is a zinc finger inhibitor and is azodicarbonamide (ADA).


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an antisense drug and is HGTV43.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent which is an immunomodulator, immune stimulator or cytokine chosen from interleukin-2 (IL-2, Aldesleukin, Proleukin), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, Multikine, Ampligen, thymomodulin, thymopentin, foscarnet, HE2000, Reticulose, Murabutide, Resveratrol, HRG214, HIV-1 Immunogen (Remune) or EP HIV-1090.


In another embodiment, the pharmaceutical combination of this invention may contain at least one other antiviral agent chosen from 2′,3′-dideoxyadenosine, 3′-deoxythymidine, 2′,3′-dideoxy-2′,3′-didehydrocytidine and ribavirin; acyclic nucleosides such as acyclovir, ganciclovir; interferons such as alpha-, beta-and gamma-interferon; glucuronation inhibitors such as probenecid; or TIBO drugs, HEPT, TSAO derivatives.


The combinations referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a pharmaceutically acceptable carrier thereof comprises a further aspect of the invention.


The individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations.


In a further embodiment, the said compound of formula (I) and said therapeutic agent are administered sequentially.


In a further embodiment, the said compound of formula (I) and said therapeutic agent are administered simultaneously.


The subject to which the compounds are administered can be, for example, a mammal or a human. Preferably, the subject is a human.


In one embodiment, the present invention further provides a pharmaceutical composition comprising at least one compound having the formula (I) or pharmaceutically acceptable salts or pharmaceutically acceptable hydrates or pharmaceutically acceptable solvates thereof and at least one pharmaceutically acceptable carrier or excipient.


In another embodiment, the invention provides the use of a compound having the formula (I) for the manufacture of a medicament for prevention and treatment of diseases associated with the modulation of CCR5 chemokine receptor activity in a host comprising administering a therapeutically effective amount of a compound of formula (I).


Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.


The term “alkyl” represents a linear, branched or cyclic hydrocarbon moiety having, for example, 1 to 10 carbon atoms, which may have one or more double bonds or triple bonds in the chain, and is optionally substituted. For example, suitable substituents include halogen, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C (R33) NR34 or C (R33) NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12aryl).


Preferred substituents for the alkyl groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, COOH, COO—C14 alkyl, CO—C14 alkyl, and phenyl.


Examples of alkyl groups include but are not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, neohexyl, allyl, vinyl, acetylenyl, ethylenyl, propenyl, isopropenyl butenyl, isobutenyl, hexenyl, butadienyl, pentenyl, pentadienyl, hexenyl, hexadienyl, hexatrienyl, heptenyl, heptadienyl, heptatrienyl, octenyl, octadienyl, octatrienyl, octatetraenyl, propynyl, butynyl, pentynyl, hexynyl, cyclopropyl, cyclobutyl, cycloheptyl, cyclohexenyl, cyclohex-dienyl and cyclohexyl.


The term alkyl is also meant to include alkyls in which one or more hydrogen atom is replaced by a halogen, i.e. an alkylhalide. Examples include but are not limited to trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethyl, chloromethyl, trifluoroethyl, difluoroethyl, fluoroethyl, trichloroethyl, dichloroethyl, chloroethyl, chlorofluoromethyl, chlorodifluoromethyl, dichlorofluoroethyl.


The term “alkenyl” refers to alkyl groups may have one or more double bonds in the chain. The term “alkynyl” refers to alkyl groups may have one or more triple bonds in their chain. The alkenyl and alkynyl groups can be optionally substituted as described above for the alkyl groups.


The term “alkoxy” represents an alkyl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, hexyloxy, isohexyloxy and neohexyloxy.


The term “alkylamino” represents an alkyl which is covalently bonded to the adjacent atom through a nitrogen atom and may be monoalkylamino or dialkylamino, wherein the alkyl groups may be the same or different. Examples include but are not limited to methylamino, dimethylamino, ethylamino, diethylamino, methylethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, isopentylamino, neopentylamino, tert-pentylamino, hexylamino, isohexylamino and neohexylamino.


The term “alkyloxycarbonyl” represents an alkyloxy which is covalently bonded to the adjacent atom through carbonyl (C═O). Examples include but are not limited to methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, tert-pentyloxycarbonyl, hexyloxycarbonyl, isohexyloxycarbonyl and neohexyloxycarbonyl.


The term “amidino” represents —C(=NR10)NR11R12, wherein R10, R11 and R12 are each independently selected from H, C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R11 and R12 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.


The term “amido” represents —CONH2, —CONHR13 and —CONR13R14 wherein R13 and R14 are each independently selected from C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle or C6-12 aralkyl, or R13 and R14 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.


The term “amino” represents a derivative of ammonia obtained by substituting one or more hydrogen atom and include —NH2, —NHR15 and —NR15R16, wherein R15 and R16 are each independently selected from C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R15 and R16 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.


The term “aryl” represents a carbocyclic moiety containing at least one benzenoid-type ring (i.e. the aryl group may be monocyclic or polycyclic), and which is optionally substituted with one or more substituents. For example, suitable substituents include halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C1-6alkoxy, C6-12aralkyloxy, C6-12aryloxy, 3 to 10 membered heterocycle, C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12 aryl).


Preferred substituents for the aryl groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, C1-4 alkyl (e.g., CH3, C2H5, isopropyl), C1-4 alkoxy (e.g., OCH3, OC2H5), halogenated C1-4 alkyl (e.g., CF3, CHF2), halogenated C1-4 alkoxy (e.g., OCF3, OC2F5), COOH, COO—C1l4 alkyl, CO—C1-4 alkyl, C1-4 alkyl-S—(e.g., CH3S, C2H5S) , halogenated C1-4 alkyl-S—(e.g., CF3S, C2F5S), benzyloxy, and pyrazolyl.


Examples of aryl include but are not limited to phenyl, tolyl, dimethylphenyl, aminophenyl, anilinyl, naphthyl, anthryl, phenanthryl or biphenyl.


The term “aralkyl” represents an aryl group attached to the adjacent atom by a C1-6alkyl. Examples include but are not limited to benzyl, benzhydryl, trityl, phenethyl, 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl and naphthylmethyl. The aryl and alkyl portions can be optionally substituted as described above.


The term “aralkyloxy” represents an aralkyl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to benzyloxy, benzhydryloxy, trityloxy, phenethyloxy, 3-phenylpropyloxy, 2-phenylpropyloxy, 4-phenylbutyloxy and naphthylmethoxy. The aryl and alkyl portions can be optionally substituted as described above.


The term “aryloxy” represents an aryl which is covalently bonded to the adjacent atom through an oxygen atom. Examples include but are not limited to phenoxy and naphthyloxy. The aryl portion can be optionally substituted as described above.


The term “guanidino” represents —NR17C(═NR18)NR19R20 wherein R17, R18, R19 and R20 are each independently selected from H, C1-6 alkyl, C6-12 aryl or C6-12 aralkyl, or R19 and R20 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.


The term “halogen” is specifically a fluoride atom, chloride atom, bromide atom or iodide atom.


The term “heterocycle” represents an optionally substituted saturated, unsaturated or aromatic cyclic moiety wherein said cyclic moiety is interrupted by at least one heteroatom selected from oxygen (O), sulfur (S) or nitrogen (N). Heterocycles may be monocyclic or polycyclic rings. For example, suitable substituents include halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C1-6alkoxy, C6-12 aryl, C6-12aralkyloxy, C6-12aryloxy, C(Q)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R31 and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12 aryl)


Preferred substituents for the heterocycle groups include halogen (Br, Cl, I or F), cyano, nitro, oxo, amino, C1-4 alkyl (e.g., CH3, C2H5, isopropyl), C1-4 alkoxy (e.g., OCH3, OC2H5), halogenated C1-4 alkyl (e.g., CF3, CHF2), halogenated C1-4 alkoxy (e.g., OCF3, OC2F5), COOH, COO—C1-4 alkyl, CO—C1-4 alkyl, C1-4 alkyl-S—(e.g., CH3S, C2H5S), halogenated C1-4 alkyl-S—(e.g., CF3S, C2F5S), benzyloxy, and pyrazolyl.


Examples of heterocycles include but are not limited to azepinyl, aziridinyl, azetyl, azetidinyl, diazepinyl, dithiadiazinyl, dioxazepinyl, dioxolanyl, dithiazolyl, furanyl, isooxazolyl, isothiazolyl, imidazolyl, morpholinyl, morpholino, oxetanyl, oxadiazolyl, oxiranyl, oxazinyl, oxazolyl, piperazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, piperidyl, piperidino, pyridyl, pyranyl ,pyrazolyl, pyrrolyl, pyrrolidinyl, thiatriazolyl, tetrazolyl, thiadiazolyl, triazolyl, thiazolyl, thienyl, tetrazinyl, thiadiazinyl, triazinyl, thiazinyl, thiopyranyl furoisoxazolyl, imidazothiazolyl, thienoisothiazolyl, thienothiazolyl, imidazopyrazolyl, cyclopentapyrazolyl, pyrrolopyrrolyl, thienothienyl, thiadiazolopyrimidinyl, thiazolothiazinyl, thiazolopyrimidinyl, thiazolopyridinyl, oxazolopyrimidinyl, oxazolopyridyl, benzoxazolyl, benzisothiazolyl, benzothiazolyl, imidazopyrazinyl, purinyl, pyrazolopyrimidinyl, imidazopyridinyl, benzimidazolyl, indazolyl, benzoxathiolyl, benzodioxolyl, benzodithiolyl, indolizinyl, indolinyl, isoindolinyl, furopyrimidinyl, furopyridyl, benzofuranyl, isobenzofuranyl, thienopyrimidinyl, thienopyridyl, benzothienyl, cyclopentaoxazinyl, cyclopentafuranyl, benzoxazinyl, benzothiazinyl, quinazolinyl, naphthyridinyl, quinolinyl, isoquinolinyl, benzopyranyl, pyridopyridazinyl and pyridopyrimidinyl.


The term “heteroaralkyl” represents a heterocycle group attached to the adjacent atom by a C1-6 alkyl. The heterocycle and alkyl portions can be optionally substituted as described above.


The term “urea” represents —N(R35)CONR36R37 wherein R35 is H or C1-6 alkyl and wherein R36 and R37 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl, or R36 and R37 are taken together with the nitrogen to which they are attached to form a 3 to 10 membered heterocycle.


The term “independently” means that a substituent can be the same or a different definition for each item.


The term “optionally substituted” represents one or more halogen, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, amino, amidino, amido, azido, cyano, guanido, hydroxyl, nitro, nitroso, urea, OS(O)2R21 (wherein R21 is selected from C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OS(O)2OR22 (wherein R22 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)2OR23 (wherein R23 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), S(O)0-2R24 (wherein R24 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), OP(O)OR25OR26, P(O)OR25OR26 (wherein R25 and R26 are each independently selected from H or C1-6 alkyl), C1-6alkyl, C6-12aralkyl, C6-12 aryl, C1-6alkoxy, C6-12aralkyloxy, C6-12aryloxy, 3 to 10 membered heterocycle, C(O)R27 (wherein R27 is selected from H, C1-6 alkyl, C6-12 aryl or 3 to 10 membered heterocycle), C(O)OR28 (wherein R28 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle), NR29C(O)R30, C(O)NR29R30 (wherein R29 is H or C1-6 alkyl and R30 is selected from H, C1-6 alkyl, C6-12 aryl, C6-12 aralkyl or 3 to 10 membered heterocycle, or R29 and R30 are taken together with the atoms to which they are attached to form a 3 to 10 membered heterocycle), SO2NR31R32, NR31SO2R32 (wherein R3, and R32 are each independently selected from the group consisting of H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle and C6-12 aralkyl), C(R33)NR34 or C(R33)NOR34 (wherein R33 and R34 are each independently selected from the group consisting of H, C1-6 alkyl, or C6-12aryl).


There is also provided “enantiomers” and “diastereoisomers” of the present invention. It will be appreciated that the compounds in accordance with the present invention can contain one or more chiral centers. The compounds in accordance with the present invention may thus exist in the form of two different optical isomers, that is (+) or (−) enantiomers or in the form of different diastereomers. All such enantiomers, diastereomers and mixtures thereof, including racemic or other ratio mixtures of individual enantiomers and diastereomers, are included within the scope of the invention. The single diastereomer can be obtained by methods well known to those of ordinary skill in the art, such as HPLC, crystallization and chromatography. The single enantiomer can be obtained by methods well known to those of ordinary skill in the art, such as chiral HPLC, enzymatic resolution and chiral auxiliary derivatization.


The optical purity is numerically equivalent to the “enantiomeric excess”. The term “enantiomeric excess” is defined in percentage (%) value as follows: [mole fraction (major enantiomer)—mole fraction (minor enantiomer)] ×100. An example of enantiomeric excess of 99% represents a ratio of 99.5% of one enantiomer and 0.5% of the opposite enantiomer.


“Oxidation levels”: When there is a sulfur atom present, the sulfur atom can be at different oxidation levels, ie. S, SO, or SO2. All such oxidation levels are within the scope of the present invention. When there is a nitrogen atom present, the nitrogen atom can be at different oxidation levels, ie. N or NO. All such oxidation levels are within the scope of the present invention.


There is also provided “pharmaceutically acceptable hydrates” of the compounds of the present invention. “Hydrates” exist when the compound of the invention incorporates water. The hydrate may contain one or more molecule of water per molecule of compound of the invention. Illustrative non-limiting examples include monohydrate, dihydrate, trihydrate and tetrahydrate. The hydrate may contain one or more molecule of compound of the invention per molecule of water. An illustrative non-limiting example include semi-hydrate. In one embodiment, the water may be held in the crystal in various ways and thus, the water molecules may occupy lattice positions in the crystal, or they may form bonds with salts of the compounds as described herein. The hydrate must be “acceptable” in the sense of not being deleterious to the recipient thereof. The hydration may be assessed by methods known in the art such as Loss on Drying techniques (LOD) and Karl Fisher titration.


There is also provided “pharmaceutically acceptable salts” of the compounds of the present invention. By the term “pharmaceutically acceptable salts” of compounds are meant those derived from pharmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acids include but are not limited to hydrochloric, hydrobromic, sulphuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicylic, succinic, toleune-p-sulphonic, tartaric, acetic, trifluoroacetic, citric, methanesulphonic, formic, benzoic, malonic, naphthalene-2-sulphonic and benzenesulphonic acids. Other acids such as oxalic, while not in themselves pharmaceutically acceptable, may be useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts.


Salts derived from appropriate bases include alkali metal, alkaline earth metal or ammonium salts. The salt(s) must be “acceptable” in the sense of not being deleterious to the recipient thereof. Non-limiting examples of such salts known by those of ordinary skill in the art include without limitation calcium, potassium, sodium, choline, ethylenediamine, tromethamine, arginine, glycinelycine, lycine, magnesium and meglumine.


There is also provided a “pharmaceutically acceptable solvates” of the compounds of the present invention. The term “solvate” means that the compound of the invention incorporates one or more pharmaceutically acceptable solvent. The solvate may contain one or more molecule of solvent per molecule of compound of the invention or may contain one or more molecule of compound of the invention per molecule of solvent. In one embodiment, the solvent may be held in the crystal in various ways and thus, the solvent molecule may occupy lattice positions in the crystal, or they may form bonds with salts of the compounds as described herein. The solvate(s) must be “acceptable” in the sense of not being deleterious to the recipient thereof. The solvation may be assessed by methods known in the art such as Loss on Drying techniques (LOD).


Reference hereinafter to a compound according to the invention includes compounds of the general formula (I) and their pharmaceutically acceptable salts, hydrates and solvates.


“Polymorphs”: It will be appreciated by those skilled in the art that the compounds in accordance with the present invention can exist in several different crystalline forms due to a different arrangement of molecules in the crystal lattice. This may include solvate or hydrate (also known as pseudopolymorphs) and amorphous forms. All such crystalline forms and polymorphs are included within the scope of the invention. The polymorphs may be characterized by methods well known in the art. Examples of analytical procedures that may be used to determine whether polymorphism occurs include: melting point (including hot-stage microscopy), infrared (not in solution), X-ray powder diffraction, thermal analysis methods (e.g. differential scanning calorimetry (DSC), differential thermal analysis (DTA), thermogravimetric analysis (TGA)), Raman spectroscopy, comparative intrinsic dissolution rate, scanning electron microscopy (SEM).


In one aspect, the present invention provides novel compounds including:


Compound 1

  • 2-(4-bromobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 2

  • 8-(3-phenylpropyl)-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 3

  • 2-(4-chlorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 4

  • 2-(4-fluorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 5

  • 8-(3-phenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 6

  • 2-(4-methylbenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 7

  • 4-[l-oxo-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzonitrile hydrochloride


Compound 8

  • 2-biphenyl-4-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 9

  • 2-naphthalen-2-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 10

  • 2-(4-bromobenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 11

  • 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 12

  • 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 13

  • 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride


Compound 14

  • 8-(3,3-diphenyl-propyl)-2-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 15

  • 8-(3,3-diphenyl-propyl)-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride


Compound 16

  • 8-(3,3-diphenyl-propyl)-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 17

  • 8-(3,3-diphenyl-propyl)-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 18

  • 2-benzothiazol-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 19

  • 8-(3,3-diphenyl-propyl)-2-(4-methanesulfonyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 20

  • 8-(3,3-diphenyl-propyl)-2-(3-phenyl-allyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 21

  • 8-(3,3-diphenyl-propyl)-2-phenethyl-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 22

  • 2-(4-benzyloxy-benzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 23

  • 2-benzofuran-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 24

  • 8-(3,3-diphenyl-propyl)-2-(4-isopropyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 25

  • 2-(5-chloro-benzo[b]thiophen-3-ylmethyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 26

  • 8-(3,3-diphenyl-propyl)-2-(4-nitro-benzyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 27

  • 2-(4-bromo-benzyl)-8-(3-pyridin-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 28

  • 2-[1-(4-bromophenyl)-ethyl]-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 29

  • 8-(3,3-diphenyl-propyl)-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride


Compound 30

  • N-{4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-phenyl}-acetamide hydrochloride


Compound 31

  • 8-(3,3-diphenyl-propyl)-2-(6-trifluoromethyl-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride


Compound 32

  • 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzoic acid hydrochloride


Compound 33

  • 8-(3,3-diphenyl-propyl)-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride


Compound 34

  • 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethylsulfanyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 35

  • 8-(3,3-diphenyl-propyl)-2-(4-methyl-cyclohexylmethyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 36

  • 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzoic acid methyl ester hydrochloride


Compound 37

  • 8-(3,3-diphenyl-propyl)-2-(5-trifluoromethyl-furan-2-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 38

  • 8-(3,3-diphenyl-propyl)-2-(4-iodo-benzyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 39

  • 2-(4-methanesulfonylbenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 40

  • 2-(4-bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 41

  • 2-(4-bromobenzyl)-8-[3-hydroxy-3-(3-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 42

  • 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 43

  • 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 44

  • 2-(4-bromobenzyl)-8-[3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 45

  • 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 46

  • 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 47

  • 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 48

  • 2-(4-bromobenzyl)-8-(3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 49

  • 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one


Compound 50

  • 2-(4-Bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 51

  • 8-(3-Benzyloxy-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 52

  • 2-(4-Bromobenzyl)-8-(3-phenoxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one


Compound 53

  • {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester


Compound 54

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 55

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,6-dimethyl-benzamide hydrochloride


Compound 56

  • Cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 57

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride


Compound 58

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2,4,6-trimethyl-phenyl)-acetamide hydrochloride


Compound 59

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-propionamide hydrochloride


Compound 60

  • {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-carbamic acid tert-butyl ester


Compound 61

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-benzamide hydrochloride


Compound 62

  • Cyclohexanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-amide hydrochloride


Compound 63

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-phenyl-acetamide hydrochloride


Compound 64

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-(2,4,6-trimethyl-phenyl)-acetamide hydrochloride


Compound 65

  • [3-(1 -oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid tert-butyl ester


Compound 66

  • {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester


Compound 67

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester


Compound 68

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochlroride


Compound 69

  • Cyclopropanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 70

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 71

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride


Compound 72

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-chloro-benzamide hydrochloride


Compound 73

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-methoxy-benzamide hydrochloride


Compound 74

  • Pyridine-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride


Compound 75

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-chloro-benzamide hydrochloride


Compound 76

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide hydrochloride


Compound 77

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride


Compound 78

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-4-chloro-benzamide hydrochloride


Compound 79

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide hydrochloride


Compound 80

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride


Compound 81

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dichloro-benzamide hydrochloride


Compound 82

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide hydrochloride


Compound 83

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-chloro-phenyl)-acetamide hydrochloride


Compound 84

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxy-phenyl)-acetamide hydrochloride


Compound 85

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-chloro-phenyl)-acetamide hydrochloride


Compound 86

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxy-phenyl)-acetamide hydrochloride


Compound 87

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide dihydrochloride


Compound 88

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxy-phenyl)-acetamide hydrochloride


Compound 89

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dichloro-phenyl)-acetamide hydrochloride


Compound 90

  • Tetrahydro-pyran-4-carboxylic acid{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 91

  • Cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 92

  • Cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 93

  • Cycloheptanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 94

  • N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclohexyl-acetamide hydrochloride


Compound 95

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 96

  • Cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 97

  • N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 98

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride


Compound 99

  • 2-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 100

  • 2-methoxy-N-(3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 101

  • Pyridine-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride


Compound 102

  • 3-chloro-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 103

  • 3-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 104

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride


Compound 105

  • 4-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 106

  • 4-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 107

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride


Compound 108

  • (R)-cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 109

  • 3,4-dichloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 110

  • 3,4-dimethoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 111

  • 2-(2-chloro-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 112

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methox-phenyl)-acetamide hydrochloride


Compound 113

  • 2-(3-chlorophenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 114

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride


Compound 115

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide dihydrochloride


Compound 116

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride


Compound 117

  • 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 118

  • Tetrahydro-pyran-4-carboxylic acid{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 119

  • Cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 120

  • Cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 121

  • Cycloheptanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 122

  • 2-cyclohexyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 123

  • (S)-cyclohexanecarboxylic acid 13-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 124

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopentyl-acetamide hydrochloride


Compound 125

  • Furan-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 126

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-ethyl-butyramide hydrochloride


Compound 127

  • Thiophene-2-carboxylic acid {3-[2-(4-brom-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 128

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dimethoxyphenyl)-acetamide hydrochloride


Compound 129

  • 2-cyclopentyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 130

  • Furan-2-carboxylic acid {3-[2-(4-methox-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 131

  • 2-ethyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide hydrochloride


Compound 132

  • Thiophene-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 133

  • 2-(3,4-dimethoxy-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 134

  • Cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 135

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 136

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride


Compound 137

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 138

  • Cyclopropanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide hydrochloride


Compound 139

  • N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 140

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide hydrochloride


Compound 141

  • 2-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 142

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-methoxy-benzamide hydrochloride


Compound 143

  • Pyridine-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide dihydrochloride


Compound 144

  • 3-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 145

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide hydrochloride


Compound 146

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride


Compound 147

  • 4-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 148

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide hydrochloride


Compound 149

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide dihydrochloride


Compound 150

  • 3,4-dichloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 151

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide hydrochloride


Compound 152

  • 2-(2-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 153

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxyphenyl)-acetamide hydrochloride


Compound 154

  • 2-(3-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 155

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride


Compound 156

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide hydrochloride


Compound 157

  • (S)-cyclohexanecarboxylic acid [3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 158

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride


Compound 159

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide hydrochloride


Compound 160

  • 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 161

  • Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 162

  • Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 163

  • Cycloheptanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 164

  • 2-cyclohexyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 165

  • 2-cyclopentyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 166

  • Furan-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 167

  • 2-ethyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide hydrochloride


Compound 168

  • Thiophene-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 169

  • 2-(3,4-dimethoxyphenyl)-N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 170

  • Cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 171

  • 4-methyl-cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 172

  • 2-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 173

  • 3-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 174

  • 4-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 175

  • 4-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 176

  • Cyclohexanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-amide hydrochloride


Compound 177

  • N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-benzamide hydrochloride


Compound 178

  • N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-phenyl-acetamide hydrochloride


Compound 179

  • {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 180

  • {1-(3,4-dichlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 181

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 182

  • Cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 183

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide dihydrochloride


Compound 184

  • 3-methyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide dihydrochloride


Compound 185

  • 2-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 186

  • Pyridine-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide trihydrochloride


Compound 187

  • 3-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 188

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-nicotinamide trihydrochloride


Compound 189

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isonicotinamide trihydrochloride


Compound 190

  • 3,4-dichloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 191

  • 3,4-dimethoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 192

  • 2-(2-chlorophenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 193

  • 2-(2-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 194

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide dihydrochloride


Compound 195

  • 2-(3-chloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 196

  • 2-(3-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 197

  • 2-(4-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 198

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-acetamide dihydrochloride


Compound 199

  • 2-(3,4-dichloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 200

  • Cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 201

  • {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 202

  • Cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 203

  • Cycloheptanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 204

  • 2-cyclohexyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 205

  • 2-cyclopentyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 206

  • Furan-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 207

  • 2-ethyl-N-[3-(1-oxo-2pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide dihydrochloride


Compound 208

  • Thiophene-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 209

  • 2-(3,4-dimethoxyphenyl)-N-[3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide dihydrochloride


Compound 210

  • Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl)-amide dihydrochloride


Compound 211

  • 4-methyl-cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 212

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 213

  • [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 214

  • (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 215

  • (S)-cyclopropanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 216

  • (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 217

  • (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-3-methyl-butyramide hydrochloride


Compound 218

  • (S)-cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 219

  • (S)-cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 220

  • [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 221

  • {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 222

  • {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 223

  • {1-(3,4-dichlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 224

  • 2-cyclopropyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 225

  • 2-cyclopropyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 226

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 227

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 228

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1(3,4-dimethoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 229

  • {1-(3,4-dimethoxyphenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 230

  • Tetrahydro-pyran-4-carboxylic acid (3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 231

  • [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid tertbutyl ester


Compound 232

  • (S)-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester


Compound 233

  • {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 234

  • {1-(3,4-dimethoxyphenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 235

  • {1-(4-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 236

  • {1-(2-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 237

  • {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 238

  • [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 239

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chlorophenyl)-propyl]-carbamic acid tert-butyl ester


Compound 240

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chlorophenyl)-propyl]-carbamic acid tert-butyl ester


Compound 241

  • {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 242

  • {1-(4-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 243

  • {1-(2-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester


Compound 244

  • {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester


Compound 245

  • (S)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide


Compound 246

  • [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 247

  • [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid tert-butyl ester


Compound 248

  • [1-(2-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester


Compound 249

  • [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester


Compound 250

  • [1-(3,4-dichlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester


Compound 251

  • [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid tert-butyl ester


Compound 252

  • (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride


Compound 253

  • (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride


Compound 254

  • (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride


Compound 255

  • (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)decane hydrochloride


Compound 256

  • (S)-8-(3-isobutyrylamino-3-phenyl-propyl)-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride


Compound 257

  • (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride


Compound 258

  • (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)decane hydrochloride


Compound 259

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride


Compound 260

  • Cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 261

  • Cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 262

  • N-{3-[2-(4-bromo-enzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride


Compound 263

  • N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl)-2-methoxy-acetamide hydrochloride


Compound 264

  • Cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 265

  • Cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 266

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride


Compound 267

  • [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester


Compound 268

  • Cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 269

  • Cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 270

  • N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride


Compound 271

  • 2-methoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-acetamide hydrochloride


Compound 272

  • Cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 273

  • Cyclopropane carboxylic acid{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 274

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride


Compound 275

  • Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 276

  • Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 277

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide hydrochloride


Compound 278

  • N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2-methoxy-acetamide hydrochloride


Compound 279

  • Cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 280

  • Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride


Compound 281

  • N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-isobutyramide dihydrochloride


Compound 282

  • Cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl)-amide dihydrochloride


Compound 283

  • Cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride


Compound 284

  • N-[3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-propionamide dihydrochloride


Compound 285

  • Cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride


Compound 286

  • Cyclopropanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride


Compound 287

  • N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-isobutyramide hydrochloride


Compound 288

  • Cyclobutanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride


Compound 289

  • Cyclopentanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride


Compound 290

  • N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-propionamide hydrochloride


Compound 291

  • N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-methoxy-acetamide hydrochloride


Compound 292

  • 2-Cyclopropyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 293

  • 2-Cyclopropyl-N-{(S)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 294

  • Cyclopentanecarboxylic acid [(S)-3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride


Compound 295

  • Cyclopropanecarboxylic acid [(S)-3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride


Compound 296

  • Cyclohexanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide hydrochloride


Compound 297

  • Cyclopropanecarboxylic acid {l-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 298

  • N-{1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 299

  • Cyclobutanecarboxylic acid {l-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 300

  • Cyclopentanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 301

  • N-{l-(3-Chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 302

  • N-{1-(3-Chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride


Compound 303

  • Cyclohexanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 304

  • Cyclopropanecarboxylic acid {l-(3-chlorophenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 305

  • N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 306

  • Cyclobutanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 307

  • Cyclopentanecarboxylic acid {1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 308

  • N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 309

  • N-{l-(3-Chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride


Compound 310

  • Cyclopropanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 311

  • N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride


Compound 312

  • Cyclobutanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 313

  • Cyclopentanecarboxylic acid [1-(3-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 314

  • N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride


Compound 315

  • N-[1-(3-Chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride


Compound 316

  • Cyclohexanecarboxylic acid [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 317

  • Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 318

  • Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 319

  • Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 320

  • Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 321

  • Cyclopropanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 322

  • Cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide dihydrochloride


Compound 323

  • Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 324

  • Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 325

  • Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro(4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 326

  • Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 327

  • Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 328

  • Cyclopentanecarboxylic acid { (S)-3-[1-oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 329

  • Cyclopentanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 330

  • N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-propionamide dihydrochloride


Compound 331

  • N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-2-methoxy-acetamide dihydrochloride


Compound 332

  • Cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 333

  • N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-isobutyramide dihydrochloride


Compound 334

  • Cyclobutanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 335

  • Cyclopentanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 336

  • N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-propionamide dihydrochloride


Compound 337

  • 2-Methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-acetamide dihydrochloride


Compound 338

  • Cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 339

  • N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl)-isobutyramide dihydrochloride


Compound 340

  • Cyclobutanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 341

  • Cyclopropanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 342

  • N-{3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-isobutyramide dihydrochloride


Compound 343

  • Cyclobutanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 344

  • Cyclopentanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-amide dihydrochloride


Compound 345

  • N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl)-propionamide dihydrochloride


Compound 346

  • N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide


Compound 347

  • (R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 348

  • (S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 349

  • Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 350

  • (R)-N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-propionamide


Compound 351

  • 3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 352

  • (S)-N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-propionamide


Compound 353

  • (R)-N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-propionamide


Compound 354

  • (S)-N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-propionamide


Compound 355

  • (R)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 356

  • (S)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 357

  • Tetrahydro-furan-3-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 358

  • 3-Oxo-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 359

  • N-[(S)-3-(1-Oxo-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide


Compound 360

  • N-[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide


Compound 361

  • N-[(S)-3-(1-Oxo-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-isobutyramide


Compound 362

  • N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-4-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide


Compound 363

  • N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-2-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide


Compound 364

  • N-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide


Compound 365

  • 1-Methyl-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 366

  • 1-Methyl-cyclohexanecarboxylic acid{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 367

  • 2-Cyclopentyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide


Compound 368

  • 2-Cyclopentyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide


Compound 369

  • 1-Methyl-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethy-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 370

  • 1-Methyl-cyclohexanecarboxylic acid[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 371

  • 2-Cyclopentyl-N-[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5)dec-8-yl)-1-phenyl-propyl]-propionamide


Compound 372

  • 2-Cyclopentyl-N-[(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-propionamide


Compound 373

  • Cyclopropanecarboxylic acid (3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 374

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride


Compound 375

  • Cyclobutanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 376

  • Tetrahydro-pyran-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 377

  • N-{3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 378

  • N-{3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 379

  • N-{l-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 380

  • N-{1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 381

  • N-[1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2,2-dimethyl-propionamide dihydrochloride


Compound 382

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 383

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 384

  • 1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 385

  • 1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 386

  • 1-Methyl-cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide dihydrochloride


Compound 387

  • 1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 388

  • 1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 389

  • 1-Methyl-cyclopropanecarboxylic acid [1-(3-chloro-phenyl)-3-(l-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 390

  • 1-Methyl-cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-propyl}-amide hydrochloride


Compound 391

  • 1-Methyl-cyclopropanecarboxylic acid {1- (4-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 392

  • Tetrahydro-pyran-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 393

  • Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 394

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride


Compound 395

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride


Compound 396

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-cyclopropyl-acetamide hydrochloride


Compound 397

  • Cyclohexanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 398

  • Cyclopropanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 399

  • N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride


Compound 400

  • Cyclobutanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 401

  • Cyclopentanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 402

  • N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride


Compound 403

  • 2-Methoxy-N-[3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-acetamide hydrochloride


Compound 404

  • 2-Cyclopropyl-N-[3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1(2-methoxy-phenyl)-propyl]-acetamide hydrochloride


Compound 405

  • Cyclohexanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 406

  • Cyclopropanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 407

  • N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-isobutyramide hydrochloride


Compound 408

  • Cyclobutanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 409

  • Cyclopentanecarboxylic acid (3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 410

  • N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-propionamide hydrochloride


Compound 411

  • N-[3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride


Compound 412

  • 2-Cyclopropyl-N-[3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-acetamide hydrochloride


Compound 413

  • Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 414

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-isobutyramide hydrochloride


Compound 415

  • Cyclobutanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 416

  • Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 417

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl)-propionamide hydrochloride


Compound 418

  • N-[3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-2-methoxy-acetamide hydrochloride


Compound 419

  • Cyclopropanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 420

  • N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-isobutyramide hydrochloride


Compound 421

  • Cyclobutanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 422

  • Cyclopentanecarboxylic acid [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 423

  • N-[3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-propionamide hydrochloride


Compound 424

  • Cyclohexanecarboxylic acid [3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-amide hydrochloride


Compound 425

  • Cyclopentanecarboxylic acid [1-(3-methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 426

  • N-[1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride


Compound 427

  • 2-Methoxy-N-[1-(3-methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-acetamide dihydrochloride


Compound 428

  • 3-Hydroxy-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 429

  • 3-Hydroxy-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 430

  • Cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 431

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 432

  • Cyclobutanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 433

  • Cyclopentanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 434

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 435

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride


Compound 436

  • Cyclohexanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 437

  • Cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 438

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 439

  • Cyclobutanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 440

  • Cyclopentanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 441

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 442

  • N-{1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride


Compound 443

  • Cyclohexanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 444

  • Cyclopropanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 445

  • N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride


Compound 446

  • Cyclobutanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 447

  • Cyclopentanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 448

  • N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride


Compound 449

  • N-[1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride


Compound 450

  • Cyclohexanecarboxylic acid [1-(2-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 451

  • Cyclopropanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 452

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 453

  • Cyclobutanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 454

  • Cyclopentanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 455

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 456

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyll-2-methoxy-acetamide hydrochloride


Compound 457

  • Cyclohexanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 458

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-propionamide hydrochloride


Compound 459

  • N-{1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-2-methoxy-acetamide hydrochloride


Compound 460

  • Cyclohexanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 461

  • Cyclopropanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 462

  • N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-isobutyramide dihydrochloride


Compound 463

  • Cyclobutanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl)-amide dihydrochloride


Compound 464

  • Cyclopentanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 465

  • N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-propionamide dihydrochloride


Compound 466

  • N-[1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-2-methoxy-acetamide dihydrochloride


Compound 467

  • Cyclohexanecarboxylic acid [1-(4-chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 468

  • Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chloro-phenyl)-propyl]-amide hydrochloride


Compound 469

  • Cyclopropanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chloro-phenyl)-propyl]-amide hydrochloride


Compound 470

  • Cyclopropanecarboxylic acid {l-(3,4-dichloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 471

  • Cyclopropanecarboxylic acid {l-(3,4-dichloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 472

  • Cyclopropanecarboxylic acid [1-(3,4-dichloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 473

  • Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chloro-phenyl)-propyl]-amide hydrochloride


Compound 474

  • Cyclopentanecarboxylic acid [3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-chloro-phenyl)-propyl]-amide hydrochloride


Compound 475

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 476

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 477

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 478

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 479

  • Cyclopentanecarboxylic acid {(S)-3-[l-oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 480

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 481

  • Cyclopentanecarboxylic acid {(S)-3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 482

  • Cyclopentanecarboxylic acid [(S)-3-(2-isobutyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride


Compound 483

  • Cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 484

  • Cyclopentanecarboxylic acid { (S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 485

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 486

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 487

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 488

  • Cyclopropanecarboxylic acid {(S)-3-[2- (4-difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 489

  • Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)-2,.8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 490

  • Cyclopropanecarboxylic acid [(S)-3-(2-cyclohexylmethyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride


Compound 491

  • Cyclopropanecarboxylic acid [(S)-3-(2-isobutyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide hydrochloride


Compound 492

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 493

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 494

  • N-[(S)-3-(2-Benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide hydrochloride


Compound 495

  • N-{(S)-3-[2-(4-Fluoro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 496

  • Cyclopropanecarboxylic acid {(S)-3-[1-oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-amide hydrochloride


Compound 497

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 498

  • N-{(S)-3-[2-(4-Chloro-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 499

  • N-{(S)-3-[2-(4-Cyano-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 500

  • N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 501

  • N-{(S)-3-[1-Oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 502

  • N-{(S)-3-[2-(4-Methylsulfanyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 503

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 504

  • 2-Methoxy-cyclopent-1-enecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide


Compound 505

  • 2-Methoxy-cyclopent-1-enecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide


Compound 506

  • Cyclopentanecarboxylic acid {1-(3,4-dichloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 507

  • Cyclopentanecarboxylic acid {1-(3,4-dichloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 508

  • Cyclopentanecarboxylic acid [1-(3,4-dichloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride


Compound 509

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide hydrochloride


Compound 510

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 511

  • Thiophene-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 512

  • Thiophene-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 513

  • (R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 514

  • (S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 515

  • Tetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 516

  • 3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 517

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 518

  • Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 519

  • 4,6-Dimethyl-pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride


Compound 520

  • Adamantane-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 521

  • N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-propionamide hydrochloride


Compound 522

  • N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2,2-dimethyl-propionamide hydrochloride


Compound 523

  • Thiophene-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 524

  • Thiophene-3-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 525

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 526

  • Tetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 527

  • N-{(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide dihydrochloride


Compound 528

  • Pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride


Compound 529

  • 4,6-Dimethyl-pyrimidine-5-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide trihydrochloride


Compound 530

  • Adamantane-1-carboxylic acid {(S)-3-[2- (4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 531

  • N-{(S)-3-[2-(4-Ethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 532

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 533

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 534

  • 2-Cyclopropyl-N-{(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 535

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 536

  • N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzenesulfonamide hydrochloride


Compound 537

  • Propane-2-sulfonic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 538

  • Propane-2-sulfonic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 539

  • Piperidine-1-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 540

  • Piperidine-1-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 541

  • Piperidine-1-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide hydrochloride


Compound 542

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride


Compound 543

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-chloro-phenyl)-urea hydrochloride


Compound 544

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxy-phenyl)-urea hydrochloride


Compound 545

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-chloro-phenyl)-urea hydrochloride


Compound 546

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxy-phenyl)-urea hydrochloride


Compound 547

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-chloro-phenyl)-urea hydrochloride


Compound 548

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxy-phenyl)-urea hydrochloride


Compound 549

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2,6-dimethyl-phenyl)-urea hydrochloride


Compound 550

  • 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride


Compound 551

  • 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride


Compound 552

  • 1-(2-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 553

  • 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea hydrochloride


Compound 554

  • 1-(3-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 555

  • 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea hydrochloride


Compound 556

  • -{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea hydrochloride


Compound 557

  • 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 558

  • 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride


Compound 559

  • 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea hydrochloride


Compound 560

  • 1-(2-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 561

  • 1-{3-[2-(4-methanesulfonylbenzyl)--oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea hydrochloride


Compound 562

  • 1-(3-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 563

  • 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea hydrochloride


Compound 564

  • 1-(4-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 565

  • 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea hydrochloride


Compound 566

  • 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea hydrochloride


Compound 567

  • 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea hydrochloride


Compound 568

  • Morpholine-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 569

  • Morpholine-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 570

  • 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 571

  • 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 572

  • {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester hydrochloride


Compound 573

  • {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride


Compound 574

  • {3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid cyclohexyl ester


Compound 575

  • {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclohexyl ester


Compound 576

  • {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclobutyl ester


Compound 577

  • {(S)-3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid cyclopentyl ester


Compound 578

  • [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclobutyl ester


Compound 579

  • [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclopentyl ester


Compound 580

  • [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid 1-methyl-cyclopentyl ester


Compound 581

  • [(S)-3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid cyclohexyl ester


Compound 582

  • {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride


Compound 583

  • {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride


Compound 584

  • [3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 585

  • {1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 586

  • {1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 587

  • [1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 588

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 589

  • {1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 590

  • {1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 591

  • [1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 592

  • {1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 593

  • [1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 594

  • {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride


Compound 595

  • {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride


Compound 596

  • {3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride


Compound 597

  • 3-(1-Oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid methyl ester dihydrochloride


Compound 598

  • {1-(2-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 599

  • {1-(2-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 600

  • [1-(2-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride


Compound 601

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 602

  • {1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 603

  • {3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid ethyl ester hydrochloride


Compound 604

  • {3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid ethyl ester dihydrochloride


Compound 605

  • 3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 606

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 607

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 608

  • [1-(4-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 609

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3,4-dimethoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 610

  • {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 611

  • {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid ethyl ester hydrochloride


Compound 612

  • [1-(3,4-Dimethoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 613

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 614

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 615

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 616

  • [1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid ethyl ester dihydrochloride


Compound 617

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 618

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 619

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 620

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3,4-dimethoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 621

  • (1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 622

  • {1-(3,4-Dimethoxy-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 623

  • [1-(3,4-Dimethoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride


Compound 624

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 625

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 626

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 627

  • [1-(3-Methoxy-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride


Compound 628

  • {1-(3-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl)-carbamic acid methyl ester hydrochloride


Compound 629

  • 1-(3-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride


Compound 630

  • {1-(4-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 631

  • {1-(4-Chloro-phenyl)-3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid methyl ester hydrochloride


Compound 632

  • [1-(4-Chloro-phenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid methyl ester dihydrochloride


Compound 633

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl}-carbamic acid methyl ester hydrochloride


Compound 634

  • [3-[2-(4-Bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 635

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 636

  • [3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 637

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride


Compound 638

  • [3-[2-(4-Methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride


Compound 639

  • (4-Bromophenyl)-[8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]dec-2-yl]-methanone hydrochloride


Compound 640

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester


Compound 641

  • 4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester


Compound 642

  • 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester


Compound 643

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide hydrochloride


Compound 644

  • N-benzyl-4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 645

  • 2-(4-bromobenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 646

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclohexyl-2-phenyl-butyramide hydrochloride


Compound 647

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclohexyl-n-methyl-2-phenyl-butyramide hydrochloride


Compound 648

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopropyl-2-phenyl-butyramide hydrochloride


Compound 649

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclobutyl-2-phenyl-butyramide hydrochloride


Compound 650

  • N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-n-methyl-2-phenyl-butyramide hydrochloride


Compound 651

  • N-cyclopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 652

  • N-cyclobutyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 653

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopentyl-2-phenyl-butyramide hydrochloride


Compound 654

  • 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-isopropyl-2-phenyl-butyramide hydrochloride


Compound 655

  • N-benzyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 656

  • 2-(4-methanesulfonylbenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl -butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 657

  • N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 658

  • N-cyclopentyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 659

  • N-isopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 660

  • 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide hydrochloride


Compound 661

  • N-benzyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 662

  • 2-(4-methoxybenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride


Compound 663

  • N-cyclohexyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 664

  • N-cyclopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 665

  • N-cyclobutyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 666

  • N-cyclopentyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 667

  • N-isopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide hydrochloride


Compound 668

  • Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 669

  • Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 670

  • Cyclopropanecarboxylic acid {(S)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 671

  • Cyclopropanecarboxylic acid {(S)-3-(2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide hydrochloride


Compound 672

  • N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 673

  • N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 674

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride


Compound 675

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide hydrochloride


Compound 676

  • N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 677

  • N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 678

  • N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 679

  • N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 680

  • N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 681

  • N-{(S)-3-[3-Oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 682

  • N-{(S)-3-[3-Oxo-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 683

  • N-{(S)-3-[3-Oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide hydrochloride


Compound 684

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 685

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 686

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 687

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 688

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 689

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 690

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 691

  • Cyclopropanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 692

  • 2-Cyclopropyl-N-{(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 693

  • N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 694

  • N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 695

  • N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 696

  • N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 697

  • N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 698

  • N-{(S)-3-[2-(4-Trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 699

  • N-{(S)-3-[2-(4-Trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide hydrochloride


Compound 700

  • 2-Cyclopropyl-N-{(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide hydrochloride


Compound 701

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 702

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 703

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 704

  • 4,4-Difluoro-cyclohexanecarboxylic acid {((S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 705

  • 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 706

  • Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 707

  • Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride


Compound 708

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide hydrochloride


Compound 709

  • Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide hydrochloride


Compound 710

  • N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 711

  • N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide hydrochloride


Compound 712

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide hydrochloride


Compound 713

  • N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide hydrochloride


Compound 714

  • Propane-2-sulfonic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 715 3-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-1,1-dimethyl-urea hydrochloride


Compound 716

  • Morpholine-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 717

  • 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide hydrochloride


Compound 718

  • {(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester hydrochloride


Compound 719

  • (S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride


    and pharmaceutically acceptable salts, hydrates or solvates thereof. While the compounds are listed above as their hydrochloride salts, this aspect of the invention includes their non-salt forms, as well as pharmaceutically acceptable salts, hydrates and solvates thereof.


It will be appreciated that the amount of a compound of the invention required for use in treatment will vary not only with the particular compound selected but also with the route of administration, the nature of the condition for which treatment is required and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian. In general however a suitable dose will be in the range of from about 0.1 to about 750 mg/kg of body weight per day, preferably in the range of 0.5 to 60 mg/kg/day, most preferably in the range of 1 to 20 mg/kg/day.


The desired dose may conveniently be presented in a single dose or as divided dose administered at appropriate intervals, for example as two, three, four or more doses per day.


The compound is conveniently administered in unit dosage form; for example containing 10 to 1500 mg, conveniently 20 to 1000 mg, most conveniently 50 to 700 mg of active ingredient per unit dosage form.


Ideally the active ingredient should be administered to achieve peak plasma concentrations of the active compound of from about 1 to about 75 μM, preferably about 2 to 50 μM, most preferably about 3 to about 30 μM. This may be achieved, for example, by the intravenous injection of a 0.1 to 5% solution of the active ingredient, optionally in saline, or orally administered as a bolus containing about 1 to about 500 mg of the active ingredient. Desirable blood levels may be maintained by a continuous infusion to provide about 0.01 to about 5.0 mg/kg/hour or by intermittent infusions containing about 0.4 to about 15 mg/kg of the active ingredient.


While it is possible that, for use in therapy, a compound of the invention may be administered as the raw chemical it is preferable to present the active ingredient as a pharmaceutical formulation. The invention thus further provides a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof together with one or more pharmaceutically acceptable carriers therefor and, optionally, other therapeutic and/or prophylactic ingredients. The carrier(s) must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.


Pharmaceutical formulations include those suitable for oral, rectal, nasal, topical (including buccal and sub-lingual), transdermal, vaginal or parenteral (including intramuscular, sub-cutaneous and intravenous) administration or in a form suitable for administration by inhalation or insufflation. The formulations may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association the active compound with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.


Pharmaceutical formulation suitable for oral administration may conveniently be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution, a suspension or as an emulsion. The active ingredient may also be presented as a bolus, electuary or paste. Tablets and capsules for oral administration may contain conventional excipients such as binding agents, fillers, lubricants, disintegrants, or wetting agents. The tablets may be coated according to methods well known in the art. Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), or preservatives.


The compounds according to the invention may also be formulated for parenteral administration (e.g. by injection, for example bolus injection or continuous infusion) and may be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilisation from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use.


For topical administration to the epidermis, the compounds according to the invention may be formulated as ointments, creams or lotions, or as a transdermal patch. Such transdermal patches may contain penetration enhancers such as linalool, carvacrol, thymol, citral, menthol and t-anethole. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or colouring agents.


Formulations suitable for topical administration in the mouth include lozenges comprising active ingredient in a flavoured base, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerin or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.


Pharmaceutical formulations suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art, and the suppositories may be conveniently formed by admixture of the active compound with the softened or melted carrier(s) followed by chilling and shaping in moulds.


Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such carriers as are known in the art to be appropriate.


For intra-nasal administration the compounds of the invention may be used as a liquid spray or dispersible powder or in the form of drops. Drops may be formulated with an aqueous or non-aqueous base also comprising one more dispersing agents, solubilising agents or suspending agents. Liquid sprays are conveniently delivered from pressurized packs.


For administration by inhalation the compounds according to the invention are conveniently delivered from an insufflator, nebulizer or a pressurized pack or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount.


Alternatively, for administration by inhalation or insufflation, the compounds according to the invention may take the form of a dry powder composition, for example a powder mix of the compound and a suitable powder base such as lactose or starch. The powder composition may be presented in unit dosage form in, for example, capsules or cartridges or e.g. gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator.


When desired the above described formulations adapted to give sustained release of the active ingredient may be employed.


When the compound (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof is used in combination with a second therapeutic active agent, the dose of each compound may be either the same as or different from that when the compound is used alone. Conventional doses and regimens are readily appreciated by those skilled in the art, including doses described in the Physicians Desk Reference, 56th edition, 2002.


The present invention is directed to the use of the compounds as modulators of CCR5 chemokine receptor activity. In particular, the compounds of the invention have been found to have activity in binding to the CCR5 receptor in the biological assay, as described in Example 15, generally with an IC50 value of less than 25 μM. The terms “modulator” or “modulation” are meant to include antagonism, agonism, mixed and partial antagonism and agonism.


Certain compounds of the present invention have also been tested in an assay for HIV activity, as described in Example 15, and generally having an IC50 value of less than 1 μM.


The purity and mass of the following examples were characterized by mass spectra (LC/MS) and or NMR spectra.


The following general schemes and examples are provided to illustrate various embodiments of the present invention and shall not be considered as limiting in scope.


The following abbreviations may be used as follows:

  • br broad
  • DCC 1,3-dicyclohexylcarbodiimide
  • DCE 1,2-dichloroethane
  • DCM dichloromethane
  • DIPEA N,N-diisopropylethylamine
  • DMF N,N-dimethylformamide
  • Hal halogen
  • LAH lithium aluminium hydride
  • TFA trifluoroacetic acid
  • THF tetrahydrofuran


The semi-preparative HPLC purification procedures used are described below:


Column: Phenomenex Luna C18(2), 5 microns, 10×250 mm


Buffer A: 3 mM HCl in H2O (pH 2.4-2.6)


Buffer B: acetonitrile


Method A: 15-55% B in 30 min. (1.4%/min)


Method B: 10-60% B in 50 min. (1%/min)


Method C: 20-50% B in 21 min. (1.4%/min)


Method D: 10-60% B in 42 min. (1.2%/min)


Method E: 15-45% B in 21 min. (1.4%/min) or


Buffer A: H2O


Buffer B: acetonitrile


Method F: 15-55% B in 40 min. (1%/min)
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Preparation 1
2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester



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Sodium hydride 600 mg (14.7 mmol) (60% suspension in mineral oil) was added in a 500 mL round bottom flask under nitrogen followed by 20 mL of anhydrous DMF and 2.5 g (9.8 mmol) of 1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester previously dissolved in 20 mL of anhydrous DMF. After agitating one hour at room temperature, 2.5 g (9.8 mmol) of 4-bromobenzylbromide diluted in 20 mL of anhydrous DMF were added and the reaction mixture was agitated an additional hour at room temperature. Then 100 mL of water were added and the solution was extracted with diethyl ether (2×150 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to yield 4.63 g 2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a yellow oil.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.12 (d, 2H), 4.31 (s, 2H), 3.8 (br d, 2H), 3.14 (t, 2H), 2.86 (br s, 2H), 1.89 (t, 2H), 1.54 (t×d, 2H), 1.37 (s, 9H), 1.32 (br d, 2H).


Preparation 2
2-(4-Bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride



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To 4.62 g of crude 2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester from preparation 1 was added 50 mL of 4N solution of dioxane/HCl. The reaction mixture was agitated 15 minutes at room temperature and 3.05 g (77.8%) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride was collected, as a colorless solid by filtration followed by trituration with diethyl ether.


1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.15 (br s, 1H), 8.83 (br s, 1H), 7.51 (d, 2H), 7.14 (d, 2H), 4.31 (s, 2H), 3.24 (br d, 2H), 3.15 (t, 2H), 2.92 (q, 2H), 1.95-1.84 (m, 4H), 1.56 (br d, 2H).


Preparation 3
2-(4-Methylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester



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This spiro compound was prepared as described in preparation 1, starting from 7 g (27.5 mmol) of 1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester, excepted it was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 20:80) yielding 8.05 g (74.9%) of 2-(4-methylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a pale yellow solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.21 (d, 2H), 7.11 (d, 2H), 4.3 (s, 2H), 3.8 (br d, 2H), 3.13 (t, 2H), 2.88 (br s, 2H), 2.43 (s, 3H), 1.89 (t, 2H), 1.54 (t×d, 2H), 1.38 (s, 9H), 1.31 (br d, 2H).


Preparation 4
2-(4-Methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester



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To a solution of 7.73 g (19.8 mmol) of 2-(4-ethylsulfanylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-arboxylic acid tert-butyl ester in 100 mL of THF, was added 18.2 g (29.7 mmol) of Oxone® in 100 mL of water. The reaction mixture was agitated overnight at room temperature. An aqueous solution of sodium hydroxide (1N, 100 mL) was added and the solution was extracted with DCM (2×200 mL). The combined organic layers were dried (Na2SO4), filtered and evaporated under reduced pressure to yield 6.62 g (79.1%) of 2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a white solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.81 (d, 2H), 7.37 (d, 2H), 4.41 (s, 2H), 3.76 (br d, 2H), 3.15 (t, 2H), 3.14 (s, 3H), 2.86 (br s, 2H), 1.89 (t, 2H), 1.52 (t×d, 2H), 1.33 (s, 9H), 1.29 (br d, 2H).


LC/MS: m/z 423.2 (MH+).


Preparation 5
2-(4-Methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride



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As described in preparation 2, 6.62 g (15.6 mmol) of 2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester was deprotected under acidic conditions giving access to 5.25 g (93.7%) of 2-(4- methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride as a white solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.04 (br s, 1H), 8.74 (br s, 1H), 7.83 (d, 2H), 7.39 (d, 2H), 4.42 (s, 2H), 3.21 (br d, 2H), 3.15 (t, 2H), 3.13 (s, 3H), 2.89 (q, 2H), 1.92 (t, 2H), 1.84 (t×d, 2H), 1.55 (br d, 2H).


Preparation 6
2-(4-Bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester



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This spiro compound was prepared as described in preparation 1, starting from 300 mg (1.18 mmol) of 3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester which was purified by flash chromatography on silica gel (ethyl acetate/hexanes 0:100 to 60:40) yielding 290 mg (58%) of 2-(4-bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester as a colorless oil.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.52 (d, 2H), 7.16 (d, 2H), 4.31 (s, 2H), 3.32 (m, 2H), 3.16 (br s, 2H), 3.02 (s, 2H), 2.25 (s, 2H), 1.4 (m, 4H), 1.35 (s, 9H).


Preparation 7
2-(4-Bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride



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As described in preparation 2, 290 mg (0.68 mmol) of 2-(4-bromobenzyl)-3-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester was deprotected under acidic conditions giving to 212 mg (86.6%) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride as a white solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 8.63 (br s, 2H), 7.52 (d, 2H), 7.17 (d, 2H), 4.32 (s, 2H), 3.07 (s, 2H), 3.00 (m, 4H), 2.33 (s, 2H), 1.65 (m, 4H).


EXAMPLE 1
2-(4-Bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-3-one hydrochloride (Compound 13)



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A mixture of 28.7 mg (80 μmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-3-one-hydrochloride, 24.4 mg (88 μmol) of 3,3-diphenylpropyl bromide and 33.1 mg (240 μmol) of potassium carbonate in 1.5 mL of anhydrous DMF was heated overnight at 60° C. After cooling to room temperature, 0.5 mL of water was added and the solution was extracted with DCM (2×2 mL). The crude material was purified by semi-preparative HPLC (method A) yielding 22.6 mg (51%) of Compound 13 as a white solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.96 (br s, 1H), 7.52 (d, 2H), 7.34-7.25 (m, 8H), 7.19-7.13 (m, 4H), 4.31 (s, 2H), 3.96 (q, 1H), 3.36 (m, 4H), 3.05 (d, 1H), 2.96-2.83 (m, 4H), 2.47 (s, 2H), 2.3 (d, 1H), 1.75 (m, 4H).


LC/MS: m/z 519.0 (MH+).


Table 1 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 1.

TABLE 1CPD#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY1embedded image2-(4-bromobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride477.87195.1% (LC/MS)2embedded image8-(2-phenylpropyl)-2-(4- trrifluoromethyl-benzyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride466.97299+(LC/MS)3embedded image2-(4-chlorobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride433.4294.8% (HPLC)4embedded image2-(4-fluorobenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride416.96590.5% (HPLC)5embedded image8-(3-phenyl-prropyl)-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride482.97192.2% (HPLC)6embedded image2-(4-methylbenzyl)-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride413.00293.7% (HPLC)7embedded image4-[1-oxo-8-(3-phenyl-propyl)-2,8- diaza-spiro[4.5]dec-2-ylmethyl]- benzonitrile hydrochloiride423.98594.1% (HPLC)8embedded image2-biphenyl-4-ylmethyl-8-(3-phenyl- propyl)-2,8-diaza-spiro[4.5]decan- 1-one hydrochloride475.07399+(HPLC)9embedded image2-naphthalen-2-ylmethyl-8-(3- phenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride449.03599+(HPLC)10embedded image2-(4-bromobenzyl)-8-(3-phenyl- butyl)-2,8-diaza-spiro[4.5]decan-1- one hydrochloride491.89890+(HPLC)11embedded image2-(4-bromobenzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride553.96999+(HPLC)12embedded image8-(3,3-diphenyl-propyl)-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]decan-1-one522.608100% (LC/MS)13embedded image2-(4-bromobenzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-3-one hydrochloride553.969>95% (LC/MS)14embedded image8-(3,3-diphenyl-propyl)-2-(3- phenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride503.126100% (LC/MS)15embedded image8-(3,3-diphenyl-propyl)-2-pyridin- 4-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.521100% (LC/MS)16embedded image8-(3,3-dipheenyl-propyl)-2-(4- methoxy-benzyl)-2,8-diaza- spiro[4.5]decan-1-one468.63793% (LC/MS)17embedded image8-(3,3-diphenyl-propyl)-2-(4- pyrazol-1-yl-benzyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride541.13598% (LC/MS)18embedded image2-benzothiazol-2-ylmethyl-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride532.14993% (LC/MS)19embedded image8-(3,3-diphenyl-propyl)-2-(4- methanesulfonyl-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride553.16398+(LC/MS)20embedded image8-(3,3-diphenyl-propyl)-2-(3- phenyl-allyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride501.1198% (LC/MS)21embedded image8-(3,3-diphenyl-propyl)-2- phenethyl-2,8-diaza- spiro[4.5]decan-1-one hydrochloride489.09998% (LC/MS)22embedded image2-(4-benzyloxy-benzyl)-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one544.735100% (LC/MS)23embedded image2-benzofuran-2-ylmethyl-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one478.63390% (LC/MS)24embedded image8-(3,3-diphenyl-propyl)-2-(4- isopropyl-benzyl)-2,8-diaza- spiro[4.,5]decan-1-one480.692100% (LC/MS)25embedded image2-(5-chloro-benzo[b]thiophen-3- ylmethyl)-8-(3,3-diphenyl-propyl)- 2,8-diaza-spiro[4.5]decan-1-one529.145100% (LC/MS)26embedded image8-(3,3-diphenyl-propyl)-2-(4-nitro- benzyl)-2,8-diaza-spiro[4.5]decan- 1-one483.609100% (LC/MS)27embedded image2-(4-bromo-benzyl)-8-(3-pyridin-2- yl-propyl)-2,8-diaza- spiro[4.5]decan-1-one442.39897% (HPLC)28embedded image2-[1-(4-bromopheenyl)-ethyl]-8-(3,3- diphenyl-propyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride567.99598+(LC/MS)29embedded image8-(3,3-diphenyl-propyl)-2-pyridin- 3-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.52198+(LC/MS)30embedded imageN-{4-[8-(3,3-diphenyl-propyl)-1- oxo-2,8-diaza-spiro[4.5]dec-2- ylmethyl]-phenyl}-acetamide hydrochloride532.12498+(LC/MS)31embedded image8-(3,3-diphenyl-propyl)-2-(6- trifluoromethyl-pyridin-3-ylmethyl)- 2,8-diaza-spiro[4.5]decan-1-one dihydrochloride580.51990+(LC/MS)32embedded image4-[8-(3,3-diphenyl-propyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-2- ylmethyl]-benzoic acid hydrochloride519.08198+(LC/MS)33embedded image8-(3,3-diphenyl-propyl)-2-pyridin- 2-ylmethyl-2,8-diaza- spiro[4.5]decan-1-one dihydrochloride512.52198+(LC/MS)34embedded image8-(3,3-diphenyl-propyl)-2-(4- trifluoromethylsulfanyl-benzyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride575.13690+(LC/MS)35embedded image8-(3,3-diphenyl-propyl)-2-(4- methyl-cyclohexylmethyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride495.14798+(LC/MS)36embedded image4-[8-(3,3-diphenyl-propyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-2- ylmethyl)-benzoic acid methyl ester hydrochloride533.10890.7% (LC/MS)37embedded image8-(3,3-diphenyl-propyl)-2-(5- trifluoromethyl-furan-2-ylmethyl)- 2,8-diaza-spiro[4.5]decan-1-one hydrochloride533.03198+(LC/MS)38embedded image8-(3,3-diphenyl-propyl)-2-(4-iodo- benzyl)-2,8-diaza-spiro[4.5]decan- 1-one564.504>95% (1H NMR)39embedded image2-(4-methanesulfonylbenzyl)-8-(3- phenyl-butyl)-2,8-diaza- spiro[4.5]decan-1-one hydrochloride491.09298+(LC/MS)




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Preparation 8
2-(4-Bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one



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To a stirred solution of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride (2.30 g, 6.39 mmol) in DMF (43 mL) was added DIPEA (4.2 mL, 3.80 mmol) followed by 3-chloro-1-phenyl-propan-1-one (1.08 g, 6.39 mmol). The reaction mixture was stirred at room temperature for 18 hours and then a saturated solution of NaHCO3 was added and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic extracts were washed with water (3×30 mL) and brine (30 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0% to 5% methanol/DCM) to give 2.53 g (87%) of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro(4.5]decan-1-one.



1H NMR (400 MHz, CDCl3): δ[ppm] 7.98-7.95 (m, 2H), 7.59-7.54 (m, 1H), 7.49-7.42 (m, 4H), 7.10-7.07 (m, 2H), 4.39 (s, 2H), 3.21 (t, 2H), 3.14 (t, 2H), 2.93-2.90 (m, 2H), 2.84 (t, 2H), 2.19-2.14 (m, 2H), 2.05-1.98 (m, 2H), 1.90 (t, 2H), 1.44-1.41 (m, 2H).


EXAMPLE 2
2-(4-Bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)- 3-phenylpropyl]-2,8-diaza-spiro[4.5]decan-1-one (Compound 40)



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To a stirred solution of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (157 mg, 0.35 mmol) in THF (3.5 mL) at 0° C. was added a 1.0 M solution of 2-methoxyphenylmagnesium bromide (1.4 mL, 1.4 mmol). The reaction mixture was warmed to room temperature and stirred for 18 hours. Water was added and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by semi-preparative HPLC (method F) to give 133 mg (69%) of Compound 40 as a yellow oil.



1H NMR (400 MHz, CDCl3): δ[ppm] 7.90 (d, 1H), 7.52-7.39 (m, 4H), 7.24 (m, 3H), 7.15 (m, 1H), 7.08-7.01 (m, 3H), 6.79 (d, 1H), 4.42-4.33 (m, 2H), 3.48 (s, 3H), 3.11 (t, 2H), 3.05 (m, 1H), 2.78 (m, 1H), 2.64 (m, 1H), 2.50-2.45 (m, 2H), 2.34 (m, 1H), 2.23 (m, 1H), 2.00-1.88 (m, 3H), 1.85 (m, 2H), 1.45-1.40 (m, 2H).


EXAMPLE 3
2-(4-Bromobenzyl)-8-[3-(2-methoxyphenyl)-3-phenylpropyl]-2,8-diaza-spiro[4.5]decan-1-one (Compound 44)



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To trifluoroacetic acid (1.4 mL) at room temperature was added portion wise sodium borohydride (67 mg, 1.775 mmol). This mixture was stirred at room temperature for 30 minutes and then a solution of 2-(4-bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (40 mg, 0.071 mmol) in DCM (0.5 mL) was slowly added. The reaction mixture was stirred at room temperature for 20 hours and then poured into an ice cold solution of sodium hydroxide (5 mL). The mixture was extracted with ethyl acetate (3×5 mL) and the combined organic extracts were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (0% to 4% methanol/DCM) to give 24 mg (61%) of Compound 44 as a yellow oil.



1H NMR (400 MHz, CDCl3): δ[ppm] 7.43 (d, 2H), 7.38-7.32 (m, 1H), 7.26-7.2 (m, 5H), 7.12-6.94 (m, 5H), 6.35 (t, 1H), 4.36 (s, 2H), 3.7 (s, 3H), 3.2-2.9 (m, 5H), 2.1-1.9 (m, 2H), 1.85 (t, 2H).


Table 2 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 2.

TABLE 2CPDMOL#MOL STRUCTURECOMPOUND NAMEWTPURITY40embedded image2-(4-bromobenzyl)-8-[3-hydroxy-3- (2-methoxyphenyl)-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one563.53293% BY HPLC41embedded image2-(4-bromobenzyl)-8-[3-hydroxy-3- (3-methoxyphenyl)-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one563,53299% BY HPLC42embedded image2-(4-bromobenzyl)-8-(3-hydroxy-3- phenyl-3-thiophen-2-yl-propyl)-2,8- diaza-spiro[4.5]decan-1-one539.53597% BY HPLC43embedded image2-(4-bromobenzyl)-8-(3-hydroxy-3- phenyl-butyl)-2,8-diaza- spiro[4.5]decan-1-one471.43699% BY HPLC44embedded image2-(4-bromobenzyl)-8-[3-(2- methoxyphenyl)-3-phenyl-propyl]- 2,8-diaza-spiro[4.5]decan-1-one547.53499% BY HPLC45embedded image2-(4-bromobenzyl)-8-[3-(3- chlorophenyl)-3-hydroxy-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one567.95294% BY HPLC46embedded image2-(4-bromobenzyl)-8-[3-(4- chlorophenyl)-3-hydroxy-3-phenyl- propyl]-2,8-diaza-spiro[4.5]decan- 1-one567.95297% BY HPLC47embedded image2-(4-bromobenzyl)-8-[3-(3- chlorophenyl)-3-phenyl-propyl]-2,8- diaza-spiro[4.5]decan-1-one551.95396% BY HPLC48embedded image32-(4-bromobenzyl)-8-(3-phenyl-3- thiophen-2-yl-propyl)-2,8-diaza- spiro[4.5]decan-1-one523.53689% BY HPLC49embedded image2-(4-bromobenzyl)-8-[3-(4- chlorophenyl)-3-phenyl-propyl]-2,8- diaza-spiro[4.5]decan-1-one551.95396% BY HPLC




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EXAMPLE 4
2-(4-Bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (Compound 50)



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To a cold stirred solution of 2-(4-bromobenzyl)-8-(3-oxo-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (350 mg, 0.769 mmol) in THF-methanol (7:3, 4.0 mL) was added NaBH4 (85 mg, 2.3 mmol). After stirring for one hour, the reaction mixture was then quenched with an aqueous solution of sodium hydroxide (1N). The reaction mixture was portioned in a separating funnel and the aqueous solution was then extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine and dried over sodium sulfate. Evaporation of the solvent gave


Compound 50 as an oil (300 mg, 85.4%).



1H NMR (400 MHz, CDCl3): δ[ppm] 7.44 (d×d, 2H), 7.40-7.3 (m, 4H), 7.26-7.23 (m, 1H), 7.09 (d×d, 2H), 4.94 (d×d, 1H), 4.39 (s, 2H), 3.14 (t, 2H), 3.1-2.9 (m, 2H), 2.7-2.5 (m, 2H), 2.3-1.8 (m, 9H), 1.6-1.4 (m, 2H).


EXAMPLE 5

8-(3-Benzyloxy-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride (Compound 51)



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To an ice-cold stirred suspension of sodium hydride (23 mg, 60% in mineral oil, 0.6 mmol) in THF (0.5 mL) was added dropwise a solution of 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (91.4 mg, 0.2 mmol) in THF (0.6 mL). After stirring the reaction mixture at 0° C. for 45 minutes benzyl bromide (0.071 mL, 0.6 mmol) was added and the mixture was then stirred overnight. The mixture was quenched with water and extracted with ethyl acetate (3×5 mL). The combined organic extracts were washed with brine, dried (Na2SO4), concentrated, and purified by semi-preparative HPLC (method B) to yield Compound 51 as a white solid (13.0 mg, 22%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.53-7.41 (m, 9H), 7.37 (t, 2H), 7.29 (m, 1H), 7.14 (t, 2H), 5.65 (d×d, 1H), 4.69 (m, 1H), 4.59 (d, 2H), 4.31 (d, 2H), 3.62 (m, 1H), 3.45 (m, 2H), 3.32 (m, 2H), 3.17 (t×d, 2H), 2.15 (m, 2H), 2.02-1.89 (m, 5H), 1.75 (m, 1H).


EXAMPLE 6
2-(4-Bromobenzyl)-8-(3-phenoxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (Compound 52)



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To a stirred solution of 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one (65 mg, 0.142 mol) and phenol (13.3 mg, 0.142 mmol) in THF was added triphenylphosphine (37 mg, 0.142 mmol) followed by diethylazodicarboxylate (DEAD) (0.023 mL, 0.142 mmol). After stirring for 24 hours, the reaction mixture was then concentrated and purified on silica gel preparative TLC using 20% ethyl acetate-hexanes as eluent. Compound 52 was isolated as oil (12 mg, 15.8%).



1H NMR (CDCl3, 400 MHz): δ[ppm] 7.40-7.0 (m, 11H), 6.82-6.76 (m, 3H), 5.19 (d×d, 1H), 4.32 (s, 2H), 3.06 (t, 2H), 2.72 (m, 2H) , 2.5-1.7 (m, 10H) , 1.4-1.25 (m, 2H)


LC/MS: m/z 534.5 (MH+).
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EXAMPLE 7
{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid tert-butyl ester (Compound 53)



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To a solution of 2.16 g (6 mmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride in 100 mL of anhydrous DCE were added successively 1.5 g (6 mmol) of (3-oxo-1-phenylpropyl)-carbamic acid tert-butyl ester and 836 μL (6 mmol) of triethylamine. The reaction mixture was agitated at room temperature for 10 minutes before adding 2 g (9 mmol) of sodium triacetoxyborohydride. After an overnight agitation, 60 mL of satured solution of sodium bicarbonate was added. The solution was then extracted with DCM, dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica gel eluting with methanol/DCM (0% to 5%) giving


Compound 53 as a white solid (2.97 g, 88.9%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.45 (d, 1H), 7.27 (m, 4H), 7.19 (m, 1H), 7.12 (d, 2H), 4.52 (q, 1H), 4.32 (s, 2H), 3.11 (t, 2H), 2.69 (m, 2H), 2.17 (m, 2H), 1.91 (br t, 2H), 1.82 (t, 2H), 1.71 (m, 4H), 1.33 (s, 9H), 1.29 (m, 2H).


Preparation 9
8-(3-Amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one



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To 2.97 g (5.33 mmol) of {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid tert-butyl ester was added 48 mL of a 20% TFA solution in DCM. The reaction mixture was agitated one hour at room temperature before neutralizing with 120 mL of an aqueous solution of sodium hydroxide (1N). The solution was then extracted with DCM, dried over sodium sulfate, filtered and evaporated in vacuo yielding 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one as a pale yellow oil (2.43 g, 100%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.32-7.24 (m, 4H), 7.17 (m, 1H), 7.12 (d, 2H), 4.31 (s, 2H), 3.81 (t, 1H), 3.1 (t, 2H), 2.72 (d×d, 2H), 2.25-2.16 (m, 2H), 1.98 (br s, 2H), 1.86 (br q, 2H), 1.81 (t, 2H), 1.73-1.59 (m, 4H), 1.29 (br d, 2H).


EXAMPLE 8
N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzamide hydrochloride (Compound 54)



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To 100 mg (100 μmol, loading of 1 mmol/g) of phenylcarboxyl activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one dissolved in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL) . The filtrates were collected and evaporated in vacuo. The crude mixture was purified by semi-preparative HPLC (method A) and 14.1 mg (39.4%) of Compound 54 was isolated as a colorless solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.64 (br s, 1H), 8.91 (d, 1H), 7.88 (d, 2H), 7.55-7.42 (m, 7H), 7.35 (t, 2H), 7.25 (t, 1H), 7.14 (d, 2H), 5.12 (m, 1H), 4.33 (s, 2H), 3.46 (m, 2H), 3.16 (m, 4H), 2.97 (m, 2H), 2.35 (m, 1H), 2.2 (m, 1H), 1.98 (m, 3H), 1.83 (t, 1H), 1.6 (br d, 2H).


LC/MS: m/z 562.0 (MH+).


Table 3 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 4.

TABLE 3CPD #MOL STRUCTURECOMPOUND NAMEMOL WTPURITY53embedded image{3-[2-(4-bromobvenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- carbamic acid tert-butyl ester556.541>95% (1H NMR)54embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride596.99498+(LC/MS)55embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5υdec-8-yl]-1-phenyl- propyl}-2,6-dimethyl-benzamide hydrochloride625.04798+(LC/MS)56embedded imageCyclohexanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride603.04198+(LC/MS)57embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-acetamide hydrochloride611.0298+(LC/MS)58embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2,4,6-trimethyl-phenyl)- acetamide hydrochloride653.10198+(LC/MS)59embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-propionamide hydrochloride625.04798+(LC/MS)60embedded image{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- methyl-carbamic acid tert-butyl ester570.568>95% (1H NMR)61embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-benzamide hydrochloride611.0298+(LC/MS)62embedded imageCyclohexanecarboxylic acid {3-[2-(4- bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- methyl-amide hydrochloride617.06898+(LC/MS)63embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-2-phenyl-acetamide hydrochloride625.04798+(LC/MS)64embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spirto[4.5]dec-8-yl]-1-phenyl- propyl}-N-methyl-2-(2,4,6-trimethyl- phenyl)-acetamide hydrochloride667.12898+(LC/MS)65embedded image[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-carbamic acid tert-butyl ester478.63395% BY HPLC66embedded image{3-[2-(4-methanesulfonyl-benzyl)-1- -oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid tert-butyl ester555.73694% (LC- MS)67embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)- propyl]-carbamic acid tert-butyl ester590.986>95% (1H NMR)68embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride534.92394.6% (LC/MS)69embedded imageCyclopropanecarboxylic acid {3-[2-(4- bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride560.96195.2% (LC/MS)70embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-issobutyramide hydrochloride562.97695% (LC/MS)71embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride577.00398+(LC/MS)72embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-chloro-benzmaide hydrochloride631.43998+(LC/MS)73embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-methoxy-benzamide hydrochloride627.01998+(LC/MS)74embedded imagePyridine-2-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5υdec-8-yl]-1-phenyl-propyl}- amide hydrochloride634.44393.7% (LC/MS)75embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methoxy-benzamide hydrochloride631.43998+(LC/MS)76embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-chloro-benzamide hydrochloride627.01998+(LC/MS)77embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride634.44398+(LC/MS)78embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-4-chloro-benzamidehydrochloride631.43998+(LC/MS)79embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-4-methoxy-benzamide hydrochloride627.01998+(LC/MS)80embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isonicotinamide dihydrochloride634.44398+(LC/MS)81embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3,4-dichloro-benzamide hydrochloride665.88498+(LC/MS)82embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3,4-dimethoxy-benzamide hydrochloride657.04598+(LC/MS)83embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-chloro-phenyl)-acetamide hydrochloride645.46594.8% (LC/MS)84embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)85embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-chloro-phenyl)-acetamide hydrochloride645.46592.9% (LC/MS)86embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)87embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-pyridin-3-yl-acetamide dihydrochloride648.46995+(LC/MS)88embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(4-methoxy-phenyl)- acetamide hydrochloride641.04698+(LC/MS)89embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3,4-dichloro-phenyl)- acetamide hydrochloride679.91195+(LC/MS)90embedded imageTetrahydro-pyran-4-carboxylic acid{3- [2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dcec-8-yl]-1-phenyl-propyl}- amide hydrochloride605.01395+(LC/MS)91embedded imageCyclopentanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride589.01498+(LC/MS)92embedded imageCyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride574.98798+(LC/MS)93embedded imageCycloheptanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride617.06898+(LC/MS)94embedded imageN-{3-[2-(4-bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclohexyl-acetamide hydrochloride617.06898+(LC/MS)95embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride486.05298+(LC/MS)96embedded imageCyclopropanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride512.0998+(LC/MS)97embedded imageN-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochlooride514.10698+(LC/MS)98embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride528.13398+(LC/MS)99embedded image2-chloro-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56895+(LC/MS)100embedded image2-methoxy-N-{3-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)101embedded imagePyridine-2-carboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide dihydrochloride585.57298+(LC/MS)102embedded image3-chloro-N-{3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56898+(LC/MS)103embedded image3-methoxy-N-{3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)104embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride585.57298+(LC/MS)105embedded image4-chloro-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride582.56898+(LC/MS)106embedded image4-methoxy-N-{3-[2-(4-methoxy-benzyl)- 1-0oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride578.14998+(LC/MS)107embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isonicotinamide dihydrochloride585.57298+(LC/MS)108embedded image(R)-cyclohexanecarboxylicc acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5]dec-8-yl]-1-phenyl-propyl}-asmide566.58100% (LC/MS)109embedded image3,4-dichloro-N-{3-[1-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- benzamide hydrochloride617..01398+(LC/MS)110embedded image3,4-dimethoxy-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- benzamide hydrochloride608.17598+(LC/MS)111embedded image2-(2-chloro-phenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride596.59598+(LC/MS)112embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(2-methox-phenyl)-acetamide hydrochloride592.17698+(LC/MS)113embedded image2-(3-chlorophenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- dspiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride5596.59598+(LC/MS)114embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3-methoxyphenyl)-acetamide hydrochloride592.17698+(LC/MS)115embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-pyridin-3-yl-acetamide dihydrochloride599.59990+(LC/MS)116embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(4-methoxyphenyl)-acetamide hydrochloride592.17698+(LC/MS)117embedded image2-(3,4-dichlorophenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride631.0495+(LC/MS)118embedded imageTetrahydro-pyran-4-carboxylic acid{3- [2-(4-methoxybeenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride556.14395+(LC/MS)119embedded imageCyclopentanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride540.14498+(LC/MS)120embedded imageCyclobutanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride526.11795+(LC/MS)121embedded imageCycloheptanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-prropyl}- amide hydrochloride568.19798+(LC/MS)122embedded image2-cyclohexyl-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride568.19798+(LC/MS)123embedded image(S)-cyclohexanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spirro[44.5]dec-8-yl]-1-phenyl-propyl}- amide566.5899% BY HPLC124embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopentyl-acetamide hydrochloride603.04198+(LC/MS)125embedded imageFuran-2-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride586.95598+(LC/MS)126embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spirro[4.5]dec-8-yl]-1-phenyl- propyl}-2-ethyl-butyramide hydrochloride591.0398+(LC/MS)127embedded imageThiophene-2-carboxylic acid {3-[2-(4- brom-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride603.02298+(LC/MS)128embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-(3,4-dimethoxyphenyl)- acetamide hydrochloride671.07298+(LC/MS)129embedded image2-cyclopentyl-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride554.17198+(LC/MS)130embedded imageFuran-2-carboxylic acid {3-[2-(4 methox-benzyl)-1-oxxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride538.08498+(LC/MS)131embedded image2-ethyl-N-{3-[2-(4-methoxybenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-butyramide hydrochloride542.1698+(LC/MS)132embedded imageThiophene-2-carbopxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride554.15198+(LC/MS)133embedded image2-(3,4-dimethoxy-phenyl)-N-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride622.20298+(LC/MS)134embedded imageCyclohexanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spirro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride554.17198+(LC/MS)135embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-beenzamide hydrochloride548.12398+(LC/MS)136embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-acetamide hydrochloride562.1598+(LC/MS)137embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride534.11798+(LC/MS)138embedded imageCyclopropanecarboxylic acid {3-[2-(4- methanesulfonylben zyl)-1-oxxo-2,8- diaza-spirro[4.5]dec-8-yl]-1-phenyl- propyl} amide hydrochloride560.15598+(LC/MS)139embedded imageN-{3-[2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride562.17195% (LC/MS)140embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-methyl-butyramide hydrochloride576.19898+(LC/MS)141embedded image2-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63398+(LC/MS)142embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-methoxy-benzamide hydrochloride626.21498+(LC/MS)143embedded imagePyridine-2-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide dihydrochloride633.63794.4% (LC/MS)144embedded image3-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63394.1% (LC/MS)145embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-methoxy-benzamide hydrochloride626.21498+(LC/MS)146embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-nictotinamide dihydrochloride633.63798+(LC/MS)147embedded image4-chloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride630.63398+(LC/MS)148embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-4-methoxy-benzamide hydrochloride626.21498+(LC/MS)149embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isonicotinamide dihydrochloride633.63798+(LC/MS)150embedded image3,4-dichloro-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-benzamide hydrochloride665.07898+(LC/MS)151embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- pheenyl-propyl}-3,4-dimethoxy- benzamide hydrochloride656.2498+(LC/MS)152embedded image2-(2-chlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride644.6688.1% (LC/MS)153embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(2-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)154embedded image2-(3-chlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride644.6693% (LC/MS)155embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(3-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)156embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-benzamide hydrochloride596.18898+(LC/MS)157embedded image(S)-cyclohexanecarboxylic acid [3-(2- benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide487.684>95% (HPLC)158embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-(4-methoxyphenyl)- acetamide hydrochloride640.24198+(LC/MS)159embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2-phenyl-acetamide hydrochloride610.21598+(LC/MS)160embedded image2-(3,4-dichlorophenyl)-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride679.10594+(LC/MS)161embedded imageCyclopentanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride588.20998+(LC/MS)162embedded imageCyclobutanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride574.18298+(LC/MS)163embedded imageCycloheptanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride616.26298+(LC/MS)164embedded image2-cyclohexyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride616.26298+(LC/MS)165embedded image2-cyclopentyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride602.23698+(LC/MS)166embedded imageFuran-2-carboxylic acid {3-[2-(4- meethanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride586.14998+(LC/MS)167embedded image2-ethyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-butyramide hydrochloride590.22598+(LC/MS)168embedded imageThiophene-2-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride602.21698+(LC/MS)169embedded image2-(3,4-dimethoxyphenyl)-N-{3-[2-(4- methanesulfonyl-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride670.26798+(LC/MS)170embedded imageCyclohexanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride602.23698+(LC/MS)171embedded image4-methyl-cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride616.26298+(LC/MS)172embedded image2-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-ylk)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)173embedded image3-chloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/MS)174embedded image4-chloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/MS)175embedded image4-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmeethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)176embedded imageCyclohexanecarboxylic acid [3-[2-(4- bromobernzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)- propyl]-amide hydrochloride637.48694.3% (LC/MS)177embedded imageN-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-benzamide hydrochloride631.43998+(LC/MS)178embedded imageN-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-2-phenyl- acetamide hydrochloride645.46598+(LC/MS)179embedded image{1-(3-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}carbamic acid tert-butyl ester542.116>95% (1H NMR)180embedded image{1-(3,4-dichlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester576.561>95% (1H NMR)181embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-acetamide dihydrochloride493.47690+(LC/MS)182embedded imageCyclopropanecarboxylic acid [3-(1-oxo- 2-pyrridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride519.51398+(LC/MS)183embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-0 diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-issobutyramide dihydrochloride521.52998+(LC/MS)184embedded image3-methyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-butyramide dihydrochloride535.55698+(LC/MS)185embedded image2-chloro-NM-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride589.99298+(LC/M S)186embedded imagePyridin-2-carboxylic acid [3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide trihydrochloride592.99598+(LC/MS)187embedded image3-methoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride585.57298+(LC/MS)188embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-nicotinamide trihydrochloride592.99598+(LC/MS)189embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-isonicotinamide trihydrochloride592.99598+(LC/MS)190embedded image3,4-dichloro-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride624.43798+(LC/MS)191embedded image3,4-dimethoxy-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-benzamide dihydrochloride615.59898+(LC/MS)192embedded image2-(2-chlorophenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride604.01898+(LC/MS)193embedded image2-(2-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59998+(LC/MS)194embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl)-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-benzamide dihydrochloride555.54698+(LC/MS)195embedded image2-(3-chloro-phenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride604.01898+(LC/MS)196embedded image2-(3-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59993.3% (LC/MS)197embedded image2-(4-methoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride599.59998+(LC/MS)198embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[45]dec-8-yl)-1-phenyl- propyl]-2-phenyl-acetamide dihydrochloride569.57393.3% (LC/MS)199embedded image2-(3,4-dichloro-phenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride638.46391.5% (LC/MS)200embedded imageCyclopentanecarboxylic acid [3-(1-oxo- 2-pyrridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride547.56798+(LC/MS)201embedded image{1-(3-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>95% (1H NMR)202embedded imageCyclobutanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride533.5495+(LC/MS)203embedded imageCycloheptanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl}- amide dihydrochloride575.62194.5% (LC/MS)204embedded image2-cyclohexyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-acetamide dihydrochloride575.62193.4% (LC/MS)205embedded image2-cyclopentyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-acetamide dihydrochloride561.59494.6% (LC/MS)206embedded imageFuran-2-carboxylic acid [3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride545.50898+(LC/MS)207embedded image2-ethyl-N-[3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)- 1-phenyl-propyl]-butyramide dihydrochloride549.58393.9% (LC/MS)208embedded imageThiophene-2-carboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-phenyl- propyl]-amide dihydrochloride561.57598+(LC/MS)209embedded image2-(3,4-dimethoxyphenyl)-N-[3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl-propyl]- acetamide dihydrochloride629.62598+(LC/MS)210embedded imageCyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[44.5]dec-8-yl)-1-phenyl-propyl]- amide dihydrochloride561.59498+(LC/MS)211embedded image4-methyl-cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride575.62192.1% (LC/MS)212embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.567>99% (LC/MS)213embedded image[3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester537.697>99% (LC/MS)214embedded image(S)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride534.92398+(LC/MS)215embedded image(S)-cyclopropanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride560.96198+(LC/MS)216embedded image(S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride562.87698+(LC/MS)217embedded image(S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-methyl-butyramide hydrochloride577.00398+(LC/MS)218embedded image(S)-cyclopentanecarboxylic acid {3-[2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride589.01498+(LC/MS)219embedded image(S)-cyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride574.98798+(LC/MS)220embedded image[3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]carbamic acid tert-butyl ester537.69795% BY HPLC221embedded image{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-carbamic acid tert-butyl ester557.52999% BY HPLC222embedded image{3-[2-(4-methoxybenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-carbamic acid tert-butyl ester508.65999% BY HPLC223embedded image{1-(3,4-dichlorophenyl)-3-[22-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[44.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester624.626>95% (1H NMR)224embedded image2-cyclopropyl-N-{3-[2-(4- methoxybenzyl)-1-oxxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- acetamide hydrochloride526.11798+(LC/MS)225embedded image2-cyclopropyl-N-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride574.18294.4% (LC/MS)226embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.56795% BY HPLC227embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride574.98798+(LC/MS)228embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spirro[4.5]dec-8-yl]-1-(3,4- dimethoxyphenyl)-propyl]-carbamic acid tert-butyl ester616.59399% BY HPLC229embedded image{1-(3,4-dimethoxyphenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester567.72297% BY HPLC230embedded imageTetrahydro-pyran-4-carboxylic acid {3- [2-(4-methanesulfonylbenzyl)-1-oxo- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride604.208>95% (HPLC)231embedded image[3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid tertbutyl ester585.762>99% (HPLC)232embedded image(S)-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid tert-butyl ester555.736>99% (HPLC)233embedded image{3-0[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-carbamic acid tert-butyl ester556.72495% BY HPLC234embedded image{1-(3,4-dimethoxyphenyl)-3-[2-(4- meethanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester615.78797% BY HPLC235embedded image{1-(4-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester542.116>90% (HNMR)236embedded image{1-(2-chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester542.116>90% (HNMR)237embedded image{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-carbamic acid tert-butyl ester513.699>90% (HNMR)238embedded image[3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester585.76295% BY HPLC239embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chlorophenyl)- propyl]-carbamic acid tert-butyl ester590.986>90% (HNMR)240embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chlorophenyl)- propyl]-carbamic acid tert-butyl ester590,986>90% (HNMR)241embedded image{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-carbamic acid tert-butyl ester562.569>90% (HNMR)242embedded image{1-(4-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>90% (HNMR)243embedded image{1-(2-chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- carbamic acid tert-butyl ester590.181>90% (HNMR)244embedded image{3-[2-(4-methanesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid tert-butyl ester561.764>90% (HNMR)245embedded image(S)-N-{3-[2-(4-0methanesulfonylbenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide525.7198+(LC/MS)246embedded image[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester586.56789% BY HPLC247embedded image[3-[2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-carbamic acid tert-butyl ester537.69786% BY HPLC248embedded image[1-(2-chlorophenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-carbamic acid tert-butyl ester513.078>90% (HNMR)249embedded image[1-(3-chlorophenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-carbamic acid tert-butyl ester513.078>90% (HNMR)250embedded image[1-(3,4-dichlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-preopyl]-carbamic acid tert-butyl ester547.523>90% (HNMR)251embedded image[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]-carbamic acid tert-butyl ester484.661>90% (HNMR)252embedded image(S)-8-[3-(cyclopropanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride560.15598+(LC/MS)253embedded image(S)-8-[3-(cyclopentanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride588.20998+(LOC/MS)254embedded image(S)-8-[3-(cyclohexanecarbonyl-amino)- 3-phenyl-propyl]-2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride602.23698+(LC/MS)255embedded image(S)-8-[3-(cyclopropanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybenzyl)- 1-oixo-2,8-diaza-spiro[4.5]decane hydrochloride512.0998+(LC/MS)256embedded image(S)-8-3-isobutyrylamino-3-phenyl- propyl)-2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]decane hydrochloride514.01698+(LC/MS)257embedded image(S)-8-[3-(cyclopentanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]decane hydrochloride540.14498+(LC/MS)258embedded image(S)-8-[3-(cyclohexanecarbonyl-amino)- 3-phenyl-propyl]-2-(4-methoxybeenzyl)- 1-oxxo-2,8-diaza-spiro[4.5]decane hydrochloride554.17198+(LC/MS)259embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-isobutyramide hydrochloride569.00598+(LC/MS)260embedded imageCyclobutanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride581.01698+(LC/MS)261embedded imageCyclopentanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride595.04298+(LC/MS)262embedded imageN-{3-[2-(4-bromo-enzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-propionamide hydrochloride554.97898+(LC/MS)263embedded imageN-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-sspiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-2-methoxy-acetamide hydrochloride570.97798+(LC/MS)264embedded imageCyclohexanecarboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride609.06998+(LC/MS)265embedded imageCyclopropanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride518.11898+(LC/MS)266embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-issobutyramide hydrochloride520.13498+(LC/MS)267embedded image[3-[2-(4-methasnesulfonylbenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxyphenyl)-propyl]-carbamic acid tert-butyl ester585.76289% BY HPLC268embedded imageCyclobutanecarboxylic acid {3-0[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride532.14598+(LC/MS)269embedded imageCyclopentanecarboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride546.17298°(LC/MS)270embedded imageN-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- sdiaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-propionamide hydrochloride506.10798+(LC/MS)271embedded image2-methoxy-N -{3-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-acetamide hydrochloride522.10698+(LC/MS)272embedded imageCyclohexanecarboxylicc acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride560.19998+(LC/MS)273embedded imageCyclopropane carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride566.18398+(LC/MS)274embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-isobutyramide hydrochloride568.19998+(LC/MS)275embedded imageCyclobutanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride580.2195.2% (LC/MS)276embedded imageCyclopentanecarboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride594.23798+(LC/MS)277embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5υdec-8-yl]-1- thiophen-2-yl-propyl}-propionamide hydrochloride554.17298+(LC/MS)278embedded imageN-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-2-methoxy- acetamide hydrochloride570.17198+(LC/MS)279embedded imageCyclohexanecarboxylic acid {3-[22-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-thiophen-2- yl-propyl}-amide hydrochloride608.62498+(LC/MS)280embedded imageCyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride525.54298+(LC/MS)281embedded imageN-[3-(1-oxxo-22-pyridin-3-ylmethyl-22,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]-isobutyramide dihydrochloride527.55798+(LC/MS)282embedded imageCyclobutanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride539.56898+(LC/MS)283embedded imageCyclopentanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spirro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride553.59598+(LC/MS)284embedded imageN-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-thiophen-2- yl-propyl]propionamide dihydrochloride513.53180.8% (LC/MS)285embedded imageCyclohexanecarboxylic acid [3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-thiophen-2-yl- propyl]-amide dihydrochloride567.62294.3% (LC/MS)286embedded imageCyclopropanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride595.40698+(LC/MS)287embedded imageN-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-isobutyramide hydrochloride597.42198+(LC/MS)288embedded imageCyclobutanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride609.43298+(LC/MS)289embedded imageCyclopentanecarboxylic acid [3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)- propyl]-amide hydrochloride623.45998+(LC/MS)290embedded imageN-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-propionamide hydrochloride583.39598+(LC/MS)291embedded imageN-[3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-2-methoxy- acetamide hydrochloride599.39498+(LC/MS)


Table 3a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 4.

TABLE 3aCPD #MOL STRUCTURECOMPOUND NAMEMOL WTPURITY292embedded image2-Cyclopropyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride574.18299% (LC/MS)293embedded image2-Cyclopropyl-N-{(S)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride526.11799% (LC/MS)294embedded imageCyclopentanecarboxylic acid [(S)- 3-(2-benzy-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride510.11898+ (LC/MS)295embedded imageCyclopropanecarboxylic acid [(S)- 3-(2-benzyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride482.06491.6% (LC/MS)296embedded imageCyclohexancarboxylic acid [3-(2- (4-bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(3- chlorophenyl)-propyl]-amide hydroxhloride637.48698% (LC/MS)297embedded imageCyclopropanecarboxylic acid {1-(3- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)298embedded imageN-{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)299embedded imageCyclobutanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56298% (LC/MS)300embedded imageCyclopentanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,87-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride574.58998% (LC/MS)301embedded imageN-{1-(3-Chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- propionamide hydropchloride543.52495% (LC/MS)302embedded imageN-{1-(3-Chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diazaq- spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)303embedded imageCyclohexanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride588.61698% (LC/MS)304embedded imageCyclopropylcarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride594.698% (LC/MS)305embedded imageN-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride596.61698% (LC/MS)306embedded imageCyclobutanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- amide hydrochloride608.62798% (LC/MS)307embedded imageCyclopentanecarboxylic acid {1-(3- chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]propyl}- amide hydrochloride622.65498% (LC/MS)308embedded imageN-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- propionamide hydrochloride582.58998% (LC/MS)309embedded imageN-{1-(3-Chlorophenyl)-3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride598.58895% (LC/MS)310embedded imageCyclopropanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride553.95893.2% (LC/MS)311embedded imageN-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- isobutyramide dihydrochloride555.97494.1% (LC/MS)312embedded imageCyclobutanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)313embedded imageCyclopentanecarboxylic acid [1-(3- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01298% (LC/MS)314embedded imageN-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94893.8% (LC/MS)315embedded imageN-[1-(3-Chlorophenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94694.4% (LC/MS)316embedded imageCyclohexanecarboxylic acid [1-(3- chlorophenyl)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-amide dihydrochloride596.03994.7% (LC/MS)317embedded imageCyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-2-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloricde519.51398% (LC/MS)318embedded imageCyclopentanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-2-ylmethyl-2,8- diaza-spiro[45]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)319embedded imageCyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride519.51398% (LC/MS)320embedded imageCyclopentanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)321embedded imageCyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-4-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride519.51398% (LC/MS)322embedded imageCyclopropanecarboxylic acid [(S)- 3-(1-oxo-2-pyridin-4-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide dihydrochloride547.56798% (LC/MS)323embedded imageCyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)324embedded imageCyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)325embedded imageCyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)326embedded imageCyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)327embedded imageCyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride499.05298% (LC/MS)328embedded imageCyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}-amide hydrochloride527.10598% (LC/MS)329embedded imageCyclopentanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-amide dihydrochloride626.46398% (LC/MS)330embedded imageN-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-propionamide dihydrochloride586.39898% (LC/MS)331embedded imageN-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-2-methoxy- acetamide dihydrochloride602.39898% (LC/MS)332embedded imageCyclopropanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride549.53998% (LC/MS)333embedded imageN-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-isobutyramide dihydrochloride551.55598% (LC/MS)334embedded imageCyclobutanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride563.56698% (LC/MS)335embedded imageCyclopentanecarboxylic acid {3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-amide dihydrochloride563.56698% (LC/MS)336embedded imageN-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-propionamide dihydrochloride537.52898% (LC/MS)337embedded image2-Methoxy-N-{3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-acetamide dihydrochloride553.52798% (LC/MS)338embedded imageCyclopropanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-amide dihydrochloride597.60498% (LC/MS)339embedded imageN-{3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-isobutylamide dihydrochloride599.6298% (LC/MS)340embedded imageCyclobutanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-amide dihydrochloride611.63198% (LC/MS)341embedded imageCyclopropanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-amide dihydrochloride598.40998% (LC/MS)342embedded imageN-{3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-isobutyramide dihydrochloride600.42598% (LC/MS)343embedded imageCyclobutanecarboxylic acid {3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-02-yl- propyl}-amide dihydrochloride612.43698% (LC/MS)344embedded imageCyclopentanecarboxylic acid {3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl-]-1- pyridin-2-yl-propyl}-amide dihydrochloride625.65898% (LC/MS)345embedded imageN-{3-[2-(4-Methanesulfonyl- benzyl}-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-pyridin-2-yl- propyl}-propionamide dihydrochloride585.59395.2% (LC/MS)346embedded imageN-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide560.71591% (HPLC)347embedded image(R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-meethanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)348embedded image(S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)349embedded imageTetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methansulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide553.7299% (HPLC)350embedded image(R)-N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-propionamide587.78184% (HPLC)351embedded image3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide565.73184% (HPLC)352embedded image(S)-N-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-phenyl-propionamide587.78186% (HPLC)353embedded image(R)-N-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-2-phenyl- propionamide510.67897% (HPLC)354embedded image(S)-N-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-2-phenyl- propionamide510.67899% (HPLC)355embedded image(R)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl-1-phe3nyl-propyl]-amide476.61797% (HPLC)356embedded image(S)-Tetrahydro-furan-2-carboxylic acid [(S)-3-(1-oxo-22-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide476.61799% (HPLC)357embedded imageTetrahydro-furan-3-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide476.61798% (HPLC)358embedded image3-Oxo-cyclopentaecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide488.62896% (HPLC)359embedded imageN-[(S)-3-(2-Oxo-2-pyridin-2- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutylamide448.60797% (HPLC)360embedded imageN-[(S)-3-(1-Oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutylamide448.60799% (HPLC)361embedded imageN-[(S)-3-(1-Oxo-2-pyridin-4- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-isobutyramide448.60798% (HPLC)362embedded imageN-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-4- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60690% (HPLC)363embedded imageN-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-2- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60698% (HPLC)364embedded imageN-{(S)-3-[1-Oxo-2-(1-oxy-pyridin-3- ylmethyl)-2,8-diaza-spiro[4.5]dec- 8-yl]-1-phenyl-propyl}- isobutyramide464.60699% (HPLC)365embedded image1-Methyl-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide565.775100% (LC/MS)366embedded image1-Methyl-cyclohexanecarboxylic acid{(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide579.802>80% (LC/MS)367embedded image2-Cyclopentyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide579.802100% (LC/MS)368embedded image2-Cyclopentyl-N-{(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide579.802100% (LC/MS)369embedded image1-Methyl-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide488.672100% (LC/MS)370embedded image1-Methyl-cyclohexanecarboxylic acid[(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide502.699100% (LC/MS)371embedded image2-Cyclopentyl-N-[(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-propionamide502.699100% (LC/MS)372embedded image2-Cyclopentyl-N-[(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-propionamide502.699100% (LC/MS)373embedded imageCyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride590.98698% (LC/MS)374embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- isobutyramide hydrochloride593.00298% (LC/MS)375embedded imageCyclobutanecarboxylic acid [3[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride605.01398% (LC/MS)376embedded imageTetrahydro-pyran-2-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide567.74799% (HPLC)377embedded imageN-{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-2,2-dimethyl- propionamide hydrochloride534.16198% (LC/MS)378embedded imageN-{3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-2,2-dimethyl-propionamide hydrochloride582.22698% (LC/MS)379embedded imageN-{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-2,2- dimethyl-propionamide hydrochloride562.57893.9% (LC/MS)380embedded imageN-{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)381embedded imageN-[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2,2- dimethyl-propionamide dihydrochloride570.00198% (LC/MS)382embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)383embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2,2-dimethyl-propionamide hydrochloride610.64398% (LC/MS)384embedded image`1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride532.14598% (LC/MS)385embedded image1-Methyl-cyclopropanecarboxylic acid {3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-thiophen-2-yl- propyl}-amide hydrochloride580.2198% (LC/MS)386embedded image1-Methyl-cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-33-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-amide dihydrochloride539.56898% (LC/MS)387embedded image1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56292.4% (LC/MS)388embedded image1-Methyl-cyclopropanecarboxylic acid {1-(3-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)389embedded image1-Methyl-cyclopropanecarboxylic acid [1-(3-chloro-phenyl)-3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride567.98592.5% (LC/MS)390embedded image1-Methyl-cyclopropanecarboxylic acid {1-(2-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)391embedded image1-Methyl-cyclopropanecarboxylic acid {1-(4-chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)392embedded imageTetrahydro-pyran-2-carboxylic acid [(S)-3-(1-oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-amide490.64494% (HPLC)393embedded imageCyclopentaecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride619.0498% (LC/MS)394embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- propionamide hydrochloride578.97598% (LC/MS)395embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)propyl]-2- methoxy-acetamide hydrochloride594.97498% (LC/MS)396embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-2- cyclopropyl-acetamide hydrochloride605.01398% (LC/MS)397embedded imageCyclohexanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-amide hydrochloride633.06798% (LC/MS)398embedded imageCyclopropanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8 diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride542.11698% (LC/MS)399embedded imageN-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-tl]-1-(2- methoxy-phenyl)-propyl]- issobutyramide hydrochloride544.13298% (LC/MS)400embedded imageCyclobutanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride556.14398% (LC/MS)401embedded imageCyclopentanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride570.1798% (LC/MS)402embedded imageN-[3-[2-(4-Methoxy-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]- propionamide hydrochloride530.10598% (LC/MS)403embedded image2-Methoxy-N-[3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-acetamide hydrochloride546.10498% (LC/MS)404embedded image2-Cyclopropyl-N-[3[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-acetamide hydrochloride556.14398% (LC/MS)405embedded imageCyclohexanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)propyl]-amide hydrochloride584.19698% (LC/MS)406embedded imageCyclopropanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride590.18198% (LC/MS)407embedded imageN-[3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-isobnutyramide hydrochloride592.19798% (LC/MS)408embedded imageCyclobutanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- meethoxy-phenyl)-propyl]-amide hydrochloride604.20898% (LC/MS)409embedded imageCyclopentanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride618.23598% (LC/MS)410embedded imageN-[3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-propionamide hydrochloride578.1798% (LC/MS)411embedded imageN-[3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-methoxy- phenyl)-propyl]-2-methoxy- acetamide hydrochloride594.16998% (LC/MS)412embedded image2-Cyclopropyl-N-[3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-acetamide hydrochloride604.20898% (LC/MS)413embedded imageCyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride590.98698% (LC/MS)414embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- isobutyramide hydrochloride593.00298% (LC/MS)415embedded imageCyclobutanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride605.01398% (LC/MS)416embedded imageCyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-methoxy- phenyl)-propyl]-amide hydrochloride619.0498% (LC/MS)417embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- propionamide hydrochloride578.97598% (LC/MS)418embedded imageN-[3-[2-(4-Bromo-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-2- methoxy-acetamide hydrochloride594.97498% (LC/MS)419embedded imageCyclopropanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride542.11698% (LC/MS)420embedded imageN-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- isobutyramide hydrochloride544.13298% (LC/MS)421embedded imageCyclobutanecarboxylic acid [3-[3- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride556.14398% (LC/MS)422embedded imageCyclopentanecarboxylic acid [3-[2- (4-methoxy-benzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-amide hydrochloride570.1798% (LC/MS)423embedded imageN-[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]- propionamide hydrochloride530.10598% (LC/MS)424embedded imageCyclohexanecarboxylic acid [3-[2- (4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-amide hydrochloride632.26198% (LC/MS)425embedded imageCyclopentanecarboxylic acid [1-(3- methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride577.59398% (LC/MS)426embedded imageN-[1-(3-Methoxy-phenyl)-3-(1-oxo- 2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride537.52898% (LC/MS)427embedded image2-Methoxy-NM-[1-(3-methoxy- phenyl)-3-(1-oxo-2-pyridin-3- ylmeethyl-2,8-diaza-spiro[4.5]dec-8- yl)-propyl]-acetamide dihydrochloride553.52798% (LC/MS)428embedded image3-Hydroxy-cyclopentanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide567.74790% (HPLC)429embedded image3-Hydroxy-cyclopentanecarboxylic acid [(S)-3-(1-oxo-2-pyridin-3- ylmethyl-2,8-diaza-spiro[4.5]dec-8- yl)-1-phenyl-propyl]-amide490.64497% (HPLC)430embedded imageCyclopropanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)431embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)432embedded imageCyclobutanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride560.56298% (LC/MS)433embedded imageCyclopentanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-amide hydrochloride574.58998% (LC/MS)434embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- propionamide hydrochloride534.52498% (LC/MS)435embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)436embedded imageCyclohexanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride588.61698% (LC/MS)437embedded imageCyclopropanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride594.698% (LC/MS)438embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-isobutyramide hydrochloride596.61698% (LC/MS)439embedded imageCyclobutanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride608.62798% (LC/MS)440embedded imageCyclopentanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride622.65498% (LC/MS)441embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-propionamide hydrochloride582.58998% (LC/MS)442embedded imageN-{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-2-methoxy-acetamide hydrochloride598.58898% (LC/MS)443embedded imageCyclohexanecarboxylic acid {1-(2- chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride636.68198% (LC/MS)444embedded imageCyclopropanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide hydrochloride553.95898% (LC/MS)445embedded imageN-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- isobutyramide dihydrochloride555.97498% (LC/MS)446embedded imageCyclobutanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)447embedded imageCyclopentanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01298% (LC/MS)448embedded imageN-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94898% (LC/MS)449embedded imageN-[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94693.6% (LC/MS)450embedded imageCyclohexanecarboxylic acid [1-(2- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride596.03998+ (LC/MS)451embedded imageCyclopropanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.53598% (LC/MS)452embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- meethoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.55198% (LC/MS)453embedded imageCyclobutanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride560.56298% (LC/MS)454embedded imageCyclopentanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride574.58998% (LC/MS)455embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- propionamide hydrochloride534.52498% (LC/MS)456embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-2- methoxy-acetamide hydrochloride550.52398% (LC/MS)457embedded imageCyclohexanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4-methoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride588.61698% (LC/MS)458embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-propionamide hydrochloride592.58998% (LC/MS)459embedded imageN-{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-0spiro[4.5]dec-8-yl]- propyl}-2-methoxy-acetamide hydrochloride598.58898% (LC/MS)460embedded imageCyclohexanecarboxylic acid {1-(4- chloro-phenyl)-3-[2-(4- meethanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride636.68198% (LC/MS)461embedded imageCyclopropanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride553.95898% (LC/MS)462embedded imageN-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl- isobutyramide dihydrochloride555.97498% (LC/MS)463embedded imageCyclobutanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride567.98598% (LC/MS)464embedded imageCyclopentanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmeethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride582.01295% (LC/MS)465embedded imageN-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- propionamide dihydrochloride541.94893.5% (LC/MS)466embedded imageN-[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-2- methoxy-acetamide dihydrochloride557.94698% (LC/MS)467embedded imageCyclohexanecarboxylic acid [1-(4- chloro-phenyl)-3-(1-oxo-2-pyridin- 3-ylmethyl-2,8-diaza-spiro[4.5]dec- 8-yl)-propyl]-amide dihydrochloride596.03994.4% (LC/MS)468embedded imageCyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chloro- phenyl)-propyl]-amide hydrochloride595.40698% (LC/MS)469embedded imageCyclopropanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chloro- phenyl)-propyl]-amide hydrochloride595.40698% (LC/MS)470embedded imageCyclopropanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride580.9898% (LC/MS)471embedded imageCyclopropanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-amide hydrochloride629.04598% (LC/MS)472embedded imageCyclopropanecarboxylic acid [1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride588.40498% (LC/MS)473embedded imageCyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(2-chloro- phenyl)-propyl]-amide hydrochloride623.45998% (LC/MS)474embedded imageCyclopentanecarboxylic acid [3-[2- (4-bromo-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-(4-chloro- phenyl)-propyl]-amide hydrochloride623.45998% (LC/MS)475embedded imageCyclopentanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride528.10898% (LC/MS)476embedded imageCyclopentanecarboxylic acid {(S)- 3[2-(4-chloro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride544.56398% (LC/MS)477embedded imageCyclopentanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride535.12898% (LC/MS)478embedded imageCyclopentanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride576.12498% (LC/MS)479embedded imageCyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(4-trifluoromethoxy- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride594.11498% (LC/MS)480embedded imageCyclopentanecarboxylic acid {(S)- 3-[2-(4-methylsulfanyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride556.21198% (LC/MS)481embedded imageCyclopentanecarboxylic acid {(S)- 3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride576.18198% (LC/MS)482embedded imageCyclopentanecarboxylic acid [(S)- 3-(2-isobutyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride476.10195% (LC/MS)483embedded imageCyclopentanecarboxylic acid {(S)- 3-[2-(4-meethanesulfonyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride588.20998% (LC/MS)484embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride540.11498% (LC/MS)485embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride500.05598% (LC/MS)486embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-chloro-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]1-phenyl- propyl}-amide hydrochloride516.5198% (LC/MS)487embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride507.07498% (LC/MS)488embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride548.0798% (LC/MS)489embedded imageCyclopropanecarboxylic acid {(S)- 3-[1-oxo-2-(4-pyrazol-1-yl-benzyl)- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride548.12798% (LC/MS)490embedded imageCyclopropanecarboxylic acid [(S)- 3-(2-cyclohexylmethyl-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride488.11299% (LC/MS)491embedded imageCyclopropanecarboxylic acid [(S)- 3-(2-isobutyl-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide hydrochloride448.04798% (LC/MS)492embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methanesulfonyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride560.15598% (LC/MS)493embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride512.0998% (LC/MS)494embedded imageN-[(S)-3-(2-Benzyl-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl)-1-phenyl- propyl]-isobutyramide hydrochloride484.0895% (LC/MS)495embedded imageN-{(S)-3-[2-(4-Fluoro-benzyl)-1- oxo-2,8-diaza-spirro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride502.0790% (LC/MS)496embedded imageCyclopropanecarboxylic acid {(S)- 3-[1-oxxo-2-(4-trifluoromethoxy- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride566.0698% (LC/MS)497embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methylsulfanyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride528.15798% (LC/MS)498embedded imageN-{(S)-3-[2-(4-Chloro-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride518.52595% (LC/MS)499embedded imageN-{(S)-3-[2-(4-Cyano-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride509.0998% (LC/MS)500embedded imageN-{(S)(-3-[2-(4-Difluoromethoxy- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride556.08690% (LC/MS)501embedded imageN-{(S)-3-[1-Oxo-2-(4- trifluoromethoxy-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride568.07691.3% (LC/MS)502embedded imageN-{(S)-3-[2-(4-Methylsulfanyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride530.17390% (LC/MS)503embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride514.10695% (LC/MS)504embedded image2-Methoxy-cyclopent-1- enecarboxylic acid {(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide579.75887% (HPLC)505embedded image2-Methoxy-cyclopent-1- enecarboxylic acid [(S)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-1-phenyl- propyl]-amide502.65584% (HPLC)506embedded imageCyclopentanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride609.03498% (LC/MS)507embedded imageCyclopentanecarboxylic acid {1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride616.45798% (LC/MS)508embedded imageCyclopentanecarboxylic acid [1- (3,4-dichloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]-amide dihydrochloride616.45798% (LC/MS)509embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-propionamide hydrochloride500.09100% (LC/MS)510embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-2,2-dimethyl- propionamide hydrochloride528.14100% (LC/MS)511embedded imageThiophene-2-cxarboxcylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spirto[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride554.16100% (LC/MS)512embedded imageThiophene-3-carboxylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride554.16100% (LC/MS)513embedded image(R)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)514embedded image(S)-Tetrahydro-furan-2-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spirro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)515embedded imageTetrahydro-furan-3-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride542.12100% (LC/MS)516embedded image3-Oxo-cyclopentanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride554.13100% (LC/MS)517embedded image4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride590.16100% (LC/MS)518embedded imageTetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride557.14100% (LC/MS)519embedded image4,6-Dimethyl-pyrimidine-5- carboxylic acid {(S)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide trihydrochloride651.08100% (LC/MS)520embedded imageAdamantane-1-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride606.2590% (LC/MS)521embedded imageN-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-propionamide hydrochloride548.1596% (LC/MS)522embedded imageN-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2,2-dimethyl-propionamide hydrochloride576.2100% (LC/MS)523embedded imageThiophene-2-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride602.22100% (LC/MS)524embedded imageThiophene-3-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride602.22100% (LC/MS)525embedded image4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride638.22100% (LC/MS)526embedded imageTetrahydro-pyran-4-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride603.82100% (LC/MS)527embedded imageN-{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-nicotinamide dihydrochloride633.64100% (LC/MS)528embedded imagePyrimidine-5-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[44.5]dec-8-yl]-1- phenyl-propyl}-amide trihydrochloride671.09100% (LC/MS)529embedded image4,6-Dimethyl-pyrimidine-5- carboxylic acid {(S)-3-[2-(4- methanesulfonyl-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide trihydrochloride699.1490% (LC/MS)530embedded imageAdamantene-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride654.32100% (LC/MS)531embedded imageN-{(S)-3-[2-(4-Ethoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride528.14100% (LC/MS)532embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride526.12100% (LC/MS)533embedded image4,4-Difluoro-cyclohexanecarboxylic acod {(S)-3-[2-(4-methoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride590.16100% (LC/MS)534embedded image2-Cyclopropyl-N-{(S)-3-[2-(4- methanesulfonyl-bgenzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-acetamide hydrochloride574.19100% (LC/MS)535embedded image4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride638.22100% (LC/MS)




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EXAMPLE 9
N-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-benzenesulfonamide hydrochloride (Compound 536)



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To 83 mg (100 μmol, loading of 1.2 mmol/g) of benzenesulfonate activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one diluted in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL) . The filtrates were collected and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method A) yielding 10.6 mg (27.9%) of Compound 536 as a colorless solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.64 (br s, 1H), 8.44 (d, 1H), 7.53 (m, 4H), 7.44 (t, 1H), 7.35 (m, 2H), 7.12 (m, 7H), 4.33 (m, 3H), 3.35 (m, 2H), 3.16 (t, 3H), 3.05 (m, 1H), 2.9 (m, 2H), 2.08 (m, 1H), 1.95 (m, 4H), 1.82 (m, 1H), 1.56 (br d, 2H).


LC/MS: m/z 598.1 (MH+).


Table 4 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 5.

TABLE 4CPD#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY537embedded imagePropane-2-sulfonic acid {(S)-3-[2-(4- methoy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride550.16100% (LC/MS)538embedded imagePropane-2-sulfonic acid {(S)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride598.2390% (LC/MS)




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EXAMPLE 10
1-{3-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenylpropyl}-3-phenyl-urea hydrochloride (Compound 542)



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To 27.3 mg (60 μmol) of 8-(3-amino-3-phenylpropyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one, diluted in 1 mL of anhydrous THF, was added 9.66 mg (80 μmol) of phenylisocyanate dissolved in 0.5 mL of anhydrous THF. The reaction mixture was agitated overnight at room temperature and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method C) yielding 18.9 mg (51.5%) of Compound 542 as a pale yellow solid.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.45 (br s, 1H), 8.64 (d, 1H), 7.51 (d, 2H), 7.37 (m, 6H), 7.28 (m, 1H), 7.21-7.13 (m, 4H), 6.93 (d, 1H), 6.87 (t×t, 1H), 4.8 (m, 1H), 4.33 (s, 2H), 3.48 (br t, 2H), 3.18-2.94 (m, 5H), 2.15 (m, 2H), 1.96 (m, 4H), 1.83 (m, 1H), 1.6 (br d, 2H).


Table 5 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 6.

TABLE 5CPD#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY539embedded imagePiperidine-1-carboxylic acid {3-[2-(4- bromobenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride604.0393.5% (LC/MS)540embedded imagePiperidine-1-carboxylic acid {3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride555.1794.5% (LC/MS)541embedded imagePiperidine-1-carboxylic acid {3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride603.22493.3% (LC/MS)542embedded image1-{3-[2-(4-bromophenyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-urea hydrochloride612.00898+(LC/MS)543embedded image1-0{3-[2-(4-bromobhenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-chloro-phenyl)-urea hydrochloride646.45394.6% (LC/MS)544embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)545embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-chloro-phenyl)-urea hydrochloride646.45398+(LC/MS)546embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)547embedded image1-{3-([2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-chloro-phenyl)-urea hydrochloride646.45398+(LC/MS)548embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-methoxy-phenyl)-urea hydrochloride642.03498+(LC/MS)549embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2,6-dimethyl-phenyl)-urea hydrochloride640.06298+(LC/MS)550embedded image1-{3-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-naphtalen-1-yl-urea hydrochloride662.06898+(LC/MS)551embedded image1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-phenyl-urea hydrochloride563.13898+(LC/MS)552embedded image1-(2-chlorophenyl)-3-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride597.58395+(LC/MS)553embedded image1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(2-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)554embedded image1-(3-chlorophenyl)-3-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride597.58398+(LC/MS)555embedded image1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(3-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)556embedded image-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-(4-methoxyphenyl)-urea hydrochloride593.16498+(LC/MS)557embedded image1-(2,6-dimethylphenyl)-33-{3-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- urea hydrochloride591.19298+(LC/MS)558embedded image1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-3-naphthalen-1-yl-urea hydrochloride613.19898+(LC/MS)559embedded image1-{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-phenyl-urea hydrochloride611.20398+(LC/MS)560embedded image1-(2-chlorophenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)561embedded image1-{3-[2-(4-methanesulfonylbenzyl)- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(2-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)562embedded image1-(3-chlorophenyl)-3-{3-[2-(4- methanesulfonylbernzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)563embedded image1-{3-[2-(4-methanesulfonylbeenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(3-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)564embedded image1-(4-chlorophenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride645.64898+(LC/MS)565embedded image1-‡3-[22-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-(4-methoxyphenyl)- urea hydrochloride641.22998+(LC/MS)566embedded image1-(2,6-dimethylphenyl)-3-{3-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-urea hydrochloride639.52798+(LC/MS)567embedded image1-{3-[2-(4-methanesulfonylnemzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-3-naphthalen-1-yl- urea hydrochloride661.26398+(LC/MS)


Table 5a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 6.

TABLE 5aCPDPUR-#MOL STRUCTURECOMPOUND NAMEMOL WTITY568embedded imageMorpholine-4-carboxylic acid {(S)-3- [2-(4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride557.14100% (LC/ MS)569embedded imageMorpholine-4-carboxylic acid {(S)-3- [2-(4-methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride605.290% (LC/ MS)570embedded image3,3-Difluoro-pyrolidine-1-carboxylicp acid {(S)-3-[2-(4-methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloiride577.12100% (LC/ MS)571embedded image3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3-[2-(4-methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl-propyl}- amide hydrochloride625.18100% (LC/ MS)




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EXAMPLE 11
(3-[2-(4-Methanesulfonylbenzyl)-1-oxo-2,8-diaza-5 spiro[4.5]dec-8-yl]-1-phenylpropyl}-carbamic acid methyl ester hydrochloride (Compound 572)



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To a stirred solution of 8-(3-amino-3-phenylpropyl)-2-(4-methanesulfonylbenzyl)-2,8-diaza-spiro[4.5]decan-1-one (27.3 mg, 0.06 mmol) in DMF-DCE (1:1, 1.0 mL) was sequentially added triethylamine (0.01 mL, 0.072 mmol) and dimethyldicarbonate (0.07 mL, 0.066 mmol). The reaction mixture was stirred overnight at room temperature, concentrated and purified by semi-preparative HPLC (method D) affording Compound 572 (17.2 mg, 52%) as a white powder.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.62 (br s, 1H), 7.88 (d, 2H), 7.44 (d, 2H), 7.33 (m, 4H), 7.25 (m, 1H), 4.59 (m, 1H), 4.47 (s, 2H), 3.50 (s, 3H), 3.42 (m, 2H), 3.22 (t, 2H), 3.19 (s, 3H), 3.09-2.91 (m, 4H), 2.12-1.95 (m, 6H), 1.86 (t, 1H), 20 1.64 (br d, 2H)


LC/MS: m/z 513.6 (MH+).


Table 6 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 7.

TABLE 6CPDMOL#MOL STRUCTURECOMPOUND NAMEWTPURITY572embedded image{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic methyl ester hydrochloride550.11698+(LC/MS)573embedded image{3-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-carbamic acid ethyl ester hydrochloride564.14398+(LC/MS)


Table 6a of compounds illustrates some additional compounds of the present invention that were synthesized using the procedure described in scheme 7.

TABLE 6aCPD#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY574embedded image{3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-carbamic acid cyclohexyl ester582.7783% (LC/MS)575embedded image{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclohexyl ester581.7899% (LC/MS)576embedded image{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclobutyl ester553.7399% (LC/MS)577embedded image{(S)-3-[2-(4-Methanesulfonyl- benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-carbamic acid cyclopentyl ester567.7599% (LC/MS)578embedded image[(S)-3-(1-Oxo-2-pyridin-3-ylmeethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclobutyl ester476.6298% (LC/MS)579embedded image[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclopentyl ester490.6599% (LC/MS)580embedded image[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid 1- methyl-cyclopentyl ester504.6897% (LC/MS)581embedded image[(S)-3-(1-Oxo-2-pyridin-3-ylmethyl- 2,8-diaza-spiro[4.5]dec-8-yl)-1- phenyl-propyl]-carbamic acid cyclohexyl ester504.68100% (LC/MS)582embedded image{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride570.9898+(LC/MS)583embedded image{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid ethyl ester hydrochloride522.1198+(LC/MS)584embedded image[3-(1-Oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-carbamic acid ethyl ester dihydrochloride529.5398+(LC/MS)585embedded image{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid ethyl ester hydrochloride550.5298+(LC/MS)586embedded image{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride598.5998+(LC/MS)587embedded image[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)588embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- chloro-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride599.498+(LC/MS)589embedded image{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid ethyl ester hydrochloride550.5298+(LC/MS)590embedded image{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride598.5998+(LC/MS)591embedded image[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)592embedded image{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- varbamic acid ethyl ester hydrochloride550.5298+(LC/MS)593embedded image[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride557.9598+(LC/MS)594embedded image{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride556.9598+(LC/MS)595embedded image{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride508.0898+(LC/MS)596embedded image{3-[2-(4-Methanesulfonyl=benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-carbamic acid methyl ester hydrochloride556.1498+(LC/MS)597embedded image[3-(1-Oxo-2-pyridin-3-ylmethyl-2,8- diaza-spiro[4.5]dec-8-yl)-1- thiophen-2-yl-propyl]-carbamic acid methyl ester dihydrochloride515.598+(LC/MS)598embedded image{1-(2-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)599embedded image{1-(2-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride554.5698+(LC/MS)600embedded image[1-(2-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)601embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- chloro-phenyl)-propyl]-carbamic acid methyl ester hydrochloride585.3798+(LC/MS)602embedded image{1-(3-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)603embedded image{3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-pyridin- 2-yl-propyl}-carbamic acid ethyl ester hydrochloride602.4198% (LC/MS)604embedded image{3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- pyridin-2-yl-propyl}-carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)605embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998% (LC/MS)606embedded image[3-[2-(4-Methoxy-benzyl)-1-oxxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride546.1198% (LC/MS)607embedded image[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (4-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798% (LC/MS)608embedded image[1-(4-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)609embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3,4- dimethoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride625.0198% (LC/MS)610embedded image{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[44.5]dec-8-yl]-propyl}- carbamic acid ethyl ester hydrochloride576.1498% (LC/MS)611embedded image{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid ethyl ester hydrochloride624.298% (LC/MS)612embedded image[1-(3,4-Dimethoxy-phenyl)-3-(1- oxo-2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride583.5698% (LC/MS)613embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998% (LC/MS)614embedded image[3-[2-(4-Methoxy-beenzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)propyl]-carbamic acid ethyyl ester hydrochloride546.1198% (LC/MS)615embedded image[3-[2-(4-Methanesulfonyl-bhenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (3-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798% (LC/MS)616embedded image[1-(3-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid ethyl ester dihydrochloride553.5398% (LC/MS)617embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698% (LC/MS)618embedded image[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(4- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898% (LC/MS)619embedded image[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (4-methoxy-phenyl)propyl]- carbamic acid methyl ester hydrochloride580.1598% (LC/MS)620embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3,4- dimeethoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride610.9998% (LC/MS)621embedded image{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- meethoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}- carbamic acid meethyl ester hydrochloride562.1198% (LC/MS)622embedded image{1-(3,4-Dimethoxy-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride610.1798% (LC/MS)623embedded image[1-(3,4-Dimethoxy-phenyl)-3-(1- oxo-2-pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride569.5398% (LC/MS)624embedded image[3-[2-(4-Bromo-benzyl)-1-oxxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698% (LC/MS)625embedded image[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(3- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898% (LC/MS)626embedded image[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (3-methoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride580.1598% (LC/MS)627embedded image[1-(3-Methoxy-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride539.5198% (LC/MS)628embedded image{1-(3-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride584.5698+(LC/MS)629embedded image[1-(3-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)630embedded image{1-(4-Chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]propyl}- carbamic acid methyl ester hydrochloride536.598+(LC/MS)631embedded image{1-(4-Chloro-phenyl)-3-[2-(4- methanesulfonyl-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]- propyl}-carbamic acid methyl ester hydrochloride584.5698+(LC/MS)632embedded image[1-(4-Chloro-phenyl)-3-(1-oxo-2- pyridin-3-ylmethyl-2,8-diaza- spiro[4.5]dec-8-yl)-propyl]- carbamic acid methyl ester dihydrochloride543.9298+(LC/MS)633embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride580.9698+(LC/MS)634embedded image[3-[2-(4-Bromo-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride594.9998+(LC/MS)635embedded image[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid methyl ester hydrochloride532.0898+(LC/MS)636embedded image[3-[2-(4-Methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1-(2- methoxy-phenyl)-propyl]-carbamic acid ethyl ester hydrochloride546.1198+(LC/MS)637embedded image[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (2-methoxy-phenyl)-propyl]- carbamic acid methyl ester hydrochloride580.1598+(LC/MS)638embedded image[3-[2-(4-Methanesulfonyl-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- (2-methoxy-phenyl)-propyl]- carbamic acid ethyl ester hydrochloride594.1798+(LC/MS)




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Preparation 10
8-(3,3-Diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one



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To a mixture of 1.49 g (7.8 mmol) of 2,8-diaza-spiro[4.5]decan-1-one hydrochloride, 2.39 g (8.6 mmol) of 3,3-diphenylpropyl bromide and 3.23 g (23.4 mmol) of potassium carbonate was added 40 mL of anhydrous DMF. The reaction mixture was stirred for 8 hours at 60° C. Then 10 mL of water was added and the solution was extracted with DCM (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated in vacuo. The yellow crude oil was purified by flash chromatography on silica gel (DCM/methanol 100:0 to 90:10) and 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one was isolated as a pale yellow solid (1.22 g, 44.9%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.49 (br s, 1H) , 7.3-7.22 (m, 8H), 7.13 (m, 2H), 3.97 (t, 1H), 3.09 (t, 2H), 2.67 (m, H), 2.13 (m, 4H), 1.86 (m, 4H), 1.63 (t×d, 2H), 1.25 (br, 2H)


Preparation 11
8-(3,3-Diphenylpropyl)-2,8-diaza-spiro[4.5]decane



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400 mg (1.14 mmol) of 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decan-1-one were dissolved in 15 mL of anhydrous THF followed by 3.44 mL of a 1M solution of LAH in THF. The reaction mixture was refluxed for 5 hours and cooled. 5 mL of water and 10 mL of aqueous solution of sodium hydroxide (1N) were successively added and the solution was stirred for an additional one hour before filtering on celite. The filtrate was extracted with DCM (2×10 mL). The organic layers were dried over sodium sulfate, filtered and evaporated in vacuo to yield 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decane as a yellow oil (365.1 mg, 95.7%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.29-7.22 (m, 8H), 7.12 (m, 2H), 3.95 (t, 1H), 3.34 (br s, 1H), 2.72 (t, 2H), 2.46 (s, 2H), 2.24-2.07 (m, 8H), 1.38 (m, 6H).


EXAMPLE 12
(4-Bromophenyl)-[8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]dec-2-yl]-methanone hydrochloride (Compound 639)



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To 100 mg (100 μmol, loading of 1 mmol/g) of 4-bromophenylcarboxyl activated ester on polymeric 4-hydroxy-2,3,5,6-tetrafluorobenzamido (TFP) resin (see preparation in J. M. Salvino et al. J. Comb. Chem. 2000, 2, 691-697), preswollen with 0.5 mL of anhydrous DMF, was added 20 mg (60 μmol) of 8-(3,3-diphenylpropyl)-2,8-diaza-spiro[4.5]decane diluted in 1 mL of DMF. The reaction was agitated overnight at room temperature. The mixture was filtered and washed with DCM (2×2 mL). The filtrates were collected and evaporated in vacuo. The crude was purified by semi-preparative HPLC (method B) yielding Compound 639 as a colorless solid (9.8 mg, 29.5%).



1H NMR (400 MHz, DMSO-d6): δ[ppm] 9.9 (br s, 1H), 7.61 (d, 2H), 7.47 (d×d, 1H), 7.43 (d, 1H), 7.3 (m, 8H), 7.18 (t, 2H), 3.96 (t, 1H), 3.52-3.28 (m, 8H), 2.94 (m, 3H), 2.79 (m, 1H), 1.89-1.63 (m, 6H).


LC/MS: m/z 519.0 (MH+).
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EXAMPLE 13
4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester (Compound 640)



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To a mixture of 500 mg (1.39 mmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride in 10 mL of anhydrous DMF was added 484 μL (2.78 mmol) of DIPEA followed by a solution of 4-bromo-2-phenyl-butyric acid methyl ester (357 mg, 1.39 mmol) in 4 mL of anhydrous DMF. Then 576 mg (4.17 mmol) of potassium carbonate were added and the reaction mixture was stirred overnight at 60° C. After cooling, the mixture was poured in water and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The crude was purified by flash chromatography on silica gel, eluting with ethyl acetate and DCM/methanol (9:1), and yielding 555 mg of Compound 640 as a colorless oil (80%).



1H NMR (400 MHz, CD2Cl2): δ[ppm] 7.47 (d, 2H), 7.34-7.24 (m, 5H), 7.11 (d, 2H), 4.38 (s, 2H), 3.73 (m, 1H), 3.66 (s, 3H), 3.13 (t, 2H), 2.85 (m, 1H), 2.72 (m, 1H), 2.35-2.24 (m, 3H), 2.07-1.81 (m, 7H), 1.37 (br d, 2H).


Preparation 12
4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid



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To a mixture of 521 mg (1.043 mmol) of 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-2-phenyl-butyric acid methyl ester in 10 mL of methanol was added 101 mg (1.56 mmol) of potassium hydroxide in 5 mL of water. The reaction mixture was refluxed for 5 hours, cooled to room temperature, diluted with water (10 mL) and treated with concentrated acetic acid. The mixture was stirred for 30 minutes and left at room temperature to allow crystallisation. 4-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid was collected as a white solid (390 mg, 77%) by filtration.



1H NMR (400 MHz, DMSO-d6): δ[ppm] 7.51 (d, 2H), 7.32-7.2 (m, 5H), 7.12 (d, 2H), 4.32 (s, 2H), 3.58 (t, 1H), 3.43 (br s, 1H), 3.12 (t, 2H), 2.77 (m, 2H), 2.3-1.99 (m, 5H), 1.83 (t, 2H), 1.73 (m, 3H), 1.33 (d, 2H).


EXAMPLE 14
4-[2- (4-Bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5] dec-8-yl]-N-cyclohexyl-2-phenyl-butyramide hydrochloride (Compound 646)



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To a mixture of 24.2 mg (50 μmol) of 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid in 0.5 mL of DCE was added 6. 4 mg (65 vol) of cyclohexylamine in 0. 5 mL of DCE and 13. 4 mg (65 μmol) of DCC in 0.5 mL of DCE. The reaction mixture was stirred at room temperature for 16 hours and concentrated. The crude mixture was purified by semi-preparative HPLC (method E) yielding 11.9 g (39%) of Compound 646 as a pale yellowish solid.



1H NMR (400 MHz, CD3OD): δ[ppm] 7.49 (d, 2H) , 7.38-7.25 (m, 5H), 7.16 (d, 2H), 4.41 (d, 2H), 3.65-3.27 (m, 8H), 3.11-2.95 (m, 3H), 2.41 (m, 1H), 2.24-2.05 (m, 4H), 1.96-1.85 (m, 2H), 1.77-1.59 (m, 5H), 1.39-1.04 (m, 5H).


Table 7 of compounds illustrates some of the compounds of the present invention that were synthesized using the procedure described in scheme 9.

TABLE 7CPD#MOL STRUCTURECOMPOUND NAMEMOL WTPURITY640embedded image54-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyric acid methyl ester499.446100% (LC/MS)641embedded image4-[2-(4-methanesulfonylbenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-butyric acid methyl ester498.641100% (LC/MS)642embedded image4-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyric acid methyl ester450.576>90% (HNMR)643embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2,N- diphenyl-butyramide hydrochloride596.99498+(LC/MS)644embedded imageN-benzyl-4-[2-(4-bromobenzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2- phenyl-butyramide hydrochloride611.0298+(LC/MS)645embedded image2-(4-bromobenzyl)-8-(4-oxo-3- phenyl-4-piperidin-1-yl-butyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride589.10498+(LC/MS)646embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclohexyl-2-phenyl-butyramide hydrochloride603.04198+(LC/MS)647embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclohexyl-n-methyl-2-phenyl- butyramide hydrochloride617.06898+(LC/MS)648embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclopropyl-2-phenyl-butyramide hydrochloride560.96198+(LC/MS)649embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclobutyl-2-phenyl-butyramide hydrochloride574.98798+(LC/MS)650embedded imageN-cyclohexyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-n-methyl- 2-phenyl-butyramide hydrochloride616.26298+(LC/MS)651embedded imageN-cyclopropyl-4-[2-(4- methanesulfonylbnzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride560.15598+(LC/MS)652embedded imageN-cyclobutyl-44-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride574.18298+(LC/MS)653embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- cyclopentyl-2-phenyl-butyramide hydrochloride589.01498+(LC/MS)654embedded image4-[2-(4-bromobenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-N- isopropyl-2-phenyl-butyramide hydrochloride562.97698+(LC/MS)655embedded imageN-benzyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride610.21598+(LC/MS)656embedded image2-(4-methanesulfonylbenzyl)-8-(4- oxo-3-phenyl-4-piperidin-1-yl- butyl)-2,8-diaza-spiro[4.5]decan-1- one hydrochloride588.20998+(LC/MS)657embedded imageN-cyclohexyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride602.23698+(LC/MS)658embedded imageN-cyclopentyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride588.20998+(LC/MS)659embedded imageN-isopropyl-4-[2-(4- methanesulfonylbenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride562.17198+(LC/MS)660embedded image4-[2-(4-methoxybenzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-2,N- diphenyl-butyramide hydrochloride548.12390.6% (LC/MS)661embedded imageN-benzyl-4-[2-(4-methoxybenzyl)- 1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 2-phenyl-butyramide hydrochloride562.1598+(LC/MS)662embedded image2-(4-methoxybenzyl)-8-(4-oxo-3- phenyl-4-piperidin-1-yl-butyl)-2,8- diaza-spiro[4.5]decan-1-one hydrochloride540.14498+(LC/MS)663embedded imageN-cyclohexyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride554.17198+(LC/MS)664embedded imageN-cyclopropyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride512.0998+(LC/MS)665embedded imageN-cyclobutyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride526.11798+(LC/MS)666embedded imageN-cyclopentyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride540.14498+(LC/MS)667embedded imageN-isopropyl-4-[2-(4- methoxybenzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-2-phenyl- butyramide hydrochloride514.10698+(LC/MS)


Table 8 of compounds illustrates some of the compounds of the present invention that can be synthesized using the procedure described in schemes 1-9.

TABLE 8CPD#MOL STRUCTURECOMPOUND NAMEMOL WT668embedded imageCyclopropanecarboxylic acid {(S)- 1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-ylp]propyl}-amide hydrochloride546.54669embedded imageCyclopropanecarboxylic acid {(S)- 1-(3-fluoro-phenyl)-3-[2-(4- methoxy-benzyl)-1-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride530.09670embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride518.12671embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-1-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-3-yl-propyl}-amide hydrochloride518.12672embedded imageN-{(S)-1-(3-Chloro-phenyl)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]prropyl}- isobutyramide hydrochloride548.56673embedded imageN-{(S)-1-(3-Fluoro-phenyl)-3-[2- (4-methoxy-benzyl)-1-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride532.1674embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-2-yl-propyl}- isobutyramide hydrochloride520.14675embedded imageN-{(S)-3-[2-(4-Methoxy-bnzyl)-1- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-3-yl-propyl}- isobutyramide hydrochloride520.14676embedded imageN-{(S)-3-[2-(4-Chloro-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride518.53677embedded imageN-{(S)(-3-[2-(4-Fluoro-benzyl)-3- oxo-2,8-diaza-spiro[44.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride502.08678embedded imageN-{(S)-3-[2-(4-Cyano-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride509.1679embedded imageN-{(S)-3-[2-(4-Ethoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-isobutyramide hydrochloride528.1214680embedded imageN-{(S)-3-[2-(4-Difluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride550.09681embedded imageN-{(S)-3-[3-Oco-2-(4- trifluoromethoxy-benzyl)-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-isobutyramide hydrochloride568.08682embedded imageN-{(S)-3-[3-Oxo-2-(4- trifluoromethyl-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-isobutyramide hydrochloride552.08683embedded imageN-{(S)-3-[3-Oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}- issobutyramide hydrochloride550.15684embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-chloro-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride516.52685embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-fluoro-benzyl)-2-oxo-2,8- dxiaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride500.06686embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride507.08687embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride526.12688embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-difluoromethoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide dihydrochloride548.08689embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-trifluoromethoxy-benzyl)- 3-oxo-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride566.07690embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-trifluoromethyl-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-amide hydrochloride550.07691embedded imageCyclopropanecarboxylic acid {(S)- 3-[3-oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride548.13692embedded image2-Cyclopropyl-N-{(S)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride526.12693embedded imageN-{(S)-3-[2-(4-Chloro-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride530.54694embedded imageN-{(S)-3-[2-(4-Fluoro-beenzyl)-3- oxo-2,8-diaza-spiro[44.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride514.09695embedded imageN-{(S)-3-[2-(4-Cyano-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride521.11696embedded imageN-{(S)-3-[2-(4-Ethoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-2-cyclopropyl- acetamide hydrochloride540.15697embedded imageN-{(S)-3-[2-(4-Difluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride562.1698embedded imageN-{(S)-3-[2-(4-Trifluoromethoxy- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride580.09699embedded imageN-{(S)-3-[2-(4-trifluoromethyl- benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-2-cyclopropyl-acetamide hydrochloride564.1700embedded image2-Cyclopropyl-N-{(S)-3-[3-oxo-2- (4-pyrazol-1-yl-benzyl)-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-acetamide hydrochloride562.16701embedded image4,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-0[2-(4-chloro-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride594.58702embedded image4,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride578.12703embedded image4,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-cyano-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride585.14704embedded image4,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[2-(4-ethoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride604.19705embedded image4,4-Difluoro- cyclohexanecarboxylic acid {(S)- 3-[3-oxo-2-(4-pyrazol-1-yl- benzyl)-2,8-diaza-spiro[4.5]dec-8- yl]-1-phenyl-propyl}-amide hydrochloride626.19706embedded imageCyclopropanecarbocylic acid {(S)- 1-(3-chloro-phenyl)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride546.54707embedded imageCyclopropanecarboxylic acid {(S)- 1-(3-fluoro-phenyl)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-propyl}-amide hydrochloride530.09708embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-2-yl-propyl}-amide hydrochloride518.12709embedded imageCyclopropanecarboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- thiophen-3-yl-propyl}-amide hydrochloride518.12710embedded imageN-{(S)-1-(3-Chloro-phenyl)-3-[2- (4-methoxy-beenzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride548.56711embedded imageN-{(S)-1-(3-Fluoro-phenyl)-3-[2- (4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-propyl}- isobutyramide hydrochloride532.1712embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-2-yl-propyl}- isobutyramide hydrochloride520.14713embedded imageN-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-thiophen-3-yl-propyl}- isobutyramide hydrochloride520.14714embedded imagePropane-2-sulfonic acid {(S)-3-[2- (4-methoxy-benzyl)-3-oxo-2,8- diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride550.16715embedded image3-{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-1,1-dimethyl- urea hydrochloride515.1716embedded imageMorpholine-4-carboxylic acid {(S)- 3-[2-(4-methoxy-benzyl)-3-oxo- 2,8-diaza-spiro[4.5]dec-8-yl]-1- phenyl-propyl}-amide hydrochloride557.14717embedded image3,3-Difluoro-yrrolidine-1- carboxylic acid {(S)-3-[2-(4- methoxy-benzyl)-3-oxo-2,8-diaza- spiro[4.5]dec-8-yl]-1-phenyl- propyl}-amide hydrochloride577.12718embedded image{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-carbamic acid methyl ester hydrochloride502.06719embedded image{(S)-3-[2-(4-Methoxy-benzyl)-3- oxo-2,8-diaza-spiro[4.5]dec-8-yl]- 1-phenyl-propyl}-carbamic acid ethyl ester hydrochloride516.08


EXAMPLE 15

The following assay methods are suitable for evaluating the compounds of the invention.


Chemokine Binding assay: Membranes (1 μg/well) from human embryonic kidney (HEK-293) cells expressing human CCR5 were incubated with 0.1 nM 125I-labeled MIP-1α (Amersham) in the presence of varying concentrations of a test compound (10000-0.01 nM) in buffer (50 mM Hepes, pH 7.3/5 mM MgCl2/1 mM CaCl2/0.5% BSA) for 90 min at room temperature. Reaction mixtures (100 μL) were filtered through Multiscreen GFB filters (Millipore) and washed six times with cold wash buffer (50 mM Hepes, pH 7.3/0.5 M NaCl, 0.1% BSA). Bound 125I-MIP-1α was quantitated by liquid scintillation counting. The nonspecific binding of 125I-labeled MIP-1α to the membrane was determined based on the radioactivity from the wells added with 100 nM non-radiolabeled MIP-1α. IC50 and KD values were calculated by using GRAPHPAD PRISM software (Intuitive Software for Science, San Diego)


HIV-1 Replication in PBMC Cultures. Isolated PBMC were stimulated in vitro with 5 μg/ml phytohemagglutinin and 50 units/ml IL-2 for 3 days. The cells were resuspended at 4×106/ml in complete medium (RPMI, 10% FBS/50 units/ml IL-2), seeded into 96-well plates (2×105/well), incubated with inhibitor for 1 h at 37° C., and infected in triplicate with 25-100 tissue culture 50% infective dose (TCID50) per well of the R5 HIV-1JR-FL strain for 3-4 h. The cells were washed twice in PBS to remove residual virus and cultured in the presence of inhibitor for 4-6 days. HIV-1 replication was determined by the presence of viral RT activity in harvested supernatant fluid. The IC50 values for the virus were determined by using GRAPHPAD PRISM software.


The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.


From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.


Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The preceding preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.


In the foregoing and in the examples, all temperatures are set forth uncorrected in degrees Celsius and, all parts and percentages are by weight, unless otherwise indicated.


The entire disclosures of all applications, patents and publications, cited herein and of corresponding U.S. Provisional Application Ser. No. 60/487,973, filed Jul. 18, 2003 is incorporated by reference herein.


The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.


From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Claims
  • 1. A compound according to formula (I):
  • 2. A compound according to claim 1, wherein said compound is of formula (Ia):
  • 3. A compound according to claim 1, wherein said compound is of formula (Ib):
  • 4. A compound according to claim 1, wherein said compound is of formula (Ic):
  • 5. A compound according to claim 1, wherein said compound is of formula (Id):
  • 6. A compound according to claim 1, wherein said compound is an (S)-enantiomer of formula (Ie):
  • 7. A compound according to claim 1, wherein W is C6-12 aryl or 3 to 10 membered heterocycle.
  • 8. A compound according to claim 1, wherein W is C6-12 aryl.
  • 9. A compound according to claim 1, wherein W is 3 to 10 membered heterocycle.
  • 10. A compound according to claim 1, wherein W is phenyl, phenyl substituted in the para (p) position, phenyl substituted with a halogen, phenyl substituted with Br, phenyl substituted with F, phenyl substituted with Cl, phenyl substituted with at least one halogen, phenyl substituted with a C1-3 alkoxy, phenyl substituted with methoxy, phenyl substituted with SO2C1-3alkyl, phenyl substituted with methanesulfonyl, phenyl substituted with halogenated C1-6 alkyl, phenyl substituted with CHF2, phenyl substituted with halogenated C1-6 alkoxy, phenyl substituted with OCF3, or pyridine.
  • 11. A compound according to claim 1, wherein R1 is:
  • 12. A compound according to claim 1, wherein R1 is:
  • 13. A compound according to claim 1, wherein R1 is:
  • 14. A compound according to claim 1, wherein R1 is:
  • 15. A compound according to claim 1, wherein R1 is:
  • 16. A compound according to claim 1, wherein R1 is:
  • 17. A compound according to claim 1, wherein R1 is:
  • 18. A compound according to claim 1, wherein R1 is:
  • 19. A compound according to claim 1, wherein R1 is:
  • 20. A compound according to claim 1, wherein R1 is:
  • 21. A compound according to claim 1, wherein R1 is:
  • 22. A compound according to claim 1, wherein R1 is:
  • 23. A compound according to claim 1, wherein R1 is:
  • 24. A compound according to claim 1, wherein R2 is C6-12 aryl or 3 to 10 membered heterocycle.
  • 25. A compound according to claim 1, wherein R2 is C6-12 aryl.
  • 26. A compound according to claim 1, wherein R2 is phenyl, phenyl substituted with halogen, phenyl substituted with Cl, phenyl substituted with at least one halogen, phenyl substituted with methoxy, or phenyl substituted with at least one methoxy.
  • 27. A compound according to claim 1, wherein R2 is 3 to 10 membered heterocycle.
  • 28. A compound according to claim 1, wherein R2 is thienyl or pyridyl.
  • 29. A compound according to claim 1, wherein R3 is H or C1-4 alkyl.
  • 30. A compound according to claim 1, wherein R3 is H or methyl.
  • 31. A compound according to claim 1, wherein said compound is selected from: 2-(4-bromobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3-phenylpropyl)-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-chlorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-fluorobenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5)decan-1-one; 8-(3-phenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-methylbenzyl)-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 4-[1-oxo-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzonitrile; 2-biphenyl-4-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-naphthalen-2-ylmethyl-8-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-3-one; 8-(3,3-diphenyl-propyl)-2-(3-phenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-pyridin-4-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-benzothiazol-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-methanesulfonyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(3-phenyl-allyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-phenethyl-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-benzyloxy-benzyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-benzofuran-2-ylmethyl-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-isopropyl-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(5-chloro-benzo[b]thiophen-3-ylmethyl)-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-nitro-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromo-benzyl)-8-(3-pyridin-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-[1-(4-bromophenyl)-ethyl]-8-(3,3-diphenyl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one; N-{4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-phenyl}-acetamide; 8-(3,3-diphenyl-propyl)-2-(6-trifluoromethyl-pyridin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one; 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl]-benzoic acid; 8-(3,3-diphenyl-propyl)-2-pyridin-2-ylmethyl-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-trifluoromethylsulfanyl -benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-methyl-cyclohexylmethyl)-2,8-diaza-spiro[4.5]decan-1-one; 4-[8-(3,3-diphenyl-propyl)-1-oxo-2,8-diaza-spiro[4.5)dec-2-ylmethyl]-benzoic acid methyl ester; 8-(3,3-diphenyl-propyl)-2-(5-trifluoromethyl-furan-2-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one; 8-(3,3-diphenyl-propyl)-2-(4-iodo-benzyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-methanesulfonylbenzyl)-8-(3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-hydroxy-3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-hydroxy-3-(3-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3-hydroxy-3-phenyl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-(2-methoxyphenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-hydroxy-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-(3-chlorophenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-(3-phenyl-3-thiophen-2-yl-propyl)-2,8-diaza-spiro[4.5]decan-1-one; 2-(4-bromobenzyl)-8-[3-(4-chlorophenyl)-3-phenyl-propyl]-2,8-diaza-spiro[4.5)decan-1-one; {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-2,6-dimethyl-benzamide; cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2,4,6-trimethyl-phenyl)-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-propionamide; {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-carbamic acid tert-butyl ester; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-benzamide; cyclohexanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-methyl-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-N-methyl-2-phenyl-acetamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-(2,4,6-trimethyl-phenyl)-acetamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-N-methyl-2-(2,4,6-trimethyl-phenyl)-acetamide; [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-carbamic acid tert-butyl ester; {3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-carbamic acid tert-butyl ester; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; cyclopropanecarboxylic acid {3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-chloro-benzamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-methoxy-benzamide; pyridine-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-chloro-benzamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-nicotinamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-chloro-benzamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-3,4-dichloro-benzamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-chloro-phenyl)-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxy-phenyl)-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-chloro-phenyl)-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-2-(3-methoxy-phenyl)-acetamide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxy-phenyl)-acetamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dichloro-phenyl)-acetamide; tetrahydro-pyran-4-carboxylic acid{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cycloheptanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromo-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclohexyl-acetamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide; 2-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; 2-methoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; pyridine-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 3-chloro-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; 3-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-nicotinamide; 4-chloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; 4-methoxy-N-{3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide; (R)-cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro [4.5]dec-8-yl]-l(R)-phenyl-propyl}-amide; 3,4-dichloro-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; 3,4-dimethoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; 2-(2-chloro-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-acetamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methox-phenyl)-acetamide; 2-(3-chlorophenyl)-N-13-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; N-13-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide; N-(3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-pyridin-3-yl-acetamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide; 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; tetrahydro-pyran-4-carboxylic acid{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cycloheptanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-cyclohexyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; (S)-cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopentyl-acetamide; furan-2-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-ethyl-butyramide; thiophene-2-carboxylic acid {3-[2-(4-brom-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3,4-dimethoxyphenyl)-acetamide; 2-cyclopentyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; furan-2-carboxylic acid {3-[2-(4-methox-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-ethyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide; thiophene-2-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-(3,4-dimethoxy-phenyl)-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl}-acetamide; cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-acetamide; cyclopropanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide; N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-isobutyramide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,18-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide; 2-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-2-methoxy-benzamide; pyridine-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 3-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methoxy-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-nicotinamide; 4-chloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-4-methoxy-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isonicotinamide; 3,4-dichloro-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3,4-dimethoxy-benzamide; 2-(2-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(2-methoxyphenyl)-acetamide; 2-(3-chlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(3-methoxyphenyl)-acetamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-benzamide; (S)-cyclohexanecarboxylic acid (3-(2-benzyl-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-(4-methoxyphenyl)-acetamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-phenyl-acetamide; 2-(3,4-dichlorophenyl)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; cyclopentanecarboxylic acid {3-(2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; cycloheptanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-cyclohexyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; 2-cyclopentyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; furan-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-ethyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-butyramide; thiophene-2-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-(3,4-dimethoxyphenyl)-N-{3-[2-(4-methanesulfonyl-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl)-amide; 4-methyl-cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 3-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 4-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 4-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; cyclohexanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chloro-phenyl)-propyl]-amide; N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-benzamide; N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-phenyl-acetamide; {1-(3-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; 1-(3,4-dichlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; cyclopropanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isobutyramide; 3-methyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide; 2-chloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; pyridine-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; 3-methoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-nicotinamide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-isonicotinamide; 3,4-dichloro-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 3,4-dimethoxy-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 2-(2-chlorophenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; 2-(2-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-benzamide; 2-(3-chloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; 2-(3-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; 2-(4-methoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-2-phenyl-acetamide; 2-(3,4-dichloro-phenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; (1-(3-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; cycloheptanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; 2-cyclohexyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; 2-cyclopentyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; furan-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; 2-ethyl-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-butyramide; thiophene-2-carboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; 2-(3,4-dimethoxyphenyl)-N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-acetamide; cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; 4-methyl-cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-phenyl-propyl]-amide; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; (S)-cyclopropanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; (S)-N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-methyl-butyramide; (S)-cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; (S)-cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; [3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; (3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester; {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester; (1-(3,4-dichlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; 2-cyclopropyl-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; 2-cyclopropyl-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3,4-dimethoxyphenyl)-propyl]-carbamic acid tert-butyl ester; 1-(3,4-dimethoxyphenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; tetrahydro-pyran-4-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-methoxy-phenyl)-propyl]-carbamic acid tertbutyl ester; (S)-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid tert-butyl ester; {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-pyridin-2-yl-propyl}-carbamic acid tert-butyl ester; {1-(3,4-dimethoxyphenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; {1-(4-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; {1-(2-chlorophenyl)-3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; (3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester; [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-(4-chlorophenyl)-propyl]-carbamic acid tert-butyl ester; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-chlorophenyl)-propyl]-carbamic acid tert-butyl ester; {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester; {1-(4-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-propyl}-carbamic acid tert-butyl ester; {1-(2-chlorophenyl)-3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-carbamic acid tert-butyl ester; (3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-carbamic acid tert-butyl ester; (S)-N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; [3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxy-phenyl)-propyl]-carbamic acid tert-butyl ester; [1-(2-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester; [1-(3-chlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester; [1-(3,4-dichlorophenyl)-3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-propyl]-carbamic acid tert-butyl ester; [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-carbamic acid tert-butyl ester; (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-[3-(cyclopropanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-(3-isobutyrylamino-3-phenyl-propyl)-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-[3-(cyclopentanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; (S)-8-[3-(cyclohexanecarbonyl-amino)-3-phenyl-propyl]-2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]decane; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide; cyclobutanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclopentanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; N-{3-[2-(4-bromo-enzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide; N-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-2-methoxy-acetamide; cyclohexanecarboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclopropanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide; [3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(2-methoxyphenyl)-propyl]-carbamic acid tert-butyl ester; cyclobutanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclopentanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-thiophen-2-yl-propyl}-amide; N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide; 2-methoxy-N-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-acetamide; cyclohexanecarboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclopropane carboxylic acid{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl}-amide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide; cyclobutanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclopentanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl1-1-thiophen-2-yl-propyl}-amide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-propionamide; N-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-thiophen-2-yl-propyl}-2-methoxy-acetamide; cyclohexanecarboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-isobutyramide; cyclobutanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide; cyclopentanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide; N-[3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-propionamide; cyclohexanecarboxylic acid [3-(1-oxo-2-pyridin-3-ylmethyl-2,8-diaza-spiro[4.5]dec-8-yl)-1-thiophen-2-yl-propyl]-amide; cyclopropanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide; N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-isobutyramide; cyclobutanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide; cyclopentanecarboxylic acid [3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-amide; N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-propionamide; N-[3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-(3-chlorophenyl)-propyl]-2-methoxy-acetamide; piperidine-1-carboxylic acid {3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; piperidine-1-carboxylic acid {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; piperidine-1-carboxylic acid {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}amide; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-chloro-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxy-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-chloro-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxy-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-chloro-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxy-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2,6-dimethyl-phenyl)-urea; 1-{3-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea; 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea; 1-(2-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea; 1-(3-chlorophenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea; {3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea; 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea; 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-phenyl-urea; 1-(2-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methanesulfonylbenzyl)--oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(2-methoxyphenyl)-urea; 1-(3-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-(3-methoxyphenyl)-urea; 1-(4-chlorophenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-1-phenyl-propyl}-3-(4-methoxyphenyl)-urea; 1-(2,6-dimethylphenyl)-3-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-urea; 1-{3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-3-naphthalen-1-yl-urea; {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester; {3-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5)dec-8-yl]-2-phenyl-butyric acid methyl ester; 4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester; 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyric acid methyl ester; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide; N-benzyl-4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; 2-(4-bromobenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl)-N-cyclohexyl-2-phenyl-butyramide; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclohexyl-N-methyl-2-phenyl-butyramide; 4-[2-(4-bromobenzyl)-1-ox6-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopropyl-2-phenyl-butyramide; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclobutyl-2-phenyl-butyramide; N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-methyl-2-phenyl-butyramide; N-cyclopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-cyclobutyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-cyclopentyl-2-phenyl-butyramide; 4-[2-(4-bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-N-isopropyl-2-phenyl-butyramide; N-benzyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; 2-(4-methanesulfonylbenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; N-cyclohexyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-cyclopentyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-isopropyl-4-[2-(4-methanesulfonylbenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; 4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2,N-diphenyl-butyramide; N-benzyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; 2-(4-methoxybenzyl)-8-(4-oxo-3-phenyl-4-piperidin-1-yl-butyl)-2,8-diaza-spiro[4.5]decan-1-one; N-cyclohexyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-cyclopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-cyclobutyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-cyclopentyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; N-isopropyl-4-[2-(4-methoxybenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-2-phenyl-butyramide; and pharmaceutically acceptable salts, hydrates and solvates thereof.
  • 32. A compound according to claim 1, wherein said compound is selected from: Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide; Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide; N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide; N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide; N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[3-Oxo-2-(4-trifluoromethoxy-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[3-Oxo-2-(4-trifluoromethyl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; N-{(S)-3-[3-Oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-isobutyramide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 2-Cyclopropyl-N-{(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; N-{(S)-3-[2-(4-Chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Difluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Trifluoromethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; N-{(S)-3-[2-(4-Trifluoromethyl-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-2-cyclopropyl-acetamide; 2-Cyclopropyl-N-{(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-acetamide; 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-chloro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2- (4-fluoro-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-cyano-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[2-(4-ethoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 4,4-Difluoro-cyclohexanecarboxylic acid {(S)-3-[3-oxo-2-(4-pyrazol-1-yl-benzyl)-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-1-(3-chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide; Cyclopropanecarboxylic acid {(S)-1-(3-fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-amide; Cyclopropanecarboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-amide; N-{(S)-1-(3-Chloro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide; N-{(S)-1-(3-Fluoro-phenyl)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-propyl}-isobutyramide; N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-2-yl-propyl}-isobutyramide; N-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-thiophen-3-yl-propyl}-isobutyramide; Propane-2-sulfonic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 3-{(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-1,1-dimethyl-urea; Morpholine-4-carboxylic acid {(S)-3-[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; 3,3-Difluoro-pyrrolidine-1-carboxylic acid {(S)-3[2-(4-methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-amide; (S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid methyl ester; {(S)-3-[2-(4-Methoxy-benzyl)-3-oxo-2,8-diaza-spiro[4.5]dec-8-yl]-1-phenyl-propyl}-carbamic acid ethyl ester; and pharmaceutically acceptable salts, hydrates or solvates thereof.
  • 33. A compound according to claim 1, wherein: Y, Z and X are each, independently, CH2, C═O or CR4R5; W is H, C1-6 alkyl, C6-12 aryl, 3 to 10 membered heterocycle, C6-12 aralkyl or C310 heteroaralkyl; R1 is H, C1-6 alkyl, C6-12 aryl, OH, NR8R9, O—C1-6 alkyl, O—C6-12 aryl, O—C6-12 aralkyl, R2 is C1-10 alkyl, C6-12 aryl or 3 to 10 membered heterocycle; R3 is H, C1-6 alkyl or C6-12 aryl; R4 and R5 are each, independently, H, C1-6 alkyl or C6-12 aryl; R6 is H or C1-4 alkyl; R7 is H, C1-10 alkyl, C6-12 aryl, 3 to 10 membered heterocycle, C6-12 aralkyl or 3 to 10 membered heteroaralkyl; or R″6 and R7 can also be taken together to form a 3 to 10 membered heterocycle; and R8 and R9 are each, independently, H or C1-6 alkyl.
  • 34. A method of modulating chemokine receptor activity in a subject comprising administering to the subject an effective amount of a compound of according to claim 1.
  • 35. A method of preventing or treating at least one disease associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of according to claim 1.
  • 36. A method of preventing or treating at least one inflammatory disease, immunoregulatory disease, organ transplantation reaction, or infectious disease in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of according to claim 1.
  • 37. A method of preventing or treating an HIV infection in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of according to claim 1.
  • 38. A method of preventing or treating at least one disease associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound of according to claim 1.
  • 39. A method of blocking cellular entry of HIV in a subject in need thereof comprising administering to the subject an effective amount of a compound according to claim 1 to block HIV from cellular entry in said subject.
  • 40. A method of delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a compound according to claim 1.
  • 41. A method of preventing or treating of a disease associated with the modulation of chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a combination of a compound according to claim 1 and at least one further therapeutic agent.
  • 42. A method of preventing or treating of a disease associated with the modulation of CCR5 chemokine receptor activity in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a combination of a compound according to claim 1 and at least one further therapeutic agent.
  • 43. A method of blocking cellular entry of HIV in a subject or for the prevention or treatment of HIV infections in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a combination of a compound according to claim 1 and at least one further therapeutic agent.
  • 44. A method for delaying the onset of AIDS or treating AIDS in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of a combination of a compound according to claim 1 and at least one further therapeutic agent.
  • 45. A method according to claim 34, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 46. A method according to claim 35, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 47. A method according to claim 36, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 48. A method according to claim 37, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 49. A method according to claim 38, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 50. A method according to claim 39, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 51. A method according to claim 40, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 52. A method according to claim 41, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 53. A method according to claim 42, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 54. A method according to claim 43, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 55. A method according to claim 44, wherein said compound is administered in an amount of 0.1-750 mg/kg of body weight per day.
  • 56. A method according to claim 34, wherein said subject is a human.
  • 57. A method according to claim 35, wherein said subject is a human.
  • 58. A method according to claim 36, wherein said subject is a human.
  • 59. A method according to claim 37, wherein said subject is a human.
  • 60. A method according to claim 38, wherein said subject is a human.
  • 61. A method according to claim 39, wherein said subject is a human.
  • 62. A method according to claim 40, wherein said subject is a human.
  • 63. A method according to claim 41, wherein said subject is a human.
  • 64. A method according to claim 42, wherein said subject is a human.
  • 65. A method according to claim 43, wherein said subject is a human.
  • 66. A method according to claim 44, wherein said subject is a human.
  • 67. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
  • 68. A composition according to claim 67, further comprising at least one further therapeutic agent.
  • 69. A pharmaceutical combination comprising a compound according to claim 1 and at least one further therapeutic agent.
  • 70. A combination according to claim 69, wherein said at least one further therapeutic agent is an antiviral agent.
  • 71. A combination according to claim 69, wherein said at least one further therapeutic agent is selected from nucleoside and nucleotide analog reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, attachment and fusion inhibitors, integrase inhibitors and maturation inhibitors.
  • 72. A combination according to claim 70, wherein said antiviral agent is selected from 3TC (lamivudine, Epivir®), AZT (zidovudine, Retrovir®), Emtricitabine (Coviracil®, formerly FTC), d4T (2′,3′-dideoxy-2′,3′-didehydro-thymidine, stavudine and Zerit®), tenofovir (Viread®), 2′,3′-dideoxyinosine (ddl, didanosine, Videx®), 2′,3′-dideoxycytidine (ddC, zalcitabine, Hivid®), Combivir® (AZT/3TC or zidovudine/lamivudine combination), Trivizir® (AZT/3TC/abacavir or zidovudine/lamivudine/abacavir combination), abacavir (1592U89, Ziagen®), SPD-754, ACH-126,443 (Beta-L-Fd4C), Alovudine (MIV-310), DAPD (amdoxovir), Racivir, 9-[(2-hydroxymethyl)-1,3-dioxolan-4-yllguanine and 2-amino-9-[(2-hydroxymethyl)-1,3-dioxolan-4-yl]adenine.
  • 73. A combination according to claim 70, wherein said antiviral agent is selected from Nevirapine (Viramune®, NVP, BI-RG-587), delavirdine (Rescriptor®, DLV), efavirenz (DMP 266, Sustiva®), (+)-Calanolide A, Capravirine (AG1549, formerly S-1153), DPC083, MIV-150, TMC120, TMC125 or BHAP (delavirdine), calanolides or L-697,661 (2-Pyridinone 3benzoxazolMeNH derivative).
  • 74. A combination according to claim 70, wherein said antiviral agent is selected from nelfinavir (Viracept®, NFV), amprenavir (141W94, Agenerase®), indinavir (MK-639, IDV, Crixivan®), saquinavir (Invirase®, Fortovase®, SQV), ritonavir (Norvir®, RTV), lopinavir (ABT-378, Kaletra®), Atazanavir (BMS232632), mozenavir (DMβ-450), fosamprenavir (GW433908), R0033-4649, Tipranavir (PNU-140690), TMC114 and VX-385.
  • 75. A combination according to claim 70, wherein said antiviral agent is selected from T-20 (enfuvirtide, Fuzeon®), T-1249, Schering C (SCH-C), Schering D (SCH-D), FP21399, PRO-140, PRO 542, PRO 452, TNX-355, GW873140 (AK602), TAK-220, UK-427,857 or soluble CD4, CD4 fragments, CD4-hybrid molecules, BMS-806, BMS-488043, AMD3100, AMD070 and KRH-2731.
  • 76. A combination according to claim 70, wherein said antiviral agent is selected from S-1360, L-870,810, L-870,812 and C-2507.
  • 77. A combination according to claim 70, wherein said antiviral agent is PA-457.
  • 78. A combination according to claim 70, wherein said antiviral agent is azodicarbonamide (ADA).
  • 79. A combination according to claim 70, wherein said antiviral agent is HGTV43.
  • 80. A combination according to claim 70, wherein said antiviral agent is selected from interleukin-2 (IL-2, Aldesleukin, Proleukin), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, Multikine, Ampligen, thymomodulin, thymopentin, foscarnet, HE2000, Reticulose, Murabutide, Resveratrol, HRG214, HIV-1 Immunogen (Remune) and EP HIV-1090.
  • 81. A combination according to claim 70, wherein said antiviral agent is selected from 2′,3′-dideoxyadenosine, 3′-deoxythymidine, 2′,3′-dideoxy-2′,3′-didehydrocytidine,ribavirin, acyclovir, ganciclovir, alpha-beta-and gamma-interferon, probenecid, TIBO drugs, HEPT, and TSAO derivatives.
Parent Case Info

This application claims the benefit of U.S. provisional application No. 60/487,973 filed Jul. 18, 2003, the entire disclosure of which is herein incorporated by reference.

Provisional Applications (1)
Number Date Country
60487973 Jul 2003 US