Bibliographic Details
| Title: |
BRIDGED SPIRO [2.4] HEPTANE DERIVATIVES AS ALX RECEPTOR AND/OR FPRL2 AGONISTS |
| Document Number: |
20120115841 |
| Publication Date: |
May 10, 2012 |
| Appl. No: |
13/321372 |
| Application Filed: |
May 17, 2010 |
| Abstract: |
The present invention relates to bridged spiro[2.4]heptane derivatives of formula (I), wherein W, Y, Z, R1 and R2 are as defined in the description, their preparation and their use as pharmaceutically active compounds as ALX receptor and/or FPRL2 agonists for the treatment of inflammatory and obstructive airways diseases. [chemical expression included] |
| Inventors: |
Bur, Daniel (Allschwil, CH); Corminboeuf, Olivier (Allschwil, CH); Cren, Sylvaine (Allschwil, CH); Grisostomi, Corinna (Allschwil, CH); Leroy, Xavier (Allschwil, CH); Richard-Bildstein, Sylvia (Allschwil, CH) |
| Assignees: |
ACTELION PHARMACEUTICALS LTD. (Allschwill, CH) |
| Claim: |
1. A compound of the formula (I) [chemical expression included] wherein W represents —CH2CH2— or —CH═CH—; Y represents a bond or a (C1-C4)alkandiyl group and R1 represents: an aryl-group or a heteroaryl-group, wherein the groups are independently unsubstituted, mono-, di- or tri-substituted, and wherein the substituents are independently selected from halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C2)alkyl-carbonyl, (C1-C2)fluoroalkyl, (C1-C2)fluoroalkoxy, nitro, cyano or phenyl, wherein the phenyl is unsubstituted or mono-substituted with halogen; benzo[d][1,3]dioxolyl; aryloxy; a cyclohexyl-group or a cyclohexenyl-group, wherein the groups are independently unsubstituted or mono-substituted with (C1-C4)alkyl; (C1-C2)alkyl-carbonyl; (C1-C4)alkoxy-carbonyl; or Y represents, together with R1, a (C4-C6)alkyl group or a amino-(C4-C6)alkyl group; Z represents —C(O)NR3—* or —CH2NR4C(O)—*, wherein the asterisks indicate the bond which is linked to R2; R2 represents: (C3-C6)cycloalkyl, which is unsubstituted or mono-substituted with hydroxy, hydroxy-methyl, R5R6N—CH2—, heterocyclyl-methyl or —CONH2; (C1-C6)alkyl, which is unsubstituted or mono-substituted with fluorine, trifluoromethyl, (C1-C4)alkylthio, (C1-C4)alkoxy-carbonyl, hydroxy, cyano, —NR5R6, —COOH, —C(O)NR7R8 or optionally mono-substituted (C1-C4)alkoxy, wherein the substituent is selected from hydroxy or heterocyclyl; or (C1-C6)alkyl, which is mono-substituted with (C3-C6)cycloalkyl, wherein the cycloalkyl is unsubstituted or mono-substituted with —NR5R6 or hydroxy; with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-substituted at a nitrogen atom with (C1-C4)alkyl, (C1-C2)alkyl-carbonyl or tert-butoxycarbonyl, and/or mono- or di-substituted at one or two of the carbon atoms with substituents independently selected from halogen, (C1-C4)alkyl or (C1-C2)alkoxy-(C1-C2)alkyl; with an aryl-group or heteroaryl-group, wherein the groups are independently unsubstituted, mono-, di- or tri-substituted, and wherein the substituents are independently selected from halogen, (C1-C4)alkyl, —CH2NHR9, —SO2NH2 or phenyl; or (C3-C5)fluoroalkyl, which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono- or di-substituted at one or two of the carbon atoms with substituents independently selected from halogen or (C1-C4)alkyl; heterocyclyl, which is unsubstituted or mono-substituted at a nitrogen atom with (C1-C6)alkyl, benzyl or tert-butoxycarbonyl or mono-substituted at a carbon atom with pyrrolidin-1-yl-methyl; an aryl-group or a heteroaryl-group, wherein the groups are independently unsubstituted, mono-, di- or tri-substituted, and wherein the substituents are independently selected from halogen, (C1-C4)alkyl or phenyl; or a group selected from 1-carbamoyl-2-phenyl-ethyl, 1-methoxymethyl-2-phenyl-ethyl, 2-morpholino-2-phenyl-ethyl, 2-phenyl-vinyl, or 2,2-dichloro-1-methyl-cyclopropyl; R3 represents hydrogen, (C1-C3)alkyl or 2-methoxy-ethyl; R2 and R3 form, together with the nitrogen that carries them, a ring of 5 to 7 members, wherein the ring is substituted with amino-(C1-C4)alkyl; R4 represents hydrogen or methyl; R5 represents hydrogen, (C1-C3)alkyl or tert-butoxycarbonyl; R6 represents hydrogen or (C1-C3)alkyl; R7 and R8 represent independently from each other hydrogen or methyl; R7 and R8 form, together with the nitrogen that carries them, a pyrrolidine or piperidine ring; and R9 represents hydrogen or tert-butoxycarbonyl; or a salt thereof. |
| Claim: |
2. The compound according to claim 1 , wherein W represents —CH2CH2— or —CH═CH—; Y represents a bond; R1 represents an aryl-group or a heteroaryl-group, wherein the groups are independently unsubstituted, mono-, di- or tri-substituted, and wherein the substituents are independently selected from halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C2)alkyl-carbonyl, or (C1-C2)fluoroalkyl; Z represents —C(O)NR3—*, wherein the asterisk indicates the bond which is linked to R2; R2 represents: (C3-C6)cycloalkyl, which is unsubstituted or mono-substituted with hydroxy or pyrrolidin-1-yl-methyl; or (C3-C6)alkyl, which is unsubstituted or mono-substituted with fluorine, trifluoromethyl, (C1-C4)alkylthio, hydroxy, cyano, —NR5R6, —C(O)NH2 or optionally mono-substituted (C1-C4)alkoxy, wherein the substituent is selected from hydroxy or heterocyclyl; or (C1-C5)alkyl, which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-substituted at a nitrogen atom with methyl or ethyl, or mono- or di-substituted at one or two of the carbon atoms with substituents independently selected from fluorine, methyl or methoxy-methyl; with an aryl-group or heteroaryl-group, wherein the groups are independently unsubstituted, mono- or di-substituted, and wherein the substituents are independently selected from (C1-C4)alkyl or —CH2NH2; or (C3-C5)fluoroalkyl, which is mono-substituted with heterocyclyl; or heterocyclyl, which is unsubstituted or mono-substituted at a carbon atom with pyrrolidin-1-yl-methyl; R3 represents hydrogen, (C1-C3)alkyl or 2-methoxy-ethyl; R5 represents hydrogen, (C1-C3)alkyl or tert-butoxycarbonyl; and R6 represents hydrogen or (C1-C3)alkyl; or a salt thereof. |
| Claim: |
3. The compound according to claim 1, wherein Y represents a bond; or a salt thereof. |
| Claim: |
4. The compound according to claim 1, wherein R1 represents an aryl-group or a heteroaryl-group, wherein the groups are independently unsubstituted or mono-substituted, and wherein the substituent is selected from halogen, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C2)alkyl-carbonyl or (C1-C2)fluoroalkyl; or a salt thereof. |
| Claim: |
5. The compound according to claim 1, wherein Z represents —C(O)NR3—*, wherein the asterisk indicates the bond which is linked to R2; or a salt thereof. |
| Claim: |
6. The compound according to claim 1, wherein R2 represents: (C3-C6)cycloalkyl, which is unsubstituted or mono-substituted with hydroxy or pyrrolidin-1-yl-methyl; or (C1-C6)alkyl, which is unsubstituted or mono-substituted with fluorine, or trifluoromethyl, (C1-C4)alkylthio, hydroxy, cyano, —NR5R6, —C(O)NH2 or optionally mono-substituted (C1-C4)alkoxy, wherein the substituent is selected from hydroxy or heterocyclyl; (C1-C5)alkyl, which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-substituted at a nitrogen atom with methyl or ethyl, or mono- or di-substituted at one or two of the carbon atoms with substituents independently selected from fluorine, methyl or methoxy-methyl; or (C1-C5)alkyl, which is mono-substituted with an aryl-group or heteroaryl-group, wherein the groups are independently unsubstituted, mono- or di-substituted, and wherein the substituents are independently selected from (C1-C4)alkyl or —CH2NH2; (C1-C5)fluoroalkyl, which is mono-substituted with heterocyclyl; or heterocyclyl, which is unsubstituted or mono-substituted at a carbon atom with pyrrolidin-1-yl-methyl; or a salt thereof. |
| Claim: |
7. The compound according to claim 1, wherein R2 represents (C1-C6)alkyl, which is unsubstituted or mono-substituted with fluorine, trifluoromethyl, (C1-C4)alkylthio, hydroxy, cyano, —NR5R6, —C(O)NR7R8 or optionally mono-substituted (C1-C4)alkoxy, wherein the substituent is selected from hydroxy or heterocyclyl; or a salt thereof. |
| Claim: |
8. The compound according to claim 1, wherein R2 represents (C1-C5)alkyl, which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono-substituted at a nitrogen atom with methyl or ethyl, or mono- or di-substituted at one or two of the carbon atoms with substituents independently selected from fluorine, methyl or methoxy-methyl; or a salt thereof. |
| Claim: |
9. The compound according to claim 1, wherein R2 represents (C1-C4)alkyl, which is mono-substituted with an aryl-group or heteroaryl-group, wherein the groups are independently unsubstituted, mono- or di-substituted, and wherein the substituents are independently selected from (C1-C4)alkyl or —CH2NH2; or a salt thereof. |
| Claim: |
10. The compound according to claim 1, selected from: (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(5-amino-pentyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-iso-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(4-amino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R)—N6-(2-N,N-dimethyl-amino-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-((3-aminomethyl-phenyl)-methyl)-(4S*,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(4-piperidinyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(pyrrolidin-3-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(2,2-dimethyl-3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(4-(N,N-diethyl-amino)-butyl)-(4S* ,7R *)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(3-hydroxy-propyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(2-carbamoyl-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6—(N-tert-butoxycarbonyl-pyrrolidin-3-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(cyclopentyl)-(4S*,7R *)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-ethoxy-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-pyrrolidinyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2,2,2-trifluoro-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-fluoro-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(N-methyl-amino)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(2-tetrahydrofuranyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(4-hydroxy-cyclohexyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-ethylsulfanyl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(5-(N,N-diethyl-amino)-pent-2-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(piperidin-3-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-tert-butoxycarbonyl-amino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(1-hydroxy-prop-2-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(2-imidazolidin-2-on-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-pyrrolidin-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(2-methoxy-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(1H-benzoimidazol-2-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(1-methyl-pyrrolidin-2-yl)-ethyl)-(4S*,7R *)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-hydroxy-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6,N6-bis-(2-methoxy-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(cyano-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-1H-pyrazol-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-[(4-aminomethyl-phenyl)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-ethyl-N6-(2-diethylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-1H-imidazol-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-([1,4]-dioxan-2-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(4-hydroxy-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(4-methyl-piperazin-1-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-amino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-methyl-N6-(2-dimethylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(4-tert-butoxycarbonyl-amino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(methyl-tert-butoxycarbonyl-amino)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-pyrrolidin-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-1H-[1,2,4]-triazol-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(furan-3-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(5-dimethyl-amino-pentyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-dimethyl-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-methoxy-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)-N6-[(1-ethyl-pyrrolidin-2-yl)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-1H-[1,2,4]-triazol-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6—(N-tert-butoxycarbonyl-piperidin-3-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(N-tert-butoxycarbonyl-amino)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-methyl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)-N6-[(2S)-1-hydroxy-4-methyl-pent-2-yl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(methoxy-carbonyl)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-(4-amino sulfonyl-phenyl)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(1-ethyl-5-methyl-1H-pyrazol-3-yl)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R)—N6, N6-bis-(2-methoxy-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-(4,5-dimethyl-1H-imidazol-2-yl)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)-N6-[(1S)-1-carbamoyl-ethyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-diethyl-amino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(pentyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(5-tert-butoxycarbonyl-amino-pentyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6—(N-(3-methyl-butyl)-piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-pyridin-2-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2,2-dimethyl-3-N-tert-butoxycarbonyl-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(1-phenyl-1H-pyrazol-5-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(cyclopropyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(hexyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(1-ethyl-3-methyl-1H-pyrazol-5-yl)-ethyl)-(4S*,7R *)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-phenyl-2-morpholino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-diethyl-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6—(N-tert-butoxycarbonyl-pyrrolidin-2-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-morpholino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(2-carbamoyl-cyclohexyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(1-piperidin-1-yl-propan-1-on-2-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6—(N-benzyl-piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-methyl-N6-hexyl-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3,3-dimethyl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6—(N-methyl-piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)-N6-(3-morpholino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(5-methyl-1H-pyrazol-4-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-tert-butoxycarbonyl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-{[(3-N-tert-butoxycarbonyl-aminomethyl)-phenyl]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-propyl-N6-(cyclopropylmethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6—(N-tert-butoxycarbonyl-piperidin-4-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(cyclohexyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6—(N-tert-butoxycarbonyl-piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-[(1S)-1-carbamoyl-2-phenyl-ethyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-[(4-N-tert-butoxycarbonyl-aminomethyl-phenyl)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6—(N-tert-butoxycarbonyl-azetidin-3-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(N-tert-butoxycarbonyl-piperidin-3-yl)-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-[(1S)-2-methoxy-1-benzyl-ethyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-[(5-methyl-3-phenyl-isoxazol-4-yl)-methyl]-(4S*,7R *)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-carbamoyl-ethyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)-N6-(3-methoxy-propyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)-N6-(tetrahydrofuran-2-yl-methyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-[(2-imidazolidin-2-on-1-yl)-ethyl]-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(cyclopropyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-hydroxy-propyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(1H-imidazol-1-yl)-propyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(5-(dimethyl-amino)-pentyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl)-(6R*)—N6-(3-pyrrolidin-1-yl-propyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-(4-methyl-piperazin-1-yl)-propyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-(4,5-dimethyl-1H-imidazol-2-yl)-ethyl)-(4S*,7R*)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Bromopyridin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Methoxyphenyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Chloro-pyridin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Benzothiazol-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Bromophenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-pyridin-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Methyl-pyridin-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-Pentyl-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-[(4-Methyl-phenyl)-methyl]-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(2-Methoxycarbonyl-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Cyclohexyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Methyl-cyclohex-1-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(5-oxo-hexyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(5-Nitro-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Chloro-thiazol-2-yl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Cyano-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Furan-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(1-(4-Bromophenyl)-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Trifluoromethoxyphenyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(2-Phenoxy-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Methyl-butyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-Butyl-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Methyl-furan-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Methyl-benzothiazol-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Phenyl-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-oxo-pentyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-(1H-Imidazol-1-yl)-propyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Chloro-pyrimidin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Bromophenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Benzothiazol-2-yl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(5-tert-Butyl-isoxazol-3-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Methyl-benzo[d]isothiazol-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(1H-Indol-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(6-Fluoro-benzothiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Ethyl-butyl)-(6R1-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-(4-Chlorophenyl)-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Benzo[2,1,3]oxadiazol-4-yl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-tert-Butyl-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Phenyl-[1,2,4]thiadiazol-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(6-Chloro-benzothiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(3-(2-Methyl-1H-indol-1-yl)-propyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(1-Methyl-1H-benzoimidazol-2-yl)-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(1H-Indol-1-yl)-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(2-(2-Methoxy-phenyl)-ethyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(3-(3,5-dimethyl-pyrazol-1-yl)-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(5-phenyl-isoxazole-4-carbonyl)-amino]-methyl-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(4-(2-oxo-pyrrolidin-1-yl)-butyrylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[(2-(2-chloro-phenyl)-acetylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(3-methoxy-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(3-(N,N-dimethyl-aminocarbonyl)-propionyl-amino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-{[(2,2-dichloro-1-methyl-cyclopropylcarbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(4-methoxycarbonyl-butanoyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-(pentanoylamino-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(2-(2,5-dimethyl-thiazol-4-yl)-acetylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(1-phenyl-1H-pyrazole-5-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-{[(3-aminocarbonyl-propionyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(4-methyl-pyridine-3-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(isobutyrylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(N-ethyl-piperidine-4-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[(3-pyridin-3-yl-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[N-(3-methoxy-propionyl)-N-methyl-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-{[(2-chloro-3-fluoro-phenyl-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(4-pyrrolidin-1-yl-butanoylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(1,5-dimethyl-1H-pyrazole-3-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(cyclopentyl-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(2-(2-methyl-thiazol-4-yl)-acetylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(2-(N,N-dimethyl-amino)-acetylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[N-(2-(2-chloro-phenyl)-acetyl)-N-methyl-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[N-(1,5-dimethyl-1H-pyrazole-3-carbonyl)-N-methyl-amino]-methyl -(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[(2-cyclopropyl-acetylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[(3-(1-methyl-1H-benzoimidazol-2-yl)-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N5-(4-Bromo-phenyl)-(6R*)-6-[(3-1H-indol-3-yl-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)-N544-Bromo-phenyl)-(6R*)-6-[(butanoylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(3-(4-fluoro-phenyl)-propionylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-[(3-phenyl-acryloylamino)-methyl]-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Bromo-phenyl)-(6R*)-6-{[(5-chloro-1,3-dimethyl-1H-pyrazole-4-carbonyl)-amino]-methyl}-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5-carboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Acetyl-phenyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Methyl-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*))-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Acetyl-thiophen-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Acetyl-furan-2-yl-methyl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Acetyl-furan-2-yl-methyl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Trifluoromethyl-phenyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Acetyl-oxazol-5-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(4,5-Dimethyl-1H-imidazol-2-yl)-ethyl)-(6R*)—N6-(4-bromophenyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Iodophenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-(iso-Butyl)-isoxazol-3-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Bromo-thiophen-4-yl-methyl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; and or (5R*)—N5-(2-Fluoro-4-bromophenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; or a salt thereof. |
| Claim: |
11. The compound according to claim 1, selected from: (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-dimethylamino-3-oxopropyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(4-amino-4-oxobutyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-pyrrolidino-3-oxopropyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(2-amino-2-oxoethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(4-ethyl-piperazin-1-yl)-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)-(4-piperidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(azetidin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-morpholino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(4-methyl-1,4-diazepan-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(4-methyl-piperazin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-pyrrolidino-4-oxobutyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(2-(2-(pyrrolidin-1-yl)ethoxy)ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-((3R,6S)-6-(pyrrolidin-1-ylmethyl)tetrahydro-2H-pyran-3-yl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(4-acetyl-piperazin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(cis-4-(pyrrolidin-1-yl-methyl)-cyclohexyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-((3R)-fluoropyrrolidino)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-((3S)-fluoropyrrolidino)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(5-pyrrolidino-pentyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(trans-4-(pyrrolidin-1-yl-methyl)-cyclohexyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl)-(6R*)—N6-(3-methylamino-3-oxopropyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Acetyl-thiazol-5-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,6-Difluoro-4-methoxy-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,3-Difluoro-4-methoxy-phenyl-methyl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Fluoro-4-methoxy-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3,5-Difluoro-4-methoxy-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Chloro-phenyl-methyl)-(6R*)-N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Fluoro-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Trifluoromethoxy-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Isopropoxy-phenyl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromo-thiazol-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Acetyl-oxazol-4-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromo-phenyl-methyl)-(6R*)-N6-(3-pyrrolidin-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(3-pyrrolidin-1-yl-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-phenyl-methyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromo-pyrid-5-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-oxazol-2-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N5-(isobutyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(isobutyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromo-phenyl-methyl)-(6R*)—N6-(isobutyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-(1H-benzoimidazol-2-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(3-(1H-benzoimidazol-2-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromo-phenyl-methyl)-(6R*)—N6-(3-(1H-benzoimidazol-2-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Methoxy-pyrid-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Bromo-pyrazin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Trifluoromethyl-pyridin-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Methyl-pyridin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(Benzo[d]oxazol-6-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Methyl-isoxazol-3-yl-methyl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Methyl-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Trifluoromethyl-1,3,4-thiadiazol-2-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Bromo-pyridin-5-yl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(2-fluoro-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-((2-imidazolidin-2-on)-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-amino-3-oxopropyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(4-diethylamino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(3-ethoxy-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-pyrrolidino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromothiazol-2-yl)-(6R*)—N6-(3-(4-methylpiperazin-1-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(2-dimethylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-dimethylamino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-(4-methylpiperazin-1-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R1-N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)-N6-((2-imidazolidin-2-on)-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromothiazol-2-yl)-(6R*)—N6-(4-diethylamino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(2-fluoroethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenylmethyl)-(6R*)—N6-(4-diethylamino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)-N6-(3-(4-methylpiperazin-1-yl)-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)-N6-(2-dimethylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N64(2-imidazolidin-2-on)-1-yl-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromothiazol-2-yl)-(6R*)—N6-(2-methoxy-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromothiazol-2-yl)-(6R*)-N6-(3-dimethylamino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromopyrid-5-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromopyrid-5-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromopyrid-2-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Chloropyrid-5-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromothiazol-5-yl-methyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Methoxyphenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Methoxyphenyl)-(6R)—N6-(3-hydroxyl-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3-fluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Chloro-pyridin-5-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Methoxyphenyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl-methyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Methoxyphenyl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-pyridin-2-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-methylphenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3-chlorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Chloro-pyridin-5-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetyl-thiazol-2-yl-methyl)-(6R*)—N6-(piperidin-4-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(2-methylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(5-amino-pentyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(4-(aminomethyl)phenyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Bromo-thiazol-2-yl)-(6R*)—N6-(2,2-dimethyl-3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(2-methylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(piperidin-4-yl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(3-(aminomethyl)phenyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(4-(aminomethyl)phenyl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(2,2-dimethyl-3-amino-propyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Bromophenyl-methyl)-(6R*)—N6-(piperidin-4-yl-methyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromo-thiazol-5-yl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Methyl-pyridin-2-yl)-(6R)—N6-(3-amino-3-oxopropyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,5-difluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,6-difluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,3-d difluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,6-difluorophenyl-methyl)-(6R)—N6-(4-pyrrolidin-1-yl-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(5-amino-pentyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(4-amino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3-fluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N6-(5-Bromo-thiazol-2-yl)-(6R)—N6-(5-amino-pentyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(piperidin-4-yl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(piperidin-4-ylmethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6,N6-(3-(aminomethyl)pentane-1,5-diyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2-fluorophenyl-methyl)-(6R)—N6-(5-amino-pentyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,3-difluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3,5-difluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-2,5-difluorophenyl-methyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(piperidin-4-yl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(isobutyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(4-tert-butoxycarbonyl-amino-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(5-tert-butoxycarbonyl-amino-pentyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(5-amino-pentyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(4-amino-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6,N6-(3-(aminomethyl)pentane-1,5-diyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromo-thiazol-2-yl)-(6R)—N6-(piperidin-4-yl-methyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromo-3-fluoro-pyridin-5-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Aminobutyl)-(6R*)—N6-(4-bromophenyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(5-Aminopentyl)-(6R*)—N6-(4-bromophenyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(Cyclohexen-1-yl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-tert-Butyl-cyclohexyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(2-(Pyridin-2-yl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-(4-Acetyl-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Trifluoromethyl-thiazol-2-yl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,4,6-Trifluorophenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,4-Dimethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)-N5-[(2-Acetyl-thiazol-4-yl)methyl]-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Chloro-2-fluorophenyl-methyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Methyl-oxazol-2-yl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-[(5-Acetyl-thiazol-2-yl)methyl]-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Acetylphenyl)-(6R*)—N6-(4-pyrrolidine-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Bromo-4-fluorophenyl-methyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Bromo-4-fluorophenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,3,5-Trifluorophenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-[(4-Methyl-1,2,5-oxadiazol-3-yl)methyl]-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Fluoro-3-trifluoromethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3,5-Dimethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Acetylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Difluoromethoxyphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-[(2-Methoxypyridin-4-yl)methyl]-(6R*)—N6-(4-pyrrolidino-butyl)-(4,3*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Fluoro-5-trifluoromethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Acetylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Chloro-5-trifluoromethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Fluoro-5-trifluoromethylphenyl-methyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Fluoro-3-trifluoromethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-[(2,6-Dichloropyridin-4-yl)methyl]-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,5-Dimethylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4,5-Dimethyl-thiazol-2-yl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Methoxy-5-methylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Chloro-3,6-difluorophenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Isopropoxyphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-Chloro-6-fluoro-3-methylphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3-Chloro-4-methoxyphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(3,4-Dimethoxyphenyl-methyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2,4-Dimethoxyphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(3,4-Dimethoxyphenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(4-Methoxyphenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(4-Bromophenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(3,4-Dimethylphenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(4-Methylphenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(4-Fluorophenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(3-Bromo-4-methoxyphenyl)ethyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(2-(2,4-Dimethylphenyl)ethyl)-(6R*)-N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-(4-Ethoxyphenyl-methyl)-(6R*)—N6-(4-pyrrolidino-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(4-Chlorophenyl)ethyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(4-Chlorophenyl)ethyl)-(6R)—N6-(2-dimethylamino-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(4-Chlorophenyl)ethyl)-(6R)—N6-(2-(pyridin-2-yl)ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(4-Chlorophenyl)ethyl)-(6R)—N6-(2-(4-aminosulfonyl-phenyl)-ethyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(2,4-Dichlorophenyl)ethyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-(4-Chlorophenyl)ethyl)-(6R)—N6—(N-isopentyl-piperidin-4-yl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3,5-difluorophenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-thiazol-2-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromo-3-trifluoromethylphenyl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R*)—N5-[(4-Acetyl-thiazol-2-yl)methyl]-(6R*)—N6-(2-methylamino-ethyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(2,5-dimethylpyrrolidin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(pyrrolidin-1-yl)pentyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(3-fluoro-4-(pyrrolidin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(2-(methoxymethyl)pyrrolidin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(4-(3,3-difluoropyrrolidin-1-yl)butyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(2-Bromo-3-fluoro-pyridin-5-yl)-(6R)—N6-(4-pyrrolidino-butyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(2-hydroxyethyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(3-hydroxypropyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(4-hydroxybutyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(2-methyl-3-hydroxyprop-2-yl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(2-(2-hydroxyethoxy)ethyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(4-hydroxy-cyclohexyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-[(1-hydroxy-cyclohexyl)methyl]-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(trans-4-(hydroxymethyl)-cyclohexyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(cis-4-(hydroxymethyl)-cyclohexyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(pyrrolidin-3-yl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(2-(N-methylamino)-ethyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(3-(N-methylamino)-propyl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(piperidin-3-yl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-[(pyrrolidin-2-yl)-methyl]-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-[(piperidin-2-yl)-methyl]-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-[(piperidin-3-yl)-methyl]-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(5-Bromothiazol-2-yl)-(6R)—N6-(azetidin-3-yl)-(4S,7R)-[4,7-ethylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(cis-4-(aminomethyl)-cyclohexyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; (5R)—N5-(4-Bromophenyl)-(6R)—N6-(trans-4-(aminomethyl)-cyclohexyl)-(4S,7R)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; end or (5R*)—N5-(2-Trifluoromethyl-pyridin-5-yl)-(6R*)—N6-(4-pyrrolidin-1-yl-butyl)-(4S*,7R*)-[4,7-ethenylene-spiro[2.4]heptane]-5,6-dicarboxamide; or a salt thereof. |
| Claim: |
12. The compound according to claim 1, wherein the salt thereof is a pharmaceutically acceptable salt thereof. |
| Claim: |
13. A pharmaceutical composition comprising, a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient. |
| Claim: |
14. A method of treating or preventing a disease comprising administering to a subject in need thereof, an effective amount of the compound according to claim 1, wherein the disease is selected from inflammatory diseases, obstructive airway diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases or amyloid-mediated disorders; and for modulating an immune responses. |
| Claim: |
15. A method of treating or preventing a disease comprising administering to a subject in need thereof, an effective amount of the composition according to claim 13, wherein the disease is selected from inflammatory diseases, obstructive airway diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases and amyloid-mediated disorders; and for modulating an immune responses. |
| Current U.S. Class: |
51421/017 |
| Current International Class: |
61; 07; 07; 07; 07; 07; 07; 07; 07; 07; 07; 07; 07; 07; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 61; 07; 07 |
| Accession Number: |
edspap.20120115841 |
| Database: |
USPTO Patent Applications |
