Patent Document ID: 20120220583
Application ID: 13410201
Patent Flag: 0

Claim One:
1. A compound of Formula II: or a pharmaceutically acceptable salt thereof, wherein each of A 1 , A 2 , A 3 and A 4 , independently, is N, CH or CR 6 , provided that no more than two of A 1 , A 2 , A 3 and A 4 is N; R 1a is H, halo, haloalkyl, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl, —N-di-C 1-6 -alkyl, CN, OH or NH 2 , wherein the C 1-6 -alkyl portion of —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl and —N-di-C 1-6 -alkyl are optionally substituted independently with 1-5 substituents of R 7 ; R 1b is H, halo, haloalkyl, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl, —N-di-C 1-6 -alkyl, CN, OH or NH 2 , wherein the C 1-6 -alkyl portion of —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl and —N-di-C 1-6 -alkyl are optionally substituted independently with 1-5 substituents of R 7 ; alternatively, R 1a and R 1b taken together with the carbon atom to which they are attached form a partially or fully saturated 3-, 4-, 5- or 6-membered ring of carbon atoms optionally including 1-2 heteroatoms selected from O, N, or S, the ring optionally substituted independently with 1-3 substituents of R 7 ; R 1c is H, halo, haloalkyl, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl, —N-di-C 1-6 -alkyl, CN, OH or NH 2 ; W is —C(═O)—, —C(═S)—, —OC(═O)—NHC(═O)—, —S(═O) b — or —NHS(═O) b —, wherein b is 1 or 2; each R 2 , independently, is halo, haloalkyl, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 alkyl, —NH—C 1-6 -alkyl, —N-di-C 1-6 -alkyl, CN, OH, NH 2 , C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalkyl or C 4-8 -cycloalkenyl, wherein the C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalkyl, C 4-8 -cycloalkenyl and the C 1-6 -alkyl portion of —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl and —N-di-C 1-6 -alkyl are optionally substituted with 1-5 substituents of R 7 ; alternatively, two adjacent R 2 groups taken together with the carbon atoms to which they are attached form a dioxolyl ring optionally substituted by 1 or 2 halo; R 2a is H or F; R 3 is CN, C 2-3 alkynyl, a partially or fully unsaturated 5- or 6-membered monocyclic ring formed of carbon atoms wherein said ring optionally including 1-3 heteroatoms selected from O, N, or S and optionally substituted with 1-5 substituents of R 7 , or R 3 is F or absent when two adjacent R 2 groups taken together with the carbon atoms to which they are attached form a dioxolyl ring; R 4 is H, halo or C 1-6 -alkyl; R 5 is H, halo, haloalkyl, oxo, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 alkyl, —N-di-C 1-6 -alkyl, CN, OH or NH 2 , wherein the C 1-6 -alkyl and the C 1-6 -alkyl portion of —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl and —N-di-C 1-6 -alkyl are optionally substituted independently with 1-5 substituents of R 7 ; X is CH 2 , CHR 6 , CR 6 R 6 , C(═O), O, NH, NR 6 , or S(O) o wherein o is 0, 1 or 2; Z is a 3-6 membered spirocyclic ring formed of carbon atoms optionally including 1-3 heteroatoms selected from O, N and S and optionally substituted independently with 1-5 substituents of R 7 ; each R 6 , independently, is halo, haloalkyl, C 1-6 -alkyl, —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl, —N-di-C 1-6 -alkyl, CN, OR 7 , NHR 7 , C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalkyl or C 4-8 -cycloalkenyl, wherein the C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-8 -cycloalkyl, C 4-8 -cycloalkenyl and the C 1-6 -alkyl portion of —O—C 1-6 -alkyl, —S—C 1-6 -alkyl, —NH—C 1-6 -alkyl and —N-di-C 1-6 -alkyl are optionally substituted with 1-5 substituents of R 7 ; or R 6 is a fully saturated or partially or fully unsaturated 5- or 6-membered monocyclic or bicyclic ring formed of carbon atoms, said ring optionally including 1-4 heteroatoms selected from O, N, or S and optionally substituted with one or more substituents of R 7 each R 7 , independently, is H, halo, haloalkyl, CN, OH, NO 2 , NH 2 , acetyl, oxo, C 1-10 -alkyl, C 2-10 -alkenyl, C 2-10 -alkynyl, C 3-10 -cycloalkyl, C 4-10 -cycloalkenyl, C 1-10 -alkylamino-, C 1-10 -dialkylamino-, C 1-10 -alkoxyl, C 1-10 -thioalkoxyl or a fully saturated or partially or fully unsaturated 3-8 membered monocyclic or a 6-12 membered bicyclic, said ring system formed of carbon atoms optionally including 1-3 heteroatoms if monocyclic or 1-6 heteroatoms if bicyclic, said heteroatoms selected from O, N, or S, wherein each of the C 1-10 -alkyl, C 2-10 -alkenyl, C 2-10 -alkynyl, C 3-10 -cycloalkyl, C 4-10 -cycloalkenyl, C 1-10 -alkylamino-, C 1-10 -dialkylamino-, C 1-10 -alkoxyl, C 1-10 -thioalkoxyl and ring of said ring system is optionally substituted independently with 1-5 substituents of halo, haloalkyl, CN, NO 2 , NH 2 , OH, oxo, methyl, methoxyl, ethyl, ethoxyl, propyl, propoxyl, isopropyl, isopropoxyl, cyclopropyl, cyclopropylmethoxyl, butyl, butoxyl, isobutoxyl, tert-butoxyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, pentyl, cyclopentyl, hexyl, cyclohexyl, C 1-10 -alkylamino-, C 1-10 -dialkylamino-, C 1-10 -thioalkoxyl, benzyl or phenyl; and m is 0, 1, 2 or 3, provided that (1) the compound is not a compound wherein Z is a four membered spirocyclic ring and R 1a and R 1b are not taken together to form a ring of carbon atoms; and (2) the compound is not (3S)—N-((1S,2R)-1-((3-cyanophenyl)methyl)-3-((4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)amino)-2-hydroxypropyl)-1-cyclobutyl-5-oxo-3-pyrrolidinecarboxamide; N-((1S,2R)-1-((3-cyanophenyl)methyl)-3-((4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)amino)-2-hydroxypropyl)tetrahydro-2-furancarboxamide; N-((1S,2R)-1-((3-cyanophenyl)methyl)-3-((4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)amino)-2-hydroxypropyl)propanamide; N-((1S,2R)-1-(3-cyanophenyl)methyl)-3-((2S,4S)-6-ethyl-3,4,4′,5′-tetrahydrospiro[chromene-2,3′-furan]-4-yl)amino)-2-hydroxypropyl)-2-(methyloxy)acetamide; 2-(((1S,2R)-1-((3-cyanophenyl)methyl)-2-hydroxy-3-((4S)-6-(4-morpholinyl)-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)amino)propyl)amino)-2-oxoethyl dimethylcarbamate; N˜1˜-((1S,2R)-3-(((4S)-6-bromo-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl)amino)-1-((3-cyanophenyl)methyl)-2-hydroxypropyl)-N˜2˜,N˜2˜-dimethylglycinamide; Methyl (4S)-4-(((2R,3S)-4-(3-cyanophenyl)-3-(N,N-dimethylglycyl)amino)-2-hydroxybutyl)amino)-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-6-carboxylate; Methyl (4S)-4-(((2R,3S)-3-(acetylamino)-4-(3-cyanophenyl)-2-hydroxybutyl)amino)-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-6-carboxylate; and Methyl (4S)-4-(((2R,3S)-4-(3-cyanophenyl)-2-hydroxy-3-(((methyloxy)acetyl)amino)butyl)amino)-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-6-carboxylate.