Trifluoromethylpropanamide derivatives as HTRA1 inhibitors

Abstract

The invention provides novel compounds having the general formula (I) ##STR00001##
wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.3, R.sup.8, R.sup.10, R.sup.11 and R.sup.23 are as described herein, compositions including the compounds and methods of using the compounds.

Claims

1. A compound of formula (I) ##STR00317## or a pharmaceutically acceptable salt thereof, wherein R.sup.2, R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are each independently selected from the group consisting of (i) H, (ii) C.sub.1-6-alkyl, and (iii) C.sub.3-8-cycloalkyl; R.sup.5 is selected from the group consisting of (i) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, ii) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, iii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, and iv) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14; R.sup.8 is selected from the group consisting of i) H, ii) hydroxy, iii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, iv) aminocarbonyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, v) aminocarbonyl-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, vi) carboxy, vii) carboxy-C.sub.1-6-alkyl, viii) C.sub.1-6-alkoxy, ix) C.sub.1-6-haloalkoxy, x) C.sub.1-6-alkoxycarbonyl, xi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, xii) C.sub.3-8-cycloalkyl, xiii) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xiv) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xv) aryl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xvi) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xvii) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xviii) heteroaryl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17 xix) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xx) heterocycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xxi) heterocycloalkyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xxii) cyano-C.sub.1-6-alkyl, and xxiii) halo-C.sub.1-6-alkoxy; R.sup.11 is selected from the group consisting of i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) C.sub.3-8-cycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) C.sub.3-8-cycloalkyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) aryl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) aryl-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20 ix) aryl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, x) aryl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xi) aryl(halo)-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xii) aryloxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiii) aryloxy-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiv) aryloxy-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xv) aryloxy(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xvi) aryloxy(halo)-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xvii) aryloxy(halo)-C.sub.1-6-alkyl, xviii) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xix) heterocycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xx) heterocycloalkyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxi) heterocycloalkyl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxii) heterocycloalkyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxiii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxiv) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxv) heteroaryl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxvi) heteroaryl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxvii) heteroaryl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxviii) heteroaryloxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxix) heteroaryloxy-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxx) heteroaryloxy(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxxi) heteroaryloxy(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxxii) aryl(cycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxxiii) aryl(heterocycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and xxxiv) aryl(hydroxy, halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20; R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are each independently selected from the group consisting of i) H, ii) cyano, iii) halogen, iv) oxo, v) C.sub.1-6-alkyl, vi) amino substituted on the nitrogen atom by two substituents independently selected from H, C.sub.1-6-alkyl, C.sub.1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl, vii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by two substituents independently selected from H, C.sub.1-6-alkyl, C.sub.1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl, viii) halo-C.sub.1-6-alkyl, ix) C.sub.3-8-cycloalkyl, x) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, xi) carboxy-C.sub.1-6-alkyl, xii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkyl, xiii) carboxy-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6alkyl, xiv) C.sub.1-6-alkoxy, xv) halo-C.sub.1-6-alkoxy, xvi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, xvii) hydroxycarbonyl-C.sub.1-6-alkoxy, xviii) carboxy-C.sub.1-6-alkoxy, xix) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6-alkoxy, xx) carboxy-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6-alkoxy, heterocycloalkyl, and xxi) cyano; and R.sup.21 and R.sup.22 are each independently selected from the group consisting of i) H, ii) C.sub.1-6-alkoxycarbonyl, iii) carboxy-C.sub.1-6-alkyl, iv) arylcarbonyl, and v) heteroarylcarbonyl.

2. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2, R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are each independently selected from the group consisting of i) H, ii) C.sub.1-6-alkyl, and iii) C.sub.3-8-cycloalkyl; R.sup.5 is selected from the group consisting of i) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, ii) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, iii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, and iv) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14; R.sup.8 is selected from the group consisting of i) H, ii) hydroxy, iii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, iv) aminocarbonyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, v) aminocarbonyl-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkylcarbonyl, C.sub.1-6-alkoxycarbonyl, C.sub.1-6-alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, vi) carboxy, vii) carboxy-C.sub.1-6-alkyl, viii) C.sub.1-6-alkoxy, ix) C.sub.1-8-haloalkoxy, x) C.sub.1-6-alkoxycarbonyl, xi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, xii) C.sub.3-8-cycloalkyl, xiii) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xiv) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xv) aryl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xvi) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xvii) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and xviii) heteroaryl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17 xix) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xx) heterocycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and xxi) heterocycloalkyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17; R.sup.11 is selected from the group consisting of i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) C.sub.3-8-cycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) C.sub.3-8-cycloalkyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) aryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) aryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) aryl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) aryl-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, ix) aryl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, x) aryl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xi) aryl(halo)-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xii) aryloxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiii) aryloxy-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiv) aryloxy-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xv) aryloxy(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xvi) aryloxy(halo)-heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xvii) aryloxy(halo)-C.sub.1-6-alkyl, xviii) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xix) heterocycloalkyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xx) heterocycloalkyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxi) heterocycloalkyl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxii) heterocycloalkyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxiii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxiv) heteroaryl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxv) heteroaryl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxvi) heteroaryl(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxvii) heteroaryl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxviii) heteroaryloxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxix) heteroaryloxy-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xxx) heteroaryloxy(halo)-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and xxxi) heteroaryloxy(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20; R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19 and R.sup.20 are each independently selected from the group consisting of i) H, ii) cyano, iii) halogen, iv) oxo, v) C.sub.1-6-alkyl, vi) amino substituted on the nitrogen atom by two substituents independently selected from H, C.sub.1-6-alkyl, C.sub.1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl, vii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by two substituents independently selected from H, C.sub.1-6-alkyl, C.sub.1-6-alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl, viii) C.sub.1-6-alkyl, ix) halo-C.sub.1-6-alkyl, x) C.sub.3-8-cycloalkyl, xi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, xii) carboxy-C.sub.1-6-alkyl, xiii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkyl, xiv) carboxy-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6alkyl, xv) C.sub.1-6-alkoxy, xvi) halo-C.sub.1-6-alkoxy, xvii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, xviii) carboxy-C.sub.1-6-alkoxy, xix) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6-alkoxy, xx) carboxy-C.sub.1-6-alkylaminocarbonyl-C.sub.1-6-alkoxy, and xxi) heterocycloalkyl; R.sup.21 and R.sup.22 are independently selected from the group consisting of i) H, ii) C.sub.1-6-alkoxycarbonyl, iii) carboxy-C.sub.1-6-alkyl, iv) arylcarbonyl, and v) heteroarylcarbonyl.

3. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is C.sub.1-6-alkyl; R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are H; R.sup.5 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, and ii) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14; R.sup.8 is selected from i) H, ii) hydroxy, iii) carboxy-C.sub.1-6-alkyl, iv) C.sub.1-6-alkoxy, v) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, vi) C.sub.3-8-cycloalkyl, vii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, viii) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, ix) pyridinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, x) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkoxycarbonyl, pyridinylcarbonyl, pyridazinylcarbonyl and pyrazinylcarbonyl, wherein pyridinylcarbonyl, pyridazinylcarbonyl and pyrazinylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xi) aminocarbonyl substituted on the nitrogen atom by H, xii) cyano-C.sub.1-6-alkyl, and xiii) halo-C.sub.1-6-alkoxy; R.sup.11 is selected from i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) naphthyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) phenyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) phenoxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, wherein heteroaryl is selected from pyrazinyl, pyridinyl, pyrimidinyl and thiophenyl, ix) pyridinyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, x) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, wherein heterocycloalkyl is selected from pyrrolidinyl and piperidinyl, xi) C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xii) phenyl(cycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiii) phenyl(heterocycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and xiv) phenyl(hydroxy, halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20; R.sup.12 is selected from i) H, ii) C.sub.1-6-alkoxy, iii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, and iv) hydroxycarbonyl-C.sub.1-6-alkoxy; R.sup.13, R.sup.14, R.sup.17 and R.sup.20 are H; R.sup.15 is selected from i) H, ii) cyano, iii) halogen, iv) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, v) carboxy-C.sub.1-6-alkoxy, and vi) amino substituted on the nitrogen atom by one H and one substituent selected from H, C.sub.1-6-alkoxycarbonyl and pyridinylcarbonyl; R.sup.16 is selected from i) H, and ii) halogen; R.sup.18 is selected from i) H, ii) halogen, iii) oxo, iv) C.sub.1-6-alkyl, v) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one H and one substituents selected from H and C.sub.1-6-alkoxycarbonyl, vi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, vii) carboxy-C.sub.1-6-alkoxy, viii) C.sub.1-6alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkoxy, ix) carboxy-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkoxy, x) halo-C.sub.1-6-alkyl, xi) halo-C.sub.1-6-alkoxy, xii) C.sub.1-6-alkoxy, and xiii) cyano; R.sup.19 is selected from i) H, ii) halogen, iii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, and iv) carboxy-C.sub.1-6-alkoxy; R.sup.21 is selected from i) H, ii) C.sub.1-6-alkoxycarbonyl, and iii) pyridinylcarbonyl; and R.sup.22 is H.

4. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is C.sub.1-6-alkyl; R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are H; R.sup.5 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, and ii) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14; R.sup.8 is selected from i) H, ii) hydroxy, iii) carboxy-C.sub.1-6-alkyl, iv) C.sub.1-6-alkoxy, v) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, vi) C.sub.3-8-cycloalkyl, vii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, viii) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and ix) pyridinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17; R.sup.11 is selected from i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) naphthyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) phenyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) phenoxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, wherein heteroaryl is selected from pyrazinyl, pyridinyl, pyrimidinyl and thiophenyl, ix) pyridinyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and x) heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, wherein heterocycloalkyl is selected from pyrrolidinyl and piperidinyl; R.sup.12 is selected from i) H, and ii) C.sub.1-6-alkoxy; R.sup.13, R.sup.14, R.sup.17 and R.sup.20 are H; R.sup.15 is selected from i) H, ii) cyano, iii) halogen, iv) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, and v) carboxy-C.sub.1-6-alkoxy; R.sup.16 is selected from i) H, and ii) halogen; R.sup.18 is selected from i) H, ii) halogen, iii) oxo, iv) C.sub.1-6-alkyl, v) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one H and one substituent selected from H and C.sub.1-6-alkoxycarbonyl, vi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, vii) carboxy-C.sub.1-6-alkoxy, viii) C.sub.1-6alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkoxy, and ix) carboxy-C.sub.1-6alkylaminocarbonyl-C.sub.1-6alkoxy; R.sup.19 is selected from i) H, ii) halogen, iii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, and iv) carboxy-C.sub.1-6-alkoxy; R.sup.21 is selected from i) H, ii) C.sub.1-6-alkoxycarbonyl, and iii) pyridinylcarbonyl; and R.sup.22 is H.

5. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is C.sub.1-6-alkyl.

6. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is isopropyl.

7. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are H.

8. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.5 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14, and ii) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.12, R.sup.13 and R.sup.14.

9. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.5 is phenyl optionally substituted with one or more substituents selected from the group consisting of one C.sub.1-6-alkoxy.

10. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 is selected from i) H, ii) hydroxy, iii) carboxy-C.sub.1-6-alkyl, iv) C.sub.1-6-alkoxy, v) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, vi) C.sub.3-8-cycloalkyl, vii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, viii) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, ix) pyridinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, x) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one or two substituents selected from H, C.sub.1-6-alkoxycarbonyl, pyridinylcarbonyl, pyridazinylcarbonyl and pyrazinylcarbonyl, wherein pyridinylcarbonyl, pyridazinylcarbonyl and pyrazinylcarbonyl are optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xi) aminocarbonyl substituted on the nitrogen atom by H, xii) cyano-C.sub.1-6-alkyl, and xiii) halo-C.sub.1-6-alkoxy.

11. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 is selected from i) H, ii) hydroxy, iii) carboxy-C.sub.1-6-alkyl, iv) C.sub.1-6-alkoxy, v) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, vi) C.sub.3-8-cycloalkyl, vii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, viii) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and ix) pyridinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17.

12. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 is selected from i) H, ii) hydroxy, iii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, iv) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and v) C.sub.1-6-alkoxy.

13. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 is selected from i) H, ii) hydroxy, iii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and iv) phenyl-C.sub.1-6-alkoxy optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17.

14. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 is phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17.

15. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.11 is selected from i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) naphthyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) phenyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) phenoxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, wherein heteroaryl is selected from pyrazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl and thiophenyl, ix) pyridinyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and x) piperazinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, xi) C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xii) phenyl(cycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiii) phenyl(haloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, xiv) phenyl(heterocycloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and xv) phenyl(hydroxy,haloalkyl)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20.

16. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.11 is selected from i) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by R.sup.21 and R.sup.22, ii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) naphtyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, v) phenyl-C.sub.3-8-cycloalkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vi) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, vii) phenoxy-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, viii) heteroaryl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, wherein heteroaryl is selected from pyrazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl and thiophenyl, ix) pyridinyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17, and x) piperazinyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17.

17. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.11 is selected from i) C.sub.3-8-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, ii) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iv) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and v) thiophenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20.

18. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.11 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, ii) phenyl-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, iii) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and iv) thiophenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20.

19. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.11 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, and ii) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20.

20. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.12 is selected from i) H, ii) C.sub.1-6-alkoxy, iii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, and iv) hydroxycarbonyl-C.sub.1-6-alkoxy.

21. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.12 is selected from i) hydroxycarbonyl-C.sub.1-6-alkoxy, and ii) C.sub.1-6-alkoxy.

22. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.12 is selected from i) H, and ii) C.sub.1-6-alkoxy.

23. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.12 is C.sub.1-6-alkoxy.

24. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.13, R.sup.14, R.sup.17 and R.sup.20 are H.

25. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.15 is selected from i) H, ii) cyano, iii) halogen, iv) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, and v) carboxy-C.sub.1-6-alkoxy, vi) amino substituted on the nitrogen atom by one H and one substituent selected from H, C.sub.1-6-alkoxycarbonyl and pyridinylcarbonyl.

26. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.15 is selected from i) H, ii) cyano, iii) halogen, iv) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, and v) carboxy-C.sub.1-6-alkoxy.

27. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.15 is selected from i) H, ii) cyano, iii) halogen, and iv) carboxy-C.sub.1-6-alkoxy, and v) amino substituted on the nitrogen atom by one H and one substituent selected from H, C.sub.1-6-alkoxycarbonyl and pyridinylcarbonyl.

28. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.15 is selected from i) H, ii) cyano, iii) halogen, and iv) carboxy-C.sub.1-6-alkoxy.

29. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.16 is H.

30. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.18 is selected from i) H, ii) halogen, iii) oxo, iv) C.sub.1-6-alkyl, v) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one H and one substituent selected from H and C.sub.1-6-alkoxycarbonyl, vi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, vii) carboxy-C.sub.1-6-alkoxy, viii) C.sub.1-6alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6-alkoxy, and ix) carboxy-C.sub.1-6alkylaminocarbonyl-C.sub.1-6-alkoxy x) halo-C.sub.1-6-alkyl, xi) halo-C.sub.1-6-alkoxy, xii) C.sub.1-6-alkoxy, and xiii) cyano.

31. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.18 is selected from i) H, ii) halogen, iii) oxo, iv) C.sub.1-6-alkyl, v) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by one H and one substituent selected from H and C.sub.1-6-alkoxycarbonyl, vi) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkoxy, vii) carboxy-C.sub.1-6-alkoxy, viii) C.sub.1-6alkoxycarbonyl-C.sub.1-6alkylaminocarbonyl-C.sub.1-6-alkoxy, and ix) carboxy-C.sub.1-6alkylaminocarbonyl-C.sub.1-6-alkoxy.

32. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.18 is selected from i) H, ii) halogen, iii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by two H, iv) carboxy-C.sub.1-6-alkoxy, v) C.sub.1-6-alkyl, and vi) halo-C.sub.1-6-alkyl.

33. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.18 is selected from i) H, ii) halogen, iii) amino-C.sub.1-6-alkyl substituted on the nitrogen atom by two H, and iv) carboxy-C.sub.1-6-alkoxy.

34. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.18 is halogen.

35. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.19 is selected from i) H, ii) halogen, iii) C.sub.1-6-alkoxycarbonyl-C.sub.1-6-alkyl, and iv) carboxy-C.sub.1-6-alkoxy.

36. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.19 is selected from i) H, and ii) halogen.

37. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.19 is halogen.

38. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.21 is selected from i) H, ii) C.sub.1-6-alkoxycarbonyl, and iii) pyridinylcarbonyl.

39. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.22 is H.

40. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is C.sub.1-6-alkyl; R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.10 and R.sup.23 are H; R.sup.5 is phenyl optionally substituted with one or more substituents selected from the group consisting of one C.sub.1-6-alkoxy; R.sup.8 is phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.15, R.sup.16 and R.sup.17; R.sup.11 is selected from i) phenyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20, ii) phenyl(halo)-C.sub.1-6-alkyl optionally substituted with one or more substituents selected from the group consisting of R.sup.18, R.sup.19 and R.sup.20; R.sup.15 is selected from i) H, ii) cyano, iii) halogen, and iv) carboxy-C.sub.1-6-alkoxy; R.sup.16 is H; R.sup.17 and R.sup.20 are H; R.sup.18 and R.sup.19 are is halogen.

41. A compound according to claim 1, selected from N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; (2S)-3-(3-chlorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-2-(3-pyridin-3-ylpropanoylamino)propanamide; N-[(2S)-3-(3-fluorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; 3-chloro-N-[(2S)-3-(3-fluorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 5-chloro-N-[(2S)-3-(3-fluorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-cyanophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 5-chloro-N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxo-3-pyridin-3-ylpropan-2-yl]benzamide; 3-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxo-3-pyridin-3-ylpropan-2-yl]benzamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-pyridin-3-ylpropanamide; N-[(2S)-3-(2-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(2-cyanophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; tert-butyl 2-[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate; tert-butyl 2-[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxo-2-(pyridine-2-carbonylamino)propyl]phenoxy]acetate; tert-butyl 2-[4-[(2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate; tert-butyl 2-[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate; tert-butyl 2-[3-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate; tert-butyl 2-[3-[(2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; (2S)-2-[(2,2-difluoro-2-phenylacetyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2,5-dichloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 3-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 1-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopropane-1-carboxamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[(2-fluoro-2-phenylacetyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 5-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; 5-bromo-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2-(4-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-methylpropanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-methoxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 3-chloro-N-[(2S)-3-methoxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-[(2-methylpropan-2-yl)oxy]propanamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]pyridine-2-carboxamide; 3-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]benzamide; 5-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-[(2-methylpropan-2-yl)oxy]propanamide; 3-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxo-3-phenylmethoxypropan-2-yl]benzamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxo-3-phenylmethoxypropan-2-yl]pyridine-2-carboxamide; tert-butyl (4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentanoate; tert-butyl (4S)-4-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentanoate; N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]-1-methylpyrrolidine-3-carboxamide; N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyridine-2-carboxamide; N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyrimidine-5-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyrimidine-5-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]-1-methylpiperidine-4-carboxamide; N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyrimidine-5-carboxamide; N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyridine-2-carboxamide; N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2S)-3-cyclohexyl-1-oxo-1-[[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]propan-2-yl]amino]propan-2-yl]naphthalene-2-carboxamide; tert-butyl N-[2-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamate; tert-butyl N-[[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenyl]methyl]carbamate; tert-butyl N-[[2-chloro-4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[2-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]phenyl]methyl]carbamate; tert-butyl 2-[6-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]pyridin-2-yl]oxyacetate; tert-butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate; tert-butyl 2-[6-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]pyridin-3-yl]oxyacetate; tert-butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]-2-oxopyridin-1-yl]acetate; tert-butyl 2-[3-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate; tert-butyl 2-[5-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]-2-oxopyridin-1-yl]acetate; tert-butyl 2-[4-[2-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethoxy]phenoxy]acetate; tert-butyl 2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate; tert-butyl 2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate; N-[3-(3-chlorophenyl)-1-[[(1S and 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-methylpyridine-2-carboxamide; N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-4-methylpyridine-3-carboxamide; N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyridine-2-carboxamide; N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyrazine-2-carboxamide; N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]propan-2-yl]pyrimidine-5-carboxamide; tert-butyl N-[[4-[[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[2-[[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]phenyl]methyl]carbamate; tert-butyl 2-[[2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate; tert-butyl 2-[[2-[3-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate; tert-butyl 2-[[2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate; tert-butyl 2-[[2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate; 2-[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 2-[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxo-2-(pyridine-2-carbonylamino)propyl]phenoxy]acetic acid; 2-[4-[(2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 2-[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 2-[3-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 2-[3-[(2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; (4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentanoic acid; (4S)-4-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentanoic acid; (2S)-2-[(2-aminoacetyl)amino]-3-(3-chlorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide, trifluoroacetic acid salt; 4-(aminomethyl)-N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide, trifluoroacetic acid salt; 4-(aminomethyl)-3-chloro-N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide, trifluoroacetic acid salt; (2S)-2-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-3-(3-chlorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide, trifluoroacetic acid salt; 2-[6-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]pyridin-2-yl]oxyacetic acid; 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 2-[6-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]pyridin-3-yl]oxyacetic acid; 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]-2-oxopyridin-1-yl]acetic acid; 2-[3-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 2-[5-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]-2-oxopyridin-1-yl]acetic acid; 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 4-(aminomethyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide, trifluoroacetic acid salt; (2S)-2-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide, trifluoroacetic acid salt; 2-[[2-[4-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetic acid; 2-[[2-[3-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetic acid; 2-[[2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetic acid; 2-[[2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetic acid; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; N-[(2S)-3-hydroxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]pyridine-2-carboxamide; 3-chloro-N-[(2S)-3-hydroxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 5-chloro-N-[(2S)-3-hydroxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; and N-[2-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]pyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof.

42. A compound according to claim 1, selected from (2S)-3-(3-Chlorophenyl)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 1-(3-chlorophenyl)-N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopropane-1-carboxamide; 5-bromo-N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2,2-difluoro-2-(3-fluorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 1-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclobutane-1-carboxamide; (2S)-2-[[2-(2,5-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2,3-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)amino]ethyl]amino]-1-oxopropan-2-yl]-1,3-dioxolane-2-carboxamide; 1-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopentane-1-carboxamide; (2S)-2-[[2,2-difluoro-2-[2-(trifluoromethoxy)phenyl]acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-ethoxyphenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 1-(2-chloro-6-fluorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopentane-1-carboxamide; 1-(2-fluorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)amino]ethyl]amino]-1-oxopropan-2-yl]cyclopentane-1-carboxamide; 2-(3-chlorophenyl)-3,3,3-trifluoro-2-hydroxy-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]propanamide; 3,3,3-trifluoro-2-hydroxy-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-[3-(trifluoromethyl)phenyl]propanamide; 2-(3,4-dichlorophenyl)-3,3,3-trifluoro-2-hydroxy-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]propanamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-(trifluoromethoxy)benzamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-(trifluoromethyl)benzamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-(trifluoromethyl)benzamide; 2-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-methylbutanamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-phenylbutanamide; (2S)-2-[[2-(4-chlorophenyl)-2-cyclopropylacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-methylbutanamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-phenylcyclopentane-1-carboxamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-methylbenzamide; 3-methoxy-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 3-cyano-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-(trifluoromethoxy)benzamide; 3-ethoxy-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; (2S)-2-[[2,2-difluoro-2-(2-methoxyphenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 4-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 3,3,3-trifluoro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-[3-(trifluoromethyl)phenyl]propanamide; 2-(difluoromethoxy)-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclobutane-1-carboxamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclohexane-1-carboxamide; N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclopentane-1-carboxamide; (2S)-2-[[(2S)-2-(4-chlorophenyl)-2-cyclobutylacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[(2R)-2-(4-chlorophenyl)-2-cyclobutylacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; N-[(2S)-3-methoxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclopentane-1-carboxamide; 1-fluoro-N-[(2S)-3-methoxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopentane-1-carboxamide; tert-butyl N-[(4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentyl]carbamate; tert-butyl N-[(5S)-5-[(3-chlorobenzoyl)amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate; tert-butyl N-[(5S)-5-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate; tert-butyl N-[[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[1-(4-chlorophenyl)cyclopentanecarbonyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[(5-chlorothiophene-2-carbonyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[(2S)-2-(4-chlorophenyl)-3-methylbutanoyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[(2R)-2-(4-chlorophenyl)-3-methylbutanoyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-2-[[2-(4-chlorophenyl)-2-cyclobutylacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxo-2-[[3-(trifluoromethyl)benzoyl]amino]propyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxo-2-[[1-(trifluoromethyl)cyclopentanecarbonyl]amino]propyl]phenyl]methyl]carbamate; tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxo-2-[[3,3,3-trifluoro-2-[3-(trifluoromethyl)phenyl]propanoyl]amino]propyl]phenyl]methyl]carbamate; 3-chloro-N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxo-3-(trifluoromethoxy)propan-2-yl]benzamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-(trifluoromethoxy)propanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-cyano-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 3-chloro-N-[(2S)-3-cyano-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; tert-butyl 2-[4-[(1S)-1-[[(2S)-2-[(5-chlorothiophene-2-carbonyl)amino]-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]phenoxy]acetate; tert-butyl 2-[4-[(1S)-1-[[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]phenoxy]acetate; N-[(2S)-5-Amino-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopentan-2-yl]-3-chlorobenzamide; N-[(2S)-6-amino-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxohexan-2-yl]-3-chlorobenzamide;2,2,2-trifluoroacetic acid; (2S)-6-amino-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]hexanamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-chlorobenzamide;2,2,2-trifluoroacetic acid; (2S)-3-[4-(aminomethyl)phenyl]-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide;2,2,2-trifluoroacetic acid; (2S)-3-[4-(aminomethyl)phenyl]-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(4-chlorophenyl)cyclopentane-1-carboxamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-5-chlorothiophene-2-carboxamide;2,2,2-trifluoroacetic acid; (2S)—N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-(4-chlorophenyl)-3-methylbutanamide;2,2,2-trifluoroacetic acid; (2R)—N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-(4-chlorophenyl)-3-methylbutanamide;2,2,2-trifluoroacetic acid; (2S)-3-[4-(aminomethyl)phenyl]-2-[[2-(4-chlorophenyl)-2-cyclobutylacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-(trifluoromethyl)benzamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclopentane-1-carboxamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3,3,3-trifluoro-2-[3-(trifluoromethyl)phenyl]propanamide;2,2,2-trifluoroacetic acid; (2S)-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2,5-dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2,2-difluoro-2-(3-fluorophenyl)acetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2,2-difluoro-2-[2-(trifluoromethoxy)phenyl]acetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-ethoxyphenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-ethylphenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 1-(4-chlorophenyl)-N-[(2S)-3-hydroxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]cyclopentane-1-carboxamide; (2S)-2-[[2,2-difluoro-2-(2-methoxyphenyl)acetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-cyanophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[(3-chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]butanediamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]butanediamide; (2S)-2-[(3-chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]pentanediamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]pentanediamide; 2-[4-[(1S)-1-[[(2S)-2-[(5-chlorothiophene-2-carbonyl)amino]-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]phenoxy]acetic acid; 2-[4-[(1S)-1-[[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]phenoxy]acetic acid; N-[(5S)-5-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide; N-[(5S)-5-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyrazine-2-carboxamide; N-[(5S)-5-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyrimidine-5-carboxamide; N-[(5S)-5-[(3-chlorobenzoyl)amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide; N-[(4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentyl]pyridine-2-carboxamide; and N-[[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]pyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof.

43. A compound according to claim 1, selected from N-[(2S)-3-methoxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1-(trifluoromethyl)cyclopentane-1-carboxamide; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-chlorobenzamide;2,2,2-trifluoroacetic acid; (2S)-3-[4-(aminomethyl)phenyl]-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide;2,2,2-trifluoroacetic acid; (2S)-3-[4-(aminomethyl)phenyl]-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide;2,2,2-trifluoroacetic acid; (2S)—N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2-(4-chlorophenyl)-3-methylbutanamide;2,2,2-trifluoroacetic acid; N-[(2S)-3-[4-(aminomethyl)phenyl]-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3-(trifluoromethyl)benzamide;2,2,2-trifluoroacetic acid; (2S)-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2,5-dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2,2-difluoro-2-(3-fluorophenyl)acetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-ethylphenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2-[4-[(1S)-1-[[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]phenoxy]acetic acid; and N-[[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]pyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof.

44. A compound according to claim 1, selected from N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; 3-chloro-N-[(2S)-3-(3-fluorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-fluorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3-cyanophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 5-chloro-N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]thiophene-2-carboxamide; (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-pyridin-3-ylpropanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-(2-cyanophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; (2S)-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; 2-[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 2-[3-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic acid; 4-(aminomethyl)-N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide, trifluoroacetic acid salt; 4-(aminomethyl)-3-chloro-N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide, trifluoroacetic acid salt; (2S)-2-[[2-[4-(aminomethyl)phenyl]acetyl]amino]-3-(3-chlorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide, trifluoroacetic acid salt; 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; 2-[3-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid; (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; and (2S)-2-[[2-(2-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; or a pharmaceutically acceptable salt thereof.

45. A process to prepare a compound according to claim 1, or a pharmaceutically acceptable salt thereof, comprising the reaction of a compound of formula (II) in oxidative conditions ##STR00318##

46. A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

47. A method for the treatment of a condition selected from the group consisting of conditions of wet or dry age-related macular degeneration, geographic atrophy, diabetic retinopathy, retinopathy of prematurity and polypoidal choroidal vasculopathy, which method comprises administering an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

48. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, when manufactured according to a process of claim 45.

Description

EXAMPLES

(1) All examples and intermediates were prepared under nitrogen atmosphere if not specified otherwise.

(2) Abbreviations: aq.=aqueous; CAS-RN=Chemical Abstracts Service Registry Number; HPLC=high performance liquid chromatography; MS=mass spectrum; sat.=saturated

Intermediate A-1

(S)-2-Amino-3-(3-chlorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide

(3) ##STR00014##

[A] tert-Butyl ((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)carbamate

(4) ##STR00015##

(5) In a round-bottomed flask, (S)-2-((tert-butoxycarbonyl)amino)-2-(4-methoxyphenyl)acetic acid (1 g, 3.55 mmol) (2S,3S)-3-amino-1,1,1-trifluoro-4-methylpentan-2-ol×HCl (0.738 g, 3.55 mmol) and HATU (1.49 g, 3.91 mmol) were dissolved in DMF (20 mL) and the mixture cooled to 0° C. Hunig's base (1.86 mL, 10.7 mmol) was added to the reaction mixture which was stirred at this temperature for 15 min, then allowed to warm up to room temperature and stirring was continued for 5 hours. The mixture was diluted with EtOAc, poured into 1N HCl (15 mL) and the aqueous layer was extracted with EtOAc (2×40 mL). Combined organics were washed with a sat. NaHCO.sub.3 solution (15 mL), then brine before being dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 70% EtOAc-heptane gradient to give the title compound (1.37 g, 86%) as a an off-white solid. MS: 435.3 (M+H.sup.+).

[B] (S)-2-Amino-2-(4-methoxyphenyl)-N-((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)acetamide

(6) ##STR00016##

(7) 4M HCl in dioxane (3.94 mL, 15.8 mmol) was added at 0° C. to a solution of tert-butyl ((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)carbamate (1.37 g, 3.15 mmol) in MeOH (18 mL). The reaction mixture was stirred at this temperature for 10 min and then allowed to warm to room temperature and stirring was continued for 6 hours. The mixture was evaporated to dryness and the residue was triturated with diisopropylether. The solid precipitate was filtered off and further dried under the high vacuum to give the title compound (1.19 g, 97%, HCl salt) as colorless solid. MS: 335.2 (M+H.sup.+).

[C] tert-Butyl ((S)-3-(3-chlorophenyl)-1-(((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)amino)-1-oxopropan-2-yl)carbamate

(8) ##STR00017##

(9) In a round-bottomed flask, (S)-2-amino-2-(4-methoxyphenyl)-N-((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)acetamide hydrochloride (0.418 g, 1.13 mmol), (2S)-2-(tert-butoxycarbonylamino)-3-(3-chlorophenyl)propanoic acid (0.338 g, 1.13 mmol) and HATU (0.471 g, 1.24 mmol) were dissolved in DMF (4 mL) and the mixture cooled to 0° C. Hünig's base (0.591 mL, 3.38 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued for 2.5 hours. The mixture was diluted with EtOAc, poured into a 1N aqueous HCl solution (5 mL) and the aqueous layer was extracted with EtOAc (2×20 mL). Combined organics were washed with a sat. NaHCO.sub.3 solution (5 mL), then brine before being dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 70% EtOAc-heptane gradient to give the title compound (0.598 g, 84%) as an off-white solid. MS: 616.4 (M+H.sup.+).

[D] (S)-2-Amino-3-(3-chlorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide

(10) ##STR00018##

(11) 4M HCl in dioxane (1.46 mL, 5.82 mmol) was added at 0° C. to a solution of tert-butyl ((S)-3-(3-chlorophenyl)-1-(((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)amino)-1-oxopropan-2-yl)carbamate (0.598 g, 0.971 mmol) in MeOH (6 mL). The reaction mixture was stirred at this temperature for 10 min and then allowed to warm up to room temperature and stirring was continued for 5 hours. The mixture was evaporated to dryness and the residue was triturated with diisopropylether. The solid precipitate was filtered off and further dried under the high vacuum to give the title compound (0.476 g, 86%, HCl salt) as an off-white solid. MS: 516.3 (M+H.sup.+).

Intermediate A-2

(S)-2-Amino-3-(3-fluorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide

(12) ##STR00019##
was prepared in analogy to intermediate A-1, but using in step C] (2S)-2-(tert-butoxycarbonylamino)-3-(3-fluorophenyl)propanoic acid, to give the title compound as light green solid as hydrochloride; MS: 500.4 (M+H.sup.+).

Intermediate A-3

(S)-2-Amino-3-(3-cyanophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide

(13) ##STR00020##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-(3-cyanophenyl)propanoic acid, to give the title compound as light brown solid as hydrochloride; MS: 507.3 (M+H.sup.+).

Intermediate A-4

(2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-3-pyridin-3-ylpropanamide

(14) ##STR00021##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-(3-pyridyl)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 483.4 (M+H.sup.+).

Intermediate A-5

(2S)-2-Amino-3-(2-cyanophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpenta-3-yl]amino]ethyl]propanamide

(15) ##STR00022##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-(2-cyanophenyl)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 483.4 (M+H.sup.+).

Intermediate A-6

tert-Butyl 2-[4-[(2S)-2-amino-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate

(16) ##STR00023##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic acid (Intermediate K-1) and replacing in step D methanol by dioxane as solvent, to give the title compound as colorless solid as hydrochloride; MS: 612.3 (M+H.sup.+).

Intermediate A-7

tert-Butyl 2-[3-[(2S)-2-amino-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate

(17) ##STR00024##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic acid (Intermediate K-2) and replacing in step D methanol by dioxane as solvent, to give the title compound as colorless solid as hydrochloride; MS: 612.3 (M+H.sup.+).

Intermediate A-8

(2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(18) ##STR00025##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)propanoic acid, to give the title compound as colorless solid as hydrochloride; MS: 406.5 (M+H.sup.+).

Intermediate A-9

(2S)-2-Amino-3-methoxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(19) ##STR00026##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-methoxy-propanoic acid, to give the title compound as a light yellow solid as hydrochloride; MS: 436.3 (M+H.sup.+).

Intermediate A-10

(S)-2-Amino-3-(tert-butoxy)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide

(20) ##STR00027##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-3-tert-butoxy-2-(tert-butoxycarbonylamino)propanoic acid and replacing in step D methanol by dioxane as solvent, to give the title compound as colorless solid as hydrochloride; MS: 478.3 (M+H.sup.+).

Intermediate A-11

(2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-3-phenylmethoxypropanamide

(21) ##STR00028##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-3-benzyloxy-2-(tert-butoxycarbonylamino)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 512.3 (M+H.sup.+).

Intermediate A-12

tert-Butyl (4S)-4-amino-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-5-oxopentanoate

(22) ##STR00029##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-5-tert-butoxy-2-(tert-butoxycarbonylamino)-5-oxo-pentanoic acid and replacing in step D methanol by dioxane as solvent, to give the title compound as colorless solid; MS: 520.3 (M+H.sup.+).

Intermediate A-13

2-[4-[[(2S)-3-(3-(Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic Acid

(23) ##STR00030##

[A] tert-Butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate

(24) ##STR00031##

(25) (S)-2-Amino-3-(3-chlorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide hydrochloride (Intermediate A-1, 0.06 g, 0.109 mmol), 4-(2-tert-butoxy-2-oxo-ethoxy)benzoic acid (0.027 g, 0.109 mmol) and HATU (0.045 g, 0.119 mmol) were dissolved in DMF (1 mL) in a round-bottomed flask, and the mixture cooled to 0° C. Hünig's base (0.057 mL, 0.326 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued for 2 hours. The mixture was diluted with EtOAc, poured into a 1N aqueous HCl solution (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed with a sat. NaHCO.sub.3 solution (5 mL), then brine before being dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.079 g, 95%) as colorless solid. MS: 750.6 (M+H.sup.+).

[B] 2-[4-[[(2S)-3-(3-Chlorophenyl)-1-[[(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic Acid

(26) ##STR00032##

(27) To a solution of tert-butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetate (0.079 g, 0.105 mmol) in DCM (0.5 mL) was added TFA (0.405 mL, 5.26 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo, the residue was triturated in diisopropylether, filtered and further dried under high vacuum to give the title compound (0.057 g, 62%) as an off-white solid. MS: 694.3 (M+H.sup.+).

Intermediate A-14

2-[3-[[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic Acid

(28) ##STR00033##
was prepared in analogy to intermediate A-13, but using in step [A] 3-(2-tert-butoxy-2-oxo-ethoxy)benzoic acid, to give the title compound as colorless solid; MS: 694.5 (M+H.sup.+).

Intermediate A-15

2-[4-[[(2S)-3-(3-Cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic Acid

(29) ##STR00034##
was prepared in analogy to intermediate A-13, but using in step [A] (S)-2-amino-3-(3-cyanophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide hydrochloride (Intermediate A-3), to give the title compound as colorless solid; MS: 685.3 (M+H.sup.+).

Intermediate A-16

2-[3-[[(2S)-3-(3-Cyanophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic Acid

(30) ##STR00035##
was prepared in analogy to intermediate A-13, but using in step [A] (S)-2-amino-3-(3-cyanophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide hydrochloride (Intermediate A-3) and 3-(2-tert-butoxy-2-oxo-ethoxy)benzoic acid, to give the title compound as colorless solid; MS: 685.3 (M+H.sup.+).

Intermediate A-17

tert-Butyl N-[(5S)-5-amino-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate

(31) ##STR00036##

[A] tert-butyl N-[(5S)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate

(32) ##STR00037##

(33) To a solution of (S)-2-amino-2-(4-methoxyphenyl)-N-((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)acetamide hydrochloride (Intermediate A-1 [B], 0.200 g, 0.539 mmol), (2S)-6-(tert-butoxycarbonylamino)-2-(9H-fluoren-9-ylmethoxycarbonylamino)hexanoic acid (0.253 g, 0.539 mmol) and HATU (0.246 g, 0.647 mmol) in DMF (2 mL) cooled to 0° C. was added Huenig's base (0.283 mL, 1.62 mmol). The reaction mixture was stirred for 15 minutes, then allowed to warm up and stirred at room temperature for 2.5 hours. The mixture was diluted with EtOAc, poured into water and the aqueous phase was extracted with EtOAc. Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 10 to 80% EtOAc-heptane gradient to give the title compound (0.350 g, 78%) as a white solid. MS: 785.4 (M+H.sup.+).

[B] tert-Butyl N-[(5S)-5-amino-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate

(34) ##STR00038##

(35) To a solution of tert-butyl N-[(5S)-5-(9H-fluoren-9-ylmethoxycarbonylamino)-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate (0.350 g, 0.446 mmol) in DMF (3 mL) was added diethylamine (0.230 mL, 2.6 mmol) and the reaction mixture stirred at room temperature for 2 hours. The solvent was evaporated to dryness and the residue was purified by silica gel flash chromatography eluting with a 0 to 15% MeOH-DCM gradient to give the title compound (0.192 g, 69%) as a light yellow solid. MS: 563.3 (M+H.sup.+).

Intermediate A-18

tert-Butyl N-[(4S)-4-amino-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-5-oxopentyl]carbamate

(36) ##STR00039##
was prepared in analogy to intermediate A-17, but using in step [A] (2S)-5-(tert-butoxycarbonylamino)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pentanoic acid, to give the title compound as a light yellow waxy solid. MS: 549.3 (M+H.sup.+).

Intermediate A-19

tert-Butyl N-[[4-[(2S)-2-amino-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenyl]methyl]carbamate

(37) ##STR00040##
was prepared in analogy to intermediate A-17, but using in step [A] (2S)-3-[4-[(tert-butoxycarbonylamino)methyl]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid, to give the title compound as a white solid. MS: 611.3 (M+H.sup.+).

Intermediate A-20

(2S)-2-Amino-3-[tert-butyl(dimethyl)silyl]oxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(38) ##STR00041##

[A] 9H-Fluoren-9-ylmethyl N-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamate

(39) ##STR00042##

(40) To a solution of (S)-2-amino-2-(4-methoxyphenyl)-N-((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)acetamide hydrochloride (Intermediate A-1 [B], 0.240 g, 0.647 mmol) in DMF (10 mL) cooled to 0° C. with an ice bath was added Huenig's base (0.565 mL, 3.24 mmol). Then, (2S)-3-[tert-butyl (dimethyl)silyl]oxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid (0.286 g, 0.647 μmol) followed by HATU (0.295 g, 0.777 mmol) were added and the reaction mixture was stirred at this temperature for 1 hour. The mixture was diluted with EtOAc, poured into a sat. NaHCO.sub.3 aqueous solution and the aqueous layer extracted with EtOAc. Combined organics were washed with NH.sub.4Cl and brine, then dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 0 to 60% EtOAc/heptane gradient to give the title compound (0.321 g, 65%) as a colorless solid. MS: 758.4 (M+H.sup.+).

[B] (2S)-2-Amino-3-[tert-butyl(dimethyl)silyl]oxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(41) ##STR00043##

(42) To a solution of 9H-fluoren-9-ylmethyl N-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamate (0.315 g, 0.416 mmol) in DCM (3 mL) was added diethylamine (0.434 mL, 4.16 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by silica gel flash chromatography, eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.161 g, 72%) as a colorless solid. MS: 536.3 (M+H.sup.+).

Intermediate A-21

(2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-3-(trifluoromethoxy)propanamide

(43) ##STR00044##

[A] Benzyl (2S)-[(2-(2-methylpropan-2-yl)oxycarbonylamino]-3-(trifluoromethoxy)propanoate

(44) ##STR00045##

(45) In a sealed tube, potassium fluoride (0.123 g, 2.12 mmol, dried on the high vacuum overnight), silver trifluoromethanesulfonate (0.385 g, 1.5 mmol), selectfluor (0.266 g, 0.750 mmol) and benzyl (2S)-2-(tert-butoxycarbonylamino)-3-hydroxy-propanoate (0.148 g, 0.5 mmol) were added successively under Argon. Then, dry EtOAc (2.5 mL), 2-fluoropyridine (0.129 mL, 1.5 mmol) and (trifluoromethyl)trimethylsilane (0.240 mL, 1.5 mmol) were added successively under argon and the reaction mixture was stirred at room temperature overnight. The mixture was filtered through a plug of Decalite and washed with EtOAc. The filtrate was evaporated and the residue purified by silica gel flash chromatography, eluting with 0-100% EtOAc/heptane gradient to give the title compound (0.064 g, 72%) as a colorless oil. MS: 308.0 (M-tBu+H.sup.+).

[B] (2S)-2-[(2-Methylpropan-2-yl)oxycarbonylamino]-3-(trifluoromethoxy)propanoic Acid

(46) ##STR00046##

(47) A solution of benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(trifluoromethoxy)propanoate (0.121 g, 0.333 mmol) in methanol (7 mL) was purged several times with Ar, then Pd on C (0.018 g, 0.017 mmol) was added and the reaction mixture was stirred at room temperature under a hydrogen atmosphere for 2 hours. The catalyst was removed by filtration and the filtrate concentrated in vacuo to give the title compound (0.085 g, 93%) as a colorless solid. MS: 272.2 (M−H.sup.−).

[C] tert-Butyl N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxo-3-(trifluoromethoxy)propan-2-yl]carbamate

(48) ##STR00047##

(49) To a solution of (S)-2-amino-2-(4-methoxyphenyl)-N-((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)acetamide hydrochloride (Intermediate A-1 [B], 0.115 g, 0.311 mmol), (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(trifluoromethoxy)propanoic acid (0.085 g, 0.311 mmol) and HATU (0.130 g, 0.342 mmol) in DMF (1 mL) cooled to 0° C. was added Huenig's base (0.163 mL, 0.933 mmol). The reaction mixture was stirred for 15 minutes, then allowed to warm up to room temperature and stirred at room temperature for 1 hour. The mixture was diluted with EtOAc, poured into water and the aqueous layer was extracted with EtOAc. Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.041 g, 22%) as a colorless solid. MS: 590.3 (M+H.sup.+).

[D] (2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-3-(trifluoromethoxy)propanamide

(50) ##STR00048##

(51) To a solution of tert-butyl N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxo-3-(trifluoromethoxy)propan-2-yl]carbamate (0.41 g, 0.069 mmol) in methanol (1 mL) was added 4M HCl in dioxane (0.174 mL, 0.695 mmol) and the reaction mixture was stirred at room temperature overnight. The mixture was evaporated to dryness and the residue was triturated with diisopropylether. The solid precipitate was filtered off and further dried under the high vacuum to give the title compound (0.034 g, 94%, HCl salt) as an orange solid. MS: 490.2 (M+H.sup.+).

Intermediate A-22

(2S)-2-amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide

(52) ##STR00049##
was prepared in analogy to intermediate A-17, but using in step [A] (2S)-4-[[diphenyl(p-tolyl)methyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-butanoic acid, to give the title compound as a yellow waxy solid. MS: 705.3 (M+H.sup.+).

Intermediate A-23

(2S)-2-Amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide

(53) ##STR00050##
was prepared in analogy to intermediate A-17, but using in step [A] (2S)-5-[[diphenyl(p-tolyl)methyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-oxo-pentanoic acid, to give the title compound as a yellow foam. MS: 719.4 (M+H.sup.+).

Intermediate A-24

(2S)-2-Amino-3-cyano-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(54) ##STR00051##
was prepared in analogy to intermediate A-1, but using in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-cyano-propanoic acid and replacing in step [D] methanol by dioxane as solvent, to give the title compound as a colorless solid as hydrochloride. MS: 431.2 (M+H.sup.+).

Intermediate B-1

(2S)-2-Amino-3-(3-chlorophenyl)-N-[(1S and 1R)-2-oxo-1-phenyl-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(55) ##STR00052##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-2-phenyl-acetic, to give the title compound as colorless solid as hydrochloride; MS: 486.2 (M+H.sup.+).

Intermediate B-2

(2S)-2-Amino-3-(3,4-dichlorophenyl)-N-[(1S and 1R)-)-2-oxo-1-phenyl-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(56) ##STR00053##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-2-phenyl-acetic and in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-(3,4-chlorophenyl)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 520.2 (M+H.sup.+).

Intermediate B-3

(2R)-2-Amino-3-(3-chlorophenyl)-N-[(1S and 1R)-)-2-oxo-1-phenyl-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(57) ##STR00054##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-2-phenyl-acetic and in step [C] (2R)-2-(tert-butoxycarbonylamino)-3-(3-chlorophenyl)propanoic acid, to give the title compound as light brown foam as hydrochloride; MS: 486.2 (M+H.sup.+).

Intermediate C-1

(2S)-2-Amino-3-(3-chlorophenyl)-N-[(1S and 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropyl-propyl]amino]ethyl]propanamide

(58) ##STR00055##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-2-(3-methoxyphenyl)acetic acid, to give the title compound as light brown gum as hydrochloride; MS: 516.2 (M+H.sup.+).

Intermediate D-1

(2S)-2-[[(2S)-2-Amino-3-(3-chlorophenyl)propanoyl]amino]-3-phenyl-N-[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]propanamide

(59) ##STR00056##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-3-phenyl-propanoic acid, to give the title compound as colorless solid as hydrochloride; MS: 500.2 (M+H.sup.+).

Intermediate D-2

(2S)-2-[[(2R)-2-Amino-3-(3-chlorophenyl)propanoyl]amino]-3-phenyl-N-[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]propanamide

(60) ##STR00057##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-3-phenyl-propanoic acid and in step [C] (2R)-2-(tert-butoxycarbonylamino)-3-(3-chlorophenyl)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 500.2 (M+H.sup.+).

Intermediate D-3

(S)-2-Amino-3-(3,4-dichlorophenyl)-N—((S)-1-oxo-3-phenyl-1-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)propan-2-yl)propanamide

(61) ##STR00058##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-3-phenyl-propanoic acid and in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-(3,4-chlorophenyl)propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 534.4 (M+H.sup.+).

Intermediate D-4

(S)-2-Amino-3-cyclohexyl-N—((S)-1-oxo-3-phenyl-1-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)propan-2-yl)propanamide

(62) ##STR00059##
was prepared in analogy to intermediate A-1, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-3-phenyl-propanoic acid and in step [C] (2S)-2-(tert-butoxycarbonylamino)-3-cyclohexyl-propanoic acid, to give the title compound as off-white solid as hydrochloride; MS: 472.3 (M+H.sup.+).

Intermediate E-1

tert-Butyl 2-[4-[(1S)-1-[[(2S)-2-amino-3-(3-fluorophenyl)propanoyl]amino]-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]phenoxy]acetate

(63) ##STR00060##
was prepared in analogy to intermediate A-2, but using in step [A] (2S)-2-(tert-butoxycarbonylamino)-2-[4-(2-tert-butoxy-2-oxo-ethoxy)phenyl]acetic acid and replacing in the deprotection steps [B] and [D] methanol by dioxane as solvent, to give the title compound as light brown solid as hydrochloride; MS: 600.4 (M+H.sup.+).

Intermediate J-1

3,3,3-Trifluoro-2-[3-(trifluoromethyl)phenyl]propanoic Acid

(64) ##STR00061##

[A] Ethyl 3,3,3-trifluoro-2-methylsulfonyloxy-2-[3-(trifluoromethyl)phenyl]propanoate

(65) ##STR00062##

(66) To a solution of ethyl 3,3,3-trifluoro-2-hydroxy-2-[3-(trifluoromethyl)phenyl]propanoate (0.5 g, 1.58 mmol) in acetonitrile (5 mL) cooled to −5° C. was added TEA (0.882 mL, 6.33 mmol). Then, methanesulfonyl chloride (0.493 μL, 6.33 mmol) was added dropwise and the solution was stirred at this temperature for 20 minutes. The mixture was poured into ice/water and extracted with DCM. Combined organics were washed with brine, dried over Na.sub.2SO.sub.4 and evaporated to dryness. The residue was purified by silica gel flash chromatography, eluting with a 0 to 40% EtOAc-heptane gradient to give the title compound (0.470 g, 75%) as a colorless liquid. MS: 299.1 (M-OS(O).sub.2CH.sub.3.sup.+).

[B] Ethyl 3,3,3-trifluoro-2-[3-(trifluoromethyl)phenyl]propanoate

(67) ##STR00063##

(68) In a sealed vessel, a solution of ethyl 3,3,3-trifluoro-2-methylsulfonyloxy-2-[3-(trifluoromethyl)phenyl]propanoate (0.470 g, 1.19 mmol) in methanol (5 mL) was purged several times with Ar, then Pd on C (0.254 mg, 0.238 mmol) was added and the reaction mixture was stirred at room temperature under 3 bar hydrogen for 10 hours. The catalyst was removed by filtration and the filtrate concentrated in vacuo to give the title compound (0.358 g, 100%) as a colorless liquid. MS: 394.3 (M−H.sup.−).

[C] 3,3,3-Trifluoro-2-[3-(trifluoromethyl)phenyl]propanoic Acid

(69) ##STR00064##

(70) To a solution of ethyl 3,3,3-trifluoro-2-[3-(trifluoromethyl)phenyl]propanoate (0.205 g, 0.683 mmol) in dioxane (1.5 mL) was added conc. HCl (0.75 mL, 9.13 mmol) and the reaction mixture was heated at reflux for 40 hours. The mixture was allowed to cool to room temperature, then DCM was added and the phases separated. The aqueous phase was extracted with DCM. Combined organics were extracted with a sat. Na.sub.2CO.sub.3 aqueous solution. Combined aqueous layers were acidified to pH 1 with a 2M HCl aqueous solution and extracted with DCM. The organic phases were washed with brine, dried over Na.sub.2SO.sub.4, filtered, and evaporated to dryness to to give the title compound (0.070 g, 37%) as a light yellow solid. MS: 543.3 (2M−H.sup.−).

Intermediate J-2

(71) ##STR00065##

[A] Ethyl 2-(3-chlorophenyl)-1,3-dioxolane-2-carboxylate

(72) ##STR00066##

(73) To a solution of 2-chloroethanol (0.503 μL, 7.5 mmol) in a 2/1 mixture of DMF/THF (6 mL) was added ethyl 2-(3-chlorophenyl)-2-oxoacetate (1.06 g, 5 mmol) and the solution was cooled to −60° C. Potassium tert-butoxide (0.842 g, 7.5 mmol) in DMF (15 mL) was added dropwise over 30 minutes at this temperature. The reaction mixture was stirred for 1.5 hours, then allowed to warm to room temperature and stirred overnight. The mixture was diluted with EtOAc, poured into a 1M NH.sub.4Cl aqueous solution and the aqueous layer was extracted with EtOAc. Combined organics were washed with water, brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness to give the title compound (1.2 g, 94%) as a colourless oil. The crude product was used in the next step with no further purification.

[B] 2-(3-Chlorophenyl)-1,3-dioxolane-2-carboxylic Acid

(74) ##STR00067##

(75) To a solution of ethyl 2-(3-chlorophenyl)-1,3-dioxolane-2-carboxylate (0.196 g, 0.764 mmol) in THF (6 mL) cooled to 0° C. was added a 1M aqueous solution of LiOH (1.53 mL, 1.53 mmol) and the reaction was stirred for 2 hours. The mixture was diluted with EtOAc, poured in a 1M KHSO.sub.4 aqueous solution and the aqueous layer was extracted with EtOAc. Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness to give the title compound (0.175 g, 100%) as a colourless oil. The crude product was used in the next step with no further purification. MS: 227.1 (M−H.sup.−).

Intermediate K-1

(2S)-2-[(2-Methylpropan-2-yl)oxycarbonylamino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic Acid

(76) ##STR00068##

[A] Benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoate

(77) ##STR00069##

(78) To a solution of benzyl (2S)-2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propanoate (0.5 g, 1.35 mmol) in DMF (20 ml) were successively added potassium carbonate (0.372 g, 2.69 mmol) and tert-butyl 2-bromoacetate (0.199 ml, 1.35 mmol). The reaction mixture was stirred overnight at room temperature. The mixture was diluted with EtOAc, poured into H.sub.2O (25 ml) and the aqueous layer was extracted with EtOAc (2×20 ml). Combined organics were dried over Na.sub.2SO.sub.4, filtered and evaporated. The crude material was purified by flash chromatography eluting with a 0 to 60% EtOAc in heptane gradient to yield the title compound (0.588 g, 88%) as a colorless solid; MS: 484.3 (M−H.sup.−).

[B] (2S)-2-[(2-Methylpropan-2-yl)oxycarbonylamino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic Acid

(79) ##STR00070##

(80) A solution of benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoate (0.588 g, 1.21 mmol) in methanol (20 ml) was purged several times with Ar, then Pd on C (0.064 g, 0.061 mmol) was added and the reaction mixture was stirred at room temperature under a hydrogen atmosphere for 1 hour. The catalyst was removed by filtration and the filtrate concentrated in vacuo to give the title compound (0.468 g, 98%) as a colorless solid; MS: 394.3 (M−H.sup.−).

Intermediate K-2

(2S)-2-[(2-Methylpropan-2-yl)oxycarbonylamino]-3-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic Acid

(81) ##STR00071##

[A] Benzyl (2S)-3-(3-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate

(82) ##STR00072##

(83) A solution of (2S)-2-(tert-butoxycarbonylamino)-3-(3-hydroxyphenyl)propanoic acid (0.5 g, 1.78 mmol) and cesium carbonate (0.290 g, 0.889 mmol) in DMF (20 mL) was stirred at room temperature for 1.5 hours. Then, benzyl bromide (0.304 g, 1.78 mmol) was added and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with EtOAc, poured into water and acetic acid was added to adjust the pH to 4. The aqueous phase was extracted with EtOAc (2×10 mL) and the combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by flash chromatography eluting with a 0 to 40% EtOAc in heptane gradient to yield the title compound (0.539 g, 82%) as a colorless and viscous oil; MS: 370.3 (M−H.sup.−).

[B] Benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoate

(84) ##STR00073##
was prepared in analogy to intermediate K-1[A], but using benzyl (2S)-3-(3-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate (Intermediate K-2 [A]), to give the title compound as colorless solid.

[C] (2S)-2-[(2-Methylpropan-2-yl)oxycarbonylamino]-3-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic Acid

(85) ##STR00074##
was prepared in analogy to intermediate K-1 [B], but using benzyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-[3-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoate (Intermediate K-2 [B]), to give the title compound as colorless foam; MS: 394.3 (M−H.sup.−).

Intermediate K-3

2-[4-[2-[(2-Methylpropan-2-yl)oxy]-2-oxoethoxy]phenoxy]acetic Acid

(86) ##STR00075##
was prepared in analogy to intermediate K-1, but using in step [A] tert-butyl 2-(4-hydroxyphenoxy)acetate instead of benzyl (2S)-2-(tert-butoxycarbonylamino)-3-(4-hydroxyphenyl)propanoate and benzyl 2-bromoacetate instead of tert-butyl 2-bromoacetate, to give the title compound as colorless solid; MS: 281.3 (M−H.sup.−).

Intermediate L-1

6-(2-(tert-Butoxy)-2-oxoethoxy)picolinic Acid

(87) ##STR00076##

[A] Benzyl 6-hydroxypicolinate

(88) ##STR00077##

(89) To a solution of 6-hydroxypyridine-2-carboxylic acid (1 g, 7.19 mmol) in DMF (15 mL) was added TEA (1.5 ml, 10.8 mmol) and the mixture was heated to 40° C. for 1 hour. Then, benzyl bromide (0.897 mL, 7.55 mmol) was added and the reaction mixture was heated to 77° C. for 3 hours. The mixture was cooled down to room temperature, diluted with EtOAc and poured into a sat. NaHCO.sub.3 solution (50 mL) and the aqueous layer was extracted with EtOAc (2×50 mL). Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered, evaporated and further dried in high vacuum to yield the crude title compound (1.33 g, 81%) as light brown solid; MS: 230.1 (M+H.sup.+).

[B] Benzyl 6-(2-(tert-butoxy)-2-oxoethoxy)picolinate

(90) ##STR00078##

(91) To a solution of benzyl 6-(2-(tert-butoxy)-2-oxoethoxy)picolinate (0.302 g, 1.32 mmol) in acetone (30 ml) were successively added potassium carbonate (0.868 g, 6.28 mmol) and tert-butyl 2-bromoacetate (0.186 mL, 1.26 mmol). The reaction mixture was heated to 65° C. for 3 h. The mixture was cooled to room temperature, the solid precipitate was filtered off and the filtrate concentrated in vacuo. The residue was purified by flash chromatography eluting with a 0 to 20% EtOAc in heptane gradient to yield the title compound (0.3 g, 70%) as a colorless solid; MS: 344.2 (M+H.sup.+).

[C] 6-(2-(tert-Butoxy)-2-oxoethoxy)picolinic Acid

(92) ##STR00079##
was prepared in analogy to intermediate K-1 [B], but using benzyl 6-(2-(tert-butoxy)-2-oxoethoxy)picolinate (Intermediate L-1 [B]), to give the title compound as colorless solid; MS: 252.3 (M−H.sup.−).

Intermediate L-2

5-(2-(tert-Butoxy)-2-oxoethoxy)picolinic Acid

(93) ##STR00080##
was prepared in analogy to intermediate L-1, but using in step [A] 5-hydroxypyridine-2-carboxylic acid, to give the title compound as yellow solid; MS: 254.2 (M+H.sup.+).

Intermediate L-3

1-(2-(tert-Butoxy)-2-oxoethyl)-2-oxo-1,2-dihydropyridine-4-carboxylic Acid

(94) ##STR00081##
was prepared in analogy to intermediate L-1, but using in step [A] 2-hydroxypyridine-4-carboxylic acid, to give the title compound as colorless solid; MS: 252.2 (M−H.sup.−).

Intermediate L-4

1-[2-[(2-Methylpropan-2-yl)oxy]-2-oxoethyl]-6-oxopyridine-3-carboxylic Acid

(95) ##STR00082##
was prepared in analogy to intermediate L-1, but using in step [A] 6-hydroxypyridine-3-carboxylic acid, to give the title compound as colorless solid; MS: 252.3 (M−H.sup.−).

Example 1

N-[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide

(96) ##STR00083##

[A] N-[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide

(97) ##STR00084##

(98) In a round-bottomed flask, (S)-2-amino-3-(3-chlorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide hydrochloride (Intermediate A-1, 0.021 g, 0.038 mmol), benzoic acid (0.005 g, 0.038 mmol) and HATU (0.016 g, 0.041 mmol) were dissolved in DMF (1 mL) and the mixture cooled to 0° C. Hunig's base (0.020 mL, 0.114 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued for 2 hours. The mixture was diluted with EtOAc, poured into 1M HCl (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed with a sat. NaHCO.sub.3 solution (5 mL), then brine before being dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.012 g, 51%) as a colorless solid. MS: 620.3 (M+H.sup.+).

[B] N-[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide

(99) ##STR00085##

(100) To a suspension of N-[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]benzamide (0.012 g, 0.019 mmol) in DCM (1 mL) was added 15% Dess-Martin periodinane in DCM solution (0.121 mL, 0.058 mmol) and the reaction mixture was stirred at room temperature overnight. A spatula of solid Na.sub.2S.sub.2O.sub.3 was added and stirring was continued for 5 min. The resulting white suspension was diluted with DCM/water, poured into a sat. NaHCO.sub.3 solution (5 mL) and then extracted with DCM (10 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 0-70% EtOAc-heptane gradient to give the title compound (0.007 g, 58%) as a colorless solid. MS: 618.3 (M+H.sup.+).

(101) The following examples listed in Table 1 were prepared in analogy to the procedures described for the preparation of example 1 by using the indicated intermediate and carboxylic acid in step [A]

(102) TABLE-US-00002 TABLE 1 Name Structure Reactant to be used in step MS Ex Aspect [A] (M + H.sup.+) 2 (2S)-3-(3-chlorophenyl)-N-[(1S)-1-(4- Intermediate A-1 647.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-(3-pyridyl)propanoic acid yl]amino]ethyl]-2-(3-pyridin-3- ylpropanoylamino)propanamide 3 N-[(2S)-3-(3-fluorophenyl)-1-[[(1S)-1-(4- Intermediate A-2 603.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyridine-2-carboxamide 4 3-chloro-N-[(2S)-3-(3-fluorophenyl)-1- Intermediate A-2 636.3 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 3-chlorobenzoic acid oxopentan-3-yl]amino]ethyl]amino]-1- oxopropan-2-yl]benzamide 5 5-chloro-N-[(2S)-3-(3-fluorophenyl)-1- Intermediate A-2 642.2 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 5-chlorothiophene-2- oxopentan-3-yl]amino]ethyl]amino]-1- carboxylic acid oxopropan-2-yl]thiophene-2-carboxamide 6 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-2 686.3 difluoroacetyl]amino]-3-(3-fluorophenyl)- and N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(3-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]propanamide 0 7 (2S)-2-[[2-(2-chlorophenyl)-2,2- Intermediate A-2 686.3 difluoroacetyl]amino]-3-(3-fluorophenyl)- and N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(2-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]propanamide 8 (2S)-2-[[2-(3-chloropehnyl)-2,2- Intermediate A-3 693.3 difluoroacetyl]amino]-3-(3-cyanophenyl)- and N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(3-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]propanamide 9 5-chloro-N-[(2S)-3-(3-cyanophenyl)-1- Intermediate A-3 649.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 5-chlorothiophene-2- oxopentan-3-yl]amino]ethyl]amino]-1- carboxylic acid oxopropan-2-yl]thiophene-2-carboxamide 10 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2- Intermediate A-4 585.5 oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1-oxo- benzoic acid 3-pyridin-3-ylpropan-2-yl]benzamide 11 3-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-4 619.5 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxo-3-pyridin-3- ylpropan-2-yl]benzamide 12 (2S)-2-[[2-(2-chlorophenyl)-2,2- Intermediate A-4 669.5 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]-3-pyridin-3-ylpropanamide 13 N-[(2S)-3-(2-cyanophenyl)-1-[[(1S)-1-(4- Intermediate A-5 610.5 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyridine-2-carboxamide 14 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-5 693.3 difluoroacetyl]amino]-3-(2-cyanophenyl)- and N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(3-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]propanamide 15 tert-butyl 2-[4-[(2S)-2-[(3- Intermediate A-6 748.4 chlorobenzyl)amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 3-chlorobenzoic acid trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetate 16 tert-butyl 2-[4-[(2S)-3-[[(1S)-1-(4- Intermediate A-6 715.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]-3-oxo-2-(pyridine- 2-carbonylamino)propyl]phenoxy]acetate 00 17 tert-butyl 2-[4-[(2S)-2-[[2-(2- Intermediate A-6 798.3 chlorophenyl)-2,2-difluoroacetyl]amino]-3- and [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(2-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetate 01 18 tert-butyl 2-[4-[(2S)-2-[[2-(3- Intermediate A-6 798.3 chlorophenyl)-2,2-difluoroacetyl]amino]-3- and [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(3-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetate 02 19 tert-butyl 2-[3-[(2S)-2-[(3- Intermediate A-7 748.3 chlorobenzoyl)amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-2[[(3S)-1,1,1- 3-chlorobenzoic acid trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetate 03 20 tert-butyl 2-[3-[(2S)-2-[[2-(2- Intermediate A-7 798.4 chlorophenyl)-2,2-difluoroacetyl]amino]-3- and [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 2-(2-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2- difluoro-acetic acid oxopentan-3-yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetate 04 21 N-[(2S)-1-[[1S)-1-(4-methoxyphenyl)-2- Intermediate A-8 509.5 oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- pyridine-2-carboxylic acid oxopropan-2-yl]pyridine-2-carboxamide 05 22 (2S)-2-[(2,2-difluoro-2- Intermediate A-8 558.4 phenylacetyl)amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2,2-difluoro-2-phenyl-acetic trifluoro-4-methyl-2-oxopentan-3- acid yl]amino]ethyl]propanamide 06 23 2,5-dichloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 576.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2,5-dichlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 07 24 3-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 542.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxoopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 08 25 1-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 582.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1-(3- yl]amino]ethyl]amino]-1-oxopropan-2- chlorophenyl)cyclopropane- yl]cyclopropane-1-carboxamide carboxylic acid 09 26 (2S)-2-[[2-(2-chlorophenyl)-2,2- Intermediate A-8 592.3 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 0 27 (2S)-2-[[2-(3-chlorophenyl)acetyl]amino]- Intermediate A-8 556.2 N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 2-(3-chlorophenyl)acetic acid oxopentan-3-yl]amino]ethyl]propanamide 28 2-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 542.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 29 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-8 592.2 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 30 (2S)-2-[[2-(2-chlorophenyl)acetyl]amino]- Intermediate A-8 556.2 N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 2-(2-chlorophenyl)acetic acid oxopentan-3-yl]amino]ethyl]propanamide 31 (2S)-2-[(2-fluoro-2-phenylacetyl)amino]- Intermediate A-8 558.3 N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 2-fluoro-2-phenyl-acetic acid oxopentan-3-yl]amino]ethyl]propanamide 32 5-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 566.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 5-chlorothiophene-2- yl]amino]ethyl]amino]-1-oxopropan-2- carboxylic acid yl]thiophene-2-carboxamide 33 5-bromo-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 594.1 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 5-bromothiophene-2- yl]amino]ethyl]amino]-1-oxopropan-2- carboxylic acid yl]thiophene-2-carboxamide 34 (2S)-2-[[2-(4-chlorophenyl)-2,2- Intermediate A-8 610.2 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(4-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 35 (2S)-2-[[2-(3,4-dichlorophenyl)-2,2- Intermediate A-8 626.3 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3,4-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 36 2-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 584.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-(3-chlorophenyl)-2-methyl- yl]amino]ethyl]amino]-1-oxopropan-2-yl]- propanoic acid 2-methylpropanamide 0 37 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-9 622.2 difluoroacetyl]amino]-3-methoxy-N-[(1S)- and 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 38 3-chloro-N-[2S)-3-methoxy-1-[[(1S)-1-(4- Intermediate A-9 572.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 39 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-10 664.5 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]-3-[(2-methylpropan-2- yl)oxy]propanamide 40 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2- Intermediate A-10 581.5 oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-3-[(2- pyridine-2-carboxylic acid methylpropan-2-yl)oxy]-1-oxopropan-2- yl]pyridine-2-carboxamide 41 3-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-10 614.5 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-3-[(2- methylpropan-2-yl)oxy]-1-oxopropan-2- yl]benzamide 42 5-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-10 620.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 5-chlorothiophene-2- yl]amino]ethyl]amino]-3-[(2- carboxylic acid methylpropan-2-yl)oxy]-1-oxopropan-2- yl]thiophene-2-carboxamide 43 (2S)-2-[[2-(2-chlorophenyl)-2,2- Intermediate A-10 666.3 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]-3-[(2-methylpropan-2- yl)oxy]propanamide 44 3-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-11 648.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxo-3- phenylmethoxypropan-2-yl]benzamide 45 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2- Intermediate A-11 615.4 oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1-oxo- pyridine-2-carboxylic acid 3-phenylmethoxypropan-2-yl]pyridine-2- carboxamide 46 tert-butyl (4S)-4-[(3-chlorobenzoyl)amino]- Intermediate A-12 656.3 5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 3-chlorobenzoic acid oxopentan-3-yl]amino]ethyl]amino]-5- oxopentanoate 0 47 tert-butyl (4S)-4-[[2-(3-chlorophenyl)-2,2- Intermediate A-12 706.4 difluoroacetyl]amino]-5-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluroo-acetic acid yl]amino]ethyl]amino]-5-oxopentanoate 48 N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(1S Intermediate B-1 590.2 and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyrazine-2-carboxamide 49 N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(1S Intermediate B-1 (M + H.sub.2O).sup.+ and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1- and 613.2 trifluoro-4-methyl-2-oxopentan-3- 1-methylpyrroldiine-3- yl]amino]ethyl]amino]propan-2-yl]-1- carboxylic acid methylpyrrolidine-3-carboxamide 50 N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1- Intermediate B-2 624.2 [[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyrazine-2-carboxamide 51 N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1- Intermediate B-2 623.2 [[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyridine-2-carboxamide 52 N-[(2S)-3-(3,4-dichloropehnyl)-1-oxo-1- Intermediate B-2 624.1 [[(1S and 1R)-2-oxo-1-phenyl-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- pyrimidine-5-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyrimidine-5-carboxamide 53 N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and Intermediate C-1 620.2 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyrazine-2-carboxamide 54 N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)- Intermediate D-1 604.2 1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4- and methyl-2-oxopentan-3-yl]amino]propan-2- pyrazine-2-carboxylic acid yl]amino]propan-2-yl]pyrazine-2- carboxamide 55 N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)- Intermediate D-1 604.2 1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4- and methyl-2-oxopentan-3-yl]amino]propan-2- pyrimidine-5-carboxylic acid yl]amino]propan-2-yl]pyrimidine-5- carboxamide 56 N-[(2S)-3-(3-chlorophenyl)-1-oxo-1-[[(2S)- Intermediate D-1 (M + H.sub.2O).sup.+ 1-oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4- and 641.3 methyl-2-oxopentan-3-yl]amino]propan-2- 1-methylpiperidine-4- yl]amino]propan-2-yl]-1-methylpiperidine- 4-carboxamide 0 57 N-[(2R)-3-(3-chlorophenyl)-1-oxo-1- Intermediate D-2 604.2 [[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrimidine-5-carboxylic acid yl]amino]propan-2-yl]amino]propan-2- yl]pyrimidine-5-carboxamide 58 N-[(2R)-3-(3-chlorophenyl)-1-oxo-1- Intermediate D-2 604.2 [[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]propan-2-yl]amino]propan-2- yl]pyrazine-2-carboxamide 59 N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1- Intermediate D-3 637.1 [[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]propan-2-yl]amino]propan-2- yl]pyridine-2-carboxamide 60 N-[(2S)-3-(3,4-dichlorophenyl)-1-oxo-1- Intermediate D-3 638.2 [[(2S)-1-oxo-3-phenyl-1-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]propan-2-yl]amino]propan-2- yl]pyrazine-2-carboxamide 61 N-[(2S)-3-cyclohexyl-1-oxo-1-[[(2S)-1- Intermediate D-4 624.3 oxo-3-phenyl-1-[[(3S)-1,1,1-trifluoro-4- and methyl-2-oxopentan-3-yl]amino]propan-2- naphthalene-2-carboxylic acid yl]amino]propan-2-yl]naphthalene-2- carboxamide 62 tert-butyl N-[2-[[(2S)-3-(3-chlorophenyl)- Intermediate A-1 671.4 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 2-(tert- oxopentan-3-yl]amino]ethyl]amino]-1- butoxycarbonylamino)acetic oxopropan-2-yl]amino]-2- acid oxoethyl]carbamate 63 tert-butyl N-[[4-[[(2S)-3-(3-chlorophenyl)- Intermediate A-1 747.7 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 4-[(tert- oxopentan-3-yl]amino]ethyl]amino]-1- butoxycarbonylamino)methyl] oxopropan-2- benzoic acid yl]carbamoyl]phenyl]methyl]carbamate 64 tert-butyl N-[[2-chloro-4-[[(2S)-3-(3- Intermediate A-1 781.3 chlorophenyl)-1-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 4-[(tert- trifluoro-4-methyl-2-oxopentan-3- butoxycarbonylamino)methyl]- yl]amino]ethyl]amino]-1-oxopropan-2- 3-chloro-benzoic acid yl]carbamoyl]phenyl]methyl]carbamate 65 tert-butyl N-[[4-[2-[[(2S)-3-(3- Intermediate A-1 (M − H.sup.−) chlorophenyl)-1-[[(1S)-1-(4- and 759.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-[4-[(tert- trifluoro-4-methyl-2-oxopentan-3- butoxycarbonylamino)methyl] yl]amino]ethyl]amino]-1-oxopropan-2- phenyl]acetic acid yl]amino]-2- oxoethyl]phenyl]methyl]carbamate 66 tert-butyl 2-[6-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 749.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluroo-4-methyl-2- Intermediate L-1 oxopentan-3-yl]amino]ethyl]amino]-1- oxopropan-2-yl]carbamoyl]pyridin-2- yl]oxyacetate 0 67 tert-butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 748.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 4-(2-tert-butoxy-2-oxo- oxopentan-3-yl]amino]ethyl]amino]-1- ethoxy)benzoic acid oxopropan-2- yl]carbamoyl]phenoxy]acetate 68 tert-butyl 2-[6-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 749.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- Intermediate L-2 oxopentan-3-yl]amino]ethyl]amino]-2- oxopropan-2-yl]carbamoyl]pyridin-3- yl]oxyacetate 69 tert-butyl 2-[4-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 749.5 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- Intermediate L-3 oxopentan-3-yl]amino]ethyl]amino]-2- oxopropan-2-yl]carbamoyl]-2-oxopyridin- 1-yl]acetate 70 tert-butyl 2-[3-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 748.5 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 3-(2-tert-butoxy-2-oxo- oxopentan-3-yl]amino]ethyl]amino]-1- ethoxy)benzoic acid oxopropan-2- yl]carbamoyl]phenoxy]acetate 71 tert-butyl 2-[5-[[(2S)-3-(3-chlorophenyl)-1- Intermediate A-1 749.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- Intermediate L-4 oxopentan-3-yl]amino]ethyl]amino]-1- oxopropan-2-yl]carbamoyl]-2-oxopyridin- 1-yl]acetate 72 tert-butyl 2-[4-[2-[[(2S)-3-(3- Intermediate A-1 778.4 chlorophenyl)-1-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- Intermediate K-3 trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]amino]-2-oxoethoxy]phenoxy]acetate 73 tert-butyl 2-[3-[[(2S)-3-(3-cyanophenyl)-1- Intermediate A-3 739.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 3-(2-tert-butoxy-2-oxo- oxopentan-3-yl]amino]ethyl]amino]-1- ethoxy)benzoic acid oxopropan-2- yl]carbamoyl]phenoxy]acetate 74 tert-butyl 2-[4-[[(2)S-3-(3-cyanophenyl)-1- Intermediate A-3 739.4 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2- 4-(2-tert-butoxy-2-oxo- oxopentan-3-yl]amino]ethyl]amino]-1- ethoxy)benzoic acid oxopropan-2- yl]carbamoyl]phenoxy]acetate 75 N-[3-(3-chlorophenyl)-1-[[(1S and 1R)-1- Intermediate C-1 619.2 (3-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyridine-2-carboxamide 76 N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and Intermediate C-1 633.2 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- 3-methylpyridine-2-carboxylic yl]amino]ethyl]amino]-1-oxopropan-2-yl]- acid 3-methylpyridine-2-carboxamide 0 77 N-[(2S)-3-(3-chlorophenyl)-1-[[(1S and Intermediate C-1 633.2 1R)-1-(3-methoxyphenyl)-2-oxo-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- 4-methylpyridine-3-carboxylic yl]amino]ethyl]amino]-1-oxopropan-2-yl]- acid 4-methylpyridine-3-carboxamide 78 N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1-(4- Intermediate A-3 610.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyridine-2-carboxamide 79 N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S Intermediate B-3 589.3 and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyridine-2-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyridine-2-carboxamide 80 N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S Intermediate B-3 590.3 and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrazine-2-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyrazine-2-carboxamide 81 N-[(2R)-3-(3-chlorophenyl)-1-oxo-1-[[(1S Intermediate B-3 590.2 and 1R)-2-oxo-1-phenyl-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- pyrimidine-5-carboxylic acid yl]amino]ethyl]amino]propan-2- yl]pyrimidine-5-carboxamide 82 tert-butyl N-[[4-[[(2S)-1-[[(1S)-1-(4- Intermediate A-8 637.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 4-[(tert- yl]amino]ethyl]amino]-1-oxopropan-2- butoxycarbonylamino)methyl] yl]carbamoyl]phenyl]methyl]carbamate benzoic acid 83 tert-butyl N-[[4-[2-[[(2S)-1-[[(1S)-1-(4- Intermediate A-8 651.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-[4-[(tert- yl]amino]ethyl]amino]-1-oxopropan-2- butoxycarbonylamino)methyl] yl]amino]-2- phenyl]acetic acid oxoethyl]phenyl]methyl]carbamate

Example 84

tert-Butyl 2-[[2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate

(103) ##STR00168##

[A] tert-Butyl 2-[[2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate

(104) ##STR00169##

(105) In a round-bottomed flask, 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetic acid (Intermediate A-13, 0.057 g, 0.082 mmol), tert-butyl 2-aminoacetate hydrochloride (0.013 g, 0.098 mmol) and HATU (0.034 g, 0.090 mmol) were dissolved in DMF (1 mL) and the mixture cooled to 0° C. Hunig's base (0.043 mL, 0.246 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued overnight. The mixture was diluted with EtOAc, poured into 1M HCl (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed with a sat. NaHCO.sub.3 solution (5 mL), then brine before being dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc-heptane gradient to give the title compound (0.049 g, 67%) as a colorless solid. MS: 807.4 (M+H.sup.+).

[B] tert-Butyl 2-[[2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate

(106) ##STR00170##
was prepared in analogy to example 1[B], but using tert-butyl 2-[[2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]carbamoyl]phenoxy]acetyl]amino]acetate, to give the title compound as colorless solid; MS: 805.5 (M+H.sup.+).

(107) The following examples listed in Table 2 were prepared in analogy to the procedures described for the preparation of example 84 by using the indicated intermediate in step [A].

(108) TABLE-US-00003 TABLE 2 Name Structure Reactant to be used in step MS Ex Aspect [A] (M + H.sup.+) 85 tert-butyl 2-[[2-[3-[[(2S)-3-(3-chlorophenyl)- Intermediate A-14 805.5 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan- tert-butyl 2-aminoacetate 3-yl]amino]ethyl]amino]-1-oxopropan-2- HCl yl]carbamoyl]phenoxy]acetyl]amino]acetate 86 tert-butyl 2-[[2-[4-[[(2S)-3-(3-cyanophenyl)- Intermediate A-15 796.4 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- tert-butyl 2-aminoacetate yl]amino]ethyl]amino]-1-oxopropan-2- HCl yl]carbamoyl]phenoxy]acetyl]amino]acetate 87 tert-butyl 2-[[2-[3-[[(2S)-3-(3-cyanophenyl)- Intermediate A-16 796.4 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- and 1,1,1-trifluoro-4-methyl-2-oxopentan-3- tert-butyl 2-aminoacetate yl]amino]ethyl]amino]-1-oxopropan-2- HCl yl]carbamoyl]phenoxy]acetyl]amino]acetate

Example 88

2-[4-[(2S)-2-[(3-Chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetic Acid

(109) ##STR00174##

(110) To a solution of tert-butyl 2-[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-3-oxopropyl]phenoxy]acetate (Example 15, 0.018 g, 0.024 mmol) in DCM (1 mL) was added TFA (0.092 mL, 1.2 mmol) and the reaction mixture was stirred at room temperature for 4 hours. The mixture was concentrated in vacuo, the residue was triturated in diisopropylether, filtered and further dried under high vacuum. The residue was purified by preparative TLC (silica gel, 7/3 EtOAc/heptane) to give the title compound (0.015 g, 92%) as a colorless solid. MS: 692.6 (M+H.sup.+).

(111) The following examples listed in Table 3 were prepared in analogy to the procedure described for the preparation of example 88 by using the indicated starting materials. Carboxylic acids were purified by preparative TLC to remove the traces amounts of remaining tert-butyl intermediate; amine products were triturated in diisopropylether and obtained as TFA salts.

(112) TABLE-US-00004 TABLE 3 Name Reactant: compound Structure obtained in example MS Ex Aspect number indicated (M + H.sup.+) 89 2-[4-[(2S)-3-[[(1S)-1-(4-methoxyphenyl)- Example 16 659.3 2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- oxopentan-3-yl]amino]ethyl]amino]-3-oxo- 2-(pyridine-2- carbonylamino)propyl]phenoxy]acetic acid 90 2-[4-[(2S)-2-[[2-(2-chlorophenyl)-2,2- Example 17 742.3 difluoroacetyl]amino]-3-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetic acid 91 2-[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2- Example 18 742.3 difluoroacetyl]amino]-3-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetic acid 92 2-[3-[(2S)-2-[(3-chlorobenzoyl)amino]-3- Example 19 692.3 [[(1S)-1-(4-methoxyphenyl)-2-oxo-2- [[(3S)-1,1,1-trifluoro-4-methyl-2- oxopentan-3-yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetic acid 93 2-[3-[(2S)-2-[[2-(2-chlorophenyl)-2,2- Example 20 742.3 difluoroacetyl]amino]-3-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenoxy]acetic acid 94 (4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)- Example 46 600.2 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-5-oxopentanoic acid 0 95 (4S)-4-[[2-(3-chlorophenyl)-2,2- Example 47 650.3 difluoroacetyl]amino]-5-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-5-oxopentanoic acid 96 (2S)-2-[(2-aminoacetyl)amino]-3-(3- Example 62 571.3 chlorophenyl)-N-[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]propanamide; TFA salt 97 4-(aminomethyl)-N-[(2S)-3-(3- Example 63 647.5 chlorophenyl)-1-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide; TFA salt 98 4-(aminomethyl)-3-chloro-N-[(2S)-3-(3- Example 64 681.3 chlorophenyl)-1-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide; TFA salt 99 (2S)-2-[[2-[4- (aminomethyl)phenyl]acetyl]amino]-3-(3- Example 65 661.3 chlorophenyl)-N-[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]propanamide; TFA salt 100 2-[6-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4- Example 66 693.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]pyridin-2-yl]oxyacetic acid 101 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1- Example 67 692.4 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetic acid 102 2-[6-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4- Example 68 693.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]pyridin-3-yl]oxyacetic acid 103 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1- Example 69 693.3 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]-2-oxopyridin-1-yl]acetic acid 104 2-[3-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1- Example 70 692.4 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetic acid 0 105 2-[5-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4- Example 71 693.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]-2-oxopyridin-1-yl]acetic acid 106 2-[4-[[(2S)-3-(3-chlorophenyl)-1-[[(1S)-1- Example 72 722.4 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetic acid 107 2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1- Example 73 683.4 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetic acid 108 2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)-1- Example 74 683.4 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetic acid 109 4-(aminomethyl)-N-[(2S)-1-[[(1S)-1-(4- Example 82 537.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide; TFA salt 110 (2S)-2-[[2-[4- Example 83 551.3 (aminomethyl)phenyl]acetyl]amino]-N- [(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]propanamide; TFA salt 111 2-[[2-[4-[[3-(3-chlorophenyl)-1-[[(1S)-1- Example 84 749.3 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetyl]amino]acetic acid 112 2-[[2-[3-[[3-(3-chlorophenyl)-1-[[(1S)-1-(4- Example 85 749.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetyl]amino]acetic acid 113 2-[[2-[4-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)- Example 86 740.4 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetyl]amino]acetic acid 114 2-[[2-[3-[[(2S)-3-(3-cyanophenyl)-1-[[(1S)- Example 87 740.3 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]carbamoyl]phenoxy]acetyl]amino]acetic acid 00

Example 115

(2S)-2-[[2-(3-Chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide

(113) ##STR00201##

(114) To a solution of (2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-3-[(2-methylpropan-2-yl)oxy]propanamide (Example 39, 0.044 g, 0.066 mmol) in DCM (1 mL) was added wet TFA (2.5% H.sub.2O) (0.355 mL, 4.64 mmol) and the reaction mixture was stirred at room temperature for 4 hours. The mixture was concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 10 to 100% EtOAc-heptane gradient and the resulting material was triturated in diisopropylether, filtered and further dried under high vacuum to give the title compound (0.024 g, 57%) as a colorless solid. MS: 608.2 (M+H.sup.+).

(115) The following examples listed in Table 4 were prepared in analogy to the procedure described for the preparation of example 115 by using the indicated starting materials.

(116) TABLE-US-00005 TABLE 4 Name Reactant: compound Structure obtained in example MS Ex Aspect number indicated (M + H.sup.+) 116 N-[(2S)-3-hydroxy-1-[[(1S)-1-(4- Example 40 525.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]pyridine-2-carboxamide 02 117 3-chloro-N-[(2S)-3-hydroxy-1-[[(1S)-1-(4- Example 41 558.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 03 118 5-chloro-N-[(2S)-3-hydroxy-1-[[(1S)-1-(4- Example 42 564.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2- yl]thiophene-2-carboxamide 04 119 (2S)-2-[[2-(2-chlorophenyl)-2,2- Example 43 608.4 difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1- (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]propanamide 05

Example 120

N-[2-[[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]pyridine-2-carboxamide

(117) ##STR00206##

[A] (2,5-Dioxopyrrolidin-1-yl) pyridine-2-carboxylate

(118) ##STR00207##

(119) To a solution of picolinic acid (0.110 g, 0.894 mmol) in DCM (4 mL) were added EDCI (0.206 g, 1.07 mmol) followed by 1-hydroxypyrrolidine-2,5-dione (0.123 mg, 1.07 mmol) and the reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into water (10 mL) and extracted with DCM (2×20 mL). The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to give the title compound (0.180 g, 91%) as off-white solid. The crude material was used in the next step. MS: 221.1 (M+H.sup.+).

[B] N-[2-[[(2S)-3-(3-Chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]pyridine-2-carboxamide

(120) ##STR00208##

(121) To a solution of (2S)-2-[(2-aminoacetyl)amino]-3-(3-chlorophenyl)-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide; TFA salt (Example 96, 0.020 g, 0.029 mmol) in DCM (1 mL) cooled to −20° C. were added (2,5-dioxopyrrolidin-1-yl) pyridine-2-carboxylate (0.006 g, 0.029 mmol) followed by triethylamine (0.012 mL, 0.088 mmol) and the reaction mixture was stirred at this temperature for 1 hour and then left to stand at 5° C. overnight. The residue was diluted with DCM, poured into water (2 mL) and the aqueous layer was extracted with DCM (2×5 mL). Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated to dryness. The residue was triturated in diisopropylether, filtered and further dried under high vacuum to give the title compound (0.015 g, 76%) as colorless solid; MS: 676.5 (M+H.sup.+).

Example 121

(2S)-3-(3-Chlorophenyl)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide

(122) ##STR00209##

[A] (2S)-3-(3-Chlorophenyl)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(123) ##STR00210##

(124) In a flask, (S)-2-amino-3-(3-chlorophenyl)-N—((S)-1-(4-methoxyphenyl)-2-oxo-2-(((2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl)amino)ethyl)propanamide hydrochloride (Intermediate A-1, 0.033 g, 0.060 mmol), 2-(3-chlorophenyl)acetic acid (0.010 g, 0.060 mmol) and HATU (0.027 g, 0.072 mmol) were dissolved in DMF (1 mL) and the mixture cooled to 0° C. Huenig's base (0.031 mL, 0.179 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued for 2 hours. The mixture was diluted with EtOAc, poured into H.sub.2O (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 10 to 100% EtOAc-heptane gradient to give the title compound (0.039 g, 96%) as a colorless solid. MS: 668.2 (M+H.sup.+).

[B] (2S)-3-(3-Chlorophenyl)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopenta-3-yl]amino]ethyl]propanamide

(125) ##STR00211##

(126) To a solution of (2S)-3-(3-chlorophenyl)-2-[[2-(3-chlorophenyl)acetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide (0.039 g, 0.059 mmol) in DCM (1 mL) was added 15% Dess-Martin periodinane in DCM solution (0.369 mL, 0.178 mmol) and the reaction mixture was stirred at room temperature for 2.5 hours. The resulting white suspension was diluted with DCM/water, poured into a sat. NH.sub.4Cl aqueous solution (5 mL) and then extracted with DCM (10 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 10-100% EtOAc-heptane gradient to give the title compound (0.024 g, 58%) as a colorless solid. MS: 666.3 (M+H.sup.+).

(127) The following examples listed in Table 5 were prepared in analogy to the procedures described for the preparation of example 121 by using the indicated intermediate and carboxylic acid in step [A]. Alanine synthons (intermediate A-8) can undergo isomerization at variable extent during Dess-Martin oxidation (step [B]), thus the stereochemistry of these final compounds can be described as S and R unless isomerization was not observed to a great extent >5%.

(128) TABLE-US-00006 TABLE 5 Name Structure Reactant to be used in step MS Ex Aspect [A] (M + H.sup.+) 122 1-(3-chlorophenyl)-N-[(2S)-3-(3- Intermediate A-1 692.3 chlorophenyl)-1-[[(1S)-1-(4-methoxyphenyl)- and 2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2- 1-(3- oxopentan-3-yl]amino]ethyl]amino]-1- chlorophenyl)cyclopropane oxopropan-2-yl]cyclopropane-1-carboxamide carboxylic acid 123 5-bromo-N-[(2S)-3-(3-cyanophenyl)-1-[[(1S)- Intermediate A-3 693.2 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 5-bromothiophene-2- yl]amino]ethyl]amino]-1-oxopropan-2- carboxylic acid yl]thiophene-2-carboxamide 124 (2S)-2-[[2,2-difluoro-2-(3- Intermediate A-8 575.3 fluorophenyl)acetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-fluorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 125 1-(3-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 596.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1-(3-chlorophenyl)cyclobutane yl]amino]ethyl]amino]-1-oxopropan-2- carboxylic acid yl]cyclobutane-1-carboxamide 126 (2S)-2-[[2-(2,5-dichlorophenyl)-2,2- Intermediate A-8 M + H.sub.2O = difluoroacetyl]amino]-N-[(1S)-1-(4- and 644.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2,5-dichlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoroacetic acid yl]amino]ethyl]propanamide 127 (2S)-2-[[2-(2,3-dichlorophenyl)-2,2- Intermediate A-8 M + H.sub.2O = difluoroacetyl]amino]-N-[(1S)-1-(4- and 644.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2,3-dichlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoroacetic acid yl]amino]ethyl]propanamide 128 2-(3-chlorophenyl)-N-[(2S and 2R)-1-[[(1S)- Intermediate A-8 614.2 1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-(3-chlorophenyl)-1,3- yl]amino]ethyl]amino]-1-oxopropan-2-yl]- dioxolane-2-carboxylic acid 1,3-dioxolane-2-carboxamide (Intermediate J-2) 129 1-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 610.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1-(4- yl]amino]ethyl]amino]-1-oxopropan-2- chlorophenyl)cyclopentane yl]cyclopentane-1-carboxamide carboxylic acid 130 (2S)-2-[[2,2-difluoro-2-[2- Intermediate A-8 642.2 (trifluoromethoxy)phenyl]acetyl]amino]-N- and [(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 2,2-difluoro-2-[2- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- (trifluoromethoxy)phenyl] yl]amino]ethyl]propanamide acetic acid 0 131 (2S)-2-[[2-(2-ethoxyphenyl)-2,2- Intermediate A-8 602.2 difluoroacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(2-ethoxyphenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 132 (2S)-2-[[2,2-difluoro-2-[2- Intermediate A-8 626.2 (trifluoromethyl)phenyl]acetyl]amino]-N- and [(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 2,2-difluoro-2-[2- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- (trifluoromethyl)phenyl]acetic yl]amino]ethyl]propanamide acid 133 1-(2-chloro-6-fluorophenyl)-N-[(2S and 2R)- Intermediate A-8 628.2 1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- and [[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan- 1-(2-chloro-6- 3-yl]amino]ethyl]amino]-1-oxopropan-2- fluorophenyl)cyclopentane yl]cyclopentane-1-carboxamide carboxylic acid 134 1-(2-fluorophenyl)-N-[(2S and 2R)-1-[[(1S)- Intermediate A-8 594.2 1-(4-methoxyphenyl)-2-oxo-2-[(1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1-(2- yl)amino]ethyl]amino]-1-oxopropan-2- fluorophenyl)cyclopentane yl]cyclopentane-1-carboxamide carboxylic acid 135 2-(3-chlorophenyl)-3,3,3-trifluoro-2-hydroxy- Intermediate A-8 640.1 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- and 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- 2-(3-chlorophenyl)-3,3,3- oxopentan-3-yl]amino]ethyl]amino]-1- trifluoro-2-hydroxy-propanoic oxopropan-2-yl]propanamide acid 136 3,3,3-trifluoro-2-hydroxy-N-[(2S)-1-[[(1S)-1- Intermediate A-8 674.2 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3,3,3-trifluoro-2-hydroxy-2-[3- yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2- (trifluoromethyl)phenyl] [3-(trifluoromethyl)phenyl]propanamide propanoic acid 137 2-(3,4-dichlorophenyl)-3,3,3-trifluoro-2- Intermediate A-8 674.1 hydroxy-N-[(2S)-1-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3,4-dichlorophenyl)-3,3,3- trifluoro-4-methyl-2-oxopentan-3- trifluoro-2-hydroxy-propanoic yl]amino]ethyl]amino]-1-oxopropan-2- acid yl]propanamide 138 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 592.2 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 2-(trifluoromethoxy)benzoic oxopropan-2-yl]-2- acid (trifluoromethoxy)benzamide 139 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 576.2 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 3-(trifluoromethyl)benzoic acid oxopropan-2-yl]-3- (trifluoromethyl)benzamide 140 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 576.2 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 2-(trifluoromethyl)benzoic acid oxopropan-2-yl]-2- (trifluoromethyl)benzamide 0 141 2-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 598.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-(4-chlorophenyl)-3-methyl- yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3- butanoic acid methylbutanamide 142 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 550.3 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 2-phenylbutanoic acid oxopropan-2-yl]-2-phenylbutanamide 143 (2S)-2-[[2-(4-chlorophenyl)-2- Intermediate A-8 596.3 cyclopropylacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(4-chlorophenyl)-2- trifluoro-4-methyl-2-oxopentan-3- cyclopropyl-acetic acid yl]amino]ethyl]propanamide 144 (2S)-2-(4-chlorophenyl)-N-[(2S)-1-[[(1S)-1- Intermediate A-8 598.2 (4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- (2S)-2-(4-chlorophenyl)-3- yl]amino]ethyl]amino]-1-oxopropan-2-yl]-3- methyl-butanoic acid methylbutanamide 145 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 576.3 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 1-phenylcyclopentane oxopropan-2-yl]-1-phenylcyclopentane-1- carboxylic acid carboxamide 146 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 522.3 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 3-methylbenzoic acid oxopropan-2-yl]-3-methylbenzamide 147 3-methoxy-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 538.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-methoxybenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 148 3-cyano-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 533.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-cyanobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 149 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 592.3 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 3-(trifluoromethoxy)benzoic oxopropan-2-yl]-3- acid (trifluoromethoxy)benzamide 150 3-ethoxy-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 552.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-ethoxybenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 0 151 (2S)-2-[[2,2-difluoro-2-(2- Intermediate A-8 588.3 methoxyphenyl)acetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2,2-difluoro-2-(2- trifluoro-4-methyl-2-oxopentan-3- methoxyphenyl)acetic acid yl]amino]ethyl]propanamide 152 4-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 542.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 4-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 153 3,3,3-trifluoro-N-[(2S)-1-[[(1S)-1-(4- methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-1-oxopropan-2-yl]-2- [3-(trifluoromethyl)phenyl]propanamide   Intermediate A-8 and 3,3,3-trifluoro-2-[3- (trifluoromethyl)phenyl] propanoic acid (Intermediate J-1) 676.5 154 2-(difluoromethoxy)-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-8 574.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 2-(difluoromethoxy)benzoic yl]amino]ethyl]amino]-1-oxopropan-2- acid yl]benzamide 155 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 554.8 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 1-(trifluoromethyl)cyclobutane oxopropan-2-yl]-1- carboxylic acid (trifluoromethyl)cyclobutane-1-carboxamide 156 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 582.8 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 1-(trifluoromethyl)cyclohexane oxopropan-2-yl]-1- carboxylic acid (trifluoromethyl)cyclohexane-1-carboxamide 157 N-[(2S)-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo- Intermediate A-8 568.2 2-[[(3S)-1,1,1-trifluoro-4-methyl-2- and oxopentan-3-yl]amino]ethyl]amino]-1- 1- oxopropan-2-yl]-1- (trifluoromethyl)cyclopentane (trifluoromethyl)cyclopentane-1-carboxamide carboxylic acid 158 (2S)-2-[[(2S)-2-(4-chlorophenyl)-2- Intermediate A-8 610.4 cyclobutylacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(4-chlorophenyl)-2- trifluoro-4-methyl-2-oxopentan-3- cyclobutyl-acetic acid yl]amino]ethyl]propanamide Chiral separation 159 (2S)-2-[[(2R)-2-(4-chlorophenyl)-2- Intermediate A-8 610.4 cyclobutylacetyl]amino]-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(4-chlorophenyl)-2- trifluoro-4-methyl-2-oxopentan-3- cyclobutyl-acetic acid yl]amino]ethyl]propanamide Chiral separation 160 N-[(2S)-3-methoxy-1-[[(1S)-1-(4- Intermediate A-9 598.4 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1- yl]amino]ethyl]amino]-1-oxopropan-2-yl]-1- (trifluoromethyl)cyclopentane (trifluoromethyl)cyclopentane-1-carboxamide carboxylic acid 0 161 1-fluoro-N-[(2S)-3-methoxy-1-[[(1S)-1-(4- Intermediate A-9 548.5 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1-fluorocyclopentane yl]amino]ethyl]amino]-1-oxopropan-2- carboxylic acid yl]cyclopentane-1-carboxamide 162 tert-butyl N-[(4S)-4-[(3- Intermediate A-18 685.3 chlorobenzoyl)amino]-5-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 3-chlorobenzoic acid trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-5- oxopentyl]carbamate 163 tert-butyl N-[(5S)-5-[(3- Intermediate A-17 699.2 chlorobenzoyl)amino]-6-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 3-chlorobenzoic acid trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-6-oxohexyl]carbamate 164 tert-butyl N-[(5S)-5-[[2-(3-chlorophenyl)-2,2- Intermediate A-17 747.4 difluoroacetyl]amino]-6-[[(1S)-1-(4- and (M − H.sup.−) methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]amino]-6-oxohexyl]carbamate 165 tert-butyl N-[[4-[(2S)-2-[(3- Intermediate A-19 747.3 chlorobenzoyl)amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 3-chlorobenzoic acid trifluoro-4-methyl-2-oxopentan-3- yl]amino]ethyl]amino]-3- oxopropyl]phenyl]methyl]carbamate 166 tert-butyl N-[[4-[(2S)-2-[[2-(3-chlorophenyl)- Intermediate A-19 697.3 2,2-difluoroacetyl]amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]amino]-3- oxopropyl]phenyl]methyl]carbamate 167 tert-butyl N-[[4-[(2S)-2-[[2,2-difluoro-2-[2- Intermediate A-19 829.6 (trifluoromethyl)phenyl]acetyl]amino]-3- and (M − H.sup.−) [[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 2,2-difluoro-2-[2- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- (trifluoromethyl)phenyl]acetic yl]amino]ethyl]amino]-3- acid oxopropyl]phenyl]methyl]carbamate 168 tert-butyl N-[[4-[(2S)-2-[[1-(4- Intermediate A-19 815.5 chlorophenyl)cyclopentanecarbonyl]amino]- and 3-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2- 1-(4- [[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan- chlorophenyl)cyclopentane 3-yl]amino]ethyl]amino]-3- carboxylic acid oxopropyl]phenyl]methyl]carbamate 169 tert-butyl N-[[4-[(2S)-2-[(5-chlorothiophene- Intermediate A-19 753.3 2-carbonyl)amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 5-chlorothiophene-2- trifluoro-4-methyl-2-oxopentan-3- carboxylic acid yl]amino]ethyl]amino]-3- oxopropyl]phenyl]methyl]carbamate 170 tert-butyl N-[[4-[(2S)-2-[[(2S)-2-(4- Intermediate A-19 803.6 chlorophenyl)-3-methylbutanoyl]amino]-3- and [[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 2-(4-chlorophenyl)-3-methyl- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- butanoic acid yl]amino]ethyl]amino]-3- Chiral separation oxopropyl]phenyl]methyl]carbamate 0 171 tert-butyl N-[[4-[(2S)-2-[[(2R)-2-(4- Intermediate A-19 803.7 chlorophenyl)-3-methylbutanoyl]amino]-3- and [[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)- 2-(4-chlorophenyl)-3-methyl- 1,1,1-trifluoro-4-methyl-2-oxopentan-3- butanoic acid yl]amino]ethyl]amino]-3- Chiral separation oxopropyl]phenyl]methyl]carbamate 172 tert-butyl N-[[4-[(2S)-2-[[2-(4-chlorophenyl)- Intermediate A-19 815.8 2-cyclobutylacetyl]amino]-3-[[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(4-chlorophenyl)-2- trifluoro-4-methyl-2-oxopentan-3- cyclobutyl-acetic acid yl]amino]ethyl]amino]-3- oxopropyl]phenyl]methyl]carbamate 173 tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4- Intermediate A-19 825.8 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and (M − H.sup.−) trifluoro-4-methyl-2-oxopentan-3- 3-(trifluoromethyl)benzoic acid yl]amino]ethyl]amino]-3-oxo-2-[[3- (trifluoromethyl)benzoyl]amino]propyl]phenyl] methyl]carbamate 174 tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4- Intermediate A-19 773.7 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 1- yl]amino]ethyl]amino]-3-oxo-2-[[1- (trifluoromethyl)cyclopentane (trifluoromethyl)cyclopentanecarbonyl]amino] carboxylic acid propyl]phenyl]methyl]carbamate 175 tert-butyl N-[[4-[(2S)-3-[[(1S)-1-(4- Intermediate A-19 861.7 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and (M − H.sup.−) trifluoro-4-methyl-2-oxopentan-3- 3,3,3-trifluoro-2-[3- yl]amino]ethyl]amino]-3-oxo-2-[[3,3,3- (trifluoromethyl)phenyl] trifluoro-2-[3- propanoic acid (trifluoromethyl)phenyl]propanoyl]amino] (Intermediate J-1) propyl]phenyl]methyl]carbamate 176 3-chloro-N-[(2S)-1-[[(1S)-1-(4- Intermediate A-21 624.3 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and (M − H.sup.−) trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxo-3- (trifluoromethoxy)propan-2-yl]benzamide 177 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-21 674.3 difluoroacetyl]amino]-N-[(1S)-1-(4- and (M − H.sup.−) methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]-3- (trifluoromethoxy)propanamide 178 (2S)-2-[[2-(3-chlorophenyl)-2,2- Intermediate A-24 617.1 difluoroacetyl]amino]-3-cyano-N-[(1S)-1-(4- and methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- 2-(3-chlorophenyl)-2,2- trifluoro-4-methyl-2-oxopentan-3- difluoro-acetic acid yl]amino]ethyl]propanamide 179 3-chloro-N-[(2S)-3-cyano-1-[[(1S)-1-(4- Intermediate A-24 567.2 methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1- and trifluoro-4-methyl-2-oxopentan-3- 3-chlorobenzoic acid yl]amino]ethyl]amino]-1-oxopropan-2- yl]benzamide 180 tert-butyl 2-[4-[(1S)-1-[[(2S)-2-[(5- Intermediate E-1 743.4 chlorothiophene-2-carbonyl)amino]-3-(3- and fluorophenyl)propanoyl]amino]-2-oxo-2- 5-chlorothiophene-2- [[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan- carboxylic acid 3-yl]amino]ethyl]phenoxy]acetate 0 181 tert-butyl 2-[4-[(1S)-1-[[(2S)-2-[[2-(3- Intermediate E-1 786.5 chlorophenyl)-2,2-difluoroacetyl]amino]-3-(3- and fluorophenyl)propanoyl]amino]-2-oxo-2- 2-(3-chlorophenyl)-2,2- [[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan- difluoro-acetic acid 3-yl]amino]ethyl]phenoxy]acetate

Example 182

N-[(2S)-5-Amino-1-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-1-oxopentan-2-yl]-3-chlorobenzamide

(129) ##STR00272##

(130) To a solution of tert-butyl N-[(4S)-4-[(3-chlorobenzoyl)amino]-5-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-5-oxopentyl]carbamate (Example 162, 0.025 g, 0.036 mmol) in DCM (0.5 mL) was added TFA (0.056 mL, 0.727 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The mixture was concentrated in vacuo, the residue was triturated in diisopropylether, filtered and further dried under high vacuum to give the title compound (0.018 g, 67%, TFA salt) as a colorless solid. MS: 585.2 (M+H.sup.+).

(131) The following examples listed in Table 6 were prepared in analogy to the procedures described for the preparation of example 182 by using the indicated starting materials.

(132) Amine products were triturated in diisopropylether and obtained as TFA salts.

(133) TABLE-US-00007 TABLE 6 Name Reactant: compound Structure obtained in example MS Ex Aspect number indicated (M + H.sup.+) 183 Example 163 184 Example 164 763.3 185 Example 165 647.3 186 Example 166 697.3 187 Example 167 731.4 188 Example 168 715.4 189 Example 169 653.3 190 0 Example 170 703.6 191 Example 171 703.6 192 Example 172 715.6 193 Example 173 681.6 194 Example 174 673.6 195 Example 175 763.6

Example 196

(2S)-2-[[2-(2,5-Dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide

(134) ##STR00286##

[A] (2S)-3-[tert-Butyl(dimethyl)silyl]oxy-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide

(135) ##STR00287##

(136) In a flask, 2-(3,4-dichlorophenyl)-2,2-difluoroacetic acid (0.020 g, 0.084 mmol) and HATU (0.032 g, 0.084 mmol) were mixed in DMF (2 mL) at 0° C., Huenig's base (0.044 μL, 0.252 mmol) was added and the reaction mixture was stirred at this temperature for 10 min. Then, (2S)-2-amino-3-[tert-butyl(dimethyl)silyl]oxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide (Intermediate A-20, 0.045 g, 0.252 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. After this time, 2-(3,4-dichlorophenyl)-2,2-difluoroacetic acid (0.020 g, 0.084 mmol) and HATU (0.032 g, 0.084 mmol) were added again to the mixture which was stirred at room temperature for a further 2 hours. The mixture was diluted with EtOAc, poured into water (10 mL) and the aqueous layer was extracted with EtOAc (2×20 mL). Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 0 to 50% EtOAc/heptane gradient to give the title compound (0.030 g, 47%) as a white solid. MS: 758.3 (M+H.sup.+).

[B] (2S)-3-[tert-Butyl(dimethyl)silyl]oxy-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide

(137) ##STR00288##

(138) To a solution of (2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]propanamide (0.028 g, 0.037 mmol) in DCM (1.5 mL) was added 15% Dess-Martin periodinane in DCM solution (0.192 mL, 0.092 mmol) and the reaction mixture was stirred at room temperature for 2 hours. The mixture was diluted with DCM/water, poured into a sat. NH.sub.4Cl aqueous solution (5 mL) and extracted with DCM (10 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 0 to 70% EtOAc/heptane gradient to give the title compound (0.020 g, 72%) as a white solid. MS: 756.3 (M+H.sup.+).

[C] (2S)-2-[[2-(3,4-Dichlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxy-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide

(139) ##STR00289##

(140) To a solution of (2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]propanamide (0.020 g, 26.4 mmol) in THF (0.5 mL) and water (0.05 mL) cooled to 0° C. with an ice bath was added 4M HCl (0.099 mL, 0.396 mmol) in dioxane and the reaction mixture was stirred at this temperature for 3 hours. The mixture was poured into water (5 mL) and extracted with EtOAc (10 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The residue was triturated in diisopropylether, the solvent was decanted and the solid precipitate was further dried on the high vacuum to give the title compound (0.012 g, 71%) as a white solid. MS: 642.1 (M+H.sup.+).

(141) The following examples listed in Table 7 were prepared in analogy to the procedures described for the preparation of example 196 by using the indicated carboxylic acid in step [A].

(142) TABLE-US-00008 TABLE 7 Reactant to be used in MS Ex Name Structure Aspect step [A] (M + H.sup.+) 197 0 2-(2,5-dichlorophenyl)- 2,2-difluoroacetic acid 642.1 198 2,2-difluoro-2-(3- fluorophenyl)acetic acid 592.2 199 2,2-difluoro-2-[2- (trifluoromethoxy)phen- yl]acetic acid 658.2 200 2-(2-ethoxyphenyl)-2,2- difluoro-acetic acid 618.2 201 2-(2-ethylphenyl)-2,2- difluoro-acetic acid 602.2 202 1-(4- chlorophenyl)cyclopentane carboxylic acid 626.2 203 2,2-difluoro-2-(2- methoxyphenyl)acetic acid 604.2 204 2-(2-cyanophenyl)-2,2- difluoro-acetic acid 599.2

Example 205

(2S)-2-[(3-Chlorobenzoyl)amino]-N—[(S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]butanediamide

(143) ##STR00298##

[A] (2S)-2-[(3-Chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide

(144) ##STR00299##

(145) In a flask, (2S)-2-amino-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide (Intermediate A-22, 0.080 g, 0.114 mmol), 3-chlorobenzoic acid (0.018 g, 0.114 mmol) and HATU (0.047 g, 0.125 mmol) were dissolved in DMF (1 mL) and the mixture cooled to 0° C. Huenig's base (0.060 ml, 0.341 mmol) was added to the reaction mixture which was stirred at this temperature for 15 min, then allowed to warm up to room temperature and stirring was continued for 5 hours. The mixture was diluted with EtOAc, poured into water (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 10 to 80% EtOAc-heptane gradient to give the title compound (0.072 g, 71%) as a light brown waxy solid. MS: 841.4 (M−H.sup.−).

[B] (2S)-2-[(3-Chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide

(146) ##STR00300##

(147) To a solution of (2S)-2-[(3-chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide (0.072 g, 0.085 mmol) in DCM (1 mL) was added 15% Dess-Martin periodinane in DCM solution (0.532 mL, 0.256 mmol) and the reaction mixture was stirred at room temperature for 4 hours. The mixture was diluted with DCM/water, poured into a sat. NH.sub.4Cl aqueous solution (10 mL) and extracted with DCM (20 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 10 to 100% EtOAc/heptane gradient to give the title compound (0.050 g, 68%) as a colourless waxy solid. MS: 839.4 (M−H.sup.−).

[C] (2S)-2-[(3-Chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]butanediamide

(148) ##STR00301##

(149) To a solution of (2S)-2-[(3-chlorobenzoyl)amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]-N′-[(4-methylphenyl)-diphenylmethyl]butanediamide (0.050 g, 0.059 mmol) in DCM (1 mL) cooled to 0° C. was added wet TFA (2.5% water, 0.227 mL, 2.97 mmol) and the reaction mixture was stirred at room temperature for 6 hours. The mixture was concentrated in vacuo and the residue was purified by silica gel flash chromatography, eluting with a 10 to 100% EtOAc/heptane gradient to give the title compound (0.027 g, 73%) as an off-white solid. MS: 585.2 (M−H.sup.−).

(150) The following examples listed in Table 8 were prepared in analogy to the procedures described for the preparation of example 205 by using the indicated intermediate and carboxylic acid in step [A]. Except for examples 206, 208 and 210 which were prepared in analogy to the procedure described for the preparation of example 196 by using the indicated intermediate and 2-(3-chlorophenyl)-2,2-difluoro-acetic acid in step [A] then following the procedures described for the preparation of example 205 in step [B] and [C].

(151) Amide products were purified by silica gel flash chromatography; carboxylic acid products were triturated in diisopropylether.

(152) TABLE-US-00009 TABLE 8 Reactant to be used MS Ex Name Structure Aspect in step [A] (M + H.sup.+) 206 02 Intermediate A-22 and 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid 635.2 207 03 Intermediate A-23 And 3-chlorobenzoic acid 599.2 208 04 Intermediate A-23 and 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid 649.2 209 05 Intermediate A-25 and 5-chlorothiophene- 2-carboxylic acid 686.4 210 06 Intermediate A-25 and 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid 730.4

Example 211

N-[(5S)-5-[[2-(3,4-Dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide

(153) ##STR00307##

[A] tert-Butyl N-[(5S)-5-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate

(154) ##STR00308##

(155) In a flask, 2-(3,4-dichlorophenyl)-2,2-difluoroacetic acid (0.045 g, 0.187 mmol) and HATU (0.078 g, 0.205 mmol) were mixed in DMF (1 mL) at 0° C., Huenig's base (0.098 μL, 0.560 mmol) was added and the reaction mixture was stirred at this temperature for 10 min. Then, tert-butyl N-[(5S)-5-amino-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate (Intermediate A-17, 0.105 g, 0.187 mmol) was added and the reaction mixture was stirred at room temperature for 4 hours. After this time, 2-(3,4-dichlorophenyl)-2,2-difluoroacetic acid (0.045 g, 0.187 mmol) and HATU (0.078 g, 0.205 mmol) were added again to the mixture which was stirred at room temperature for a further 2 hours. The mixture was diluted with EtOAc, poured into water (10 mL) and the aqueous layer was extracted with EtOAc (2×20 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 0 to 100% EtOAc/heptane gradient to give the title compound (0.030 g, 20%) as a light brown solid. MS: 783.4 (M+H.sup.+).

[B] (2S)-6-Amino-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]hexanamide

(156) ##STR00309##

(157) 4M HCl in dioxane (0.096 mL, 388 mmol) was added at 0° C. to a solution of tert-butyl N-[(5S)-5-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]carbamate (0.030 g, 39 mmol) in MeOH (1 mL). The reaction mixture was stirred at this temperature for 10 min and then allowed to warm to room temperature and stirring was continued overnight. The mixture was evaporated to dryness and the residue was triturated with diisopropylether. The solid precipitate was filtered off and further dried under the high vacuum to give the title compound (0.027 g, 93%, HCl salt) as light yellow solid. MS: 683.3 (M+H.sup.+).

[C] N-[(5S)-5-[[2-(3,4-Dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide

(158) ##STR00310##

(159) In a flask, (2S)-6-amino-2-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-N-[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]hexanamide hydrochloride (0.027 g, 0.038 mmol), pyridine-2-carboxylic acid (0.005 g, 0.038 mmol) and HATU (0.016 g, 0.042 mmol) were mixed in DMF (1 mL) and the mixture cooled to 0° C. Huenig's base (0.020 mL, 0.114 mmol) was added to the reaction mixture which was stirred at this temperature for 10 min, then allowed to warm up to room temperature and stirring was continued for 4 hours. The mixture was diluted with EtOAc, poured into H2O (5 mL) and the aqueous layer was extracted with EtOAc (2×10 mL). Combined organics were washed brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 100% EtOAc/heptane gradient to give the title compound (0.021 g, 70%) as a colorless solid. MS: 790.3 (M+H.sup.+).

[D] N-[(5S)-5-[[2-(3,4-Dichlorophenyl)-22-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide

(160) ##STR00311##

(161) To a solution of N-[(5S)-5-[[2-(3,4-dichlorophenyl)-2,2-difluoroacetyl]amino]-6-[[(1S)-1-(4-methoxyphenyl)-2-oxo-2-[[(2S,3S)-1,1,1-trifluoro-2-hydroxy-4-methylpentan-3-yl]amino]ethyl]amino]-6-oxohexyl]pyridine-2-carboxamide (0.021 g, 0.027 mmol) in DCM (0.5 mL) was added 15% Dess-Martin periodinane in DCM solution (0.168 mL, 0.081 mmol) and the reaction mixture was stirred at room temperature for 3 hours. The resulting white suspension was diluted with DCM/water, poured into a sat. NH.sub.4Cl aqueous solution (5 mL) and then extracted with DCM (10 mL). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and evaporated. The residue was purified by silica gel flash chromatography, eluting with a 10-100% EtOAc-heptane gradient to give the title compound (0.016 g, 71%) as a colorless solid. MS: 788.2 (M+H.sup.+).

(162) The following examples listed in Table 9 were prepared in analogy to the procedures described for the preparation of example 211 by using the indicated intermediate and carboxylic acids in step [A] and [C] respectively.

(163) TABLE-US-00010 TABLE 9 Reactant to be used MS Ex Name Structure Aspect in step [A] and [C] (M + H.sup.+) 212 Intermediate A-17; 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid and pyrazine-2- carboxylic acid 755.2 213 Intermediate A-17 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid and pyrimidine-5- carboxylic acid 755.4 214 Intermediate A-17; 3-chlorobenzoic acid and pyridine-2- carboxylic acid 704.3 215 Intermediate A-18; 3-chlorobenzoic acid and pyridine-2- carboxylic acid 690.3 216 Intermediate A-19; 2-(3-chlorophenyl)- 2,2-difluoro-acetic acid and pyridine-2- carboxylic acid 802.4

Example A

(164) A compound of formula (I) can be used in a manner known per se as the active ingredient for the production of tablets of the following composition:

(165) TABLE-US-00011 Per tablet Active ingredient 200 mg Microcrystalline cellulose 155 mg Corn starch 25 mg Talc 25 mg Hydroxypropylmethylcellulose 20 mg Total amount 425 mg

Example B

(166) A compound of formula (I) can be used in a manner known per se as the active ingredient for the production of capsules of the following composition:

(167) TABLE-US-00012 Per capsule Active ingredient 100.0 mg Corn starch 20.0 mg Lactose 95.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg Total amount 220.0 mg