DK2880026T3 - Dihydropyridon-p1 som faktor xia-hæmmere - Google Patents

Dihydropyridon-p1 som faktor xia-hæmmere Download PDF

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DK2880026T3
DK2880026T3 DK13747625.5T DK13747625T DK2880026T3 DK 2880026 T3 DK2880026 T3 DK 2880026T3 DK 13747625 T DK13747625 T DK 13747625T DK 2880026 T3 DK2880026 T3 DK 2880026T3
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oxo
methyl
tetrahydropyridin
nonadeca
chloro
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Wu Yang
James R Corte
Paul J Gilligan
Donald J P Pinto Pinto
William R Ewing
Andrew K Dilger
Yufeng Wang
Tianan Fang
Kumar B Pabbisetty
Ii Leon M Smith
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Bristol Myers Squibb Co
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Claims (18)

  1. DIHYDR0PYRID0N-P1 SOM FAKTOR XIA-HÆMMERE
    1. Forbindelse med formlen (XI):
    eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra en 6-leddet aryl og en 5- til 6-leddet heterocyklus, hvor aryl og heterocyklussen er substitueret med 1-4 R4; ring B uafhængigt er udvalgt fra en 6-leddet aryl og en 5- til 1 O-leddet heterocyklus, hvor aryl og heterocyklussen er substitueret med 1-4 R3; G1 uafhængigt er udvalgt fra en C3_i0-carbocyklus en 5- til 10-leddet heterocyklus hvor carbocyklussen og heterocyklussen er substitueret med 1-4 R8; X1 uafhængigt er udvalgt fra CR7 og N; — er en eventuel binding; Y uafhængigt er udvalgt fra -NH-C(O)- og -C(0)-NH-; R1 og R2 uafhængigt er udvalgt fra H, halogen, haloalkyl, Ci_4-alkyl (eventuelt substitueret med R6), hydroxyl og alkoxy (eventuelt substitueret med R6) og C3_5-cycloalkyl eventuelt substitueret med R6; R3 uafhængigt er udvalgt fra H, =0, halogen, haloalkyl, Ci_4-alkyl (eventuelt substitueret med R6), C2j4alkenyl (eventuelt substitueret med R6), CM-alkynyl (eventuelt substitueret med R6), CN, N02, -(CH2)n-OR5, -(CII2)n-NR5R5, -(CII2)n-C(0)0R5, -(CII2)n-NR9C(0)0R5, -(CII2)n-NR9C(0)R5, -(CII2)n-NR9C(N-CN)NHR5, -(CH2)n-NR9C(NH)NHR5, -(CII2)n-N=CR'NR3R\ -(CH2)n-NR9C(0)NR5R5, -(CH2)n- C(0)NR5R5, -(CH2)n-NR9C(S)NR9C(0)R5, -(CH2)n-S(0)pR12, -(CH2)n-S(0)pNR5R5, -(CH2)n- NR9S(0)PNR5R5, -(CH2)n-NR9S(0)pR12, -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor eventuelt to tilstødende R3 grupper på carbocyklussen og heterocyklussen kan danne en ring, der eventuelt er substitueret med R6; R4 uafhængigt er udvalgt fra H, OH, halogen, CN, Ci_4-alkyl, Ci_4-haloalkyl, Ci_4-alkoxy, -C(0)NH2, -C(0)NH(CI.4-alkyl), -C(0)N(CI4-alkyl)2, C3.<,-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklusen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Ci_4-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl, amino, substitueret amino), C3_10-carbocyklus og 4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor alterantivt R3 og R3 sammen - A - med det nitrogenatom, hvortil de begge er bundet, danner en heterocyklisk ring, der eventuelt er substitueret med R6; R6 uafhængigt cr udvalgt fra OH, =0, -(CH2)nNH2, -(CH2)nCN, halogen, Ci^-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0Ci_4-alkyl, -(CH^-OCi^-alkyl, -(CH2)n-C3.i0 carbocyklus, -(CH2)n-4- til 10-leddet heterocyklus og -(CH2)n-4- til 1 O-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R10; R7 uafhængigt er udvalgt fra H, hydroxyl, alkoxy, halogen, methyl, ethyl og isopropyl; R8 uafhængigt er udvalgt fra H, halogen, CN, NH2, C^-alkyl, haloalkyl, alkylcarbonyl, alkoxy, haloalkoxy, -(CH2)n-aryl, -(CH2)n-C3_,5-cycloalkyl og -(CH2)n-4- til 6-leddet heterocyklus; hvor eventuelt to tilstødende R8 grupper på carbocyklussen og heterocyklussen kan danne en ring, der eventuelt er substitueret med R10; R9 er H eller Ci_6-alkyl; R10 uafhængigt er udvalgt fra C^-alkyl (eventuelt substitueret med R11), C2_6-alkenyl, C2.6-alkynyl, -(CH2)n-C3_6-cycloalkyl, -0-4- til 1 O-leddet heterocyklus (eventuelt substitueret med R11), F, Cl, Br, CN, N02, =0, C02H, -(CH2)n-OC].5-alkyl, -(CH2)n-ORn og -(CH2)n-NRuRn; R11, ved hver forekomst, uafhængigt er udvalgt fra H, Ci_5-alkyl, -(CH2)n-OH, C3_6-cycloalkyl og phenyl, eller R11 og R11 sammen med det nitrogenatom, hvortil de begge er bundet, danner en heterocyklisk ring, der eventuelt er substitueret med C^-alkyl; R12 er Q_(,-alkyl eventuelt substitueret med R11; m er et heltal, der er uafhængigt udvalgt fra O og 1; n, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra O, 1, 2, 3 og 4; p, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra O, 1 og 2, forudsat at følgende forbindelser er udelukket: r»1
    (VIII) hvor ring A uafhængigt er udvalgt fra
    —- er en eventuel binding; R1 uafhængigt er udvalgt fra H, hydroxyl og Ci_4-alkyl; R2, ved hver forekomst, uafhængigt er udvalgt fra H og hydroxyl; R4 uafhængigt er udvalgt fra H, OH, F, OCi_4-alkyl og CN; R8a uafhængigt er udvalgt fra H, F, Cl og Br; R8b uafhængigt er udvalgt fra H og F; og R8c uafhængigt er udvalgt fra II, F og Cl.
  2. 2. Forbindelse ifølge krav 1 med formlen (XII):
    eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra phenyl og en 5- til 6-leddet heterocyklus; G1 uafhængigt er udvalgt fra aryl, C3_6-cycloalkyl og en 5- til 6-leddet heterocyklus hvor aryl, cycloalkyl og heterocyklussen er substitueret med 1-4 R8; R1 og R2 uafhængigt er udvalgt fra H, halogen, CF3, Ci_6-alkyl og hydroxyl; R3 uafhængigt er udvalgt fra H, halogen, haloalkyl, Ci^-alkyl (eventuelt substitueret med R6), C24-alkenyl (eventuelt substitueret med R6), CN, N02, -(CH2)n-OR5, -(CH2)n-NR5R5, -(CH2)n- C(0)OR5, -(CH2)n-NHC(0)0R5, -(CH2)n-NHC(0)R5, -(CH2)n-NHC(N- CN)NHR5, -(CH2)n-NHC(NH)NHR5, -(CH2)n-N=CHNR5R5, -(CH2)n-NHC(0)NR5R5, -(CH2)n-C(0)NR5R5, (CH2)n-NHC(S)NR9C(0)R5,-(CH2)n-S(0)pR12, -(CH2)n-S(0)pNR5R5, -(CH2)n-NHS(0)pNR5R5, -(CH2)n-NHS(0)pR12, -(CH2)n-C3_io-carbocyklus og -(CH2)„-4- til 10- leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor eventuelt to tilstødende R3 grupper på carbocyklussen og heterocyklussen kan danne en ring, der eventuelt er substitueret med R6; R3a uafhængigt er udvalgt fra H og halogen; R3b uafhængigt er udvalgt fra H, halogen og CN; R4 uafhængigt er udvalgt fra H, OH, F, Cl, Br, Ci_4-alkyl, Ci_4-alkoxy, CF3, CN, C3_6-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklussen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Ci4-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl, amino, substitueret amino), -(CH2)„-C3_io -carbocyklus og -(CH2)„-4- til 10-leddet heterocyklus, hvor carbocyklussen og hetero cyklus sen eventuelt er substitueret med R6; R6 uafhængigt er udvalgt fra -(CH2)n-OH, =0, NH2, -(CH2)n-CN, halogen, C].6-alkyl, -(CH2)n-C(0)OH, -(CH2)n-C(0)OC14-alkyl, -(CH2)n-OC14-alkyl, -(CH2)n-C3.6-cycloalkyl, -(CH2)n-4- til 10-leddet heterocyklus og -0-(CH2)n-4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10; R7 uafhængigt er udvalgt fra H, F, methyl og ethyl; R8 uafhængigt er udvalgt fra H, halogen, CN, NH2, C^-alkyl, haloalkyl, alkylcarbonyl, alkoxy, haloalkoxy, aryl, C3_6-cycloalkyl og 4- til 6-leddet heterocyklus; hvor eventuelt to tilstødende R8 gmpper kan tages sammen for at danne en carbocyklus eller heterocyklus omfattende carbonatomer og 1 til 4 heteroatomer, der er udvalgt fra N, NH, N(Ci_4-alkyl), O og S(0)p, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med OH, NH2, halogen og Ci_6-alkyl; m er et heltal, der er uafhængigt udvalgt fra 0 og 1; n, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra 0, 1 og 2; og p, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra 0, 1 og 2.
  3. 3. Forbindelse ifølge krav 2 med formlen (XIII):
    eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra phenyl og en 5- til 6-leddet heterocyklus; G1 uafhængigt er udvalgt fra aryl, C3_6-cycloalkyl og en 5- til 6-leddet heterocyklus, hvor aryl, cycloalkyl og heterocyklussen er substitueret med 1 til 4 R8; R1 og R2 uafhængigt er udvalgt fra H, halogen, CF3, Ci_6-alkyl og hydroxyl; R3 uafhængigt er udvalgt fra H, halogen, haloalkyl, Ci4-alkyl (eventuelt substitueret med R6), C24-alkenyl (eventuelt substitueret med R6), CN, N02, -(CH2)n-OR5, -(CH2)n-NR5R5, -(CH2)n- C(0)OR5, -(CH2)n-NHC(0)0R5, -(CH2)n-NHC(0)R5, -(CH2)n-NHC(N- CN)NHR5, -(CH2)n-NHC(NH)NHR5, -(CH2)n- N=CHNR5R5, -(CH2)n-NHC(0)NR5R5, -(CH2)n-NHC(0)NR5R5-, -(CH2)n-C(0)NR5R5, (CH2)n-NR9C(S)NR9C(0)R5, -(CH2)n-S(0)pR12, -(CH2)n-S(0)pNR5R5, -(CH2)n-NHS(0)pNR5R5, -(CH2)n- NHS(0)pR12, -(CH2)n-C3_io-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; R3b uafhængigt cr udvalgt fra H, F, Cl, CN, C(0)0F1 og C(0)OCi^-alkyl; R4 uafhængigt er udvalgt fra H, OH, F, Cl, Br, Ci_6-alkyl, Ci_6-alkoxy, CF3, CN, C3_6-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklussen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Ci^-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor alternativt to tilstødende R5 grupper kan tages sammen for at danne en carbocyklus eller heterocyklus eventuelt substitueret med R6; R7 uafhængigt er udvalgt fra H, F, methyl og ethyl; R6 uafhængigt er udvalgt fra OH, NH2, halogen, C^-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0C14-alkyl, -(CH2)n-OC1.4-alkyl, =0, -(CH2)n-C3.6-cycloalkyl og -(CH2)n-4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10; R8 uafhængigt er udvalgt fra H, halogen, CN, NH2, C^-alkyl, alkylcarbonyl, haloalkyl, alkoxy, haloalkoxy, aryl, C3.6-cycloalkyl og 4- til 6-leddet heterocyklus; hvor eventuelt to tilstødende R8 grupper kan tages sammen for at danne en carbocyklus eller heterocyklus omfattende carbonatomer og 1 til 4 heteroatomer, der er udvalgt fra N, NH, N(Ci_4-alkyl), O og S(0)p, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med OH, NH2, halogen og C4.6-alkyl; n, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra 0, 1 og 2; og p, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra 0, 1 og 2.
  4. 4. Forbindelse ifølge krav 2 med formlen (XIV):
    eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A er udvalgt fra phenyl, imidazol, pyridin, pyridazin, pyrimidin, pyridon og pyridazinon; G1 uafhængigt er udvalgt fra phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, furyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, piperazinyl, piperidinyl, morpholinyl og oxadiazolyl, hver substitueret med 1 til 4 Rs; R1 og R2 uafhængigt er udvalgt fra H, F, Ci^-alkyl, alkoxy og hydroxyl; Rla og R2a uafhængigt er udvalgt fra H, F og hydroxyl; R3 uafhængigt er udvalgt fra H, halogen, haloalkyl, Ci^-alkyl (eventuelt substitueret med R6), C2-r alkcnyl (eventuelt substitueret med R6), C2-4-alkynyl (eventuelt substitueret med R6), CN, NO2, -(CH2)n-OR5, NR5R5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -NHC(0)NR5R5-, -C(0)NR5R5, -(CH2)n-NHC(S)NHC(0)R5, -NHS(0)2CM-alkyl, -(CH2)n-C3.10 -carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor eventuelt to tilstødende R3 grupper danner en heterocyklus eventuelt substitueret med R6; R3b uafhængigt er udvalgt fra H, F, CN, C(0)0H og C(0)OCi_4-alkyl; R4 uafhængigt er udvalgt fra H, OH, F, Cl, Br, C·^ alkyl, Q.g-alkoxy, CF3, CN, C3_6-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklusen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, C14. alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_io-carbocyklus og -(CH2)n-4- til 10-lcddct heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; R6 uafhængigt er udvalgt fra OH, NH2, halogen, Ci_6-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)OCi^-alkyl, -(CH2)n-OCi^-alkyl, =0, C3.6-cycloalkyl og 4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10; R7 uafhængigt er udvalgt fra H og methyl; R8 uafhængigt er udvalgt fra H, halogen, CN, NH2, Ci_6-alkyl, alkylcarbonyl, haloalkyl, alkoxy, haloalkoxy, aryl, C3_6-cycloalkyl og 4- til 6-leddet heterocyklus.
  5. 5. Forbindelse ifølge krav 4, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra
    G1 uafhængigt er udvalgt fra
    R1 og R2 uafliængigt er udvalgt fra H, F, methyl, ethyl, isopropyl og hydroxyl; Rla og R2a uafhængigt er udvalgt fra H, F og OH; R3 uafhængigt er udvalgt fra H, F, Cl, Br, I, haloalkyl, C^-alkyl (eventuelt substitueret med R6), C24-alkenyl (eventuelt substitueret med R6), CN, -(CH2)„-OR5, NR5R5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -NHC(0)NR5R5-, -C(0)NR5R5, -(CH2)n-NHC(S)NHC(0)R5, -NHS(0)2Ci_ 4alkyl, -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor eventuelt to tilstødende R3 grupper danner en heterocyklus eventuelt substitueret med R6; R3b uafhængigt er udvalgt fra H, F, CN, C(0)0H og C(0)OCi_4-alkyl; R4 uafhængigt er udvalgt fra H, OH, F, Cl, Br, Ci_6-alkyl, Ci_6-alkoxy, CF3, CN, C3.6-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklussen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Ci^-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; R6 uafhængigt er udvalgt fra OH, NH2, halogen, C^-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0C4j4-alkyl, -(CH2)n-OCiJ4-alkyl, =0, C3.6-cycloalkyl og 4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10; R7 uafhængigt er udvalgt fra H og methyl; R8 uafhængigt er udvalgt fra H, Ci_6-alkyl, alkylcarbonyl, haloalkyl, aryl, C3_6-cyloalkyl og 4- til 6-leddet heterocyklus; R8auafhængigt er udvalgt fra H, halogen, CN, C^-alkyl, C(0)Clj4-alkyl, OCi_3-alkyl, CF3, OCHF2, NIIC(0)Ci_4-alkyl, aryl, C3.6-cycloalkyl og 4- til 6-leddet heterocyklus; Rsb uafhængigt er udvalgt fra H og halogen; og R8c uafhængigt er udvalgt fra H, halogen, CN, Ci_4-alkyl, alkoxy, NH2 og haloalkoxy.
  6. 6. Forbindelse ifølge krav 5, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: R3 uafhængigt er udvalgt fra H, F, Cl, Br, I, C2_4-alkenyl (eventuelt substitueret med R6), CN, -(CH2)n-OR5, NR5R5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -C(0)NR5R5, -NHC(S)NHC(0)R5, -NHS(0)2C1^-alkyl, -(CH2)n-C3.10-carbocyklus og -(CH2)n-4- til 6-leddet heterocyklus omfattende carbonatomer og 1-4 heteroatomer, der er udvalgt fra N, O og S(0)p, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; R3b uafhængigt er udvalgt fra H, F, CN, C(0)0H og C(0)0C1_4-alkyl; R5 uafhængigt er udvalgt fra H, C^-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 6-leddet heterocyklus omfattende carbonatomer og 1 til 4 heteroatomer, der er udvalgt fra N, O og S(0)p, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; og R6 uafhængigt er udvalgt fra OH, NH2, halogen, Ci_6-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0CiJ4-alkyl, -(CH2)n-OCM-alkyl, =0, C3_6-cycloalkyl, 4- til 10-leddet heterocyklus, -0-4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10.
  7. 7. Forbindelse ifølge krav 6, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: R3 uafhængigt er udvalgt fra H, F, Cl, Br, I, CM-alkenyl (eventuelt substitueret C(O)OH), CN, -(CH2)n-OR5, NR5R5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -C(0)NR5R5, -NHC(S)NHC(0)R5, -NHS(0)2C]j4-alkyl og -(CH2)n-4- til 6-leddet heterocyklus udvalgt fra triazolyl og tetrazolyl, der hver eventuelt er substitueret med R6; R3b uafhængigt er udvalgt fra H, F, CN, C(0)0H og C(0)0Ci_4-alkyl; R5 uafhængigt er udvalgt fra H, Ci^-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 6-leddet heterocyklus udvalgt fra pyrazinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, piperazinyl, piperidinyl, morpholinyl, oxanyl og oxadiazolyl, der hver eventuelt er substitueret med R6; og R6 uafhængigt er udvalgt fra OH, -(CH2)n-OH, NH2, halogen, Cl45-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0Ci_4-alkyl, -(CH2)n-OCi4-alkyl, =0, C3_6-cycloalkyl og 4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10.
  8. 8. Forbindelse ifølge krav 7, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: R3 uafhængigt er udvalgt fra H, F, Cl, Br, I, C2j4-alkenyl (eventuelt substitueret C(O)OH), CN, -(CH2)n-OR5, NHR5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -C(0)NR5R5, -NHC(S)NHC(0)R5, -NHS(0)2Ci4-alkyl og -(CH2)n-4- til 6-lcddct heterocyklus udvalgt fra triazolyl og tetrazolyl, der hver eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Ci^-alkyl,; -(CH2)i_3-OH, -(CH2)i_3-OCi_4-alkyl, -(CH2)i_3-C(0)0H, -(CH2)1_3-C(0)0C1_4-alkyl, -(CH^-NH,, -(CH^-NHC^-alkyl, -(CH2)1.3-N(C1.4-alkyl)2, -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 6-leddet heterocyklus udvalgt fra
    R6 uafhængigt er udvalgt fra H, -(CH2)„-OH, NH2, halogen, Ci_6-alkyl, -(CH2)n-CN, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)OCM-alkyl, -(CH2)n-OC^-alkyl, =0, C3.6-cycloalkyl, 4- til 10-leddet heterocyklus, -0-4- til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10.
  9. 9. Forbindelse ifølge krav 8 med formlen (XV):
    eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra
    R1 og R2 uafhængigt er udvalgt fra H, F, C^-alkyl, alkoxy og hydroxyl; Rla, ved hver forekomst, uafhængigt er udvalgt fra H, F og hydroxyl; R3 uafhængigt er udvalgt fra H, F, Cl, Br, I, C2^-alkenyl (eventuelt substitueret C(O)OH), CN, -(CH2)„-OR5, NHR5, -(CH2)n-C(0)0R5, -NHC(0)0R5, -NHC(0)R5, -NHC(0)NR5R5, -C(0)NR5R5, -NHC(S)NHC(0)R5, -NHS(0)2C]4-alkyl og -(CH2)n-4- til 6-leddet heterocyklus udvalgt fra triazolyl og tetrazolyl, der hver eventuelt er substitueret med R6; R4 uafhængigt er udvalgt fra H, OH, F, OCi_4-alkyl, Ci_4-alkyl, CN, C3_6-cycloalkyl, aryl og 5- til 6-leddet heterocyklus, hvor cycloalkyl, aryl og heterocyklusen eventuelt er substitueret med R6; R5 uafhængigt cr udvalgt fra H, Ci^-alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl), -(CH2)n-C3_i0-carbocyklus og -(CH2)„-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; R6 uafhængigt er udvalgt fra OH, NH2, halogen, C^-alkyl, C3_6-cycloalkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0Ci_4-alkyl, -(CH^-OCi^-alkyl, =0, C3.6-cycloalkyl, 4- til 10-leddet heterocyklus og -0-4-til 10-leddet heterocyklus, hvor cycloalkyl og heterocyklussen eventuelt er substitueret med R10; R8a uafhængigt er udvalgt fra H, F, Cl, Br, CN, OCH3, CH3, C(0)CH3, CF3, OCHF2, NnC(0)C|_4-alkyl, aryl, C3_6-cycloalkyl og 4- til 6-leddet heterocyklus, R8b uafhængigt er udvalgt fra H og F; R8c uafhængigt er udvalgt fra H, F, Cl og OCH3; og n, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra O, 1 og 2.
  10. 10. Forbindelse ifølge krav 9, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: R8a uafhængigt er udvalgt fra H, F, Cl, Br, CN, OCH3, CH3, C(0)CH3, CF3, OCHF2, ΝΗ0(0)^_4-alkyl, phenyl, C3_6-cycloalkyl og 4 til 6-leddet heterocyklus udvalgt fra pyrazol, imidazol, triazol, tetrazol, pyridin, der hver eventuelt er substitueret med R10; Rsb uafhængigt er udvalgt fra H og F; og R8c uafhængigt er udvalgt fra H, F, Cl og OCH3.
  11. 11. Forbindelse ifølge krav 1, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring A uafhængigt er udvalgt fra
    ring B er en 5- til 10-leddet heterocyklus substitueret med 1 til 4 R3; G1 uafhængigt er udvalgt fra
    R1 og R2 uafhængigt er udvalgt fra H, F, methyl, ethyl, isopropyl og hydroxyl; R3 uafhængigt er udvalgt fra H, =0, halogen, haloalkyl, Ci_4-alkyl eventuelt substitueret med R6, CM-alkenyl eventuelt substitueret med R6, C2.4-alkynyl eventuelt substitueret med R6, CN, N02, -(CH2)n-OR5, -(CH2)n-NR5R5, -(CH2)n-C(0)0R5, -(CH2)n-NR9C(0)0R5, -(CH2)n-NR9C(0)R5, -(CH2)n-NR9C(N-CN)NHR5, -(CH2)n-NR9C(NH)NHR5, -(CH2)n-N=CR9NR5R5, -(CH2)n-NR9C(0)NR5R5, -(CH2)n- C(0)NR5R5, -(CH2)n-NR9C(S)NR9C(0)R5, -(CH2)n-S(0)pR12, -(CH2)n-S(0)pNR5R5, -(CH2)n- NR9S(0)PNR5R5, -(CH2)n-NR9S(0)pR12, -(CH2)n-C3_i0-carbocyklus og -(CH2)n-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; hvor eventuelt to tilstødende R3 grupper på carbocyklussen og heterocyklussen kan danne en ring, der eventuelt er substitueret med R6. R4 uafhængigt er udvalgt fra H, OH, halogen, CN, Ci.4-alkyl, Ci_4-haloalkyl, Ci_4-alkoxy, -C(0)NH2, -C(0)NH(Ci_4-alkyl), -C(0)N(Ci4-alkyl)2, C3_6-cycloalkyl, aryl og 5- til 6-lcddct heterocyklus, hvor cycloalkyl, aryl og heterocyklussen eventuelt er substitueret med R6; R5 uafhængigt er udvalgt fra H, Q4 alkyl (eventuelt substitueret med halogen, hydroxyl, alkoxy, carboxy, alkoxycarbonyl, amino, substitueret amino), C3.10-carbocyklus og 4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R6; alternativt hvor R5 og R5 sammen med det nitrogenatom, hvortil de begge er bundet, danner en heterocyklisk ring, der eventuelt er substitueret med R6; R6 uafhængigt er udvalgt fra OH, =0, -(CH2)nNH2, -(CH2)nCN, halogen, Ci_6-alkyl, -(CH2)n-C(=0)0H, -(CH2)n-C(=0)0C1.4-alkyl, -(CH2)n-OC1.4-alkyl, -(CH2)n-C3.10-carboklus og -(CH2)n-4- til 10-leddet heterocyklus, -0-4- til 10-leddet heterocyklus, hvor carbocyklussen og heterocyklussen eventuelt er substitueret med R10; R7 uafhængigt er udvalgt fra H, F, methyl og ethyl; R8 uafhængigt er udvalgt fra H, Ci_6-alkyl, alkylcarbonyl, haloalkyl, aryl, C3_6-cycloalkyl og 4- til 6-leddet heterocyklus. RSiluafhængigt er udvalgt fra H, halogen, CN, Ci_3-alkyl, C(0)Ci_4-alkyl, OCi_3-alkyl, CF3, OCHF2, NHC(0)Ci_4-alkyl, aryl, C3_6-cycloalkyl og 4- til 6-leddet heterocyklus; R8b uafhængigt er udvalgt fra H og halogen; og RSc uafhængigt er udvalgt fra H, halogen, CN, Ci_4-alkyl, alkoxy, NH2 og haloalkoxy; R10 uafhængigt er udvalgt fra Ci^-alkyl eventuelt substitueret med R11, C2_6-alkenyl, C2_6-alkynyl, -(CH2)n-C3_6-cycloalkyl, -0-4- til 1 O-leddet heterocyklus (eventuelt substitueret med R11), F, Cl, Br, CN, N02, =0, C02H, -(CH2)i1-OC1.5-alkyl, -(CH2)n-ORn og -(CH2)n-NR11R11; R11, ved hver forekomst, uafhængigt er udvalgt fra H, Ci_5-alkyl, C3_6-cycloalkyl og phenyl, eller R11 og R11 sammen med det nitrogenatom, hvortil de begge er bundet, danner en heterocyklisk ring, der eventuelt er substitueret med C1_4-alkyl; R12 er Ci_6-alkyl eventuelt substitueret med R11; m er et heltal, der er uafhængigt udvalgt fra O og 1; n, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra O, 1, 2, 3 og 4; p, ved hver forekomst, er et heltal, der er uafhængigt udvalgt fra O, 1 og 2.
  12. 12. Forbindelse ifølge krav 11, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor: ring B er udvalgt fra
    — er en eventuel binding; R3 uafhængigt er udvalgt fra H, =0, halogen, Ci_4-alkyl eventuelt substitueret med R6, -OR5, -NR5R5, -C(0)0R5, -NR9C(0)0R5, -(CH2)n-NR9C(0)R5, -(CH2)n-C(0)NR5R5, -S(0)pNR5R5 og C3-10-carbocyklus; og R5 uafhængigt er udvalgt fra H og Ci^-alkyl.
  13. 13. Forbindelse ifølge krav 1, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt deraf, hvor forbindelsen er udvalgt fra gruppen, der består af: methyl A-[(10R,14S)-14-[4-(3-chlor-2-fhror-6-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,/]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (1); methyl Α-[( 1 OR, 145)-14-[4-(3 -chlor-2-fluor-6-methylphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (2); methyl A-[( 1 OR, 145)-14-[4-(3 -chlor-6-cyan-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (3); methyl A-[(107^14iS)-14-[4-(2-cyan-6-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (4); methyl A-[(10A,14b)-14-[4-(4-chlor-3-fluorpyridin-2-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (5); methyl N-[(10R,14S)-14-[4-(4-chlor-3-methoxypyridin-2-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (6); methyl N-[(10R,14S)-14-[4-(3,6-dicyan-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (7); methyl N-[(10R,14S)-14-[4-(3-amino-6-cyan-lH-indazol-7-yl)-6-oxo-l,2,3,6-tctrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (8); methyl N-[(10R,14S)-14-[4-(3-amino-6-cyan-l,2-benzoxazol-7-yl)-6-oxo-l,2,3,6- tetrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (9); methyl A-[(107?,145)-14-[4-(4-chlor-3-fluorpyridin-2-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]iionadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (10); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,6-dihydropyridazin-l-yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (ii); (1 OR, 14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (12); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl- 8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (13); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-fLuor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (14); (10R,14S)-5-chlor-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (15); (1 OR, 14S)-14-[4-(3-chlor-2,6-ditluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-5-[(pyrimidin-2-yl)amino]-8,16-diazatricyclo[ 13.3.1.0i,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (16); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-methoxy-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (17); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-hydroxy-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (18); (10R,14S)-4-chlor-14-[4-(3-chlor-2,6-difluorphcnyl)-6-oxo-l,2,3,6-tctrahydropyridin-l-yl]-5-hydroxy-10-methyl-8,16-diazatricyclo[13.3.L0i,7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (19); (10R,14S)-4,6-dichlor-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-hydroxy-10-methyl-8,16-diazatricyclo[13.3.1.0z’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (20); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-5-[(5-methyl-l,3,4-oxadiazol-2-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (21); methyl A-[(10A,145)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9,12-dioxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (22); (14R)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo- 8.16- diazatricyclo[13.3.1.02’']nonadeca-l(18),2,4,6,15(19),16-hexaen-5-carbonitril, TFA-salt (23); methyl N-[(14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-8-oxo- 9.16- diazatricyclo[13.3.1.02’']nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (24); methyl A-[(107^145)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6- tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl]carbamat, TFA-salt (25); methyl A-[(10A,145)-14-[4-(3-chlor-6-cyan-2-iluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (26); tert-butyl N-[(10R,14S)-14-[4-(3-chlor-2,6-dilluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (27); (145)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-carboxylsyre, TFA-salt (28); (145)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-carboxamid, TFA-salt (29); methyl A-[(10A,145)-14-[4-(3-chlor-6-cyan-2-iluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9,17-dioxo-8,l 6-diazatricyclo[l 3.3.1.02,7]nonadeca-l (18),2,4,6,15(19)-pentaen-5-yl]carbamat, TFA-salt (30); methyl A-[(10R,145)-14-{4-[3-chlor-6-(difluormethoxy)-2-fluorphenyl]-6-oxo-l,2,3,6- tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl]carbamat, TFA-salt (31); methyl A-[(10i?,145)-14-{4-[3-chlor-6-(difluormethoxy)-2-fluorphenyl]-6-oxo-l,2,3,6- tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl]carbamat, TFA-salt (32); (107?, 145)-14-[4-(3 -chlor-6-cyan-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10-methyl- 9- oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-carboxamid, TFA-salt (33); (14S)-14-[4-(6-acctyl-3 -chlor-2-fluorphcnyl)-6-oxo-1,2,3,6-tctrahydropyridin-1 -yl] -10-mcthyl-9-oxo-8,16-diazatncyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-carboxamid, TFA-salt (34); (14S)-14-[4-(3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-carboxamid, TFA-salt (35); methyl N-[(10R,14S)-14-{4-[5-chlor-2-(trifluormethyl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (36); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-5-[(5-methyl-l,3,4-oxadiazol-2-yl)amino]-8,18-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (37); (14S)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl-5-(4H-l,2,4-triazol-3-yl)-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (38); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)amino] - 10-methyl-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (39); 2-(5-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-i(19),2,4,6,15,17-hexaen-5-yi]amino}-l,3,4-oxadiazol-2-yl)acetonitril, TFA-salt (40); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-{[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl] amino} -10-methyl-8,16-diazatricyclo[ 13.3.1,02,7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (41); ethyl 2-(5-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]- 10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]amino}-l,3,4-oxadiazol-2-yl)acetat, TFA-salt (42); methyl N-[(10R,14S)-14-[4-(6-brom-2-fhior-3-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,/]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (43); methyl N-[(10R,14S)-14-{4-[5-chlor-2-(difluormethoxy)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’']nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (44); (1 OR, 14S)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl- 8.16- diazatricyclo[l 3.3.1.02,,]nonadeca-l (19),2,4,6,15,17-hexaen-9-on, TFA-salt (45); (1 OR, 14S)-14-[4-(3,6-dicyan-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl- 8.16- diazatricyclo[13.3.1.02’']nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (46); (10R,14S)-14-[4-(3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (47); (10R,14S)-14-[4-(6-acctyl-3-chlor-2-fluorphcnyl)-6-oxo-l,2,3,6-tctrahydropyridin-l-yL]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (48); 4-chlor-3-fluor-2-{l-[(10R,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}benzonitril, TFA-salt (49); 3-fluor-2-{l-[(10R,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}benzonitril, TFA-salt (50); (10R,14S)-14-[4-(3-chlor-2-fluor-6-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (51); (1 OR, 14S)-14-(4-(3-chlor-6-cyclopropyl-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (52); 2-(tert-butoxy)ethyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6- tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.0i’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl]carbamat, TFA-salt (53); 2-hydroxyethyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorplienyl)-6-oxo-l,2,3,6-tetrahydropyridm-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (54); (10R,14S)-14-{4-[3-chlor-2-nuor-6-(lFI-pyrazol-4-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridm-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.027]nonadeca-l(19),2,4,6,15,17-liexaen-9-on, TFA-salt (55); (10R,14S)-14-{4-[3-chlor-2-fluor-6-(pyridin-4-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (56); (10R,14S)-14-[4-(3-clilor-2-fluor-6-phenylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4.6,15,17-hexaen-9-on, TFA-salt (57); (10R,14S)-14-{4-[3-clilor-2-iluor-6-(pyridin-3-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (58); (10R,14S)-14-{4-[3-chlor-2-iluor-6-(l-methyl-lFl-pyrazol-4-yl)phenyl]-6-oxo-l,2,3,6-tctrahydropyridin-l-yl}-10-mcthyl-8,16-diazatricyclo[13.3.1.02’7]nonadcca-l(19),2,4,6,15,17-hcxacn-9-on, TFA-salt; (59); (10R,14S)-14-{4-[3-chlor-6-(l,3-dimethyl-lH-pyrazol-4-yl)-2-fluorphenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (60); (10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4-iodo-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (61); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4-iodo-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (62); j-acetyi-l-L(1^14S)-14-[4-(3-cnIor-2,6-diiluorphenyI)-6-oxo-l,z,3,6-tetrahydropyridm-l-yiJ-IU-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]thiourea (63); methyl N-[( 1 OR, 14S)-14-[4-(3 -chlor-2,6-difluorphcnyl)-5-mcthyl-6-oxo-1,2,3,6-tctrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.0!2’7!]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (64); (10R,14S)-14-[4-(3-chlor-2-fluorphenyl)-2-oxo-l,2-dihydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (65); (10R,14S)-14-[4-(6-amino-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (66); (10R,14S)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (67); (10R,14S)-14-{4-[3-chlor-2-fluor-6-(lH-l,2,3,4-tetrazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (68); (10R,14S)-5-brom-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, TFA-salt (69); (10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-16-ium-16-olat, TFA-salt (70); (10R,14S)-14-{4-[5-chlor-2-(lH-l,2,4-triazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (71); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl- 5,8,16-triazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (72); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-3-methyl-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (73); (10R,14S)-14-{4-[5-chlor-2-(3-methyl-lH-l,2,4-triazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (74); N-[(10R, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]acetamid, TFA-salt (75); N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]methanesulfonamid, TFA-salt (76); methyl N-[(10R,1 IE, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l- yl]-10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02,,]nonadeca-l (19),2(7),3,5,11,15,17-heptaen-5-yl]carbamat, TFA-salt (77); methyl N-[(10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,6-dihydropyridazin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (78) ; methyl N-[(10R,14S)-14-[4-(3-chlor-6-cyan-2-fluorphenyl)-6-oxo-l,6-dihydropyridazin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (79) ; (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl]-3-fluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (80); (14R, 18 S)-18-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -14-methyl-8,12,20-triazatetracyclo[17.3.1.02'11.04'9]tricosa-l(23),2,4(9),5,10,19,21-heptaene-7,13-dion, TFA-salt (81); (2Z)-3-[(10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,/]nonadeca-l(19),2,4,6,15,17-hexaen-4-yl]prop-2-enoic acid, 2 TFA-salt: (82); (13R, 17S)-17-[4-(3 -chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -6,13 -dimethyl-12-oxo-7,ll,19-triazatetracyclo[16.3.1.02’10.04’8]docosa-l(22),2,4(8),5,9,18,20-heptaene-5-carboxylsyre, TFA-salt (83); (13R, 17S)-17-[4-(3 -chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -13 -methyl- 7.11.19- triazatetracyclo[l 6.3.1.02,1°.04,8]docosa-l (22),2,4(8),9,18,20-hexaen-6,12-dion, TFA-salt (84); (13R, 17S)-17-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl]-6,13-dimethyl- 7,1 l,19-triazatetracyclo[16.3.1.02’10.04’8]docosa-l(22),2,4(8),5,9,18,20-heptaen-12-one, TFA-salt (85); (14R, 18 S)-18-[4-(3 -chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 14-methyl- 8.12.20- triazatetracyclo[17.3.1.02,11.04’9]tricosa-l(23),2(l l),3,9,19,21-hexaen-7,13-dion, TFA-salt (86); fert-butyl 2-{[(10R,14S)-14-[4-(3-chlor-2,6-dilluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamoyl}acetat, TFA-salt (87); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-5-[(pyridin-2-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, 2TFA-salt (88); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-5-[(pyridin-4-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (89); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-5-[(pyrimidin-4-yl)amino]-8,16-diazatricyclo[ 13.3.1.0i,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (90); (1 OR, 14S)-5-amino-14-[4-(3 -chlor-2,6-difluorphenyl)-2-oxo-1,2-dihydropyridin-1 -yl] - 10-methyl- 8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on, 2 TFA-salt (91); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-2-oxo-1,2-dihydropyridin-1 -yl] -10-methyl-5-[(pyrimidin-2-yl)amino]-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (92); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-5-[(pyrazin-2-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (93); methyl N-[(10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-2-oxo-2,5-dihydro-lH-pyrrol-l-yl]- 10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (94); (105.145) -14-[4-(3-chlor-2,6-difluoiphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-(propan-2-yl)-8,16-diazatricyclo[13.3.1.0z’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-9-on, TFA-salt (95); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-(propan-2-yl)-8,16-diazatricyclo[13.3.1.0z’7]nonadcca-l(18),2,4,6,15(19),16-hcxacn-9-on, TFA-salt (96); methyl N-[(10R,14S)-10-methyl-14-[4-(l-methyl-lH-imidazol-5-yl)-6-oxo-l,2,3,6- tetrahydropyridin-l-yl]-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (97); methyl N-[(10R,14S)-14-(4-cyclohexyl-6-oxo-l,2,3,6-tetrahydropyridin-l-yl)-10-methyl-9-oxo- 8.16- diazatricyclo[13.3.1.02’']nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (98); methyl N-[(10R,14S)-14-[4-(5-chlorpyridin-3-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-i(19),2,4,6,15,17-hexaen-5-yl]carbamat, bis TFA-salt (99); (105.145) -14-{4-[3-chlor-2-fluor-6-(lH-l,2,3,4-tetrazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-(propan-2-yl)-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-9-on, TFA-salt (100); methyl N-[(10R, 14S)-14-[4-(l -benzyl-lFI-imidazol-5-yl)-6-oxo-1,2,3,6-tetrahydropyridin-l -yl]-10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1,02,7]nonadeca-1 (19),2,4,6,15,17-hexaen-5-yl]carbamat, bis TFA-salt (101); methyl N-[(10R, 14S)-14-[4-(3-chlor-6-cyan-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat, TFA-salt (102); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-{[5-(furan-2-yl)-l,3,4-oxadiazol-2-yl]amino}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (103); methyl N-[( 1 OR, 14S)-14-[4-(6-cyan-2-fluor-3 -methylphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10-methyl -9-oxo-8,16-diazatricyclo[ 13.3.1,02,/]nonadeca-1(l8),2,4,6,l5(l9),l6-hexaen-5-y1]carbamat, TFA-salt (104); (14S)- 14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l, 2,3,6-tetrahydropyridin-l -yl]-10-methyl-9-oxo- 8.16- diazatricyclo[13.3.1.02’']nonadeca-l(18),2,4,6,15(19),16-hexaen-5-carboxylsyre, TFA-salt (105); (14S)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-carboxylsyre, TFA-salt (106); (14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo- 8.16- diazatricyclo[13.3.1.02’']nc>nadeca-l(18),2,4,6,15(19),16-hexaen-5-carboxamid, TFA-salt (107); (14S)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-carboxamid, TFA-salt (108); (14S)-14-[4-(3-chlor-2,6-difluo^henyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo- 8.16- diazatricyclo[13.3.1.02’,]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-carboiiitril, TFA-salt (109); methyl N-[( 1 OR, 14S)-14-[4-(5-chlor-2-methylphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (110); methyl N-[(10R,14S)-14-[4-(2,6-difluor-3-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (in); methyl N-[(10R,14S)-14-[4-(2-fluor-3-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (112); methyl N-[(10R,14S)-14-[4-(2-fluor-5-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-i(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (113); methyl N-[(10R,14S)-14-[4-(2,3-dimethylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (114); methyl N-[(10R,14S)-14-[4-(2-lluor-3-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (115); methyl N-[(10R,14S)-14-[4-(2-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (116); methyl N-[(10R,14S)-14-[4-(4-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (117); methyl N-[(10R,14S)-14-[4-(3-chlor-2-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,l 6-diazatricyclo[l 3.3.1.02,7]noriadeca-1 (18),2,4,6,15(19),16-hexaen-5-yl]carbamat (118); methyl N-[(10R,14S)-14-[4-(3-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (119); methyl N-[(10R,14S)-14-[4-(3-chlor-2-methylphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]noiiadeca-l(18),2,4,6,15(19),16-hexaeii-5-yl]carbamat, TFA-salt (120); methyl N-[(10R,14S)-14-[4-(5-chlor-2-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (121); methyl N-[(10R,14S)-14-[4-(3-chlor-4-methoxyphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat, TFA-salt (122); methyl N-[(14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- hydroxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02'7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (123); methyl N-[(14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- hydroxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02'7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (124); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphcnyl)-6-oxo-1,2,3,6-tctrahydropyridin-1 -yl] -10-mcthyl-5-{[(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]amino}-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (125); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-5-{[(3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]arnino}-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (126); (10R, 14S)-5-{[(3S,4R, 5S, 6R)-3-amino-4,5-dihydroxy-6-(hydro xymethyl)oxan-2 -yl] amino} -14-[4-(3 -chlor-2,6-difluoiphenyl)-6-oxo-1,2,3,6-tetrahydiOpyridiii-1 -yl] -10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (127); (2S,3S,4S,5R)-6-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]amino}- 3,4,5-trihydroxyoxan-2-carboxylsyre (128); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-{[(3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-methoxyoxan-2-yl]amino}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (129); N-[(3S,4R,5S,6R)-2-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.0i’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl] amino } -4,5-dihydroxy-6-(hydroxymethyl)oxan-3 -yl] acetamid (130); (1 OR, 14S)-14-(4-(3-chhar-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-5-{[(3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]amino}-8,16-diazatricyclo[13.3.1.02’7]nonadcca-l(19),2,4,6,15,17-hcxacn-9-on (131); tert-butyl N-[(3R,4S,5S,6R)-2-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.0i’7]nonadeca-l(19),2,4,6,15,17-hexaen- 5-yl] amino } -4,5-dihydroxy-6-(hydroxymethyl)oxan-3 -yl] carbamat (132); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5- {[(3R,4R,5S,6R)-5-{[(2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-{[(2R,3R,4S,5S,6R)-3,4,5- trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}oxan-2-yl]oxy}-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]amino}-10-methyl-8,16-diazatricyclo[13.3.1.02'7]nonadeca-l(19),2,4,6,15,17-hexaen-9-on (133); methyl (2S,3S,4S,5R)-3,4,5-tris(acctyloxy)-6-{[(10R,14S)-14-[4-(3-chlor-2,6-difluorphcnyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1 (19),2,4,6,15,17-hexaen-5-yl]amino}oxan-2-carboxylat (134); methyl N-[(10R,14S)-17-chlor-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02’7]octadeca-l(17),2,4,6,15(18)-pentaen-5-yl]carbamat, TFA-salt ( 135); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9,1 l-dioxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (136); (10R,14S)-4-brom-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-mcthyl-8,16-diazatricyclo[13.3.1.02’7]nonadcca-l(19),2(7),3,5,15,17-hcxacn-9-on (137); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-4-carbonitril (138); (1 OR, 14S)-14-(4-(3 -cyan-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-4-carbonitril (139); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-4-(2H-l,2,3,4-tetrazol-5-yl)-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (140); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl]-4,10-dimethyl- 8,16-diazatricyclo[13.3.1.02’']nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (141); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-2-oxo-l,2,3,4-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (142); (10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4-fhior-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (143); methyl (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-4-carboxylat (144); (10R,14S)-14-[4-(3-chlor-2,6-difluorphcnyl)-6-oxo-l,2,3,6-tctrahydropyridin-l-yl]-4-fLuor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (145); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-4-carboxylsyre (146); (10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4-fluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (147); (10R, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-te trahydropyridin-l-yl]-4-(hydroxymethyl)-10-methyl-8, i 6-diazatricyclo[ 13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17 -hexaen-9-on (148); (10R, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-te trahydropyridin-l-yl]-5-(hydroxymethyl)-10-methyl-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-9-on (149); 4-chlor-3-fluor-2-{l-[(10R,14S)-4-fluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}benzonitril (150); methyl N-[(10R,14S)-14-[4-(3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.027]octadeca-l(17),2,4,6,15(18)-pentaen-5-yl]carbamat (151); methyl N-[(15S)-15-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-8-oxo- 9.17- diazatricyclo[14.3.1.02’7]icosa-l(20),2(7),3,5,16,18-hexaen-5-yl]carbamat, TFA-salt (152); methyl N-[( 1 OR, 14S)-10-methyl-14-(4-(3 -methylcyclohexyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 - yl]-9-oxo-8,16-diazatricyclo[13.3.1.027]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (153); methyl N-[( 1 OR, 14S)-14-[4-(2-aminopyridin-4-yl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (154); methyl N-[( 1 OR, 14S)-10-methyl-9-oxo-14-[6-oxo-4-(piperidin-4-yl)-1,2,3,6-tetrahydropyridin-1 -yl]-8,16-diazatricyclo[13.3.1.0z’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (155); methyl N-[(10R,14S)-14-[4-(2-chlorpyridin-4-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (156) ; methyl N-[(10R,14S)-14-[4-(6-chlorpyridin-2-yl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (157) ; methyl N-[( 1 OR, 14S)-10-methyl-14-(4-(1 -methylpiperidin-2-yl)-6-oxo-1,2,3,6-tetrahydropyridin-l-yl]-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, 2 TFA-salt (158) ; methyl N-[( 1 OR, 14S)-10-methyl-14-(4-(3 -methylcyclohexyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 - yl]-9-oxo-8,16-diazatricyclo[13.3.1.027]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (159); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]- 10.17- dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02’7]octadeca-l(17),2,4,6,15(18)-pentaen-5-yl]carbamat, TFA-salt (160); methyl N-[(l OR, 14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l ,2,3,6-tetrahydropyridin-l -yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat (161); (10R, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-te trahydropyridin-l-yl]-10-methyl-8-azatricyclo[13.3.1.02’']nonadeca-l(19),2,4,6,15,17-hexaen-9-on (162); methyl (1 OR, 14S)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat (163); methyl (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- mcthyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadcca-l(19),2,4,6,15,17-hcxacn-4-carboxylat (164); methyl (10R,14R)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat (165); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphcnyl)-6-oxo-1,2,3,6-tctrahydropyridin-1 -yl] -10-mcthyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylsyre (166); (1 OR, 14S)-14-[4-(6-brom-3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylsyre (167); methyl (10R,14S)-14-[4-(3,6-dicyan-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10- methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-4-carboxylat (168); methyl (10R, 14S)-14-(4-(3 -chlor-2-fluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] - 10-methyl- 9- oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-4-carboxylat (169); methyl (10R,14S)-14-[4-(3-chlor-6-cyan-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-4-carboxylat (170); methyl N-[(10R,14S)-14-[4-(6-acetyl-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (171); methyl (10R,14S)-14-[4-(6-acetyl-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]- 10- methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-4-carboxylat (172); methyl N-[(10R,14S)-14-[4-(3-chlor-6-cyan-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(18),2,4,6,15(19),16-hexaen-5-yl]carbamat (173); methyl (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-2-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat (174); methyl (10R,14R)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]- 10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat (175); methyl (10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-2-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat (176); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-di£luorphenyl)-3-methyl-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (177) ; methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-3-methyl-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (178) ; N-(4-chlor-3-fLuor-2-{l-[(10R,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02'7]nonadeca- l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-2,2,2-trifluoracetamid (179) ; methyl N-[(10S,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-ll-fluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.i.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (180) ; methyl N-[(10R,14S)-14-[4-(3-chlor-6-ethynyl-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,/]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (181); methyl N-[(10R,14S)-14-{4-[3-chlor-2-fluor-6-(lH-l,2,3-triazol-4-yl)phenyl]-6-oxo-l,2,3,6- tetrahydropyridin-1 -yl} -10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-5-yl]carbamat (182); N-(4-chlor-3-fLuor-2-{l-[(10R,14S)-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca- l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}phenyl)acetamid (183); (10R,14S)-14-{4-[3-chlor-2-fluor-6-(lH-l,2,3,4-tetrazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridiii-l-yl}-4-fluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]iioiiadeca-l(19),2(7),3,5,15,17-hexaen-9-on (184); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-2-oxo-l,2-dihydropyridin-l-yl]-10-methyl-5,8,16-triazatricyclo[13.3.1.02’/]nonadcca-l(19),2(7),3,5,15,17-hcxacn-9-on (185); methyl (10R,14S)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6- tetrahydropyridin-1 -yl} -10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02’7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-4-carboxylat (186); (10R,14S)-14-{4-[3-chlor-2-fluor-6-(trifluormethyl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-9-oxo-8,16-diazatricyclo[ 13.3.1.02,7]nonadeca-1 (19),2(7),3,5,15,17-hexaen-4-carboxylsyre (187); (10R,14S)-14-{4-[5-chlor-2-(lH-l,2,3-triazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-4-fluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (188); (10R,14S)-14-{4-[5-chlor-2-(lH-l,2,3-triazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (189); methyl N-[(10R,14S)-14-[4-(3-brom-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat (190); methyl N-[(10R,14S)-14-[4-(6-acetyl-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l- yl]-17-fluor-10-methyl-9-oxo-8-azatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat (191); l-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]guanidine, 2 TFA-salt (192); (10R,14S)-5-amino-4-brom-l 4-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l ,2,3,6-tetrahydropyridin-l - yl]-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (193); methyl N-[(14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-8-oxo-9,16-diazatricyclo[13.3.1.02,7]nonadeca-l(19),2(7),3,5,15,17-hexaen-5-yl]carbamat (194); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-5-[(pyridin-3-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, (195); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-5-[(pyridazin-3-yl)amino]-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, 2 TFA-salt (196); methyl (10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,/]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylat, 2 TFA-salt (197); (10R,14S)-5-amino-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2,4,6,15,17-hexaen-4-carboxylsyre, 2 TFA-salt (198); (14R,18S)-18-[4-(3-cHor-2,6-difluorpheiiyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-5-hydroxy-14-methyl-8,12,20-triazatetracyclo[17.3.1.02,11.04’9]tricosa-l(23),2,4(9),5,10,19,21-heptaene-7,13-dion, TFA-salt (199); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphcnyl)-2-oxo-1,2-dihydropyridin-1 -yl]-3-fluor- 10-mcthyl- 8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (200); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-3,5-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (201); (10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-3,5-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on (202); (1 OR, 14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl]-3,4-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (203); (10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-3,4-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (204); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4,5-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (205); (10R,14S)-14-[4-(6-brom-3-chlor-2-fluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-4,5-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (206); 4-chlor-2-{l-[(10R,14S)-3,5-difluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}-3-fluorbenzonitril, TFA-salt (207) ; 4-chlor-2-{l-[(10R,14S)-3,4-difluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}-3-iluorbenzonitril, TFA-salt (208) ; 2-{l-[(10R,14S)-3,4-difluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}-3-fluorbenzen-l,4-dicarbonitril, TFA-salt (209); 2-{l-[(10R,14S)-4,5-difluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}-3-fluorbenzen-l,4-dicarbonitril, TFA-salt (210); 4-chlor-2-{l-[(10R,14S)-4,5-diiluor-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-14-yl]-6-oxo-l,2,3,6-tetrahydropyridin-4-yl}-3-fluorbenzonitril, TFA-salt (211); (10R,14S)-14-[4-(3-chlor-2-fluorphenyl)-2-oxo-l,2-dihydropyridin-l-yl]-3,5-difluor-10-methyl- 8.16- diazatricyclo[13.3.1.02’']nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (212); methyl (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]noiiadeca-l(19),2(7),3,5,15,17-liexaen-3-carboxylat, TFA-salt (213); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 -yl] -10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadcca-l(19),2(7),3,5,15,17-hcxacn-3-carboxylsyrc, TFA-salt (214); (10R,14S)-14-{4-[3-chlor-2-iluor-6-(lH-l,2,3,4-tetrazol-l-yl)phenyl]-6-oxo-l,2,3,6-tetrahydropyridin-l-yl}-4,5-difluor-10-methyl-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,15,17-hexaen-9-on, TFA-salt (215); methyl N-[(12E,15S)-15-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-8-oxo-9,17-diazatricyclo[14.3.1.02’7]icosa-l(20),2(7),3,5,12,16,18-heptaen-5-yl]carbamat, TFA-salt (216); (1 OR, 14S)-14-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-1,2,3,6-tetrahydropyridin-1-yl] -10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02’7]nonadeca-l(19),2(7),3,5,i5,17-hexaen-3-carbonitril, TFA-salt (217); methyl N-[( 1 OR, 14S)-10-methyl-14-(4-(3 -methylcyclohexyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 - yl]-9-oxo-8,16-diazatricyclo[13.3.1.027]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (218); methyl N-[(15S)-15-[4-(3-chlor-2,6-dilluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-9-oxo- 8.17- diazatricyclo[14.3.1.02’']icosa-l(20),2(7),3,5,16,18-hexaen-5-yl]carbamat, TFA-salt (219); (10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10,17-dimethyl-8,16,18-triazatricyclo[13.2.1.0^7]octadeca-l(17),2,4,6,15(18)-pentaen-9-on, TFA-salt (220); 13-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-9-methyl-4,5,7,15-tetraazatricyclo[12.3.1.02’6]octadeca-l(18),2(6),3,14,16-pentaen-8-on, 2TFA-salt (221); (9R,13S)-13-[4-(3-chlor-2,6-diiluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-9-methyl-8-oxo-2,3,7,15-tetraazatricyclo[12.3.1.02’6]octadeca-l(18),3,5,14,16-pentaene-4-carboxylsyre (222); (9R, 13 S)-13-(4-(3-chlor-2,6-difluorphenyl)-6-oxo-l ,2,3,6-tetrahydropyridin-l-yl]-4-cyclopropyl-9-methyl-2,3,7,15-tetraazatricyclo[12.3.1.02’6]octadeca-l(18),3,5,14,16-pentaen-8-on (223); methyl N-[(9R, 13 S)-l 3-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l ,2,3,6-tetrahydropyridin-l -yl] -9- methyl-8-oxo-2,3,7,15-tetraazatricyclo[12.3.1.02’6]octadeca-l(18),3,5,14,16-pentaen-4-yl]carbamat (224); methyl N-[( 1 OR, 14S)-10-methyl-14-(4-(3 -methylcyclohexyl)-6-oxo-1,2,3,6-tetrahydropyridin-1 - yl]-9-oxo-8,16-diazatricyclo[13.3.1.027]nonadeca-l(19),2,4,6,15,17-hexaen-5-yl]carbamat, TFA-salt (225) og (226); methyl N-[(10R,14S)-14-[4-(3-chlor-2,6-difluorphenyl)-6-oxo-l,2,3,6-tetrahydropyridin-l-yl]-10-methyl-9-oxo-17-(pyrimidin-5-yl)-8,16,18-triazatricyclo-[13.2.1.02’7]octadeca-l(17),2,4,6,15(18)-pentaen- 5-yl]carbamat (227).
  14. 14. Farmaceutisk sammensætning, der omfatter én eller flere forbindelser ifølge et hvilket som helst af kravene 1-13 og en farmaceutisk acceptabel bærer eller fortynder.
  15. 15. Forbindelse ifølge et hvilket som helst af kravene 1-13, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse som et medikament.
  16. 16. Forbindelse ifølge et hvilket som helst af kravene 1-13, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandling og/eller profylakse af en tromboembolisk forstyrrelse.
  17. 17. Forbindelse ifølge et hvilket som helst af kravene 1-13, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandling og/eller profylakse af en tromboembolisk forstyrrelse, hvor den tromboemboliske forstyrrelse cr udvalgt fra arterial kardiovaskulærc tromboemboliske forstyrrelser, venous kardiovaskulære tromboemboliske forstyrrelser og tromboemboliske forstyrrelser i hjertets kamre eller i den perifere cirkulation.
  18. 18. Forbindelse ifølge et hvilket som helst af kravene 1-13, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandling og/eller profylakse af en tromboembolisk forstyrrelse, hvor den tromboemboliske forstyrrelse er udvalgt fra ustabil angina, et akut konorart syndrom, atrieflimren, myokardieinfarkt, transient iskæmisk attack, apopleksi, atherosklerose, perifer okklusiv arteriesygdom, venetrombose, dyb venetrombose, thrombophlebitis, arterieemboli, koronararteritrombose, cerebral arterietrombose, cerebral emboli, nyreemboli, lungeemboli og trombose forbundet med medicinske implantater, anordninger eller procedurer, hvor blod eksponeres for en kunstig overflade, der fremmer trombose.
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