A compound of Formula I, enantiomers and pharmaceutically acceptable salts thereof: wherein R 1 is (R y) k 1 -(Y 1) n 1 -(X 1) m 1 -R x, (R y) k 1 -(X 1) m 1 -(Y 1) n 1 -R x or halogen, Y 1 is C or S 2, X 1 is NH or O, R y is C 1-4 alkanediyl, C 2-4 alkenediyl or C 2-4 alkynediyl, R x is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, or H; k 1 is 0 or 1, n 1 is 0 or 1, m 1 is 0 or 1, R 2 is H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halogen, OC 1-4 alkyl, OC 2-4 alkenyl, or OC 2-4 alkynyl; R 3 is -(CH 2) n 3 -C(Y 3)-(X 3) m 3 -(CH 2) k 3 -R 3a, n 3 is an integer in the range of 0 to 2, Y 3 is S or O, X 3 is S, NH, or O, m 3 is 0 or 1, k 3 is 0 or 1, R 3a is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl Het 3, Ar 3, HetCyc 3 or Cyc 3, Het 3 is a 5- to 10-membered heteroaromatic ring or ring system containing one or more heteroatoms selected from the group consisting of N, O, and S, Ar 3 is a 6- to 10-membered aromatic ring or ring system, HetCyc 3 is a 3- to 8-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of N, O, and S, Cyc 3 is a 3- to 8-membered cyclyl; R 4 is halogen, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, C 1-4 alkyl, C 2-4 alkenyl or C 2-4 alkynyl; R 5 is hydrogen, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, OH, C 1-4 alkyl, C 2-4 alkenyl, or C 2-4 alkynyl, each C 1-4 alkyl, C 2-4 alkenyl, or C 2-4 alkynyl independently optionally substituted with 1 to 3 halogens; R 6 is H, OH, halogen, or NH 2; R 7 is H, halogen, OH, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, or OC 2-4 alkynyl; R 8 is -(CH 2) n 8 -(C) m 8 -R 8a, n 8 is an integer from 1 to 2, m 8 is an integer from 0 to 1, and R 8a is an aromatic or heteroaromatic ring having 5 or 6 ring members, optionally substituted with at least 1 substituent selected from the group consisting of OH, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, CO 2 -C 1-4 alkyl, CO 2 -C 2-4 alkenyl, CO 2 -C 2-4 alkynyl, halogen, CONH 2, CN, COOH, -OCO-C 1-4 alkyl, -OCO-C 2-4 alkenyl, -OCO-C 2-4 alkynyl, -NHCO-C 1-4 alkyl, -NHCO-C 2-4 alkenyl, -NHCO-C 2-4 alkynyl, NH 2, NHC 1-4 alkyl, NHC 2-4 alkenyl, NHC 2-4 alkynyl, N(C 1-4 alkyl) 2, N(C 2-4 alkenyl) 2, N(C 2-4 alkynyl) 2, CONHC 1-4 alkyl, CONHC 2-4 alkenyl, CONHC 2-4 alkynyl, CON(C 1-4 alkyl) 2, CON(C 2-4 alkenyl) 2, CON(C 2-4 alkynyl) 2; or R 8a is an aromatic or heteroaromatic ring having 5 or 6 ring members fused with an additional optionally substituted cyclic, heterocyclic, aromatic, or heteroaromatic ring. R 1 is (R y) k 1 -(Y 1) n 1 -(X 1) m 1 -R x, (R y) k 1 -(X 1) m 1 -(Y 1) n 1 -R x or halogen, Y 1 is C or S 2, X 1 is NH or O, R y is C 1-4 alkanediyl, C 2-4 alkenediyl or C 2-4 alkynediyl, R x is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, or H; k 1 is 0 or 1, n 1 is 0 or 1, m 1 is 0 or 1, R 2 is H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halogen, OC 1-4 alkyl, OC 2-4 alkenyl, or OC 2-4 alkynyl; R 3 is -(CH 2) n 3 -C(Y 3)-(X 3) m 3 -(CH 2) k 3 -R 3a, n 3 is an integer in the range of 0 to 2, Y 3 is S or O, X 3 is S, NH, or O, m 3 is 0 or 1, k 3 is 0 or 1, R 3a is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl Het 3, Ar 3, HetCyc 3 or Cyc 3, Het 3 is a 5- to 10-membered heteroaromatic ring or ring system containing one or more heteroatoms selected from the group consisting of N, O, and S, Ar 3 is a 6- to 10-membered aromatic ring or ring system, HetCyc 3 is a 3- to 8-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of N, O, and S, Cyc 3 is a 3- to 8-membered cyclyl; R 4 is halogen, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, C 1-4 alkyl, C 2-4 alkenyl or C 2-4 alkynyl; R 5 is hydrogen, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, OH, C 1-4 alkyl, C 2-4 alkenyl, or C 2-4 alkynyl, each C 1-4 alkyl, C 2-4 alkenyl, or C 2-4 alkynyl independently optionally substituted with 1 to 3 halogens; R 6 is H, OH, halogen, or NH 2; R 7 is H, halogen, OH, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, or OC 2-4 alkynyl; R 8 is -(CH 2) n 8 -(C) m 8 -R 8a, n 8 is an integer from 1 to 2, m 8 is an integer from 0 to 1, and R 8a is an aromatic or heteroaromatic ring having 5 or 6 ring members, optionally substituted with at least 1 substituent selected from the group consisting of OH, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, OC 1-4 alkyl, OC 2-4 alkenyl, OC 2-4 alkynyl, CO 2 -C 1-4 alkyl, CO 2 -C 2-4 alkenyl, CO 2 -C 2-4 alkynyl, halogen, CONH 2, CN, COOH, -OCO-C 1-4 alkyl, -OCO-C 2-4 alkenyl, -OCO-C 2-4 alkynyl, -NHCO-C 1-4 alkyl, -NHCO-C 2-4 alkenyl, -NHCO-C 2-4 alkynyl, NH 2, NHC 1-4 alkyl, NHC 2-4 alkenyl, NHC 2-4 alkynyl, N(C 1-4 alkyl) 2, N(C 2-4 alkenyl) 2, N(C 2-4 alkynyl) 2, CONHC 1-4 alkyl, CONHC 2-4 alkenyl, CONHC 2-4 alkynyl, CON(C 1-4 alkyl) 2, CON(C 2-4 alkenyl) 2, CON(C 2-4 alkynyl) 2; or R 8a is an aromatic or heteroaromatic ring having 5 or 6 ring members fused with an additional optionally substituted cyclic, heterocyclic, aromatic, or heteroaromatic ring.